Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Basel, Missionsstrasse 24, 4055 Basel, Switzerland.
J Bone Miner Metab. 2010;28(1):68-76. doi: 10.1007/s00774-009-0101-7. Epub 2009 Jun 17.
Concurrent use of bisphosphonate therapy reduces the anabolic effect of teriparatide. Consequently, in clinical practice bisphosphonates are discontinued and teriparatide therapy held for a few months to allow bone turnover to increase. We aimed to evaluate the effect of prior bisphosphonate exposure and the effect of bisphosphonate wash-out on the treatment response to teriparatide. Thirty-nine patients with primary osteoporosis (mean age 63.6 +/- 14.0 years), including 26 patients previously treated with oral bisphosphonates (median duration 53 months) and 13 bisphosphonate-naïve patients were started on teriparatide (20 mug daily) and followed prospectively over 12 months. The primary study outcome was change in bone formation markers (PINP, bone ALP, osteocalcin). Secondary outcomes included changes in bone resorption (betaCTX) and 12-month changes in BMD. Markers of bone formation increased early during teriparatide therapy and were followed by an increase in betaCTX (p < 0.001). The magnitude of the increase in bone markers was comparable in both patient groups irrespective of prior bisphosphonate exposure; similarly, increases in BMD after 12 months were not significantly different between bisphosphonate-pretreated and bisphosphonate-naïve patients (lumbar spine 7.1 vs. 8.9%, p = 0.58; total hip 4.1 vs. 1.1%, p = 0.48). The response of teriparatide was not related to the duration of bisphosphonate wash-out (median duration 4.2 months). This study confirms that beneficial effects of teriparatide on intermediate bone endpoints can be translated into clinical practice with less constringent methodological circumstances than in RCTs. Furthermore, as bisphosphonate wash-out does not appear to influence the treatment effect, teriparatide therapy can be started immediately after ceasing bisphosphonate therapy and wash-out.
同时使用双膦酸盐治疗会降低特立帕肽的合成代谢作用。因此，在临床实践中，会停用双膦酸盐，并暂停特立帕肽治疗几个月，以增加骨转换。我们旨在评估先前使用双膦酸盐暴露和双膦酸盐冲洗对特立帕肽治疗反应的影响。39 名原发性骨质疏松症患者（平均年龄 63.6+/-14.0 岁），包括 26 名以前接受过口服双膦酸盐治疗的患者（中位持续时间 53 个月）和 13 名从未使用过双膦酸盐的患者，开始接受特立帕肽（20 微克/天）治疗，并前瞻性随访 12 个月。主要研究结果是骨形成标志物（PINP、骨 ALP、骨钙素）的变化。次要结局包括骨吸收的变化（βCTX）和 12 个月时 BMD 的变化。在特立帕肽治疗早期，骨形成标志物增加，随后βCTX 增加（p<0.001）。无论先前是否使用过双膦酸盐，两组患者的骨标志物增加幅度相似；同样，12 个月后 BMD 的增加在双膦酸盐预处理和未使用过双膦酸盐的患者之间也无显著差异（腰椎 7.1% vs. 8.9%，p=0.58；全髋 4.1% vs. 1.1%，p=0.48）。特立帕肽的反应与双膦酸盐冲洗的持续时间无关（中位持续时间 4.2 个月）。这项研究证实，特立帕肽对中间骨终点的有益影响可以在临床试验中转化为更宽松的方法学环境，而不是在 RCT 中。此外，由于双膦酸盐冲洗似乎不会影响治疗效果，因此可以在停止双膦酸盐治疗和冲洗后立即开始特立帕肽治疗。
