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Randomised double-blind, positive-controlled trial to assess the efficacy of glucosamine/chondroitin sulfate for the treatment of dogs with osteoarthritis
Abstract
Thirty-five dogs were included in a randomised, double-blind, positive controlled, multi-centre trial to assess the efficacy of an orally-administered glucosamine hydrochloride and chondroitin sulfate (Glu/CS) combination for the treatment of confirmed osteoarthritis of hips or elbows. Carprofen was used as a positive control. Dogs were re-examined on days 14, 42 and 70 after initiation of treatment. Medication was then withdrawn and dogs were re-assessed on day 98. Response to treatment was based on subjective evaluation by participating veterinarians who recorded their findings at each visit. Dogs treated with Glu/CS showed statistically significant improvements in scores for pain, weight-bearing and severity of the condition by day 70 (P<0.001). Onset of significant response was slower for Glu/CS than for carprofen-treated dogs. The results show that Glu/CS has a positive clinical effect in dogs with osteoarthritis.
... Therefore, investigation of alternative treatment options, including nutraceuticals, to manage the clinical signs of OA is warranted. 6,7 The pathogenesis of OA is complex, but damage by synovial free radicals has been identified as a key process. Oxidative stress causes decreased chondrogenesis with subsequent cartilage thinning and is an important aspect in the pathogenesis of OA. 8 Humans suffering from OA have higher concentrations of oxidants and lower concentrations of antioxidants in synovial fluid, supporting their contribution to the development of OA. 9 Vitamin E (VE) is a potent antioxidant found naturally in plants, and in vitro testing on animals has elucidated its ability to decrease the effects of oxidative stress on cartilage. ...
... To identify a difference of 1 unit in clinical lameness score between placebo and treatment groups (mean score control group, 18 ± 1; mean score treatment group, 17 ± 1) with a power of 0.95 and alpha error probability of 0.05 the required sample size was estimated to be 27 per group (54 total). 6 We aimed to recruit 68 dogs (34 per group) to account for an approximately 20% case dropout or loss to follow-up. ...
... The scoring system yielded a numerical value for each component of the examination, from 1 to 5 (Table A1). The scoring system was adapted from another study assessing supplementation in the treatment of OA. 6 Body condition scores (BCS; 0-9) and body weight was recorded at each visit to account for obese animals and any changes in body weight throughout the study. ...
Background
Vitamin E has a positive effect in the management of osteoarthritis in humans, and in a previous study of dogs. It has been suggested to decrease C‐reactive protein concentrations and liver enzyme activities in humans and animals.
Objective
To assess the effect of vitamin E supplementation on lameness, pain, pain medication requirement, clinical pathology variables, and quality of life in large‐breed dogs with naturally occurring osteoarthritis.
Animals
Fifty‐seven client‐owned dogs with naturally occurring osteoarthritis.
Methods
Dogs received either vitamin E or placebo for 90 days in a randomized, placebo‐controlled, double‐blinded, prospective clinical trial. Clinical lameness scores, pain medication requirements, and owner questionnaires were used to assess response to treatment every 30 days. Blood samples were collected at enrollment and at the end of the study period.
Results
Vitamin E administration did not improve pain, lameness, or quality of life as assessed by owners and veterinarians. Vitamin E supplementation did not decrease the requirement for rescue pain relief. No changes in clinical pathology variables were observed after 90 days of vitamin E supplementation. Body weight was negatively associated with the lameness scores and requirement for rescue pain relief.
Conclusion
Vitamin E supplementation did not have any observable positive effects in dogs with naturally occurring osteoarthritis.
... Various combinations of glucosamine hydrochloride and chondroitin sulfate are probably the most common nutraceuticals used in dogs with OA (6). Based on the available literature (5,(13)(14)(15)(16)(17)(18), the evidence for a benefit of glucosamine and chondroitin in is mixed. ...
... At each timepoint, a full orthopedic evaluation was performed (after gait analysis), and Orthopedic Assessment Scores (OAS) recorded. The OAS system was originally described by Moreau et al. (5) and adapted by McCarthy et al. (15). Lameness, joint mobility, pain on palpation, weight-bearing and the overall impact were assessed, and scored as outlined in Table 1. ...
... The results for the glucosamine/chondroitin group were similar to previous studies that measured GRFs at ∼1 month following initiation of treatment (5,21). However, previous studies have reported positive effects of glucosamine/chondroitin for the treatment of OA-pain after 70 days of treatment (15), and 90 days of treatment (16). It is possible that positive effects of glucosamine/chondroitin would have been seen with a longer duration of treatment. ...
Introduction
Glucosamine hydrochloride and chondroitin sulfate are commonly used in dogs with OA, but evidence around efficacy is mixed. This study evaluated the effectiveness of glucosamine and chondroitin sulfate, marine based fatty acid compounds (PCSO-524 and EAB-277), and carprofen for the alleviation of canine hip OA pain. This was a prospective, block-randomized, double-blinded, placebo-controlled clinical trial.
Methods
Seventy-five owned pet dogs with hip OA were assigned randomly into five treatment groups: PCSO-524, Glucosamine and chondroitin sulfate, EAB-277, carprofen, and Placebo (sunflower oil). Peak vertical force (PVF) and subjective orthopedic assessment scores (OAS) were evaluated before treatment (week 0), and at weeks 2, 4, and 6 during treatment.
Results
At week 2, the carprofen group showed a significant increase in PVF (3.14 ± 5.33; mean ± SD). After 4 weeks, the increases in PVF of the PCSO-524 (3.90 ± 3.52), EAB-277 (4.17 ± 4.94), and carprofen (3.08 ± 5.87) groups were significant, and significantly greater than placebo (0.08 ± 1.90) and glucosamine (−0.05 ± 6.34) groups. After 6 weeks, the change of PVF in the PCSO-524 (4.14 ± 4.65), EAB-277 (4.45 ± 4.23), and carprofen (4.21 ± 6.52) groups were significant and significantly higher than the placebo group (−0.33 ± 3.65). The change in PVF in the glucosamine group (1.08 ± 5.49) lay between the placebo group and the other treatment groups. The OAS did not show any significant change in any group.
Discussion
PCSO-524 and EAB-277, but not glucosamine/chondroitin, resulted in significant improvements in PVF from baseline after 4 weeks, and 6 weeks, and to a similar degree to that seen with carprofen.
... Carrig (1997) and colleagues discussed the correlation between age and irregularities and abnormal cartilage surfaces in large dog breeds (Carrig, 1997;Loeser et al., 2016). These alterations are due to biochemical modifications in the pattern of cartilage throughout life, which become weak and less resistant to damage over time, as described in dogs (McCarthy et al., 2007;McDevitt & Muir, 1976;Ytrehus et al., 2007). However, in the present study, age did not influence the results. ...
... However, in the present study, age did not influence the results. This may be because the animals in our study were younger than the human subjects (55-64 years) (Ytrehus et al., 2007) and dogs (7-9 years) (McDevitt & Muir, 1976;McCarthy et al., 2007McCarthy et al., , 2012) that were the subject of previous studies. Throughout life, various factors, such as weight-bearing and weight gain (McCarthy et al., 2007), traumas, or joint instability, can lead to adaptation of the joint, particularly in athletes. ...
... This may be because the animals in our study were younger than the human subjects (55-64 years) (Ytrehus et al., 2007) and dogs (7-9 years) (McDevitt & Muir, 1976;McCarthy et al., 2007McCarthy et al., , 2012) that were the subject of previous studies. Throughout life, various factors, such as weight-bearing and weight gain (McCarthy et al., 2007), traumas, or joint instability, can lead to adaptation of the joint, particularly in athletes. ...
Racehorses are exposed to repetitive overload during training and competition, causing joint hyperextension, tissue fatigue, and ultimately skeletal failure. Some degree of bone changes, such as sclerosis, are expected in equine athletes, as adaptation to the biomechanical rigors of training and racing. Understanding the imaging characteristics of the equine joint surface and subchondral bone would allow earlier detection of injuries or adaptation, improving prognosis and training programs. This study sought to describe the joint surface structural patterns and the periarticular structures of the third metacarpal bone (MC3). Both forelimbs of eight horses engaged in daily training programs, aged 3–5 years, which were euthanized for reasons unrelated to the metacarpophalangeal (MCP) joints, were collected. Specimens were evaluated through macroscopic inspection, radiography, ultrasonography, and microscopic examinations, such as optical microscopy and microtomography. Analysis of the microtomography images showed that 50% of the samples had higher trabecular thickness in the lateral condyle. Comparison of each imaging examination revealed that ultrasound images were most closely related to the histological examination (p = .29) in terms of sensitivity, while macroscopic and radiographic examinations differed most between evaluators. Finally, the irregularities and modifications observed in the articular cartilage surface and subchondral bone were normal adaptations of the anatomical structures of trained racehorses, which should be considered during clinical examination.
... In the present study, as expected Rimadyl TM in the first 6 weeks of treatment had an almost immediate effect on the perceived assessment of pain and activity, as it has been reported in previous clinical studies with carprofen, meloxicam, or etodolac in OA dogs [7,43,37]. In several clinical studies conducted in OA dogs, carprofen (Rimadyl TM ) has been used: 1) alone for the treatment of OA in dogs [26,59,40] as a positive control or in combination with nutraceuticals [37,25,18]. ...
... In the present study, as expected Rimadyl TM in the first 6 weeks of treatment had an almost immediate effect on the perceived assessment of pain and activity, as it has been reported in previous clinical studies with carprofen, meloxicam, or etodolac in OA dogs [7,43,37]. In several clinical studies conducted in OA dogs, carprofen (Rimadyl TM ) has been used: 1) alone for the treatment of OA in dogs [26,59,40] as a positive control or in combination with nutraceuticals [37,25,18]. In addition to inhibition of COX-1 and COX-2 activities [51], carprofen has been reported to simultaneously reduce progression of morphological changes in cartilage and subchondral bone in OA dogs [45]. ...
... In contrast to Rimadyl TM , the apparent anti-inflammatory effect of BVP-01 took longer to occur. This is consistent with a longer period required for an anti-inflammatory nutraceutical to have an effect than NSAID's [24,47,37,20,31,17,12,43,60]. However, serious adverse effects with the long-term use of the COX inhibiting NSAIDs have been associated with hepatic, renal, cardiovascular and GI systems [42,44,40,3,48,29,46,53,6]. ...
... 13 Nutritional management, including the feeding of therapeutic diets formulated for joint health, dietary supplementation with selected nutraceuticals, and facilitation of weight loss when needed, may help to prevent or slow the progression of osteoarthritis. 3,4,11,[13][14][15][16][17][18][19][20][21][22][23] ...
... [57][58][59][60] Glucosamine also decreases signs of pain associated with osteoarthritis in dogs. 23 In a randomized, double-blinded, positive-controlled study 23 in which dogs with osteoarthritis received either carprofen or glucosamine and chondroitin sulfate for 70 days, assessment of the animals by veterinarians indicated that by the end of the study period, dogs in both the glucosamine-chondroitin sulfate and carprofen groups had significant subjective improvements in scores for pain, weight bearing, and overall condition, compared with the findings at baseline (prior to the described interventions). However, the onset of improvement in signs of osteoarthritis in the glucosamine-chondroitin sulfate group was delayed, compared with results for the carprofen group, suggesting that continuous dietary supplementation at an appropriate dose should be provided and that more time may be needed to observe such benefits. ...
... [57][58][59][60] Glucosamine also decreases signs of pain associated with osteoarthritis in dogs. 23 In a randomized, double-blinded, positive-controlled study 23 in which dogs with osteoarthritis received either carprofen or glucosamine and chondroitin sulfate for 70 days, assessment of the animals by veterinarians indicated that by the end of the study period, dogs in both the glucosamine-chondroitin sulfate and carprofen groups had significant subjective improvements in scores for pain, weight bearing, and overall condition, compared with the findings at baseline (prior to the described interventions). However, the onset of improvement in signs of osteoarthritis in the glucosamine-chondroitin sulfate group was delayed, compared with results for the carprofen group, suggesting that continuous dietary supplementation at an appropriate dose should be provided and that more time may be needed to observe such benefits. ...
... Physical exercises on an aquatic treadmill contribute to weight control, a crucial factor in therapeutic management to avoid joint overload [21,24]. The physical properties of water decrease the relative weight of the animal due to buoyancy, and the increased density challenges the muscles more than air [20,42]. These properties make underwater treadmills and swimming ideal exercises for animals with arthropathy, providing greater energy expenditure and less joint impact [11], and are particularly important in the multimodal treatment of canine obesity in dogs with osteoarthritis [11,21,42,56]. ...
... The physical properties of water decrease the relative weight of the animal due to buoyancy, and the increased density challenges the muscles more than air [20,42]. These properties make underwater treadmills and swimming ideal exercises for animals with arthropathy, providing greater energy expenditure and less joint impact [11], and are particularly important in the multimodal treatment of canine obesity in dogs with osteoarthritis [11,21,42,56]. ...
Hip dysplasia is a prevalent hereditary condition affecting dogs and cats, characterized by inadequate development of the hip joint. This condition leads to pain due to capsular distension, microfractures, and joint incongruity in young animals, ultimately progressing to osteoarthritis in adult and elderly animals. The pursuit of pain relief and improved quality of life for individuals with osteoarthritis has been a focal point in several studies. In this context, veterinary physiotherapy has gained prominence in small animal practice, serving as both palliative care and a supportive modality in the clinical or post-surgical management of degenerative joint diseases. Laser therapy and hydrotherapy, recognized for their analgesic effects and capacity to promote muscle mass gain, have garnered attention for their potential efficacy in treating joint diseases. This study aims to evaluate the therapeutic effects of super pulsed laser therapy and controlled low-impact exercises (water treadmill) on a patient recovering from surgery involving bilateral femoral head and forehead resection. We observed positive outcomes, including pain resolution, improved muscle mass, and enhanced range of motion, contributing to the patient's overall recovery.
... 4) showed strong evidence of non-effect and a significant statistical difference in efficacy from the other categories (ctg. 1, 2, 3 and 5) in the meta-analysis. Of the nine trials assessed in this review, only one [49] showed an improvement in the condition of the animals assessed, but this was using a non-validated subjective tool and for only one assessment time (at day 70), a difference not present before (day 14 or 42) or after (day 90). It should be noted that dosing was reduced by one third between days 42 and 70 and stopped after day 70, while the authors concluded that there was non-inferiority of the nutraceuticals vs. a positive control using carprofen in their OA dogs [49]. ...
