title: High Bone Mass is associated with bone-forming features of osteoarthritis in non-weight bearing joints independent of body mass index.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  HBM is positively associated with OA in non-weight-bearing joints, independent of BMI. HBM-associated 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.
authors.affiliation: Musculoskeletal Research Unit, School of Clinical Sciences, University of Bristol, UK. Electronic address: celia.gregson@bristol.ac.uk.
authors.forename: C L
authors.initials: CL
authors.lastname: Gregson
authors.affiliation: Musculoskeletal Research Unit, School of Clinical Sciences, University of Bristol, UK; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
authors.forename: S A
authors.initials: SA
authors.lastname: Hardcastle
authors.affiliation: Musculoskeletal Research Unit, School of Clinical Sciences, University of Bristol, UK.
authors.forename: A
authors.initials: A
authors.lastname: Murphy
authors.affiliation: Musculoskeletal Research Unit, School of Clinical Sciences, University of Bristol, UK.
authors.forename: B
authors.initials: B
authors.lastname: Faber
authors.affiliation: Department of Medicine, Norwich Medical School, University of East Anglia, Norwich, UK.
authors.forename: W D
authors.initials: WD
authors.lastname: Fraser
authors.affiliation: Department of Radiology, North Bristol NHS Trust, Bristol, UK.
authors.forename: M
authors.initials: M
authors.lastname: Williams
authors.affiliation: MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
authors.forename: G
authors.initials: G
authors.lastname: Davey Smith
authors.affiliation: Musculoskeletal Research Unit, School of Clinical Sciences, University of Bristol, UK.
authors.forename: J H
authors.initials: JH
authors.lastname: Tobias
mesh_terms: D015992:Body Mass Index; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D003710:Demography; D005260:Female; D006801:Humans; D007596:Joints / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D010003:Osteoarthritis / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D010012:Osteogenesis; D016474:Weight-Bearing
keywords: Bone; Epidemiology; Hand; Osteoarthritis; Osteophyte; X-ray