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Arthritis Research & Therapy Feb 2021Bisphosphonates have been proposed as possible disease-modifying drugs in osteoarthritis. However, the evidence of their efficacy is poor and their outcomes presented a... (Review)
Review
Bisphosphonates have been proposed as possible disease-modifying drugs in osteoarthritis. However, the evidence of their efficacy is poor and their outcomes presented a great heterogeneity. Therefore, the aim of this study is to systematically review the main effects of bisphosphonate use on synovial joint tissues and biochemical markers in preclinical studies over the past two decades (2000-2020). Three databases (Pubmed, Scopus, and Web of Science) were searched, and after screening, twenty-six studies with five different types of bisphosphonates were included in the review. The animal model selected, the type of bisphosphonate used, the therapy duration, and the main effects of individual drugs on synovial tissues were evaluated. Additionally, the quality and risk of bias assessments were performed using the Animals in Research Reporting In Vivo Experiments guidelines and the Systematic Review Centre for Laboratory animal Experimentation tool. Studies showed high variability in experimental designs. Consequently, the comparison of the findings in order to draw specific conclusions about the effectiveness of the drugs is complicated. However, the results of this systematic review suggested that bisphosphonates seemed to reduce the osteoarthritic changes in a dose-dependent manner showing better chondroprotective effects at high doses. Besides, a time-dependent efficacy was also detected in terms of cartilage status. One can conclude that the disease stage of the time-point of treatment initiation may constitute a key factor in the antiresorptive drug efficacy. Generally, we noted that bisphosphonate administration seemed to show positive subchondral bone conservation and fewer biomarker alterations. However, they did not appear to suppress the osteophyte development and their chondroprotective effect is highly variable among the studies. Bisphosphonates appeared to show a positive anti-inflammatory effect on the synovial membrane. However, only a few included publications were focused on their investigation. Regarding the therapy duration, there is a significant lack of evidence on evaluating their effectiveness in preclinical long-term studies and further experimental studies may be needed to examine the pharmacological response in these circumstances. This systematic review might help to clarify the efficacy of bisphosphonates and their function as disease-modifying treatments in osteoarthritis.
Topics: Animals; Bone Density Conservation Agents; Diphosphonates; Osteoarthritis; Osteophyte; Pharmaceutical Preparations
PubMed: 33618776
DOI: 10.1186/s13075-021-02446-6 -
Arthritis Research & Therapy Aug 2015Bone is an integral part of the osteoarthritis (OA) process. We conducted a systematic literature review in order to understand the relationship between non-conventional... (Review)
Review
INTRODUCTION
Bone is an integral part of the osteoarthritis (OA) process. We conducted a systematic literature review in order to understand the relationship between non-conventional radiographic imaging of subchondral bone, pain, structural pathology and joint replacement in peripheral joint OA.
METHODS
A search of the Medline, EMBASE and Cochrane library databases was performed for original articles reporting association between non-conventional radiographic imaging-assessed subchondral bone pathologies and joint replacement, pain or structural progression in knee, hip, hand, ankle and foot OA. Each association was qualitatively characterised by a synthesis of the data from each analysis based upon study design, adequacy of covariate adjustment and quality scoring.
RESULTS
In total 2456 abstracts were screened and 139 papers were included (70 cross-sectional, 71 longitudinal analyses; 116 knee, 15 hip, six hand, two ankle and involved 113 MRI, eight DXA, four CT, eight scintigraphic and eight 2D shape analyses). BMLs, osteophytes and bone shape were independently associated with structural progression or joint replacement. BMLs and bone shape were independently associated with longitudinal change in pain and incident frequent knee pain respectively.
CONCLUSION
Subchondral bone features have independent associations with structural progression, pain and joint replacement in peripheral OA in the hip and hand but especially in the knee. For peripheral OA sites other than the knee, there are fewer associations and independent associations of bone pathologies with these important OA outcomes which may reflect fewer studies; for example the foot and ankle were poorly studied. Subchondral OA bone appears to be a relevant therapeutic target.
SYSTEMATIC REVIEW
PROSPERO registration number: CRD 42013005009.
