Bone mineral density (BMD) and bone turnover are both heritable. Although bone turnover affects bone mass, it is not clear whether these parameters are under common genetic or environmental control. The relative contribution of genetic and environmental factors to the determination of an index of bone turnover, bone specific alkaline phosphatase (BSAP), and the extent of common genetic regulation with BMD, were examined in 97 female twin pairs, aged 50 +/- 15 years (mean +/- SD), consisting of 48 monozygotic (MZ) and 49 dizygotic (DZ) pairs. BSAP was analyzed by radioimmunometric assay. Bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN) was measured by dual-energy X-ray absorptiometry. Twin resemblance for variable traits was assessed by intraclass correlation coefficients. Estimates of genetic and environmental components of variance were based on univariate and multivariate genetic models. As expected, BSAP in premenopausal women (9.8 +/- 4.3 microg/L) was significantly lower than in postmenopausal women (13.3 +/- 6.6 microg/L, p < 0.001), but similar to the subgroup of postmenopausal women on hormone replacement therapy (10.8 +/- 2.6 microg/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), the intrapair difference in BSAP was not significantly correlated with the intrapair difference in BMD for MZ twin pairs. After adjustment for menopausal status, the intraclass correlation for BSAP was significantly 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, respectively. By multivariate analyses, genes specifically influencing BSAP 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 shared environmental factors affecting BSAP and BMD. These findings indicate that BSAP and BMD are heritable and negatively correlated. However, the genetic loci influencing BSAP and BMD appear to be largely independent as are any environmental factors.