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Change in knee osteoarthritis cartilage detected by delayed gadolinium enhanced magnetic resonance imaging following treatment with collagen hydrolysate: A pilot randomized controlled trial
Abstract
To determine whether either of two magnetic resonance imaging approaches - delayed gadolinium enhanced magnetic resonance imaging of cartilage (dGEMRIC), or T2 mapping - can detect short-term changes in knee hyaline cartilage among individuals taking a formulation of collagen hydrolysate.
Single center, prospective, randomized, placebo-controlled, double-blind, pilot trial of collagen hydrolysate for mild knee osteoarthritis (OA). Participants were allowed to continue the prior analgesic use. The primary outcome was change in dGEMRIC T1 relaxation time in the cartilage regions of interest at the 24-week timepoint. Secondary endpoints included the change in dGEMRIC T1 relaxation time between baseline and 48 weeks, the change in T2 relaxation time at 0, 24 and 48 weeks, the symptom and functional measures obtained at each of the visits, and overall analgesic use.
Among a sample of 30 randomized subjects the dGEMRIC score increased in the medial and lateral tibial regions of interest (median increase of 29 and 41 ms respectively) in participants assigned to collagen hydrolysate but decreased (median decline 37 and 36 ms respectively) in the placebo arm with the changes between the two groups at 24 weeks reaching significance. No other significant changes between the two groups were seen in the other four regions, or in any of the T2 values or in the clinical outcomes.
These preliminary results suggest that the dGEMRIC technique may be able to detect change in proteoglycan content in knee cartilage among individuals taking collagen hydrolysate after 24 weeks.
... Enrolled participants had diagnoses raging from mild to moderate knee OA, with only one study including patients with severe knee OA (28). The follow-up duration varied across studies, ranging from 10 weeks (29) to 48 weeks (30). The trials reported the usage of undenatured collagen and hydrolysed collagen, with chicken sternal cartilage being the most frequently used collagen source (27,29,31,32). ...
... Regarding the selection of reported results, two studies (29, 32) prompted some concerns, while the remainder presented a low risk of bias. Overall, four studies were rated as low risk (30,31,34,35), and seven studies were classified as having some concerns (11, 26-29, 32, 33). The complete risk of bias assessment is depicted in Figure 2. ...
... Out of the studies included in the analysis, 7 reported adverse events (11,26,29,30,34,35). These events were generally categorised as non-severe. ...
Objectives:
To perform a systematic review and meta-analysis to assess the clinical efficacy of collagen-based supplements on knee osteoarthritis (OA) symptoms.
Methods:
Until October 2023, we conducted searches on the MEDLINE, EMBASE, Web of Science, and Scopus databases to identify randomised controlled trials (RCTs) that reported the effects of oral collagen-based supplements on knee OA. Quantitative data from outcomes were pooled using a random- or fixed-effects model (depending on inter-study variability) and the generic inverse variance method. The Cochrane Risk of Bias 2.0 tool was employed to assess the risk of bias.
Results:
This systematic review incorporated information of 870 participants included from 11 RCTs, with 451 allocated to the collagen supplementation group and 419 to the placebo group. The meta-analysis revealed an overall significant improvement of both function [MD, -6.46 (95% CI -9.52, -3.40); I2=75%; p=0.00001] and pain scores [MD, -13.63 (95% CI -20.67, -6.58); I2=88%; p=0.00001], favouring collagen supplementation.
Conclusions:
The results of this meta-analysis suggest that oral collagen administration relieves OA symptoms. Our findings revealed noteworthy improvements, statistically and clinically, in both functional and pain scores.
... In the pre-clinical period, it was demonstrated that collagen peptides can stimulate chondrocytes to synthesize cartilage extracellular matrix (ECM) macromolecules and could thus provide support by counteracting progressive tissue degeneration [28][29][30][31][32]. The results of McAlindon et al. (2011) [33] suggest that the anabolic processes of collagen peptides on the joint cartilage can be translated to clinical investigations. Several clinical studies demonstrated symptomatic improvement after collagen peptide treatment in patients with joint health problems [33][34][35][36][37][38][39][40][41][42]. ...
... In the pre-clinical period, it was demonstrated that collagen peptides can stimulate chondrocytes to synthesize cartilage extracellular matrix (ECM) macromolecules and could thus provide support by counteracting progressive tissue degeneration [28][29][30][31][32]. The results of McAlindon et al. (2011) [33] suggest that the anabolic processes of collagen peptides on the joint cartilage can be translated to clinical investigations. Several clinical studies demonstrated symptomatic improvement after collagen peptide treatment in patients with joint health problems [33][34][35][36][37][38][39][40][41][42]. ...
... The results of McAlindon et al. (2011) [33] suggest that the anabolic processes of collagen peptides on the joint cartilage can be translated to clinical investigations. Several clinical studies demonstrated symptomatic improvement after collagen peptide treatment in patients with joint health problems [33][34][35][36][37][38][39][40][41][42]. However, most of these trials included participants with osteoarthritis [33][34][35][37][38][39][40]. ...
The intake of specific collagen peptides (SCPs) has been shown to decrease activity-related knee pain in young, physically active adults. This trial investigated the effect of a 12-week SCP supplementation in a wider age range of healthy men and women over 18 years with functional knee and hip pain during daily activities. A total of 182 participants were randomly assigned to receive either 5 g of specific collagen peptides (CP-G) or a placebo (P-G). Pain at rest and during various daily activities were assessed at baseline and after 12 weeks by a physician and participants using a 10-point numeric rating scale (NRS). The intake of 5 g SCP over 12 weeks significantly reduced pain at rest (p = 0.018) and during walking (p = 0.032) according to the physician’s evaluation. Participants in the CP-G also reported significantly less pain when climbing stairs (p = 0.040) and when kneeling down (p < 0.001) compared to the P-G. Additionally, after 12 weeks, restrictions when squatting were significantly lower in the CP-G compared with the P-G (p = 0.014). The daily intake of 5 g of SCP seems to benefit healthy adults with hip and knee joint discomforts by reducing pain during daily activities.
... The clinical efficacy and safety of CHs and CH-derived peptides have been demonstrated in several trials and summarized in Table 1 [51][52][53][54][55][56][57][58][59][60][61]. The supplement primarily helps manage OA pain and increase mobility, but recent work has also demonstrated improvements in bone health and cartilage characteristics, especially in patients engaging in a physical exercise program [55,59]. ...
... The clinical efficacy and safety of CHs and CH-derived peptides have been demonstrated in several trials and summarized in Table 1 [51][52][53][54][55][56][57][58][59][60][61]. The supplement primarily helps manage OA pain and increase mobility, but recent work has also demonstrated improvements in bone health and cartilage characteristics, especially in patients engaging in a physical exercise program [55,59]. [60] A randomized double-blind, placebo-controlled study design was completed over 6 months on 250 subjects with primary knee OA to assess the efficacy of CH on OA pain and joint function [51]. ...
... Accordingly, high-risk groups could possibly benefit from supplementation at a young age (e.g., below 25 y) and possibly delay the onset of joint damage, but this remains to be assessed. More recent work by McAlindon et al. (2011) demonstrated that, in a randomized, placebo-controlled, double-blind imaging study, changes in proteoglycan content in knee cartilage, as well as improvement in cartilage morphology, were observed after 24 weeks of CH treatment [59]. ...
Osteoarthritis (OA) is the most common joint disorder, with a social and financial burden that is expected to increase in the coming years. Currently, there are no effective medications to treat it. Due to limited treatment options, patients often resort to supplements, such as collagen hydrolysates (CHs). CHs are products with low molecular weight (MW) peptides, often between 3 and 6 kDa, and are a result of industrialized processed collagen. Collagen extraction is often a by-product of the meat industry, with the main source for collagen-based products being bovine, although it can also be obtained from porcine and piscine sources. CHs have demonstrated positive results in clinical trials related to joint health, such as decreased joint pain, increased mobility, and structural joint improvements. The bioactivity of CHs is primarily attributed to their bioactive peptide (BAP) content. However, there are significant knowledge gaps regarding the digestion, bioavailability, and bioactivity of CH-derived BAPs, and how different CH products compare in that regard. The present review discusses CHs and their BAP content as potential treatments for OA.
... [19][20][21] Collagen is a well-established human food source of peptides, some of which appear to enter the blood intact 22,23 and have a range of bioactive properties. 24 Collagen has been found to enhance synthesis or growth in a range of musculoskeletal tissues, such as cartilage, 25 ligament, 26 and bone. 27,28 Specific to musculotendinous tissues, collagen peptides have been shown to induce myoblast differentiation and myotube hypertrophy in mouse skeletal muscle cells in-vitro by activating the mTOR signaling pathway, 29 upregulate human gene expression related to signal transduction pathways activated in muscular remodeling 30 and there is emerging evidence that collagen supplementation in humans can enhance the rehabilitation of injured tendons. ...
... Additionally, based on visual inspection the seven contiguous slices around the suspected maximum anatomical cross-sectional area (ACSA MAX ; i.e., three either side of the suspected ACSA MAX ) were assessed to ensure the single image with the highest ACSA (i.e., ACSA MAX ) of that muscle was measured (and this was confirmed by inspection of the anatomical cross-sectional area-muscle length curve). The following number of images were segmented along the length of each muscle (mean of pre-and post-image number before calculating a mean across all participants): RF, 27 (range 24-30); VM, 27 (range 24-30); VI, 29 (range 27-33); VL, 29 (range 25-31); BFsh, 23 (range 19-25); BFlh, 24 (range 20-29); SM, 23 (range [19][20][21][22][23][24][25][26][27]; ST, 26 (range 23-32); gluteus maximus, 24 (range [20][21][22][23][24][25][26][27]. The volume of each muscle was calculated as the area under the anatomical cross-sectional area-muscle length curve following cubic spline interpolation (1000 point; GraphPad Prism 8; GraphPad Software). ...
... Additionally, based on visual inspection the seven contiguous slices around the suspected maximum anatomical cross-sectional area (ACSA MAX ; i.e., three either side of the suspected ACSA MAX ) were assessed to ensure the single image with the highest ACSA (i.e., ACSA MAX ) of that muscle was measured (and this was confirmed by inspection of the anatomical cross-sectional area-muscle length curve). The following number of images were segmented along the length of each muscle (mean of pre-and post-image number before calculating a mean across all participants): RF, 27 (range 24-30); VM, 27 (range 24-30); VI, 29 (range 27-33); VL, 29 (range 25-31); BFsh, 23 (range 19-25); BFlh, 24 (range 20-29); SM, 23 (range [19][20][21][22][23][24][25][26][27]; ST, 26 (range 23-32); gluteus maximus, 24 (range [20][21][22][23][24][25][26][27]. The volume of each muscle was calculated as the area under the anatomical cross-sectional area-muscle length curve following cubic spline interpolation (1000 point; GraphPad Prism 8; GraphPad Software). ...
Aim:
Bioactive collagen peptides (CP) have been suggested to augment the functional, structural (size and architecture) and contractile adaptations of skeletal muscle to resistance training (RT), but with limited evidence. This study aimed to determine if CP vs placebo (PLA) supplementation enhanced the functional and underpinning structural, and contractile adaptations after 15 weeks of lower body RT.
Methods:
Young healthy males were randomized to consume either 15 g of CP (n=19) or PLA (n=20) once every day during a standardized program of progressive knee extensor, knee flexor and hip extensor RT 3 times/wk. Measurements pre and post RT included: knee extensor and flexor isometric strength; quadriceps, hamstrings and gluteus maximus volume with MRI; evoked twitch contractions, 1RM lifting strength and architecture (with ultrasound) of the quadriceps.
