Cosman F, Nieves J, Woelfert L, Shen V, Lindsay R
Clinical Research and Regional Bone Centers, Helen Hayes Hospital, West Haverstraw, New York, USA.
J Bone Miner Res. 1998 Jun;13(6):1051-5. doi: 10.1359/jbmr.1998.13.6.1051.
In rodent osteoporosis models, anabolic activity of parathyroid hormone (PTH) is preserved in the presence of antiresorptive agents. Anabolic activity is also preserved when PTH is administered to estrogenized postmenopausal women. In contrast, in the ewe treated with tiludronate, PTH-induced stimulation of bone turnover did not occur. To determine whether PTH in combination with alendronate could be a viable treatment for osteoporosis, we performed a short-term study of postmenopausal women with osteoporosis (n = 10) already on alendronate 10 mg/day to determine whether PTH could increase bone formation assessed biochemically. Patients continued alendronate alone (n = 5) or continued alendronate with 400 IU/day subcutaneous human PTH (1-34) added for 6 weeks. Subjects receiving PTH had serum and urine sampling weekly during PTH treatment and for 5 weeks thereafter. Sampling was performed approximately biweekly for subjects who had been on alendronate alone for 11 weeks. Samples were analyzed for osteocalcin (OC), propeptide of type I procollagen (PICP), bone-specific alkaline phosphatase (BSAP), cross-linked urinary N-telopeptide (NTX), and free urinary pyridinoline (PYD). Markers of bone formation increased within 3 weeks in the PTH plus alendronate group, with mean peak levels at 5-7 weeks: OC 49%, p < 0.01; PICP 61%, p < 0.01; and BSAP 24%, p = 0.12. Levels returned to baseline after discontinuing PTH, with PICP declining the most rapidly. There were no significant changes at any time in the alendronate alone group. There were no increments in either urinary NTX or PYD in either treatment group throughout the observation period. The bone turnover marker changes seen with PTH plus alendronate were similar to those seen with PTH plus hormone replacement. These data suggest that: PTH can stimulate bone formation, evidenced by elevations of bone formation markers, even in the presence of a potent bisphosphonate; in the presence of alendronate, PTH-stimulated bone formation precedes stimulation of bone resorption, suggesting that PTH stimulates bone formation de novo; and the combination of PTH and alendronate may be a viable treatment option for postmenopausal women with osteoporosis.
在啮齿动物骨质疏松模型中，甲状旁腺激素（PTH）的合成代谢活性在抗吸收剂存在的情况下得以保留。当给雌激素化的绝经后女性使用PTH时，合成代谢活性也能保留。相比之下，在用替鲁膦酸盐治疗的母羊中，未出现PTH诱导的骨转换刺激。为了确定PTH联合阿仑膦酸盐是否可能成为骨质疏松症的一种可行治疗方法，我们对已服用阿仑膦酸盐10毫克/天的绝经后骨质疏松女性（n = 10）进行了一项短期研究，以确定PTH是否能增加通过生化方法评估的骨形成。患者继续单独服用阿仑膦酸盐（n = 5）或继续服用阿仑膦酸盐并添加400国际单位/天的皮下人PTH（1 - 34），持续6周。接受PTH治疗的受试者在PTH治疗期间每周进行血清和尿液采样，并在之后的5周内继续采样。对于单独服用阿仑膦酸盐11周的受试者，大约每两周进行一次采样。对样本进行骨钙素（OC）、I型前胶原前肽（PICP）、骨特异性碱性磷酸酶（BSAP）、交联尿N - 端肽（NTX）和游离尿吡啶啉（PYD）的分析。PTH加阿仑膦酸盐组的骨形成标志物在3周内升高，平均峰值水平出现在5 - 7周：OC升高49%，p < 0.01；PICP升高61%，p < 0.01；BSAP升高24%，p = 0.12。停用PTH后水平恢复到基线，其中PICP下降最快。单独使用阿仑膦酸盐组在任何时候都没有显著变化。在整个观察期内，两个治疗组的尿NTX和PYD均无增加。PTH加阿仑膦酸盐时骨转换标志物的变化与PTH加激素替代时观察到的变化相似。这些数据表明：即使在强效双膦酸盐存在的情况下，PTH也能刺激骨形成，表现为骨形成标志物升高；在阿仑膦酸盐存在的情况下，PTH刺激的骨形成先于骨吸收的刺激，这表明PTH从头刺激骨形成；PTH和阿仑膦酸盐的联合可能是绝经后骨质疏松女性的一种可行治疗选择。
