ArticleLiterature Review

The effectiveness of prolotherapy in treating knee osteoarthritis in adults: A systematic review

March 2017
British Medical Bulletin 122(1):1-18

DOI:10.1093/bmb/ldx006

Authors:

Fadi Hassan

Heart of England NHS Foundation Trust

Suad Trebinjac

DPRC

William Delany Murrell

Institute for Mobility and Longevity

Introduction: Osteoarthritis (OA) often leads to symptoms such as pain, stiffness and decreased function. OA is treated with a wide range of modal- ities, both conservatively and surgically. Prolotherapy has been used to treat various musculoskeletal problems and has shown some promise. Sources of data: Searches of the electronic databases, PubMed, ISI web of science, PEDro and SPORTDiscus, were conducted for all Level 1–4 studies published from inception through to December 2016. Areas of agreement: Ten studies were evaluated and results show signifi- cant improvement in scores for pain, function and range of motion, both in the short term and long term. Patient satisfaction was also high in these patients (82%). Areas of controversy: Meta-analysis was not possible due to heterogeneity of outcome measures and populations. Growing points: Moderate evidence suggests that prolotherapy is safe and can help achieve significant symptomatic control in individuals with OA.

Нетрадиційні методи лікування остеоартрозу колінного суглоба

Article

Full-text available

May 2023

Сьогодні лікування остеоартрозу (ОА), як і раніше, є серйозною проблемою для медицини. Незважаючи на те, що багато широко використовуваних консервативних методів лікування ОА колінного суглоба визнані ефективними, триває пошук нових методів. Оскільки суглобовий хрящ має обмежений потенціал відновлення, ефективні методи лікування залишаються складними актуальними завданнями. Інноваційна терапія спрямована на пошук найкращого способу лікування для уповільнення прогресування ОА. Актуальними є епідеміологічні та клінічні дослідження ОА, оскільки епідеміологічні дослідження виявляють фактори ризику виникнення і прогресування цього захворювання, а клінічні дослідження відіграють важливу роль для нових методів лікування ОА, включно з пероральною, ін’єкційною та внутрішньосуглобовою терапією. Сьогодні провідні фахівці з лікування ОА продовжують дискутувати щодо корисності внутрішньосуглобових ін’єкцій (ВСІ) та доходять різних висновків. Мета дослідження: провести огляд літератури про лікування ОА колінного суглоба з аналізом інноваційних методів лікування щодо використання внутрішньосуглобових ін’єкцій (як-от: збагачена тромбоцитами плазма, терапія стовбуровими клітинами, пролотерапія, блокада генікулярного (колінного) нерва) та їх переваг і недоліків задля визначення можливих напрямків лікування, які є більш безпечними й економічно ефективними для пацієнта. Матеріали та методи. Пошук наукової інформації проведений в електронних базах PubMed, Google Scholar. Результати. У цьому огляді наведені методи лікування ОА із застосуванням внутрішньосуглобових ін’єкцій біологічно-фармакологічних засобів, як-от: збагачена тромбоцитами плазма, терапія стовбуровими клітинами та пролотерапія, блокада генікулярного нерва. Висновки. Зважаючи на мультидисциплінарний підхід, що включає біофармакологічні та немедикаментозні методи лікування ОА, внутрішньосуглобові ін’єкції можна розглядати як ефективну місцеву терапію ОА.

Rejeneratif tıbbın tarihsel gelişimi ve terminolojisi

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Aug 2022

Procedural Treatments for Knee Osteoarthritis: A Review of Current Injectable Therapies

Article

Full-text available

Feb 2020
Pain Res Manag

Knee osteoarthritis is a common painful degenerative condition affecting the aging Canadian population. In addition to pain and disability, osteoarthritis is associated with depression, comorbid conditions such as diabetes, and increased caregiver burden. It is predicted to cost the Canadian healthcare system $7.6 billion dollars by 2031. Despite its high cost and prevalence, controversy persists in the medical community regarding optimal therapies to treat knee osteoarthritis. A variety of medications like nonsteroidal anti-inflammatories and opioids can cause severe side effects with limited benefits. Total knee arthroplasty, although a definitive management, comes with risk such as postoperative infections, revisions, and chronic pain. Newer injectable therapies are gaining attention as alternatives to medications because of a safer side effect profile and are much less invasive than a joint replacement. Platelet-rich plasma is beginning to replace the more common injectable therapies of intra-articular corticosteroids and hyaluronic acid, but larger trials are needed to confirm this effect. Small studies have examined prolotherapy and stem cell therapy and demonstrate some benefits. Trials involving genicular nerve block procedures have been successful. As treatments evolve, injectable therapies may offer a safe and effective pathway for patients suffering from knee osteoarthritis.

Effects of Short Wave Diathermy Added on Dextrose Prolotherapy Injections in Osteoarthritis of the Knee

Article

Full-text available

Feb 2020

Objective: To show the effects of short wave diathermy (SWD) added on prolotherapy injections in osteoarthritis (OA) of the knee on pain, physical functioning, and quality of life. Design: This is a single-blinded randomized controlled study. Setting: Physical Medicine and Rehabilitation Department of a university hospital. Subjects: Sixty-three patients with OA of the knee with Kellgren-Lawrence class 2 or 3 were included in the study. Methods: Patients were randomized into two groups, first being dextrose prolotherapy+SWD and the second being dextrose prolotherapy with sham SWD. Patients were injected with dextrose prolotherapy solutions in the beginning, third, and sixth week of the study, for a total of three times, and took 20 min of SWD after injection (true or sham). Outcome measures: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analogue Scale (VAS) for pain, and Short Form Health Survey (SF-36) were applied before, after (sixth week), and at the third month of treatment. Results: Both groups showed improvements in VAS, WOMAC, and SF-36 scores (p < 0.05). Between-group analyses showed no significant differences (p > 0.05). Conclusions: This study shows that prolotherapy is effective for pain, functionality, and quality of life in patients with OA of the knee. The effects of additional SWD require more evidence. More studies of higher quality are required to make a statement.

Dextrose Prolotherapy for Symptomatic Knee Osteoarthritis: Feasibility, Acceptability, and Patient-Oriented Outcomes in a Pilot-Level Quality Improvement Project

Article

Jan 2019

Objectives: Knee osteoarthritis (KOA) is a growing health problem with limited nonsurgical treatment options. Prolotherapy is an injection-based technique for chronic KOA pain; health plan coverage is limited, presenting an access barrier. A local health plan recently included coverage for prolotherapy for KOA, but uptake and treatment response in routine care are unknown. The authors conducted a pilot-level quality improvement (QI) project to explore the feasibility, acceptability, and effects of prolotherapy for painful KOA in a primary care setting. Design: QI prospective case series. Setting/location: Outpatient: invitation letters were sent to symptomatic KOA patients with a primary care provider whose health plan covered prolotherapy. Subjects: Primary care patients with KOA. Intervention: Intra- and extra-articular prolotherapy injections: patients received up to six prolotherapy sessions. Outcome measures: Primary: Feasibility: response rate to invitation to utilize prolotherapy. Acceptability: patient adherence to, and satisfaction with, three or more prolotherapy sessions. Secondary: Survey based (the Western Ontario McMaster University Osteoarthritis Index, WOMAC, 0-100; EuroQOL 5-D). Objectively assessed: function (30-sec chair stand, 4 × 10 m walk, 9-step stair-climb), overall activity (ActiGraph wGT3X accelerometer), treadmill gait analysis, and preferred walking speed. Outcome analysis (paired t-test) was per protocol, comparing follow-up and baseline outcome data at ∼8 months. Results: Thirty-nine patients were invited, 11 responded, and 7 patients (59.6 ± 9.3 years, 6 female) received 5.0 ± 1.1 prolotherapy sessions. Satisfaction was high. Their WOMAC scores improved by 27.6 ± 19.5 points (p = 0.02) at 8.4 months. Functional testing improved by 8.0 ± 3.6 sec (p = 0.003) in the 4 × 10 m walk. There were no group differences between baseline and follow-up in chair stand, stair-climb, accelerometry, or gait outcomes. Five patients increased their preferred walking speed (p = 0.001). Conclusions: These data suggest that prolotherapy in this primary care clinic is feasible and acceptable. Self-reported improvement is similar to that of efficacy studies; office-based, objectively assessed functional assessment can be performed. Further evaluation is warranted.

Effectiveness of dextrose prolotherapy for chronic musculoskeletal pain: A prospective observational study

Article

Full-text available

Nov 2024

The increasing prevalence and burden of musculoskeletal conditions has led to an interest in effective nonsurgical solutions, which are more cost efficient and minimally invasive. Prolotherapy is an alternative therapeutic procedure used for management of chronic musculoskeletal conditions which involves injection of irritant solution into affected area. Primary objective of this study was to assess effectiveness of prolotherapy in relieving pain. This study was undertaken to assess the effectiveness of prolotherapy with Inj. Ropivacaine 0.25% & Dextrose 12.5% in patients with chronic musculoskeletal pain. The primary objective was to evaluate reduction in pain 3 months after procedure. Secondary objectives were to assess number of sessions of prolotherapy required, patient satisfaction and complications if any. Seventy patients of either sex aged 18 years and above, diagnosed with a chronic musculoskeletal pain condition, who were selected for the prolotherapy as the treatment modality, were included in the study. All patients received prolotherapy with 0.25% ropivacaine and 12.5% in the involved area. A Wilcoxon signed-rank test showed that there was statistically significant difference in mean VAS, 3 months after prolotherapy as compared to mean VAS pre-procedure. The mean VAS reduced from 6.61 ± 0.95 at the beginning of the study, reduced to 0.88 ± 1.95 by the end of the study (p = 0.000.) Maximum volume of drug required for adequate pain relief by prolotherapy was 30 cc with the mean of 17.53 ± 7.28. 58.3% of the study population needed 2 sessions of prolotherapy while 10% required 3 sessions. 80% of patients, had more than 50% pain relief at the end of 3rd month after prolotherapy. Prolotherapy using 12.5% Dextrose + 0.25% Ropivacaine offers minimally invasive, cost effective and safe management option for patient with chronic musculoskeletal pain.

Prolotherapy in Musculoskeletal Disorders, Guideline for Orthopedic Application

Article

Full-text available

Jan 2023

Comparative Efficacy of Intra-Articular Injection, Physical Therapy, and Combined Treatments on Pain, Function, and Sarcopenia Indices in Knee Osteoarthritis: A Network Meta-Analysis of Randomized Controlled Trials

Article

Full-text available

Mar 2023
INT J MOL SCI

Knee osteoarthritis (KOA) is associated with a high risk of sarcopenia. Both intra-articular injections (IAIs) and physical therapy (PT) exert benefits in KOA. This network meta-analysis (NMA) study aimed to identify comparative efficacy among the combined treatments (IAI+PT) in patients with KOA. Seven electronic databases were systematically searched from inception until January 2023 for randomized controlled trials (RCTs) reporting the effects of IAI+PT vs. IAI or PT alone in patients with KOA. All RCTs which had treatment arms of IAI agents (autologous conditioned serum, botulinum neurotoxin type A, corticosteroids, dextrose prolotherapy (DxTP), hyaluronic acid, mesenchymal stem cells (MSC), ozone, platelet-rich plasma, plasma rich in growth factor, and stromal vascular fraction of adipose tissue) in combination with PT (exercise therapy, physical agent modalities (electrotherapy, shockwave therapy, thermal therapy), and physical activity training) were included in this NMA. A control arm receiving placebo IAI or usual care, without any other IAI or PT, was used as the reference group. The selected RCTs were analyzed through a frequentist method of NMA. The main outcomes included pain, global function (GF), and walking capability (WC). Meta-regression analyses were performed to explore potential moderators of the treatment efficacy. We included 80 RCTs (6934 patients) for analyses. Among the ten identified IAI+PT regimens, DxTP plus PT was the most optimal treatment for pain reduction (standard mean difference (SMD) = −2.54) and global function restoration (SMD = 2.28), whereas MSC plus PT was the most effective for enhancing WC recovery (SMD = 2.54). More severe KOA was associated with greater changes in pain (β = −2.52) and WC (β = 2.16) scores. Combined IAI+PT treatments afford more benefits than do their corresponding monotherapies in patients with KOA; however, treatment efficacy is moderated by disease severity.

A Comprehensive Update of Prolotherapy in the Management of Osteoarthritis of the Knee

Article

May 2022

This is a comprehensive review of the literature focusing on the use of prolotherapy in the treatment of osteoarthritis of the knee. It covers the background, efficacy, and advantages of prolotherapy in the management of osteoarthritis symptoms and then covers the existing evidence of the use of prolotherapy for this purpose. Current treatments for osteoarthritis of the knee are numerous, yet patients continue to endorse chronic pain and poor quality of life. Prolotherapy is a treatment that has been inadequately studied with poor sample sizes and lack of standardization between trials. However, in recent years the literature on prolotherapy in the treatment of knee osteoarthritis has grown. Although there is still a lack of homogeneity, trials have shown that dextrose prolotherapy, autologous conditioned serum, hyaluronic injections, and normal saline administered either intra- or peri-articularly are comparable in reducing pain scores to other primary treatment options. The mechanism of action for prolotherapy is still unclear, but researchers have found that prolotherapy plays some role in cartilage growth or chondrogenesis and has been shown to have improved radiographic outcomes. Prolotherapy appears to be a safe treatment alternative that has been shown to improve stiffness, pain, function, and quality of life in osteoarthritis of the knee. Knee osteoarthritis is remarkably prevalent in the United States and is one of the most common causes of disability in the elderly population. Although there are many treatment options, patients continue to live with chronic pain which can incur high costs for patients. A safe, long-term, and effective solution has not yet been identified. Prolotherapy has been shown to be a safe option for improving pain, function, and quality of life as effectively as other treatment options.

Improvement in Pain and Quality of Life After Ultrasound-Guided Saphenous Nerve Block in Patients With Knee Osteoarthritis

Article

Full-text available

May 2022

Introduction Osteoarthritis (OA) of the knee is a common complaint in the elderly population and results in considerable disability in advanced stages. Though many pharmacological, electrotherapeutic, and interventional options are available for the effective treatment of knee OA in the early stages, these modalities fail to provide effective and long-term relief in some cases where peripheral nerve blocks may prove beneficial. Hence, this study was conducted to assess the efficacy of the saphenous nerve block in knee pain due to OA. Objective To evaluate improvement in pain and quality of life after ultrasound-guided saphenous nerve block in patients with knee OA. Material and methods An interventional prospective study in patients with knee OA, with medial compartment knee pain, was conducted from March 2016 to March 2017. All patients were evaluated prior to the procedure, and then at one week, one month, three months, and six months. The pain was evaluated using the visual analog scale (VAS) and functional improvement using the Knee injury and Osteoarthritis Outcome Score (KOOS). Results Forty patients with unilateral knee OA underwent saphenous nerve block. Fifty percent of the patients reported pain relief within one week, whereas 58%, 33%, and 23% exhibited relief at subsequent follow-ups at one, three, and six months. A statistically significant difference (p < 0.0001) was observed in pain (VAS and KOOS pain) and functional scales (KOOS symptom, quality of life (QOL), and activities of daily living (ADL)) at follow-up evaluations. Conclusion Ultrasound-guided saphenous nerve block results in a significant improvement in pain and QOL in patients with knee OA.

The Efficacy of Ozone Prolotherapy Compared to Intra-Articular Hypertonic Saline Injection in Reducing Pain and Improving the Function of Patients with Knee Osteoarthritis: A Randomized Clinical Trial

Article

Full-text available

Aug 2021
EVID-BASED COMPL ALT

Background: Knee osteoarthritis is a common disease that is associated with chronic pain and disability in patients. Prolotherapy is a complementary therapeutic approach for improving pain and function in patients with osteoarthritis. We aimed to compare the effect of hypertonic saline with ozone plus hypertonic saline in improving the symptoms of osteoarthritis in the patients. Materials and Method. In this clinical trial, thirty-four adults with painful primary knee osteoarthritis for at least three months were randomized to two groups: ozone plus hypertonic saline 5% and hypertonic saline 5% alone. Prolotherapy and thrice follow-up with two-week intervals were done. The outcome measures included Oxford Knee Scale (OKS), Western Ontario McMaster University Osteoarthritis Index (WOMAC), and Visual Analog Scale (VAS), which were obtained from the patients before the injection and after the 2nd and 4th weeks after the start of the study. Results: The mean age of the participants was 60.12 ± 7.54 years. There were no statistically significant differences between demographic characteristics before the injection between the two groups (p > 0.05). The results showed that VAS and OKS values decreased over time (p < 0.001) in each group, but there was no significant difference in the reduction of those between the two treatment groups (p = 0.734 and p = 0.734, respectively). Both interventions improved the mean values of WOMAC pain, WOMAC stiffness, WOMAC act, and WOMAC total. However, there was no significant difference in WOMAC pain reduction rate (p = 0.465), WOMAC stiffness rate (p = 0.656), WOMAC act rate (p = 0.376), and WOMAC total rate between the two methods (p = 0.528). Conclusion: The results showed that intra-articular prolozone therapy and hypertonic saline injection can lead to improvement of pain and function in patients with knee osteoarthritis at the same status without any significant difference.