... Of the nine trials assessed in this review, only one [49] showed an improvement in the condition of the animals assessed, but this was using a non-validated subjective tool and for only one assessment time (at day 70), a difference not present before (day 14 or 42) or after (day 90). It should be noted that dosing was reduced by one third between days 42 and 70 and stopped after day 70, while the authors concluded that there was non-inferiority of the nutraceuticals vs. a positive control using carprofen in their OA dogs [49]. ...
With osteoarthritis being the most common degenerative disease in pet animals, a very broad panel of natural health products is available on the market for its management. The aim of this systematic review and meta-analysis, registered on PROSPERO (CRD42021279368), was to test for the evidence of clinical analgesia efficacy of fortified foods and nutraceuticals administered in dogs and cats affected by osteoarthritis. In four electronic bibliographic databases, 1578 publications were retrieved plus 20 additional publications from internal sources. Fifty-seven articles were included, comprising 72 trials divided into nine different categories of natural health compound. The efficacy assessment, associated to the level of quality of each trial, presented an evident clinical analgesic efficacy for omega-3-enriched diets, omega-3 supplements and cannabidiol (to a lesser degree). Our analyses showed a weak efficacy of collagen and a very marked non-effect of chondroitin-glucosamine nutraceuticals, which leads us to recommend that the latter products should no longer be recommended for pain management in canine and feline osteoarthritis.
... The study performed by Adebowale et al. (123) demonstrated an oral bioavailability of 12% for glucosamine hydrochloride and 5% for chondroitin sulfate. Despite the differences in clinical studies from a point of view of design, products and results, there have been some wellconducted studies that provide more insight into the use of glucosamine and chondroitin (124)(125)(126)(127)(128)(129)(130)(131). These studies evaluated joint function, comfort of the patient, and the overall safety profile of the supplement. ...
... The follow-up ranged from 2 to 6 months, with dosing around 40-62.5 mg/kg/d for glucosamine hydrochloride and 12-50 mg/kg/d for chondroitin sulfate in dogs, doubled for cats (132). No improvement was observed with objective outcomes in any study, and mild improvement was observed with non-validated subjective clinical scoring at three time-points in one study [Day 90,120,and 150 (129)] and in one time-point in another study [Day 70 (127)]. Little is known about the actual effects of glucosamine and chondroitin at the level of the joint in either late or early stages of OA (133,134). ...
The Canadian consensus guidelines on OA treatment were created from a diverse group of experts, with a strong clinical and/or academic background in treating OA in dogs. The document is a summary of the treatment recommendations made by the group, with treatments being divided into either a core or secondary recommendation. Each treatment or modality is then summarized in the context of available research based support and clinical experience, as the treatment of OA continues to be a multimodal and commonly a multidisciplinary as well as individualized approach. The guidelines aim to help clinicians by providing clear and clinically relevant information about treatment options based on COAST defined OA stages 1–4.
... Da mesma forma, no Guideline mais recente do Colégio Americano de Reumatologia para o manejo da osteoartrite em humanos, o uso destas substâncias foi contraindicado. Em contrapartida, McCarthy et al. (2007) demonstraram em um estudo randomizado duplo cego, com controle positivo, que cloridrato de glicosamina e sulfato de condroitina apresentaram efeito clínico positivo em cães com artrite após 70 dias de tratamento. ...
... Doses de 22 a 44 mg/kg de glicosamina, por via oral dia (Papich, 2009) e de 13 a 30 mg/kg de SC, por via oral (Plumb, 2008) têm sido recomendadas. McCarthy et al. (2007) utilizaram uma formulação comercial de glicosamina, SC e associações em cães com osteoartrite, obtendo resultados positivos, seguindo a posologia recomendada pelo fabricante, com 1g de ingrediente ativo duas vezes por dia para cães pesando 5-19,9 kg, corroborando a escolha utilizada neste experimento; assim devido à variedade de formulações, acredita-se que a melhor opção para a escolha da posologia é seguir a recomendação do fabricante. ...
O objetivo do presente estudo foi comparar o número de discos intervertebrais da coluna toracolombar mineralizados em cães jovens da raça Dachshund, que receberam ou não suplementação com sulfatos de condroitina, glicosaminoglicanos e manganês. Vinte filhotes de quatro meses de idade foram divididos em dois grupos de dez, sendo a seguir submetidos a dois protocolos de tratamento durante 240 dias. Grupo nutracêutico (GN) recebeu um tablete, ao dia, por via oral, contendo nutracêuticos e excipientes. Grupo controle (GC) recebeu um tablete, ao dia, por via oral, contendo os mesmos excipientes do GN. Imagens tomográficas foram obtidas nos momentos zero e após oito meses de tratamento. O percentual de animais classificados com mineralização foi mais elevado no GC quando comparados com GN (64,3% x 44,3%), diferença esta que para a margem de erro fixada (5%) se mostra significativa entre os grupos em relação à presença de mineralização (p < 0,05 risco relativo igual a 1,45 com intervalo que exclui o valor 1,00). No GN as maiores frequências de mineralização ocorreram no disco intervertebral T09-10 (70,0%), T11-12 e T13-L1 (50,0%) e, no GC, T09-10 (90,0%) e T10-11 (80,0%). Pode-se concluir que a administração da associação de manganês, sulfatos de condroitina e glicosamina, durante o primeiro ano de vida, em cães da raça Dachshund Miniatura, diminuiu o número de mineralizações discais na coluna toracolombar.
... Some studies in dogs identified benefits to receiving GCS supplements. In one clinical trial with 35 client-owned dogs, pain on palpation was lower after GCS administration (82). Other studies failed to identify clinical improvement in dogs receiving a GCS supplement (83,84), possibly because OA has wide-ranging consequences and because GCS would not eliminate all consequences of OA. ...
Osteoarthritis (OA) is a ubiquitous problem affecting dog joints, particularly the hip, elbow, stifle, and spine. OA most often results from developmental orthopedic problems such as hip dysplasia, elbow dysplasia, and patellar luxation and from injuries to the cranial cruciate ligament. Several management approaches have been proposed to manage OA, including steps to modulate growth, physical activity, and exercise, nutrition and nutritional supplementation, medications, physical rehabilitation, and surgical procedures. This article is the first in a series of articles that propose steps for practical OA management in dogs at various life stages. The review presented here focuses on growing dogs. The text describes the early pathophysiology and diagnosis of OA. The physical, nutritional, analgesic, and surgical management options of OA in growing dogs are presented. The application of these management options is described for three dogs. The overall approach to the management of OA in growing dogs is discussed.
... Supplementation with chondroitin sulfate (CS) has been suggested for the treatment of degenerative joint diseases, and can be performed orally, subcutaneously, intramuscularly or even directly locally (intra-articular or intradiscal) (McCarthy, et al., 2007;Raynauld et al., 2016). However, the wide range of methodologies used in studies analyzing the adjuvant effects of nutraceuticals and their associations regarding different routes of application, dosages and treatment period for degenerative joint disease are reasons for controversy in recommending their prescription (Stuber et al., 2011;Fernández-Martín et al., 2021). ...
The present study evaluated the influence of bone marrow-derived stem cells (BM-SC) and chondroitin sulfate (CS) on histological changes in intervertebral disc (IVD). A randomized clinical trial was conducted, thirty-six healthy New Zealand rabbits were randomly distributed into four different groups (n=9): con-trol group (A), stem cell group (B), chondroitin sulfate group (C), and associa-tion of stem cells with chondroitin sulfate group (D). All animals underwent the experimental disc degeneration procedure. Group A received two intradiscal applications of DEM (Dulbecco’s modified eagle’s medium), one and two weeks after intervertebral disc degeneration (IVDD), while group B received two intradiscal applications of 1.2 x 106 BM-SC at the same time interval as group A. After IVDD, group C received eight subcutaneous applications of CS at a dose of 5 mg/kg, one application every seven days. In contrast, group D received the association of the techniques used in groups B and C. Sixty days after the end of the interventions, all animals were euthanized, then the crani-ocaudal thickness of the IVD was measured, and IVDD was classified in scores according to the histological grading model. All groups that received CS had thicker IVDs, and all the treated groups presented better scores on several items and a better overall score. It was possible to conclude that in the species studied, the isolated use of CS or BM-SC was statistically significant in improv-ing the histopathological aspects of IVDD, however, the combination of treat-ments did not prove to be more efficient.
... Instead, comprehensive symptom management is achievable through physiotherapy (rehabilitation) complemented by nutraceutical integration. Unlike surgical approaches, physiotherapy addresses the underlying muscular, tendinous, and ligamentous changes associated with CFD [19,29,32,41] (Table 1). Table 1. ...
Hip dysplasia is a prevalent hereditary condition affecting dogs and cats, characterized by inadequate development of the hip joint. This condition leads to pain due to capsular distension, microfractures, and joint incongruity in young animals, ultimately progressing to osteoarthritis in adult and elderly animals. The pursuit of pain relief and improved quality of life for individuals with osteoarthritis has been a focal point in several studies. In this context, veterinary physiotherapy has gained prominence in small animal practice, serving as both palliative care and a supportive modality in the clinical or post-surgical management of degenerative joint diseases. Laser therapy and hydrotherapy, recognized for their analgesic effects and capacity to promote muscle mass gain, have garnered attention for their potential efficacy in treating joint diseases. This study aims to evaluate the therapeutic effects of super pulsed laser therapy and controlled low-impact exercises (water treadmill) on a patient recovering from surgery involving bilateral femoral head and forehead resection. We observed positive outcomes, including pain resolution, improved muscle mass, and enhanced range of motion, contributing to the patient's overall recovery.
... Instead, comprehensive symptom management is achievable through physiotherapy (rehabilitation) complemented by nutraceutical integration. Unlike surgical approaches, physiotherapy addresses the underlying muscular, tendinous, and ligamentous changes associated with CFD [19,29,32,41] (Table 1). ...
Hip dysplasia is a prevalent hereditary condition affecting dogs and cats, characterized by inadequate development of the hip joint. This condition leads to pain due to capsular distension, microfractures, and joint incongruity in young animals, ultimately progressing to osteoarthritis in adult and elderly animals. The pursuit of pain relief and improved quality of life for individuals with osteoarthritis has been a focal point in several studies. In this context, veterinary physiotherapy has gained prominence in small animal practice, serving as both palliative care and a supportive modality in the clinical or post-surgical management of degenerative joint diseases. Laser therapy and hydrotherapy, recognized for their analgesic effects and capacity to promote muscle mass gain, have garnered attention for their potential efficacy in treating joint diseases. This study aims to evaluate the therapeutic effects of super pulsed laser therapy and controlled low-impact exercises (water treadmill) on a patient recovering from surgery involving bilateral femoral head and forehead resection. We observed positive outcomes, including pain resolution, improved muscle mass, and enhanced range of motion, contributing to the patient's overall recovery.
... and chondroitin are frequently utilized in the management of osteoarthritis, although there is limited data available regarding appropriate dosage and efficacy (Bhathal A. et al., 2017). A recent study suggested that administration of glucosamine and chondroitin for 70 days led to improvements in subjective pain scores, weight-bearing, and overall condition compared to baseline values (Millis D. , Levine D., 2014) However, other studies have demonstrated minimal or no discernible effect (McCarthy G. et al., 2007). ...
Osteoarthritis is a common condition in dogs, particularly affecting elderly individuals, and the chronic pain it causes significantly impacts the quality of life of affected dogs. First, we will focus on the joint, the physiopathology of osteoarthritis, and the mechanisms of arthritic pain production, and then discuss the existing treatments. There are numerous treatments available for managing this complex osteoarticular condition, but unconventional therapies are increasingly of interest to owners of canine species. Phytotherapy harnesses the healing properties of plants for treatment in a less toxic, more natural, and more cost-effective manner, offering a wide range of therapeutic options for animals. The objective of this review is to evaluate the present evidence backing treatments for canine osteoarthritis. This includes non-steroidal anti-inflammatory drugs, piprants, monoclonal antibodies, adjunctive analgesics, structuremodifying osteoarthritis drugs, phytotherapy, and regenerative therapies.
... Based on current literature, the beneficial effects of glucosamine and chondroitin in the treatment of canine OA can neither be confirmed or denied as clinical trials have had mixed results. McCarthy et al. (2007) found dogs consuming glucosamine/chondroitin had statistically significant improvements in scores for pain, weight-bearing and OA severity by day 70, and was non-inferior to carprofen at day 70. Contrastingly, Scott et al. (2017) found that dogs treated with oral glucosamine hydrochloride and chondroitin sulphate for 90 days did not display increased activity levels when compared with a placebo, although owner assessment scores increased, indicating a possible caregiver placebo effect. ...
Osteoarthritis is a progressive degenerative disease process that affects a significant proportion of the canine population, impacting these animals' quality of life. Currently, there is no cure and treatment consists of managing the clinical signs of pain and reduced mobility. There are many treatments for canine osteoarthritis and in this review we discuss the evidence base behind non‐pharmaceutical, non‐surgical treatments of this disease. These treatments include weight management, nutraceuticals, acupuncture, physiotherapies such as therapeutic exercise, hydrotherapy as well as other therapeutic modalities including photobiomodulation therapy, electromagnetic field therapy and others.
... A glucosamina e sulfato de condroitina são componentes da cartilagem e apresentam uma melhora na dor do paciente quando suplementados na dieta (McCarthy et al., 2007). Ademais, é constado que tais componentes, em conjunto ao ácido hialurônico, se mostram elevados em soros de cães com osteoartrite, o qual é indicado a partir do aumento do epítopo WF6 no uso de anticorpos monoclonais. ...