Results:
Percentage changes in maximum strength (isometric or 1RM) did not differ between groups (0.684≤P≤0.929). Increases in muscle volume were greater (quadriceps 15.2 vs. 10.3%; vastus medialis (VM) 15.6 vs. 9.7%; total muscle volume 15.7 vs. 11.4%; [all] P≤0.032) or tended to be greater (hamstring 16.4 vs. 12.5%; gluteus maximus 16.6 vs. 12.9%; 0.089≤P≤0.091) for CP vs. PLA. There were also greater increases in twitch peak torque (22.3 vs. 12.3%; P=0.038) and angle of pennation of the VM (16.8 vs. 5.8%, P=0.046), but not other muscles, for CP vs. PLA.
Conclusions:
CP supplementation produced a cluster of consistent effects indicating greater skeletal muscle remodelling with RT compared to PLA. Notably, CP supplementation amplified the quadriceps and total muscle volume increases induced by RT.
... Collagen peptides can be found in function meals like collagen-fortified snacks or drinks for those who have joint problems or bone health difficulties. These goods may promote bone density and flexibility in joints (McAlindon et al., 2011).To satisfy certain protein requirements, collagen peptides can be incorporated to customized protein drinks or smoothies (van Vliet, Burd and van Loon, 2015). Collagen peptides can be found in function meals like collagenfortified snacks or drinks for those who have joint problems or bone health difficulties. ...
... Collagen peptides can be found in function meals like collagenfortified snacks or drinks for those who have joint problems or bone health difficulties. These goods may promote bone density and flexibility in joints (McAlindon et al., 2011). Because of its advantages for skin health, collagen peptides are frequently employed in customized nutrition. ...
Particularly in the form of collagen peptides, collagen, an important structural protein present in many animal tissues, has drawn much interest for its possible health advantages. In this study, we look at the methods for isolating, characterizing, and extracting collagen peptides from fish sources. Due to its great availability and sustainability, fish collagen is a possible replacement for conventional collagen sources. Fish collagen peptides must be extracted using a number of processes, including demineralization, deproteinization, and acid or enzymatic treatment. These procedures are necessary to produce collagen that is very pure and bioactive. For characterizing isolated collagen peptides, methods including SDS-PAGE, FTIR spectroscopy, and amino acid analysis are frequently used to evaluate their quality and make-up. The subject of contemporary research has been the biological functions of collagen peptides generated from fish. These peptides have demonstrated a range of health-promoting qualities, including as antioxidant, anti-inflammatory, and anti-aging activities. They have also shown promise in boosting joint health, skin health, and wound healing. Fish collagen peptides are useful additives in medications, cosmetics, and nutritional supplements due to their bioavailability and bioactivity. Additionally, new research has demonstrated the potential of fish collagen peptides to improve gastrointestinal, bone, and cardiovascular health. These results indicate that fish collagen peptides have several uses in the nutraceutical and functional food industries
... Up to date, several clinical trials regarding the use of collagen as a food supplement for joint health have been published. Most of the studies have evaluated the therapeutic potential of either native type II collagen [89][90][91][92][93][94][95][96][97][98] or hydrolyzed collagens [99][100][101][102][103][104][105][106][107] in patients with OA. However, both types of collagens have been also tested in non-osteoarthritic individuals suffering joint discomfort [108][109][110][111][112][113]. ...
... Besides improvements in pain and function, changes in cartilage degradation have also been detected. In 2011, McAlindon et al. [99] reported an increase in proteoglycan content in knee cartilage after 24 weeks of treatment with 10 g/day of a specific hydrolyzed collagen formulation. ...
Osteoarthritis (OA) is the most common joint disease, generating pain, disability, and socioeconomic costs worldwide. Currently there are no approved disease-modifying drugs for OA, and safety concerns have been identified with the chronic use of symptomatic drugs. In this context, nutritional supplements and nutraceuticals have emerged as potential alternatives. Among them, collagen is being a focus of particular interest, but under the same term different types of collagens coexist with different structures, compositions, and origins, leading to different properties and potential effects. The aim of this narrative review is to generally describe the main types of collagens currently available in marketplace, focusing on those related to joint health, describing their mechanism of action, preclinical, and clinical evidence. Native and hydrolyzed collagen are the most studied collagen types for joint health. Native collagen has a specific immune-mediated mechanism that requires the recognition of its epitopes to inhibit inflammation and tissue catabolism at articular level. Hydrolyzed collagen may contain biologically active peptides that are able to reach joint tissues and exert chondroprotective effects. Although there are preclinical and clinical studies showing the safety and efficacy of food ingredients containing both types of collagens, available research suggests a clear link between collagen chemical structure and mechanism of action.
... Oral supplementation of hydrolyzed collagen peptides (Fortigel ® ) has been shown to be an effective adjuvant to non-invasive therapies currently in use for problems related to wear and aging of articular cartilages. In 2011, McAlindon et al., demonstrated a significant increase in the density of proteoglycans in hyaline cartilage by objectifying this data with a specific MRI method (dGEMRIC) [28]. ...
... Vitamin C plays a not entirely clear role in OA and spinal pain, but its deficiency has been often associated with such conditions [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]. The possible protective role of vitamin C in OA might be due to its antioxidant effects [40]. ...
... Only MRI can directly visualise cartilage in a clinical modality, but its use is unfeasible for regular evaluation due to limited availability, a need for general anaesthesia and significant costs (D'Anjou et al. 2008). However, MRI evaluations of OA-affected joints in humans have revealed improvements in cartilage structure after 24 weeks of taking CH (Gonçalves 2017, McAlindon et al. 2011. Earlier evaluations of cartilage structure have not been performed to the author's knowledge, and the onset of these structural changes in cartilage in relation to the duration of CH intake is yet to be clarified. ...
Osteoarthritis (OA) is a common disease in dogs with severe impact on their welfare. The multimodal management of OA includes feeding therapeutic diets and nutraceuticals to slow down OA progression. Collagen hydrolysates (CH) are a nutritional supplement that may exert anabolic effects on osteoarthritic joint cartilage as well as disease-modifying effects. After oral intake, CH is absorbed, mainly as amino acids, di- and tripeptides that are transported amongst others to the joint. In addition to reducing cartilage degradation, CH metabolites may reduce synovial inflammation and subchondral bone sclerosis during OA. Preliminary evidence in dogs suffering from the consequences of OA support the clinical efficacy of CH with reported reductions in lameness. However, effects on biomarker level of cartilage metabolism and inflammation are inconclusive. Additionally, current studies show a lack of standardised dosing regimens and the use of not validated outcomes. Future work should therefore elucidate further on the bioavailability of CH in dogs in order to establish adequate dosing recommendations. Furthermore, high-quality placebo-controlled randomised controlled trials are essential to dstudies have evaluated the cetermine the clinical efficacy of CH to reduce lameness, prevent OA progression and thereby improve the level of evidence.
... Previous in vivo studies have reported that hydrolyzed collagen oral supplementation has significantly improve skin conditions as: hydration, elasticity, firmness, reduce wrinkles, among others (Jhawar et al., 2020;Bolke et al., 2019;Addor et al., 2018;Kim et al., 2018), while also promoting orthopedic benefits such as increased bone strength, density, mass, improved joint mobility, and reduced pain (Wei et al., 2009;Bruyère et al., 2012;McAlindon et al., 2011). ...
Background and Objective
In recent years, the consumption of fish products has led to a worrying trend where approximately two-thirds of the total amount of fish is discarded as waste. At the same time, scientific interest in exploring natural collagen sources for cosmetics and dietary supplements has increased. This study explores the potential of valorizing sardine scales (Sardina pilchardus), a by-product of the canning industry, through the extraction of collagen for potential use in dermocosmetic formulations and food supplements.
Methods
Collagen from sardine scales was obtained though acid and enzymatic extraction. The collagen extracts were characterized by UV-Vis, FTIR spectroscopy, SDS-PAGE, powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The collagen was hydrolysed with papain to small peptides. Subsequently, the biological activities of acid-soluble collagen as well as the collagen peptides in terms of antioxidant and antimicrobial activity were evaluated. Furthermore, the capacity of collagen peptides to permeate the intestinal barrier, simulated with caco-2 cells, was evaluated.
Results
Purified collagen extracts were obtained from sardine scales, with enzymatic extraction method having a yield three times higher than the acid method. The SDS-PAGE analysis confirmed the extraction of type I collagen as well as its hydrolysis into small fragments (25–12 kDa). In terms of biological activities, collagen and collagen peptides have not demonstrated antimicrobial activity. However, regarding antioxidant activity, collagen peptides showed three times more capacity compared to non-hydrolyzed collagen. Meanwhile, in 6 h, about 6.37% of collagen peptides could permeate the intestinal barrier.
Conclusion
This work represents a continuous effort to advance our understanding and utilization of Portuguese marine waste resources, with focus on the valorization of sardine co-products for the development of food supplement or cosmetic formulations, contributing to the sustainable evolution of the circular blue economy.
... p=0.03) and the lateral tibia (25.5±60.2; p=0.02) after 24 weeks [59]. Additionally, evidence shows that consumption of oral HC decreased the number of additional treatments necessary to reduce activity-related knee pain in young adults [60]. ...
Background: The musculoskeletal system, due to inherent structure and function, lends itself to contributing toward joint pain, whether from inflammatory disorders such as rheumatoid arthritis, degenerative diseases such as osteoarthritis, or trauma causing soft tissue injury. Administration of peptides for treatment of joint pain or inflammation is an emerging line of therapy that seeks to offer therapeutic benefits while remaining safe and relatively non-invasive. Purpose: The purpose of this study is to review the current literature on existing oral peptide agents, intra-articular peptide agents, and new developments in human trials to assess route of administration (RoA) for drug delivery in terms of soft tissue regeneration. Study Design: Narrative Review. Methods: A comprehensive literature search was conducted using the PubMed database. The search included medical subject headings (MeSH) terms related to peptide therapy, soft tissue regeneration, and RoA. Inclusion criteria comprised articles focusing on the mechanisms of action of peptides, clinical or biochemical outcomes, and review articles. Exclusion criteria included insufficient literature or studies not meeting the set evidence level. Conclusion: The review identified various peptides demonstrating efficacy in soft tissue repair. Oral and intra-articular peptides showed distinct advantages in soft tissue regeneration, with intra-articular routes providing localized effects and oral routes offering systemic benefits. However, both routes have limitations in bioavailability and absorption. Still in their infancy, further inquiries/research into the properties and efficacy of emerging peptides will be necessary before widespread use. As a viable alternative prior to surgical intervention, peptide treatments present as promising candidates for positive outcomes in soft tissue regeneration.
... There are examples of clinical trials implementing CLG-Hs to treat osteoarthritis and other bonerelated diseases [140][141][142]. Clinical studies have demonstrated that the daily oral administration of CLG peptides can significantly increase bone mineral density in postmenopausal women [141]. ...
Biomaterials have been the subject of extensive research, with their applications in medicine and pharmacy expanding rapidly. Collagen and its derivatives stand out as valuable biomaterials due to their high biocompatibility, biodegradability, and lack of toxicity and immunogenicity. This review comprehensively examines collagen from various sources, its extraction and processing methods, and its structural and functional properties. Preserving the native state of collagen is crucial for maintaining its beneficial characteristics. The challenges associated with chemically modifying collagen to tailor its properties for specific clinical needs are also addressed. The review discusses various collagen-based biomaterials, including solutions, hydrogels, powders, sponges, scaffolds, and thin films. These materials have broad applications in regenerative medicine, tissue engineering, drug delivery, and wound healing. Additionally, the review highlights current research trends related to collagen and its derivatives. These trends may significantly influence future developments, such as using collagen-based bioinks for 3D bioprinting or exploring new collagen nanoparticle preparation methods and drug delivery systems.
... The dGEMRIC analysis showed high GAG content in regenerated cartilage after 3 years, aligning with histological findings of the cartilage at 1 year [122]. Additionally, McAlindon et al. used dGEMRIC imaging to demonstrate short-term (6 months) changes in knee hyaline cartilage following collagen hydrolysate treatment in 30 patients with mild to moderate OA [123]. ...