Dextrose prolotherapy in knee osteoarthritis: A systematic review and meta-analysis

Article

May 2021

Objective To summarize the evidence for dextrose prolotherapy in knee osteoarthritis. Data sources The authors searched PubMed and Embase from inception to September 2020. All publications in the English language were included without demographic limits. Study selection Randomized clinical trials comparing the effects of any active interventions or placebo versus dextrose prolotherapy in patients with knee osteoarthritis were included. Data extraction Potential articles were screened for eligibility, and data was extracted independently. The risk of bias was assessed using the Cochrane Risk of Bias tool. Meta-analysis was performed on clinical trials with similar parameters. The Strength of Recommendation Taxonomy (SORT) was used for evaluating the strength of recommendations. Data synthesis In total, eleven articles (n = 837 patients) met the search criteria and were included. The risk-of-bias analysis revealed two studies to be of low risk. The overall effectiveness was calculated using a meta-analysis method. Prolotherapy was no different from platelet-rich plasma on the pain subscales at the 6-month time point. Prolotherapy was inferior to platelet-rich plasma at 6 months (MD 0.45, 95% CI 0.06–0.85, p = 0.03) on the stiffness subscale. Prolotherapy was found to be safe with no major adverse effects. Conclusion Prolotherapy in knee osteoarthritis confers potential benefits for pain but the studies are at high risk of bias. Based on two well-designed studies, dextrose prolotherapy may be considered in knee osteoarthritis (strength of recommendation B). This treatment is safe and may be considered in patients with limited alternative options (strength of recommendation C).

Prolotherapy for chronic low back pain: a review of literature

Article

Full-text available

Apr 2021
BRIT MED BULL

Introduction: Low back pain is common and imposes major societal burdens for patient suffering and costs. Prolotherapy injections are used for musculoskeletal conditions including tendinopathies, osteoarthritis and low back pain to enhance soft-tissue healing. This review aims to clarify the place of prolotherapy in chronic low back pain (CLBP). Sources of data: Using multiple databases, a systematic search was performed to identify studies detailing the use of prolotherapy to manage CLBP. A total of 12 articles was included in the present work. Areas of agreement: Considering the level of evidence and the quality of the studies assessed using the modified Coleman Score, prolotherapy is an effective management modality for CLBP patients in whom conservative therapies failed. Areas of controversy: The presence of co-interventions and the clinical heterogeneity of the work contributes to confound the overall conclusions. Growing points and areas for research: The analysis of the studies included in the review, using appropriate tools, showed how their quality has decreased over the years, reflecting the need for appropriately powered well planned and performed randomized control trials.

Dextrose Prolotherapy for Muscle, Tendon and Ligament Injury or Pathology: A Systematic Review

Article

Full-text available

Oct 2020

Background: Prolotherapy with dextrose has recently gained attention as a potential treatment for muscle, ligament or tendon pathology/injury. Questions/Purpose: This review aimed to: 1) evaluate the main outcome of dextrose prolotherapy treatment for muscle, ligament or tendon pathology/injury; 2) determine the concentrations of dextrose and protocol of injection; and 3) assess complications or adverse effects after dextrose prolotherapy. Methods: Four electronic databases were searched for related published articles. Articles that met the following criteria were included in this review: 1) articles on peer-reviewed level 1 to 4 studies; 2) articles published in English; 3) articles on dextrose prolotherapy study for tendon or ligament or muscle injury/pathology; and 5) articles that describe dose of dextrose. Published articles that met this inclusion criteria were included in this systematic review. Systematic Review Article Rhatomy et al.; ARRB, 35(10): 43-62, 2020; Article no.ARRB.61771 44 Results: Twenty four studies fulfilled inclusion criteria,consisting of seventeen clinical studies, four animal studies and three invitro studies. Eleven studies reported there were improvement of functional outcome after dextrose prolotherapy. Three Studies reported improvement of patient satisfaction after dextroprolotherapy in supraspinatus tear, Achilles tendinopathy. And patellar tendinopathy, meniscus tear and anterior tibiofibular ligament tear. Three studies reported there are increasing of neovascularization in Achilles tendinopathy and patellar tendinopathy in animal studies, increasing of inflammatory response in animal studies and in vitro studies and increasing of cell proliferation and collagen production. Nine studies (52%) use dextrose 25% concentration. A few adverse effects were reported and minor effect, such as discomfort Minor soreness, extreme pain, skin burns 2nd grade, hypotension, Deep Vein Thrombosis (DVT) (patient has history DVT). Conclusions: Dextrose Prolotherapy is a potentially effective treatment for patients with muscle, tendon or ligament tear or pathology. Efficacy in long term follow-up, as single therapy or first-line therapy cannot be determined from the current literature.

Identification of early response to hypertonic dextrose prolotherapy markers in knee osteoarthritis patients by an inflammation-related cytokine array

Preprint

Full-text available

May 2020

BACKGROUND/AIM Osteoarthritis (OA) is one of the most common forms of arthritis, and hypertonic dextrose prolotherapy has long been used clinically to treat knee OA. The aim of this study was to investigate the inflammation-related protein-expression profile characterizing the efficacy of the hypertonic dextrose prolotherapy in knee OA as prognostic markers. METHODS OA patients over the age of 65 were recruited for Western Ontario McMaster University Osteoarthritis (WOMAC) index, knee X ray evaluation and knee joint synovial fluid analysis before and after hypertonic dextrose prolotherapy. The expressions of inflammation-related factors were measured using a novel cytokine antibody array methodology. The cytokine levels were quantified by quantitative protein expression and analyzed by ELISA using the patients’ knee-joint synovial fluid. The WOMAC Index and minimum joint space width prior to receiving the intra-articular injection and at 2-week intervals were compared. RESULTS 12 patients who received OA intervention were enrolled and finally a clinical evaluation of 12 knee joints and knee synovial fluid samples were analyzed. In this study, after receiving hypertonic dextrose prolotherapy, the OA patients clearly demonstrated a significant improvement in WOMAC index and increasing tendency in the medial minimum joint space width after intervention. Meanwhile, we observed a significantly associated tendency between the high-glucose treatment of knee OA and the upregulation of MMP2, TIMP-1, EGF, CXCL9 and IL-22. These findings provide knee OA patients receiving hypertonic dextrose prolotherapy, which accompanying with the improvement of knee pain, stiffness, and function and increasing tendency in the medial minimum joint space width.

The Effects of Dextrose Prolotherapy in Symptomatic Knee Osteoarthritis: A Randomized Controlled Study

Article

Mar 2020

Objective: To investigate the effects of dextrose prolotherapy in patients with knee osteoarthritis (KOA). Design: A prospective, randomized-controlled interventional trial. Setting: An outpatient pain medicine clinic. Participants: The study included 66 patients aged 40-70 years with chronic knee pain refractory to conservative therapy and diagnosed as grade II or III KOA according to the Kellgren-Lawrence classification. The patients were assigned to dextrose prolotherapy group (PG; n = 22), saline group (SG; n = 22), or control group (CG; n = 22). Interventions: The intra- and extra-articular dextrose prolotherapy and saline injections were administered to the PG and SG, respectively, at 0, 3, and 6 weeks. The patients were blinded to their injection group status. A home-based exercise program was prescribed for all patients in all three groups. Outcome measures: The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, activity pain, stiffness severity measured using a visual analog scale (VAS), and the health-related quality of life (HRQoL) scores measured using the Short Form-36 (SF-36) subscales were recorded at the baseline, 6-week, and 18-week follow-ups. Results: The WOMAC-pain and VAS-activity pain scores decreased significantly in the PG compared to the SG (p = 0.002 and p < 0.001, respectively) and CG (p < 0.001 and p < 0.001, respectively) at 18 weeks. The WOMAC-stiffness scores decreased in the PG compared to the CG at 18 weeks (p < 0.001). The WOMAC physical functioning scores were improved in the PG compared to the CG at 18 weeks (p < 0.001). The physical component scores of the HRQoL were significantly improved in the PG compared to the CG at 18 weeks (p = 0.016), but the mental component scores of the HRQoL showed no significant differences. Conclusions: These findings suggest that dextrose prolotherapy is effective at reducing pain and improving the functional status and quality of life in patients with KOA.

The effect of dextrose prolotherapy on patients diagnosed with knee osteoarthritis: A comprehensive systematic review and meta‐analysis of interventional studies

Article

Full-text available

Jun 2024

Background and Aims The primary objective of this systematic review and meta‐analysis was to assess the impact of dextrose prolotherapy on individuals diagnosed with knee osteoarthritis (KOA). Methods To conduct a thorough investigation, a variety of leading international databases were checked, including PubMed (Medline), Scopus, Web of Sciences, EMBASE (Elsevier), ClinicalTrials.gov, and the Cochrane Library. The search covered a period from January 2000 to the end of June 2023, which facilitated the collection of relevant studies. Results The findings of the study revealed that when the studies utilizing the Western Ontario McMaster Universities Index tool (WOMAC) were combined, patients with KOA who received prolotherapy experienced an improvement in function compared with those who received other treatments (SMD: 0.20; 95% Confidence Interval [1]: −0.11, 0.51; p value SMD = 0.221; I²: 78.49%; pheterogeneity < 0.001). Additionally, there was a decrease in mean pain and stiffness among patients who received prolotherapy compared with those who received other treatments or a placebo [(SMD: −0.95; 95% CI: ‐1.14, −0.76; p value SMD < 0.001; I²: 59.35%; pheterogeneity = 0.070) and (SMD: −0.21; 95% CI: −0.32, −0.10; p value SMD < 0.001; I²: 88.11%; pheterogeneity < 0.001)]. Furthermore, based on the Visual Analog Scale (VAS) score, there was a reduction of 0.81 units out of 10 in mean pain for patients with KOA who received prolotherapy (SMD: −0.81; 95% CI: −5.63, 4.10; p value SMD = 0.693; I²: 48.54%; pheterogeneity = 0.08). Conclusion Drawing from the data analysis performed in this meta‐analysis, it is apparent that dextrose prolotherapy exhibits promising effectiveness in reducing joint pain and stiffness, as well as improving functional performance in individuals suffering from KOA. Furthermore, it is recommended that forthcoming studies incorporate follow‐up periods to guide decisions concerning the duration of prolotherapy's effects.

Comparison of the Effectiveness between Oral NSAIDs and Dextrose Prolotherapy in Knee Osteoarthritis

Article

Full-text available

Apr 2023

Non-steroidal anti-inflammatory drugs (NSAIDs) are the first treatment choice for pain relief in osteoarthritis (OA). However, known to have an 85% risk of side effects on the gastrointestinal and a 40% chance of cardiovascular complications. In addition, in certain classes of NSAIDs, the risk of chronic kidney disease increases due to long-term consumption. On the other hand, dextrose prolotherapy is a regenerative therapy. This study aimed to compare the effectiveness of oral NSAIDs with dextrose prolotherapy in knee OA based on clinical features. This study used an observational method (cross-sectional) conducted in three locations; Jember Clinic Hospital, Balung Hospital, and Harapan Mulya Kertonegoro Jenggawah Clinic from September 2021 to March 2022. Of the 75 population, 23 patients with mild to moderate knee OA were divided into two groups; 15 samples of dextrose prolotherapy and eight samples of oral NSAIDs. Data in the study showed the mean WOMAC score in the dextrose prolotherapy group was 12.4±11.7, while the oral NSAID group was 34.75±17.6. A total of 14 samples experienced a decrease in scores after switching from oral NSAIDs to dextrose prolotherapy. Bivariate analyses were performed using Mann-Whitney and Wilcoxon tests. Both statistical tests show a p=0.001 (p<0.05). Thus, this study concluded that dextrose prolotherapy was more effective than oral NSAIDs in knee OA.

A comparison between hypertonic dextrose prolotherapy and conventional physiotherapy in patients with knee osteoarthritis

Article

Full-text available

Aug 2023

The aim of the present study was to compare the efficacy of hypertonic dextrose prolotherapy (HDP) with conventional physiotherapy (CPT) in improving symptoms in females with knee osteoarthritis (OA). The present study included 60 patients with a diagnosis of knee OA. The patients were randomly assigned to the HDP (n=30) and CPT (n=30) groups. The patients in the HDP group were treated with a dextrose injection into the knee joint (25% dextrose) and around the knee (15% dextrose) in two sessions for 1 month, while those in the CPT group received a hot pack, transcuta‑ neous electrical nerve stimulation and therapeutic ultrasound in five sessions a week for 4 weeks. Prior to commencing the treatment, and at 1 and 3 months post‑treatment, all the patients were evaluated using the visual analog scale (VAS), Western Ontario and McMaster Osteoarthritis Index (WOMAC), the goniometric measurement of active knee range of motion (ROM), a 50‑m walking test and isokinetic knee muscle strength measurements. There were no statistically significant differences between the two groups as regards the demographic characteristics at pre‑treatment (P>0.05). However, at 1 and 3 months post‑treatment, the scores of all the outcome parameters were significantly improved in the HDP group compared with the CPT group (P<0.05 for all). In both groups, a significant improvement was observed in the VAS scores, WOMAC total values and ROM following the treatments, with the greatest improvement observed in the HDP group (P<0.001). The isokinetic quadriceps peak torque measurements were increased in both groups following treatment. All the scores exhibited a statistically significant improvement in the HDP group at both 1 and 3 months post‑treatment. On the whole, the results of the present study demonstrate that both HDP and CPT are effective treatment modalities to relieve pain, and increase functionality and strength in patients with knee OA. However, greater improvements in pain and functionality can be achieved with prolotherapy

Effectiveness of radiofrequency rhizotomies of genicular nerves for treating chronic pain in knee osteoarthritis

Article

Nov 2022

Background: Osteoarthritis (OA) is the most common cause of lower extremity disability in the elderly, primarily affecting lower extremity joints, such as the knee and hip. Elder patients with comorbidities may not be suitable candidates for surgery. For these difficult to treat cases, radiofrequency (RF) rhizotomies may be an effective alternative treatment. Likewise, it has been found that RF therapy can improve joint function and reduce pain by preventing the transmission of pain signals thus easing the patient. Objective: To evaluate the effectiveness of radiofrequency rhizotomies of genicular nerves in treating knee pain caused by knee osteoarthritis. Results: A total of 100 patients were enrolled in the current study. The mean age of patients was 62.7+9.7. Majority of the patients were female (69%), married (79%), and overweight (58.0%). Regarding affected knee sites, 39% had left, 34% right and 29% had both knees affected, respectively. There was a significant difference in mean scores among patients before and after treatment follow-up. The mean pain score before starting the treatment was 7.63+1.11, in the 1st week. The follow up mean pain score was 3.94+0.874, which further reduced in the 12th week to 1.51+1.12. The pain score, OKS and HADs significantly improved from baseline to 12th week follow up which shows that RFA was an effective treatment for OA knee pain (P-value <0.05) which shows that Radiofrequency rhizotomies of genicular nerves was an effective treatment for OA knee pain (P-value <0.05). Conclusion: Radiofrequency rhizotomies of genicular nerves is a safe and effective treatment option for patients suffering from chronic pain caused by knee OA.

Prolotherapy in knee osteoarthritis

Article

Full-text available

Aug 2021

Gonarthrosis is a very frequent entity and affects a large group of patients especially above 40 years, conservative treatment is the first line and includes prolotherapy. To update knowledge regarding the use of prolotherapy in patients with gonarthrosis. The information was searched and analyzed over a period of two months (February 1, 2020 to April 30, 2020) and the following words were used: prolotherapy, regenerative injection therapy and chronic musculoskeletal pain. Based on the information obtained, a bibliographic review of a total of 203 articles published in the PubMed, Hinari, SciELO and Medline databases was carried out using the search manager and reference manager EndNote, 39 selected citations were used to make the review, including 32 of the last five years, also consulted a book. The concentrations to be used both intra and periarticular, indications and mechanisms of action are mentioned. The frequency of its application is described, as well as the comparison with other intra-articular treatment methods. Reference is made to the duration of its effect and complications. Prolotherapy by administering intra-articular hypertonic dextrose is a useful method in the treatment of patients with gonarthrosis, its easy application, availability and low complication rate make it a feasible and effective conservative method.

Application of Botulinum Toxin in Musculoskeletal Disorders

Chapter

Jan 2022

IonicRF™: a Novel Step in Technology for Radiofrequency Ablation Treatments

Article

Jan 2022

Radiofrequency ablation (RFA) has been utilized since the 1970s to treat various painful conditions. The technology has evolved from its initial use to treat lumbar facet mediated pain with monopolar lesioning to now treat a plethora of chronic pain conditions. This article reviews Abbott Corporation's (IL, USA) IonicRF™ generator. The IonicRF generator utilizes an intelligent power algorithm that improves efficiency and reduces procedure time. The generator also carries a wide range of RFA therapies such as monopolar, bipolar, pulsed or pulsed dose radiofrequency. Additionally, the IonicRF RFA generator is compatible with the Simplicity™ RF probe (Abbott) which allows for efficient and effective denervation of the sacroiliac joint.

