Lindsay R, Nieves J, Formica C, Henneman E, Woelfert L, Shen V, Dempster D, Cosman F
Clinical Research Center, Helen Hayes Hospital, Haverstraw 10993, USA.
Lancet. 1997 Aug 23;350(9077):550-5. doi: 10.1016/S0140-6736(97)02342-8.
Small increases in bone mass are commonly seen with existing treatments for osteoporosis, which reduce bone remodelling and primarily prevent bone loss. Since these drugs reduce but do not eliminate risk of fractures, an anabolic agent that would increase bone mass and potentially cure the underlying skeletal problem is needed.
We did a 3-year randomised controlled trial to find out the effects of 1-34 human parathyroid hormone (hPTH [1-34], 400 U/25 micrograms daily subcutaneously) in postmenopausal women with osteoporosis taking hormone-replacement therapy (n = 17). The controls were women taking hormone-replacement therapy only (n = 17). The primary outcome was bone-mineral density of the lumbar vertebrae, with bone-mineral density at other sites and vertebral fractures as secondary endpoints.
Patients taking hormone-replacement therapy and PTH (1-34) had continuous increase in vertebral bone-mineral density during the 3 years, whereas there was no significant change in the control group. The total increase in vertebral bone-mineral density was 13.0% (p < 0.001); 2.7% at the hip (p = 0.05); and 8.0% in total-body bone mineral (p = 0.002). No loss of bone mass was found at any skeletal site. Increased bone mass was associated with a reduction in the rate of vertebral fractures, which was significant when fractures were taken as a 15% reduction in vertebral height (p = 0.04). During the first 6 months of treatment, serum osteocalcin concentration, which reflects bone formation, increased by more than 55%, whereas excretion of crosslinked n-telopeptide, which reflects bone resorption, increased by only 20%, which suggests some uncoupling of bone formation and resorption. By 6 months, there were similar increases in both markers, which gradually returned towards baseline as the study progressed. Vertebral bone-mineral density increased most during the first year of PTH treatment.
We found that PTH has a pronouned anabolic effect on the central skeleton in patients on hormone-replacement therapy. PTH also increases total-body bone mineral, with no detrimental effects at any skeletal site. The increased vertebral mass was associated with a reduced rate of vertebral fracture, despite increased bone turnover. Bone-mass changes may be consistent with a reduction in all osteoporotic fractures. If confirmed in larger studies, these data have important implications for the treatment of postmenopausal osteoporosis.
现有骨质疏松症治疗方法通常会使骨量有小幅增加，这些方法可减少骨重塑并主要预防骨质流失。由于这些药物虽能降低但不能消除骨折风险，因此需要一种能增加骨量并可能治愈潜在骨骼问题的合成代谢药物。
我们进行了一项为期3年的随机对照试验，以研究1-34人甲状旁腺激素（hPTH [1-34]，每日皮下注射400 U/25微克）对接受激素替代疗法的绝经后骨质疏松症女性（n = 17）的影响。对照组为仅接受激素替代疗法的女性（n = 17）。主要结局是腰椎骨密度，其他部位的骨密度和椎体骨折作为次要终点。
接受激素替代疗法和PTH（1-34）的患者在3年期间椎体骨密度持续增加，而对照组无显著变化。椎体骨密度的总增加量为13.0%（p < 0.001）；髋部为2.7%（p = 0.05）；全身骨矿物质为8.0%（p = 0.002）。在任何骨骼部位均未发现骨质流失。骨量增加与椎体骨折发生率降低相关，当骨折定义为椎体高度降低15%时具有显著性（p = 0.04）。在治疗的前6个月，反映骨形成的血清骨钙素浓度增加超过55%，而反映骨吸收的交联N-端肽排泄量仅增加20%，这表明骨形成和吸收存在一定程度的解偶联。到6个月时，两种标志物均有类似增加，并随着研究进展逐渐恢复至基线水平。PTH治疗的第一年椎体骨密度增加最多。
我们发现PTH对接受激素替代疗法的患者的中轴骨骼有显著的合成代谢作用。PTH还能增加全身骨矿物质，且对任何骨骼部位均无有害影响。尽管骨转换增加，但椎体骨量增加与椎体骨折发生率降低相关。骨量变化可能与所有骨质疏松性骨折的减少相一致。如果在更大规模的研究中得到证实，这些数据对绝经后骨质疏松症的治疗具有重要意义。