Topics: Arthralgia; Bone Density; Bone and Bones; Cartilage, Articular; Cross-Sectional Studies; Diagnostic Imaging; Humans; Joints; Osteoarthritis; Osteophyte
PubMed: 26303219
DOI: 10.1186/s13075-015-0735-x -
Osteoarthritis and Cartilage Jul 2021To systematically review observational studies for the association between features detected on ultrasound (US) and magnetic resonance imaging (MRI) and, symptoms, signs... (Meta-Analysis)
Meta-Analysis
Synovitis and bone marrow lesions associate with symptoms and radiographic progression in hand osteoarthritis: a systematic review and meta-analysis of observational studies.
AIMS
To systematically review observational studies for the association between features detected on ultrasound (US) and magnetic resonance imaging (MRI) and, symptoms, signs and radiographic progression of hand osteoarthritis (OA).
METHODS
Medline, Web of Science, EMBASE, CINAHL and AMED were searched from inception to 14 January 2020 to identify relevant studies. Quality of studies was assessed using the Newcastle-Ottawa scales and data were extracted. Odds ratios (OR) and linear regression coefficients and 95% confidence intervals (CI) were pooled using the random-effects model (METAN package, Stata v16.1). Heterogeneity and publication bias were assessed.
RESULTS
Thirty-two studies using US and MRI comprising 1,350 and 638 participants respectively were included. While only grey-scale synovitis (GSS) associated with AUSCAN-pain (pooled Regression coefficient (95% CI): 0.46 (0.13-0.79); 0-20 scale for AUSCAN-pain), US-detected osteophytes, GSS and power Doppler (PD) [pooled ORs (95% CI): 2.68(2.16-3.33), 2.38(1.74-3.26) and 2.04 (1.45-2.88)] as well as MRI-detected bone marrow lesions (BMLs), synovitis, osteophytes, and central bone erosions (CBEs) associated with joint tenderness [pooled ORs (95% CI): 2.59(2.12-3.18), 2.17(1.85-2.54), 2.15(1.55-2.99), and 2.41 (1.45-4.02)] respectively. US-detected GSS and PD associated with radiographic progression of CBEs [pooled ORs 5.37, 5.08], osteophytes [pooled ORs 5.17, 6.45], and joint space narrowing (pooled ORs 4.28, 4.36) whilst MRI-detected synovitis and BMLs associated with increasing KL grades with pooled ORs 2.92, 2.54 respectively.
CONCLUSIONS
US and MRI-detected structural and inflammatory changes associate with tenderness, whilst articular inflammation and subchondral bone damage associate with radiographic hand OA progression. There was inconsistent relationship between these changes and pain.
Topics: Bone Marrow; Disease Progression; Hand Joints; Humans; Magnetic Resonance Imaging; Observational Studies as Topic; Osteoarthritis; Osteophyte; Synovitis; Ultrasonography
PubMed: 33895290
DOI: 10.1016/j.joca.2021.03.018 -
Animals : An Open Access Journal From... May 2021Glucosamine and chondroitin sulfate have been proposed due to their physiological and functional benefits in the management of osteoarthritis in companion animals.... (Review)
Review
Glucosamine and Chondroitin Sulfate: Is There Any Scientific Evidence for Their Effectiveness as Disease-Modifying Drugs in Knee Osteoarthritis Preclinical Studies?-A Systematic Review from 2000 to 2021.
Glucosamine and chondroitin sulfate have been proposed due to their physiological and functional benefits in the management of osteoarthritis in companion animals. However, the scientific evidence for their use is still controversial. The purpose of this review was to critically elucidate the efficacy of these nutraceutical therapies in delaying the progression of osteoarthritis, evaluating their impact on the synovial knee joint tissues and biochemical markers in preclinical studies by systematically reviewing the last two decades of peer-reviewed publications on experimental osteoarthritis. Three databases (PubMed, Scopus and, Web of Science) were screened for eligible studies. Twenty-two articles were included in the review. Preclinical studies showed a great heterogeneity among the experimental designs and their outcomes. Generally, the evaluated nutraceuticals, alone or in combination, did not seem to prevent the subchondral bone changes, the synovial inflammation or the osteophyte formation. However, further experimental studies may be needed to evaluate their effect at those levels. Regarding the cartilage status and biomarkers, positive responses were identified in approximately half of the evaluated articles. Furthermore, beneficial effects were associated with the pre-emptive administrations, higher doses and, multimodality approaches with some combined therapies. However, additional studies in the long term and with good quality and systematic design are required.