Survey of Platelet-Riched Plasma Injection with and without Calcium Gluconate in Treatment of Patients with Knee Osteoarthritis

Article

Full-text available

Feb 2021

Introduction: The most common cause of knee pain is knee osteoarthritis, many surgical and non‐surgical treatments have been proposed but the preferred treatment remains unknown. One of the non‐surgical treatments was PRP (plasma reach platate) injection in these patients. Various studies have shown the improvement of the effect of PRP injection with substances such as calcium gluconate, so the aim of this study was to evaluate the effect of PRP with and without calcium gluconate on the clinical results of intra‐articular injection of this substance in patients with knee osteoarthritis. Methods: This was a cohort study in which patients were divided into two groups: PRP injection and PRP injection with calcium gluconate. The results of the study were evaluated by KOOS questionnaire and pain by VAS. A significance level of 0.05 was considered. Result: Generally, during the study, the pain level in patients after receiving both treatments significantly decreased during the six‐month period, while the pain in the case group significantly decreased. (P Value <0.05). Discussion: From the results of this study, it can be concluded that simultaneous injection of PRP and calcium gluconate can further improve the results of injection. Key words: Platelet‐Rich Plasma,Knee, Osteoarthritis of knee,Calcium Gluconate,Conservative Treatment

Evaluation of the effect of a three-color ladder management model for knee osteoarthritis in the community

Article

Apr 2021

Objective: To explore the application effect of a three-color ladder management system for knee osteoarthritis in the community. Methods: Eighty-six patients with knee osteoarthritis in our community were obtained for study and randomly grouped. The control group received routine management, while the research group received three-color ladder management for 12 months. The knee joint function (WOMAC score), pain degree (VAS score), joint flexibility, health-related behavior score, self-care ability scale (exercise of self-care agency scale (ESCA) score), quality of life (knee osteoarthritis quality of life scale (AIMS2-SF) score) and knee replacement rate were compared between the two groups before and after management, and the changes of patients' visits and treatment costs before and after management were observed. Results: After 12 months, the scores of WOMAC and VAS in the research group were significantly lower than those of the control group (P<0.05), while the scores of joint flexibility and extension, cognition, behavior and condition of Omaha System health-related behaviors, ESCA and AIMS2-SF were significantly higher than those of the control group (P<0.05). After 12 months, the monthly visits and expenses of green cards, yellow cards and red cards in the research group were significantly lower than those before entering the group (P<0.05). After 12 months, the knee replacement rate was 20.93% (9/43) in the research group, while it was 27.91% (12/43) in the control group, with no significant difference between the two groups (P>0.05). Conclusion: The three-color ladder management system for knee osteoarthritis patients in the community can reduce the number of doctor visits and overall expenses, improve knee joint function, reduce pain, improve self-management ability and quality of life, and it has high community popularization.

History of regenerative medicine in the field of orthopedics

Article

Full-text available

Jun 2020

The demand and surge of regenerative medical treatments for various musculoskeletal disorders and injuries have increased exponentially in the recent past. We have reviewed the evolution of these treatments, from the past to the present times. This era has seen a paradigm shift from the replacement to regenerative methods of treatment for many orthopedic disorders. The regenerative medicine helps in restoring the natural tissue in the body at the diseased area. From the ancient methods of provoking tissue healing by noxious stimuli, now, many sophisticated and scientifically proven techniques of regeneration of tissues have come up and are being used globally. Cell therapies have been used as a treatment for a variety of musculoskeletal pathologies including osteoarthritis, cartilage defects, tendinopathies, delayed union and non-unions, non-union of fractures, and treatment of avascular necrosis of femoral head and other bones. Cellular therapies, with or without tissue engineering, seem to the future of regenerative medicine and these may make the replacement of a diseased joint or bone redundant in the near future.

Efficacy of Intra-Articular Hypertonic Dextrose (Prolotherapy) for Knee Osteoarthritis: A Randomized Controlled Trial

Article

May 2020

Purpose: To test the efficacy of intra-articular hypertonic dextrose prolotherapy (DPT) vs normal saline (NS) injection for knee osteoarthritis (KOA). Methods: A single-center, parallel-group, blinded, randomized controlled trial was conducted at a university primary care clinic in Hong Kong. Patients with KOA (n = 76) were randomly allocated (1:1) to DPT or NS groups for injections at weeks 0, 4, 8, and 16. The primary outcome was the Western Ontario McMaster University Osteoarthritis Index (WOMAC; 0-100 points) pain score. The secondary outcomes were the WOMAC composite, function and stiffness scores; objectively assessed physical function test results; visual analogue scale (VAS) for knee pain; and EuroQol-5D score. All outcomes were evaluated at baseline and at 16, 26, and 52 weeks using linear mixed model. Results: Randomization produced similar groups. The WOMAC pain score at 52 weeks showed a difference-in-difference estimate of -10.34 (95% CI, -19.20 to -1.49, P = 0.022) points. A similar favorable effect was shown on the difference-in-difference estimate on WOMAC function score of -9.55 (95% CI, -17.72 to -1.39, P = 0.022), WOMAC composite score of -9.65 (95% CI, -17.77 to -1.53, P = 0.020), VAS pain intensity score of -10.98 (95% CI, -21.36 to -0.61, P = 0.038), and EuroQol-5D VAS score of 8.64 (95% CI, 1.36 to 5.92, P = 0.020). No adverse events were reported. Conclusion: Intra-articular dextrose prolotherapy injections reduced pain, improved function and quality of life in patients with KOA compared with blinded saline injections. The procedure is straightforward and safe; the adherence and satisfaction were high.

Knee and Shoulder joint pain-Tata Motors Hospital

Conference Paper

Full-text available

Apr 2019

Ashok Jadon

Changing life style have changed the pattern of patients coming with complaints of pain in our pain clinic. The prevalence of Knee pain and shoulder pain is increasing day by day. Previously 80% of our patients were coming with back pain and 20% with pains of other body parts. Now, 50% of patients coming to us either knee pain or shoulder pain (with or without neck pain). This article is focussed on available modern treatment of pain relief in knee and shoulder pain conditions.

Prolotherapy: Practices, Experiences and Observations Concerning Adverse Effects of Physician in Turkey

Article

Full-text available

Jan 2019

Dextrose prolotherapy for rotator cuff lesions: the challenges and the future

Article

Full-text available

Oct 2018

Radiofrequency techniques to treat chronic knee pain: a comprehensive review of anatomy, effectiveness, treatment parameters, and patient selection

Article

Full-text available

Sep 2018

Background The use of radiofrequency ablation (RFA) procedures to treat chronic knee pain has surged in the past decade, though many questions remain regarding anatomical targets, selection criteria, and evidence for effectiveness. Methods A comprehensive literature review was performed on anatomy, selection criteria, technical parameters, results of clinical studies, and complications. Databases searched included MEDLINE and Google Scholar, with all types of clinical and preclinical studies considered. Results We identified nine relevant clinical trials, which included 592 patients, evaluating knee RFA for osteoarthritis and persistent postsurgical pain. These included one randomized, placebo-controlled trial, one randomized controlled trial evaluating RFA as add-on therapy, four comparative-effectiveness studies, two randomized trials comparing different techniques and treatment paradigms, and one non-randomized, controlled trial. The results of these studies demonstrate significant benefit for both reduction and functional improvement lasting between 3 and 12 months, with questionable utility for prognostic blocks. There was considerable variation in the described neuroanatomy, neural targets, radiofrequency technique, and selection criteria. Conclusion RFA of the knee appears to be a viable and effective treatment option, providing significant benefit to well-selected patients lasting at least 3 months. More research is needed to better identify neural targets, refine selection criteria to include the use of prognostic blocks, optimize treatment parameters, and better elucidate relative effectiveness compared to other treatments.

Efficacy of intra-articular hypertonic dextrose prolotherapy versus normal saline for knee osteoarthritis: A protocol for a triple-blinded randomized controlled trial

Article

Full-text available

May 2018
BMC Compl Alternative Med

Background: Knee Osteoarthritis (KOA) is a very common condition with prevalence rising with age. It is a major contributor to global disability and has a large socioeconomic burden worldwide. Conservative therapies have marginal effectiveness, and surgery is reserved for severe symptomatic KOA. Dextrose Prolotherapy (DPT) is an evidence-based injection-based therapy for chronic musculoskeletal conditions including KOA. The standard "whole joint" injection method includes intra-articular injection and multiple extra-articular injections at soft tissue bony attachments. The procedure is painful and requires intensive procedural training often unavailable in conventional medical education, which potentially limits access. Intra-articular injection offers the possibility of a less painful, more accessible treatment. The aim of this project is to assess the clinical efficacy of intra-articular injection of DPT versus normal saline (NS) for KOA. Method: Seventy-six participants with KOA will be recruited from the community. We will conduct a single center, parallel group, superiority randomized controlled trial comparing DPT and NS injections, with blinding of physician, participants, outcome assessors and statisticians. Each group will receive injections at week 0, 4, 8 and 16. The primary outcome will be the Western Ontario McMaster University Osteoarthritis Index pain scale (WOMAC), and secondary outcomes include WOMAC composite score, the WOMAC function and stiffness subscale, the Visual Analogue Score of pain, objective physical function tests (the 30 s chair stand, 40- m fast paced walk test, the Timed up and go test) and the EuroQol-5D (EQ-5D). All outcomes will be evaluated at baseline, and 16, 26 and 52 weeks. All analyses will be conducted on an intention-to-treat basis using linear mixed regression models. Discussion: This paper presents the rationale, design, method and operational aspects of the trial. The findings will determine whether IA DPT, an inexpensive and simple injection, is a safe and effective non-surgical option for KOA. The results can be translated directly to clinical practice, with potentially substantial impact to patient care. Trial registration: The trial ( ChiCTR-IPC-15006617 ) is registered under Chinese Clinical Trials Registry on 17th June 2015.

The Effect of Intra-Articular Injection of Hypertonic Saline Versus Dextrose Prolotherapy for Knee Osteoarthritis

Article

Full-text available

Jun 2024

Background: Knee osteoarthritis (OA) is the most common chronic arthritis worldwide, often causing knee stiffness, pain, and functional impairment. This study aims to compare the effects of Dextrose prolotherapy and Hypertonic saline prolotherapy on knee pain, stiffness, and function in patients with knee OA. Methods: The study was conducted as a randomized clinical trial. Patients meeting radiological and clinical criteria for knee OA were sequentially contacted and provided written informed consent. Participants were randomly assigned to receive injections of Hypertonic saline (n = 30) or dextrose prolotherapy (n = 33). The primary outcome measure was clinical manifestations assessed using the compound score of the Western Ontario and McMaster University Arthritis Index (WOMAC). Results: Within-group analysis revealed significant differences in outcome scores for both treatments after 6 months. Both Hypertonic saline and dextrose prolotherapy showed significant improvements in the Visual Analog Scale (VAS), WOMAC composite score, pain, stiffness, and function. In the first month, VAS scores were higher with hypertonic saline compared to dextrose. Additionally, stiffness decreased more with dextrose than with hypertonic saline. After 6 months of treatment, although not statistically significant, hypertonic saline showed better outcomes in the mean WOMAC composite score and pain sub-score compared to dextrose. Conclusions: Among patients with knee OA, Hypertonic saline prolotherapy administered by a trained specialist yields safe and significant improvements in knee pain, stiffness, and function. Our results suggest no significant difference in VAS and WOMAC scores between hypertonic saline and dextrose prolotherapy.

Interventional Techniques for the Management of Knee Osteoarthritis: A Literature Review

Article

Full-text available

Oct 2023

Osteoarthritis of the knee is a prevalent condition that causes pain, discomfort, and disability that can severely impact the quality of life. This literature review aims to review the various interventional pain management techniques available to treat knee osteoarthritis. It analyzes the efficacy of various interventions such as intra-articular corticosteroids, prolotherapy, viscosupplementation, platelet-rich plasma, and genicular nerve blocks with radiofrequency ablation or cryoneurolysis. We searched databases for studies published in the past 20 years. A total of 37 articles were included. The literature supports the idea that a comprehensive treatment plan consisting of the various aforementioned techniques can provide relief for patients while delaying or avoiding joint replacement surgery.

A comparative analysis of prolotherapy efficacy in patients with knee osteoarthritis across varied dextrose concentrations

Article

Aug 2023
CLIN RHEUMATOL

Objective: To compare the effectiveness of prolotherapy with dextrose concentrations of 5%, 10%, and 20% in patients diagnosed with knee osteoarthritis. Methods: This study was planned as a prospective, randomized controlled interventional trial. Prolotherapy at 5% dextrose concentration in group 1, 10% in group 2, and 20% in group 3 was applied to the knee intra-articularly and periarticularly at 0, 3, and 6 weeks, and a home exercise program was given. Group 4 received a home exercise program. All groups received hotpack therapy at weeks 0, 3, and 6. Outcome measures included the visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), knee range of motion, timed up and go test, and Short Form-36. Results: A total of 128 patients were divided into 4 groups. At the 6th and 12th weeks, VAS scores were significantly lower in groups 2 and 3 than in group 4 (p < 0.05). At the 12th week, the WOMAC pain score was significantly lower in group 3 than in group 4, and WOMAC physical function and WOMAC total scores were significantly lower in groups 1, 2, and 3 than in group 4 (p < 0.05). Week 6 active and passive knee flexion and week 12 passive knee flexion were significantly higher in group 3 than in group 4 (p < 0.05). Conclusions: Although no significant difference was observed among the dextrose prolotherapy groups, higher dextrose concentrations demonstrated a greater improvement compared to the control group. Therefore, the use of 20% dextrose is recommended due to its significant superiority. Long-term follow-up and placebo-controlled studies are needed. Trial registration: ClinicalTrial.gov Identifier: NCT05537077, registration date: 09.03.2022, retrospectively registered. Key Points • The utilization of dextrose prolotherapy has gained popularity in the management of osteoarthritis, aiming to harness its regenerative and proliferative properties. However, the comparative efficacy of various concentrations of dextrose prolotherapy in treating knee osteoarthritis remains unexplored in the literature. This study aimed to address this gap by comparing different concentrations of dextrose prolotherapy in the treatment of knee osteoarthritis. The findings revealed no statistically significant difference among the various concentrations of dextrose prolotherapy for knee osteoarthritis treatment.

Effectiveness of Different Concentrations of Dextrose Prolotherapy in Osteoarthritis Knee: A Double-Blind Randomised Comparative Study

Article

Dec 2022

Background Intra-articular dextrose prolotherapy (DPT) is reported to improve the outcomes in the treatment of the osteoarthritis (OA) knee. Outcomes may be variable as per the concentration of the agent, scales for evaluation, patients’ perception and severity of the disease. Methods This was a double-arm double-blind randomised prospective study. As per computer-generated randomisation, participants were divided into two Groups A and B and subjected to four intra-articular injections either of 12.5% or 25% dextrose, respectively, at 0, 3 rd , 6 th and 9 th week. Outcomes are measured by two scales, i.e., Visual Analogue Scale (VAS) at all subsequent visits, 12 th and 20 th week, and knee injury osteoarthritis outcome score (KOOS) (five subscales) at baseline and 20 th week (at 95% confidence interval, and P < 0.05 significant). A common exercise regimen was given to both groups. Results A total of 78 patients were enrolled, out of which only 50 participants (25 in each group) completed the study. Both the treatment arms were age- and sex-matched with a female preponderance of 64% and males 36%. Following treatment, the VAS score of both the groups showed parallel improvement in the first three visits, but Group B was found to be statistically significant for 9 th week ( P = 0.024) onwards ( P = 0.0071 at 12 th and P = 0.013 at 20 th week). The KOOS score also improved in both groups but the Group B had a superior effect compared with Group A in all the subscales ( P < 0.05). Conclusion Intra-articular DPT improves the symptomatic picture of patients with OA knee in a concentration-dependent manner. It also showed a dose–response relationship following serial injections on VAS. DPT is found to be cost-effective, safe and beneficial therapy for OA knee.

Therapeutic Dextrose Injection: Prolotherapy, Perineural Injection Therapy, and Hydrodissection

Chapter

Mar 2022

In the search for biologically active, disease-modifying treatment modalities for chronic pain, three forms of dextrose injection—prolotherapy, perineural injection therapy, and hydrodissection—have emerged as effective for many conditions. Each is discrete but related by the injectant (dextrose) and the clinical tradition from which each is derived. This chapter reviews the origins of dextrose-related injection therapy, outlines the basic science and clinical evidence behind each, and describes the role of ultrasound guidance in the clinical conduct of each.

