Instituto de Investigaciones Metabólicas, Buenos Aires, Argentina.
Curr Med Res Opin. 2010 Nov;26(11):2627-33. doi: 10.1185/03007995.2010.524121. Epub 2010 Oct 5.
To determine the safety and efficacy of full-length parathyroid hormone, PTH(1-84), treatment for up to 36 months by evaluating bone mineral density (BMD) changes, bone histomorphometric indices, and clinical fracture incidence in postmenopausal women with osteoporosis.
The TOP trial demonstrated increased lumbar spine BMD (6.9%) versus placebo after 18 months of PTH(1-84) treatment and reduced the incidence of new vertebral fractures (61%; p = 0.001). The therapeutic benefits of long-term treatment of postmenopausal women with PTH(1-84) are unknown.
The safety and efficacy of 36 months of once-daily dosing with 100 µg PTH(1-84) in postmenopausal women with osteoporosis were assessed. Women receiving placebo during the TOP trial were eligible for PTH(1-84) in the extension study.
NCT00172120.
Lumbar spine BMD increased by 8.5% above baseline (p < 0.001) at 36 months of PTH(1-84) treatment, remaining stable during the last 12 months of treatment. Increases in total hip and femoral neck BMD occurred more slowly, reaching 3.2% and 3.4%, respectively above baseline at 36 months (p < 0.001). The total hip BMD showed no signs of reaching a limiting value although the femoral neck plateaued from months 24 to 36. Seven patients had vertebral fractures during the placebo phase of the TOP trial and before entering the extension study, but this rate decreased with the introduction of PTH(1-84) therapy, resulting in a single worsened vertebral fracture in the first 6 months and no further vertebral fractures from months 6 to 36. Treatment over 36 months with PTH(1-84) was well-tolerated and iliac crest biopsies showed no adverse effects on bone.
There was no placebo group for BMD comparisons. The number of patients assessed for fracture incidence was small.
PTH(1-84) treatment for 36 months resulted in significant increases in BMD at the lumbar spine and hip, was associated with a lower incidence of vertebral fracture when compared to before therapy initiation, and was well-tolerated. The continuous increases in total hip BMD suggest that prolonged PTH(1-84) treatment may be beneficial for postmenopausal osteoporosis. Increased BMD at the femoral neck and lumbar spine also showed favourable changes but plateaued between 24 and 36 months. Long-term treatment was not associated with abnormalities in bone biopsies.
通过评估骨密度（BMD）变化、骨组织形态计量学指标和临床骨折发生率，确定全长甲状旁腺激素（PTH[1-84]）治疗长达 36 个月的安全性和有效性，用于治疗绝经后骨质疏松症女性。
TOP 试验表明，与安慰剂相比，PTH[1-84]治疗 18 个月后腰椎 BMD 增加了 6.9%（p<0.001），并且新发椎体骨折的发生率降低了 61%（p=0.001）。PTH[1-84]治疗绝经后妇女的长期治疗的治疗益处尚不清楚。
评估了绝经后骨质疏松症女性每日一次接受 100µg PTH[1-84]治疗 36 个月的安全性和有效性。TOP 试验中接受安慰剂的女性有资格在扩展研究中接受 PTH[1-84]治疗。
NCT00172120。
PTH[1-84]治疗 36 个月时，腰椎 BMD 比基线增加了 8.5%（p<0.001），并且在治疗的最后 12 个月内保持稳定。全髋和股骨颈 BMD 的增加较为缓慢，分别在 36 个月时比基线增加了 3.2%和 3.4%（p<0.001）。尽管股骨颈在 24 至 36 个月期间趋于平稳，但全髋 BMD 似乎没有达到限制值。7 名患者在 TOP 试验的安慰剂阶段和进入扩展研究之前有椎体骨折，但随着 PTH[1-84]治疗的引入，该比率降低，在最初 6 个月内出现了一次恶化的椎体骨折，从第 6 个月到第 36 个月没有进一步的椎体骨折。PTH[1-84]治疗 36 个月以上耐受性良好，髂嵴活检未显示骨不良影响。
没有安慰剂组用于 BMD 比较。评估骨折发生率的患者人数较少。
与治疗前相比，PTH[1-84]治疗 36 个月可显著增加腰椎和髋部的 BMD，与椎体骨折发生率降低相关，并且耐受性良好。全髋 BMD 的持续增加表明，延长 PTH[1-84]治疗可能对绝经后骨质疏松症有益。股骨颈和腰椎 BMD 的增加也显示出有利的变化，但在 24 至 36 个月之间趋于平稳。长期治疗与骨活检异常无关。