Articular cartilage damage and degeneration are among hallmark manifestations of joint injuries and arthritis, classically osteoarthritis. Cartilage compositional MRI (Cart-C MRI), a quantitative technique, which aims to detect early-stage cartilage matrix changes that precede macroscopic alterations, began development in the 1990s. However, despite the significant advancements over the past three decades, Cart-C MRI remains predominantly a research tool, hindered by various technical and clinical hurdles. This paper will review the technical evolution of Cart-C MRI, delve into its clinical applications, and conclude by identifying the existing gaps and challenges that need to be addressed to enable even broader clinical application of Cart-C MRI.
... In all these clinical trials, an improvement in the WOMAC index and other indexes of joint functionality and discomfort was observed. [27][28][29][30][31] Results from experimental studies have revealed that collagen is capable to reduce articular pain and a biomarker of cartilage degradation-CTX-II in the plasma and urine. 32 In the present study using high-functional "Wellnex" CPs, CTX-II levels showed a significant reduction in all test groups. ...
Objective
The various functionalities of collagen peptides have generated a large interest in utilizing the bioactive peptides as a nutritional therapy to ameliorate various physiological degenerative conditions. Collagen peptides are observed to reduce the pain and aligned difficulties with respect to osteoarthritis. Here we report the enhanced ameliorating property of novel high-functional “Wellnex” Type J collagen peptides following a double-blind randomized active and placebo-controlled 5-arm clinical trial (n = 100) by using it as a nutritional supplement in subjects with knee joint osteoarthritis in comparison with conventional bovine collagen peptides. The efficacy, safety, and tolerability were also studied.
Design
Dosages of 2.5, 5.0, and 10.0 g of high-functional Type J bovine collagen peptides, 10.0 g of conventional collagen peptides, and 10.0 g of placebo were given to the 5 groups for a period of 90 days. The Western Ontario McMaster Universities Arthritis Index (WOMAC) score, Pain Scale, Quality of Life (QoL), Physician’s Impression of change Score (PICS), serum C-terminal cross-linked telopeptide of type II collagen (CTX-II) levels and Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS) parameters were monitored.
Results
Type J 2.5 g showed significant improvement in WOMAC, QoL, CTX, and MOAKS and observed to be equivalent to conventional collagen peptide 10-g supplementation in terms of efficacy.
Conclusion
The two significant outcomes of the study were that Type J 10.0 g, Type J 5.0 g, Type J 2.5 g and conventional collagen peptides 10.0 g supplementation were observed to be beneficial nutraceutical therapies for knee joint osteoarthritis, and Type J 2.5 g supplementation was equivalent to conventional collagen peptides 10.0-g supplementation in terms of efficacy.
... This is currently the only study to investigate a dose-response effect of collagen ingestion on changes in collagen synthesis after exercise, albeit in jump-rope exercise not RE. Although no study has examined a collagen dose-response relationship without exercise, chronic collagen supplementation alone has been shown to induce improvements in bone mineral density [22] and cartilage health [23], suggesting that collagen ingestion might stimulate human connective tissue collagen synthesis independently of exercise. Thus, just as ingestion of 40 g whey protein has been shown to augment the muscle protein synthesis response to RE more than 20 g [24], it is possible that collagen ingestion may further augment the RE-induced rise in collagen synthesis [12,13] in a dose-response manner. ...
Background: Resistance exercise (RE) stimulates collagen synthesis in skeletal muscle and tendon but there is limited and equivocal evidence regarding an effect of collagen supplementation and exercise on collagen synthesis. Furthermore, it is not known if a dose-response exists regarding the effect of hydrolyzed collagen (HC) ingestion and RE on collagen synthesis.
Objective: We aimed to determine the HC dose-response effect on collagen synthesis following high-intensity RE in resistance-trained young men.
Methods: Using a double-blind, randomized cross-over design, 10 resistance-trained men (age: 26±3 years; height: 1.77±0.04 m; mass: 79.7±7.0 kg) ingested 0g, 15g or 30g HC with 50mg vitamin C 1h prior to performing four sets’ barbell back-squat RE at 10-repetition maximum load, after which they rested for six hours. Blood samples were collected throughout each of the three interventions to analyse procollagen type Ⅰ N-terminal propeptide (PⅠNP) and β-isomerized C-terminal telopeptide of type I collagen (β-CTX) concentration, and the concentration of 18 collagen amino acids.
Results: The serum PⅠNP concentration x time area-under-the-curve (AUC) was greater for 30g (267±79 μg∙L-1∙h) than 15g (235±70 μg∙L-1∙h, P=0.039) and 0g HC (219±88 μg∙L-1∙h, P=0.005) but there was no difference between 0g and 15g HC (P=0.675). The AUCs of glycine and proline were greater for 30g than for 15g and 0g HC (P<0.05). Plasma β-CTX concentration decreased from -1h to +6h (P<0.05), with no differences between interventions.
Conclusion: The greater PINP AUC suggests 30g HC ingested prior to high-intensity RE augments whole body collagen synthesis more than 15g and 0g HC in resistance-trained young men.
... However, evidence now suggests that certain peptides, including collagen, can cross the intestinal epithelium, enter circulation, and ultimately exert a range of systemic physiological effects (11)(12)(13). Collagen peptide (CP) supplementation has been reported to enhance synthesis rates or growth in a range of musculoskeletal tissues (cartilage [14], ligament [15], and bone [16]). In the context of RT, the effects of CP supplementation on skeletal muscle have begun to receive some attention, including previous work from our laboratory (17), with reports of augmented muscle function (18,19), growth (17)(18)(19)(20), and/or intrinsic contractile properties (17). ...
Purpose:
Collagen peptide supplementation has been reported to enhance synthesis rates or growth in a range of musculoskeletal tissues and could enhance tendinous tissue adaptations to resistance training (RT). This double-blind placebo-controlled study aimed to determine if tendinous tissue adaptations, size (patellar tendon cross-sectional area [CSA] and vastus lateralis [VL] aponeurosis area) and mechanical properties (patellar tendon), following 15 weeks of RT could be augmented with collagen peptide (CP) vs. placebo (PLA) supplementation.
Methods:
Young healthy recreationally active men were randomized to consume either 15 g of CP (n = 19) or PLA (n = 20) once every day during a standardized program of lower-body RT (3 times/wk). Measurements pre- and post-RT included: patellar tendon CSA and VL aponeurosis area (via MRI); patellar tendon mechanical properties during isometric knee extension ramp contractions.
Results:
No between-group differences were detected for any of the tendinous tissue adaptations to RT (ANOVA group x time, 0.365 ≤ P ≤ 0.877). There were within-group increases in VL aponeurosis area (CP: +10.0%, PLA: +9.4%), patellar tendon stiffness (CP: +17.3% PLA: +20.9%) and Young's Modulus (CP: +17.8%; PLA: +20.6%) in both groups (paired t-tests [all] P ≤ 0.007). There were also within-group decreases in patellar tendon elongation (CP: -10.8%, PLA: -9.6%) and strain (CP: -10.6%, PLA: -8.9%) in both groups (paired t-tests [all] P ≤ 0.006). Whilst no within-group changes in patellar tendon CSA (mean or regional) occurred for CP or PLA, a modest overall time effect (n = 39) was observed for mean (+1.4%) and proximal region (+2.4%) patellar tendon CSA (ANOVA, 0.017 ≤ P ≤ 0.048).
Conclusions:
In conclusion, CP supplementation did not enhance RT-induced tendinous tissue remodelling (either size or mechanical properties) compared to PLA within a population of healthy young males.
... It has been discussed that the radiography-based definition of structural eligibility is one of the reasons for failure of DMOAD trials. [6][7][8][9][10] Several plausible explanations exist to elaborate on this statement. First, the definition of OA disease severity based on radiography is limited due to lack of reproducibility of radiographic joint space measurements. ...
Despite decades of research efforts and multiple clinical trials aimed at discovering efficacious disease-modifying osteoarthritis (OA) drugs (DMOAD), we still do not have a drug that shows convincing scientific evidence to be approved as an effective DMOAD. It has been suggested these DMOAD clinical trials were in part unsuccessful since eligibility criteria and imaging-based outcome evaluation were solely based on conventional radiography. The OA research community has been aware of the limitations of conventional radiography being used as a primary imaging modality for eligibility and efficacy assessment in DMOAD trials. An imaging modality for DMOAD trials should be able to depict soft tissue and osseous pathologies that are relevant to OA disease progression and clinical manifestations of OA. Magnetic resonance imaging (MRI) fulfills these criteria and advances in technology and increasing knowledge regarding imaging outcomes likely should play a more prominent role in DMOAD clinical trials. In this perspective article, we will describe MRI-based tools and analytic methods that can be applied to DMOAD clinical trials with a particular emphasis on knee OA. MRI should be the modality of choice for eligibility screening and outcome assessment. Optimal MRI pulse sequences must be chosen to visualize specific features of OA.
... [43] McAlindon ve ark.'nın 2011 yılında yayımladıkları prospektif, randomize, plasebo kontrollü, çift-kör, pilot bir çalışmada, 48 hafta boyunca tip 2 hidrolize kollajen verilen orta derece diz osteoartriti olan hastalarda gelişmiş kıkırdak manyetik rezonans (MR) görüntüleme ile hastaların diz kıkırdağında bulunan hiyalin kıkırdak miktarında atış görülürken [DGEMRIC (Delayed gadolinium enhanced MRI of cartilage) score] plasebo kullananlarda incelme görülmüştür. [44] ...
... This suggests that the inclusion of collagen peptides and specific-gelatin products in combination with an intermittent exercise program may enhance collagen synthesis, which could play a beneficial role in injury prevention and tissue repair. In this sense, research has shown that supplementation with hydrolyzed collagen (≈10 g per day) can increase cartilage thickness in patients with osteoarthritis [114] and decrease knee pain in athletes [115]. Indeed, the recent systematic review performed by Kahtri et al. (2021) [47] concluded that 'collagen peptides and specific gelatin products have strong evidence in improving joint pain and functionality (especially at doses of 15 g/day)'. ...
It is estimated that three to five million sports injuries occur worldwide each year. The highest incidence is reported during competition periods with mainly affectation of the musculo-skeletal tissue. For appropriate nutritional management and correct use of nutritional supplements, it is important to individualize based on clinical effects and know the adaptive response during the rehabilitation phase after a sports injury in athletes. Therefore, the aim of this PRISMA in Exercise, Rehabilitation, Sport Medicine and Sports Science PERSiST-based systematic integrative review was to perform an update on nutritional strategies during the rehabilitation phase of musculoskeletal injuries in elite athletes. After searching the following databases: PubMed/Medline, Scopus, PEDro, and Google Scholar, a total of 18 studies met the inclusion criteria (Price Index: 66.6%). The risk of bias assessment for randomized controlled trials was performed using the RoB 2.0 tool while review articles were evaluated using the AMSTAR 2.0 items. Based on the main findings of the selected studies, nutritional strategies that benefit the rehabilitation process in injured athletes include balanced energy intake, and a high-protein and carbohydrate-rich diet. Supportive supervision should be provided to avoid low energy availability. The potential of supplementation with collagen, creatine monohydrate, omega-3 (fish oils), and vitamin D requires further research although the effects are quite promising. It is worth noting the lack of clinical research in injured athletes and the higher number of reviews in the last 10 years. After analyzing the current quantitative and non-quantitative evidence, we encourage researchers to conduct further clinical research studies evaluating doses of the discussed nutrients during the rehabilitation process to confirm findings, but also follow international guidelines at the time to review scientific literature.
... Relatively short duration, more acute exercise training bouts also increases the expression of lysl oxidase the primary enzyme involved in collagen synthesis and cross-linking [40], increasing collagen synthesis [31], creating a denser, stiffer, and stronger ECM [30]. In a study of patients ≥49 years of age with mild-to-moderate severity knee osteoarthritis, McAlindon et al. [59] found that the daily consumption of 10 g of collagen hydrolysate improved medial and lateral tibial hyaline cartilage health in patients with mild knee osteoarthritis. In agreement with this finding, a 24-week randomized clinical trial in college age varsity sport and club team athletes with activity-related knee pain showed that collagen hydrolate significantly decreased pain levels [27]. ...
