Cartilage Biomarkers Coll2-1 and Coll2-1NO2 Are Associated with Knee OA MRI Features and Are Helpful in Identifying Patients at Risk of Disease Worsening.

OBJECTIVE: To assess the cross-sectional association between serum levels of Coll2-1 and Coll2-1NO2, two cartilage degradation biomarkers; the burden of magnetic resonance imaging (MRI) features and clinical outcomes; and to evaluate the predictive value of these biomarkers on progression. DESIGN: A total of 121 subjects with knee osteoarthritis (OA) were followed during 1 year with pain, function, and MRI assessment (PRODIGE study). Type II collagen-specific biomarker Coll2-1 and its nitrated form Coll2-1NO2 were directly measured in serum using immunoassays at baseline and after 3-, 6-, and 12-month follow-up. RESULTS: Serum Coll2-1 and Coll2-1NO2 were correlated with several baseline knee features quantified with Whole-Organ Magnetic Resonance Imaging Score (WORMS). Coll2-1 was significantly correlated with periarticular cysts/bursitis (ρ = 0.29, P < 0.01), subarticular bone attrition (ρ = 0.25, P = 0.01), subarticular cysts (ρ = 0.24, P = 0.02), and articular cartilage integrity (ρ = 0.23, P = 0.03) WORMS subscores for the whole joint as well as with the medial femorotibial joint sum score (ρ = 0.26, P = 0.01) and medial femorotibial joint cartilage (ρ = 0.23, P = 0.02). Coll2-1NO2 correlated with WORMS total score (ρ = 0.23, P = 0.02), WORMS scores in the patellofemoral (ρ = 0.23, P = 0.02) and medial femorotibial compartments (ρ = 0.21, P = 0.03), with osteophytes scores (ρ = 0.27, P < 0.01), subarticular cysts (ρ = 0.24, P = 0.019), and intraarticular loose bodies (ρ = 0.27, P = 0.007). Baseline Coll2-1NO2 was higher in subjects with a pain worsening (426.4 pg/mL [278.04-566.95]) as compared to non-progressors (306.84 pg/mL [200.37-427.84]) over 1 year (AUC = 0.655, P = 0.015). CONCLUSION: Serum cartilage biomarkers Coll2-1 and Coll2-1NO2 are associated with several knee OA features quantified with WORMS. Our study also shows that the baseline value of Coll2-1NO2 is positively associated with pain worsening.

Safety concerns with the long-term management of osteoporosis.

INTRODUCTION: Postmenopausal osteoporosis is a chronic disease that exerts a significant burden on both individuals and the community. Hence, there is a requirement for long-term treatment to be associated with a positive benefit-risk balance. AREAS COVERED: In this descriptive review, the long-term safety of calcitonin, selective estrogen receptor modulators (SERMs), bisphosphonates, denosumab and strontium ranelate was reviewed based on randomized controlled trials of 3 years or longer supplemented by extension study data and data from large, observational studies. EXPERT OPINION: Rare adverse events become apparent with all currently available treatments for osteoporosis with long-term therapy. Due to the rarity of these adverse events and to the worldwide burden of osteoporosis, the benefit-risk balance remains in favor of the beneficial effects of treatment on an outcome rather than the probability of an adverse effect. No single antiosteoporosis agent is appropriate for all patients. Treatment decisions should be made on an individual basis, taking into account the relative benefits and risks in different patient populations.

How to define responders in osteoarthritis.

BACKGROUND: Osteoarthritis is a clinical syndrome of failure of the joint accompanied by varying degrees of joint pain, functional limitation, and reduced quality of life due to deterioration of articular cartilage and involvement of other joint structures. SCOPE: Regulatory agencies require relevant clinical benefit on symptoms and structure modification for registration of a new therapy as a disease-modifying osteoarthritis drug (DMOAD). An international Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and International Osteoporosis Foundation was convened to explore the current burden of osteoarthritis, review current regulatory guidelines for the conduct of clinical trials, and examine the concept of responder analyses for improving drug evaluation in osteoarthritis. FINDINGS: The ESCEO considers that the major challenges in DMOAD development are the absence of a precise definition of the disease, particularly in the early stages, and the lack of consensus on how to detect structural changes and link them to clinically meaningful endpoints. Responder criteria should help identify progression of disease and be clinically meaningful. The ideal criterion should be sensitive to change over time and should predict disease progression and outcomes such as joint replacement. CONCLUSION: The ESCEO considers that, for knee osteoarthritis, clinical trial data indicate that radiographic joint space narrowing >0.5 mm over 2 or 3 years might be a reliable surrogate measure for total joint replacement. On-going research using techniques such as magnetic resonance imaging and biochemical markers may allow the identification of these patients earlier in the disease process.