Biomechanics and Spine Research Group, Queensland University of Technology, Brisbane, QLD, Australia.
St Vincent's Department of Surgery, University of Melbourne, Melbourne, VIC, Australia.
Biomech Model Mechanobiol. 2020 Oct;19(5):1765-1780. doi: 10.1007/s10237-020-01307-6. Epub 2020 Feb 25.
One of only a few approved and available anabolic treatments for severe osteoporosis is daily injections of PTH (1-34). This drug has a specific dual action which can act either anabolically or catabolically depending on the type of administration, i.e. intermittent or continuous, respectively. In this paper, we present a mechanistic pharmacokinetic-pharmacodynamic model of the action of PTH in postmenopausal osteoporosis. This model accounts for anabolic and catabolic activities in bone remodelling under intermittent and continuous administration of PTH. The model predicts evolution of common bone biomarkers and bone volume fraction (BV/TV) over time. We compared the relative changes in BV/TV resulting from a daily injection of 20 [Formula: see text]g of PTH with experimental data from the literature. Simulation results indicate a site-specific bone gain of 8.66[Formula: see text] (9.4 ± 1.13[Formula: see text]) at the lumbar spine and 3.14[Formula: see text] (2.82 ± 0.72[Formula: see text]) at the femoral neck. Bone gain depends nonlinearly on the administered dose, being, respectively, 0.68[Formula: see text], 3.4[Formula: see text] and 6.16[Formula: see text] for a 10, 20 and 40 [Formula: see text]g PTH dose at the FN over 2 years. Simulations were performed also taking into account a bone mechanical disuse to reproduce elderly frail subjects. The results show that mechanical disuse ablates the effects of PTH and leads to a 1.08% reduction of bone gain at the FN over a 2-year treatment period for the 20 [Formula: see text]g of PTH. The developed model can simulate a range of pathological conditions and treatments in bones including different PTH doses, different mechanical loading environments and combinations. Consequently, the model can be used for testing and generating hypotheses related to synergistic action between PTH treatment and physical activity.
甲状旁腺素（1-34）是目前唯一被批准用于严重骨质疏松症的治疗药物，且只能通过每日注射的方式给药。这种药物具有特定的双重作用，其作用方式取决于给药类型，即间歇性或连续性。在本文中，我们提出了一种甲状旁腺素在绝经后骨质疏松症中作用的机制-药效动力学模型。该模型考虑了在间歇性和连续性给予甲状旁腺素的情况下，骨重塑的合成代谢和分解代谢活动。该模型预测了常见骨生物标志物和骨体积分数（BV/TV）随时间的变化。我们将每日注射 20μg 甲状旁腺素引起的 BV/TV 相对变化与文献中的实验数据进行了比较。模拟结果表明，腰椎的骨量增加了 8.66%[Formula: see text]（9.4 ± 1.13%[Formula: see text]），股骨颈的骨量增加了 3.14%[Formula: see text]（2.82 ± 0.72%[Formula: see text]）。骨量的增加与给药剂量呈非线性关系，在 2 年内，FN 处分别给予 10、20 和 40μg 甲状旁腺素时，骨量增加量分别为 0.68%、3.4%和 6.16%。同时还考虑了骨力学废用来模拟老年虚弱的患者。结果表明，力学废用会消除甲状旁腺素的作用，导致在 2 年的治疗期间，FN 处的骨量增加减少 1.08%。所开发的模型可以模拟包括不同剂量的甲状旁腺素、不同的机械加载环境和组合等多种病理条件和治疗方法。因此，该模型可用于测试和生成与甲状旁腺素治疗与体育活动协同作用相关的假设。
