GENETIC AND ENVIRONMENTAL CORRELATIONS BETWEEN BONE-FORMATION AND BONE-MINERAL DENSITY - A TWIN STUDY

Bone mineral density (BMD) and bone turnover are both heritable. Altho ugh bone turnover affects bone mass, it is not clear whether these par ameters are under common genetic or environmental control. The relativ e contribution of genetic and environmental factors to the determinati on of an index of bone turnover, bone specific alkaline phosphatase (B SAP), and the extent of common genetic regulation with BMD, were exami ned in 97 female twin pairs, aged 50 +/- 15 years (mean +/- SD), consi sting of 48 monozygotic (MZ) and 49 dizygotic (DZ) pairs. BSAP was ana lyzed by radioimmunometric assay. Bone mineral density (BMD) at the lu mbar spine (LS) and femoral neck (FN) was measured by dual-energy X-ra y absorptiometry. Twin resemblance for variable traits was assessed by intraclass correlation coefficients. Estimates of genetic and environ mental components of variance were based on univariate and multivariat e genetic models. As expected, BSAP in premenopausal women (9.8 +/- 4. 3 mu g/L) was significantly lower than in postmenopausal women (13.3 /- 6.6 mu g/L, p < 0.001), but similar to the subgroup of postmenopaus al women on hormone replacement therapy (10.8 +/- 2.6 mu g/L, p = 0.15 ). Although BSAP and BMD were correlated in a cross-sectional analysis (r = -0.35, p < 0.001 for LS-BMD; r = -0.16, p = 0.03 for FN-BMD), th e intrapair difference in BSAP was not significantly correlated with t he intrapair difference in BMD for MZ twin pairs. After adjustment for menopausal status, the intraclass correlation for BSAP was significan tly higher in MZ than DZ twins (0.60 +/- 0.09 vs. 0.27 +/- 0.13, p = 0 .03). Univariate model-fitting analyses indicated a heritability of 63 % for BSAP, and 77% and 72% for lumbar spine and femoral neck BMD, res pectively. By multivariate analyses, genes specifically influencing BS AP accounted for 16% of the total genetic variance in LS-BMD and 4% of the total genetic variance in FN-BMD. There was no evidence for share d environmental factors affecting BSAP and BMD. These findings indicat e that BSAP and BMD are heritable and negatively correlated. However, the genetic loci influencing BSAP and BMD appear to be largely indepen dent as are any environmental factors. (C) 1998 by Elsevier Science In c. All rights reserved.