Effects of Intra-Articular Coinjections of Hyaluronic Acid and Hypertonic Dextrose on Knee Osteoarthritis: A Prospective, Randomized, Double-Blind Trial

Article

Apr 2022
ARCH PHYS MED REHAB

Objective To determine whether intra-articular coinjection with hypertonic dextrose improves the outcome of hyaluronic acid (HA) prolotherapy for knee osteoarthritis Design Prospective, randomized, double-blind trial Setting Medical center in Taiwan Participants In total, 104 participants who fulfilled the American College of Rheumatology clinical and radiographic criteria for knee osteoarthritis with a Kellgren-Lawrence score of 2 or 3 were recruited. Interventions The participants were blocked randomized to the treatment (HA/hypertonic dextrose) or control (HA/normal saline) group. Ultrasound-guided knee intra-articular injections were administered once a week for 3 weeks. Main Outcome Measures The primary outcomes were performance-based physical function measures (regular and fastest walking speed, stair-climbing time, and chair-rising time), and the secondary outcomes were the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Injury and Osteoarthritis Outcome (KOOS). The outcome measures were assessed before the injections and at 1 week and 1, 3, and 6 months after the injections. The data were analyzed through repeated-measures analysis of covariance. Results Significant intergroup difference-in-differences favoring the treatment group were observed for improvements in stair-climbing time (−1.6, 95% CI: −0.38 to −1.17, P = .38) and WOMAC physical function (−21.1, 95% CI: −1.85 to 0.94, P = .045) at 6 months. The group × time interaction effects favored the treatment group for regular (P = .001) and fastest walking speed (P = .001), chair-rising time (P = .038); WOMAS stiffness (P < .001) and physical function (P = .003); and KOOS for pain (P = .035), other symptoms (P = .022), and quality of life (P = .012). Conclusions Compared with HA plus normal saline coinjections, HA plus dextrose coinjections resulted in more significant improvements in stair-climbing time and physical function at 6 months, effectively decreased pain, and improved physical function and physical functional performance from 1 week to 6 months. HA plus dextrose coinjections could be a suitable adjuvant therapy for patients with knee osteoarthritis.

Identification of early response to hypertonic dextrose prolotherapy markers in knee osteoarthritis patients by an inflammation-related cytokine array

Article

Jan 2022

Background: Osteoarthritis (OA) is one of the most common forms of arthritis, and hypertonic dextrose prolotherapy has long been used clinically to treat knee OA. The aim of this study was to investigate the inflammation-related protein-expression profile characterizing the efficacy of the hypertonic dextrose prolotherapy in knee OA as prognostic markers. Methods: OA patients over the age of 65 were recruited for Western Ontario McMaster University Osteoarthritis (WOMAC) index, knee X ray evaluation and knee joint synovial fluid analysis before and after hypertonic dextrose prolotherapy. The expressions of inflammation-related factors were measured using a novel cytokine antibody array methodology. The cytokine levels were quantified by quantitative protein expression and analyzed by ELISA using the patients' knee-joint synovial fluid. Results: The WOMAC Index and minimum joint space width prior to receiving the intra-articular injection and at 2-week intervals were compared. 12 patients who received OA intervention were enrolled and finally a clinical evaluation of 12 knee joints and knee synovial fluid samples were analyzed. In this study, after receiving hypertonic dextrose prolotherapy, the OA patients clearly demonstrated a significant improvement in WOMAC index and increasing tendency in the medial minimum joint space width after intervention. Meanwhile, we observed a significantly associated tendency between the high-glucose treatment of knee OA and the upregulation of MMP2, TIMP-1, EGF, CXCL9 and IL-22. Conclusion: These findings provide knee OA patients receiving hypertonic dextrose prolotherapy, which accompanying with the improvement of knee pain, stiffness, and function and increasing tendency in the medial minimum joint space width.

Imaging-Guided Palliative Procedures: Tendon and Bursa Injection

Chapter

Mar 2021

Musculoskeletal pain and inflammation is a common problem in patients post both chemotherapy and radiotherapy and may occur as a direct result of the drugs, radiation, and surgery or may reflect exacerbation of pre-existing tendinopathy and bursitis.

Extracorporeal Shockwave Therapy With a Modified Technique on Tendon and Ligament for Knee Osteoarthritis: A Randomized Controlled Trial

Article

Feb 2021

Background: There have been no definitive guidelines on the treatment method and specific points in the body. Purpose: The aim of the study was to investigate the effects of extracorporeal shockwave therapy on treating the main tendons and ligaments of knee osteoarthritis. Method: A total of 36 patients with knee osteoarthritis were enrolled in trial and organized into two groups: 3-wk extracorporeal shockwave therapy for the intervention group and 3-wk sham extracorporeal shockwave therapy for control group. Both groups received the same physical therapies: (1) transcutaneous electrical nerve stimulation, (2) magnetic field treatment, and (3) quadricep muscle strength training. Evaluation was performed before the start of treatment, at third week after the start of treatment, and 1 wk after the end of treatment. The study used randomized controlled trials (level of evidence, 1). Result: Eextracorporeal shockwave therapy group had significant improvement in WOMAC pain score, physical function, and total score (mean difference = -2.8, P < 0.001; -5.1, P = 0.02; -8.3, P = 0.004, respectively), Visual Analog Scale score (mean difference = -2.3, P < 0.001), and the distance of 6-min walk test (mean difference = 28.7, P = 0.01) in the 1 wk after the end of treatment. Statistical significance in WOMAC pain, physical function, and total scores (mean difference = -3.0, P = 0.001; -5.6, P = 0.02; -9.3, P = 0.004, respectively) and Visual Analog Scale score (mean difference = -1.2, P = 0.027) was observed between the extracorporeal shockwave therapy group and control group. Conclusions: Extracorporeal shockwave therapy for the tendons and ligaments has clinical benefits for pain and physical function improvement in knee osteoarthritis. In addition, improvement in physical performance was observed in the short-term follow-up.

Whiplash Injury Successfully Treated with Prolotherapy: A Case Report with Long-Term Follow Up

Article

Sep 2020

Background: Chronic whiplash-associated disorder (WAD) can develop after flexion/extension injuries and may be refractory to standard-of-care therapies. Aim: To present successful treatment of severe, longstanding, treatment resistant WAD with prolotherapy. Materials & methods: Four, monthly sessions of fluoroscopically guided prolotherapy with phenol-glycerin-glucose. Electronic data on pain (visual analog score), disability (Oswestry Disability Index), pain interference, depression, anxiety, sleep and quality of life were collected with University of Washington’s (WA, USA) online tool for a total of 21 months. This study conforms to the Case Report Guidelines (CARE). Results: Significant improvement was achieved and maintained through 18 months after treatment in all assessed pain and functional measures. Conclusion: Regenerative medicine, including prolotherapy may be an appropriate treatment option for carefully selected patients with WAD.

Rheumatologic Rehabilitation

Chapter

Jan 2021

Rheumatology is a branch of medicine devoted to the evaluation, diagnosis, and management of musculoskeletal disorders or other connective diseases, including arthritis and sort tissue lesions. This chapter emphasizes diagnosis, evaluation, medical management, and rehabilitation of arthritis. For diagnosis of arthritis, a combination of history-taking and physical examination is the first step, followed by laboratory tests and image studies, if necessary. Evaluation of rheumatic disease may follow the model of the International Classification of Functioning, Disability and Health (ICF). The medical treatment of rheumatic disease includes analgesics, nonsteroidal antiinflammatory drugs (oral or topical use), corticosteroids (oral or local use), opioids, duloxetine, hyaluronic acid, hypertonic glucose, platelet-rich plasma, and disease-modifying antirheumatic drugs (DMARDs). Over the past two decades many DMARDs have been developed, including conventional synthetic, target synthetic, and biologic DMARDs, which can modify the disease course, although both minor and serious side effects exist. In patients with intractable pain, severe joint destruction, or poor response to long-term medical treatment and rehabilitation, surgery may be considered. Surgical techniques include total joint replacement, osteotomy, lavage and debridement, arthrodesis, tendon repair, and synovectomy. Among them, total joint replacement has been proven effective for different types of arthritis. In this chapter, common types of arthritis and rehabilitation interventions for arthritis, including exercise, physical modalities, orthoses, patient education, energy conservation techniques, and joint protection principles, are introduced, and the principles of rehabilitation for arthritis are reviewed, especially regarding osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis.

Clinical Applications of Dextrose Prolotherapy in Sports

Chapter

Sep 2020

Prolotherapy is applied in a form of injections to tendons, ligaments, muscles, capsules, and joints. It can provide benefits to patients suffering shoulder, elbow, wrist/hand, hip, knee, and ankle/foot pain. Neck and back injuries are also treated with prolotherapy. This chapter explains in detail what are the most common sports injuries affecting peripheral joints, the mechanism of their onset, and how dextrose prolotherapy can help in their management.

The Use of Augmented Reality to Raise Awareness of the Differences Between Osteoarthritis and Rheumatoid Arthritis

Chapter

Jul 2020
ADV EXP MED BIOL

Arthritis is one of the most common disease states worldwide but is still publicly misunderstood and lacks engaging public awareness materials. Within the UK, the most prevalent types of arthritis are osteoarthritis (OA) and rheumatoid arthritis (RA). The two are commonly mistaken as the same disease but, in fact, have very different pathogenesis, symptoms and treatments. This chapter describes a study which aimed to assess whether an augmented reality (AR) application could be used to raise awareness about the difference between OA and RA.

Physical therapy, intra-articular dextrose prolotherapy, botulinum neurotoxin, and hyaluronic acid for knee osteoarthritis: Randomized clinical trial

Article

Apr 2020
INT J REHABIL RES

This study aimed to compare the efficacy of four treatments in the management of knee osteoarthritis. We carried out a randomized clinical trial with four study arms in an outpatient Department of Physical Medicine and Rehabilitation at a University Hospital. In total, 120 patients with knee osteoarthritis ≥50 years of age were randomly allocated to four groups. The primary outcome was knee pain in visual analog scale and the secondary outcome was the Knee Injury and Osteoarthritis Outcome Score. The exercise was prescribed daily for all participants throughout the study. For physical therapy (group 1), participants received superficial heat, transcutaneous electrical nerve stimulation and pulsed ultrasound. We administered a single intra-articular injection of botulinum neurotoxin type A (group 2) and three injections of hyaluronic acid (group 3) or 20% dextrose (group 4) to patients in the corresponding groups. Mixed analysis of variance showed that there was statistically significant difference between the groups in pain (P < 0.001), and Knee Injury and Osteoarthritis Outcome Score (P < 0.001). Pairwise between- and within-group comparisons showed that botulinum neurotoxin and dextrose prolotherapy were the most, and hyaluronic acid was the least efficient treatments for controlling pain and recovering function in patients. An intra-articular injection of botulinum toxin type A or dextrose prolotherapy is effective first-line treatments. In the next place stands physical therapy particularly if the patient is not willing to continue regular exercise programs. Our study was not very supportive of intra-articular injection of hyaluronic acid as an effective treatment of knee osteoarthritis.

Is prolotherapy effective in reducing pain and improving function in patients with knee OA?

Article

Jul 2019

Kas İskelet Sistemi Ağrılarında Proloterapi Enjeksiyonları

Article

Sep 2019

Ilker Solmaz

Proloterapi, az miktarda irritan solüsyonun normal hücre ve doku büyümesini uyarmak amacıyla ağrılı, hasarlı veya dejenere olmuş tendon ve ligamentlerin yapışma bölgelerine (entezis) uygulandığı enjeksiyonları içeren rejeneratif bir tedavi yöntemidir. Bu yöntem kas iskelet sistemi kaynaklı ağrıların tedavisinde 80 yıldan uzun süredir kullanılmaktadır. Proloterapi’nin kas iskelet sistemi sorunlarında kullanımı, ağrının ligamentlerdeki zayıflama sonucu ortaya çıkan relaksasyona bağlı olduğu ve bu ligamentlerin tahriş edici, hücre proliferasyonunu uyarıcı solüsyonların enjeksiyonları ile güçlendirilebileceği düşüncesine dayandırılmaktadır.Ligament relaksasyonu; genel olarak ligament içeriğindeki liflerin dayanıklılığının bozulduğu durum olarak tanımlanmaktadır. İrritan solüsyonların enjeksiyonları ile tendon ve ligamentlerde fibroblast hiperplazisi, hücre proliferasyonu, kollojen lif çapında artış gibi histolojik yapısal değişikliklerin yanısıra tendon ve ligament gücünde artış da gözlenmektedir. Bu etki, yara iyileşme mekanizmasının tetiklenmesine bağlı oluşmaktadır.Proloterapi enjeksiyonlarının eklem ağrıları ve eklem laksitesi, kronik bel ağrısı, epikondilit, tendinopatiler, aşırı kullanım yaralanmaları gibi kas iskelet sistemi sorunlarındaki etkinliğini araştıran çalışmaların artması ile birlikte son dönemde bu rejeneratif tedavi yöntemine ilgi giderek artmaktadır.

Prolotherapy for Musculoskeletal Pain and Disability in Low- and Middle-Income Countries

Article

Aug 2019
Phys Med Rehabil Clin

Chronic musculoskeletal pain and disability dramatically reduce quality and quantity of life worldwide, disproportionately so in low- and middle-income countries. Complementary therapies not typically learned in conventional medical training have much to offer but are under-utilized. Prolotherapy is an injection-based complementary therapy supported by high-quality evidence for osteoarthritis, tendinopathy, and low back pain. Prolotherapy addresses causes of pain and disability at the tissue level, is straightforward to learn, and relies on common, inexpensive material, and requires no refrigeration. Not-for-profit organizations are delivering prolotherapy to underserved patients in low- and middle-income countries through service-learning projects.

Image guided injection therapies in athletes—Do they work and what should we be using?

Article

Dec 2018
EUR J RADIOL

In the modern management of the injured elite athlete, the goals of guided injection therapies have extended beyond simple reduction of pain to enhancement of tissue healing and accelerated return to competition, faster than natural healing can allow. This article will review the injection therapies which are frequently used in elite sports injury management and describe other less commonly used injection therapies that are available to the treating clinician and athlete. The evidence base, where available, for each treatment option will be summarised.

Initial treatment of complete rotator cuff tear and transition to surgical treatment: systematic review of the evidence

Article

Full-text available

Jun 2016

Background: rotator cuff tear affects many peo- ple. Natural history, and evidence for non-opera- tive treatment remains limited. Our objective is to assess evidence available for the efficacy and morbidity of commonly used systemic medica- tions, physiotherapy, and injections alongside evaluating any negative long-term effects. Methods: a systematic search was performed of PubMed, Cochrane, EMBASE and CINAHL dates (1 January 1960 - 1 December 2014), search terms: ‘rotator cuff tear’, ‘natural history’, ‘atraumatic’, ‘in- jection’, ‘physiotherapy’or ‘physical therapy’, ‘injec- tion’, ‘corticosteroid’, ‘PRP‘, ‘MSC’, risk of conserv- ative treatment’, and ‘surgical indication’. Results: eleven studies were included. The mean Coleman Methodology Score modified for conser- vative therapy is 69.21 (range 88-44) (SD 12.31). This included 2 RCTs, 7 prospective, and 2 retro- spective studies. Evidence suggests it is safe to monitor symptomatic rotator cuff tears, as tear size and symptoms are not correlated with pain, function, and/or ultimate outcome. Conclusions: complete rotator cuff tears may be ef- fectively treated with injections, exercise in the short and intermediate terms respectively. Negative effect of corticosteroids on rotator cuff tissue has not been demonstrated. Timing to end conservative treatment is unknown, but likely indicated when a patient demonstrates increased weakness and loss of function not recoverable by physiotherapy.

Healing effects of prolotherapy in treatment of knee osteoarthritis healing effects of prolotherapy in treatment of knee osteoarthritis

Article

Full-text available

Apr 2016

Purpose Prolotherapy is an injection therapy for chronic musculoskeletal pain. We conducted a two-arm controlled trial to assess the efficacy of prolotherapy for knee osteoarthritis (OA). Materials and methods A total of 104 adults with at least 6 months of painful primary knee OA were treated with dextrose prolotherapy (group I). They were divided into two subgroups: Ia and Ib. Subgroup Ia was treated with both techniques of prolotherapy (Hackett technique - classic, traditional prolotherapy - and Lyftgot technique - neural prolotherapy), whereas subgroup Ib was treated with the Hackett technique only. Extra-articular and intra-articular injections were administered at 1, 2, and 3 months, with as needed additional treatments at months 4 and 5. A total of 24 adults with at least 6 months of painful primary knee OA were treated with physiotherapy (group II). Outcome measures included the following: clinical assessment; visual analogue scale (VAS), 10; Western Ontario McMaster University Osteoarthritis Index (WOMAC), 96 points; plain radiographs; and musculoskeletal ultrasound. Postprocedure hot packs were applied, and at-home massage and exercises were taught. Results 128 Patients enrolled in the study were matched with each other for sex, age, disease durations, and BMI. Subgroups Ia and Ib reported a significant improvement as regards the clinical assessment, VAS, WOMAC, and radiological assessment at 12 months, compared with their baseline at month 0 and compared with group II (P ≤ 0.001). At 12 months, the mean ± SD of VAS was 0.32 ± 0.27 for subgroup Ia, 0.44 ± 0.5 for subgroup Ib, and 9.9 ± 1.65 for group II, and the mean ± SD of WOMAC was 11.32 ± 10.3 for subgroup Ia, 18.5 ± 10.25 for subgroup Ib, and 79.5 ± 22.63 for group II. Postprocedure application of hot packs, massage, and paracetamol resulted in diminution of injection-related pain. There were no adverse events. Conclusion Prolotherapy resulted in clinically sustained improvement of pain, function, and radiological assessment, which means that the healing effects of prolotherapy is better than that of physiotherapy. The combination of the two prolotherapy techniques Results in quicker and better improvement for patients in terms of the clinical assessment, VAS, and WOMAC.