PubMed: 34072407
DOI: 10.3390/ani11061608 -
Rheumatology Advances in Practice 2024We aimed to explore the radiographic definitions of types of New Bone formation (NBF) by focusing on the terminology, description and location of the findings. (Review)
Review
OBJECTIVES
We aimed to explore the radiographic definitions of types of New Bone formation (NBF) by focusing on the terminology, description and location of the findings.
METHODS
Three systematic literature reviews were conducted in parallel to identify the radiographic spinal NBF definitions for spondyloarthritis (SpA), Diffuse Idiopathic Skeletal Hyperostosis (DISH) and Osteorathritis (OA). Study characteristics and definitions were extracted independently by two reviewers. Definitions were analysed and collated based on whether they were unique, modified or established from previous research.
RESULTS
We identified 33 studies that indicated a definition for the NBF in SpA, 10 for DISH and 7 for spinal OA. In SpA, the variations in syndesmophytes included the description as well as the subtypes and locations. The differentiation of syndesmophytes from osteophytes were included in 12 articles, based on the origin and the angle of the NBF and associated findings. The definitions of DISH varied in the number of vertebrae, level and laterality. For OA, five articles indicated that osteophytes arose from the anterior or lateral aspects of the vertebral bodies, and two studies required a size cut-off.
DISCUSSION
Our ultimate aim is to create formal NBF definitions for SpA, DISH and OA guided by an atlas, through a Delphi exercise with international experts. The improved ability to differentiate these conditions radiographically will not only allow the clinicians to accurately approach patients but also will help the researchers to better classify patient phenotypes and focus on accurate radiographic outcomes.
PubMed: 38827363
DOI: 10.1093/rap/rkae061 -
Frontiers in Medicine 2020High resolution peripheral quantitative computed tomography (HR-pQCT) is a 3-dimensional imaging modality with superior sensitivity for bone changes and abnormalities....
High resolution peripheral quantitative computed tomography (HR-pQCT) is a 3-dimensional imaging modality with superior sensitivity for bone changes and abnormalities. Recent advances have led to increased use of HR-pQCT in inflammatory arthritis to report quantitative volumetric measures of bone density, microstructure, local anabolic (e.g., osteophytes, enthesiophytes) and catabolic (e.g., erosions) bone changes and joint space width. These features may be useful for monitoring disease progression, response to therapy, and are responsive to differentiating between those with inflammatory arthritis conditions and healthy controls. We reviewed 69 publications utilizing HR-pQCT imaging of the metacarpophalangeal (MCP) and/or wrist joints to investigate arthritis conditions. Erosions are a marker of early inflammatory arthritis progression, and recent work has focused on improvement and application of techniques to sensitively identify erosions, as well as quantifying erosion volume changes longitudinally using manual, semi-automated and automated methods. As a research tool, HR-pQCT may be used to detect treatment effects through changes in erosion volume in as little as 3 months. Studies with 1-year follow-up have demonstrated progression or repair of erosions depending on the treatment strategy applied. HR-pQCT presents several advantages. Combined with advances in image processing and image registration, individual changes can be monitored with high sensitivity and reliability. Thus, a major strength of HR-pQCT is its applicability in instances where subtle changes are anticipated, such as early erosive progression in the presence of subclinical inflammation. HR-pQCT imaging results could ultimately impact decision making to uptake aggressive treatment strategies and prevent progression of joint damage. There are several potential areas where HR-pQCT evaluation of inflammatory arthritis still requires development. As a highly sensitive imaging technique, one of the major challenges has been motion artifacts; motion compensation algorithms should be implemented for HR-pQCT. New research developments will improve the current disadvantages including, wider availability of scanners, the field of view, as well as the versatility for measuring tissues other than only bone. The challenge remains to disseminate these analysis approaches for broader clinical use and in research.
