Kippo K, Hannuniemi R, Isaksson P, Laurén L, Osterman T, Peng Z, Tuukkanen J, Kuurtamo P, Väänänen H K, Sellman R
Leiras Oy, Biomedical Research Center, Turku, Finland.
J Bone Miner Res. 1998 Feb;13(2):287-96. doi: 10.1359/jbmr.1998.13.2.287.
Daily oral clodronate treatment was evaluated in Sprague-Dawley rats for its ability to inhibit estrogen-deficiency-induced changes in femoral neck, femoral diaphysis, and lumbar vertebrae (L4-L5). Six-month-old ovariectomized (OVX) rats were administered by gavage a vehicle (Veh) or clodronate (100 or 500 mg/kg/day). Sham-operated (SHAM) control rats received the vehicle (n = 15/group). Treatment was started on the day of operation and continued for 3 months. Trabecular bone volume (BV/TV) and structural variables (trabecular number, Tb.N; thickness, Tb.Th; separation, Tb.Sp; and trabecular bone pattern factor, Tb.Pf) were assessed on secondary spongiosa of the right femoral neck Furthermore, cantilever bending test of the left femoral neck and compression test of L4, ash weight of L5, and morphometric studies of femoral diaphysis were carried out, and serum and urinary markers of bone turnover were determined. The OVX/Veh group had higher levels of serum osteocalcin and alkaline phosphatase and higher urinary excretion of deoxypyridinoline/creatinine than the SHAM/Veh group at 3 months postsurgery, and clodronate reduced these changes. BV/TV of femoral neck, bone mass of L5, and the maximum loads of the femoral neck and L4 were lower after OVX than SHAM operation. Although clodronate prevented trabecular bone loss in the femoral neck and preserved Tb.Pf at the SHAM control level, it failed to preserve the mechanical strength at the femoral neck However, in lumbar vertebrae, clodronate prevented the loss of bone mass and mechanical properties. Furthermore, there was a good positive correlation between maximum load of L4 and the ash weight of L5 (n = 58, r = 0.69, p < 0.001). In the femoral neck (n = 55), Tb.Pf correlated negatively with BV/TV and Tb.N (r = -0.59 and r = -0.55;p < 0.001, respectively) and positively with Tb.Sp (r = 0.61, p < 0.001). In femoral mid-diaphysis, there were no significant changes in cortical bone geometry in any of the groups. We conclude that orally administered clodronate suppresses the enhanced bone turnover in adult OVX rats and preserves trabecular bone volume and connectivity in the femoral neck In the axial skeleton, clodronate has a beneficial effect on lumbar vertebral bone mass and strength.
在Sprague-Dawley大鼠中评估了每日口服氯膦酸盐治疗抑制雌激素缺乏引起的股骨颈、股骨干和腰椎（L4-L5）变化的能力。对6月龄去卵巢（OVX）大鼠经口灌胃给予赋形剂（Veh）或氯膦酸盐（100或500mg/kg/天）。假手术（SHAM）对照大鼠给予赋形剂（每组n = 15）。治疗在手术当天开始，持续3个月。评估右股骨颈次级松质骨的骨小梁体积（BV/TV）和结构变量（骨小梁数量，Tb.N；厚度，Tb.Th；间距，Tb.Sp；以及骨小梁骨模式因子，Tb.Pf）。此外，对左股骨颈进行悬臂弯曲试验和L4的压缩试验，测定L5的灰重，并对股骨干进行形态计量学研究，同时测定骨转换的血清和尿液标志物。术后3个月，OVX/Veh组血清骨钙素和碱性磷酸酶水平较高，脱氧吡啶啉/肌酐尿排泄量高于SHAM/Veh组，氯膦酸盐减少了这些变化。OVX术后股骨颈的BV/TV、L5的骨量以及股骨颈和L4的最大负荷均低于假手术组。尽管氯膦酸盐可防止股骨颈骨小梁骨丢失并将Tb.Pf维持在假手术对照水平，但它未能维持股骨颈的机械强度。然而，在腰椎，氯膦酸盐可防止骨量和力学性能的丧失。此外，L4的最大负荷与L5的灰重之间存在良好的正相关（n = 58，r = 0.69，p < 0.001）。在股骨颈（n = 55）中，Tb.Pf与BV/TV和Tb.N呈负相关（r = -0.59和r = -0.55；p均< 0.001），与Tb.Sp呈正相关（r = 0.61，p < 0.001）。在股骨干中部，任何组的皮质骨几何结构均无显著变化。我们得出结论，口服氯膦酸盐可抑制成年OVX大鼠增强的骨转换，并保留股骨颈的骨小梁体积和连通性。在中轴骨骼中，氯膦酸盐对腰椎骨量和强度具有有益作用。