Hypertonic dextrose injections (prolotherapy) in the treatment of symptomatic knee osteoarthritis: A systematic review and meta- analysis

Article

Full-text available

May 2016

Hypertonic dextrose injections (prolotherapy) is an emerging treatment for symptomatic knee osteoarthritis (OA) but its efficacy is uncertain. We conducted a systematic review with meta-analysis to synthesize clinical evidence on the effect of prolotherapy for knee OA. Fifteen electronic databases were searched from their inception to September 2015. The primary outcome of interest was score change on the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Three randomized controlled trials (RCTs) of moderate risk of bias and one quasi–randomized trial were included, with data from a total of 258 patients. In the meta-analysis of two eligible studies, prolotherapy is superior to exercise alone by a standardized mean difference (SMD) of 0.81 (95% CI: 0.18 to 1.45, p = 0.012), 0.78 (95% CI: 0.25 to 1.30, p = 0.001) and 0.62 (95% CI: 0.04 to 1.20, p = 0.035) on the WOMAC composite scale; and WOMAC function and pain subscale scores respectively. Moderate heterogeneity exists in all cases. Overall, prolotherapy conferred a positive and significant beneficial effect in the treatment of knee OA. Adequately powered, longer-term trials with uniform end points are needed to better elucidate the efficacy of prolotherapy.

Subcutaneous prolotherapy treatment of refractory knee, shoulder, and lateral elbow pain

Article

Full-text available

Jan 2007

John Lyftogt

Therapeutic effects of prolotherapy with intra-articular dextrose injection in patients with moderate knee osteoarthritis: a single-arm study with 6 months follow up

Article

Full-text available

Apr 2015
Ther Adv Musculoskelet Dis

Prolotherapy is an injection-based complementary treatment, which has shown promising results in the treatment of different musculoskeletal disorders. The aim of this study was to determine the therapeutic efficacy of dextrose prolotherapy on pain, range of motion, and function in patients with knee osteoarthritis (OA). In this single-arm prospective study, participants with symptomatic moderate knee osteoarthritis underwent prolotherapy with intra-articular injection of 20% dextrose water at baseline, and at 4 weeks and 8 weeks later. Patients were followed for 24 weeks. Pain severity at rest and activity, according to the visual analog scale (VAS), articular range of motion (ROM), and Western Ontario and McMaster Universities arthritis index (WOMAC) scores were measured at baseline, 4, 8, and 24 weeks later. A total of 24 female patients (average age: 58.37 ± 11.8 years old) received 3-monthly injection therapies. Before the treatment, the mean articular range of motion was 105.41 ± 11.22°. Mean VAS scale at rest and activity was 8.83 ± 1.37 and 9.37 ± 1.31, respectively. At the end of week 24, knee ROM increased by 8°. Pain severity in rest and activity decreased to 4.87 ± 1.39, 45.86%, and 44.23%, respectively (p < 0.001). Total WOMAC score and its subcategories showed a continuous improvement trend in all the evaluation sessions, so that at the end of the study, the total score decreased by 30.5 ± 14.27 points (49.58%) (p < 0.001). Improvements of all parameters were considerable until week 8, and were maintained throughout the study period. Prolotherapy with three intra-articular injections of hypertonic dextrose given 4 weeks apart for selected patients with knee OA, resulted in significant improvement of validated pain, ROM, and WOMAC-based function scores, when baseline levels were compared at 24 weeks. Further studies with randomized controlled trials involving a comparison group are suggested to confirm these findings.

Investigation the efficacy of intra-articular prolotherapy with erythropoietin and dextrose and intra-articular pulsed radiofrequency on pain level reduction and range of motion improvement in primary osteoarthritis of knee

Article

Full-text available

Aug 2014
J Res Med Sci

Osteoarthritis is one of the most common diseases and the knee is the most commonly affected joint. Intra-articular prolotherapy is being utilized in acute and chronic pain management setting. This study was designed to compare the efficacy of three methods of intra-articular knee joint therapies with erythropoietin, dextrose, and pulsed radiofrequency. After approval by the Ethics Committee and explaining the therapeutic method to volunteers, 70 patients who were suffering from primary knee osteoarthrosis went through one of the treatment methods (erythropoietin, dextrose, and pulsed radiofrequency). The study was double-blind randomized clinical trial performed from December 2012 to July 2013. Patients' pain level was assessed through the visual analog pain scale (VAS), and range of motion (ROM) was measured by goniometric method. Furthermore, patients' satisfaction was assessed before and after different treatment methods in weeks 2, 4, and 12. For analysis, Chi-square, one-way ANOVA, and repeated measured ANOVA were utilized. The demographic results among the three groups did not indicate any statistical difference. The mean VAS in erythropoietin group in the 2(nd), 4(th), and 12(th) weeks was 3.15 ± 1.08, 3.15 ± 1.08, and 3.5 ± 1.23, respectively (P ≤ 0.005). Knee joint ROM in the erythropoietin group in the 2(nd), 4(th), and 12(th) weeks was 124 ± 1.50, 124 ± 1.4, and 123 ± 1.53 respectively (P ≤ 0.005). Satisfaction score in the 12(th) week in erythropoietin group was extremely satisfied 15%, satisfied 55%, and moderately satisfied 30%, (P = 0.005). No specific side-effects were observed. Intra-articular prolotherapy with erythropoietin was more effective in terms of pain level reduction and ROM improvement compared with dextrose and pulsed radiofrequency.

Hypertonic Dextrose Injections (Prolotherapy) for Knee Osteoarthritis: Results of a Single-Arm Uncontrolled Study with 1-Year Follow-Up

Article

Full-text available

Apr 2012
J ALTERN COMPLEM MED

The objective of this study was to determine whether prolotherapy, an injection-based complementary treatment for chronic musculoskeletal conditions, improves pain, stiffness, and function in adults with symptomatic knee osteoarthritis (KOA) compared to baseline status. This was a prospective, uncontrolled study with 1-year follow-up. The study was conducted in an outpatient setting. Adults with at least 3 months of symptomatic KOA, recruited from clinical and community settings, participated in the study. Participants received extra-articular injections of 15% dextrose and intra-articular prolotherapy injections of 25% dextrose at 1, 5, and 9 weeks, with as-needed treatments at weeks 13 and 17. Primary outcome measure was the validated Western Ontario McMaster University Osteoarthritis Index (WOMAC). Secondary outcome measure was the validated Knee Pain Scale (KPS). Tertiary outcome measure was procedure-related pain severity and participant satisfaction. Thirty-six (36) participants (60 ± 8.7 years old, 21 female) with moderate-to-severe KOA received an average of 4.3 ± 0.7 prolotherapy injection sessions over a 17-week treatment period and reported progressively improved scores during the 52-week study on WOMAC and KPS measures. Participants reported overall WOMAC score improvement 4 weeks after the first injection session (7.6 ± 2.4 points, 17.2%), and continued to improve through the 52-week follow-up (15.9 ± 2.5 points, p<0.001, 36.1%). KPS scores improved in both injected (p<0.001) and uninjected knees (p<0.05). Prescribed low-dose opioid analgesia effectively treated procedure-related pain. Satisfaction was high and there were no adverse events. Female gender, age 46-65 years old, and body-mass index of 25 kg/m(2) or less were associated with greater improvement on the WOMAC instrument. In adults with moderate to severe KOA, dextrose prolotherapy may result in safe, significant, sustained improvement of knee pain, function, and stiffness scores. Randomized multidisciplinary effectiveness trials including evaluation of potential disease modification are warranted to further assess the effects of prolotherapy for KOA.

The role of intra-articular hyaluronan (Sinovial(A (R))) in the treatment of osteoarthritis

Article

Full-text available

Nov 2010
RHEUMATOL INT

Osteoarthritis (OA) leads to significant pain and disability. For pain relief, a tailored approach using non-pharmacological and pharmacological therapies is recommended. If adequate symptom relief is not achieved with acetaminophen, other pharmacological options include non-steroidal anti-inflammatory drugs (NSAIDs), topical analgesics, intra-articular corticosteroids and intra-articular hyaluronic acid (HA) viscosupplementation. Most of these therapies generally do not improve functional ability or quality of life or are associated with tolerability concerns. In OA patients, concentration and molecular weight (MW) of HA are reduced, diminishing elastoviscosity of the synovial fluid, joint lubrication and shock absorbancy, and possibly anti-inflammatory, analgesic and chondroprotective effects. In knee OA, viscosupplementation with 3-5 weekly intra-articular HA injections diminishes pain and improves disability, generally within 1 week and for up to 3-6 months and is well tolerated. HAs have comparable efficacy as NSAIDs, with less gastrointestinal adverse events, and compared with intra-articular corticosteroids, benefits last generally longer. High MW hylans provide comparable benefits versus HA, albeit with an increased risk of immunogenic adverse events. In mild-to-moderate hip OA, intra-articular injection of HA moderately improved pain and function, generally for up to 3 months with no serious adverse events. Efficacy in other joints is being evaluated. Viscosupplementation with intra-articular Sinovial(®) (other trade names: Yaral(®), Intragel(®)) injections (an HA of low-medium MW) relieves pain and improves function in OA of the knee, and other joints including the carpometacarpal joint of the thumb and the shoulder. HA viscosupplementation, including use of Sinovial(®), is a valuable treatment approach for OA patients, if other therapies are contraindicated or have failed.

Cost-effectiveness of Total Knee Arthroplasty in the United States Patient Risk and Hospital Volume

Article

Full-text available

Jul 2009

Total knee arthroplasty (TKA) relieves pain and improves quality of life for persons with advanced knee osteoarthritis. However, to our knowledge, the cost-effectiveness of TKA and the influences of hospital volume and patient risk on TKA cost-effectiveness have not been investigated in the United States. We developed a Markov, state-transition, computer simulation model and populated it with Medicare claims data and cost and outcomes data from national and multinational sources. We projected lifetime costs and quality-adjusted life expectancy (QALE) for different risk populations and varied TKA intervention and hospital volume. Cost-effectiveness of TKA was estimated across all patient risk and hospital volume permutations. Finally, we conducted sensitivity analyses to determine various parameters' influences on cost-effectiveness. Overall, TKA increased QALE from 6.822 to 7.957 quality-adjusted life years (QALYs). Lifetime costs rose from

37,100 (no TKA) to

57 900 after TKA, resulting in an incremental cost-effectiveness ratio of

18,300 per QALY. For high-risk patients, TKA increased QALE from 5.713 to 6.594 QALY, yielding a cost-effectiveness ratio of

28,100 per QALY. At all risk levels, TKA was more costly and less effective in low-volume centers than in high-volume centers. Results were insensitive to variations of key input parameters within policy-relevant, clinically plausible ranges. The greatest variations were seen for the quality of life gain after TKA and the cost of TKA. Total knee arthroplasty appears to be cost-effective in the US Medicare-aged population, as currently practiced across all risk groups. Policy decisions should be made on the basis of available local options for TKA. However, when a high-volume hospital is available, TKAs performed in a high-volume hospital confer even greater value per dollar spent than TKAs performed in low-volume centers.

A systematic review of four injection therapies for lateral epicondylosis: Prolotherapy, polidocanol, whole blood and platelet-rich plasma

Article

Full-text available

Nov 2008
BRIT J SPORT MED

To appraise existing evidence for prolotherapy, polidocanol, autologous whole blood and platelet-rich plasma injection therapies for lateral epicondylosis (LE). Systematic review. Medline, Embase, CINAHL, Cochrane Central Register of Controlled Trials, Allied and Complementary Medicine. Search strategy: names and descriptors of the therapies and LE. All human studies assessing the four therapies for LE. Results of five prospective case series and four controlled trials (three prolotherapy, two polidocanol, three autologous whole blood and one platelet-rich plasma) suggest each of the four therapies is effective for LE. In follow-up periods ranging from 9 to 108 weeks, studies reported sustained, statistically significant (p<0.05) improvement in visual analogue scale primary outcome pain score measures and disease-specific questionnaires; relative effect sizes ranged from 51% to 94%; Cohen's d ranged from 0.68 to 6.68. Secondary outcomes also improved, including biomechanical elbow function assessment (polidocanol and prolotherapy), presence of abnormalities and increased vascularity on ultrasound (autologous whole blood and polidocanol). Subjects reported satisfaction with therapies on single-item assessments. All studies were limited by small sample size. There is strong pilot-level evidence supporting the use of prolotherapy, polidocanol, autologous whole blood and platelet-rich plasma injections in the treatment of LE. Rigorous studies of sufficient sample size, assessing these injection therapies using validated clinical, radiological and biomechanical measures, and tissue injury/healing-responsive biomarkers, are needed to determine long-term effectiveness and safety, and whether these techniques can play a definitive role in the management of LE and other tendinopathies.

Osteoarthritis: New insights. Part 1: The disease and its risk factors. Annals of Internal Medicine, 133, 635-646

Article

Full-text available

Nov 2000

Osteoarthritis is the most common form of arthritis, affecting millions of people in the United States. It is a complex disease whose etiology bridges biomechanics and biochemistry. Evidence is growing for the role of systemic factors (such as genetics, dietary intake, estrogen use, and bone density) and of local biomechanical factors (such as muscle weakness, obesity, and joint laxity). These risk factors are particularly important in weight-bearing joints, and modifying them may present opportunities for prevention of osteoarthritis-related pain and disability. Major advances in management to reduce pain and disability are yielding a panoply of available treatments ranging from nutriceuticals to chondrocyte transplantation, new oral anti-inflammatory medications, and health education. This article is part 1 of a two-part summary of a National Institutes of Health conference. The conference brought together experts on osteoarthritis from diverse backgrounds and provided a multidisciplinary and comprehensive summary of recent advances in the prevention of osteoarthritis onset, progression, and disability. Part 1 focuses on a new understanding of what osteoarthritis is and on risk factors that predispose to disease occurrence. It concludes with a discussion of the impact of osteoarthritis on disability.

Updated Method Guidelines for Systematic Reviews in the Cochrane Collaboration Back Review Group

Article

Full-text available

Jul 2003
SPINE

Descriptive method guidelines. To help reviewers design, conduct, and report reviews of trials in the field of back and neck pain. In 1997, the Cochrane Collaboration Back Review Group published method guidelines for systematic reviews. Since its publication, new methodologic evidence emerged and more experience was acquired in conducting reviews. All reviews and protocols of the Back Review Group were assessed for compliance with the 1997 method guidelines. Also, the most recent version of the Cochrane Handbook (4.1) was checked for new recommendations. In addition, some important topics that were not addressed in the 1997 method guidelines were included (e.g., methods for qualitative analysis, reporting of conclusions, and discussion of clinical relevance of the results). In May 2002, preliminary results were presented and discussed in a workshop. In two rounds, a list of all possible recommendations and the final draft were circulated for comments among the editors of the Back Review Group. The recommendations are divided in five categories: literature search, inclusion criteria, methodologic quality assessment, data extraction, and data analysis. Each recommendation is classified in minimum criteria and further guidance. Additional recommendations are included regarding assessment of clinical relevance, and reporting of results and conclusions. Systematic reviews need to be conducted as carefully as the trials they report and, to achieve full impact, systematic reviews need to meet high methodologic standards.

Burden of major musculoskeletal conditions

Article

Full-text available

Feb 2003
B WORLD HEALTH ORGAN

Musculoskeletal conditions are a major burden on individuals, health systems, and social care systems, with indirect costs being predominant. This burden has been recognized by the United Nations and WHO, by endorsing the Bone and Joint Decade 2000-2010. This paper describes the burden of four major musculoskeletal conditions: osteoarthritis, rheumatoid arthritis, osteoporosis, and low back pain. Osteoarthritis, which is characterized by loss of joint cartilage that leads to pain and loss of function primarily in the knees and hips, affects 9.6% of men and 18% of women aged > 60 years. Increases in life expectancy and ageing populations are expected to make osteoarthritis the fourth leading cause of disability by the year 2020. Joint replacement surgery, where available, provides effective relief. Rheumatoid arthritis is an inflammatory condition that usually affects multiple joints. It affects 0.3-1.0% of the general population and is more prevalent among women and in developed countries. Persistent inflammation leads to joint destruction, but the disease can be controlled with drugs. The incidence may be on the decline, but the increase in the number of older people in some regions makes it difficult to estimate future prevalence. Osteoporosis, which is characterized by low bone mass and microarchitectural deterioration, is a major risk factor for fractures of the hip, vertebrae, and distal forearm. Hip fracture is the most detrimental fracture, being associated with 20% mortality and 50% permanent loss in function. Low back pain is the most prevalent of musculoskeletal conditions; it affects nearly everyone at some point in time and about 4-33% of the population at any given point. Cultural factors greatly influence the prevalence and prognosis of low back pain.