Purpose
Sports injuries among youth and adolescent athletes are a growing concern, particularly at the knee. Based on our current understanding of microtrauma and anterior cruciate ligament (ACL) healing characteristics, this clinical commentary describes a comprehensive plan to better manage ACL microtrauma and mitigate the likelihood of progression to a non-contact macrotraumatic ACL rupture.
Methods
Medical literature related to non-contact ACL injuries among youth and adolescent athletes, collagen and ACL extracellular matrix metabolism, ACL microtrauma and sudden failure, and concerns related to current sports training were reviewed and synthesized into a comprehensive intervention plan.
Results
With consideration for biopsychosocial model health factors, proper nutrition and modified sports training with increased recovery time, a comprehensive primary ACL injury prevention plan is described for the purpose of better managing ACL microtrauma, thereby reducing the incidence of non-contact macrotraumatic ACL rupture among youth and adolescent athletes.
Conclusion
Preventing non-contact ACL injuries may require greater consideration for reducing accumulated ACL microtrauma. Proper nutrition including glycine-rich collagen peptides, or gelatin-vitamin C supplementation in combination with healthy sleep, and adjusted sports training periodization with increased recovery time may improve ACL extracellular matrix collagen deposition homeostasis, decreasing sudden non-contact ACL rupture incidence likelihood in youth and adolescent athletes. Successful implementation will require compliance from athletes, parents, coaches, the sports medicine healthcare team, and event organizers. Studies are needed to confirm the efficacy of these concepts.
Level of evidence
V
... Supplemental doses of CH used in the literature were mainly 10 g/day, and one RCT of 250 patients with knee OA reported significantly decreased pain and improved functioning following supplementation of 10 g CH daily over 6 months compared with placebo, results that were seen at all stages of OA. 63 Contrary to the trial above, disease severity may dictate outcomes. One pilot RCT of 30 individuals with mild knee OA over 24 weeks reported no symptom relief with 10 g/day CH, but magnetic resonance imaging (MRI) changes were detected, 64 indicating that although symptoms may not have been relieved, internal improvements were affected. A second RCT of 389 patients supplemented with 10 g/day CH for 24 weeks reported no significant differences with placebo on measures of pain and physical function. ...
Orally administered collagen in its many different forms is recognised as a highly biocompatible, safe form of supplementation, which has the potential to act on the body as an anti-inflammatory and antioxidant, and through structural remodelling and reduced lipotoxicity. The aim of this systematic review was to determine diseases where collagen has been indicated; assess safety, bioavailability and efficacy; and to provide therapeutic recommendations. It was concluded that collagen supplementation is strongly indicated for its positive therapeutic effect on pain management of osteoarthritis, balancing blood sugars in type II diabetes, wound healing, skin ageing, and post-exercise body composition and strength. Promising results were also seen for the use of collagen supplementation in osteoporosis, hypertension, rheumatoid arthritis, tendinopathy, cellulite, atopic dermatitis, sarcopenia and brittle nail syndrome. Although therapeutic recommendations were indicated in most of these diseases, owing in the large part to the use of these supplements as part of dual therapy or the uncertainty over translatability of branded products it was concluded that more studies are required to make definitive recommendations. There was a lack of clinical evidence to support the use of collagen for weight loss in obesity, gut health and in fibromyalgia.
... The growing activity in the field of cartilage damage creates a need for validated clinical outcome scores whose special emphasis was given to patients with cartilage injuries [19]. Different from the Lysholm, Tegner, and international knee documentation committee (IKDC) scores, the Western Ontario and McMaster Universities Index (WOMAC) is commonly used to measure the patients with osteoarthritis (OA) [20]. However, the population presenting with focal cartilage lesions after ACLR is generally younger and more active as compared to patients with OA [21]. ...
Background: Comparing to anterior cruciate ligament reconstructions (ACLR) with free hamstring tendon (FHT), ACLR with preserved tibial-insertion hamstring tendon (HT-PTI) could ensure the blood supply of the graft and avoid graft necrosis. Yet, whether HT-PTI could protect the cartilage and clinical outcomes in mid-long period after ACLR was still unclear. Purpose: To compare the cartilage change and clinical results between the HT-PTI and FHT in 5 years after ACLR. Study design: Randomized controlled trial; Level of evidence, 2. Methods: A total of 45 patients who underwent isolated ACLR with the autograft of hamstring tendons were enrolled and randomized into 2 groups. The study group undertook ACLR with HT-PTI, whereas the control group had FHT. At pre-operation, and 6, 12, 24, and 60 months post-operation, all cases underwent evaluation with Knee Injury and Osteoarthritis Outcome Score (KOOS), and MR examination. The knee cartilage was divided into 8 sub-regions of which the T2 value and cartilage volume on MRI were measured and documented. The data of two groups were compared and their correlations were analyzed. Results: A total of 18 patients in the HT-PTI group and 19 patients in the FHT group completed the follow-up. The KOOS scores were improved at each follow-up time point (p < 0.001), reached the most superior at 12 months and maintained until 60 months but had no significant difference between the two groups. At 60 months, the cartilage in most subregions in FHT group had higher T2 values than those of pre-operation (p < 0.05) and also higher than HT-PTI group; The cartilage volume changes (CV%) are positive at 6 months and negative from 12 to 60 months in the FHT group, while being negative at all time points in the HT-PTI group. The values of absolute CV% in most subregions in FHT group were significantly higher than those in the HT-PTI group at 6 and 60 months (p < 0.05). Conclusion: The improvement of KOOS score peaked at 12 months in all cases and had no difference between the two groups. The cartilage in the FHT group had more volume loss, earlier and wider damage than that in the HT-PTI group within 5 years. No significant correlation was found among KOOS score, CV%, and T2 value.
... These can be delivered to synovial joints via capillaries, directly affecting ECM metabolism in articular cartilage and immune cells such as macrophages [27]. As described above, there have been several studies showing the direct effects of collagen derivatives on cultured chondrocytes and immune cells [26][27][28][29]. In contrast, there have been relatively few studies on the mechanism behind the effects of free amino acids on joint health. ...
Joint problems impair performance during exercise and daily activities and influence quality of life. The present study aimed to examine the effects of a combination of six non-essential amino acids (6AA) on joint conditions in an adult population. A total of 50 participants aged between 20 and 64 years with joint discomfort but no diagnosed joint disorder were randomly and blindly assigned to a control or 6AA group. The 6AA group took 12 g of the non-essential amino acid formulation orally (4 g three times a day) and the control group took equivalent doses of a placebo. Each group maintained the daily dose for 12 weeks. Primary outcome measures were evaluated with the visual analogue scale (VAS), the Japanese Knee Osteoarthritis Measure (JKOM), and the Japanese Orthopaedic Association score (JOA). These tests were taken before the experiment began at 4 weeks and 12 weeks after the intervention. The results of the VAS indicated that 6AA improved joint pain, discomfort, and stiffness both during a resting state and during normal activity. Participants’ scores on the JKOM and JOA also showed significant improvements in the group that had taken the 6AA supplement. These results demonstrate that 6AA improves symptoms of joint problems, such as pain, discomfort, stiffness, and difficulty in performing daily activities after 4 weeks of daily consumption.
... A seminal study conducted with 250 primary knee arthritis subjects, who were given the same amount as reported earlier, i.e., 10 g collagen hydrolysates per day for 180 days, concluded that the collagen hydrolysates are safe as a functional food ingredient and potentially improve the knee joint complications in arthritis [141]. In another randomized double-blind pilot trial study, McAlindon et al. investigated the effect of collagen hydrolysates in osteoarthritic cartilage, using delayed gadolinium enhanced magnetic resonance imaging of cartilage (dGEMRIC) technique and reported a higher dGEMRIC score in the medial and lateral tibial regions of interest for collagen hydrolysate treated group compared to placebo groups [142]. ...
In biology, collagen-biomaterial regulates several signaling mechanisms of bone and immune cells involved in tissue repair and any imbalance in collagen turnover may affect the homeostasis of cells, becoming a major cause of several complications. In this case, the administration of oral collagen may play a potential role in returning cells to their normal function. For several decades, the beneficial effects of collagen have been explored widely, and thus many commercial products are available in cosmetics, food, and biomedical fields. For instance, collagen-based-products have been widely used to treat the complications of cartilage-related-disorders. Many researchers are reporting the anti-arthritogenic properties of collagen-based materials. In contrast, collagen, especially type-II collagen (CII), has been widely used to induce arthritis by immunization in an animal-model with or without adjuvants, and the potentially immunogenic-properties of collagen have been continuously reported for a long time. Additionally, the immune tolerance of collagen is mainly regulated by the T-lymphocytes and B-cells. This controversial hypothesis is getting more and more evidence nowadays from both sides to support its mechanism. Therefore, this review links the gap between the arthritogenic and anti-arthritogenic effects of collagen and explored the actual mechanism to understand the fundamental concept of collagen in arthritis. Accordingly, this review opens-up several unrevealed scientific knots of collagen and arthritis and helps the researchers understand the potential use of collagen in therapeutic applications.
... Collagen peptides are defined by high concentrations of the amino acids glycine (Gly), hydroxyproline (Hyp), and proline (Pro). Numerous studies have demonstrated that collagen hydrolyzate can enhance chondrocyte biosynthesis of type II collagen in vitro, suggesting that it may be used to treat osteoarthritis (Oesser et al., 1999;Ameye and Chee, 2006;Bello and Oesser, 2006;Mcalindon et al., 2011). ...
Osteoarthritis (OA) is a common type of arthritis characterized by degeneration of the articular cartilage and joint dysfunction. Various pharmacological and non-pharmacological techniques have been used to manage these diseases. Due to the diverse therapeutic properties of marine collagen, it has received considerable attention in its pharmacological application. Thus, the purpose of this study was to compare the efficacy of jellyfish collagen, collagen peptide, other sources of marine collagen, and glycine in treating OA. In the OA rat model, an anterior cruciate ligament transection combined with medial meniscectomy surgery (ACLT + MMx) was used to induce osteoarthritis in rats. Two weeks before surgery, male Sprague–Dawley rats were fed a chow-fat diet. After 6 weeks of treatment with collagen, collagen peptide, and glycine, the results show that they could inhibit the production of proinflammatory cytokines and their derivatives, such as COX-2, MMP-13, and CTX-II levels; therefore, it can attenuate cartilage degradation. Moreover, collagen peptides can promote the synthesis of collagen type II in cartilage. These results demonstrate that collagen and glycine have been shown to have protective properties against OA cartilage degradation. In contrast, collagen peptides have been shown to show cartilage regeneration but less protective properties. Jellyfish collagen peptide at a dose of 5 mg/kg b. w. has the most significant potential for treating OA because it protects and regenerates cartilage in the knee.
... 9 10 g hidrolize kollajen tüketimi sonrası manyetik rezonans ile görüntülemede diz kıkırdağının kalınlığının artması, kıkırdaktaki kollajenin sentezinde artıştan dolayı olabileceği belirtilmiştir. 10 Jelatin desteğinin kollajen sentezine etkisine bakılmış olan randomize çift kör kesitsel bir çalışmada, 5 gr ya da 15 gr C vitamininden zenginleştirilmiş jelatin ya da placebo verilmiş; 8 sağlıklı erkekte, 6 dakikalık ip atlama seansları sonrasındaki kan örneklerinde jelatin miktarı arttıkça dolaşımdaki glisin, prolin, hidroksiproin ve hidroksilizin miktarlarının arttığı gözlemlenmiştir. Egzersizden 1 saat önce 15 g jelatin alanlarda kanda tip I kollajenin amino terminal propeptid miktarının iki katına çıktığı gözlemlenmiştir. ...
