Zhang X Z, Kalu D N, Erbas B, Hopper J L, Seeman E
Endocrine Unit, Austin and Repatriation Medical Center, University of Melbourne, Melbourne, Australia.
J Bone Miner Res. 1999 May;14(5):802-9. doi: 10.1359/jbmr.1999.14.5.802.
Peak volumetric bone mineral density (BMD) is determined by the growth in bone size relative to the mineral accrued within its periosteal envelope. Thus, reduced peak volumetric BMD may be the result of reduced mineral accrual relative to growth in bone size. Because sex steroids and growth hormone (GH) influence bone size and mass we asked: What are the effects of gonadectomy (Gx) on bone size, bone mineral content (BMC), areal and volumetric BMD in growing male and female rats? Does GH deficiency (GH-) reduce the amount of bone in the (smaller) bone, i.e., reduce volumetric BMD? Does GH- alter the effect of Gx on bone size and mineral accrual? Gx or sham surgery was performed at 6 weeks in GH- and GH replete (GH+) Fisher 344 male and female rats. Changes in bone size, volume, BMC, areal and volumetric BMD, measured using dual X-ray absorptiometry (DPX-L), were expressed as percentage of controls at 8 months (mean +/- SEM). All results shown were significant (p < 0.05 level) unless otherwise stated. In GH+ and GH- males, respectively, Gx was associated with: lower femur volume (24%, 25%), BMC (43%, 45%), areal BMD (21%, 14%), and volumetric BMD (30%, 28%); lower spine (L1-L3) volume (26%, 28%), BMC (26%, 30%), and areal BMD (28%, 12%), but not volumetric BMD. Following Gx, GH+ females had increased femur volume (11%), no effect on BMC, decreased areal BMD (6%) and decreased volumetric BMD (17%); GH- females had no change in femur volume, but decreased femur BMC (24%), areal BMD (10%), and volumetric BMD (25%). In GH+ and GH- females, respectively, Gx was associated with a decrease in spine (L1-L3) BMC (12%, 15%), areal BMD (16%, 15%), and volumetric BMD (10%, 16%) with no change in volume. Deficits in non-Gx GH- relative to non-Gx GH+ (males, females, respectively) were: femur BMC (49%, 37%), areal BMD (23%, 8%), volume (19%, 19%) and volumetric BMD (37%, 22%); spine (L1-L3) BMC (46%, 42%), areal BMD (37%, 43%), volume (10%, 15%), and volumetric BMD (40%, 33%). Testosterone and GH are growth promoting in growing male rats, producing independent effects on bone size and mass; deficiency produced smaller appendicular bones with reduced volumetric BMD because deficits in mass were greater than deficits in size. At the spine, the reduction in size and accrual were proportional, resulting in a smaller bone with normal volumetric BMD. In growing female rats, estrogen was growth limiting at appendicular sites; deficiency resulted in a GH-dependent increase in appendicular size, relatively reduced accrual, and so, reduced volumetric BMD in a bigger bone. At the spine, accrual was reduced while growth in size was normal, thus volumetric BMD was reduced in the normal sized bone. Understanding the pathogenesis of low volumetric BMD requires the study of the differing relative growth in size and mass of the axial and appendicular skeleton in the male and female and the regulators of the growth of these traits.
峰值骨体积矿物质密度（BMD）取决于骨大小相对于其骨膜包壳内矿物质积累的增长情况。因此，峰值骨体积BMD降低可能是矿物质积累相对于骨大小增长减少的结果。由于性激素和生长激素（GH）会影响骨大小和骨量，我们提出以下问题：去势（Gx）对生长中的雄性和雌性大鼠的骨大小、骨矿物质含量（BMC）、面积BMD和体积BMD有何影响？GH缺乏（GH-）是否会减少（较小的）骨骼中的骨量，即降低体积BMD？GH-是否会改变Gx对骨大小和矿物质积累的影响？在6周龄时，对GH-和GH充足（GH+）的Fisher 344雄性和雌性大鼠进行Gx或假手术。使用双能X线吸收仪（DPX-L）测量的骨大小、体积、BMC、面积BMD和体积BMD的变化表示为8个月时对照组的百分比（平均值±标准误）。除非另有说明，所有显示的结果均具有显著性（p<0.05水平）。在GH+和GH-雄性大鼠中，Gx分别与以下情况相关：股骨体积降低（24%，25%）、BMC降低（43%，45%）、面积BMD降低（21%，14%）和体积BMD降低（30%，28%）；脊柱（L1-L3）体积降低（26%，28%）、BMC降低（26%，30%）和面积BMD降低（28%，12%），但体积BMD无变化。Gx后，GH+雌性大鼠的股骨体积增加（11%），对BMC无影响，面积BMD降低（6%），体积BMD降低（17%）；GH-雌性大鼠的股骨体积无变化，但股骨BMC降低（24%）、面积BMD降低（10%）和体积BMD降低（25%）。在GH+和GH-雌性大鼠中，Gx分别与脊柱（L1-L3）BMC降低（12%，15%）、面积BMD降低（16%，15%）和体积BMD降低（10%，16%）相关，体积无变化。相对于非Gx的GH+（雄性、雌性分别），非Gx的GH-的不足情况为：股骨BMC降低（49%，37%）、面积BMD降低（23%，8%）、体积降低（19%，19%）和体积BMD降低（37%，22%）；脊柱（L1-L3）BMC降低（46%，42%）、面积BMD降低（37%，43%）、体积降低（10%，15%）和体积BMD降低（40%，33%）。睾酮和GH对生长中的雄性大鼠有促进生长作用，对骨大小和骨量产生独立影响；缺乏会导致附属骨骼变小，体积BMD降低，因为骨量不足大于骨大小不足。在脊柱，大小和积累的减少是成比例的，导致骨骼变小但体积BMD正常。在生长中的雌性大鼠中，雌激素在附属部位限制生长；缺乏会导致GH依赖性的附属部位大小增加、积累相对减少，因此在较大的骨骼中体积BMD降低。在脊柱处，积累减少而大小增长正常，因此在正常大小的骨骼中体积BMD降低。了解低体积BMD的发病机制需要研究雄性和雌性中轴骨和附属骨骼在大小和质量上不同的相对生长情况以及这些特征生长的调节因子。
