Clarke B L, Ebeling P R, Jones J D, Wahner H W, O'Fallon W M, Riggs B L, Fitzpatrick L A
Division of Endocrinology, Mayo Clinic, Rochester, Minnesota 55905, USA.
J Clin Endocrinol Metab. 1996 Jun;81(6):2264-70. doi: 10.1210/jcem.81.6.8964862.
Changes in bone mineral metabolism with aging in healthy men and the roles of various factors in the pathogenesis of age-related changes in quantitative bone histomorphometry in men are poorly defined. To clarify these changes and factors, serum and urinary biochemical parameters and iliac crest bone biopsies were evaluated in 43 healthy men, aged 20-80 yr. The static histomorphometric parameters, cancellous bone volume and osteoblast-osteoid interface, decreased by 40.0% and 19.2%, respectively, between 20-80 yr of age. The dynamic histomorphometric parameters, double and single labeled osteoid, also decreased by 18.6% and 18.0%, respectively, over this period. None of the other static or dynamic histomorphometric parameters changed with age in this population sample of healthy men. Univariate analysis of static bone histomorphometric parameters and biochemical parameters revealed significant correlations between osteoid surface and intact PTH (r = 0.37; P = 0.015); osteoclast surface and serum total testosterone (r = 0.36; P = 0.016), estradiol (r = 0.40; P = 0.009), and FSH (r = 0.49; P = 0.001); osteoblast-osteoid interface and serum phosphate (r = 0.31; P = 0.046); and cortical thickness and serum total calcium (r = 0.38; P = 0.013). Univariate analysis of dynamic bone histomorphometric parameters and biochemical parameters revealed correlations between mineral apposition rate and serum total testosterone (r = 0.32; P = 0.037); total volume-referent bone formation rate and serum osteocalcin (r = 0.43; P = 0.004), total testosterone (r = 0.47; P = 0.001), estradiol (r = 0.35; P = 0.023), and dehydroepinadrosterone sulfate (r = 0.31; P = 0.045); and mean wall thickness and serum total calcium (r = 0.36; P = 0.019) and creatinine clearance (r = 0.42; P = 010). Mineralization lag time and serum phosphate (r = -0.39; P = 0.012) and urinary total pyridinoline (r = 0.36; P = 0.023), and mean wall thickness and urinary total pyridinoline (r = -0.38; P = 0.013), were inversely correlated. Multiple regression analysis using all-subset analysis comparing cancellous bone volume to serum and urinary biochemical parameters in these men indicated that the log free androgen index and body weight best predicted the age-related decline in iliac crest cancellous bone volume (r2 = 0.19; P = 0.015). Multiple regression analysis by the same method, comparing bone density at different skeletal sites to bone histomorphometric parameters, indicated that lumbar spine bone mineral density (BMD) was best predicted by cancellous bone volume and mineral apposition rate (r2 = 0.31; P = 0.001), femoral neck BMD by cancellous bone volume and osteoid surface (r2 = 0.19; P = 0.020), femoral greater trochanter BMD by cortical thickness and single labeled osteoid surface (r2 = 0.13; P = 0.060), and total body BMD by cancellous bone volume and surface-based bone formation rate (r2 = 0.31; P = 0.001). In summary, cancellous bone volume, osteoblast-osteoid interface, and double and single labeled osteoid decreased with age in this sample of healthy men. The lack of detectable change in bone density at some skeletal sites in these men may be due to the small sample size or other confounding factors. Multivariate analysis suggests that different combinations of histomorphometric parameters predict bone density at different skeletal sites, and that cancellous bone volume predicts bone density at the lumbar spine, femoral neck, and total body, but not at the femoral greater trochanter. We conclude that alterations in several biochemical parameters are important in the pathogenesis of age-related bone loss in healthy men.
健康男性随年龄增长骨矿物质代谢的变化以及各种因素在男性定量骨组织形态计量学中与年龄相关变化的发病机制中的作用尚不清楚。为了阐明这些变化和因素，对43名年龄在20 - 80岁的健康男性进行了血清和尿液生化参数以及髂嵴骨活检评估。在20 - 80岁之间，静态组织形态计量学参数，即松质骨体积和成骨细胞 - 类骨质界面，分别下降了40.0%和19.2%。在此期间，动态组织形态计量学参数，即双标记和单标记类骨质，也分别下降了18.6%和18.0%。在这个健康男性人群样本中，其他静态或动态组织形态计量学参数均未随年龄变化。对静态骨组织形态计量学参数和生化参数的单因素分析显示，类骨质表面与完整甲状旁腺激素之间存在显著相关性（r = 0.37；P = 0.015）；破骨细胞表面与血清总睾酮（r = 0.36；P = 0.016）、雌二醇（r = 0.40；P = 0.009）和促卵泡激素（r = 0.49；P = 0.001）之间存在显著相关性；成骨细胞 - 类骨质界面与血清磷酸盐之间存在显著相关性（r = 0.31；P = 0.046）；皮质厚度与血清总钙之间存在显著相关性（r = 0.38；P = 0.013）。对动态骨组织形态计量学参数和生化参数的单因素分析显示，矿化沉积率与血清总睾酮之间存在相关性（r = 0.32；P = 0.037）；总体积参照骨形成率与血清骨钙素（r = 0.43；P = 0.004）、总睾酮（r = 0.47；P = 0.001）、雌二醇（r = 0.35；P = 0.023）和硫酸脱氢表雄酮（r = 0.31；P = 0.045）之间存在相关性；平均壁厚度与血清总钙（r = 0.36；P = 0.019）和肌酐清除率（r = 0.42；P = 0.010）之间存在相关性。矿化延迟时间与血清磷酸盐（r = -0.39；P = 0.012）和尿总吡啶啉（r = 0.36；P = 0.023）呈负相关，平均壁厚度与尿总吡啶啉（r = -0.38；P = 0.013）呈负相关。使用全子集分析对这些男性的松质骨体积与血清和尿液生化参数进行多元回归分析表明，游离雄激素指数对数和体重最能预测髂嵴松质骨体积与年龄相关的下降（r2 = 0.19；P = 0.015）。通过相同方法对不同骨骼部位的骨密度与骨组织形态计量学参数进行多元回归分析表明，腰椎骨密度（BMD）最好由松质骨体积和矿化沉积率预测（r2 = 0.31；P = 0.001），股骨颈BMD由松质骨体积和类骨质表面预测（r2 = 0.19；P = 0.020），股骨大转子BMD由皮质厚度和单标记类骨质表面预测（r2 = 0.13；P = 0.060），全身BMD由松质骨体积和基于表面的骨形成率预测（r2 = 0.31；P = 0.001）。总之，在这个健康男性样本中，松质骨体积、成骨细胞 - 类骨质界面以及双标记和单标记类骨质随年龄下降。这些男性中某些骨骼部位骨密度缺乏可检测到的变化可能是由于样本量小或其他混杂因素。多变量分析表明，组织形态计量学参数的不同组合可预测不同骨骼部位的骨密度，并且松质骨体积可预测腰椎、股骨颈和全身的骨密度，但不能预测股骨大转子的骨密度。我们得出结论，几种生化参数的改变在健康男性与年龄相关的骨质流失发病机制中很重要。
