Additive genetic effects on circulating periostin contribute to the heritability of bone microstructure

Abstract

Context: Genetic factors account for 60-80% of the areal bone mineral density (aBMD) variance, whereas the heritability ofbonemicrostructure is not clearly established.aBMDandmicrostructure 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. Subjects and 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,wemeasured serum SOST (sSOST) and serum POSTN (sPOSTN), distal radius and tibia microstructure, hip and lumbar spine aBMD, and bone turnover markers, Heritability (h2,%) was calculated as twice the slope of the regression (-) between parents and offspring. Results: cPOSTN levels were significantly higher in men thanwomenand in offspring than parents. h2 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 h2 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, h2 values decreased for several TbandCtboneparameters, but not foraBMD.In contrast, adjusting for sSOST did not alter h2 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 bycommongenetic effects.