Shen V, Liang X G, Birchman R, Wu D D, Healy D, Lindsay R, Dempster D W
Regional Bone Center, Helen Hayes Hospital, New York State Department of Health, West Haverstraw, NY 10993, USA.
Bone. 1997 Jul;21(1):71-8. doi: 10.1016/s8756-3282(97)00070-7.
Estrogen and calcium deficiencies increase both bone resorption and formation, whereas immobilization mainly decreases bone formation. How these functionally different risk factors for bone loss interact in cancellous bone undergoing modeling or remodeling activity is not well understood. Mature (6-month-old) female rats were subjected to sham operation (sham), ovariectomy (ovx), dietary calcium deficiency (LoCa, 0.1% Ca), and sciatic and femoral denervation (IM), ovx+IM, or LoCa+IM for 4 weeks. The primary spongiosa, the region of active modeling within 1 mm of the growth plate, in ovx, LoCa, and IM groups showed a decrease in cancellous bone volume, trabecular number, and connectivity when compared to sham controls. Groups combining two risk factors exhibited additive changes when compared with single risk factor groups. In the secondary spongiosa, an area with little modeling activity, ovx and LoCa groups, as expected, lost bone. In contrast with the primary spongiosa, IM alone did not induce bone loss in the secondary spongiosa, and the groups with a combination of IM and ovx or IM and LoCa showed a greater bone loss than either ovx or LoCa alone. Ovx and LoCa groups showed increases in both bone formation rate and eroded surface in the secondary spongiosa, while IM groups showed a decrease in bone formation rate. Combining IM with either ovx or LoCa resulted in increased eroded surface. The effects on cortical bone were assessed at the tibio-fibular junction. A trend toward decreased percentage of cortical bone area and an increase in marrow cavity area were observed in the combined deficiency groups only. These changes were the result of a statistically significant increase in endosteal eroded surface in IM+ovx and IM+LoCa groups. Our results demonstrate that immobilization-induced bone loss is restricted to the primary spongiosa where most modeling events occur. However, the inhibitory effect of IM on bone formation in the secondary spongiosa is unmasked in remodeling sites when a high turnover state is provided by either estrogen or dietary calcium deficiency. These results suggest that the presence of a risk factor, such as immobilization, which in the short-term causes inhibition of bone formation, does not predispose the skeleton to rapid cancellous bone loss except when accompanied by modeling or high turnover.
雌激素缺乏和钙缺乏会同时增加骨吸收和骨形成，而制动主要会减少骨形成。对于正在进行塑形或重塑活动的松质骨而言，这些功能上不同的骨质流失风险因素是如何相互作用的，目前还不太清楚。将成熟（6个月大）雌性大鼠进行假手术（假手术组）、卵巢切除术（去卵巢组）、饮食钙缺乏（低钙组，0.1%钙）以及坐骨神经和股神经去神经支配（制动组）、去卵巢+制动组或低钙+制动组处理4周。在去卵巢组、低钙组和制动组中，生长板1毫米内的活跃塑形区域即初级骨小梁，与假手术对照组相比，松质骨体积、骨小梁数量和连通性均降低。与单一风险因素组相比，两种风险因素组合的组呈现出相加性变化。在次级骨小梁这个塑形活动较少的区域，如预期的那样，去卵巢组和低钙组出现了骨质流失。与初级骨小梁不同，单独制动在次级骨小梁中并未诱导骨质流失，并且制动与去卵巢或制动与低钙组合的组比单独的去卵巢组或低钙组表现出更大的骨质流失。去卵巢组和低钙组在次级骨小梁中的骨形成率和侵蚀表面均增加，而制动组的骨形成率降低。将制动与去卵巢或低钙相结合会导致侵蚀表面增加。在胫腓关节处评估对皮质骨的影响。仅在联合缺乏组中观察到皮质骨面积百分比降低和骨髓腔面积增加的趋势。这些变化是由于去神经支配+去卵巢组和去神经支配+低钙组骨内膜侵蚀表面在统计学上显著增加所致。我们的结果表明，制动诱导的骨质流失仅限于大多数塑形事件发生的初级骨小梁。然而，当雌激素缺乏或饮食钙缺乏导致高转换状态时，在重塑部位，制动对次级骨小梁中骨形成的抑制作用就会显现出来。这些结果表明，存在如制动这样的风险因素，虽然短期内会导致骨形成受到抑制，但除非伴有塑形或高转换，否则不会使骨骼易于快速出现松质骨流失。