Osteoartrose ou doença articular degenerativa é uma afecção comum em cães e gatos com grande relevância na medicina veterinária, acometendo principalmente membros locomotores do quadril e prejudicando a qualidade de vida do paciente. Por promover uma degeneração dos componentes articulares, trata-se de uma enfermidade progressiva e de ação lenta, a qual ocorre por diversos fatores. Essa pode ser primária, secundária ou erosiva havendo também classificações com que diz respeito ao grau da doença do animal. O diagnóstico, apesar de ser de difícil detecção na fase inicial, é baseado nos achados clínicos, exame físico de palpação dos membros afetados e exames de imagem que concluem o diagnóstico com precisão. Os tratamentos são inúmeros e dependem de diversos fatores, assim como o prognóstico, que incluem membro afetado, grau de lesão, histórico do paciente entre outros parâmetros a serem analisados. Atualmente ainda há discussões entre os profissionais sobre o melhor método de conduta, principalmente para o tratamento, mas cada vez mais os resultados tem se mostrado mais satisfatórios. Diante de tal complexidade, o presente artigo tem como objetivo aprofundar os estudos com enfoque no quadril que é uma das mais acometidas na rotina da clínica veterinária de pequenos animais, permitindo uma maior eficiência no tratamento e evolução da compreensão da dor.
... The scale used was based on the work from McCarthy et al. 40 For animal welfare, no animals were included with 5 points in any of the parameters. ...
OBJECTIVE
To demonstrate the efficacy and safety of mesenchymal stem cells (MSCs) for xenogeneic use with intra-articular administration in dogs with osteoarthritis.
ANIMALS
80 client-owned dogs with naturally occurring osteoarthritis in elbow or hip.
PROCEDURES
A multicentric, double-blinded, parallel, randomized and placebo-controlled clinical trial was performed. After intra-articular injection of equine umbilical cord MSCs, dogs were reexamined at weeks 4, 8, and 12 using a force platform (gait analysis), orthopedic assessment, and validated owner questionnaire. Eighteen months after treatment, a long-term follow-up was done.
RESULTS
Best results were obtained 8 weeks after treatment, where 63% of the patients showed an improvement in the gait analysis. Also 8 weeks after treatment, 77% of the dogs improved in the orthopedic examination; 65% of the owners considered that the treatment improved their pet’s quality of life 8 weeks after treatment. The long-term follow-up revealed that 59% of the owners observed a duration of effect longer than 6 months after a single intra-articular injection of equine umbilical cord MSCs. No systemic or permanent adverse events were detected at any time point.
CLINICAL RELEVANCE
Results of this study demonstrated the safety and efficacy of intra-articular administration of xenogeneic MSCs for the treatment of canine osteoarthritis.
... Additionally, we created covariates for lifestyle factors that preliminary evidence suggests might affect physical activity and/or cognition. If dogs received glucosamine and/or other joint supplements daily, they were considered "affected" in the joint supplement category [51]. If dogs received omega 3, vitamins, probiotics, antioxidants, taurine, carnitine, and/or coenzyme Q10 daily, they were considered "affected" in the neuroprotective supplement category [26,[52][53][54][55]. ...
Canine cognitive dysfunction (CCD) is a form of dementia that shares many similarities with Alzheimer's disease. Given that physical activity is believed to reduce risk of Alzheimer's disease in humans, we explored the association between physical activity and cognitive health in a cohort of companion dogs, aged 6-18 years. We hypothesized that higher levels of physical activity would be associated with lower (i.e., better) scores on a cognitive dysfunction rating instrument and lower prevalence of dementia, and that this association would be robust when controlling for age, comorbidities, and other potential confounders. Our sample included 11,574 companion dogs enrolled through the Dog Aging Project, of whom 287 had scores over the clinical threshold for CCD. In this observational, cross-sectional study, we used owner-reported questionnaire data to quantify dog cognitive health (via a validated scale), physical activity levels, health conditions, training history, and dietary supplements. We fit regression models with measures of cognitive health as the outcome, and physical activity-with several important covariates-as predictors. We found a significant negative relationship between physical activity and current severity of cognitive dysfunction symptoms (estimate = - 0.10, 95% CI: - 0.11 to - 0.08, p < 0.001), extent of symptom worsening over a 6-month interval (estimate = - 0.07, 95% CI: - 0.09 to - 0.05, p < 0.001), and whether a dog reached a clinical level of CCD (odds ratio = 0.53, 95% CI: 0.45 to 0.63, p < 0.001). Physical activity was robustly associated with better cognitive outcomes in dogs. Our findings illustrate the value of companion dogs as a model for investigating relationships between physical activity and cognitive aging, including aspects of dementia that may have translational potential for Alzheimer's disease. While the current study represents an important first step in identifying a relationship between physical activity and cognitive function, it cannot determine causality. Future studies are needed to rule out reverse causation by following the same dogs prospectively over time, and to evaluate causality by administering physical activity interventions.
... We also chose these specific evaluation moments based on previous reports on the evaluation of OA treatment in dogs (30)(31)(32)(33). However, additional or different evaluation moments can be selected, for example, to correspond with treatments times. ...
The aim of this study was to document the effects of mesotherapy in working dogs diagnosed with hip osteoarthritis (OA) and related pain. Ten police working dogs with hip OA and related pain were treated with a combination of lidocaine, piroxicam, and thiocolchicoside, injected in multiple intradermal points. Seven treatment sessions were conducted. The Canine Brief Pain Inventory (CBPI) and the Hudson Visual Analogue Scale (HVAS) were used in the assessment of response to treatment compared to evaluation before treatment (T0), after 15 d, 30 d, 60 d, 90 d, 120 d, 150 d, and 180 d after initial treatment. Results were compared using the Wilcoxon signed-rank test. Significant differences were experienced in CBPI scores comparing moments with T0: at 15 d (P = 0.03 for Pain Interference Score - PIS) and P = 0.02 for Pain Severity Score - PSS), 30 d (P < 0.05 for PIS and P < 0.05 for PSS), 60 d (P = 0.04 for PIS and P = 0.01 for PSS) and 180 d (P = 0.04 for PSS). Individual treatment results were considered successful in 40% of animals at 15 d and 30 d, 66.7% at 60 d, 44% at 90 d, 37.5% at 120 d, and 25% at 150 d. The HVAS scores showed no significant differences. Mesotherapy may be an option for the treatment of canine musculoskeletal-related pain. Further studies are required.
... A grade ⅖ lameness was identified on gait analysis (►Video 3). 12 No cranial tibial thrust was identified during awake examination. Full extension of the digits of the left hindlimb caused mild discomfort; however, no difference in digit position was identified during stance examination. ...
This case report describes the use of a Z-plasty tenotomy and anastomosis to surgically lengthen the deep digital flexor (DDF) tendons of digits 2 to 5 of the pelvic limb in a 6-year-old male castrated Greyhound. The procedure was used to treat contracture of this tendon complex which developed after a series of complications secondary to proximal osteotomies utilized for the treatment of cranial cruciate ligament rupture. The dog was evaluated for lameness associated with left cranial cruciate ligament rupture and excessive tibial plateau slope; accordingly, a combined tibial plateau levelling osteotomy and cranial closing wedge ostectomy was performed. Postoperatively, the dog developed substantial DDF tendon contracture that led to severe digital hyperflexion and contributed to a non-weight bearing lameness. The dog received intensive rehabilitation therapy but failed to substantially improve; therefore, all of the weight-bearing left hindlimb DDF tendons were lengthened with a Z-plasty tenotomy and anastomosis followed by further rehabilitation. Follow-up evaluation 44 months postoperatively documented mild, intermittent left hindlimb lameness on gait observation and confirmed success of the Z-plasty procedure via ultrasonographic evaluation. Conservative treatment alone was unsuccessful in managing DDF tendon contracture in this dog. Z-plasty tenotomy and anastomosis of the DDF tendon allowed for return-to-acceptable function in this case.
... Before treatment initiation and at 4 and 8 wk, each dog was evaluated by the study veterinarian at the respective veterinary hospital, who assessed locomotion, joint pain, weight-bearing, and crepitus on a 5-point scale based on a subjective scoring system as previously reported (19). Baseline assessments included patient signalment, use of NSAID medication, and/or diseasemodifying supplements (if applicable), presence of unilateral or bilateral lameness, body weight, and body condition score (BCS) on a scale of 1 to 9. Study veterinarians at both locations had extensive training and experience in the specialty of canine rehabilitation, with active or pending Board certification in the American College of Veterinary Sports Medicine and Rehabilitation. ...
Osteoarthritis is the most common joint disease in dogs. Despite the use of nonsteroidal anti-inflammatory drugs (NSAIDs), many owners seek natural therapies; either to augment the response to NSAIDs, or as a replacement. Substantial research has been directed to investigation of novel therapies. A randomized, double-blinded, controlled study was conducted to assess the efficacy of a herbal remedy for treatment of canine osteoarthritis pain. Client-owned dogs (N = 24) with osteoarthritis were enrolled between 2 veterinary hospitals. Each dog underwent veterinary and owner assessment at 0, 4, and 8 weeks, using the Canine Brief Pain Inventory and Hudson activity scale. Blood was collected for a complete blood (cell) count (CBC) and serum chemistry analysis. The product was deemed to be safe and well-tolerated at the manufacturer recommended dosage, with no significant changes seen in the CBC or serum biochemical analyses. Aside from1 dog that developed gastrointestinal upset, all other dogs tolerated the supplement without complication. The supplement did not statistically improve clinical signs in dogs based on veterinary or owner assessments of lameness. There was a treatment/time effect when assessing veterinary pain scores; however, post-hoc analysis suggests no observable benefit of treatment compared with the placebo group at any time point.
... 10 Several studies have suggested that GS and CS supplements increase the synthesis of proteoglycans 11 and deliver anti-catabolic, 12 chondro-protective 11,13 and mild anti-inflammatory effects, [14][15][16] which may contribute to the beneficial results seen in-vitro and in vivo models. [17][18][19][20][21] However, there is limited orthodontic evidence of pharmaceutical enhancement showing that the use of GS and CS improves condylar cartilage adaptation secondary to functional appliance therapy. Therefore, the aim of the present investigation was to quantitatively and qualitatively analyse the effects of GS/CS supplementation on condylar cartilage remodelling during functional appliance therapy. ...
Objectives
The purpose of this study was to qualitatively and quantitatively analyse the effect of glucosamine sulfate and chondroitin sulfate supplements on condylar remodelling in conjunction with bite-jumping functional appliance therapy in rats.
Materials and methods
The study involved 140 three-week-old, female rats which were divided into a control group (CG), a supplementation group (SG), a functional appliance (bite-jumping) group (FG) and a bite-jumping appliance and supplement recipient group (FSG). The animals were sacrificed at Day 0, Day 7 and at Day 21 after appliance placement, as well as seven days following appliance removal. The condylar head from each animal was blindly scanned using micro-computed tomography (μCT). Qualitative evaluation and volumetric measurements of the condyles, including total condylar volume (TCoV), posterior condylar volume (PCoV), total cartilage volume (TCaV) and posterior cartilage volume (PCaV), were undertaken using VGStudioMax software.
Results
One hundred and thirty-five rats were analysed, some of which responded to the intervention with a protruded bite (Class III response) while others responded with a retruded bite (Class II response). The TCoV and PCoV of the CG decreased during the experimental period. The functional appliance alone and the combination of the functional appliance with the supplement had a significant effect on TCoV and PCoV over the intervention period ( p < 0.01), peaking at Day 7. There was no statistically significant difference in TCaV between animals that experienced Class II and Class III bite responses at Days 21 and 28 ( p > 0.05). However, at Day 21, the PCaV increased significantly in those animals which displayed a Class II bite response ( p < 0.05). The shape of the condyles in FG and FSG varied significantly from that of the condyles in CG and SG.
Conclusion
Supplement therapy was found to enhance the normal biological response to functional appliance therapy in a rat model, particularly after the functional appliance was removed. Further research using an immuno-histochemical analysis of a modified bite-jumping appliance and improved food delivery is recommended.
... However, heterogeneous results were obtained in different animal studies and their function as disease-modifying drugs is still controversial. Some published clinical trials in dogs treated with glucosamine and chondroitin sulfate, reported positive clinical effects with significant pain relief [16], whereas in other publications, no significant differences were found between treated and untreated dogs [17,18]. ...
Simple Summary
Osteoarthritis is the most common progressive joint disease diagnosed in companion animals and its management continues to be a significant challenge. Nutraceuticals have been widely investigated over the years in the treatment of osteoarthritis and among them, glucosamine and chondroitin sulfate treatments are probably the most common therapies used in veterinary management. However, heterogeneous results were obtained among animal studies and the evidence of their efficacy is still controversial. Animal models have a crucial role in studying the histological changes and evaluating the therapy efficacy of different drugs. Consequently, we consider it may be of interest to evaluate the effectiveness of the most representative nutraceuticals in experimental animal studies of osteoarthritis. In this systematic review, we found a large inconsistency among the experimental protocols, but a positive cartilage response and biochemical modulation were observed in half of the evaluated articles, mainly associated with pre-emptive administrations and with some therapies’ combinations. Even though some of these results were promising, additional data are needed to draw solid conclusions, and further studies evaluating their efficacy in the long term and focusing on other synovial components may be needed to clarify their function.
Abstract
Glucosamine and chondroitin sulfate have been proposed due to their physiological and functional benefits in the management of osteoarthritis in companion animals. However, the scientific evidence for their use is still controversial. The purpose of this review was to critically elucidate the efficacy of these nutraceutical therapies in delaying the progression of osteoarthritis, evaluating their impact on the synovial knee joint tissues and biochemical markers in preclinical studies by systematically reviewing the last two decades of peer-reviewed publications on experimental osteoarthritis. Three databases (PubMed, Scopus and, Web of Science) were screened for eligible studies. Twenty-two articles were included in the review. Preclinical studies showed a great heterogeneity among the experimental designs and their outcomes. Generally, the evaluated nutraceuticals, alone or in combination, did not seem to prevent the subchondral bone changes, the synovial inflammation or the osteophyte formation. However, further experimental studies may be needed to evaluate their effect at those levels. Regarding the cartilage status and biomarkers, positive responses were identified in approximately half of the evaluated articles. Furthermore, beneficial effects were associated with the pre-emptive administrations, higher doses and, multimodality approaches with some combined therapies. However, additional studies in the long term and with good quality and systematic design are required.
... Nutraceuticals are natural supplements widely used in veterinary medicine as a multimodal treatment of OA [8][9][10][11][12][13]. Glucosamine and chondroitin sulfate synergistically contribute to cartilage formation and repair [14]; they also decrease the signs of pain associated with OA [15]. In the last decades, several Authors reports the widespread use of plant derivatives as pharmaceutical grades nutrients [7]. ...
