Wang Huan, Tao Liyuan, Liu Dongyang, Yan Xiaoyan, Li Haiyan, Song Chunli
Department of Orthopedics, Peking University Third Hospital, Beijing, China.
Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China.
J Orthop Surg Res. 2025 Jul 17;20(1):669. doi: 10.1186/s13018-025-06083-6.
Accumulating evidence highlights the critical role of circadian rhythms in regulating bone turnover. Bone turnover markers, including parathyroid hormone, C-terminal telopeptide of type I collagen, and N-terminal propeptide of type I procollagen, all exhibit distinct diurnal variations. Teriparatide, a recombinant parathyroid hormone analog, demonstrates time-dependent efficacy influenced by these endogenous rhythms. However, the impact of administration timing on bone metabolism remains underexplored.
This randomized, open-label, exploratory trial investigates the impact of teriparatide administration timing by comparing subcutaneous injection at 08:00 versus 20:00 on bone turnover markers in postmenopausal women with osteoporosis.
Twenty-eight participants (aged 60-70 years, lumbar spine T-score ≤ -3.0) will be randomized in a 1:1 ratio to receive 20 µg/day of teriparatide via subcutaneous injection at either 08:00 or 20:00 for 12 weeks. All participants will receive standardized calcium (1000-1500 mg/day) and cholecalciferol (800-1200 IU/day) supplementation throughout the study period. The primary outcomes are the between-group differences in serum parathyroid hormone, C-terminal telopeptide of type I collagen, and N-terminal propeptide of type I procollagen profiles, which will be assessed at baseline, 4 weeks, and 12 weeks. Secondary outcomes will evaluate the safety profile during the trial.
This trial is expected to provide crucial insights into optimizing teriparatide administration timing, potentially guiding personalized dosing strategies to enhance bone formation and reduce fracture risk in osteoporosis. The findings may inform future research on circadian rhythm-aligned therapies.
ClinicalTrials.gov ID NCT06951776.
越来越多的证据表明昼夜节律在调节骨转换中起关键作用。骨转换标志物，包括甲状旁腺激素、I型胶原C端肽和I型前胶原N端前肽，均表现出明显的昼夜变化。特立帕肽，一种重组甲状旁腺激素类似物，其疗效受这些内源性节律影响，呈现出时间依赖性。然而，给药时间对骨代谢的影响仍未得到充分研究。
本项随机、开放标签的探索性试验，通过比较在08:00和20:00皮下注射特立帕肽，研究给药时间对绝经后骨质疏松症女性骨转换标志物的影响。
28名参与者（年龄60 - 70岁，腰椎T值≤ -3.0）将按1:1比例随机分组，在08:00或20:00皮下注射20μg/天的特立帕肽，持续12周。在整个研究期间，所有参与者将接受标准化的钙（1000 - 1500mg/天）和胆钙化醇（800 - 1200IU/天）补充。主要结局是血清甲状旁腺激素、I型胶原C端肽和I型前胶原N端前肽谱在组间的差异，将在基线、4周和12周时进行评估。次要结局将评估试验期间的安全性。
本试验有望为优化特立帕肽给药时间提供关键见解，可能指导个性化给药策略，以增强骨形成并降低骨质疏松症的骨折风险。研究结果可能为未来关于昼夜节律同步疗法的研究提供参考。
ClinicalTrials.gov标识符NCT06951776。
