Bakr Mahmoud M, Kelly Wendy L, Brunt Athena R, Paterson Bradley C, Massa Helen M, Morrison Nigel A, Forwood Mark R
School of Medical Sciences and Menzies Health Institute Queensland Griffith University Gold Coast Queensland Australia.
School of Dentistry and Oral Health Griffith University Gold Coast Queensland Australia.
JBMR Plus. 2020 Aug 6;4(9):e10387. doi: 10.1002/jbm4.10387. eCollection 2020 Sep.
Parathyroid hormone (PTH) and bisphosphonates (BPs), including alendronate (ALN), have opposing effects on bone dynamics. The extent to which PTH remains effective in the treatment of stress fracture (SFx) in the presence of an ongoing BP treatment has not been tested. SFx was induced in 150 female Wistar rats, divided into five equal groups ( = 30). All rats were pretreated with ALN (1 μg/kg/day) for 14 days prior to SFx induction, followed by ALN cessation or continuation for the duration of the experiment; this was combined with daily PTH (8 μg/100 g/day) on SFx induction for 14 days, followed by cessation or continuation of ALN after SFx induction or an equivalent vehicle as a control. Ulnas were examined 2 weeks or 6 weeks following SFx. Two toluidine blue- and two tartrate-resistant acid phosphatase-stained sections were examined for histomorphometric analysis using Osteomeasure software. There was a significant interaction between the effects of time and treatment type on the woven bone width and apposition rate, as well as an improvement in the woven bone architecture. However, woven bone variables remained unaffected by the cessation or continuation of ALN. Cessation of ALN increased osteoclast number when compared with the ALN-PTH continuation group ( = 0.006), and vehicle ( = 0.024) after 2 weeks. There was a significant interaction between the effects of time and treatment type on the number of osteoclasts per unit BMU area and length. The number of osteoclasts per unit BMU area and length was significantly greater in ALN cessation groups. It was concluded that intermittent short-duration iPTH treatment effectively increased remodeling of SFx with a concurrent BP treatment, provided that BP was ceased at the time of SFx. Our results could help develop shorter iPTH treatment protocols for the clinical management of SFxs and guide clinical decision-making to cease BP treatment in cases of SFx. © 2020 The Authors. published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.
甲状旁腺激素（PTH）和双膦酸盐（BPs），包括阿仑膦酸盐（ALN），对骨动力学具有相反的作用。在持续进行双膦酸盐治疗的情况下，PTH在治疗应力性骨折（SFx）中保持有效程度尚未得到测试。在150只雌性Wistar大鼠中诱导产生应力性骨折，将其分为五组，每组30只。在诱导应力性骨折前，所有大鼠均用阿仑膦酸盐（1μg/kg/天）预处理14天，然后在实验期间停止或继续使用阿仑膦酸盐；这与在诱导应力性骨折时每日给予PTH（8μg/100g/天）14天相结合，随后在诱导应力性骨折后停止或继续使用阿仑膦酸盐，或使用等量赋形剂作为对照。在应力性骨折后2周或6周检查尺骨。使用Osteomeasure软件检查两片甲苯胺蓝染色切片和两片抗酒石酸酸性磷酸酶染色切片以进行组织形态计量学分析。在编织骨宽度和沉积率方面，时间和治疗类型的效应之间存在显著交互作用，并且编织骨结构有改善。然而，编织骨变量不受阿仑膦酸盐停止或继续使用的影响。与阿仑膦酸盐 - PTH继续使用组相比，停止使用阿仑膦酸盐后2周时破骨细胞数量增加（P = 0.006），与赋形剂组相比也增加（P = 0.024）。在每单位骨多细胞单位（BMU）面积和长度的破骨细胞数量方面，时间和治疗类型的效应之间存在显著交互作用。在阿仑膦酸盐停止使用组中，每单位BMU面积和长度的破骨细胞数量显著更多。得出的结论是，间歇性短期皮下注射PTH治疗在同时进行双膦酸盐治疗的情况下可有效增加应力性骨折的重塑，前提是在应力性骨折发生时停止使用双膦酸盐。我们的结果有助于制定更短的皮下注射PTH治疗方案用于应力性骨折的临床管理，并指导临床决策在应力性骨折病例中停止双膦酸盐治疗。© 2020作者。由Wiley Periodicals LLC代表美国骨与矿物质研究学会出版