Introduction
Osteoarthritis is a progressive degenerative joint disease which is high prevalent in dogs. In the late stage of the disease, it determines chronic neuropathic pain which leads to reduced quality-of-life in affected patients. To date it has not yet been identified a specific treatment, but it has been proved that nutraceutical and dietary supplements may play an important role in controlling inflammation and pain. The aim of this study was to evaluate, by the use of force plate gait analysis, the clinical efficacy of Boswellia and Curcuvet® combined with conventional nutraceutical therapy compared with conventional nutraceutical alone in dogs affected by osteoarthritis.
Materials and methods
Twenty client-owned dogs, over 12 months old and 20 kg of body-weight, with a confirmed diagnosis of Osteoarthritis, were included in this randomized, double-blinded study. The dogs were randomly divided into two groups: the first group (A) received a conventional nutraceutical (consisted in a preparation of glucosamine, chondroitin sulfate, fish-oil containing 80% of omega 3-fatty acid, vitamin C and E, saccharomyces Cerevisiae) with a combination of acid boswellic and Curcuvet®, while the second group (B) received a conventional nutraceutical. All the enrolled dogs underwent a washout period before starting the treatment with nutraceuticals products which were the only admitted treatment over the study period. A full orthopaedic and neurologic examination, and force plate gait analysis were performed before starting the treatment, at 45, 90, and 60 days post-treatment. Ground reaction forces were recorded and analyzed.
Results
Twenty dogs were enrolled in the study. In both groups there was an increasing values of ground reaction forces. These results might indicate that both nutraceutical products determined a better condition in terms of pain feeling but that effect is much more visible after 60 days from the end of the administration in treated group.
Discussion
In conclusion Curcuvet in combination with Boswellic acid could be considered a valid aid in a multimodal treatment for canine osteoarthritis.
... Joint health often is the primary reason working dog handlers want to supplement. Although the evidence still is growing, products with glucosamine hydrochloride, 8 chondroitin sulfate, or avocado soybean unsaponifiables should be considered. 9 Supplementation with omega-3 fatty acids for their anti-inflammatory properties also may be of benefit for working dogs. ...
Canine sports medicine and rehabilitation recently have evolved to embody the optimization of performance, injury prevention, and mitigation of musculoskeletal degeneration. This article discusses the diverse factors and considerations of working dog wellness and injury prevention and the importance of recognizing normal and abnormal posture and anatomic structure for performance evaluation and early indication of musculoskeletal injury. The importance of a canine physical fitness program is highlighted and the need for a 4-phase recovery plan to determine if a working dog can safely return to work after injury discussed.
... The benefits of the use of glucosamine for osteoarthritis have long been agreed with skepticism due to the lack of reliable information regarding their absorption, pharmacokinetics, and mechanism of action. Pharmacokinetic studies on glucosamine in dogs using 14 C-glucosamine and 35 S-labeled chondroitin sulfate found that 87% of an orally administered dose of radiolabelled glucosamine and 70% of the labeled chondroitin sulfate were absorbed [69]. Other studies reported that glucosamine was bioavailable after oral dosing and had a tropism for articular cartilage [70]. ...
This study is aiming to investigate the protective effect of glucosamine, risedronate (alone or in combination)
on articular cartilage in experimental model of immobilized rat knee. Twenty-five adult male albino rats were divided
into five groups (five rats each): control group, immobilized group, glucosamine-treated group, risedronate-treated group,
and group treated by a combination of glucosamine and risedronate. The articular cartilage was obtained for histological,
immunohistochemical and morphometric studies. The immobilized group showed manifestations of osteoarthritis in the
form of significant decrease of articular cartilage thickness with surface erosions, shrunken chondrocytes with pyknotic nuclei
and marked manifested fall of chondrocyte number. There was manifested reduction of collagen contents of the articular
cartilage using Masson trichrome stain. Safranin O–Fast Green revealed low proteoglycan contents. The collagen type II
was also declined. The manikin score was 7.8. Risedronate improved this manifestation slightly more than glucosamine, but
combination of booth drugs caused significant improvement of the damaged articular cartilage caused by immobilization. Oral
administration of glucosamine and risedronate improved the degenerative changes of rat knee articular cartilage that follow
immobilization. This improvement was more remarkable when both drugs were used in combination.
... At T1, T2, T3 and T4, the veterinarian, blinded to treatment, used an ordinal scoring system to assess the severity of clinical symptoms [46]. The degree of lameness was graded on a scale of 1-5 as follows: The degree of lameness was graded on a scale of 1-5 as follows: 1: (Walks normally); 2: (Slightly lame when walking); 3: (Moderately lame when walking); 4: (Severely lame when walking); and 5: (Severely lame when walking). ...
Background
Lameness caused by osteoarthritis (OA) is one of the main causes of disability in elderly dogs. Non-steroidal anti-inflammatory drugs (NSAIDs) are important tools in the treatment of canine OA. In recent years, due to the many side effects of NSAIDs, patients cannot tolerate or do not want to take the risk of NSAIDs. People are becoming more and more interested in new treatments for canine OA, and so-called nutritional supplements have emerged. Puerarin has a wide range of pharmacological activities and is often used as a clinical prescription drug and dietary supplement in China. However, the effect of puerarin on canine OA has not been evaluated. Therefore, the purpose of this study is to evaluate the anti-inflammatory and anti-cartilage degradation effects of puerarin in a canine OA model induced by anterior cruciate ligament transection (ACLT), and to detect the serum inflammatory factor interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) levels and cartilage degradation biomarker C-terminal telopeptides of collagen type II (CTX-II), cartilage oligomeric matrix protein (COMP) and chondroitin sulfate 846 epitope (CS 846) levels in serum and synovial fluid at different periods of puerarin administration. ResultsEight weeks after the administration, the veterinarian performed clinical and imaging evaluations to comprehensively evaluate the protective effect of puerarin on canine OA. Daily oral administration of 20 mg/kg puerarin can significantly inhibit the expression of IL-1β, IL-6 and TNF-α in serum within 8 weeks ( P < 0.05), and its anti-inflammatory effect is similar to oral celecoxib (negative control group). Puerarin has a certain protective effect on articular cartilage and can reduce the level of biomarkers CTX-II, COMP and CS 846 in serum and synovial fluid in the early stage of OA ( P < 0.05). In addition, the clinical scores and radiographs scores were significantly reduced after 8 weeks of puerarin treatment ( P < 0.05). Conclusions
Canine OA cartilage may be mediated through anti-inflammatory, anti-metabolism and anabolic effects, and strongly down-regulate the inflammatory factors IL-1β, IL-6 and TNF-α and cartilage degradation biomarkers CTX-II, COMP and CS 846 are related, providing a good alternative therapy for OA.
... Weight reduction is referred to have a positive effect on the control of clinical signs of lameness in dogs with hip OA (Impellizeri et al., 2000). Dietary oral supplementation with chondroitin/glucosamine sulfate (McCarthy et al., 2007), omega-3 fish oil fatty acids (Fritsch et al., 2010), and beta-1,3/1,6-glucans (Beynen and Legerstee, 2010) are examples of adjuvant strategies to reduce clinical signs of OA and to prevent progression of the degenerative process. Other options include intraarticular injections of hyaluronan (Brandt et al., 2004) and intramuscular administration of polysulfated glycosaminoglycan (Fujiki et al., 2007). ...
Background:
Osteoarthritis (OA) is a major cause of chronic pain and lameness in dogs. Platelet-rich plasma (PRP) is a concentrate of growth and differentiation factors from the blood, which can be used in regenerative medicine strategies.
Aim:
The main aim of this study was to evaluate the effect of allogeneic PRP on the treatment of canine OA.
Methods:
Five dogs from several breeds, between 6 and 12 years old, and from both genders were studied. Clinical and imageological examinations diagnosed OA in the knee, tibiotarsal, elbow, and intercarpal joints. These dogs were refractory to medical therapy and to physical rehabilitation protocols that included shockwave therapy, laser therapy, electrostimulation, hydrotherapy, and diathermy.Animals were treated with allogeneic PRP obtained from the blood of the five dogs, which was processed in a pool. Echoguided intra-articular PRP injection was administered under sedation and after aseptic field preparation. Lameness at walk and trot (five grades) and pain (five scores) were evaluated before treatment and 30, 60, and 90 days post-treatment.
Results:
All animals presented improvements at 30 and 60 days in both parameters. Four dogs showed a decrease of three grades of lameness after 90 days and there was complete absence of lameness in 2 days. Pain was reduced from severe and moderate to mild in all the dogs after 30 days, and among them, three revealed no pain after 90 days.
Conclusion:
This study sheds light on the applicability and safety of a single administration of allogeneic PRP in osteoarthritic dogs.
... There is substantial evidence that polyunsaturated fatty acids from vegetable and fish oil (e.g., eicosapentaenoic, docosahexaenoic, and linoleic acid) exert important benefits in a range of veterinary diseases, from atopic dermatitis [5][6][7] to renal insufficiency [8,9] and cognitive dysfunction syndrome [10]. Moreover, omega-3 essential fatty acids have been widely and successfully applied to osteoarthritis [11][12][13][14][15], similarly to glucosamine [16][17][18][19] and the organosulfur compound methylsulfonylmethane [4]. Thus, the interaction between illness, health, and nutritional status is multifactorial and complex. ...
Virtually every cellular process is affected by diet and this represents the foundation of dietary management to a variety of small animal disorders. Special attention is currently being paid to a family of naturally occurring lipid amides acting through the so-called autacoid local injury antagonism, i.e., the ALIA mechanism. The parent molecule of ALIAmides, palmitoyl ethanolamide (PEA), has being known since the 1950s as a nutritional factor with protective properties. Since then, PEA has been isolated from a variety of plant and animal food sources and its proresolving function in the mammalian body has been increasingly investigated. The discovery of the close interconnection between ALIAmides and the endocannabinoid system has greatly stimulated research efforts in this field. The multitarget and highly redundant mechanisms through which PEA exerts prohomeostatic functions fully breaks with the classical pharmacology view of “one drug, one target, one disease”, opening a new era in the management of animals’ health, i.e., an according-to-nature biomodulation of body responses to different stimuli and injury. The present review focuses on the direct and indirect endocannabinoid receptor agonism by PEA and its analogues and also targets the main findings from experimental and clinical studies on ALIAmides in animal health and wellbeing.
... A associação de glucosamina e sulfato de condroitina é utilizada para o tratamento de osteoartrite em humanos e animais e apresenta efeito reparador articular com consequente alívio da dor (McCarthy et al, 2007) e foi utilizada para reduzir a degeneração articular dos joelhos devido ao quadro de luxação patelar bilateral, além da instabilidade vertebral. ...
Intervertebral Disc Disease (IVDD) is the main spinal cord disease in dogs, especially of chondrodisthrophic breeds, and it’s characterized by structural degeneration of discs, following protrusion or extrusion of debris to the medullar canal, compression and variable degrees of pain, paresis and ataxia. Surgical descompressive intervention coupled with disc fenestration are the treatment of choice as it promotes faster recovery with higher succes rates, not withou important morbidity and mortality. The conservative management is considered when the pacient has mild clinical signs, doesn’t have severe medullar compression or contusion lesions on imaging tests, as well as when there are restrictions associated with the clinical state of the pacient or the higher costs of surgical treatment.
... The benefits of the use of glucosamine for osteoarthritis have long been agreed with skepticism due to the lack of reliable information regarding their absorption, pharmacokinetics, and mechanism of action. Pharmacokinetic studies on glucosamine in dogs using 14 C-glucosamine and 35 S-labeled chondroitin sulfate found that 87% of an orally administered dose of radiolabelled glucosamine and 70% of the labeled chondroitin sulfate were absorbed [69]. Other studies reported that glucosamine was bioavailable after oral dosing and had a tropism for articular cartilage [70]. ...
This study is aiming to investigate the protective effect of glucosamine, risedronate (alone or in combination) on articular cartilage in experimental model of immobilized rat knee. Twenty-five adult male albino rats were divided into five groups (five rats each): control group, immobilized group, glucosamine-treated group, risedronate-treated group, and group treated by a combination of glucosamine and risedronate. The articular cartilage was obtained for histological, immunohistochemical and morphometric studies. The immobilized group showed manifestations of osteoarthritis in the form of significant decrease of articular cartilage thickness with surface erosions, shrunken chondrocytes with pyknotic nuclei and marked manifested fall of chondrocyte number. There was manifested reduction of collagen contents of the articular cartilage using Masson trichrome stain. Safranin O-Fast Green revealed low proteoglycan contents. The collagen type II was also declined. The manikin score was 7.8. Risedronate improved this manifestation slightly more than glucosamine, but combination of booth drugs caused significant improvement of the damaged articular cartilage caused by immobilization. Oral administration of glucosamine and risedronate improved the degenerative changes of rat knee articular cartilage that follow immobilization. This improvement was more remarkable when both drugs were used in combination.
... The benefits of the use of glucosamine for osteoarthritis have long been agreed with skepticism due to the lack of reliable information regarding their absorption, pharmacokinetics, and mechanism of action. Pharmacokinetic studies on glucosamine in dogs using 14 C-glucosamine and 35 S-labeled chondroitin sulfate found that 87% of an orally administered dose of radiolabelled glucosamine and 70% of the labeled chondroitin sulfate were absorbed [69]. Other studies reported that glucosamine was bioavailable after oral dosing and had a tropism for articular cartilage [70]. ...
Objectives: This study is aiming to investigate the protective effect of glucosamine, risedronate
(alone or in combination) on articular cartilage in experimental model of immobilised rat knee.
Methods. Twenty-five adult male albino rats were divided into five groups (five rats each): control
group, an immobilised group, glucosamine-treated group, risedronate-treated group, and a group
treated by a combination of glucosamine and risedronate. The articular cartilage was obtained for
histological, immunohistochemical and morphometric studies.
Results. The immobilised group showed manifestations of osteoarthritis in the form of significant
decrease of articular cartilage thickness with surface erosions, shrunken chondrocytes with pyknotic
nuclei and marked manifested fall of chondrocyte number. There was manifested reduction of
collagen contents of the articular cartilage using Masson trichrome stain. Safranin O fast green
revealed low proteoglycan contents. The collagen type II was also declined. The manikin score was
7.8. Risedronate improved this manifestation slightly more than glucosamine, but combination of
both drugs caused significant improvement of the damaged articular cartilage caused by
immobilisation.