PubMed: 32766262
DOI: 10.3389/fmed.2020.00337 -
Knee Surgery, Sports Traumatology,... Dec 2023Elucidating subchondral bone remodeling in preclinical models of traumatic meniscus injury may address clinically relevant questions about determinants of knee...
PURPOSE
Elucidating subchondral bone remodeling in preclinical models of traumatic meniscus injury may address clinically relevant questions about determinants of knee osteoarthritis (OA).
METHODS
Studies on subchondral bone remodeling in larger animal models applying meniscal injuries as standardizing entity were systematically analyzed. Of the identified 5367 papers reporting total or partial meniscectomy, meniscal transection or destabilization, 0.4% (in guinea pigs, rabbits, dogs, minipigs, sheep) remained eligible.
RESULTS
Only early or mid-term time points were available. Larger joint sizes allow reporting higher topographical details. The most frequently reported parameters were BV/TV (61%), BMD (41%), osteophytes (41%) and subchondral bone plate thickness (39%). Subchondral bone plate microstructure is not comprehensively, subarticular spongiosa microstructure is well characterized. The subarticular spongiosa is altered shortly before the subchondral bone plate. These early changes involve degradation of subarticular trabecular elements, reduction of their number, loss of bone volume and reduced mineralization. Soon thereafter, the previously normal subchondral bone plate becomes thicker. Its porosity first increases, then decreases.
CONCLUSION
The specific human topographical pattern of a thinner subchondral bone plate in the region below both menisci is present solely in the larger species (partly in rabbits), but absent in rodents, an important fact to consider when designing animal studies examining subchondral consequences of meniscus damage. Large animal models are capable of providing high topographical detail, suggesting that they may represent suitable study systems reflecting the clinical complexities. For advanced OA, significant gaps of knowledge exist. Future investigations assessing the subchondral bone in a standardized fashion are warranted.
Topics: Animals; Dogs; Guinea Pigs; Humans; Rabbits; Bone Remodeling; Cartilage, Articular; Disease Models, Animal; Meniscus; Models, Animal; Osteoarthritis, Knee; Sheep; Swine; Swine, Miniature
PubMed: 37742232
DOI: 10.1007/s00167-023-07579-6 -
Arthroplasty Today Feb 2023Additional distal femoral resection is a common technique to address a flexion contracture during primary total knee arthroplasty (TKA) but can lead to midflexion...
BACKGROUND
Additional distal femoral resection is a common technique to address a flexion contracture during primary total knee arthroplasty (TKA) but can lead to midflexion instability and patella baja. Prior reports regarding the magnitude of knee extension obtained with additional femoral resection have varied. This study sought to systematically review research describing the effect of femoral resection on knee extension and to perform meta-regression to estimate this relationship.
METHODS
A systematic review was conducted using MEDLINE, PubMed, and Cochrane databases by combining the terms ("flexion contracture" OR "flexion deformity") AND ("knee arthroplasty" OR "knee replacement") to identify 481 abstracts. In total, 7 articles reporting change in knee extension after additional femoral resection or augmentation across 184 knees were included. The mean value for knee extension, its standard deviation, and the number of knees tested were recorded for each level. Meta-regression was performed using weighted mixed-effects linear regression.
RESULTS
Meta-regression estimated that each 1mm resected from the joint line produced a 2.5° gain of extension (95% confidence interval, 1.7 to 3.2). Sensitivity analyses excluding outlying observations estimated each 1mm resected from the joint line produced a 2.0° gain of extension (95% confidence interval, 1.9 to 2.2).
CONCLUSIONS
Each millimeter of additional femoral resection is likely to produce only a 2° improvement in knee extension. Thus, an additional resection of 2 mm is likely to improve knee extension by less than 5°. Alternative techniques, including posterior capsular release and posterior osteophyte resection, should be considered in correcting a flexion contracture during TKA.
