The Role of Bone in Osteoarthritis Progression

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DESCRIPTION (provided by applicant): The anatomic and biomechanical properties of peri-articular bone play a primary role in the dispersion of loading forces across the joint. Indeed, 30-50% of a load across a knee is absorbed by peri-articular bone compared to only 1-3% by articular cartilage. The attenuation of loading forces by peri-articular bone is critical in protecting articular cartilage from damage. However, thickening of subchondral bone and disruption of peri-articular trabecular architecture occur early in osteoarthritis (OA), and may even antedate cartilage damage. These changes, together with the later development of gross pathological disruption of subchondral bone by 'cysts', attrition and trabecular collapse (common in OA), are likely to impair the capability of peri-articular bone to attenuate compressive forces and further predispose to progression. Clinical studies provide further evidence that pathological processes in peri-articular bone influence the course of OA. OA knees with abnormal peri-articular scintigraphic appearances, or subchondral bone marrow lesions on MRI, have greater risk for progression. Measures of systemic bone health such as bone density (BMD) and vitamin D also strongly influence the risk of OA progression. This suggests that the nature of the peri-articular bone response in OA predicates stabilization or progression, and that this may be influenced by systemic bone factors such as BMD and vitamin D. These observations compel us to study the longitudinal role of peri-articular bone in OA to increase understanding of the mechanisms of progression, refine predictive models, and suggest tissue-targeted interventions. Technical modifications to dual x-ray absorptiometry (DXA) and magnetic resonance imaging (MRI) protocols offer appealing approaches to measurement of BMD and trabecular morphology of peri-articular bone. The Osteoarthritis Initiative (OAI) cohort provides an unequalled opportunity to study the role of peri- articular and systemic bone factors in the progression of knee OA in a large sample whose comprehensive evaluations include annual measurement of cartilage volume by 3-Tesla MRI. The proposed ancillary study would be deployed in the progression subcohort and would add longitudinal DXA BMD measurement of both knees and right femoral neck, knee peri-articular trabecular morphometry using high-resolution MRI, bone marrow lesion, cyst and meniscal damage scores, serum 25-hydroxy vitamin D, parathormone (PTH), and vitamin D receptor genotyping. All these data will join and enrich the OAI public data set at specified time points.