Extended report Ann Rheum Dis 2011;70:1625–1630. doi:10.1136/ard.2010.144147 1625 ABSTRACT Objective To study the association between metacarpal bone mineral density (BMD) loss and progressive hand osteoarthritis (OA) over 2 years. Methods Using the Kellgren–Lawrence (KL) grading scale and the Osteoarthritis Research Society International Atlas, standardised hand radiographs of 181 patients with primary OA at multiple sites (mean age 60 years, 80% women, mean body mass index 27 kg/ m 2 ) were assessed for hand OA at baseline (KL ≥2 in two or more hand joints) and progressive hand OA over 2 years ( ≥1 point increase in total osteophyte and joint space narrowing score in patients with hand OA at baseline). Changes in BMD were measured over 2 years in metacarpals 2–4 by digital x-ray radiogrammetry. Accelerated BMD loss was defined as loss of >3 mg/ cm 2 /year. Logistic regression analyses were performed to assess the associations between BMD loss and progressive hand OA. Results The baseline prevalence of hand OA was 68% and, after 2 years, 32% of these patients had progressive hand OA. Accelerated BMD loss was present in 79% of the patients with progressive hand OA compared with 60% and 57% of the patients with non-progressive hand OA and no hand OA, respectively. BMD loss was independently associated with progressive hand OA compared with non-progressive hand OA with a RR (95% CI) of 2.1 (1.1 to 4.3). Conclusion Accelerated metacarpal BMD loss is associated with progressive hand OA over a period of 2 years; knowledge of common mechanisms may lead to development of therapeutic interventions for hand OA. Osteoarthritis (OA) is a heterogeneous disease characterised by degradation of articular cartilage, changes in subchondral bone and osteophyte for- mation at the joint margins leading to joint fail- ure. The disease has a major impact on the patient owing to increased morbidity and mortality and on society owing to high healthcare costs. 1 The pathogenesis of OA is incompletely under- stood, but thought to be multifactorial involving degenerative, biomechanical, metabolic, hormonal and genetic factors. 2 Within OA, hand OA seems to be a separate subset of the disease compared with knee and hip OA with differences in genetic fac- tors, pathogenesis and disease course. 3 Increasing evidence supports the involvement of local and low-grade systemic inflammation in the pathogen- esis of OA, especially in the hands. With sensitive imaging modalities, inflammatory signs such as synovitis in interphalangeal joints in the hands is frequently seen in patients with OA. 4–6 In patients with OA, increased levels of proinflammatory cytokines in synovial fluid 7 8 and of high sensitive C-reactive protein (hsCRP) in peripheral blood are found. 9 10 Experimental animal studies have provided sub- stantial evidence suggesting that inflammatory activity plays an important role in the pathogen- esis of osteoporosis or bone mineral density (BMD) loss. 11 In healthy subjects, levels of inflammatory markers, such as interleukin 1β and interleukin 6, tumour necrosis factor α and hsCRP, are associ- ated with, and predictive for, changes in BMD over time. 12–14 In patients with rheumatoid arthritis, measurement of localised BMD loss over time has been shown to be associated with radiographic joint damage progression over time and to indicate inflammatory bone involvement. 15 16 In patients with OA, the level of BMD loss and the relation to the development or progression of OA is less clear. In contrast to data of cross-sectional studies, 17–21 longitudinal data on the relation between BMD and OA are limited. Two studies investigating changes in BMD in OA showed generalised BMD loss over time in hand, hip and knee OA. 22 23 Only one study investigated both BMD and OA param- eters longitudinally, showing that generalised BMD loss was associated with progressive knee OA. 24 To our knowledge, no data exist on the association between localised BMD loss and progressive OA in the hands. We hypothesised that accelerated localised BMD loss might be present in hand OA and associated with disease progression, as a marker for an inflam- matory pathway of the disease. Therefore, we investigated the relationship between changes in BMD at the metacarpals and radiographic progres- sion of hand OA over a period of 2 years. PATIENTS AND METHODS Study design and patient selection Patients were selected from the Genetics ARthrosis and Progression (GARP) cohort. 25 The cohort comprises 191 Caucasian sibling pairs with symptomatic primary OA, defined according to the American College of Rheumatology criteria, at multiple sites in the hands or in at least two of the following joint sites: hands, knees, hips or spine (cervical and lumbar). 26–28 Patients with sec- ondary OA—namely, congenital or developmen- tal diseases, bone dysplasias, local factors such as severe scoliosis and hypermobility, metabolic dis- eases, intra-articular fractures, inflammatory joint Accelerated metacarpal bone mineral density loss is associated with radiographic progressive hand osteoarthritis M Güler-Yüksel, 1 J Bijsterbosch, 1 C F Allaart, 1 I Meulenbelt, 2 H M Kroon, 3 I Watt, 3 W F Lems, 4,5 M Kloppenburg 1 1 Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands 2 Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands 3 Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands 4 Department of Rheumatology, VU Medical Center, Amsterdam, The Netherlands 5 Department of Rheumatology, Jan van Breemen Institute, Amsterdam, The Netherlands Correspondence to M Güler-Yüksel, Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands; m.yuksel@lumc.nl Accepted 1 May 2011 Published Online First 27 May 2011