title: The sex-specific association of serum osteoprotegerin and receptor activator of nuclear factor kappaB legend with bone mineral density in older adults: the Rancho Bernardo study.
abstract: OBJECTIVE
  The role of osteoprotegerin (OPG) and its receptor activator of nuclear factor kappaB legend (RANKL) in the regulation of bone in humans remain unclear. We examined the sex-specific associations of serum OPG, RANKL, and their ratio with bone mineral density (BMD) in older adults.
  
  
  METHODS
  Participants were 681 community-dwelling adults, ages 45-90 years, who had serum OPG and RANKL measured and bone density scans in 1988-1991, with follow-up scans 5 and/or 10 years later.
  
  
  METHODS
  Analyses were sex-specific; women using and not using estrogen were evaluated separately. Cross-sectional analyses used multivariable regression models; longitudinal analyses used repeated measures mixed effects models.
  
  
  RESULTS
  In cross-sectional analyses, age- and weight-adjusted serum OPG levels were significantly positively associated with BMD at the lumbar spine in men, and at the femoral neck, total hip, and lumbar spine in women using estrogen, but not in non-users of estrogen. RANKL concentrations were significantly and inversely associated with BMD in men only, and at the total hip. Neither OPG nor RANKL was significantly associated with bone loss. Results for the RANKL/OPG ratio were the same as those for RANKL alone.
  
  
  CONCLUSIONS
  These results suggest a modulatory effect of both endogenous and exogenous sex hormones on the biologic interaction of OPG, RANKL, and bone.
authors.affiliation: Department of Family and Preventive Medicine, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0607, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Stern
authors.forename: Gail A
authors.initials: GA
authors.lastname: Laughlin
authors.forename: Jaclyn
authors.initials: J
authors.lastname: Bergstrom
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Barrett-Connor
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000502:physiology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D015914:Estrogen Replacement Therapy; D005260:Female; D005272:Femur Neck / Q000502:physiology; D006801:Humans; D016014:Linear Models; D008159:Lumbar Vertebrae / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000378:metabolism*; D053244:Osteoprotegerin / Q000097:blood*; D017698:Postmenopause / Q000097:blood; D011446:Prospective Studies; D053245:RANK Ligand / Q000097:blood*; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand; C505688:TNFSF11 protein, human