During the recovery process after tendon injuries having proper nutrition can positively in�fluence the healing period. Some of the nutrients regarding to tendon health are collagen, vitamin C, glycine, copper, gelatin, hydrolyzed collagen and some anti-inflammatory nutrients like curcumin. Even though there is some evidence about these nutrients, taking into consideration that most of the experi�ments were based on animal trials and the low number of sample sizes, it is still early to make a precise statement about these nutrients. The increasing market of nutritional supplements and the misleading advertisements may cause athletes to make imprudent choices. This section aims to enlighten whether of the aforementioned nutrients rely on solid evidence or is it too early to make precise recommendations to the athletes.
... In contrast to milk proteins, dietary collagen is rich in glycine (>30% of all of the amino acid in the supplement) and this might be enough to augment collagen synthesis in response to training (Oikawa et al., 2020). Even though we did not directly measure collagen synthesis, combining the rapid delivery of glycine and other enriched amino acids (that peak 40-60 min postingestion; Alcock et al., 2019) with loading that is known to increase in collagen synthesis (Alcock et al., 2019;McAlindon et al., 2011;Paxton et al., 2012;Shaw et al., 2017) improved performance over exercise alone, providing indirect evidence that collagen supplementation increased matrix collagen synthesis. ...
Background:
Exercise and vitamin C-enriched collagen supplementation increase collagen synthesis, potentially increasing matrix density, stiffness, and force transfer.
Purpose:
To determine whether vitamin C-enriched collagen (hydrolyzed collagen [HC] + C) supplementation improves rate of force development (RFD) alongside a strength training program.
Methods:
Using a double-blinded parallel design, over 3 weeks, healthy male athletes (n = 50, 18-25 years) were randomly assigned to the intervention (HC + C; 20 g HC + 50 mg vitamin C) or placebo (20 g maltodextrin). Supplements were ingested daily 60 min prior to training. Athletes completed the same targeted maximal muscle power training program. Maximal isometric squats, countermovement jumps, and squat jumps were performed on a force plate at the same time each testing day (baseline, Tests 1, 2, and 3) to measure RFD and maximal force development. Mixed-model analysis of variance compared performance variables across the study timeline, whereas t tests were used to compare the change between baseline and Test 3.
Results:
Over 3 weeks, maximal RFD in the HC + C group returned to baseline, whereas the placebo group remained depressed (p = .18). While both groups showed a decrease in RFD through Test 2, only the treatment group recovered RFD to baseline by Test 3 (p = .036). In the HC + C group, change in countermovement jumps eccentric deceleration impulse (p = .008) and eccentric deceleration RFD (p = .04) was improved. A strong trend was observed for lower limb stiffness assessed in the countermovement jumps (p = .08). No difference was observed in maximal force or squat jump parameters.
Conclusion:
The HC + C supplementation improved RFD in the squat and countermovement jump alongside training.
... A previous ultrasonographic tissue characterisation study has shown that structural integrity is decreased in both Achilles tendons in people with unilateral Achilles tendinopathy [19]. As dietary supplementation of hydrolysed collagen appears to have systemic effects on collagen-dense tissue [20][21][22], we aimed to study both tendons of each individual patient, independent of whether participants had uni-or bilateral symptoms. ...
... [10,11] Preclinical studies have shown that the single administration of collagen peptides has a beneficial effect on bone metabolism. [20,21] According to the current state of research, the positive effect of collagen peptides in cartilage, [22][23][24][25][26] tendon and ligament [27] tissue may be due to molecular biological processes such as the stimulation of elastin, collagen type I and III formation. ...
Background:
The effects of specific collagen peptides on bone mineral density (BMD) in subjects with osteoporosis or osteopenia have already been investigated in 131 postmenopausal women in a randomized controlled trial. The purpose of this follow-up observation was to determine the longer-term effects of the same specific bioactive collagen peptides after a total intervention time of 4 years.
Methods:
In this open-label follow-up observation, 31 postmenopausal women with reduced BMD (initial T-score lower than-1 of either the femoral neck or the lumbar spine) completed the follow-up. BMD was measured via dual energy X-ray absorptiometry. Absolute changes in BMD and T-scores in the spine and femoral neck were assessed. The number of fractures was also recorded. All participants received specific bioactive collagen peptides.
Results:
Supplementation with bioactive collagen peptides during follow-up led to a clinically relevant increase in BMD in the spine. These findings were consistent with the results for the femoral neck.
Conclusions:
Long-term supplementation with specific bioactive collagen peptides appears to be effective in counteracting losses in BMD. Moreover, significant increases in BMD could contribute to improved bone stability.
Introduction
Musculoskeletal discomfort is prevalent in primary care, with conditions such as osteoarthritis and osteoporosis being significant contributors. Collagen, particularly type I, is a major structural protein found in connective tissues. The supplementation of type I hydrolyzed collagen has been investigated for its potential benefits in musculoskeletal health.
Objective
This systematic review aims to evaluate the current literature on the effects of type I hydrolyzed collagen supplementation on bones, muscles, and joints.
Methods
A systematic search was conducted in August 2024 using four electronic databases - PubMed, Scopus, EMBASE, and CINAHL. The inclusion criteria were randomized controlled trials (RCTs) and systematic reviews evaluating oral supplementation with type I hydrolyzed collagen. Exclusion criteria were pre-clinical studies, experimental studies, studies not focusing on type I hydrolyzed collagen, studies with beauty-related endpoints, studies that combined collagen with other ingredients, and unblinded, nonrandomized, and uncontrolled trials.
Results
Out of 4,246 articles screened, 36 RCTs met the inclusion criteria. The study protocols varied in population, health conditions, and study duration. Studies focused on bone health faced limitations that prevent definitive conclusions about the effects of collagen supplementation. In contrast, studies on joint health reported beneficial outcomes, such as pain reduction, improvements in clinical parameters, increased physical mobility, and enhanced ankle function. The muscle health studies were inconsistent, with positive effects predominantly observed when supplementation was associated with physical exercise.
Conclusion
Collagen supplementation demonstrates promising results. However, heterogeneity among studies limits the generalizability of findings. Future research should prioritize standardized protocols and consistent outcome measures.
Objectives
To evaluate whether osteopathic and related manual interventions improve adult mental health (depression, anxiety, stress) and psychophysiological measures (eg, heart rate variability, skin conductance).
Design
Systematic review and meta-analysis of randomised controlled trials (RCTs).
Data sources
PubMed, MEDLINE (Ovid), Scopus, Cochrane, and AMED, searched through September 2024.
Eligibility criteria
English-language RCTs with ≥30 participants investigating osteopathic or related manual therapies (eg, myofascial release, high-velocity low-amplitude thrusts) delivered by qualified practitioners, compared with no treatment or sham, and reporting immediate postintervention mental health or psychophysiological outcomes.
Data extraction and synthesis
Full-text screening, risk-of-bias assessment and data extraction were conducted independently by multiple reviewers using a standardised Joanna Briggs Institute (JBI) Extraction Form. Risk of bias was assessed using the JBI Critical Appraisal Checklist. For meta-analyses, Hedges’ g (with 95% CIs) was calculated from postintervention means and SD. Random-effects models accounted for heterogeneity, and prediction intervals were calculated to assess uncertainty in effect estimates.
Results
20 RCTs were included. Osteopathic interventions reduced depression (Hedges’ g =−0.47, 95% CI: −0.86 to –0.09, p=0.02) and increased skin conductance (Hedges’ g =0.67, 95% CI: 0.00 to 1.34, p=0.05). Depression improvements were greater in pain populations (Hedges’ g =−0.61, 95% CI: –1.06 to –0.17, p=0.01). However, wide prediction intervals and moderate heterogeneity indicate uncertainty in true effect sizes, and limited studies and sample sizes restrict assessment of publication bias.
Conclusions
Osteopathic and related manual therapies may reduce depression and influence certain psychophysiological markers, particularly in pain populations, but uncertainty and heterogeneity limit confidence. More rigorous, larger, and longitudinal RCTs are needed.
Trial registration number
This meta-analysis was not formally registered, though the protocol and search strategy can be found at Open Science Framework, registration identification: https://osf.io/jrtpx/ .
Osteoarthritis is a widely prevalent disease of the whole joint including cartilage, bone, and soft tissues. The increasing importance of imaging and assessment of all joint structures has been recognized. Conventional radiography is still the first and most commonly used imaging technique for evaluation of patients with a known or suspected diagnosis of OA, although its limitations are nowadays well known. MRI continues to play a critical role in understanding the natural history of the disease and in guiding future therapies, thanks to its ability to image the knee as a whole organ and to directly and three-dimensionally evaluate morphology and composition of articular structures such as cartilage and menisci. In this chapter, we will give insight into the roles and limitations of conventional radiography and MRI in the imaging of OA and describe the use of other modalities including ultrasound, tomosynthesis, computed tomography, and nuclear medicine in clinical practice and research in OA, particularly focusing on the assessment of knee. Lastly, we will describe the evolving application of artificial intelligence in the imaging of OA.
It is well-known that huge amounts of bio-based materials are generated in the food industry, leading to an increase in concern for the environment and economy. However, the benefits gained from bio-based materials that are classified as proteins, carbohydrates, lipids, and bioactive compounds should be critically considered. The chapter presents an overview of bio-based materials from the food industry, conventional, novel, and combined novel processing methods, and applications in various food products. Furthermore, in order to successfully utilize bio-based materials in the food industry, strategies toward industrial ecology are also discussed. Finally, several examples of successful utilization of bio-based materials and recommendations for further studies of the utilization and applications throughout the chapter are also reported.
Osteoarthritis is a progressive, irreversible debilitating whole joint disease that affects millions of people worldwide. Despite the availability of various options (non‐pharmacological and pharmacological treatments and therapy, orthobiologics, and surgical interventions), none of them can definitively cure osteoarthritis in patients. Strategies based on the controlled release of therapeutic compounds via biocompatible materials may provide powerful tools to enhance the spatiotemporal delivery, expression, and activities of the candidate agents as a means to durably manage the pathological progression of osteoarthritis in the affected joints upon convenient intra‐articular (injectable) delivery while reducing their clearance, dissemination, or side effects. The goal of this review is to describe the current knowledge and advancements of controlled release to treat osteoarthritis, from basic principles to applications in vivo using therapeutic recombinant molecules and drugs and more innovatively gene sequences, providing a degree of confidence to manage the disease in patients in a close future.
Biomaterials have been the subject of extensive research, and their applications in medicine and pharmacy are expanding rapidly. Collagen and its derivatives stand out as valuable biomaterials due to their high biocompatibility, biodegradability, and lack of toxicity and immunogenicity. This review comprehensively examines collagen from various sources, its extraction and processing methods, and its structural and functional properties. Preserving the native state of collagen is crucial for maintaining its beneficial characteristics. The challenges associated with chemically modifying collagen to tailor its properties for specific clinical needs are also addressed. The review discusses various collagen-based biomaterials, including solutions, hydrogels, powders, sponges, scaffolds, and thin films. These materials have broad applications in regenerative medicine, tissue engineering, drug delivery, and wound healing. Additionally, the review highlights current research trends related to collagen and its derivatives. These trends may significantly influence future developments, such as using collagen-based bioinks for 3D bioprinting or exploring new collagen nanoparticle preparation methods and drug delivery systems.
Objective
Osteoarthritis (OA) is the most common joint disorder in humans and dogs. Due to its chronic progressive nature, the predominant clinical signs after a certain point are pain and immobility. The similar pathogenesis allows conclusions to be drawn from canine to human OA. Current treatments are limited and often attempt to treat OA symptoms rather than improve joint structure and function. Collagen hydrolysates as oral supplements are a promising therapeutic option to achieve this advanced therapeutic aim in both species. The effects of oral supplementation were therefore investigated in canine OA patients.