Managing Osteoarthritic Knee Pain

Article

Full-text available

Nov 2007

Osteoarthritis is one of the most common forms of arthritis seen in primary care practice. Pain associated with this condition is the chief complaint of most patients, prompting them to seek medical attention. Pain can originate from the synovial membrane, joint capsule, periarticular muscles and ligaments, and periosteum and subchondral bone, among other sources. Although osteoarthritis is traditionally thought of as a noninflammatory type of arthritis, inflammatory mechanisms can be present. Therefore, management of osteoarthritic pain involves both nonpharmacologic and pharmacologic modes of therapy. Nonpharmacologic approaches include osteopathic manipulative treatment, physical therapy, exercise, use of assistive devices, and weight reduction. Pharmacologic options may be topical, intra-articular, or oral in route of administration and include acetaminophen, nonsteroidal anti-inflammatory drugs, and opioids. Patients often benefit from combinations of therapeutic modalities. Although pain relief is a chief motivator for patients with osteoarthritis to seek medical attention, a secondary benefit of successful treatment is slowing the decrease in patients' quality of life.

Response of Knee Ligaments to Prolotherapy in a Rat Injury Model

Article

Full-text available

Jul 2008

Prolotherapy is an alternative therapy for chronic musculoskeletal injury including joint laxity. The commonly used injectant, D-glucose (dextrose), is hypothesized to improve ligament mechanics and decrease pain through an inflammatory mechanism. No study has investigated the mechanical effects of prolotherapy on stretch-injured ligaments. Dextrose injections will enlarge cross-sectional area, decrease laxity, strengthen, and stiffen stretch-injured medial collateral ligaments (MCLs) compared with controls. Dextrose prolotherapy will increase collagen fibril diameter and density of stretch-injured MCLs. Controlled laboratory study. Twenty-four rats were bilaterally MCL stretch-injured, and the induced laxity was measured. After 2 weeks, 32 MCLs were injected twice, 1 week apart, with either dextrose or saline control; 16 MCLs received no injection. Seven uninjured rats (14 MCLs) were additional controls. Two weeks after the second injection, ligament laxity, mechanical properties (n = 8), and collagen fibril diameter and density (n = 3) were assessed. The injury model created consistent ligament laxity (P < .05) that was not altered by dextrose injections. Cross-sectional area of dextrose-injected MCLs was increased 30% and 90% compared with saline and uninjured controls, respectively (P < .05). Collagen fibril diameter and density were decreased in injured ligaments compared with uninjured controls (P < .05), but collagen fibril characteristics were not different between injured groups. Dextrose injections increased the cross-sectional area of MCLs compared with saline-injected and uninjured controls. Dextrose injections did not alter other measured properties in this model. Our results suggest that clinical improvement from prolotherapy may not result from direct effects on ligament biomechanics.

Preferences in the management of osteoarthritis of the hip and knee: Results of a survey of community-based rheumatologists in the United States

Article

Jun 1996

Objective. To determine rheumatologists' preferences in the medical management of osteoarthritis (OA) of the hip and knee, and examine possible variations in these preferences. Methods. A stratified random sample of 1,001 rheumatologists in community-based practice in the United States was surveyed by mail. Results. Responses were obtained from 594 subjects (529 white, 499 male, mean ± SD age 47.4 ± 8.1 years). Over 80% used acetaminophen or nonaspirin, nonsteroidal antiinflammatory drugs (NSAIDs) either always or frequently for the management of OA of the hip and knee. A majority used the following non-pharmacologic methods either always or frequently: weight loss, cane or crutch, physical and/or occupational therapy referral, and exercise. Variation in practice preferences was noted by age (<47 versus ≥47 years), sex, board certification in rheumatology, and number of patients seen per month. Respondents felt that severe pain and limitation of function were the most important factors in recommending total join arthroplasty for patients. Conclusion. These data demonstrate that practicing rheumatologists most often use either acetaminophen and/or NSAIDs in combination with non-pharmacologic methods in the medical management of OA of the hip and knee. The existence of variation in practice preferences has policy implications.

Dextrose prolotherapy for knee osteoarthritis: Results of a randomized controlled trial

Poster

Sep 2011

Osteoarthritis Research Society International (OARSI) World Congress on Osteoarthritis. [Poster Presentation]

Intra-articular corticosteroid for knee osteoarthritis

Article

Oct 2015

Background: Knee osteoarthritis is a leading cause of chronic pain, disability, and decreased quality of life. Despite the long-standing use of intra-articular corticosteroids, there is an ongoing debate about their benefits and safety. This is an update of a Cochrane review first published in 2005. Objectives: To determine the benefits and harms of intra-articular corticosteroids compared with sham or no intervention in people with knee osteoarthritis in terms of pain, physical function, quality of life, and safety. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE (from inception to 3 February 2015), checked trial registers, conference proceedings, reference lists, and contacted authors. Selection criteria: We included randomised or quasi-randomised controlled trials that compared intra-articular corticosteroids with sham injection or no treatment in people with knee osteoarthritis. We applied no language restrictions. Data collection and analysis: We calculated standardised mean differences (SMDs) and 95% confidence intervals (CI) for pain, function, quality of life, joint space narrowing, and risk ratios (RRs) for safety outcomes. We combined trials using an inverse-variance random-effects meta-analysis. Main results: We identified 27 trials (13 new studies) with 1767 participants in this update. We graded the quality of the evidence as 'low' for all outcomes because treatment effect estimates were inconsistent with great variation across trials, pooled estimates were imprecise and did not rule out relevant or irrelevant clinical effects, and because most trials had a high or unclear risk of bias. Intra-articular corticosteroids appeared to be more beneficial in pain reduction than control interventions (SMD -0.40, 95% CI -0.58 to -0.22), which corresponds to a difference in pain scores of 1.0 cm on a 10-cm visual analogue scale between corticosteroids and sham injection and translates into a number needed to treat for an additional beneficial outcome (NNTB) of 8 (95% CI 6 to 13). An I(2) statistic of 68% indicated considerable between-trial heterogeneity. A visual inspection of the funnel plot suggested some asymmetry (asymmetry coefficient -1.21, 95%CI -3.58 to 1.17). When stratifying results according to length of follow-up, benefits were moderate at 1 to 2 weeks after end of treatment (SMD -0.48, 95% CI -0.70 to -0.27), small to moderate at 4 to 6 weeks (SMD -0.41, 95% CI -0.61 to -0.21), small at 13 weeks (SMD -0.22, 95% CI -0.44 to 0.00), and no evidence of an effect at 26 weeks (SMD -0.07, 95% CI -0.25 to 0.11). An I(2) statistic of ≥ 63% indicated a moderate to large degree of between-trial heterogeneity up to 13 weeks after end of treatment (P for heterogeneity≤0.001), and an I(2) of 0% indicated low heterogeneity at 26 weeks (P=0.43). There was evidence of lower treatment effects in trials that randomised on average at least 50 participants per group (P=0.05) or at least 100 participants per group (P=0.013), in trials that used concomittant viscosupplementation (P=0.08), and in trials that used concomitant joint lavage (P≤0.001).Corticosteroids appeared to be more effective in function improvement than control interventions (SMD -0.33, 95% CI -0.56 to -0.09), which corresponds to a difference in functions scores of -0.7 units on standardised Western Ontario and McMaster Universities Arthritis Index (WOMAC) disability scale ranging from 0 to 10 and translates into a NNTB of 10 (95% CI 7 to 33). An I(2) statistic of 69% indicated a moderate to large degree of between-trial heterogeneity. A visual inspection of the funnel plot suggested asymmetry (asymmetry coefficient -4.07, 95% CI -8.08 to -0.05). When stratifying results according to length of follow-up, benefits were small to moderate at 1 to 2 weeks after end of treatment (SMD -0.43, 95% CI -0.72 to -0.14), small to moderate at 4 to 6 weeks (SMD -0.36, 95% CI -0.63 to -0.09), and no evidence of an effect at 13 weeks (SMD -0.13, 95% CI -0.37 to 0.10) or at 26 weeks (SMD 0.06, 95% CI -0.16 to 0.28). An I(2) statistic of ≥ 62% indicated a moderate to large degree of between-trial heterogeneity up to 13 weeks after end of treatment (P for heterogeneity≤0.004), and an I(2) of 0% indicated low heterogeneity at 26 weeks (P=0.52). We found evidence of lower treatment effects in trials that randomised on average at least 50 participants per group (P=0.023), in unpublished trials (P=0.023), in trials that used non-intervention controls (P=0.031), and in trials that used concomitant viscosupplementation (P=0.06).Participants on corticosteroids were 11% less likely to experience adverse events, but confidence intervals included the null effect (RR 0.89, 95% CI 0.64 to 1.23, I(2)=0%). Participants on corticosteroids were 67% less likely to withdraw because of adverse events, but confidence intervals were wide and included the null effect (RR 0.33, 95% CI 0.05 to 2.07, I(2)=0%). Participants on corticosteroids were 27% less likely to experience any serious adverse event, but confidence intervals were wide and included the null effect (RR 0.63, 95% CI 0.15 to 2.67, I(2)=0%).We found no evidence of an effect of corticosteroids on quality of life compared to control (SMD -0.01, 95% CI -0.30 to 0.28, I(2)=0%). There was also no evidence of an effect of corticosteroids on joint space narrowing compared to control interventions (SMD -0.02, 95% CI -0.49 to 0.46). Authors' conclusions: Whether there are clinically important benefits of intra-articular corticosteroids after one to six weeks remains unclear in view of the overall quality of the evidence, considerable heterogeneity between trials, and evidence of small-study effects. A single trial included in this review described adequate measures to minimise biases and did not find any benefit of intra-articular corticosteroids.In this update of the systematic review and meta-analysis, we found most of the identified trials that compared intra-articular corticosteroids with sham or non-intervention control small and hampered by low methodological quality. An analysis of multiple time points suggested that effects decrease over time, and our analysis provided no evidence that an effect remains six months after a corticosteroid injection.

Osteoarthritis: New Insights. Part 1: The Disease and Its Risk Factors

Article

Oct 2000

David Felson

Osteoarthritis is the most common form of arthritis, affecting millions of people in the United States. It is a complex disease whose etiology bridges biomechanics and biochemistry. Evidence is growing for the role of systemic factors (such as genetics, dietary intake, estrogen use, and bone density) and of local biomechanical factors (such as muscle weakness, obesity, and joint laxity). These risk factors are particularly important in weightbearing joints, and modifying them may present opportunities for prevention of osteoarthritis-related pain and disability. Major advances in management to reduce pain and disability are yielding a panoply of available treatments ranging from nutriceuticals to chondrocyte transplantation, new oral anti-inflammatory medications, and health education. This article is part 1 of a two-part summary of a National Institutes of Health conference. The conference brought together experts on osteoarthritis from diverse backgrounds and provided a multidisciplinary and comprehensive summary of recent advances in the prevention of osteoarthritis onset, progression, and disability. Part 1 focuses on a new understanding of what osteoarthritis is and on risk factors that predispose to disease occurrence. It concludes with a discussion of the impact of osteoarthritis on disability. Ann Intern Med. 2000;133:635-646. www.annals.org For author affiliations and current addresses, see end of text.

Hypertonic Dextrose Injection (Prolotherapy) for knee osteoarthritis: Long term outcomes

Article

Apr 2015
COMPLEMENT THER MED

Knee osteoarthritis (OA) is a common, debilitating chronic disease. Prolotherapy is an injection therapy for chronic musculoskeletal pain. Recent 52-week randomized controlled and open label studies have reported improvement of knee OA-specific outcomes compared to baseline status, and blinded saline control injections and at-home exercise therapy (p<0.05). However, long term effects of prolotherapy for knee OA are unknown. We therefore assessed long-term effects of prolotherapy on knee pain, function and stiffness among adults with knee OA. Post clinical-trial, open-label follow-up study. Outpatient; adults with mild-to-severe knee OA completing a 52-week prolotherapy study were enrolled. Participants received 3-5 monthly interventions and were assessed using the validated Western Ontario McMaster University Osteoarthritis Index, (WOMAC, 0-100 points), at baseline, 12, 26, 52 weeks, and 2.5 years. 65 participants (58±7.4 years old, 38 female) received 4.6±0.69 injection sessions in the initial 17-week treatment period. They reported progressive improvement in WOMAC scores at all time points in excess of minimal clinical important improvement benchmarks during the initial 52-week study period, from 13.8±17.4 points (23.6%) at 12 weeks, to 20.9±2.8 points, (p<0.05; 35.8% improvement) at 2.5±0.6 years (range 1.6-3.5 years) in the current follow-up analysis. Among assessed covariates, none were predictive of improvement in the WOMAC score. Prolotherapy resulted in safe, significant, progressive improvement of knee pain, function and stiffness scores among most participants through a mean follow-up of 2.5 years and may be an appropriate therapy for patients with knee OA refractory to other conservative care. Copyright © 2015 Elsevier Ltd. All rights reserved.

Supplementary Methods in the Nonsurgical Treatment of Osteoarthritis

Article

Jan 2015

Effects of Prescription Nonsteroidal Antiinflammatory Drugs on Symptoms and Disease Progression Among Patients With Knee Osteoarthritis: Long-Term Effects of NSAIDs on Knee OA

Article

Oct 2014

Objective The effect of short-term and long-term use of nonsteroidal antiinflammatory drugs (NSAIDs) on structural change is equivocal. The aim of this study was to estimate the extent to which short- and long-term use of prescription NSAIDs relieve symptoms and delay structural progression among patients with radiographically confirmed osteoarthritis (OA) of the knee.Methods We applied a new-user design among participants with confirmed OA not reporting NSAID use at the time of enrollment in the Osteoarthritis Initiative. Participants were evaluated for changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscales (n = 1,846) and joint space width was measured using serial radiographs and a customized software tool (n = 1,116) over 4 years. We used marginal structural modeling to estimate the effect of NSAIDs.ResultsCompared to participants who never reported prescription NSAID use, those reporting use at 1 or 2 assessments had no clinically important changes, but those reporting prescription NSAID use at all 3 assessments had, on average, 0.88 point improvement over the followup period (95% confidence interval [95% CI] −0.46 to 2.22) in pain, 0.72 point improvement (95% CI −0.12 to 1.56) in stiffness, and 4.27 points improvement (95% CI −0.31 to 8.84) in function. The average change in joint space width was 0.28 mm less among those reporting NSAID use at 3 assessments relative to nonusers (95% CI −0.06 to 0.62). Recent NSAID use findings were not clinically or statistically significant.Conclusion Long-term, but not short-term, NSAID use was associated with an a priori-defined minimally important clinical change in stiffness, physical function, and joint space width, but not pain. While showing modest clinical importance, the estimates did not reach statistical significance.

A rationale for prolotherapy

Article

Jan 1991

Allen R Banks

Dextrose and Morrhuate Sodium Injections (Prolotherapy) for Knee Osteoarthritis: A Prospective Open-Label Trial

Article

Mar 2014
J ALTERN COMPLEM MED

Objectives: This study determined whether injection with hypertonic dextrose and morrhuate sodium (prolotherapy) using a pragmatic, clinically determined injection schedule for knee osteoarthritis (KOA) results in improved knee pain, function, and stiffness compared to baseline status. Design: This was a prospective three-arm uncontrolled study with 1-year follow-up. Setting: The setting was outpatient. Participants: The participants were 38 adults who had at least 3 months of symptomatic KOA and who were in the control groups of a prior prolotherapy randomized controlled trial (RCT) (Prior-Control), were ineligible for the RCT (Prior-Ineligible), or were eligible but declined the RCT (Prior-Declined). Intervention: The injection sessions at occurred at 1, 5, and 9 weeks with as-needed treatment at weeks 13 and 17. Extra-articular injections of 15% dextrose and 5% morrhuate sodium were done at peri-articular tendon and ligament insertions. A single intra-articular injection of 6 mL 25% dextrose was performed through an inferomedial approach. Outcome measures: The primary outcome measure was the validated Western Ontario McMaster University Osteoarthritis Index (WOMAC). The secondary outcome measure was the Knee Pain Scale and postprocedure opioid medication use and participant satisfaction. Results: The Prior-Declined group reported the most severe baseline WOMAC score (p=0.02). Compared to baseline status, participants in the Prior-Control group reported a score change of 12.4±3.5 points (19.5%, p=0.002). Prior-Decline and Prior-Ineligible groups improved by 19.4±7.0 (42.9%, p=0.05) and 17.8±3.9 (28.4%, p=0.008) points, respectively; 55.6% of Prior-Control, 75% of Prior-Decline, and 50% of Prior-Ineligible participants reported score improvement in excess of the 12-point minimal clinical important difference on the WOMAC measure. Postprocedure opioid medication resulted in rapid diminution of prolotherapy injection pain. Satisfaction was high and there were no adverse events. Conclusions: Prolotherapy using dextrose and morrhuate sodium injections for participants with mild-to-severe KOA resulted in safe, significant, sustained improvement of WOMAC-based knee pain, function, and stiffness scores compared to baseline status.

