Johnston Sara, Andrews Sharon, Shen Victor, Cosman Felicia, Lindsay Robert, Dempster David W, Iida-Klein Akiko
Helen Hayes Hospital, Regional Bone Center, 51 North Route 9W, West Haverstraw, New York 10993, USA.
Endocrinology. 2007 Sep;148(9):4466-74. doi: 10.1210/en.2007-0229. Epub 2007 Jun 14.
A cyclic PTH regimen is as effective as a daily regimen on bone density gain in humans and in improving bone quality in mice. Our previous murine study evaluated the effects of a cyclic PTH regimen in the absence of a bisphosphonate, whereas our human study addressed the effects of a cyclic PTH regimen in the presence of ongoing alendronate (ALN) treatment. Accordingly, the current study examined the effects of cyclic or daily PTH regimens in combination with ALN on bone quality and bone density in mice. Twenty-week-old, female C57BL/6J mice were treated with the following sc injections (n = 10): 1) vehicle for 5 d/wk (control); 2) ALN (20 microg/kg x d) 3 d/wk (ALN); 3) human PTH(1-34) (40 microg/kg x d) 5 d/wk (daily PTH); 4) daily PTH in addition to ALN (daily PTH plus ALN); 5) PTH 5 d/wk and vehicle 5 d/wk alternating weekly (cyclic PTH); 6) cyclic PTH in addition to ALN (cyclic PTH plus ALN); and 7) PTH and ALN alternating weekly (alt PTH and ALN). Bone mineral density was measured weekly by dual-energy x-ray absorptiometry, and at 7 wk, bone markers, bone structure, and bone strength were evaluated by biochemical assays, peripheral quantitative computed tomography and mechanical testing, respectively. At 7 wk, all treatments significantly increased femoral and vertebral bone mineral density. ALN slightly decreased endosteal circumference, whereas PTH increased periosteal circumference, resulting in significant increases in femoral cortical thickness in all groups. PTH and ALN enhanced bone strength synergistically in the lumbar vertebrae and additively in the femur. Combined therapy, however, had no effects on bone markers. The results show that combinations of ALN and PTH, in both daily and cyclic regimens, produce more beneficial effects than treatment with either agent alone, suggesting that the mechanisms of actions of ALN and PTH on bone quality may be complementary.
一种循环甲状旁腺激素（PTH）给药方案在增加人体骨密度以及改善小鼠骨质量方面与每日给药方案效果相当。我们之前的小鼠研究评估了在不使用双膦酸盐的情况下循环PTH给药方案的效果，而我们的人体研究探讨了在持续使用阿仑膦酸钠（ALN）治疗的情况下循环PTH给药方案的效果。因此，本研究检测了循环或每日PTH给药方案联合ALN对小鼠骨质量和骨密度的影响。对20周龄的雌性C57BL/6J小鼠进行如下皮下注射（n = 10）：1）每周5天注射赋形剂（对照组）；2）每周3天注射ALN（20微克/千克×天）（ALN组）；3）每周5天注射人PTH(1 - 34)（40微克/千克×天）（每日PTH组）；4）除ALN外每日注射PTH（每日PTH加ALN组）；5）每周5天注射PTH，每周5天注射赋形剂，每周交替进行（循环PTH组）；6）除ALN外循环注射PTH（循环PTH加ALN组）；7）PTH和ALN每周交替注射（交替PTH和ALN组）。每周通过双能X线吸收法测量骨矿物质密度，在第7周时，分别通过生化检测、外周定量计算机断层扫描和力学测试评估骨标志物、骨结构和骨强度。在第7周时，所有治疗均显著增加了股骨和椎骨的骨矿物质密度。ALN略微减小了骨内膜周长，而PTH增加了骨膜周长，导致所有组的股骨皮质厚度显著增加。PTH和ALN在腰椎协同增强骨强度，在股骨则为相加作用。然而，联合治疗对骨标志物没有影响。结果表明，无论是每日还是循环给药方案，ALN和PTH联合使用比单独使用任何一种药物产生的有益效果更多，这表明ALN和PTH对骨质量的作用机制可能是互补的。