Method
In a systematic, placebo-controlled, double-blind interventional study in 31 dogs with naturally occurring OA, the efficacy of oral supplementation of specific bioactive collagen peptides (BCP) was tested in comparison to the approved combination of the active substances omega-3 fatty acids and vitamin E. The dogs were examined on a horizontal treadmill with 4 integrated piezoelectric force plates at the beginning and end of a twelve-week test period. At both points, the owners completed a specific questionnaire containing the validated Canine Brief Pain Inventory (CBPI) and the dogs were fitted with accelerometers to record total daily activity data.
Results
Only the oral supplementation of BCP resulted in a significant improvement of several kinetic parameters measured using a force-plate fitted treadmill, and the quality of life assessed by CBPI, while accelerometry was unaffected by the intervention.
Conclusion
The results of this three-month BCP supplementation study using objective measurement parameters in dogs with naturally occurring OA demonstrate an efficacy, suggesting the therapeutic use of BCP in canine OA patients and demonstrating the relevance of this collagen hydrolysate formulation for the treatment of OA in human patients as well.
Anterior cruciate ligament (ACL) injuries mainly arise from non-contact mechanisms during sport performance, with most injuries occurring among youth or adolescent-age athletes, particularly females. The growing popularity of elite-level sport training has increased the total volume, intensity and frequency of exercise and competition loading to levels that may exceed natural healing capacity. Growing evidence suggests that the prevailing mechanism that leads to non-contact ACL injury from sudden mechanical fatigue failure may be accumulated microtrauma. Given the consequences of primary ACL injury on the future health and quality of life of youth and adolescent athletes, the objective of this review is to identify key “recovery science” factors that can help prevent these injuries. Recovery science is any aspect of sports training (type, volume, intensity, frequency), nutrition, and sleep/rest or other therapeutic modalities that may prevent the accumulated microtrauma that precedes non-contact ACL injury from sudden mechanical fatigue failure. This review discusses ACL injury epidemiology, current surgical efficacy, the native ACL vascular network, regional ACL histological complexities such as the entheses and crimp patterns, extracellular matrix remodeling, the concept of causal histogenesis, exercise dosage and ligament metabolism, central nervous system reorganization post-ACL rupture, homeostasis regulation, nutrition, sleep and the autonomic nervous system. Based on this information, now may be a good time to re-think primary ACL injury prevention strategies with greater use of modified sport training, improved active recovery that includes well-planned nutrition, and healthy sleep patterns. The scientific rationale behind the efficacy of regenerative orthobiologics and concomitant therapies for primary ACL injury prevention in youth and adolescent athletes are also discussed.
Introduction and purpose: In our work, we focused on presenting the role of collagen supplementation and its impact on skin and joint health. We considered studies discussing the differences in the effects of collagen from various plant and animal sources. We also examined the influence of the degree of hydrolysis on the absorbability of the supplement. The aim of the paper is to comprehensively summarize knowledge on collagen supplementation, differentiating between its sources and forms. Material and methods: In our paper, we endeavored to address the subject of oral collagen supplementation comprehensively. We explored studies about various forms and sources of collagen. We also delved into the collagen supplementation impact on skin and joints health and impact of additives in enhancing the positive effect of collagen . State of knowledge: Oral collagen supplementation can be beneficial for skin and joints health. It promote collagen synthesis in human body increasing strength of skin and joints. The higher the degree of collagen hydrolysis, the more easily it is absorbed by the body. Additives in the form of vitamin C and A can enhance collagen synthesis. Results and conclusions: This review article indicates a growing interest in oral collagen supplementation and its impact on health. Although there are encouraging findings regarding positive effects, further research is necessary to better understand and determine the optimal conditions for achieving maximum supplementation benefits. This information may be crucial for clinical decisions made by physicians regarding joint reinforcement and anti-aging effects on the skin.
Objective
To investigate the efficacy and safety of collagen derivatives for osteoarthritis.
Design
PubMed, Embase, and Cochrane Library were searched till June 2023 for randomized controlled trials (RCTs) investigating collagen derivatives for treating osteoarthritis. Data were independently extracted by two authors. The risk of bias was assessed using the RoB 2 tool. A random-effects meta-analysis was performed within a frequentist framework. The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations approach.
Results
A total of 35 RCTs involving 3165 patients were included. The main analysis of the primary outcome was based on 25 RCTs involving 2856 patients. Collagen derivatives exerted small-to-moderate effects on pain alleviation (standardized mean difference [SMD] −0.35, 95% confidence interval [CI] −0.48 to −0.22, moderate certainty) and function improvement (SMD −0.31, 95%CI −0.41 to −0.22, high certainty) compared with the control. Collagen derivatives were safe; they did not increase the risk of withdrawal or adverse events compared with the control. The trial sequential analyses indicated that this study had sufficient statistical power for deriving definitive conclusions, confirming the robustness of our findings.
Conclusions
Strong evidence supports the efficacy and safety of collagen derivatives for osteoarthritis treatment.
The review considers the full spectrum of currently known autoantigens in osteoarthritis (OA) and discusses their role in the development and/or persistence of synovitis and the initiation of subsequent destruction of articular cartilage with the development of an autoimmune response and auto-inflammation. Of great interest are methods of drug prevention of OA considering autoimmunity responses and associated auto-inflammation, including the use of pharmaconutraceuticals.
Preclinical and clinical studies of the safety and efficacy of pharmaconutraceuticals containing native type II collagen are presented. A clear relationship between the composition/chemical structure of the collagen components and its mechanism of action and efficacy is discussed. Taking into account the autoimmune pathogenesis of OA, new combined pharmaconutraceuticals aimed at reducing the manifestations of autoinflammation (chondroitin sulfate, glucosamine sulfate) are developed. They have an optimal ratio of active ingredients with a sufficient level of evidence, which allows enhancing their beneficial pharmacological effects.
Collagen is one of the main components of the extracellular matrix of the dermis and articular cartilage and influences the body’s mechanical, organizational, and tissue formation properties. Produced from food industry by-products, it is considered a nutraceutical product widely used as an ingredient or supplement in food, pharmaceutical, and cosmetic industries. This study aimed to conduct a literature review on the scientific evidence regarding the beneficial effects of collagen consumption in the treatment of skin and orthopedic diseases. Literature data have shown that hydrolyzed collagen supplementation promotes skin changes, such as decreased wrinkle formation; increased skin elasticity; increased hydration; increased collagen content, density, and synthesis, which are factors closely associated with aging-related skin damage. Regarding orthopedic changes, collagen supplementation increases bone strength, density, and mass; improves joint stiffness/mobility, and functionality; and reduces pain. These aspects are associated with bone loss due to aging and damage caused by strenuous physical activity. Thus, this review addresses the economic and health potential of this source of amino acids and bioactive peptides extracted from food industry by-products.
Rheumatoid arthritis (RA) and osteoarthritis (OA) both are chronic diseases affecting joints. Immune response against collagen in both diseases may have a role in the initiation and progression of the disease. There is a hypothesis that suppression of immune response vs collagen could be a therapeutic approach in RA and OA. Exposure of gut immune system to collagen is a way to suppress immune response against collagen in the joints. So, the current systematic review is aimed to evaluate the effects of collagen supplementation in OA and RA patients. In the current systematic review, online electronic databases including PubMed/MEDLINE, Web of Sciences and Scopus were searched and finally 19 articles were included. The enrolled articles evaluated the effects of collagen supplementation on treatment of OA (n = 9) and RA (n = 10). Intact (n = 4) and hydrolyzed (n = 5) collagen were used to treat OA. All of the studies on RA used intact and type II collagen in their intervention. The last trials on collagen supplementation in RA and OA patients were performed in 2011 and 2016, respectively. High adverse effects of collagen supplementation and its low efficiency compared to routine treatments were reported by several included studies. Also, risk of bias assessment showed that most of the studies had poor quality. Therefore, it is not possible to definitely decide on the beneficial or detrimental effects of collagen supplementation on OA and RA patients. Further studies are needed to reach a final decision.
Previous studies have advocated that collagen peptide supplementation (CPS) can positively affect cardiovascular health. However, the widespread impact of CPS on cardiovascular disease-related markers is not fully resolved. Consequently, the current systematic review and meta-analysis aimed to assess the efficacy of CPS on cardiovascular disease-related markers. A systematic search in the Scopus, PubMed, and ISI Web of Science databases were completed to identify relevant randomized, placebo-controlled trials (RCTs) published up to November 2021. Mean Differences were pooled using a random-effects model, while publication bias, sensitivity analyses, and heterogeneity were assessed using previously validated methods. Twelve RCTs, comprising of a total of eleven measured markers, were selected for the quantitative analysis. Pooled data revealed that CPS significantly decreased fat mass (-1.21 kg; 95% CI: -2.13, -0.29; I ² = 0.0%; p = 0.010), and increased fat-free mass, based on body mass percentage (1.49 %; 95% CI: 0.57, 2.42; I ² = 0.0%; p = 0.002). Moreover, collagen peptide supplementation led to a significant decrease in serum low-density lipoprotein (-4.09 mg/dl; 95% CI: -8.13, -0.04; I ² = 93.4%; p = 0.048) and systolic blood pressure (-5.04 mmHg; 95 % CI: -9.22, -0.85; I ² = 98.9%; p = 0.018). Our analysis also indicated that CPS did not affect glycemic markers. Our outcomes indicate that CPS reduces fat mass, low-density lipoprotein, and systolic blood pressure while increasing fat-free mass. Future investigations with longer CPS duration are needed to expand on our results.
Osteoarthritis (OA) is the most common joint disease that significantly affects the patients’ quality of life and requires significant medical and social investments for treatment and rehabilitation. There are no therapeutic agents which would be able to regenerate lost or damaged hyaline cartilage. The objective: to assess the efficacy and safety of the chondroprotective parapharmaceutical agent Flexogial in the complex treatment of patients with initial stages of the knee ОА. Materials and methods. 12-weeks study was conducted with the participation of 60 patients with knee OA aged 53,7±2,9 years, women – 36 (60%), men – 24 (40%) with the initial stages of the disease (I–II radiological stage). The main clinical group consisted of 30 patients who took the chondroprotective complex agent Flexogial 15 ml once a day; the comparison group included 30 patients who were administered glucosamine sulfate 1500 mg in a monopreparation taken once a day. Efficacy of the treatment was evaluated using the VAS scale, Tegner’s scale, Lisholm scale at the beginning of treatment, after 6 and 12 weeks in dynamics with subsequent statistical processing of the results. Results. The study demonstrated better indicators of functional activity and less pain intensity in the affected joints in patients of the main group who took the parapharmaceutical agent Flexogial compared to the group of patients who took glucosamine monopreparation with the same number of registered adverse events in both groups of patients (5%). Conclusions. The results of the presented clinical study proved the advantage of use of the combined chondroprotective drinking complex Flexogial in comparison with the monopharmaceutical preparation glucosamine sulfate in the treatment of patients with early stages knee OA in terms of the effect on the intensity of pain and improvement in the parameters of the functional activity of patients after 6 and 12 weeks with the same frequency of registered adverse events.
Purpose of Review
Osteoarthritis (OA) is the most common forms of arthritis in the general population, accounting for more pain and functional disability than any other musculoskeletal disease. There are currently no approved disease modifying drugs for OA. In the absence of effective pharmacotherapy, many patients with OA turn to nutritional supplements and nutraceuticals, including collagen derivatives. Collagen hydrolyzates and ultrahydrolyzates are terms used to describe collagens that have been broken down into small peptides and amino acids in the presence of collagenases and high pressure.
Recent Findings
This article reviews the relevant literature and serves as a White Paper on collagen hydrolyzates and ultrahydrolyzates as emerging supplements often advertised to support joint health in OA. Collagen hydrolyzates have demonstrated some evidence of efficacy in a handful of small scale clinical trials, but their ability to treat and reverse advanced joint disease remains highly speculative, as is the case for other nutritional supplements.
Summary
The aim of this White Paper is to stimulate research and development of collagen-based supplements for patients with OA and other musculoskeletal diseases at academic and industrial levels. This White Paper does not make any treatment recommendations for OA patients in the clinical context, but simply aims to highlight opportunities for scientific innovation and interdisciplinary collaboration, which are crucial for the development of novel products and nutritional interventions based on the best available and published evidence.