Conclusion: Oral administration of glucosamine and risedronate improved the degenerative
changes of rat knee articular cartilage that follow immobilisation. This improvement was more
remarkable when both drugs were used in combination.
Key Words
Knee, Immobilisation, Glucosamine, Risedronate, Osteoarthritis
Introduction
With little to no regulation of the supplement markets and a paucity of quality information regarding clinical utility of individual marketed supplements, it is difficult for veterinarians to provide any evidence-based recommendations to owners. The current study aimed to provide clinically useful comparative efficacy data on certain marketed supplements.
Methods
Using a prospective, block-randomized, double-blinded, placebo-controlled design, one hundred and one pet dogs with clinical hip OA-associated pain with one side worse than the other (index limb) were randomly assigned to one of four treatment groups: Green lipped Mussel plus Krill oil extracts (Antinol® Rapid, EAB-277); Biota orientalis extracts (4CYTE™ Epiitalis® Forte); an NSAID (meloxicam); or placebo (sunflower oil). Peak vertical force (PVF, expressed as a percentage of bodyweight) of the index limb, orthopedic assessment score (OAS) and hematology and blood chemistry values were evaluated before treatment (week 0), at 2, 4 and 6 weeks during treatment.
Results
At 6 weeks, the changes from baseline in PVF of the index limb in the EAB-277 and meloxicam groups were significantly greater than the change in the placebo and 4CYTE™ groups, and the placebo and 4CYTE groups were not different from each other. At 6 weeks, there were significant differences between the groups for overall OAS scores with the lowest scores (least impairment) in the EAB-277 and meloxicam groups, followed by the 4CYTE group and then the placebo group.
Discussion
Results of this study indicate that meloxicam and EAB-277 have significant objectively measured benefits in managing OA-related pain in dogs compared to placebo, but 4CYTE does not differ from placebo.
Background:
Cranial cruciate ligament disease is one of the leading causes of pelvic limb claudication in canines and osteoarthritis in the stifle joint. Historically, studies have focused on surgical options to improve the stability of the stifle joint, although none of the techniques described in the literature prevents the development of osteoarthritis.
Aim:
This study aimed at proving the presence of osteoarthritis at the time of diagnosis of cranial cruciate ligament rupture, as well as evaluating the benefits of administering diacerein (DAR) or chondroprotective coadjuvants to the extracapsular fabelo-tibial technique.
Methods:
Seventeen dogs aged between 2 and 8, weighing more than 25 kg, with no predilection for breed or sex, were operated on using this technique. These were divided into three groups: DAR, Chondroprotector (CP), and Control. The animals were treated for 90 days and controlled clinically, radiologically, and using multidimensional scales for pain and quality of life. The statistical analysis used was descriptive and through non-parametric tests.
Results:
All patients had some degree of osteoarthritis at the beginning of the study associated with the presence of pain. The treated groups improved the claudication scores; however, the changes were significant for the DAR group. The pain score improved in all animals, including those in the Control group; however, the differences were significant only in the treated groups. On the other hand, no significant differences were detected in the radiological studies, so it would be convenient to perform this study over more than 90 days.
Conclusion:
The surgical treatment accompanied by drugs that act on the degradation of articular cartilage has better clinical results.
Le but de cette revue systématique et métanalyse était d’examiner les évidences d’efficacité clinique analgésique des diètes enrichies et nutraceutiques testés chez des chiens arthrosiques. À partir de quatre bases de données bibliographiques électroniques, 1096 publications ont été retracées, en plus de 20 publications provenant de sources internes. Cinquante-quatre articles ont été inclus, comprenant 69 essais et permettant d’établir 9 catégories de traitement. L’évaluation d’efficacité, modulée par le niveau de qualité des essais, établit une évidence analgésique, avec effet clinique, pour les diètes enrichies et les suppléments à base d’oméga-3, ainsi que ceux à base de cannabidiol (à moindre degré). Nos analyses démontrent aussi une faible efficacité du collagène, et un non-effet marqué des nutraceutiques à base de chondroïtine – glucosamine qui nous pousse à recommander que ces derniers produits ne soient plus conseillés pour la gestion des douleurs en arthrose canine. Mots-Clés : Arthrose, Nutraceutiques, Compléments alimentaires, Diètes thérapeutiques, Douleur, Animal, Locomotion, Qualité méthodologique, Évidences scientifiques, Validation métrologique
The typical canine rehabilitation patient with orthopedic disease may differ in its nutritional needs, with the assumption that most patients will be on a complete and balanced commercial dog food that is not enriched with agents for ameliorating their condition. For a significant number of rehabilitation patients, obesity is a major issue where hypocaloric diet plans are often implemented and are covered extensively elsewhere (VCNA Small Animal Practice May 2021). The focus of this article will be implementation of physical activity or structured physical exercise protocols and how they might be used in combination with a typical hypocaloric diet plan, a diet low in calories. Considering the limited information regarding physical activity or structured exercise programs in dogs, a human comparative assessment of efficacy is fundamental as a baseline of information regarding typical interventions. In addition, many of these long-term rehabilitation cases typically exhibit osteoarthritis (OA) and as part of case management, there is a need to implement nutrient or nutraceutical intervention to either diminish the progression of OA or help with pain control measures, particularly for the nonsteroidal anti-inflammatory intolerant patient. Nutraceutical intervention comes in many forms from botanicals to nutritional enhancement; botanicals will be covered elsewhere in this issue. This overview of nutraceuticals will cover nonbotanical interventions including fish oil, glucosamine/chondroitin, avocado/soybean unsaponifiables, undenatured collagen, green lipped mussel, and egg shell membrane supplementation.
PICO question
Does treatment with a non-steroidal anti-inflammatory drug (NSAID) with supplementation of marine-derived omega-3 fatty acids (n-3FAs) compared to the NSAID alone, result in an increased ability to exert force by the osteoarthritic limb(s) of dogs or alleviate other measures of osteoarthritis?
Clinical bottom line
Category of research question
Treatment
The number and type of study designs reviewed
Two prospective, block-randomised, clinical trials
Strength of evidence
None
Outcomes reported
Kwananocha et al. (2016) investigated administration of carprofen supplemented with marine-derived n-3 FAs, to carprofen alone, administered over 4 weeks. Vijarnsorn et al. (2019) investigated administration of firocoxib supplemented with n-3FA, to firocoxib alone, for 4 weeks. There were no statistical differences between treatment groups at week 2 and week 4 post-treatment for either study. Both studies also reported orthopaedic assessment score (OAS) based on scoring the extent of patient lameness and pain in the affected joint. There were no statistical changes in OASs between treatment groups at week 2 or week 4 post-treatment for either study
Conclusion
There is no evidence that marine-derived n-3 FAs provide additional benefit when used as adjunctive agents with NSAIDs for the treatment of canine osteoarthritis
How to apply this evidence in practice
The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources.
Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.
Osteoarthritis is prevalent in the UK canine population and has a clear impact on animal welfare. Treatment of osteoarthritis is advised to be multimodal, with nutraceuticals becoming a popular part of this approach. However, veterinary nutraceuticals are not subject to any regulation and systematic reviews are still uncommon in the veterinary field, which makes evaluating these products difficult. This article looks at the most commonly used veterinary supplements and how to critically evaluate the evidence of their efficacy. Evidence is promising for omega-3 fatty acids but is limited for other common ingredients. There are limited numbers of rigorous, randomised controlled trials and veterinary studies are often hampered by small sample sizes. Standardisation of reporting, as performed in human medicine, is needed to allow more robust systematic reviews of nutraceuticals to subsequently enable vets to make more informed decisions.
This article reviews the current literature on osteoarthritis in pet and laboratory guinea pigs. The associated clinical signs, diagnosis and treatment of osteoarthritis in pet guinea pigs will be discussed, with options for analgesia detailed. This condition is thought to be common in pet guinea pigs, even from an early age in some genetic lines, although osteoarthritis often goes undiagnosed in this species until advanced disease is present, posing a major welfare concern. Increasing awareness of this condition in veterinary practitioners should aid early diagnosis in pets and help improve their quality of life. Prevention may be possible using oral protective nutritional supplements to slow down the progression of this disease at an early stage. Lifestyle changes are also discussed for the management of this condition in pet guinea pigs.
Working dogs are athletes, but have a wide variety of work types and durations that impact their dietary needs. Their basic nutritional needs do not change: all dogs need a complete and balanced diet, fed in proper proportions to maintain optimal body condition. However, with increasing muscle work and endurance, the amounts of specific nutrients (particularly the macronutrients, protein, fat, and carbohydrates) must be adjusted. This article provides an overview of the key aspects of working canine nutrition and provides the nutritional science behind the recommendations made.
The objective of this study was to assess veterinarians' understanding of nutraceutical use in humans and companion animals and their motivation and circumstances for recommending nutraceuticals to clients. We administered a cross-sectional survey to veterinarians attending continuing education sessions at the University of Georgia (USA) College of Veterinary Medicine from 2012 to 2015 (N = 126). Information regarding veterinarians' age, year of graduation, practice focus, and typical approaches to nutraceutical use was compiled from the returned surveys. The results indicated that veterinarians are more familiar with nutraceutical use in animals than in humans and primarily recommend nutraceuticals to their clients for preventative purposes and/or due to client interest. Veterinarians believed that nutraceuticals were most useful for osteoarthritis and therefore use omega-3 fatty acid and glucosamine/chondroitin products more often than other products for both their patients and their own pets. Safety and efficacy were the most important considerations when deciding which nutraceuticals to recommend to clients. The survey results show that veterinarians are familiar with nutraceuticals and open to their use in patients when they perceive these products to be safe and efficacious.
Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.
Cartilage tissue damage and diseases are the most common clinical situation that occurs because of aging and injury, thereby causing pain and loss of mobility. The inability of cartilage tissue to self-repair is instrumental in developing tissue engineered substitutes. To this effect, the present study aims to engineer cartilage construct by culturing umbilical cord blood-derived human mesenchymal stem cells (hMSCs) on novel 3D porous scaffolds developed from natural biopolymers, silk fibroin (SF) and chitosan (CS), with addition of cartilage matrix components, glucosamine (Gl) and chondroitin sulfate (Ch). The presence of Gl and Ch is expected to enhance cartilage regeneration. The developed SF/CS-Gl-Ch scaffolds possess desired pore size in the range 56.55-168.15 μm, 88-92% porosity, 44.7-46.8̊ contact angle, controlled swelling and biodegradability. Upon culturing under dynamic condition in a spinner flask bioreactor, the scaffold supported hMSCs attachment, proliferation, and further promoted chondrogenic differentiation. Cartilage-specific matrix and gene (Collagen II, Sox9 and aggrecan) expression analyses by histology, immunophenotype, immunofluorescence and quantitative PCR studies showed superiority of cell-scaffold construct generated in dynamic culture towards cartilage tissue generation as compared to cell aggregates formed by pellet culture. This study demonstrates the potentiality of SF/CS-Gl-Ch porous scaffold for the development of tissue construct for cartilage regeneration under dynamic culture condition.
Currently, in the United States, every fifth adult dog or horse suffers from arthritis. The two most common types of arthritis are osteoarthritis (OA) and rheumatoid arthritis (RA). OA occurs with greater frequency than RA. OA is an inflammatory heterogeneous chronic degenerative joint disease (DJD) characterized by chronic and progressive degradation of the articular cartilage, osteophyte formation, thickening and sclerosis of the subchondral bone, bone marrow lesions, hypertrophy of bone at the margin, synovitis, synovial fluid effusion, and fibrosis. Common clinical signs and symptoms associated with OA in dogs and horses include limping, immobility, stiffness of joints, crepitus, periarticular swelling, palpable effusion, and pain upon manipulation of the joint and limb. The pathophysiology of OA is very complex because there are multiple etiologies for this disease, and as a result, treatment is complicated. Pain and inflammation associated with OA are often managed by pharmacological suppression or surgery among a few other modalities. NSAIDs are known to have severe side effects, and surgery is very expensive, so the use of nutraceuticals appears to be a viable alternative for prevention and treatment of OA. This chapter describes various nutraceuticals that have the potential to exert antioxidative, anti-inflammatory, antinociceptive, and chondroprotective effects in osteoarthritis.
The aim of this study was to evaluate the efficacy and safety of the intra-articular (IA) injection of botulinum toxin type A (BoNT/A) to the management of chronic pain in dogs. In a randomized, controlled, double-blinded study sixteen dogs with osteoarthritis secondary to hip dysplasia were distributed into two groups: 25 IU BoNT/A (BoNT) or saline solution (Control) was administered IA in each affected joint. All dogs received oral supplements (90 days) and carprofen (15 days). The dogs were assessed by a veterinarian on five occasions and the owner completed an assessment form at the same time (baseline to 90 days). The data were analyzed using unpaired-t test, Fisher’s exact test, analysis of variance and the Tukey’s test (P<0.05). There were no differences between groups in the veterinarian and owner assessments. Lower scores were observed in both groups during 90 days after IA therapy in the owner assessments (P<0.001). Compared with baseline, the Vet score was lower from 15-90 days after IA injection in the BoNT group, and at 15 and 30 days in the Control group (P<0.001). Both treatments were safe and reduced the clinical signs associated with hip osteoarthritis. However, IA BoNT/A (25 IU) did not provide better pain relief than the control treatment.
Chondroprotective agents are widely prescribed in veterinary medicine for the treatment of degenerative joint disease. The agents exert multiple effects on articular cartilage but the avascular nature of cartilagenous tissue clouds the mechanism(s) whereby such agents are presented to joint surfaces. We explored whether the active agents comprising the chondroprotective agent Cosequin(R) circulate in serum at levels which may have beneficial effects on maintaining cartilage integrity. Cosequin(R), a mixture of sodium chondroitin sulfate, glucosamine HCl and manganese ascorbate, was given orally to normal canines for 30 days. The biosynthetic and degradative responses of bovine cartilage exposed to canine serum were monitored with standard radiolabeling methods. Metabolic responses were assessed by comparison with serum samples taken prior to dosing. The median level of serum glycosaminoglycan (GAG) levels at 30 days was increased by 42% (P < 0.005) with little change in free or bound hexosamine levels. Cartilage segments cultured in a 1:1 mixture of canine serum. Ham's F-12 media had a 50% increase in GAG biosynthesis (P < 0.02) while median proteolytic degradation was reduced by 59% (P < 0.055). The data suggests that Cosequin(R) given orally over extended periods of time elevates levels of circulating agents which stimulate cartilage metabolism while inhibiting cartilage degradation.