Fit and Strong! Plus: Design of a Comparative Effectiveness Evaluation of a Weight Management Program for Older Adults with Osteoarthritis

Article

Dec 2013

Osteoarthritis (OA) is the most common chronic condition and principal cause of disability among older adults. The current obesity epidemic has contributed to this high prevalence rate. Fortunately both OA symptoms and obesity can be ameliorated through lifestyle modifications. Physical activity (PA) combined with weight management improves physical function among obese persons with knee OA but evidence-based interventions that combine PA and weight management are limited for this population. This paper describes a comparative effectiveness trial testing an evidence-based PA program for adults with lower extremity (LE) OA, Fit and Strong!, against an enhanced version that also addresses weight management based on the evidence-based Obesity Reduction Black Intervention Trial (ORBIT). Adult participants (n=400) with LE OA, age 60+, overweight/obese, and not meeting PA requirements of>=150minutes per week, are randomized to one of the two programs. Both 8-week interventions meet 3 times per week and include 60minutes of strength, flexibility, and aerobic exercise instruction followed by 30minutes of education/group discussion. The Fit and Strong! education sessions focus on using PA to manage OA; whereas Fit and Strong! Plus addresses PA and weight loss management strategies. Maintenance of behavior change is reinforced in both groups during months 3 - 24 through telephone calls and mailed newsletters. Outcomes are assessed at baseline, and 2, 6, 12, 18, and 24months. Primary outcomes are dietary change at 2months followed by weight loss at 6months that is maintained at 24months. Secondary outcomes assess PA, physical performance, and anxiety/depression.

Association Between Disease-Specific Quality of Life and Magnetic Resonance Imaging Outcomes in a Clinical Trial of Prolotherapy for Knee Osteoarthritis

Article

Jul 2013

To assess the relationship between knee osteoarthritis (KOA)-specific quality-of-life (QoL) and intra-articular cartilage volume (CV) in participants treated with prolotherapy. KOA is characterized by CV loss and multifactorial pain. Prolotherapy is an injection therapy reported to improve KOA-related QoL compared to blinded saline injections and at-home exercise but the mechanism of action is unknown. Two-arm (Prolotherapy, Control), partially blinded, controlled trial. Outpatient. Participants: 37 adults with ≥3 months of symptomatic KOA. Prolotherapy: 5 monthly injection sessions; Control: blinded saline injections or at-home exercise. Primary: KOA-specific QoL scores (baseline, 5, 9, 12, 26, 52 weeks; Western Ontario McMaster University Osteoarthritis Index, WOMAC). Secondary: KOA-specific pain, stiffness, function (WOMAC subscales), magnetic resonance imaging (MRI)-assessed CV (baseline, 52 weeks). Knee-specific QoL improvement among Prolotherapy participants exceeded that of Controls (17.6±3.2 versus 8.6±5.0 points, p=0.05) at 52 weeks. Both groups lost CV over time (p<0.05); no between-group differences were noted (p=0.98). While Prolotherapy participants lost CV at varying rates, those who lost the least CV ("Stable CV") had the greatest improvement in pain scores. Among Prolotherapy, but not Control participants, the change in CV and the change in pain (but not stiffness or function) scores were correlated; each 1% CV loss was associated with 2.7% less improvement in pain score (p<0.05). Prolotherapy resulted in safe, substantial improvement in KOA-specific QoL compared to Control over 52-weeks. Among prolotherapy participants, but not Controls, MRI-assessed CV change (CV stability) predicted pain severity score change, suggesting prolotherapy may have pain-specific disease-modifying effect. Further research is warranted.

Dextrose Prolotherapy for Knee Osteoarthritis: A Randomized Controlled Trial

Article

May 2013
ANN FAM MED

Purpose: Knee osteoarthritis is a common, debilitating chronic disease. Prolotherapy is an injection therapy for chronic musculoskeletal pain. We conducted a 3-arm, blinded (injector, assessor, injection group participants), randomized controlled trial to assess the efficacy of prolotherapy for knee osteoarthritis. Methods: Ninety adults with at least 3 months of painful knee osteoarthritis were randomized to blinded injection (dextrose prolotherapy or saline) or at-home exercise. Extra- and intra-articular injections were done at 1, 5, and 9 weeks with as-needed additional treatments at weeks 13 and 17. Exercise participants received an exercise manual and in-person instruction. Outcome measures included a composite score on the Western Ontario McMaster University Osteoarthritis Index (WOMAC; 100 points); knee pain scale (KPS; individual knee), post-procedure opioid medication use, and participant satisfaction. Intention-to-treat analysis using analysis of variance was used. Results: No baseline differences existed between groups. All groups reported improved composite WOMAC scores compared with baseline status (P <.01) at 52 weeks. Adjusted for sex, age, and body mass index, WOMAC scores for patients receiving dextrose prolotherapy improved more (P <.05) at 52 weeks than did scores for patients receiving saline and exercise (score change: 15.3 ± 3.5 vs 7.6 ± 3.4, and 8.2 ± 3.3 points, respectively) and exceeded the WOMAC-based minimal clinically important difference. Individual knee pain scores also improved more in the prolotherapy group (P = .05). Use of prescribed postprocedure opioid medication resulted in rapid diminution of injection-related pain. Satisfaction with prolotherapy was high. There were no adverse events. Conclusions: Prolotherapy resulted in clinically meaningful sustained improvement of pain, function, and stiffness scores for knee osteoarthritis compared with blinded saline injections and at-home exercises.

Studies of surgical outcome after patellar tendinopathy: clinical significance of methodological deficiencies and guidelines for future studies

Article

Jul 2008
SCAND J MED SCI SPOR

Patellar tendinopathy is often treated surgically after failure of conservative treatment but clinical experience suggests that results are not uniformly excellent. The aim of this review was to (i) identify the different surgical techniques that have been reported and compare their success rates, and (ii) critically assess the methodology of studies that have reported surgical outcomes. Twenty-three papers and two abstracts were included in the review. Surgical procedures were categorized and outcomes summarized. Using ten criteria, an overall methodology score was derived for each paper. Criteria for which scores were generally low (indicating methodological deficiency) concerned the type of study, subject selection process and outcome measures. We found a negative correlation between papers’ reported success rates and overall methodology scores (r=−0.57, P<0.01). There was a positive correlation between year of publication and overall methodology score (r=0.68, P<0.001). We conclude that study methodology may influence reported surgical outcome. We suggest practical guidelines for improving study design in this area of clinical research, as improved study design would provide clinicians with a more rigorous evidence-base for treating patients who have recalcitrant patellar tendinopathy.

Effect of Regenerative Injection Therapy on Function and Pain in Patients with Knee Osteoarthritis: A Randomized Crossover Study

Article

Jul 2012
PAIN MED

We assessed the effectiveness of regenerative injection therapy (RIT) to relieve pain and restore function in patients with knee osteoarthritis. Crossover study where participants were randomly assigned to receive exercise therapy for 32 weeks in combination with RIT on weeks 0, 4, 8, and 12 or RIT on weeks 20, 24, 28, and 32. Thirty-six patients with chronic knee osteoarthritis. RIT, which is made up of injections of 1 cc of 15% dextrose 0.6% lidocaine in the collateral ligaments and a 5 cc injection of 20% dextrose 0.5% lidocaine inside the knee joint. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index of severity of osteoarthrosis symptoms (WOMAC) score (range: 0-96). Following 16 weeks of follow-up, the participants assigned to RIT presented a significant reduction of their osteoarthritis symptoms (mean ± standard deviation: -21.8 ± 12.5, P < 0.001). WOMAC scores in this group did not change further during the last 16 weeks of follow-up, when the participants received exercise therapy only (-1.2 ± 10.7, P = 0.65). WOMAC scores in the first 16 weeks did not change significantly among the participants receiving exercise therapy only during this period (-6.1±13.9, P=0.11). There was a significant decrease in this groups' WOMAC scores during the last 16 weeks when the participants received RIT (-9.3±11.4, P=0.006). After 36 weeks, WOMAC scores improved in both groups by 47.3% and 36.2%. The improvement attributable to RIT alone corresponds to a 11.9-point (or 29.5%) decrease in WOMAC scores. The use of RIT is associated with a marked reduction in symptoms, which was sustained for over 24 weeks.

American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee

Article

Apr 2012

To update the American College of Rheumatology (ACR) 2000 recommendations for hip and knee osteoarthritis (OA) and develop new recommendations for hand OA. A list of pharmacologic and nonpharmacologic modalities commonly used to manage knee, hip, and hand OA as well as clinical scenarios representing patients with symptomatic hand, hip, and knee OA were generated. Systematic evidence-based literature reviews were conducted by a working group at the Institute of Population Health, University of Ottawa, and updated by ACR staff to include additions to bibliographic databases through December 31, 2010. The Grading of Recommendations Assessment, Development and Evaluation approach, a formal process to rate scientific evidence and to develop recommendations that are as evidence based as possible, was used by a Technical Expert Panel comprised of various stakeholders to formulate the recommendations for the use of nonpharmacologic and pharmacologic modalities for OA of the hand, hip, and knee. Both “strong” and “conditional” recommendations were made for OA management. Modalities conditionally recommended for the management of hand OA include instruction in joint protection techniques, provision of assistive devices, use of thermal modalities and trapeziometacarpal joint splints, and use of oral and topical nonsteroidal antiinflammatory drugs (NSAIDs), tramadol, and topical capsaicin. Nonpharmacologic modalities strongly recommended for the management of knee OA were aerobic, aquatic, and/or resistance exercises as well as weight loss for overweight patients. Nonpharmacologic modalities conditionally recommended for knee OA included medial wedge insoles for valgus knee OA, subtalar strapped lateral insoles for varus knee OA, medially directed patellar taping, manual therapy, walking aids, thermal agents, tai chi, self management programs, and psychosocial interventions. Pharmacologic modalities conditionally recommended for the initial management of patients with knee OA included acetaminophen, oral and topical NSAIDs, tramadol, and intraarticular corticosteroid injections; intraarticular hyaluronate injections, duloxetine, and opioids were conditionally recommended in patients who had an inadequate response to initial therapy. Opioid analgesics were strongly recommended in patients who were either not willing to undergo or had contraindications for total joint arthroplasty after having failed medical therapy. Recommendations for hip OA were similar to those for the management of knee OA. These recommendations are based on the consensus judgment of clinical experts from a wide range of disciplines, informed by available evidence, balancing the benefits and harms of both nonpharmacologic and pharmacologic modalities, and incorporating their preferences and values. It is hoped that these recommendations will be utilized by health care providers involved in the management of patients with OA.

Neurogenic Inflammation and Particulate Matter (PM) Air Pollutants

Article

Jan 2002
NEUROTOXICOLOGY

Exposure to a class of airborne pollutants known as particulate matter (PM) is an environmental health risk of global proportions. PM is thought to initiate and/or exacerbate respiratory disorders, such as asthma and airway hyper-responsiveness and is epidemiologically associated with causing death in the elderly and those with pre-existing respiratory or cardiopulmonary disease. Plausible mechanisms of action to explain PM inflammation and its susceptible sub-population component are lacking. This review describes a series of published studies which indicate that PM initiates airway inflammation through sensory neural pathways, specifically by activation of capsaicin-sensitive vanilloid (e.g. VR1) irritant receptors. These acid-sensitive receptors are located on the sensory C nerve fibers that innervate the airways as well as on various immune and non-immune airway target cells. The activation of these receptors results in the release of neuropeptides from the sensory terminals that innervate the airways. Their interactions with airway target cells, result in signs of inflammation (e.g. bronchoconstriction, vasodilation, histamine release, mucous secretion etc.). Our data have linked the activation of the VR1 receptors to the surface charge carried on the colloidal particulates which constitute PM pollution. Related studies have examined how genetic and non-genetic factors modify the sensitivity of these irritant receptors and enhance the inflammatory responsiveness to PM. In summary, this review proposes a mechanism by which neurogenic elements initiate and sustain PM-mediated airway inflammation. Although neurogenic influences have been appreciated in normal airway homeostasis, they have not, until now, been associated with PM toxicity. The sensitivity of the sensory nervous system to irritants and its interactions with pulmonary target tissues, should encourage neuroscientists to explore the relevance of neurogenic influences to toxic disorders involving other peripheral target systems.

Statistical power ANALYSIS for the Behavioral sciences

Article

Jan 1988
J AM STAT ASSOC

Jacob Cohen

Incluye bibliografía e índice

Prolotherapy in Primary Care Practice

Article

Mar 2010

Prolotherapy is an injection-based complementary and alternative medical therapy for chronic musculoskeletal pain. Prolotherapy techniques and injected solutions vary by condition, clinical severity, and practitioner preferences; over several treatment sessions, a fairly small volume of an irritant or sclerosing solution is injected at sites on painful ligament and tendon insertions and in adjacent joint space during several treatment sessions. Prolotherapy is becoming increasingly popular in the United States and internationally and is actively used in clinical practice. Prolotherapy has been assessed as a treatment for various painful chronic musculoskeletal conditions that are refractory to "standard of care" therapies. Although anecdotal clinical success guides the use of prolotherapy for many conditions, clinical trial literature supporting evidence-based decision-making for the use of prolotherapy exists for low back pain, several tendinopathies, and osteoarthritis.

Estimating the size of treatment effects: Moving beyond P values

Article

Oct 2009

Objective: To increase understanding of effect size calculations among clinicians who over-rely on interpretations of P values in their assessment of the medical literature. Design: We review five methods of calculating effect sizes: Cohen's d (also known as the standardized mean difference)-used in studies that report efficacy in terms of a continuous measurement and calculated from two mean values and their standard deviations; relative risk-the ratio of patients responding to treatment divided by the ratio of patients responding to a different treatment (or placebo), which is particularly useful in prospective clinical trials to assess differences between treatments; odds ratio- used to interpret results of retrospective case-control studies and provide estimates of the risk of side effects by comparing the probability (odds) of an outcome occurring in the presence or absence of a specified condition; number needed to treat-the number of subjects one would expect to treat with agent A to have one more success (or one less failure) than if the same number were treated with agent B; and area under the curve (also known as the drug-placebo response curve)-a six-step process that can be used to assess the effects of medication on both worsening and improvement and the probability that a medication-treated subject will have a better outcome than a placebo-treated subject. Conclusion: Effect size statistics provide a better estimate of treatment effects than P values alone.

Transcutaneous electrostimulation for osteoarthritis of the knee

Article

Oct 2009

Osteoarthritis is the most common form of joint disease and the leading cause of pain and physical disability in the elderly. Transcutaneous electrical nerve stimulation (TENS), interferential current stimulation and pulsed electrostimulation are used widely to control both acute and chronic pain arising from several conditions, but some policy makers regard efficacy evidence as insufficient. To compare transcutaneous electrostimulation with sham or no specific intervention in terms of effects on pain and withdrawals due to adverse events in patients with knee osteoarthritis. We updated the search in CENTRAL, MEDLINE, EMBASE, CINAHL and PEDro up to 5 August 2008, checked conference proceedings and reference lists, and contacted authors. Randomised or quasi-randomised controlled trials that compared transcutaneously applied electrostimulation with a sham intervention or no intervention in patients with osteoarthritis of the knee. We extracted data using standardised forms and contacted investigators to obtain missing outcome information. Main outcomes were pain and withdrawals or dropouts due to adverse events. We calculated standardised mean differences (SMDs) for pain and relative risks for safety outcomes and used inverse-variance random-effects meta-analysis. The analysis of pain was based on predicted estimates from meta-regression using the standard error as explanatory variable. In this update we identified 14 additional trials resulting in the inclusion of 18 small trials in 813 patients. Eleven trials used TENS, four interferential current stimulation, one both TENS and interferential current stimulation, and two pulsed electrostimulation. The methodological quality and the quality of reporting was poor and a high degree of heterogeneity among the trials (I(2) = 80%) was revealed. The funnel plot for pain was asymmetrical (P < 0.001). The predicted SMD of pain intensity in trials as large as the largest trial was -0.07 (95% CI -0.46 to 0.32), corresponding to a difference in pain scores between electrostimulation and control of 0.2 cm on a 10 cm visual analogue scale. There was little evidence that SMDs differed on the type of electrostimulation (P = 0.94). The relative risk of being withdrawn or dropping out due to adverse events was 0.97 (95% CI 0.2 to 6.0). In this update, we could not confirm that transcutaneous electrostimulation is effective for pain relief. The current systematic review is inconclusive, hampered by the inclusion of only small trials of questionable quality. Appropriately designed trials of adequate power are warranted.

