High Bone Mass is associated with bone-forming features of osteoarthritis in non-weight bearing joints independent of body mass index

Objectives: High Bone Mass (HBM) is associated with (a) radiographic knee osteoarthritis (OA), partly mediated by increased BMI, and (b) pelvic enthesophytes and hip osteophytes, suggestive of a bone-forming
phenotype. We aimed to establish whether HBM is associated with radiographic features of OA in non weight-bearing (hand) joints, and whether such OA demonstrates a bone-forming phenotype.

Methods: HBM cases (BMD Z-scores ≥+3.2) were compared with family controls. A blinded assessor graded all PA hand radiographs for: osteophytes (0-3), joint space narrowing (JSN)(0-3), subchondral sclerosis (0-1), at the index Distal Interphalangeal Joint (DIPJ) and 1st Carpometacarpal Joint (CMCJ), using an
established atlas. Analyses used a random effects logistic regression model, adjusting a priori for age and gender. Mediating roles of BMI and bone turnover markers (BTMs) were explored by further adjustment.

Results: 314 HBM cases (mean age 61.1years, 74% female) and 183 controls (54.3years, 46% female) were included. Osteophytes (grade≥1) were more common in HBM (DIPJ: 67% vs. 45%, CMCJ: 69% vs. 50%), with adjusted OR [95% CI] 1.82 [1.11, 2.97], p=0.017 and 1.89 [1.19, 3.01], p=0.007 respectively; no differences were seen in JSN. Further adjustment for BMI failed to attenuate ORs for osteophytes in HBM cases vs. controls; DIPJ 1.72 [1.05, 2.83], p=0.032, CMCJ 1.76 [1.00, 3.06], p=0.049. Adjustment for BTMs (concentrations lower amongst HBM cases) did not attenuate ORs.

Conclusions: HBM is positively associated with OA in non weight-bearing joints, independent of BMI. HBMassociated OA is characterised by osteophytes, consistent with a bone-forming phenotype, rather than JSN reflecting cartilage loss. Systemic factors (e.g. genetic architecture) which govern HBM may
also increase bone-forming OA risk.