Chondroitin sulfate (Condrosulf) was characterized for structure, physiochemical properties and purity. This glycosaminoglycan has a relative molecular mass of about 14,000, a sulfate-to-carboxyl ratio of 0.95 due to the high percentage of monosulfated disaccharides (38% 6-monosulfate and 55% 4-monosulfate) and a low amount of disulfated disaccharides (1.1%) inside the polysaccharide chains. No other glycosaminoglycans were detected in the preparation. Chondroitin sulfate was labelled by reduction with sodium 3H-borohydride and administered by oral route in the rat and dog. More than 70% of radioactivity was absorbed and found in urine and tissues. The plasma radioactivity was fractionated by size-exclusion chromatography in three fractions: radioactivity associated with high, intermediate and low molecular mass compounds. The peak value of the concentration of high molecular mass radioactivity compounds in plasma was reached after 1.6 and 2.1 h for the rat and dog, respectively. After 36 h the high molecular mass radioactivity compounds were still present in plasma of dog and rat. After 24 h radioactivity was higher in the intestine, liver, kidneys, synovial fluid and cartilage than in other tissues. Condroitin sulfate was orally administered to man (healthy volunteer) in a single daily dose of 0.8 g and in two daily doses of 0.4 g. The results showed that both forms of administration determined a significant increase of plasma concentration of chondroitin sulfate as compared with predose value over a full 24 h period. Elimination constant values and tmax (of the first administration in the case of fractionated dose) were almost the same for the two administrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Osteoarthritis (OA) is the most common form of arthritis, and it is often associated with significant disability and an impaired quality of life.
To review all randomized controlled trials (RCTs) evaluating the effectiveness and toxicity of glucosamine in OA.
We searched MEDLINE, PREMEDLINE, EMBASE, AMED, ACP Journal Club, DARE, CDSR, and the CCTR. We also wrote letters to content experts, and hand searched reference lists of identified RCTs and pertinent review articles. All searches were updated in January 2005.
Relevant studies met the following criteria: 1) RCTs evaluating the effectiveness and safety of glucosamine in OA, 2) Both placebo controlled and comparative studies were eligible, 3) Both single blinded and double blinded studies were eligible.
Data abstraction was performed independently by two investigators and the results were compared for degree of agreement. Gotzsche's method and a validated tool (Jadad 1996) were used to score the quality of the RCTs. Continuous outcome measures were pooled using standardized mean differences (SMD) as the measure of effect size. Dichotomous outcome measures were pooled using relative risk ratios (RR).
Analysis restricted to eight studies with adequate allocation concealment failed to show benefit of glucosamine for pain and WOMAC function. Collectively, the 20 analyzed RCTs found glucosamine favoured placebo with a 28% (change from baseline) improvement in pain (SMD -0.61, 95% CI -0.95, -0.28) and a 21% (change from baseline) improvement in function using the Lequesne index (SMD -0.51 95% CI -0.96, -0.05). However, the results are not uniformly positive, and the reasons for this remain unexplained. WOMAC pain, function and stiffness outcomes did not reach statistical significance. In the 10 RCTs in which the Rotta preparation of glucosamine was compared to placebo, glucosamine was found to be superior for pain (SMD -1.31, 95% CI -1.99, -0.64) and function using the Lequesne index (SMD -0.51, 95% CI -0.96, -0.05). Pooled results for pain (SMD -0.15, 95% CI -0.35, 0.05) and function using the WOMAC index (SMD 0.03, 95% CI -0.18, 0.25) in those RCTs in which a non-Rotta preparation of glucosamine was compared to placebo did not reach statistical significance. In the four RCTs in which the Rotta preparation of glucosamine was compared to an NSAID, glucosamine was superior in two, and equivalent in two. Two RCTs using the Rotta preparation showed that glucosamine was able to slow radiological progression of OA of the knee over a three year period (SMD 0.24, 95% CI 0.04, 0.43). Glucosamine was as safe as placebo in terms of the number of subjects reporting adverse reactions (RR=0.97, 95% CI, 0.88, 1.08).
This update includes 20 studies with 2570 patients. Pooled results from studies using a non-Rotta preparation or adequate allocation concealment failed to show benefit in pain and WOMAC function while those studies evaluating the Rotta preparation show that glucosamine was superior to placebo in the treatment of pain and functional impairment resulting from symptomatic OA. WOMAC outcomes of pain, stiffness and function did not show a superiority of glucosamine over placebo for both Rotta and non-Rotta preparations of glucosamine. Glucosamine was as safe as placebo.
This painful condition cannot be cured. But by using the right combination of nutrition, physical therapy, and drugs, you can help control pain and improve mobility in your patients.
Among the many mediators of inflammation, the prostaglandins (PGs) are of great importance. They are released by almost any type of chemical or mechanical stimulus. The key enzyme in their synthesis is prostaglandin endoperoxide synthase (PGHS) or cyclooxygenase (COX) which possesses two catalytic sites. The first, a cyclooxygenase active site, converts arachidonic acid to the endoperoxide PGG2. The second, a peroxidase active site, then converts the PGG2 to another endoperoxide PGH2. PGH2 is further processed by specific isomerases to form PGs, prostacyclin and thromboxane A2. Of the PGs, PGE2 and prostacyclin are the main inflammatory mediators. Cyclooxygenase activity has long been studied in preparations from sheep seminal vesicles and a purified, enzymatically-active COX was isolated in 19761. We now know that COX exists in at least two isoforms, COX-1 and COX-2.
Carprofen (D,L-6-chlor-alphamethylcarbazole-2-acetic acid) is a nonsteroidal anti-inflammatory drug with demonstrated therapeutic activity in the relief of clinical signs of degenerative joint disease in laboratory animal models and in human trials. The double-blind clinical study, reported herein, compared the therapeutic efficacy of carprofen with that of a placebo, in the acute relief of clinical canine degenerative joint disease. Twohundred and nine cases were collected from 10 studies in three geographic regions of the USA. The results of logistic analysis showed that dogs treated with carprofen were 24.8 times more likely to receive a positive evaluation by the veterinarian than those treated with a placebo (p <0.01). The odds of showing improvement, when evaluated by the owners, were 13.4 times greater than placebo (p <0.01). The evaluation from the veterinarian and the owner had excellent agreement (Kappa = 0.997) for dogs treated with carprofen and good agreement (Kappa = 0.667) for those treated with the placebo. Regional differences in response rate were not found in these studies. This trial demonstrated that carprofen is efficacious, across geographic regions, in the acute relief of clinical signs associated with canine degenerative joint disease.
Carprofen is a new anti-inflammatory drug (NSAID) with analgesic potency. Side effects reported are few. Dogs with degenerative joint disease (DSD) treated with carprofen were 24.8 times more likely to respond favourably than placebo-treated dogs (p <0.01). This study concluded that carprofen is an effective NSAID in relieving the clinical signs of DSD in dogs.
Twenty-five horses with degenerative joint disease that fit the conditions of the study were treated with a glucosamine-chrondroitin sulfate compound (CosequinR:Nutramax Laboratories Inc., Baltimore, MD) to evaluate its effectives in decreasing lameness. All horses were confirmed to have degenerative joint disease (DJD) by physical examination, diagnostic intra-articular anesthesia, and radiographs or fluoroscopy of the distal interphalangeal, metacarpophalangeal, tarsometatarsal or carpal joints. All horses weighing less than 545 kg were given 9 g of the glucosamine-chondroitin sulfate compound orally twice daily for 6 weeks. Horses weighing more than 545 kg were given 12 g twice daily for 6 weeks. Each 3 g measure included 1,800 mg of glucosamine hydrochloride, 600 mg of purified chondroitin sulfate, 16 mg of manganese, and 104 mg of ascorbate. Lameness grade, flexion test grade and stride length (cm) were measured at an initial examination and re-evaluated at 2, 4, and 6 week follow-up examinations. Repeated measurement analysis was implemented to assess the lameness using SAS computer package (Statistical Analysis System, Cary, NC). Within 2 weeks of the start of administration of the glucosamine-chondroitin sulfate compound, the lameness grade, flexion test, and stride length were significantly (P < 0.0001) improved. A further significant improvement in lameness was evident at 4 weeks (p = 0.04), while flexion score (p = 0.2) and stride length (P = 1.0) did not show further improvement. The age of horses was not a significant factor in the improvement of the lameness grade, flexion test, or stride length (p = 0.2, p = 0.07 and p = 0.2, respectively), implying that the achieved results were true irrespective of horse age.
The objective of this study was to evaluate the effects of a chondroprotective agent on hematologic, hemostatic, and biochemical variables in clinically normal cats when administered at twice the recommended levels for 30 days. Fifteen clinically normal female domestic shorthaired cats were used. Twelve cats were given a chondroprotective agent orally, twice daily for 30 days. Three cats served as environmental controls and did not receive any treatment. The Wilcoxon's rank sum with a Bonferroni correction was used to evaluate the data statistically. Hematologic, hemostatic, and biochemical variables were assessed before treatment and on days 3, 14, and 30 of treatment. All cats remained healthy and showed no adverse reactions to treatment. No clinically and statistically significant shift outside a standard reference range was noted for any parameter. Hematocrit and red blood cell concentrations were decreased from pretreatment concentrations during days 3, 14, and 30 of treatment; however, these values were within a standard reference range at all time points. No significant changes were noted in platelet count, prothrombin time, or activated partial thromboplastin time. There were significant decreases in platelet aggregation response to high and low concentrations of collagen on day 3 and to the high concentration of collagen on days 14 and 30 compared with pretreatment values, but these values were not different from those of untreated cats. There was an increased time to response with the high concentration but not the low concentration of collagen on days 3, 14, and 30. Some parameters, such as potassium, anion gap, alkaline phosphatase, and bicarbonate, showed changes from pretreatment values at some but not all days of treatment. However, median concentrations remained within normal reference ranges, suggesting that these minor shifts were not indicative of clinical significance. Oral chondroprotective agents are widely prescribed in veterinary medicine for the treatment of degenerative joint disease. Safety studies have been performed in dogs; however, to date little is known about the safety of their use in cats. In this study, administration of this chondroprotective agent did not result in any clinically important change in hematologic, biochemical, and hemostatic variables when administered to healthy adult cats for 30 days at twice the recommended dosage.
Three proposed chondroprotective agents (CP), namely glucosamine sulfate (GAS), chondroitin sulfate (CS) and glycosaminoglycan-peptide complex (GP-C), were tested on differentiated human articular chondrocytes cultured in clusters. Chondrocyte productions of proteoglycans (PG), type II collagen (coll. II) and prostaglandin E2 (PGE2) were established by specific radioimmunoassays applied to the culture medium (CM) and in chondrocyte clusters (CC). Collagenolytic activity was assayed in CM. DNA synthesis, studied by measuring 3H-thymidine incorporation, was unaffected by CS and GAS. GP-C, at low concentration, stimulated DNA synthesis. GP-C, at higher doses, induced a high increase in PG and coll. II productions. GAS and CS induced a stimulatory effect limited to PG production. None of the CP tested here affected the basal PGE2 production by human chondrocytes.
A pharmacological approach to glycosaminoglycans (GAG) is presented, reviewing their synthesis, functions and in particular their mechanism as drugs. The application of GAG sulfates in osteoarthritis therapy is examined in detail.
Nonsteroidal antiinflammatory drugs (NSAIDs) constitute a class of pharmacologically active agents with similar therapeutic actions and side effects, despite diverse chemical structures. NSAIDs inhibit the enzyme cyclo-oxygenase and, thus, decrease inflammation mediated by prostaglandins. Toxicoses due to NSAIDs are manifested primarily by gastrointestinal upset and hemorrhage and by renal damage. Management consists of detoxification measures, in addition to supportive and symptomatic care. The article outlines the incidence, clinical toxicity, mode of action, and pharmacokinetics of nonsteroidal antiinflammatory drugs. The toxic effects of NSAIDs on individual organ systems are described, and general management recommendations for the treatment of NSAID toxicoses are presented.
The pharmacokinetics, organ distribution, metabolism and excretion of glucosamine were studied in the dog giving uniformly labelled [14C]-glucosamine (sulfate), i.v. or orally, in single doses. Immediately after i.v. administration, the radioactivity in plasma is due to glucosamine, and freely diffuses into organs and tissues. This radioactivity disappears quickly from plasma (initial t1/2 = 13 min, terminal t1/2 = 118 min). After 30-60 min the radioactivity in plasma is no longer due to glucosamine, but is incorporated into alpha- and beta-globulins. The protein-incorporated radioactivity is found already 20-30 min after i.v. administration, reaches a peak after 8 h and then slowly disappears, with a t1/2 = 2.9 days. Of the administered radioactivity, more than 34% is excreted in the urine, mainly as glucosamine, and 1.7% is excreted in the feces. Radioactivity is excreted also as [14C]-CO2 in the expired air. The radioactivity, after i.v. administration, diffuses rapidly from blood into the body. Some organs show an active uptake of radioactivity, e.g. the liver and the kidney. Other tissues, such as the articular cartilage, also have an active uptake. In most other organs the radioactivity found can be explained by passive diffusion processes from plasma. After oral administration of a single dose of [14C]-glucosamine the radioactivity is quickly and almost completely absorbed from the gastrointestinal tract. The pattern of disappearance, metabolic transformation, tissue distribution and excretion of the radioactivity are consistent with those found after i.v. administration.(ABSTRACT TRUNCATED AT 250 WORDS)
A double-blind trial was carried out in 40 out-patients with unilateral osteoarthrosis of the knee to compare the efficacy and tolerance of oral treatment with 1.5 g glucosamine sulphate or 1.2 g ibuprofen daily over a period of 8 weeks. Pain scores decreased faster during the first 2 weeks in the ibuprofen than in the glucosamine treatment group. Although the rate of decrease was slower, the reduction in pain scores was continued throughout the trial period in patients an glucosamine and the difference between the two groups turned significantly in favour of glucosamine at Week 8. No significant differences were observed in swelling or any of the other parameters monitored. Tolerance was satisfactory with both treatments, with only minor complaints being reported by 2 patients on glucosamine compared with 5 patients on ibuprofen.