Osteoarthritis (OA) is the most prevalent chronic disease in the elderly, and it is generally diagnosed at an advanced state when treatment is difficult if not impossible. The early form of OA is characterized by an elevated water content in the cartilage tissue. The purpose of this study was to verify in vivo if changes in the water content of patellar cartilage typically occurring in early OA can be detected using T(2) mapping MRI methods.
Twenty healthy volunteers performed 60 knee bends in order to compress their patellar cartilage thereby reducing its water content. MR images of the patellar cartilage were acquired immediately following exercise and after 45 min of rest. Patellar cartilage thickness and T(2) maps were determined and their difference between the time points evaluated.
Cartilage thickness increased by 5.4+/-1.5% from 2.94+/-0.15 mm to 3.10+/-0.15 mm (P< 0.001) following 45 min of rest, while T(2) increased by 2.6+/-1.0% from 23.1+/-0.5 ms to 23.7+/-0.6 ms (P< 0.05).
Small, physiologic changes in the water content of patellar cartilage and the concomitant change in proteoglycan and collagen density following exercise can be detected using MRI. The proposed T(2)-mapping method, together with other non-invasive MR cartilage imaging techniques, could aid in the early diagnosis of OA.
The sensitivity of magnetic resonance imaging to biochemical and biophysical changes in the extracellular matrix of articular cartilage give it the potential to noninvasively detect the earliest changes of cartilage damage. The transverse relaxation time (T2) of cartilage has been shown to be a sensitive parameter for evaluation of early degeneration in articular cartilage, particularly changes in water and collagen content and tissue anisotropy. Although initial application has been in microimaging of small cartilage explants, in vivo techniques have been developed for cartilage T2 mapping of human joints. In addition to potential application in development of new pharmaceuticals and surgical techniques for preserving cartilage, in vivo cartilage T2 mapping can improve understanding of arthritis, cartilage aging, and response of cartilage to exercise.
To evaluate the effects of moderate exercise on glycosaminoglycan (GAG) content in knee cartilage in subjects at high risk of knee osteoarthritis (OA).
Forty-five subjects (16 women, mean age 46 years, mean body mass index 26.6 kg/m(2)) who underwent partial medial meniscus resection 3-5 years previously were randomized to undergo a regimen of supervised exercise 3 times weekly for 4 months or to a nonintervention control group. Cartilage GAG content, an important aspect of the biomechanical properties of cartilage, was estimated by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC), with results expressed as the change in the T1 relaxation time in the presence of Gd-DTPA (T1[Gd]).
Thirty of 45 patients were examined by dGEMRIC at baseline and followup. The exercise group (n = 16) showed an improvement in the T1(Gd) compared with the control group (n = 14) (15 msec versus -15 msec; P = 0.036). To study the dose response, change in the T1(Gd) was assessed for correlation with self-reported change in physical activity level, and a strong correlation was found in the exercise group (n = 16, r(S) = 0.70, 95% confidence interval [95% CI] 0.31-0.89) and in the pooled group of all subjects (n = 30, r(S) = 0.74, 95% CI 0.52-0.87).
This in vivo cartilage monitoring study in patients at risk of knee OA who begin exercising indicates that adult human articular cartilage has a potential to adapt to loading change. Moderate exercise may be a good treatment not only to improve joint symptoms and function, but also to improve the knee cartilage GAG content in patients at high risk of developing OA.
For the purposes of classification, it should be specified whether osteoarthritis (OA) of the knee is of unknown origin (idiopathic, primary) or is related to a known medical condition or event (secondary). Clinical criteria for the classification of idiopathic OA of the knee were developed through a multicenter study group. Comparison diagnoses included rheumatoid arthritis and other painful conditions of the knee, exclusive of referred or paraarticular pain. Variables from the medical history, physical examination, laboratory tests, and radiographs were used to develop sets of criteria that serve different investigative purposes. In contrast to prior criteria, these proposed criteria utilize classification trees, or algorithms.
Clinical criteria for the classification of patients with hip pain associated with osteoarthritis (OA) were developed through a multicenter study. Data from 201 patients who had experienced hip pain for most days of the prior month were analyzed. The comparison group of patients had other causes of hip pain, such as rheumatoid arthritis or spondylarthropathy. Variables from the medical history, physical examination, laboratory tests, and radiographs were used to develop different sets of criteria to serve different investigative purposes. Multivariate methods included the traditional "number of criteria present" format and "classification tree" techniques. Clinical criteria: A classification tree was developed, without radiographs, for clinical and laboratory criteria or for clinical criteria alone. A patient was classified as having hip OA if pain was present in combination with either 1) hip internal rotation greater than or equal to 15 degrees, pain present on internal rotation of the hip, morning stiffness of the hip for less than or equal to 60 minutes, and age greater than 50 years, or 2) hip internal rotation less than 15 degrees and an erythrocyte sedimentation rate (ESR) less than or equal to 45 mm/hour; if no ESR was obtained, hip flexion less than or equal to 115 degrees was substituted (sensitivity 86%; specificity 75%). Clinical plus radiographic criteria: The traditional format combined pain with at least 2 of the following 3 criteria: osteophytes (femoral or acetabular), joint space narrowing (superior, axial, and/or medial), and ESR less than 20 mm/hour (sensitivity 89%; specificity 91%). The radiographic presence of osteophytes best separated OA patients and controls by the classification tree method (sensitivity 89%; specificity 91%). The "number of criteria present" format yielded criteria and levels of sensitivity and specificity similar to those of the classification tree for the combined clinical and radiographic criteria set. For the clinical criteria set, the classification tree provided much greater specificity. The value of the radiographic presence of an osteophyte in separating patients with OA of the hip from those with hip pain of other causes is emphasized.
For the purposes of classification, it should be specified whether osteoarthritis (OA) of the knee is of unknown origin (idiopathic, primary) or is related to a known medical condition or event (secondary). Clinical criteria for the classification of idiopathic OA of the knee were developed through a multicenter study group. Comparison diagnoses included rheumatoid arthritis and other painful conditions of the knee, exclusive of referred or para-articular pain. Variables from the medical history, physical examination, laboratory tests, and radiographs were used to develop sets of criteria that serve different investigative purposes. In contrast to prior criteria, these proposed criteria utilize classification trees, or algorithms.
Quantitative assessment of radiographic features, in particular joint space width, are important in the diagnosis and treatment of knee osteoarthritis (OA). Protocols defining radiographic procedures are essential to maintain quality control and hence reliable and reproducible measurement of these features. Criteria governing variability in radiographic procedures are discussed and include defining the precise radio-anatomical position of the joint, standard criteria for X-ray beam alignment, allowance for inherent radiographic magnification and precise definition of anatomical boundaries. Protocols incorporating these criteria are described for standard radiography of the anteroposterior view of the tibiofemoral compartment in the standing semi-flexed position, and for the standing lateral and axial views of the patellofemoral joint. In these views, the radio-anatomical position of the joint is based upon the principal that there is only one plane in which the central ray of the X-ray beam will pass between the margins of the joint space so that both margins and space are optimally defined, in a position consistent with the functional loading of that joint.
Despite the compelling need mandated by the prevalence and morbidity of degenerative cartilage diseases, it is extremely difficult to study disease progression and therapeutic efficacy, either in vitro or in vivo (clinically). This is partly because no techniques have been available for nondestructively visualizing the distribution of functionally important macromolecules in living cartilage. Here we describe and validate a technique to image the glycosaminoglycan concentration ([GAG]) of human cartilage nondestructively by magnetic resonance imaging (MRI). The technique is based on the premise that the negatively charged contrast agent gadolinium diethylene triamine pentaacetic acid (Gd(DTPA)2-) will distribute in cartilage in inverse relation to the negatively charged GAG concentration. Nuclear magnetic resonance spectroscopy studies of cartilage explants demonstrated that there was an approximately linear relationship between T1 (in the presence of Gd(DTPA)2-) and [GAG] over a large range of [GAG]. Furthermore, there was a strong agreement between the [GAG] calculated from [Gd(DTPA)2-] and the actual [GAG] determined from the validated methods of calculations from [Na+] and the biochemical DMMB assay. Spatial distributions of GAG were easily observed in T1-weighted and T1-calculated MRI studies of intact human joints, with good histological correlation. Furthermore, in vivo clinical images of T1 in the presence of Gd(DTPA)2- (i.e., GAG distribution) correlated well with the validated ex vivo results after total knee replacement surgery, showing that it is feasible to monitor GAG distribution in vivo. This approach gives us the opportunity to image directly the concentration of GAG, a major and critically important macromolecule in human cartilage.
Several investigations showed a positive influence of orally administered gelatin on degenerative diseases of the musculo-skeletal system. Both the therapeutic mechanism and the absorption dynamics, however, remain unclear. Therefore, this study investigated the time course of gelatin hydrolysate absorption and its subsequent distribution in various tissues in mice (C57/BL). Absorption of (14)C labeled gelatin hydrolysate was compared to control mice administered (14)C labeled proline following intragastric application. Plasma and tissue radioactivity was measured over 192 h. Additional "gut sac" experiments were conducted to quantify the MW distribution of the absorbed gelatin using SDS-electrophoresis and HPLC. Ninety-five percent of enterally applied gelatin hydrolysate was absorbed within the first 12 h. The distribution of the labeled gelatin in the various tissues was similar to that of labeled proline with the exception of cartilage, where a pronounced and long-lasting accumulation of gelatin hydrolysate was observed. In cartilage, measured radioactivity was more than twice as high following gelatin administration compared to the control group. The absorption of gelatin hydrolysate in its high molecular form, with peptides of 2.5-15kD, was detected following intestinal passage. These results demonstrate intestinal absorption and cartilage tissue accumulation of gelatin hydrolysate and suggest a potential mechanism for previously observed clinical benefits of orally administered gelatin.
To review the current status of collagen hydrolysate in the treatment of osteoarthritis and osteoporosis.
Review of past and current literature relative to collagen hydrolysate metabolism, and assessment of clinical investigations of therapeutic trials in osteoarthritis and osteoporosis.
Hydrolyzed gelatin products have long been used in pharmaceuticals and foods; these products are generally recognized as safe food products by regulatory agencies. Pharmaceutical-grade collagen hydrolysate (PCH) is obtained by hydrolysis of pharmaceutical gelatin. Clinical studies suggest that the ingestion of 10 g PCH daily reduces pain in patients with osteoarthritis of the knee or hip; blood concentration of hydroxyproline is increased. Clinical use is associated with minimal adverse effects, mainly gastrointestinal, characterized by fullness or unpleasant taste. In a multicenter, randomized, doubleblind, placebo-controlled trial performed in clinics in the United States, United Kingdom, and Germany, results showed no statistically significant differences for the total study group (all sites) for differences of mean pain score for pain. There was, however, a significant treatment advantage of PCH over placebo in German sites. In addition, increased efficacy for PCH as compared to placebo was observed in the overall study population amongst patients with more severe symptomatology at study onset. Preferential accumulation of 14C-labeled gelatin hydrolysate in cartilage as compared with administration of 14C-labeled proline has been reported. This preferential uptake by cartilage suggests that PCH may have a salutary effect on cartilage metabolism. Given the important role for collagen in bone structure, the effect of PCH on bone metabolism in osteoporotic persons has been evaluated. Studies of the effects of calcitonin with and without a collagen hydrolysate-rich diet suggested that calcitonin plus PCH had a greater effect in inhibiting bone collagen breakdown than calcitonin alone, as characterized by a fall in levels of urinary pyridinoline cross-links. PCH appeared to have an additive effect relative to use of calcitonin alone.
Collagen hydrolysate is of interest as a therapeutic agent of potential utility in the treatment of osteoarthritis and osteoporosis. Its high level of safety makes it attractive as an agent for long-term use in these chronic disorders.