Preferences in the management of osteoarthritis of the hip and knee: Results of a survey of community-based rheumatologists in the United States

Article

Jun 1996

To determine rheumatologists' preferences in the medical management of osteoarthritis (OA) of the hip and knee, and examine possible variations in these preferences. A stratified random sample of 1,001 rheumatologists in community-based practice in the United States was surveyed by mail. Responses were obtained form 594 subjects (529 white, 499 male, mean +/- SD age 47.4 +/- 8.1 years). Over 80% used acetaminophen or nonaspirin, nonsteroidal antiinflammatory drugs (NSAIDs) either always or frequently for the management of OA of the hip and knee. A majority used the following nonpharmacologic methods either always or frequently: weight loss, cane or crutch, physical and/or occupational therapy referral, and exercise. Variation in practice preferences was noted by age (< 47 versus > or = 47 years), sex, board certification in rheumatology, and number of patients seen per month. Respondents felt that severe pain and limitation of function were the most important factors in recommending total join arthroplasty for patients. These data demonstrate that practicing rheumatologists most often use either acetaminophen and/or NSAIDs in combination with nonpharmacologic methods in the medical management of OA of the hip and knee. The existence of variation in practice preferences has policy implications.

Osteoarthritis

Article

Sep 1997

Randomized prospective blind controlled study of dextrosed prolotherapy for knee osteoarthritis with and without ACL laxity

Article

Apr 2000
Alternative Ther Health Med

Use of prolotherapy (injection of growth factors or growth factor stimulators). Determine the effects of dextrose prolotherapy on knee osteoarthritis with or without anterior cruciate ligament (ACL) laxity. Prospective randomized double-blind placebo-controlled trial. Outpatient physical medicine clinic. Six months or more of pain along with either grade 2 or more joint narrowing or grade 2 or more osteophytic change in any knee compartment. A total of 38 knees were completely void of cartilage radiographically in at least 1 compartment. Three bimonthly injections of 9 cc of either 10% dextrose and .075% lidocaine in bacteriostatic water (active solution) versus an identical control solution absent 10% dextrose. The dextrose-treated joints then received 3 further bimonthly injections of 10% dextrose in open-label fashion. Visual analogue scale for pain and swelling, frequency of leg buckling, goniometrically measured flexion, radiographic measures of joint narrowing and osteophytosis, and KT1000-measured anterior displacement difference (ADD). All knees: Hotelling multivariate analysis of paired observations between 0 and 6 months for pain, swelling, buckling episodes, and knee flexion range revealed significantly more benefit from the dextrose injection (P = .015). By 12 months (6 injections) the dextrose-treated knees improved in pain (44% decrease), swelling complaints (63% decrease), knee buckling frequency (85% decrease), and in flexion range (14 degree increase). Analysis of blinded radiographic readings of 0- and 12-month films revealed stability of all radiographic variables except for 2 variables which improved with statistical significance. (Lateral patellofemoral cartilage thickness [P = .019] and distal femur width in mm [P = .021]. Knees with ACL laxity: 6-month (3 injection) data revealed no significant improvement. However, Hotelling multivariate analysis of paired values at 0 and 12 months for pain, swelling, joint flexion, and joint laxity in the dextrose-treated knees, revealed a statistically significant improvement (P = .021). Individual paired t tests indicated that blinded measurement of goniometric knee flexion range improved by 12.8 degrees (P = .005), and ADD improved by 57% (P = .025). Eight out of 13 dextrose-treated knees with ACL laxity were no longer lax at the conclusion of 1 year. Prolotherapy injection with 10% dextrose resulted in clinically and statistically significant improvements in knee osteoarthritis. Preliminary blinded radiographic readings (1-year films, with 3-year total follow-up period planned) demonstrated improvement in several measures of osteoarthritis severity. ACL laxity, when present in these osteoarthritic patients, improved.

Recent Socioeconomic Trends in Orthopaedic Practice

Article

Aug 2001

In the last fifteen years, there have been great changes in the American health-care system. Driven by an increasingly persistent concern about double-digit increases in expenditures, large employers have led a mass migration from indemnity insurance to managed care1. The transition process has not been particularly smooth, however, leading to a backlash against managed care on the part of the general public and physicians2,3. In this article, we examine socioeconomic trends in orthopaedic practice that occurred during this period, including issues related to the workforce, the changing population, and managed care. Between 1970 and 1997, the number of orthopaedic surgeons in the United States increased by 145%, from 7537 to 18,5004. The nation’s population increased during that period as well, but not nearly as fast, resulting in almost a doubling of the ratio of orthopaedic surgeons to the population, from 3.6 per 100,000 in 1970 to 6.9 per 100,000 in 1997. The distribution of orthopaedists is not uniform across the country; the highest density is in New England and the lowest, in the Midwest and South Central regions of the country. Among the areas with more than the national average of orthopaedists per 100,000 people are Evanston, Illinois (9.8); Hartford and New Haven, Connecticut (9.3 each); Providence, Rhode Island (9.3); and San Francisco, California (9.1). Those with fewer than the national average include Tucson, Arizona (6.1); Detroit and Ann Arbor, Michigan (5.7 and 4.9, respectively); Manhattan, New York (5.6); Las Vegas, Nevada (5.2); and Memphis, Tennessee (5.0)5. An important implication of these trends is that orthopaedists today—especially those in areas with the highest density of orthopaedic surgeons—have fewer patients available to treat than did their counterparts thirty years ago. This raises many important questions. Was there a deficit in the …

Joint stabilization through induced ligament sclerosis

Article

Nov 1953
Ohio Med

G S HACKETT

The sources of pain in knee osteoarthritis: Editorial review

Article

Oct 2005

David Felson

To review the mechanisms for the production of pain in knee osteoarthritis. Nociception is produced by stimulation of unmyelinated and small myelinated fibers in the joint and surrounding tissue. To produce pain, the stimuli must be either repeated or spatially clustered. When they reach the spinal cord, stimuli are subject to two inhibitory effectors: interneurons and descending central neurons. Inflammation lowers the threshold for nociception. In the joint, tissues containing nociceptors include primarily the joint capsule, ligaments, synovium, bone, and in the knee, the outer edge of the menisci. Nociceptive stimuli are likely to emanate from one or more of these locations in people with knee pain. This review does not cover psychological aspects of pain. Nociception in the knee is complex, and the nociceptive stimuli are related to but fundamentally different from those producing cartilage loss. Better appreciation for these processes will facilitate the development of new treatments.

A Systematic Review of Prolotherapy for Chronic Musculoskeletal Pain

Article

Oct 2005
CLIN J SPORT MED

Prolotherapy, an injection-based treatment of chronic musculoskeletal pain, has grown in popularity and has received significant recent attention. The objective of this review is to determine the effectiveness of prolotherapy for treatment of chronic musculoskeletal pain. We searched Medline, PreMedline, Embase, CINAHL, and Allied and Complementary Medicine with search strategies using all current and historical names for prolotherapy and injectants. Reference sections of included articles were scanned, and content area specialists were consulted. All published studies involving human subjects and assessing prolotherapy were included. Data from 34 case reports and case series and 2 nonrandomized controlled trials suggest prolotherapy is efficacious for many musculoskeletal conditions. However, results from 6 randomized controlled trials (RCTs) are conflicting. Two RCTs on osteoarthritis reported decreased pain, increased range of motion, and increased patellofemoral cartilage thickness after prolotherapy. Two RCTs on low back pain reported significant improvements in pain and disability compared with control subjects, whereas 2 did not. All studies had significant methodological limitations. There are limited high-quality data supporting the use of prolotherapy in the treatment of musculoskeletal pain or sport-related soft tissue injuries. Positive results compared with controls have been reported in nonrandomized and randomized controlled trials. Further investigation with high-quality randomized controlled trials with noninjection control arms in studies specific to sport-related and musculoskeletal conditions is necessary to determine the efficacy of prolotherapy.

Viscosupplementation for treatment of osteoarthritis of the knee

Article

Feb 2006

AUTHORS' CONCLUSIONS: Based on the aforementioned analyses, viscosupplementation is an effective treatment for OA of the knee with beneficial effects: on pain, function and patient global assessment; and at different post injection periods but especially at the 5 to 13 week post injection period. It is of note that the magnitude of the clinical effect, as expressed by the WMD and standardised mean difference (SMD) from the RevMan 4.2 output, is different for different products, comparisons, timepoints, variables and trial designs. However, there are few randomised head-to-head comparisons of different viscosupplements and readers should be cautious, therefore, in drawing conclusions regarding the relative value of different products. The clinical effect for some products, against placebo, on some variables at some timepoints is in the moderate to large effect-size range. Readers should refer to relevant tables to review specific detail given the heterogeneity in effects across the product class and some discrepancies observed between the RevMan 4.2 analyses and the original publications. Overall, the analyses performed are positive for the HA class and particularly positive for some products with respect to certain variables and timepoints, such as pain on weight bearing at 5 to 13 weeks postinjection. In general, sample-size restrictions preclude any definitive comment on the safety of the HA class of products; however, within the constraints of the trial designs employed no major safety issues were detected. In some analyses viscosupplements were comparable in efficacy to systemic forms of active intervention, with more local reactions but fewer systemic adverse events. In other analyses HA products had more prolonged effects than IA corticosteroids. Overall, the aforementioned analyses support the use of the HA class of products in the treatment of knee OA.

Tandem-Pore K+ Channels Mediate Inhibition of Orexin Neurons by Glucose

Article

Jul 2006
NEURON

Glucose-inhibited neurons orchestrate behavior and metabolism according to body energy levels, but how glucose inhibits these cells is unknown. We studied glucose inhibition of orexin/hypocretin neurons, which promote wakefulness (their loss causes narcolepsy) and also regulate metabolism and reward. Here we demonstrate that their inhibition by glucose is mediated by ion channels not previously implicated in central or peripheral glucose sensing: tandem-pore K(+) (K(2P)) channels. Importantly, we show that this electrical mechanism is sufficiently sensitive to encode variations in glucose levels reflecting those occurring physiologically between normal meals. Moreover, we provide evidence that glucose acts at an extracellular site on orexin neurons, and this information is transmitted to the channels by an intracellular intermediary that is not ATP, Ca(2+), or glucose itself. These results reveal an unexpected energy-sensing pathway in neurons that regulate states of consciousness and energy balance.

Exercise for osteoarthritis of the hip or knee (Cochrane Review)

Article

Feb 2003

Biomechanical factors, such as reduced muscle strength and joint mal-alignment, have an important role in the initiation and progression of osteoarthritis (OA) of the hip or knee. Currently, there is no known cure for OA, however, disease-related factors, such as impaired muscle function and reduced fitness, are potentially amenable to therapeutic exercise. To determine whether land-based therapeutic exercise is beneficial for people with OA of the hip or knee in terms of reduced joint pain, improved physical function and/or the patient's global assessment of therapeutic effectiveness. Five databases (the Cochrane Controlled Trials Register, the Cochrane Musculoskeletal Group Trials Register, MEDLINE, CINAHL, PEDro) were searched up until November 2002. All randomized controlled trials comparing some form of land-based therapeutic exercise (as opposed to exercises conducted in the water) with a non-exercise group. Two reviewers independently extracted data and assessed methodological quality. All analyses were conducted on continuous outcomes. Only 2 studies totaling about 100 participants, could potentially provide data on people with OA of the hip. However, for OA of the knee, 17 included studies provided data on 2562 participants. For pain, combining the results revealed a beneficial treatment effect (standardised mean difference) of.39 (95% confidence interval (CI).30 -.47) while for self-reported physical function a beneficial treatment effect of.31 (95% CI.23 -.39). Group format programs appeared to be as effective as treatments provided on a one-to-one basis. The results were sensitive to various aspects of study design methodology. Land-based therapeutic exercise was shown to reduce pain and improve physical function for people with OA of the knee. There were insufficient data to provide useful guidelines on optimal exercise type or dosage. Supervised exercise classes appeared to be as beneficial as treatments provided on a one-to-one basis.

WITHDRAWN: Non-aspirin, non-steroidal anti-inflammatory drugs for treating osteoarthritis of the knee

Article

Feb 2006

BACKGROUND: Osteoarthritis(OA) is the most common rheumatic disease. Simple analgesics are now accepted as the appropriate first line pharmacological treatment of uncomplicated OA. Non-aspirin NSAIDs are licensed for the relief of pain and inflammation arising from rheumatic disease. OBJECTIVES: To determine whether there is a difference in the relative efficacy of individual non-steroidal anti-inflammatory drugs (NSAIDs) when used in the management of osteoarthritis (OA) of the knee. SEARCH STRATEGY: We searched Medline (1966-1995) and Bids Embase (Jan-Dec, 1980-1995). The searches were limited to publications in the English language, and were last performed in November 1996. We used modified Cochrane Collaboration search strategy to identify all randomised controlled trials. The MeSH heading "osteoarthritis" was combined with the generic names of the 17 non-aspirin NSAIDs licensed in the UK for the management of OA in general practice. The search of Embase used the term "osteoarthritis" if present in the abstract, title or keywords, and was combined with the generic names of the 17 non-aspirin NSAIDs, only if they were mentioned in the title, abstract or keywords. SELECTION CRITERIA: All double blind, randomised controlled trials, in the English language, comparing the efficacy of two non-aspirin NSAIDs in the management of osteoarthritis of the knee, were selected. Only trials with subjects aged 16 years and over, with clinical and/or radiological confirmation of the diagnosis of OA knee were included. Studies which compared one "trial" NSAID with one "reference" NSAID were included provided they were non-aspirin NSAIDs available in the UK and were licensed for the treatment of OA by general practitioners. Trials which were placebo-controlled and which also involved the comparison of two NSAIDs were also included. DATA COLLECTION AND ANALYSIS:(...)

Early Inflammatory Response of Knee Ligaments to Prolotherapy in a Rat Model

Article

Jun 2008
J ORTHOP RES

Prolotherapy is an alternative injection-based therapy for chronic musculoskeletal pain. Three different proliferants, D-glucose (dextrose), phenol-glucose-glycerine (P2G), and sodium morrhuate, used in prolotherapy are hypothesized to strengthen and reorganize chronically injured soft tissue and decrease pain through modulation of the inflammatory process. Our hypothesis is that commonly used prolotherapy solutions will induce inflammation (leukocyte and macrophage infiltration) in medial collateral ligaments (MCLs) compared to needlestick, saline injection, and no-injection controls. MCLs of 84 Sprague- Dawley rats were injected one time at both the tibial and femoral insertions. Immunohistochemistry (IHC) was used to determine the inflammatory response at three locations (tibial and femoral insertions and midsubstance) 6, 24, and 72 h after dextrose injection compared to saline- and no-injection controls and collagenase (positive control) (n = 4). qPCR was used to analyze gene expression 24 h postinjection (n = 4). Sodium morrhuate, P2G, and needlestick control were also investigated after 24 h (n = 4). In general, inflammation (CD43+, ED1+, and ED2+ cells) increased after prolotherapy injection compared to no-injection control but did not increase consistently compared to saline and needlestick control injections. This response varied by both location and proliferant. Inflammation was observed at 6 and 24 h postinjection but was resolved by 72 h compared to no-injection controls (p < 0.05). CD43+ leukocytes and ED2+ macrophages increased compared to needlestick and saline-injection control, respectively, 24 h postinjection (p < 0.05). Prolotherapy injections created an inflammatory response, but this response was variable and overall, not uniformly different from that caused by saline injections or needlestick procedures.

Oral or transdermal opioids for osteoarthritis of the knee or hip

Jan 2014
COCHRANE DB SYST REV

B R Da Costa
E Nuesch
R Kasteler

da Costa BR, Nuesch E, Kasteler R, et al. Oral or transdermal opioids for osteoarthritis of the knee or hip. Cochrane Database Syst Rev 2014;Cd003115.

Supplementary methods in the nonsurgical treatment of osteoarthritis

Jan 2015
785-92

Ma Percope De Andrade
Tv Campos
Gm Abreu-E-Silva

Percope de Andrade MA, Campos TV, Abreu-E-Silva GM. Supplementary methods in the nonsurgical treatment of osteoarthritis. Arthroscopy 2015;31:785–92.

Bierma-Zeinstra Braces and orthoses for osteoarthritis of the knee

Jan 2015
COCHRANE DB SYST REV

T Duivenvoorden
R W Brouwer
T M Van Raaij

Duivenvoorden T, Brouwer RW, van Raaij TM, et al. Bierma-Zeinstra Braces and orthoses for osteoarthritis of the knee. Cochrane Database Syst Rev 2015;CD004020.

The effectiveness of prolotherapy in treating knee osteoarthritis in adults: A systematic review

Abstract

No full-text available

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