GENETIC INFLUENCE ON BONE TURNOVER IN POSTMENOPAUSAL TWINS

Postmenopausal bone mass is determined by both peak bone mass and subs equent bone loss. Previous studies have shown that peak bone mass is u nder genetic influence mediated partly by factors affecting bone forma tion. The rate of bone loss increases markedly after the menopause, bu t is highly variable from subject to subject. The aims of this study w ere to determine whether postmenopausal bone turnover was under geneti c control, which should be linked to the genetic influence on the rate of postmenopausal bone loss. A classical twin study was performed tha t compared the intraclass correlations in monozygotic (MZ) twins with those in dizygotic (DZ) twins, with any difference assumed to be due t o genetic factors. Markers of bone formation and resorption were measu red in 240 untreated postmenopausal twins, aged 45-69 yr, on the avera ge 12.3 yr (SD, 6.0) postmenopause, including 61 MZ pairs and 59 DZ pa irs. The intraclass correlation coefficient of MZ twin pairs, rMZ (95% confidence interval), for 2 specific markers of bone formation, serum osteocalcin and bone-specific alkaline phosphatase, were higher than the corresponding rDZ [0.67 (range, 0.59-0.75) us. 0.48 (range, 0.35-0 .61;P = 0.06) for osteocalcin and 0.53 (range, 0.41-0.65) us. 0.21 (ra nge, 0.01-0.41; P = 0.02) for bone-specific alkaline phosphatase]. For serum propeptide of type I collagen, a type I collagen synthesis mark er that exhibits only a slight increase after menopause, a high propor tion of its variance was explained by genetic factors [rMZ = 0.82 (0.7 7-0.87), rDZ = 0.33 (0.16-0.50); P < 0.001]. The correlations for bone resorption measured by three distinct urinary markers, total deoxypyr idinoline and two cross-linked type I collagen peptides (CrossLaps and NTX), that increase markedly after menopause were higher in MZ than i n DZ pairs, but the difference reached significance only for NTX (P = 0.03). For urinary free deoxypyridinoline, a marker reflecting bone co llagen degradation that increases moderately after menopause, the prop ortion of the variance explained by genetic factors was highly signifi cant (P = 0.002). In conclusion, our data indicate that a proportion o f the variance in postmenopausal levels of both bone formation and res orption markers are explained by genetic factors, but this contributio n was clearly significant only for markers that do not change markedly at the menopause. These data suggest that the contribution of genetic factors to overall postmenopausal bone turnover and possibly bone los s is likely to be small.