Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA.
Department of Materials Science and Engineering, Cornell University, Ithaca, NY, USA.
Calcif Tissue Int. 2020 Mar;106(3):303-314. doi: 10.1007/s00223-019-00634-w. Epub 2019 Nov 29.
Anti-resorptive and anabolic treatments can be used sequentially to treat osteoporosis, but their effects on bone composition are incompletely understood. Osteocytes may influence bone tissue composition with sequential therapies because bisphosphonates diffuse into the canalicular network and anabolic treatments increase osteocyte lacunar size. Cortical bone composition of osteopenic, ovariectomized (OVX) rats was compared to that of Sham-operated rats and OVX rats given monotherapy or sequential regimens of single approved anti-osteoporosis medications. Adult female Sprague-Dawley rats were OVX (N = 37) or Sham-OVXd (N = 6). After 2 months, seven groups of OVX rats were given three consecutive 3-month periods of treatment with vehicle (V), h-PTH (1-34) (P), alendronate (A), or raloxifene (R), using the following orders: VVV, PVV, RRR, RPR, AAA, AVA, and APA. Compositional properties around osteocyte lacunae of the left tibial cortex were assessed from Raman spectra in perilacunar and non-perilacunar bone matrix regions. Sequential treatments involving parathyroid hormone (PTH) caused lower mean collagen maturity relative to monotherapies. Mean mineral:matrix ratio was 2.2% greater, mean collagen maturity was 1.4% greater, and mean carbonate:phosphate ratio was 2.2% lower in the perilacunar than in the non-perilacunar bone matrix region (all P < 0.05). These data demonstrate cortical bone tissue composition differences around osteocytes caused by sequential treatment with anti-osteoporosis medications. We speculate that the region-specific differences demonstrate the ability of osteocytes to alter bone tissue composition adjacent to lacunae.
抗吸收和合成代谢治疗可用于序贯治疗骨质疏松症，但它们对骨成分的影响尚不完全清楚。破骨细胞可能会通过序贯治疗影响骨组织组成，因为双膦酸盐扩散到管腔网络，合成代谢治疗增加破骨细胞陷窝大小。与假手术（Sham）操作组和单独接受一种批准的抗骨质疏松药物治疗的卵巢切除（OVX）组相比，骨质疏松 OVX 大鼠的皮质骨成分被进行了比较。成年雌性 Sprague-Dawley 大鼠接受 OVX（N = 37）或 Sham-OVXd（N = 6）。2 个月后，7 组 OVX 大鼠接受连续 3 个月的治疗，分别给予 vehicle（V）、h-PTH（1-34）（P）、阿仑膦酸钠（A）或雷洛昔芬（R），治疗顺序为 VVV、PVV、RRR、RPR、AAA、AVA 和 APA。从周围破骨细胞陷窝的左胫骨皮质的 Raman 光谱评估 perilacunar 和非 perilacunar 骨基质区域的组成特性。涉及甲状旁腺激素（PTH）的序贯治疗与单独治疗相比，胶原成熟度平均值较低。perilacunar 骨基质区域的矿化基质比（mean mineral:matrix ratio）高 2.2%，胶原成熟度高 1.4%，碳酸盐：磷酸盐比（mean carbonate:phosphate ratio）低 2.2%（均 P < 0.05）。这些数据表明，抗骨质疏松药物序贯治疗导致破骨细胞周围皮质骨组织组成的差异。我们推测，区域特异性差异表明破骨细胞具有改变陷窝周围骨组织组成的能力。
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