title: Bone mineral density and risk of incident and progressive radiographic knee osteoarthritis in women: the Framingham Study.
abstract: OBJECTIVE
  To examine the relations of bone mineral density (BMD) and change in BMD to risk of incident and progressive radiographic knee osteoarthritis (OA) in a longitudinal cohort study.
  
  
  METHODS
  Female participants aged 63 to 91 years (mean age 71) in the Framingham Study received anteroposterior weight bearing knee radiographs at biennial examinations 18 (1983-85) and 22 (1992-93). Knee radiographs were given scores for global severity of OA (Kellgren-Lawrence scale: range 0 to 4) and for the presence of osteophytes and joint space narrowing (range 0 to 3). Femoral neck BMD was assessed using dual photon absorptiometry at examination 20 and dual x-ray absorptiometry at examination 22. We examined the relations of BMD at examination 20 and its change between examination 20 and examination 22 to incident and progressive knee OA, as well as to worsening of individual radiographic features adjusting for age, body mass index, and other potential confounding factors.
  
  
  RESULTS
  In total, 473 women (ages 63 to 91 yrs) had complete assessments. Over 8 years of followup, risk of incident radiographic knee OA increased from 5.6% among women in the lowest age-specific quartile of BMD to 14.2, 10.3, and 11.8% among women in the 2nd, 3rd, and highest quartiles, respectively. Multivariate adjusted OR of incident OA for each increase quartile of BMD were 1.0, 2.5, 2.0, and 2.3, respectively (p for trend = 0.222). This was mainly reflected in an increased risk of osteophyte development. However, risk of progressive OA decreased from 34.4 to 22.0, 20.3, and 18.9% as BMD increased. Compared to those in the lowest quartile of BMD, adjusted OR for progressive disease were 0.3, 0.2, and 0.1 among women in the 2nd, 3rd, and highest quartiles (p for trend <0.001), respectively, mainly due to its effect on lowering the risk of joint space loss. Compared to those who lost BMD >0.04 g/cm2 over the followup period, women who gained BMD were at increased risk of incident but at a significantly decreased risk of progressive knee OA. BMD change was not associated with osteophyte development, but gain in BMD lowered the risk of joint space loss.
  
  
  CONCLUSIONS
  High BMD and BMD gain decreased the risk of progression of radiographic knee OA, but may be associated with an increased risk of incident knee OA. The protective effect was mainly through its influence on reducing the risk of joint space loss. Our results offer insights into how bone may affect the course of the most common joint disease, and thus may have potential therapeutic implications.
authors.affiliation: Arthritis Center, Boston University School of Medicine, MA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: M T
authors.initials: MT
authors.lastname: Hannan
authors.forename: C E
authors.initials: CE
authors.lastname: Chaisson
authors.forename: T E
authors.initials: TE
authors.lastname: McAlindon
authors.forename: S R
authors.initials: SR
authors.lastname: Evans
authors.forename: P
authors.initials: P
authors.lastname: Aliabadi
authors.forename: D
authors.initials: D
authors.lastname: Levy
authors.forename: D T
authors.initials: DT
authors.lastname: Felson
mesh_terms: D015502:Absorptiometry, Photon; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density; D015331:Cohort Studies; D005260:Female; D005272:Femur Neck / Q000473:pathology; D006801:Humans; D015994:Incidence; D007719:Knee Joint / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging* / Q000453:epidemiology* / Q000473:pathology; D015995:Prevalence; D012307:Risk Factors