| Summary: | Introduction: Epidemiological studies have reported an association between increased bone mineral density (BMD) and osteoarthritis (OA); however, whether increased BMD is a true risk factor for OA remains unclear. To address this question in a novel way, I aimed to determine the prevalence and phenotype of OA in a population of individuals with extremely High Bone Mass (HBM). Methods: HBM cases, defined by dual X-ray absorptiometry (DXA) BMD Zscores, were compared with unaffected family members and general population controls from the Chingford and Hertfordshire cohort studies. The clinical OA phenotype in HBM was established by comparing relevant outcomes such as joint replacement and joint pain in HBM cases versus family controls. The prevalence and phenotype of radiographic OA in HBM was determined through blinded systematic grading of OA features on hip and knee X-rays, with scores compared between the HBM and control groups. Analyses used logistic / linear regression, adjusted for age, gender and body mass index (BMI) with generalised estimating equations to account for within-person clustering, using Stata. Results: HBM cases reported a higher prevalence of joint replacement compared with the family control group (adjusted odds ratio [95% confidence interval] 2.42 [1.06,5.56], p=0.037). An increased prevalence of both radiographic hip (1.52 [1.09,2.11], p=0.013) and knee (1.62 [1.22,2.16], p=O.OOI) OA was seen in HBM cases compared with the combined control group. The radiographic OA phenotype in HBM was predominantly characterised by bone-forming features such as osteophytes and subchondral sclerosis. HBM was also associated with the presence of radiographic pelvic enthesophytes (bony spurs at tendon/ligament insertions) and altered acetabular morphology consistent with a mild skeletal dysplasia. Conclusion: These findings support an increased risk of both clinical and radiographic OA in HBM compared with the general population. Common underlying mechanisms regulating bone formation may underpin both HBM and certain phenotypes of OA.
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