The effects of high-dose calcitriol and individualized exercise on bone metabolism in breast cancer survivors on hormonal therapy: a phase II feasibility trial.
The effects of high-dose calcitriol and individualized exercise on bone metabolism in breast cancer survivors on hormonal therapy: a phase II feasibility trial.
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高剂量骨化三醇和个体化运动对激素治疗乳腺癌幸存者骨代谢的影响：II 期可行性试验。
DOI：
10.1007/s00520-018-4094-4
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Mustian,KarenM
中科院分区：
文献类型：
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作者：
Peppone,LukeJ;Ling,Marilyn;Huston,AlissaJ;Reid,MaryE;Janelsins,MichelleC;Puzas,JEdward;Kamen,Charles;DelGiglio,Auro;Asare,Matthew;Peoples,AnitaR;Mustian,KarenM
癌症治疗引起的骨丢失（CTIBL）是乳腺癌治疗的长期副作用。骨化三醇和负重运动都能改善乳腺癌患者的骨代谢，但在乳腺癌人群中尚未得到证实。我们使用了一种新的高剂量骨化三醇方案与个性化的运动干预，以改善骨代谢在breast cancer survivors.MethodsWe招募了41名受试者，这个开放标签，2 × 2析因，随机可行性试验。乳腺癌幸存者随机接受以下治疗：（1）骨化三醇（45微克/周），（2）个体化运动，渐进式步行和阻力训练，（3）两者兼而有之，或（4）每日多种维生素（对照条件），持续12周。主要结果包括骨形成、骨吸收和骨重建指数（骨形成和骨吸收的复合指标）生物标志物的变化。安全性指标包括临床和生化不良事件。对这些终点进行主效应分析。结果高钙血症仅限于3例I级病例，无≥ 2级病例。在运动者中，100%的人进行了规定的有氧训练，44.4%的人进行了规定的抗阻训练。骨化三醇显著改善骨形成（Cohen’s d = 0.64;p< 0.01），导致骨重建指数的非显著增加（Cohen’s d = 0.21;p= 31）。运动未能改善任何的骨生物标志物。ConclusionsBoth骨化三醇和运动被证明是可行的，耐受性良好。骨化三醇显著改善骨形成，导致骨代谢的净增加。运动干预的依从性不佳，这可能导致运动对骨代谢缺乏影响。
IntroductionCancer treatment-induced bone loss (CTIBL) is a long-term side effect of breast cancer therapy. Both calcitriol and weight-bearing exercise improve bone metabolism for osteoporotic patients, but are unproven in a breast cancer population. We used a novel high-dose calcitriol regimen with an individualized exercise intervention to improve bone metabolism in breast cancer survivors.MethodsWe accrued 41 subjects to this open label, 2 × 2 factorial, randomized feasibility trial. Breast cancer survivors were randomized to receive the following: (1) calcitriol (45 micrograms/week), (2) individualized exercise with progressive walking and resistance training, (3) both, or (4) a daily multivitamin (control condition) for 12 weeks. Primary outcomes included changes in biomarkers of bone formation, bone resorption, and the bone remodeling index, a composite measure of bone formation and resorption. Safety measures included clinical and biochemical adverse events. A main effect analysis was used for these endpoints.ResultsHypercalcemia was limited to three grade I cases with no grade ≥ 2 cases. Among exercisers, 100% engaged in the prescribed aerobic training and 44.4% engaged in the prescribed resistance training. Calcitriol significantly improved bone formation (Cohen’s d = 0.64;p< 0.01), resulting in a non-significant increase in the bone remodeling index (Cohen’s d = 0.21;p= 31). Exercise failed to improve any of the bone biomarkers.ConclusionsBoth calcitriol and exercise were shown to be feasible and well tolerated. Calcitriol significantly improved bone formation, resulting in a net increase of bone metabolism. Compliance with the exercise intervention was sub-optimal, which may have led to a lack of effect of exercise on bone metabolism.