Seventy dogs were included in a randomized, controlled, multicenter trial to test the efficacy of carprofen (2.2 mg/kg of body weight, PO, q 12 h) for relief of clinical signs associated with osteoarthritis. Thirty-six dogs received carprofen, and 34 received a placebo. Response of the dogs was evaluated by comparing results of force plate examination and a graded lameness examination performed before and immediately after 2 weeks of treatment, and by obtaining a subjective assessment of the dog's posttreatment condition from owners and participating veterinarians. A physical examination, CBC, serum biochemical analyses, urinalysis, and fecal occult blood test were performed before and after treatment to monitor safety. For force plate evaluation, the odds ratio was 3.3, meaning that a dog treated with carprofen was 3.3 times more likely to have a positive response than was a dog treated with the placebo. For evaluation by a veterinarian, the odds ratio was 3.5, and for owner evaluation, the odds ratio was 4.2. Institution where dogs were treated did not have a significant effect on results. A variety of reactions that may have been related to the medication (placebo or carprofen) were recorded; however, none were considered serious. Serum alanine aminotransferase activity was high in 3 dogs (2 that received placebo and 1 that received carprofen) at the conclusion of treatment; none of the 3 dogs were clinically ill. Ten dogs (5 that received placebo and 5 that received caprofen) had negative pretreatment and positive posttreatment fecal occult blood test results.
To evaluate the effect of a chondroprotective agent on hematologic, hemostatic, and biochemical variables in clinically normal dogs when administered over 30 days.
13 clinically normal Beagles of either sex.
Hematologic and hemostatic variables were assessed prior to treatment and on days 3, 14, and 30 of treatment. Biochemical variables were assessed before treatment and on day 30 of treatment.
Significant (P < 0.05) decreases were noted in hematocrit, hemoglobin, WBC, and segmented neutrophil variables on days 3 and 14 of treatment. A significant decrease in red distribution width was noted on days 3 and 30, in RBC count on day 3, and in lymphocyte numbers on day 30. There were also significant reductions of aggregation in response to adenosine diphosphate and collagen on days 14 and 30. Significant decreases were noted in total ATP release in response to collagen on days 14 and 30, as well as significant decrease in platelet count on days 14 and 30. No changes were noted in prothrombin time, activated partial thromboplastin time, mucosal bleeding time, or biochemical variables during the study.
Administration of this chondroprotective agent causes minor but not clinically important changes in hematologic and hemostatic variables in young, clinically normal dogs.
Oral chondroprotective agents are widely prescribed in veterinary medicine for the treatment of degenerative joint disease; however, to date, little is known about safety of their use.
The goal of any clinical trial involving modulation of osteoarthritis is to assess the efficacy of a proposed therapy. This article attempts to provide some insight into assessing the outcome of clinical trials involving the management of osteoarthritis and reviews select key areas within clinical trials that need to be evaluated during critical analysis of any proposed therapeutic product.
Patients with osteoarthritis (OA) of the knee were treated with chondroitin sulfate (CS, Condrosulf, IBSA, Lugano, CH) in a randomized, double-blind, placebo-controlled study, performed in two centres. The efficacy and tolerability of oral CS capsules 2 x 400 mg/day vs placebo was assessed in a 6-month study period. Patients with idiopathic or clinically symptomatic knee OA, with Kellgren and Lawrence radiological scores I-III, were included in this trial. Clinical controls were performed at months 0, 1, 3 and 6. Eighty patients completed the 6-month treatment period. Lequesne's Index and spontaneous joint pain (VAS) decreased constantly in the CS group; on the contrary, slight variations of the scores were reported in the placebo group. The walking time, defined as the minimum time to perform a 20-meter walk, showed a statistically significant constant reduction only in the CS group. ANOVA with repeated measures showed a statistically significant difference in favor of the CS group for these three parameters. During the study, patients belonging to the placebo group reported a higher paracetamol consumption, but this consumption was not statistically different between the two treatment groups. Efficacy judgements were significant in favor of the CS group. Both treatments were very well tolerated. All these results strongly suggest that chondroitin sulfate acts as a symptomatic slow-acting drug in knee OA.
Endoscopy was undertaken to examine the gastroduodenal mucosa of 24 healthy dogs after seven days and again after 28 days of oral non-steroidal anti-inflammatory drug (NSAID) administration. The dogs were divided into four groups. One group received ketoprofen (1 mg/kg every 24 hours), one group carprofen (2 mg/kg every 12 hours for seven days followed by 2 mg/kg every 24 hours), a third group meloxicam suspension (0.2 mg/kg every 24 hours), and the last group gelatin (one capsule every 24 hours). Serum biochemical and complete blood count parameters did not change significantly after NSAID administration. Gastroduodenal lesions were observed in 17 dogs, but in all cases these were mild to moderate. The dogs receiving gelatin or carprofen showed the fewest and the least severe lesions, although there was no statistically significant difference between the three test drugs and the control group (P < or = 0.05). None of the dogs showed any clinical signs related to the gastrointestinal lesions.
A 16-week randomized, double-blind, placebo-controlled crossover trial of a combination of glucosamine HCl (1,500 mg/day), chondroitin sulfate (1,200 mg/day), and manganese ascorbate (228 mg/day) in degenerative joint disease (DJD) of the knee or low back was conducted.
Thirty-four males from the U.S. Navy diving and special warfare community with chronic pain and radiographic DJD of the knee or low back were randomized. A summary disease score incorporated results of pain and functional questionnaires, physical examination scores, and running times. Changes were presented as a percentage of the patient's average score.
Knee osteoarthritis symptoms were relieved as demonstrated by the summary disease score (-16.3%; p = 0.05), patient assessment of treatment effect (p = 0.02), visual analog scale for pain recorded at clinic visits (-26.6%; p = 0.05) and in a diary (-28.6%; p = 0.02), and physical examination score (-43.3%; p = 0.01). Running times did not change. The study neither demonstrated, nor excluded, a benefit for spinal DJD. Side effect frequency was similar to that at baseline. There were no hematologic effects.
The combination therapy relieves symptoms of knee osteoarthritis. A larger data set is needed to determine the value of this therapy for spinal DJD. Short-term combination therapy appears safe in this setting.
To evaluate the effects of orally administered glucosamine hydrochloride (GlAm)-chondroitin sulfate (CS) and GlAm-CS-S-adenosyl-L-methionine (SAMe) on chemically induced synovitis in the radiocarpal joint of dogs.
32 adult mixed-breed dogs.
For 21 days, all dogs received a sham capsule (3 groups) or GlAm-CS (prior treatment group) in a double-blinded study. Unilateral carpal synovitis was induced by injecting the right radiocarpal joint with chymopapain and the left radiocarpal joint (control joint) with saline (0.9% NaCl) solution. Joints were injected on alternate days for 3 injections. After induction of synovitis, 2 groups receiving sham treatment were given GlAm-CS or GlAm-CS-SAMe. Another group continued to receive sham capsules (control group). Joint inflammation was quantified, using nuclear scintigraphy, before injection of joints and days 13, 20, 27, 34, 41, and 48 after injection. Lameness evaluations were performed daily.
Dogs given GlAm-CS before induction of synovitis had significantly less scintigraphic activity in the soft-tissue phase 48 days after joint injection, significantly less uptake in the bone phase 41 and 48 days after joint injection, and significantly lower lameness scores on days 12 to 19, 23, and 24 after injection, compared with other groups.
Analysis of results of this study suggest that prior treatment with GlAm-CS for 21 days had a protective effect against chemically induced synovitis and associated bone remodeling. Prior treatment with GlAm-CS also reduced lameness in dogs with induced synovitis.
The objective of this study was to evaluate the oral combination of glucosamine HCl, sodium chondroitin sulfate and manganese ascorbate for the treatment of osteoarthritis (OA) of the knee.
A randomized placebo-controlled study design was implemented. We recruited 93 patients with OA of the knee from a single center. The intervention group received 1000 mg FCHG49 glucosamine HCl, 800 mg TRH122 low molecular weight sodium chondroitin sulfate and 152 mg manganese ascorbate twice daily (Cosamin DS). Patients were evaluated initially and then every 2 months for 6 months. The primary outcome was the Lesquene Index of severity of osteoarthritis of the knee (ISK).
Patients with radiographically mild or moderate OA (N=72) in the intervention group showed significant improvement in the ISK at 4 and 6 months (P=0.003 and P=0.04, respectively). The response rate to the medication was 52% vs a 28% response rate to placebo. Patients with radiographically severe osteoarthritis (N=21) did not show significant improvements in the ISK. There was a 17% incidence of adverse events in the intervention group and 19% in the placebo group.
The studied combination of glucosamine HCl, sodium chondroitin sulfate and manganese ascorbate was found to be effective for the treatment of radiographically mild to moderate OA of the knee as measured by the ISK. This is the first U.S. study of these agents.
Supplements of glucosamine hydrochloride, low molecular weight chondroitin sulfate, and manganese ascorbate were tested separately and in combination for their ability to retard progression of cartilage degeneration in a rabbit instability model of osteoarthrosis. Computerized quantitative histologic evaluation of safranin O stained sections of the medial femoral condyles measured the grade and extent of tissue involvement of lesions. Severe lesions (Mankin grade greater than 7) were absent in all animals supplemented with a dietary mixture of glucosamine, chondroitin sulfate, and manganese ascorbate. Total linear involvement (mm of lesioned surface) and total grade (mean grade x number of lesions per animal) were reduced significantly in animals given the combination compared with controls (59% and 74% respectively). Animals supplemented with glucosamine, chondroitin sulfate, or manganese ascorbate alone had less moderate and severe tissue involvement than controls but not to the extent of the combined group. In vitro, a combination of glucosamine hydrochloride and chondroitin sulfate acted synergistically in stimulating glycosaminoglycan synthesis (96.6%). Chondroitin sulfate and manganese ascorbate but not glucosamine were effective in inhibiting degradative enzyme activity. These data suggest that the disease modifying effect (the ability to retard progression of cartilage degeneration) of a mixture of glucosamine, chondroitin sulfate, and manganese ascorbate is more efficacious than either agent alone.
To evaluate effects of an orally administered mixture of chondroitin sulfate, glucosamine hydrochloride and manganese ascorbate (CS-G-M) on articular cartilage metabolism in dogs with cranial cruciate ligament (CCL) deficient and reconstructed knees, as reflected by concentrations of synovial fluid 3B3, 7D4 and total sulfated glycosaminoglycan (GAG).
Sixteen adult dogs that underwent unilateral CCL transection were randomized into four groups. Thereafter, group I (N=3) had a sham CCL reconstruction, group II (N=3) had CS-G-M and sham CCL reconstruction, group III (N=5) had CCL reconstruction, and group IV (N=5) had CS-G-M and CCL reconstruction. Synovial fluid collected at 0, 1, 3 and 5 months was examined by ELISA for 3B3 and 7D4 epitope, and by DMMB assay for total GAG.
Synovial fluid from CCL transected knees of CS-G-M treated dogs contained significantly elevated concentrations of 3B3 (P=0.029), 7D4 (P=0.036) and 7D4/GAG (P=0.007) in comparison to controls, in a cross-sectional analysis at 3 months. Furthermore, 7D4 and 7D4/GAG concentrations remained significantly elevated (P=0.012) in CCL transected knees of CS-G-M treated dogs over the 5 month period. However, when epitope concentrations were expressed as a ratio of CCL-transected to contralateral non-operated knee, treatment effect of CS-G-M was no longer significant. Reconstruction of the CCL had no significant effect on synovial fluid epitope.
Administration of CS-G-M was associated with altered concentrations of 3B3 and 7D4 epitope in synovial fluid, suggesting that these compounds may act to modulate articular cartilage matrix metabolism in vivo.
Osteoarthritis (OA) is the most common form of arthritis, and it is often associated with significant disability and an impaired quality of life.
To review all randomized controlled trials (RCTs) evaluating the effectiveness and toxicity of glucosamine in osteoarthritis (OA).
We searched MEDLINE, Embase, and Current Contents up to November 1999, and the Cochrane Controlled Trials Register. We also wrote letters to content experts, and hand searched reference lists of identified RCTs and pertinent review articles.
Relevant studies met the following criteria: 1) RCTs evaluating the effectiveness and safety of glucosamine in OA, 2) Both placebo based and comparative studies were eligible, 3) Both single blinded and double-blinded studies were eligible.
Data abstraction was performed independently by two investigators and the results were compared for degree of agreement. Gotzsche's method and a validated tool (Jadad 1995) were used to score the quality of the RCTs. Continuous outcome measures were pooled using standardized mean differences. Dichotomous outcome measures were pooled using Peto Odds Ratios.
Collectively, the 16 identified RCTs provided evidence that glucosamine is both effective and safe in OA. In the 13 RCTs in which glucosamine was compared to placebo, glucosamine was found to be superior in all RCTs, except one. In the four RCTs in which glucosamine was compared to an NSAID, glucosamine was superior in two, and equivalent in two.
Further research is necessary to confirm the long term effectiveness and toxicity of glucosamine therapy in OA. Most of the trials reviewed only evaluated the Rotta preparation of glucosamine sulfate. It is not known whether different glucosamine preparations prepared by different manufacturers are equally effective in the therapy of OA.
The therapeutic effect of a nutritional supplement consisting of a combination of glucosamine hydrochloride (FCHG49), purified sodium chondroitin sulfate (TRH122), and manganese ascorbate (GCM) ³ was investigated in the rat model of collagen-induced autoimmune arthritis (CIA). The GCM compound was mixed with a palatable nutritional paste (Nutri-cal® [NC]). Oral administration of the NC/GCM compound was initiated in 26 rats 10 days before immunization and continued until the day of sacrifice. One group of 12 control rats was given no oral agents; a second group of 12 control rats received NC only. Evaluations included arthritis index (AI) scoring by three independent evaluators, histologic index (HI) scoring of lesions, T-cell proliferation, and serological studies for antibody classes and subclasses. Both the AI and HI criteria showed a statistically significant reduction in the prevalence of CIA in rats pretreated with the NC/GCM (54%) compared to the combined control groups (96%, χ ² analysis P < 0.001). Rats fed the NC/GCM also exhibited a significant decrease in the severity of autoimmune arthritis in both the AI and HI compared to control Group 2 (immunized-NC) (χ ² analysis P < 0.05). Histological studies verified the decreased incidence of arthritis in the NC/GCM group compared to control Group 2.
