Garnero P, Arden N K, Griffiths G, Delmas P D, Spector T D
INSERM U-403, Hôpital E. Herriot, Lyon, France.
J Clin Endocrinol Metab. 1996 Jan;81(1):140-6. doi: 10.1210/jcem.81.1.8550741.
Postmenopausal bone mass is determined by both peak bone mass and subsequent bone loss. Previous studies have shown that peak bone mass is under genetic influence mediated partly by factors affecting bone formation. The rate of bone loss increases markedly after the menopause, but is highly variable from subject to subject. The aims of this study were to determine whether postmenopausal bone turnover was under genetic control, which should be linked to the genetic influence on the rate of postmenopausal bone loss. A classical twin study was performed that compared the intraclass correlations in monozygotic (MZ) twins with those in dizygotic (DZ) twins, with any difference assumed to be due to genetic factors. Markers of bone formation and resorption were measured in 240 untreated postmenopausal twins, aged 45-69 yr, on the average 12.3 yr (SD, 6.0) postmenopause, including 61 MZ pairs and 59 DZ pairs. 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) vs. 0.48 (range, 0.35-0.61; P = 0.06) for osteocalcin and 0.53 (range, 0.41-0.65) vs. 0.21 (range, 0.01-0.41; P = 0.02) for bone-specific alkaline phosphatase]. For serum propeptide of type I collagen, a type I collagen synthesis marker that exhibits only a slight increase after menopause, a high proportion of its variance was explained by genetic factors [rMZ = 0.82 (0.77-0.87), rDZ = 0.33 (0.16-0.50); P < 0.001]. The correlations for bone resorption measured by three distinct urinary markers, total deoxypyridinoline and two cross-linked type I collagen peptides (CrossLaps and NTX), that increase markedly after menopause were higher in MZ than in DZ pairs, but the difference reached significance only for NTX (P = 0.03). For urinary free dexoypyridinoline, a marker reflecting bone collagen degradation that increases moderately after menopause, the proportion of the variance explained by genetic factors was highly significant (P = 0.002). In conclusion, our data indicate that a proportion of the variance in postmenopausal levels of both bone formation and resorption markers are explained by genetic factors, but this contribution 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 loss is likely to be small.
绝经后骨量由峰值骨量和随后的骨质流失共同决定。既往研究表明，峰值骨量受遗传影响，部分由影响骨形成的因素介导。绝经后骨质流失速率显著增加，但个体之间差异很大。本研究的目的是确定绝经后骨转换是否受遗传控制，这应与对绝经后骨质流失速率的遗传影响相关。进行了一项经典的双胞胎研究，比较了单卵双胞胎（MZ）和双卵双胞胎（DZ）的组内相关性，任何差异均假定由遗传因素导致。在240名未经治疗的绝经后双胞胎中测量了骨形成和骨吸收标志物，这些双胞胎年龄在45 - 69岁，平均绝经后12.3年（标准差为6.0），包括61对MZ双胞胎和59对DZ双胞胎。对于两种特定的骨形成标志物血清骨钙素和骨特异性碱性磷酸酶，MZ双胞胎对的组内相关系数rMZ（95%置信区间）高于相应的rDZ[骨钙素分别为0.67（范围0.59 - 0.75）对0.48（范围0.35 - 0.61；P = 0.06），骨特异性碱性磷酸酶分别为0.53（范围0.41 - 0.65）对0.21（范围0.01 - 0.41；P = 0.02）]。对于I型胶原血清前肽，一种在绝经后仅略有增加的I型胶原合成标志物，其很大一部分变异由遗传因素解释[rMZ = 0.82（0.77 - 0.87），rDZ = 0.33（0.16 - 0.50）；P < 0.001]。通过三种不同的尿标志物（总脱氧吡啶啉和两种交联I型胶原肽（CrossLaps和NTX））测量的骨吸收相关性，这些标志物在绝经后显著增加，MZ双胞胎对中的相关性高于DZ双胞胎对，但差异仅在NTX方面达到显著水平（P = 0.03）。对于尿游离脱氧吡啶啉，一种反映骨胶原降解且在绝经后适度增加的标志物，由遗传因素解释的变异比例非常显著（P = 0.002）。总之，我们的数据表明，绝经后骨形成和骨吸收标志物水平的一部分变异由遗传因素解释，但这种贡献仅在绝经时无明显变化的标志物中才明显显著。这些数据表明，遗传因素对总体绝经后骨转换以及可能的骨质流失的贡献可能较小。
