title: The genetics of bone loss: challenges and prospects.
abstract: BACKGROUND
  A strong genetic influence on bone mineral density has been long established, and modern genotyping technologies have generated a flurry of new discoveries about the genetic determinants of bone mineral density (BMD) measured at a single time point. However, much less is known about the genetics of age-related bone loss. Identifying bone loss-related genes may provide new routes for therapeutic intervention and osteoporosis prevention.
  
  
  METHODS
  A review of published peer-reviewed literature on the genetics of bone loss was performed. Relevant studies were summarized, most of which were drawn from the period 1990-2010.
  
  
  RESULTS
  Although bone loss is a challenging phenotype, available evidence supports a substantial genetic contribution. Some of the genes identified from recent genome-wide association studies of cross-sectional BMD are attractive candidate genes for bone loss, most notably genes in the nuclear factor κB and estrogen endocrine pathways. New insights into the biology of skeletal development and regulation of bone turnover have inspired new hypotheses about genetic regulation of bone loss and may provide new directions for identifying genes associated with bone loss.
  
  
  CONCLUSIONS
  Although recent genome-wide association and candidate gene studies have begun to identify genes that influence BMD, efforts to identify susceptibility genes specific for bone loss have proceeded more slowly. Nevertheless, clues are beginning to emerge on where to look, and as population studies accumulate, there is hope that important bone loss susceptibility genes will soon be identified.
authors.affiliation: Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. bmitchel@medicine.umaryland.edu
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
authors.forename: Laura M
authors.initials: LM
authors.lastname: Yerges-Armstrong
mesh_terms: D015519:Bone Density / Q000235:genetics*; D004967:Estrogens / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000235:genetics; D010024:Osteoporosis / Q000453:epidemiology / Q000235:genetics*
chemical_list: D004967:Estrogens; D016328:NF-kappa B