Altman-Singles Allison R, Jeong Yonghoon, Tseng Wei-Ju, de Bakker Chantal Mj, Zhao Hongbo, Lott Carina, Robberts Juhanna, Qin Ling, Han Lin, Kim Do-Gyoon, Liu X Sherry
McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Pennsylvania State University, Berks Campus, Reading, PA, USA.
J Bone Miner Res. 2017 Aug;32(8):1703-1715. doi: 10.1002/jbmr.3165. Epub 2017 Jun 13.
Postmenopausal osteoporosis is often treated with bisphosphonates (eg, alendronate, [ALN]), but oversuppression of bone turnover by long-term bisphosphonate treatment may decrease bone tissue heterogeneity. Thus, alternate treatment strategies after long-term bisphosphonates are of great clinical interest. The objective of the current study was to determine the effect of intermittent parathyroid hormone (PTH) following 12 weeks of ALN (a bisphosphonate) treatment in 6-month-old, ovariectomized (OVX) rats on bone microarchitecture, bone remodeling dynamics, and bone mechanical properties at multiple length scales. By using in vivo μCT and 3D in vivo dynamic bone histomorphometry techniques, we demonstrated the efficacy of PTH following ALN therapy for stimulating new bone formation, and increasing trabecular thickness and bone volume fraction. In healthy bone, resorption and formation are coupled and balanced to sustain bone mass. OVX results in resorption outpacing formation, and subsequent bone loss and reduction in bone tissue modulus and tissue heterogeneity. We showed that ALN treatment effectively reduced bone resorption activity and regained the balance with bone formation, preventing additional bone loss. However, ALN treatment also resulted in significant reductions in the heterogeneity of bone tissue mineral density and tissue modulus. On the other hand, PTH treatment was able to shift the bone remodeling balance in favor of formation, with or without a prior treatment with ALN. Moreover, by altering the tissue mineralization, PTH alleviated the reduction in heterogeneity of tissue material properties induced by prolonged ALN treatment. Furthermore, switching to PTH treatment from ALN improved bone's postyield mechanical properties at both the whole bone and apparent level compared to ALN alone. The current findings suggest that intermittent PTH treatment should be considered as a viable treatment option for patients with prior treatment with bisphosphonates. © 2017 American Society for Bone and Mineral Research.
绝经后骨质疏松症通常采用双膦酸盐类药物（如阿仑膦酸钠，[ALN]）进行治疗，但长期使用双膦酸盐治疗过度抑制骨转换可能会降低骨组织的异质性。因此，长期使用双膦酸盐后的替代治疗策略具有重大临床意义。本研究的目的是确定在6月龄去卵巢（OVX）大鼠中，给予12周ALN（一种双膦酸盐）治疗后，间歇性甲状旁腺激素（PTH）对多个长度尺度下的骨微结构、骨重塑动力学和骨力学性能的影响。通过使用体内μCT和三维体内动态骨组织形态计量学技术，我们证明了ALN治疗后PTH刺激新骨形成、增加小梁厚度和骨体积分数的疗效。在健康骨骼中，吸收和形成相互耦合且平衡，以维持骨量。OVX导致吸收超过形成，随后出现骨质流失以及骨组织模量和组织异质性降低。我们发现，ALN治疗有效降低了骨吸收活性，并恢复了与骨形成的平衡，防止了进一步的骨质流失。然而，ALN治疗也导致骨组织矿物质密度和组织模量的异质性显著降低。另一方面，无论之前是否接受过ALN治疗，PTH治疗都能够使骨重塑平衡向有利于形成的方向转变。此外，通过改变组织矿化，PTH减轻了长期ALN治疗引起的组织材料性能异质性降低。此外，与单独使用ALN相比，从ALN转换为PTH治疗可改善全骨和表观水平下骨的屈服后力学性能。目前的研究结果表明，对于先前接受过双膦酸盐治疗的患者，间歇性PTH治疗应被视为一种可行的治疗选择。© 2017美国骨与矿物质研究学会。