PubMed: 36845290
DOI: 10.1016/j.artd.2022.101083 -
The Cochrane Database of Systematic... Jul 2019Osteoarthritis affecting the knee is common and represents a continuum of disease from early cartilage thinning to full-thickness cartilage loss, bony erosion, and...
BACKGROUND
Osteoarthritis affecting the knee is common and represents a continuum of disease from early cartilage thinning to full-thickness cartilage loss, bony erosion, and deformity. Many studies do not stratify their results based on the severity of the disease at baseline or recruitment.
OBJECTIVES
To assess the benefits and harms of surgical intervention for the management of symptomatic mild to moderate knee osteoarthritis defined as knee pain and radiographic evidence of non-end stage osteoarthritis (Kellgren-Lawrence grade 1, 2, 3 or equivalent on MRI/arthroscopy). Outcomes of interest included pain, function, radiographic progression, quality of life, short-term serious adverse events, re-operation rates and withdrawals due to adverse events.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase up to May 2018. We also conducted searches of ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform for ongoing trials. Authors of trials were contacted if some but not all their participants appeared to fit our inclusion criteria.
SELECTION CRITERIA
We included randomised controlled trials that compared surgery to non-surgical interventions (including sham and placebo control groups, exercise or physiotherapy, and analgesic or other medication), injectable therapies, and trials that compared one type of surgical intervention to another surgical intervention in people with symptomatic mild to moderate knee osteoarthritis.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials and extracted data using standardised forms. We analysed the quality of evidence using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach.
MAIN RESULTS
A total of five studies involving 566 participants were identified as eligible for this review. Single studies compared arthroscopic partial meniscectomy to physical therapy (320 participants), arthroscopic surgery (debridement ± synovectomy ± chondroplasty) to closed needle joint lavage with saline (32 participants) and high tibial osteotomy surgery to knee joint distraction surgery (62 participants). Two studies (152 participants) compared arthroscopic surgery (washout ± debridement; debridement) to a hyaluronic acid injection. Only one study was at low risk of selection bias, and due to the difficulty of blinding participants to their treatment, all studies were at risk of performance and detection bias.Reporting of results in this summary has been restricted to the primary comparison: surgical intervention versus non-surgical intervention.A single study, included 320 participants with symptoms consistent with meniscal tear. All subjects had the meniscal tear confirmed on knee MRI and radiographic evidence of mild to moderate osteoarthritis (osteophytes, cartilage defect or joint space narrowing). Patients with severe osteoarthritis (KL grade 4) were excluded. The study compared arthroscopic partial meniscectomy and physical therapy to physical therapy alone (a six-week individualised progressive home exercise program). This study was at low risk of selection bias and outcome reporting biases, but was susceptible to performance and detection biases. A high rate of cross-over (30.2%) occurred from the physical therapy group to the arthroscopic group.Low-quality evidence suggests there may be little difference in pain and function at 12 months follow-up in people who have arthroscopic partial meniscectomy and those who have physical therapy. Evidence was downgraded to low quality due to risk of bias and imprecision.Mean pain was 19.3 points on a 0 to 100 point KOOS pain scale with physical therapy at 12 months follow-up and was 0.2 points better with surgery (95% confidence interval (CI) 4.05 better to 3.65 points worse with surgery, an absolute improvement of 0.2% (95% CI 4% better to 4% worse) and relative improvement 0.4% (95% CI 9% better to 8% worse) (low quality evidence). Mean function was 14.5 on a 0 to 100 point KOOS function scale with physical therapy at 12 months follow-up and 0.8 points better with surgery (95% CI 4.3 better to 2.7 worse); 0.8% absolute improvement (95% CI 4% better to 3% worse) and 2.1% relative improvement (95% CI 11% better to 7% worse) (low quality evidence).Radiographic structural osteoarthritis progression and quality of life outcomes were not reported.Due to very low quality evidence, we are uncertain if surgery is associated with an increased risk of serious adverse events, incidence of total knee replacement or withdrawal rates. Evidence was downgraded twice due to very low event rates, and once for risk of bias.At 12 months, the surgery group had a total of three serious adverse events including fatal pulmonary embolism, myocardial infarction and hypoxaemia. The physical therapy alone group had two serious adverse events including sudden death and stroke (Peto OR 1.58, 95% CI 0.27 to 9.21); 1% more events with surgery (95% CI 2% less to 3% more) and 58% relative change (95% CI 73% less to 821% more). One participant in each group withdrew due to adverse events.Two of 164 participants (1.2%) in the physical therapy group and three of 156 in the surgery group underwent conversion to total knee replacement within 12 months (Peto OR 1.76, 95% CI 0.43 to 7.13); 1% more events with surgery (95% CI 2% less to 5% more); 76% relative change (95% CI 57% less to 613% more).