GCM treatment failed to alter T-cell proliferation and antibody production to bovine type-II collagen, indicating that its effects are not due to alteration of the antigen-specific immune response.
Glucosamine sulfate is able to stimulate proteoglycan synthesis by chondrocytes and has mild anti-inflammatory properties. In clinical trials, glucosamine sulfate was more effective than placebo in controlling the symptoms of osteoarthritis (OA). In order to better characterize this therapeutic activity, we conducted a randomized, double-blind, parallel-group study of glucosamine sulfate 500 mg t.i.d. vs ibuprofen 400 mg t.i.d., orally for 4 weeks. The study included 200 hospitalized patients with active OA of the knee, symptoms for at least 3 months and a Lequesne's index of at least 7 points. Patients were evaluated weekly. Response was defined as a reduction in the Lequesne's index by at least 2 points if the enrollment value was higher than 12 points, or by at least 1 point if the enrollment value was 12 or less points, together with a positive overall assessment by the investigator. The improvement tended to be sooner under ibuprofen (48% responders vs 28% after the 1st treatment week; P = 0.06, Fisher's Exact test), but there was no difference from the 2nd week onward, with a success rate of 52% in the ibuprofen group and of 48% in the glucosamine group (P = 0.67) at the end of treatment. The average Lequesne's index at enrollment was around 16 points and decreased by over 6 points in both groups, again with the above described trend. On the other hand, 35% of patients on ibuprofen reported adverse events, mainly of gastrointestinal origin, vs 6% adverse events with glucosamine (P < 0.001, Fisher's Exact test). The number of adverse event related drop-outs was different between the two groups (7% vs 1%, respectively; P = 0.035). Glucosamine sulfate was therefore as effective as ibuprofen on symptoms of knee OA. These data confirm glucosamine sulfate as a safe symptomatic Slow Acting Drug for OA.
Absorption, Distribution, Metabolismus und Exkretion von Glucosaminsulfat / Eine Übersicht
Gegenstand der vorliegenden Arbeit ist eine Übersicht über die Literatur zur Absorption, Distribution, Metabolismus und Exkretion (ADME) von Glucosamin (Gl) bei Mensch und Tier nach Verabreichung von kristallinem Glucosaminsulfat (CGS).
Intravenöse Verabreichung von CGS
Beim Menschen verschwindet Gl nach einer einmaligen intravenösen Bolus-injektion von 1005 mg CGS (628 mg Gl) mit einer empirischen Halbwertszeit von 1,11 h aus dem Plasma. Untersuchungen mit ¹⁴C-markiertem Gl (¹⁴C-Gl), das mit 502 mg CGS verabreicht wurde, haben gezeigt, daß das Verschwinden von Gl auf den Einbau der Substanz in die Plasma-globuline zurückzuführen ist, der mit einer Verzögerung von 0,45 h und einer Geschwindigkeitskonstanten von 0,26 h⁻¹ abläuft. Die Radioaktivität erreicht den Maximalwert nach 10 h und wird mit einer Halbwertszeit von 95 h ausgeschieden. Nach einmaliger i.v. Gabe von 502 mg durch ¹⁴C-G1 nachweisbaren CGS, wurden innerhalb von 120 h 29 % der verabreichten Dosis im Harn ausgeschieden. Übereinstimmende Ergebnisse wurden auch bei Ratte und Hund erzielt, wobei die Radioaktivität binnen kurzer Zeit in Leber, Nieren und anderen Geweben -einschließlich Gelenkknorpel - nachweisbar war.
Beim Menschen wurde die Harnausscheidung mittels der Ionenaustauscherchromatographie untersucht. Nach einer intravenösen Bolusinjektion von 1005 mg CGS fanden sich innerhalb von 24 h 38 % der verabreichten Dosis vorwiegend in den ersten 8 h nach der Verabreichung im Harn. Ähnliche Ergebnisse wurden mit durch ¹⁴C-G1 nachweisbarem CGS erzielt. Auch bei Ratte und Hund kam es mit durch ¹⁴C-GL nachweisbarem CGS zu übereinstimmenden Ergebnissen. Die Ausscheidung von Radioaktivität im Kot war geringfügig.
Die bei der Ratte aus ¹⁴CO2 ermittelte Ausscheidung der Radioaktivität in der Atemluft betrug innerhalb von 144 h 49 % der verabreichten Dosis. 16 % davon wurden in den ersten 6 h ausgeschieden.
Intramuskuläre Verabreichung von CGS
Beim Menschen kam es nach einmaliger intramuskulärer Injektion von 502 mg durch ¹⁴C-G1 nachweisbarem CGS zu ähnlichen Resultaten wie nach der intravenösen Gabe.
Orale Gabe von CGS
Beim Menschen lag der Gl-Spiegel im Plasma nach einer einmaligen Gabe von 7,5 g CGS unter der Nachweisgrenze der Ionenaustauscherchromatographie (3 μg/ ml). Nach einmaliger Gabe von 314 mg durch ¹⁴C-G1 nachweisbarem CGS erschien die Radioaktivität mit einer Verzögerung von 1,5 h in den Plasmaglobulinen inkorporiert und nahm mit einer Geschwindigkeitskonstanten von 0,24 h⁻¹ zu. 9 h nach Verabreichung war der Maximalwert erreicht Dann wurde die Radioaktivität mit einer Halbwertszeit von 58 h ausgeschieden. Die aufgrund der AUC-Werte der in die Globuline inkorporierten Radioaktivität ermittelte absolute orale Bioverfügbarkeit, lag bei 44 %. Innerhalb von 120 h wurden 11,3 % der verabreichten Dosis mit dem Kot ausgeschieden. Dies läßt darauf schließen, daß zumindest 88,7 % der verabreichten Dosis aus dem Magen-Darm-Trakt resorbiert worden waren. Die Differenz von 45 % läßt sich wahrscheinlich durch einen hepatischen First-Pass-Effekt erklären. Bei Untersuchungen an Ratten, die 126-3768 mg durch ¹⁴C-Gl nachweisbares CGS erhalten hatten, wurde ein linearer Zusammenhang zwischen der Dosierung und den AUC-Werten sowie den Cmax der Radioaktivität im gesamten und im depro-teinisierten Plasma gefunden.
Die Ausscheidung von Gl im 24-h-Urin des Menschen wurde mittels der Ionenaustauscherchromatographie bestimmt. Nach einmaliger Gabe von 7,5 g CGS betrug sie 1,19 % der verabreichten Dosis und war vor allem in den ersten 8 Stunden nach Verabreichung zu beobachten. Nach 7tägiger Gabe von 1884 mg nahm die tägliche Gl-Ausscheidung im Harn von 1,60 % der Tagesdosis in den ersten 24 h auf 2,22 % in den letzten 24 h zu. Nach dem zweiten Behandlungstag stellte sich ein Steady state ein.
Die Harnausscheidung im Steady state nach wiederholter Gabe läßt den Schluß zu, daß die tägliche Verabreichung von 1884 mg CGS in Form von 3mal täglich 1 Dragée oder einmal täglich als orale Lösung bioäquivalent ist.
Die Ausscheidung der Radioaktivität mit der Atemluft als ¹⁴CO2 lag bei der Ratte innerhalb von 144 h bei 82 % der verabreichten Dosis, wobei 61 % davon in den ersten 6 h ausgeschieden wurden.
Wechselwirkung von Gl mit der ADME von Glucose
Absorption, Distribution, Metabolismus und Exkretion von Glucose wurden bei der Ratte nach intravenöser oder oraler Verabreichung von ¹⁴C markierter Glucose untersucht. Hinsichtlich der Plasmakinetik und Gewebsverteilung gab es grundlegende Unterschiede zwischen Glucose und Gl. Während exogene Glucose die Energie für biochemische Prozesse liefert, wirkt exogenes Gl hauptsächlich als Substrat für die Biosynthese von Mucopolysacchariden und Biopolymeren in den Gelenken und Knochen. Hinweise auf eine Wechselwirkung zwischen oral verabreichtem Gl und Absorption, Distribution, Metabolismus und Exkretion von Glucose waren nicht zu beobachten.
The aim of this study was to evaluate the joint count for erosions in patients with erosive osteoarthritis (EOA) of the hands treated with 800 mg/day of orally administered chondroitin sulfate plus naproxen, compared with that of patients administered naproxen only. Twenty-four consecutive patients (22 women and two men, mean age 53.0 +/- 6) suffering from symptomatic OA and with radiographic characteristics of EOA were studied. The patients were divided into two groups of 12 patients each. The first group took naproxen 500 mg/day only. The second group was treated with chondroitin sulfate 800 mg/day orally plus naproxen 500 mg/day. Radiological hand examinations were performed at baseline and again after 12 and 24 months. In both groups, the joint count for erosions showed a general tendency to increase over time. Progression of erosions at 24 months was lower in patients treated with 800 mg/day chondroitin sulfate plus naproxen than in patients taking naproxen only (p <0.05). Chondroitin sulfate failed to stop the usual time-associated progression in the number of finger joints presenting erosions in EOA of the hands. It was, however, associated with a lower increase in the number of finger joints with erosions detected after 2 years of radiological observation.
The purpose of this study was to determine the oral bioavailability and pharmacokinetics of a glucosamine (GL) and the disaccharides of chondroitin sulfate (CS) after single and multiple-dosing of a GL/CS combination (Cosamin, Cosequin).
Male beagle dogs (n = 8, 12 kg) received the following treatments: (1) IV GL (500 mg)/CS (400 mg), (2) p.o. GL (1500 mg)/CS (1200 mg), (3) p.o. GL (2000 mg)/CS (1600 mg), (4) p.o. GL (1500 mg)/CS (1200 mg) QD for days 1-7 and p.o. GL (3000 mg)/CS (2400 mg) from days 8 to 14. Blood samples were collected over 24 h and glucosamine and the disaccharides of chondroitin sulfate were determined. Pharmacokinetic analysis was performed on glucosamine and total chondroitin sulfate disaccharides and parameters were compared across treatments using ANOVA with post hoc analysis.
After the IV administration, glucosamine declined rapidly in a bi-exponential fashion with a mean (+/- S.D.) elimination t(1/2) of 0.52 (0.25) h. GL absorption was relatively fast (C(max) = 8.95 microg/ml, and T(max) 1.5 h after 1500 mg dose) and the mean bioavailability of glucosamine after single dosing was approximately 12%. The extent of absorption of chondroitin sulfate as indicated by the mean C(max) (21.5 microg/ml) and mean AUC (187 microg/ml h) of total disaccharides after dosing (1600 mg) provides evidence that chondroitin sulfate is absorbed orally. The bioavailability of CS ranged from 4.8 to 5.0% after single dosing and 200-278% upon multiple dosing.
The results of this study show that both glucosamine and chondroitin sulfate (measured as total disaccharides) are bioavailable after oral dosing. In addition, the low molecular weight chondroitin sulfate used in this study displays significant accumulation upon multiple dosing.
The efficacy, tolerance and ease of administration of a nutraceutical, carprofen or meloxicam were evaluated in a prospective, double-blind study on 71 dogs with osteoarthritis. The client-owned dogs were randomly assigned to one of the three treatments or to a placebo control group. The influence of osteoarthritis on the dogs' gait was described by comparing the ground reaction forces of the arthritic dogs and 10 normal dogs. Before the treatments began, and 30 and 60 days later, measurements were made of haematological and biochemical variables and of the ground reaction forces of the arthritic limb, and subjective assessments were made by the owners and by the orthopaedic surgeons. Changes in the ground reaction forces were specific to the arthritic joint, and were significantly improved by carprofen and meloxicam but not by the nutraceutical; the values returned to normal only with meloxicam. The orthopaedic surgeons assessed that there had been an improvement with carprofen and meloxicam, but the owners considered that there had been an improvement only with meloxicam. The blood and faecal analyses did not reveal any changes. The treatments were well tolerated, except for a case of hepatopathy in a dog treated with carprofen.
Chondroprotectants and nutraceuticals have become attractive adjunctive or alternative treatments for cats and dogs suffering from osteoarthritis. Osteoarthritic patients can be managed satisfactorily in most situations with optimization of body condition, exercise modification, anti-inflammatory therapy, and the use of chondroprotectants agents. Presently, recommendations cannot be made as to which chondroprotectant is best for each dog and cat afflicted with osteoarthritis. Head-to-head comparisons of these products have not been made, and it is not known when the different mediators of osteoarthritis play an important role. Currently, the best recommendation is to use products that have well-designed experimental and clinical research evaluating efficacy and safety, and products that are manufactured under the high quality standards practiced by the pharmaceutical industry.
The purpose of this study was to determine if glucosamine (GL) hydrochloride (FCHG49) and low molecular weight (LMW) chondroitin sulfate (CS) (TRH122) are absorbed after oral administration to horses. The bioavailability of LMWCS was evaluated by quantifying the total disaccharides found in the plasma following chondroitinase ABC digestion.
Two separate studies were conducted. In study 1, ten adult horses received the following four treatments in a randomized crossover fashion: (1) i.v. LMWCS (3 g of 8 kDa), (2) p.o. LMWCS (3 g of 8 kDa), (3) i.v. LMWCS (3 g of 16.9 kDa) and (4) p.o. LMWCS (3 g of 16.9 kDa). Each group received 9 g GL with LMWCS. In a second study, each horse (n=2) was randomly assigned to receive either i.v. administration of GL HCl (9 g) or p.o. administration of GL HCl (125 mg/kg). Blood samples were collected, assayed and pharmacokinetic parameters were determined.
GL was absorbed after oral dosing with a mean C(max) of 10.6 (6.9) microg/ml and a mean T(max) of 2.0 (0.7) h. The extent of absorption of LMWCS after dosing with both the 8.0 and 16.9 kDa provides evidence that LMWCS is absorbed orally. C(max) and AUC were higher (p<0.05) for the 16.9 kDa material compared with 8.0 kDa. However, the 16.9 kDa bioavailability was less than 8.0 kDa, but this difference was not significant.
This study provides the first report of the bioavailability of orally administered GL and LMWCS in the horse.
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