title: Individuals with high bone mass have an increased prevalence of radiographic knee osteoarthritis.
abstract: We previously reported an association between high bone mass (HBM) and a bone-forming phenotype of radiographic hip osteoarthritis (OA). As knee and hip OA have distinct risk factors, in this study we aimed to determine (i) whether HBM is also associated with knee OA, and (ii) whether the HBM knee OA phenotype demonstrates a similar pattern of radiographic features to that observed at the hip. HBM cases (defined by DXA BMD Z-scores) from the UK-based HBM study were compared with unaffected family controls and general population controls from the Chingford and Hertfordshire cohort studies. A single blinded observer graded AP weight-bearing knee radiographs for features of OA (Kellgren-Lawrence score, osteophytes, joint space narrowing (JSN), sclerosis) using an atlas. Analyses used logistic regression, adjusting a priori for age and gender, and additionally for BMI as a potential mediator of the HBM-OA association, using Stata v12. 609 HBM knees in 311 cases (mean age 60.8years, 74% female) and 1937 control knees in 991 controls (63.4years, 81% female) were analysed. The prevalence of radiographic knee OA, defined as Kellgren-Lawrence grade≥2, was increased in cases (31.5% vs. 20.9%), with age and gender adjusted OR [95% CI] 2.38 [1.81, 3.14], p<0.001. The association between HBM and osteophytosis was stronger than that for JSN, both before and after adjustment for BMI which attenuated the ORs for knee OA and osteophytes in cases vs. controls by approximately 50%. Our findings support a positive association between HBM and knee OA. This association was strongest for osteophytes, suggesting HBM confers a general predisposition to a subtype of OA characterised by increased bone formation.
authors.affiliation: Musculoskeletal Research Unit, School of Clinical Sciences, University of Bristol, UK; MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, UK. Electronic address: Sarah.Hardcastle@bristol.ac.uk.
authors.forename: S A
authors.initials: SA
authors.lastname: Hardcastle
authors.affiliation: Musculoskeletal Research Unit, School of Clinical Sciences, University of Bristol, UK; University of Exeter Medical School, Exeter, UK.
authors.forename: P
authors.initials: P
authors.lastname: Dieppe
authors.affiliation: Musculoskeletal Research Unit, School of Clinical Sciences, University of Bristol, UK.
authors.forename: C L
authors.initials: CL
authors.lastname: Gregson
authors.affiliation: Oxford NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK; Arthritis Research UK (ARUK) Centre for Sports, Exercise and Osteoarthritis, University of Oxford, Nuffield Orthopaedic Centre, Oxford, UK.
authors.forename: N K
authors.initials: NK
authors.lastname: Arden
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
authors.forename: T D
authors.initials: TD
authors.lastname: Spector
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Hart
authors.affiliation: MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
authors.forename: M H
authors.initials: MH
authors.lastname: Edwards
authors.affiliation: MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
authors.forename: E M
authors.initials: EM
authors.lastname: Dennison
authors.affiliation: Oxford NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK; NIHR Nutrition Biomedical Research Centre, University of Southampton, Southampton, UK.
authors.forename: C
authors.initials: C
authors.lastname: Cooper
authors.affiliation: Musculoskeletal Research Unit, School of Clinical Sciences, University of Bristol, UK.
authors.forename: A
authors.initials: A
authors.lastname: Sayers
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, School of Social and Community Medicine, University of 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: D000368:Aged; D015992:Body Mass Index; D001842:Bone and Bones / Q000473:pathology*; D016022:Case-Control Studies; D003710:Demography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging* / Q000453:epidemiology*; D015995:Prevalence; D011859:Radiography; D012044:Regression Analysis; D006113:United Kingdom / Q000453:epidemiology
keywords: Bone mineral density; DXA; High bone mass; Osteoarthritis