OA phenotypes, rather than disease stage, drive structural progression – identification of structural progressors from 2 phase III randomized clinical studies with symptomatic knee OA

SummaryBackground/PurposeThe aim of this study was to identify key characteristics of disease progression through investigation of the association of radiographic progression over two years with baseline Joint Space Width (JSW), Kellgren–Lawrence (KL) grade, Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain, Joint Space Narrowing (JSN), and BMI.MethodsData from 2206 subjects (4390 knees) were combined for this post-hoc analysis of two randomized, double-blind, multi-center, placebo-controlled phase III trials (NCT00486434 and NCT00704847) that evaluated the efficacy and safety of 2-years treatment with oral salmon calcitonin of subjects with painful knee osteoarthritis (OA).ResultsThere was a clear positive and significant correlation between KL grade and WOMAC pain and total WOMAC, albeit the variance in pain measures was from min-to-max for all KL categories, emphasizing the heterogeneity of this patient population and pain perception. 32% of target knees did not progress, and only 51% had changes over minimum significant change (MSC). BMI, KL-Score and WOMAC pain was diagnostic, but only KL-score and pain had prognostic value, albeit pain in a non-linear manner.ConclusionThese data clearly describe significant associations between KL grade, JSW, pain and BMI in patients with symptomatic knee OA. KL grade, BMI and WOMAC pain were diagnostically associated with OA based on JSW but only KL-score and pain in a non-linier fashion was prognostic. 50% of patients did not progress more than MSC, highlighting the importance for identification of structural progressors and the phenotypes associated with these. These results suggest that disease phenotypes, rather than disease status, are responsible for disease progression

Calcitonin is involved in cartilage homeostasis: Is calcitonin a treatment for OA?

Osteoarthritis (OA) is the most common form of degenerative joint diseases and a major cause of disability and impaired quality of life in the elderly. Recent observations suggest that calcitonin may act on both osteoclasts and chondrocytes. The present review was sought to summarize emerging observations from the molecular level to the preliminary clinical findings of possible chondroprotective effects of calcitonin. This review summarizes peer-reviewed articles found using pre-defined search criteria and published in the PubMed database before January 2006. In addition, abstracts from the OsteoArthritis Research Society International (OARSI) conferences in the time period 2000–2005 have been included in the search. Ample evidence for the effect of calcitonin on bone resorption was found. Support for direct effects of calcitonin on chondrocytes on matrix synthesis and inhibition of cartilage degradation have been published. In addition, clinical evidence for the effect of calcitonin on cartilage degradation is emerging. Several independent lines of evidence suggest a direct chondroprotective effect of calcitonin in addition to the well-established effect on bone resorption. Given the currently limited availability of chondroprotective agents, much expectation regards the ongoing clinical assessment of calcitonin therapy for the prevention and treatment of OA