The functional integrity of articular cartilage is dependent on the maintenance of the extracellular matrix (ECM), a process which is controlled by chondrocytes. The regulation of ECM biosynthesis is complex and a variety of substances have been found to influence chondrocyte metabolism. In the present study we have investigated the effect of degraded collagen on the formation of type II collagen by mature bovine chondrocytes in a cell culture model. The culture medium was supplemented with collagen hydrolysate (CH) and biosynthesis of type II collagen by chondrocytes was compared to control cells treated with native type I and type II collagen and a collagen-free protein hydrolysate. The quantification of type II collagen by means of an ELISA technique was confirmed by immunocytochemical detection as well as by the incorporation of (14)C-proline in the ECM after a 48 h incubation. Chondrocytes in the control group were maintained in the basal medium for 11 days. The presence of extracellular CH led to a dose-dependent increase in type II collagen secretion. However, native collagens as well as a collagen-free hydrolysate of wheat proteins failed to stimulate the production of type II collagen in chondrocytes. These results clearly indicate a stimulatory effect of degraded collagen on the type II collagen biosynthesis of chondrocytes and suggest a possible feedback mechanism for the regulation of collagen turnover in cartilage tissue.
Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) is a new imaging technique to estimate joint cartilage glycosaminoglycan content by T1-relaxation time measurements after penetration of the hydrophilic contrast agent Gd-DTPA(2-). This study compares dGEMRIC in age-matched healthy volunteers with different levels of physical activity: Group 1 (n = 12): nonexercising individuals; Group 2 (n = 16): individuals with physical exercise averaging twice weekly; Group 3 (n = 9): male elite runners. dGEMRIC was performed 2 hr after an intravenous injection of Gd-DTPA(2-) at 0.3 mmol/kg body weight. T1 differed significantly between the three different levels of physical exercise. T1 values (mean of medial and lateral femoral cartilage) for Groups 1, 2, and 3 were: 382 +/- 33, 424 +/- 22 and 476 +/- 36, respectively (ms, mean +/- SD) (P = 0.0004, 1 vs. 2 and 0.0002, 2 vs. 3). Irrespective of the exercise level, T1 was longer in lateral compared to medial femoral cartilage (P = 0.00005; n = 37). In conclusion, this cross-sectional study indicates that human knee cartilage adapts to exercise by increasing the glycosaminoglycan content. Furthermore, results suggest a compartmental difference within the knee with a higher glycosaminoglycan content in lateral compared to medial femoral cartilage. A higher proportion of extracellular water, i.e., larger distribution volume, may to some extent explain the high T1 in the elite runners.
Quantification of changes in T(2) relaxation time, in human cartilage, with progression of osteoarthritis (OA), and evaluation of qualitative correlations with clinical evaluation, histology and polarized light microscopy (PLM). Cartilage-bone plugs were harvested from fresh cadaveric knees (n = 10) and specimens after surgical knee replacement (n = 2) at 12 locations, including lateral and medial sides of tibia, femora and patella. Magnetic resonance imaging was performed at 1.5 Tesla using a.2D spin echo sequence. Histological slices were assessed for OA severity through a grading scale based on combined histological and PLM results. T(2) values in clinically moderate OA were generally higher than in severe OA and normal cartilage. Significant association was established between normal and early OA subjects and T(2) variation, in the medial compartment of the knee (p < 0.05) but especially in the medial tibial cartilage (p < 0.00005). As expected, medial and lateral tibio-femoral compartments underwent more severe degeneration. Additionally, there were intracompartmental variation of the relaxation times and histological patterns, which demonstrate the underlying focal involvement of OA in the knee. Furthermore, T(2) values reflected OA pathogenesis with a positive correlation with histology grading scale. Finally, increased T(2) is correlated to histological degeneration of cartilage and may be a good marker for early OA in tibial articular cartilage.
Delayed contrast-enhanced MRI of cartilage (dGEMRIC) is a noninvasive technique to study cartilage glycosaminoglycan (GAG) content in vivo. This study evaluates dGEMRIC in patients with preradiographic degenerative cartilage changes. Seventeen knees in 15 patients (age 35-70) with arthroscopically verified cartilage changes (softening and fibrillations) in the medial or lateral femoral compartment, knee pain, and normal weight-bearing radiography were included. MRI (1.5 T) was performed precontrast and at 1.5 and 3 hr after an intravenous injection of Gd-DTPA(2-) at 0.3 mmol/kg body weight. T(1) measurements were made in regions of interest in medial and lateral femoral cartilage using sets of five turbo inversion recovery images. Precontrast, R(1) (R(1) = 1/T(1), 1/s) was slightly lower in diseased compared to reference compartment, indicating increased hydration (P = 0.01). Postcontrast, R(1) was higher in diseased than in reference compartment at 1.5 hr, 3.45 +/- 0.90 and 2.64 +/- 0.58 (mean +/- SD), respectively (P < 0.01), as well as at 3 hr, 2.94 +/- 0.60 and 2.50 +/- 0.37, respectively (P = 0.01). The washout of the contrast medium was faster in diseased cartilage as shown by a higher R(1) at 1.5 than at 3 hr in the diseased but not in the reference compartment. In conclusion, dGEMRIC can identify GAG loss in early stage cartilage disease with a higher sensitivity at 1.5 than 3 hr.
Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) reflects cartilage glycosaminoglycan (GAG) distribution. The technique assumes that the plasma levels of the contrast agent Gd-DTPA(2-) are the same across individuals after intravenous (IV) injection, when dosing by weight. However, adipose tissue has lower extracellular water (ECW) than lean tissue. The aims of this study were to measure (1) plasma Gd-DTPA(2-) levels vs body mass index (BMI), and (2) dGEMRIC vs BMI after correcting for the dose-BMI effect.
(1) Plasma Gd-DTPA(2-) levels were analyzed at 3-90 min after IV injection per body weight in 24 individuals with BMI between 21.5 and 46.5. (2) dGEMRIC was compared with BMI in 19 asymptomatic volunteers and 23 with osteoarthritis (OA).
(1) Plasma Gd-DTPA(2-) kinetics were similar in obese and non-obese groups, however, overall concentration was higher in the obese group. A very obese subject (BMI 45) would have 1.4 times higher Gd-DTPA(2-) concentration than a lean subject (BMI 20), which translates into a bias in dGEMRIC of up to 20%. (2) With dose bias taken into account, dGEMRIC showed no correlation with BMI in asymptomatic knees. In OA knees, unnarrowed femoral compartments demonstrated a negative correlation between dGEMRIC and BMI (R=0.57, P=0.004). No correlation was seen in radiographically narrowed compartments.
BMI can be a source of dosing bias in dGEMRIC and a correction factor should be considered in cross-sectional studies with a large range of BMI. There is no correlation between dGEMRIC and BMI in asymptomatic knees, but a negative correlation in OA knees.
Hip dysplasia leads to abnormal loading of articular cartilage, which results in osteoarthritis. Pelvic osteotomies such as the Bernese periacetabular osteotomy can improve the mechanics of the joint, but the results are variable and appear to depend on the amount of preexisting arthritis. Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) is a technique designed to measure early arthritis, and it potentially could be used to select hips with too severe arthritis to benefit from a joint-preserving reconstructive procedure. The purpose of our study was to identify radiographic, clinical, and magnetic resonance imaging measurements that predict failure after pelvic osteotomy.
We performed a cohort study of forty-seven patients undergoing a Bernese periacetabular osteotomy for the treatment of hip dysplasia. Our goal was to identify preoperative radiographic factors, such as the grade of arthritis, joint congruency, and the dGEMRIC index, that are associated with a poor outcome after osteotomy.
Hips in which the osteotomy did not fail had a significant decrease in pain compared with their status preoperatively (p < 0.0001). Hips in which the osteotomy did fail had had significantly more arthritis on preoperative radiographs (as demonstrated by the joint space width and the Tönnis grade [p = 0.01]), more subluxation (p = 0.02), and a lower dGEMRIC index (p < 0.001) than the hips in which the osteotomy did not fail. Multivariate analysis identified the dGEMRIC index as the most important predictor of failure of the osteotomy.
Bernese periacetabular osteotomy for the treatment of hip dysplasia can decrease pain and improve function in symptomatic dysplastic hips. The dGEMRIC index, as an early measure of osteoarthritis, appears to be useful for identifying poor candidates for a pelvic osteotomy.
Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.
Many new therapeutic strategies have been and are being developed to prevent, correct, or slow the progression of osteoarthritis. Our ability to evaluate the efficacy of these techniques, or to determine the situations for which they might provide the most benefit, critically depends on diagnostic measures that can serve as proxies for the present or predicted state of the cartilage. We focus here on a body of work surrounding the development of magnetic resonance imaging (MRI) techniques to noninvasively image the glycosaminoglycan (GAG) concentration of articular cartilage. These techniques are based on the concept of fixed charge in cartilage resulting from the glycosaminoglycans. Starting with sodium MRI, and the subsequent development of delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) based on proton MRI, these techniques permit "visualization" of the charged GAG distribution in cartilage in vitro or in vivo. The dGEMRIC technique has been used in preliminary clinical studies to understand treatment strategies and to monitor disease, and as such is allowing studies that a decade ago would have been impossible. This new technical capability offers the promises of speeding development of effective therapies and focusing their use in areas where they can be most successful.
No other between-group differences were detected. The Student t-test was used
- T E Mcalindon
No other between-group differences were detected. The Student t-test was used.
T.E. McAlindon et al. / Osteoarthritis and Cartilage 19 (2011) 399e405
Drafting of the article: Timothy E. McAlindon, Melynn Nuite, Deborah Burstein, Klaus Flechsenhar. Critical revision of the article for important intellectual content Klaus Flechsenhar. Final approval of the article: all authors. Provision of study materials or patients: Timothy E
- Timothy E Analysis
- Nitya Mcalindon
- Robin Krishnan
- Lori Lyn Ruthazer
- Deborah Price
- John Griffith Burstein
- Timothy E Mcalindon
- Klaus Flechsenhar
Analysis and interpretation of the data: Timothy E. McAlindon,
Nitya Krishnan, Robin Ruthazer, Lori Lyn Price, Deborah
Burstein, John Griffith.
Drafting of the article: Timothy E. McAlindon, Melynn Nuite,
Deborah Burstein, Klaus Flechsenhar.
Critical revision of the article for important intellectual
content: Timothy E. McAlindon, Melynn Nuite, Robin Ruthazer,
Lori Lyn Price, Deborah Burstein, John Griffith, Klaus
Flechsenhar.
Final approval of the article: all authors.
Provision of study materials or patients: Timothy E. McAlindon,
Melynn Nuite, Klaus Flechsenhar.
Statistical expertise: Robin Ruthazer, Lori Lyn Price, John
Griffith.
Obtaining of funding: Timothy E. McAlindon, Klaus
Flechsenhar.
Collection and assembly of data: Melynn Nuite
- Administrative
- Deborah Krishnan
- Klaus Burstein
- Flechsenhar
Administrative, technical, or logistic support: Nitya Krishnan,
Deborah Burstein, Klaus Flechsenhar.
Collection and assembly of data: Melynn Nuite, Nitya Krishnan,
Robin Ruthazer, Lori Lyn Price, Deborah Burstein.
The change in 24-week WOMAC stiffness score between randomization groups was of borderline statistical significance (P ¼ 0.08)
- M L Gray
- D Burstein
- Y J Kim
- A Maroudas
All reported values are (mean AE SD). The change in 24-week WOMAC stiffness score
between randomization groups was of borderline statistical significance (P ¼ 0.08).
No other between-group differences were detected. The Student t-test was used.
References
1. Gray ML, Burstein D, Kim YJ, Maroudas A, 2007 Elizabeth
Winston Lanier Award Winner. Magnetic resonance imaging of
cartilage glycosaminoglycan: basic principles, imaging technique, and clinical applications. J Orthop Res 2008;26:281e91.