title: OPG and sRANKL serum levels and incident hip fracture in postmenopausal Caucasian women in the Women's Health Initiative Observational Study.
abstract: OBJECTIVE
  The osteoprotogerin/receptor activator of NF-kappa β/receptor activator of NF-kappa β ligand (OPG/RANK/RANKL) pathway plays a critical role in bone remodeling. This study investigated associations between serum levels of OPG, soluble RANKL (sRANKL), and the ratio of OPG/sRANKL to risk of incident hip fracture.
  
  
  METHODS
  A nested case-control study was conducted among postmenopausal, Caucasian women aged 50-79 at baseline (1993-1998), followed for hip fracture through March 2005 in the Women's Health Initiative Observational Study. 400 incident hip fracture cases were selected and individually matched to 400 controls with no prior fracture or incident hip fracture. Matching factors were baseline age, enrollment date and hormone therapy (HT) exposure. Baseline serum OPG and sRANKL levels were measured using high sensitivity ELISA. Odds ratios were computed for quartiles of each biomarker adjusting for matching factors and hip fracture risk factors.
  
  
  RESULTS
  Serum OPG was significantly associated with older age, low physical activity and poorer physical function in control women. sRANKL was inversely associated with total calcium intake in control women, but not associated with age or other fracture risk factors. The odds ratio for hip fracture comparing the highest to lowest quartiles of OPG was 2.28 (95% confidence interval (CI), 1.45-3.61) after adjusting for the matching variables (p-value for linear trend <0.001), and 1.87 (95% CI, 1.15-3.04; p for linear trend=0.02) after adjusting for self-rated health status, physical activity and physical functioning. No significant associations between sRANKL or the ratio of OPG/sRANKL and hip fracture risk were observed.
  
  
  CONCLUSIONS
  Serum OPG levels were independently associated with a nearly twofold increased risk of hip fracture in postmenopausal women.
authors.affiliation: Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M3-A410, POB 19024, Seattle, WA 98109-1024, USA. alacroix@whi.org
authors.forename: Andrea Z
authors.initials: AZ
authors.lastname: LaCroix
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Jackson
authors.forename: Aaron
authors.initials: A
authors.lastname: Aragaki
authors.forename: Charles
authors.initials: C
authors.lastname: Kooperberg
authors.forename: Jane A
authors.initials: JA
authors.lastname: Cauley
authors.forename: Zhao
authors.initials: Z
authors.lastname: Chen
authors.forename: Meryl S
authors.initials: MS
authors.lastname: Leboff
authors.forename: David
authors.initials: D
authors.lastname: Duggan
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006620:Hip Fractures / Q000097:blood*; D006801:Humans; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood*; D017698:Postmenopause / Q000097:blood*; D053245:RANK Ligand / Q000097:blood*
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand
keywords: Hip fracture; OPG; Osteoporosis; Osteoprotogerin; Postmenopausal women; RANK; RANKL; WHI; Women's Health Initiative; osteoprotogerin; receptor activator of NF-kappa β; receptor activator of NF-kappa β ligand; sRANKL; soluble receptor activator of NF-kappa β ligand