AUTHORS' CONCLUSIONS
The review found no placebo-or sham-controlled trials of surgery in participants with symptomatic mild to moderate knee osteoarthritis. There was low quality evidence that there may be no evidence of a difference between arthroscopic partial meniscectomy surgery and a home exercise program for the treatment of this condition. Similarly, low-quality evidence from a few small trials indicates there may not be any benefit of arthroscopic surgery over other non-surgical treatments including saline irrigation and hyaluronic acid injection, or one type of surgery over another. We are uncertain of the risk of adverse events or of progressing to total knee replacement due to very small event rates. Thus, there is uncertainty around the current evidence to support or oppose the use of surgery in mild to moderate knee osteoarthritis. As no benefit has been demonstrated from the low quality trials included in this review, it is possible that future higher quality trials for these surgical interventions may not contradict these results.
Topics: Arthroscopy; Humans; Osteoarthritis, Knee; Pain Measurement; Quality of Life; Randomized Controlled Trials as Topic; Severity of Illness Index
PubMed: 31322289
DOI: 10.1002/14651858.CD012128.pub2 -
Arthritis Research & Therapy Jun 2018Approaches for the prevention and treatment of hip osteoarthritis (OA) remain limited. There are recent data suggesting that low birth weight (LBW) and preterm birth may...
BACKGROUND
Approaches for the prevention and treatment of hip osteoarthritis (OA) remain limited. There are recent data suggesting that low birth weight (LBW) and preterm birth may be risk factors for hip osteoarthritis. This has the potential to change the current paradigm of hip osteoarthritis prevention by targeting early life factors. The aim of this review was to examine the available evidence for an association of LBW and preterm birth with hip OA. The potential cost implications associated with total hip arthroplasty were also evaluated.
METHODS
Ovid Medline, EMBASE, and Cinahl were searched up until August 2017 using MeSH terms and key words. Methodological quality was evaluated using the National Heart Lung and Blood Institute (NHLBI) quality assessment tool. Qualitative evidence synthesis was performed to summarise the results. Bradford Hill's criteria for causation including the temporal relationship, consistency, strength of the association, specificity, dose-response relationship, and analogy were used to assess the evidence for causation. Economic modelling was used to calculate the potential economic burden associated with LBW or preterm birth related total hip arthroplasty using Australian data from 2012 to 2015.
RESULTS
Five studies, ranging from high to low quality, were included. Hip bone shape abnormalities examined included developmental hip dysplasia and immature hip, and hip osteoarthritis included osteophytes and total hip arthroplasty. A causal link between low birth weight or preterm birth and hip osteoarthritis was found. Of the 30,477 total hip arthroplasties performed for hip osteoarthritis in Australia in 2015, 5791 were estimated to be born preterm and 5273 with low birth weight. This equated to a potential total hip arthroplasty cost of AU$145,136,082 and AU$132,150,222 for these subgroups, respectively.
CONCLUSION
Available data suggest that low birth weight and preterm birth are associated with hip bone shape abnormalities and hip osteoarthritis requiring total hip arthroplasty, with a substantial associated financial burden. Given the current lack of effective treatment and prevention strategies for hip osteoarthritis, this offers a new avenue for reducing the future burden of hip osteoarthritis.
Topics: Cost of Illness; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Osteoarthritis, Hip; Pregnancy; Premature Birth; Risk Assessment; Risk Factors
PubMed: 29884206
DOI: 10.1186/s13075-018-1627-7