骨质疏松症序贯治疗对低骨量成年大鼠小梁骨的影响。
Effects of sequential osteoporosis treatments on trabecular bone in adult rats with low bone mass.
机构信息
Center for Musculoskeletal Health and Department of Medicine, University of California Davis Medical Center, 4625 2nd Avenue, Suite 1002, Sacramento, CA, 95817, USA.
出版信息
Osteoporos Int. 2014 Jun;25(6):1735-50. doi: 10.1007/s00198-014-2678-5. Epub 2014 Apr 11.
UNLABELLED
We used an osteopenic adult ovariectomized (OVX) rat model to evaluate various sequential treatments for osteoporosis, using FDA-approved agents with complementary tissue-level mechanisms of action. Sequential treatment for 3 months each with alendronate (Aln), followed by PTH, followed by resumption of Aln, created the highest trabecular bone mass, best microarchitecture, and highest bone strength.
INTRODUCTION
Individual agents used to treat human osteoporosis reduce fracture risk by ∼ 50-60%. As agents that act with complementary mechanisms are available, sequential therapies that mix antiresorptive and anabolic agents could improve fracture risk reduction, when compared with monotherapies.
METHODS
We evaluated bone mass, bone microarchitecture, and bone strength in adult OVX, osteopenic rats, during different sequences of vehicle (Veh), parathyroid hormone (PTH), Aln, or raloxifene (Ral) in three 90-day treatment periods, over 9 months. Differences among groups were evaluated. The interrelationships of bone mass and microarchitecture endpoints and their relationship to bone strength were studied.
RESULTS
Estrogen deficiency caused bone loss. OVX rats treated with Aln monotherapy had significantly better bone mass, microarchitecture, and bone strength than untreated OVX rats. Rats treated with an Aln drug holiday had bone mass and microarchitecture similar to the Aln monotherapy group but with significantly lower bone strength. PTH-treated rats had markedly higher bone endpoints, but all were lost after PTH withdrawal without follow-up treatment. Rats treated with PTH followed by Aln had better bone endpoints than those treated with Aln monotherapy, PTH monotherapy, or an Aln holiday. Rats treated initially with Aln or Ral, then switched to PTH, also had better bone endpoints, than monotherapy treatment. Rats treated with Aln, then PTH, and returned to Aln had the highest values for all endpoints.
CONCLUSION
Our data indicate that antiresorptive therapy can be coupled with an anabolic agent, to produce and maintain better bone mass, microarchitecture, and strength than can be achieved with any monotherapy.
目的
我们使用骨质疏松的成年去卵巢（OVX）大鼠模型，用经 FDA 批准且具有互补组织作用机制的药物，来评估各种序贯治疗骨质疏松的方法。用阿伦膦酸钠（Aln）、甲状旁腺激素（PTH）、再用 Aln 依次序贯治疗 3 个月，可使小梁骨量、微结构和骨强度达到最高。
引言
用于治疗人类骨质疏松的单一药物可降低骨折风险约 50-60%。随着具有互补作用机制的药物的出现，与单一疗法相比，混合抗吸收和合成代谢药物的序贯治疗可能会提高骨折风险降低。
方法
我们在 9 个月内，用 3 个 90 天的治疗期，在成年 OVX、骨质疏松大鼠中，评估了不同序列的 Veh、PTH、Aln 或雷洛昔芬（Ral）对骨量、骨微结构和骨强度的影响。评估了各组之间的差异。研究了骨量和微结构终点之间的相互关系及其与骨强度的关系。
结果
雌激素缺乏导致骨丢失。与未治疗的 OVX 大鼠相比，单独用 Aln 治疗的 OVX 大鼠的骨量、微结构和骨强度明显更好。用 Aln 药物假期治疗的大鼠，其骨量和微结构与 Aln 单药治疗组相似，但骨强度明显较低。用 PTH 治疗的大鼠具有明显更高的骨终点，但在没有后续治疗的情况下，PTH 停药后所有终点都丢失。用 PTH 治疗后再用 Aln 治疗的大鼠的骨终点优于 Aln 单药治疗、PTH 单药治疗或 Aln 假期治疗。先用 Aln 或 Ral 治疗，然后改用 PTH 的大鼠的骨终点也优于单一疗法。先用 Aln 治疗，再用 PTH 治疗，然后再用 Aln 治疗的大鼠，所有终点的数值最高。
结论
我们的数据表明，抗吸收治疗可以与合成代谢药物联合使用，从而产生和维持比任何单一疗法更好的骨量、微结构和强度。
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