title: Additive Genetic Effects on Circulating Periostin Contribute to the Heritability of Bone Microstructure.
abstract: BACKGROUND
  Genetic factors account for 60-80% of the areal bone mineral density (aBMD) variance, whereas the heritability of bone microstructure is not clearly established. aBMD and microstructure are under the control of osteocytes, which regulate bone formation through the expression of molecules such as sclerostin (SOST) and periostin (POSTN).
  
  
  OBJECTIVE
  We hypothesized that additive genetic effects contribute to serum levels of SOST and POSTN and thereby to the individual variance of bone microstructure.
  
  
  METHODS
  In a retrospective analysis of 432 subjects from the Geneva Retiree Cohort age 64.9 ± 1.4 years and 96 of their offspring age 37.9 ± 5.7 years, we measured serum SOST (sSOST) and serum POSTN (sPOSTN), distal radius and tibia microstructure, hip and lumbar spine aBMD, and bone turnover markers, Heritability (h(2), %) was calculated as twice the slope of the regression (β) between parents and offspring.
  
  
  RESULTS
  cPOSTN levels were significantly higher in men than women and in offspring than parents. h(2) values for bone microstructural traits ranged from 22-64% depending on the envelope (trabecular [Tb] or cortical [Ct]) and skeletal site (radius or tibia), whereas h(2) for sPOSTN and sSOST was 50% and 40%, respectively. sPOSTN was positively associated with Tb bone volume on total volume and Ct thickness, and negatively with Ct porosity. The associations for Ct parameters remain significant after adjustment for propetide of type-I procollagen, cross-linked telopeptide of type I collagen, femoral neck aBMD, sex or age. After adjustment of bone traits for sPOSTN, h(2) values decreased for several Tb and Ct bone parameters, but not for aBMD. In contrast, adjusting for sSOST did not alter h(2) values for bone traits.
  
  
  CONCLUSIONS
  Additive genetic effects account for a substantial proportion of the individual variance of bone microstructure, sPOSTN, and sSOST. sPOSTN is largely inherited as a sex-related trait and carries an important contribution to the heritability of bone microstructure, indicating that these traits are at least partly determined by common genetic effects.
authors: Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospitals & Faculty of Medicine, 1211 Geneva 14, Switzerland.
authors: N
authors: N
authors: Bonnet
authors: Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospitals & Faculty of Medicine, 1211 Geneva 14, Switzerland.
authors: E
authors: E
authors: Biver
authors: Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospitals & Faculty of Medicine, 1211 Geneva 14, Switzerland.
authors: C
authors: C
authors: Durosier
authors: Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospitals & Faculty of Medicine, 1211 Geneva 14, Switzerland.
authors: T
authors: T
authors: Chevalley
authors: Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospitals & Faculty of Medicine, 1211 Geneva 14, Switzerland.
authors: R
authors: R
authors: Rizzoli
authors: Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospitals & Faculty of Medicine, 1211 Geneva 14, Switzerland.
authors: S
authors: S
authors: Ferrari
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D015519:Bone Density / Q000235:genetics*; D019485:Bone Morphogenetic Proteins / Q000097:blood; D001842:Bone and Bones / Q000378:metabolism / Q000648:ultrastructure*; D015815:Cell Adhesion Molecules / Q000097:blood*; D004843:Epistasis, Genetic / Q000502:physiology; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D010287:Parent-Child Relations; D016062:Porosity; D019655:Quantitative Trait, Heritable; D012189:Retrospective Studies
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D015815:Cell Adhesion Molecules; D005819:Genetic Markers; C512835:POSTN protein, human; C422903:SOST protein, human