Ste-Marie Louis G, Schwartz Sherwyn L, Hossain Anwar, Desaiah Durisala, Gaich Gregory A
Centre de Recherche CHUM, Montreal, Canada.
J Bone Miner Res. 2006 Feb;21(2):283-91. doi: 10.1359/JBMR.051020. Epub 2005 Oct 31.
The effects of teriparatide when given in combination with HRT were studied in postmenopausal women with low bone mass or osteoporosis. The data provide evidence that the adverse event profile for combination therapy with teriparatide + HRT together is consistent with that expected for each treatment alone and that the BMD response is greater than for HRT alone.
Teriparatide [rhPTH(1-34)], given as a once-daily injection, activates new bone formation in patients with osteoporosis. Hormone replacement therapy (HRT) prevents osteoporosis by reducing bone resorption and formation. Combination therapy with these two compounds, in small clinical trials, increased BMD and reduced vertebral fracture burden. The purpose of this study was to determine whether teriparatide provided additional effect on BMD when given in combination with HRT.
A randomized, double-blind, placebo-controlled study was conducted in postmenopausal women with either low bone mass or osteoporosis. Patients were randomized to placebo subcutaneous plus HRT (n = 125) or teriparatide 40 microg/day (SC) plus HRT (TPTD40 + HRT; n = 122) for a median treatment exposure of 13.8 months. Approximately one-half of the patients in each group were pretreated with HRT for at least 12 months before randomization. Patients received 1000 mg calcium and 400-1200 IU of vitamin D daily as oral supplementation. BMD was measured by DXA.
Compared with HRT alone, TPTD40 + HRT produced significant (p < 0.001) increases in spine BMD (14% versus 3%), total hip (5.2% versus 1.6%), and femoral neck (5.2% versus 2%) at study endpoint. BMD, in whole body and ultradistal radius, was higher, and in the one-third distal radius was lower, in the combination therapy but not in the HRT group. Serum bone-specific alkaline phosphatase and urinary N-telopeptide/Cr were increased significantly (p < 0.01) in the women receiving TPTD40 + HRT compared with HRT. A similar profile of BMD and bone markers was evident in both randomized patients as well as in subgroups of patients not pretreated or pretreated with HRT. Patients tolerated both the treatments well. Nausea and leg cramps were more frequently reported in the TPTD40 + HRT group.
Adding teriparatide, a bone formation agent, to HRT, an antiresorptive agent, provides additional increases in BMD beyond that provided by HRT alone. The adverse effects of teriparatide when added to HRT were similar to the adverse effects described for teriparatide administered alone. Whether teriparatide was initiated at the same time as HRT or after at least 1 year on HRT, the incremental increases over HRT alone were similar.
对低骨量或骨质疏松的绝经后女性研究了特立帕肽与激素替代疗法（HRT）联合使用的效果。数据表明，特立帕肽+HRT联合治疗的不良事件谱与每种治疗单独使用时预期的一致，且骨密度（BMD）反应大于单独使用HRT。
特立帕肽[重组人甲状旁腺激素（1-34）]每日注射一次，可激活骨质疏松患者的新骨形成。激素替代疗法（HRT）通过减少骨吸收和形成来预防骨质疏松。在小型临床试验中，这两种化合物的联合治疗增加了骨密度并减轻了椎体骨折负担。本研究的目的是确定特立帕肽与HRT联合使用时是否对骨密度有额外影响。
对低骨量或骨质疏松的绝经后女性进行了一项随机、双盲、安慰剂对照研究。患者被随机分为皮下注射安慰剂+HRT组（n = 125）或特立帕肽40μg/天（皮下注射）+HRT组（TPTD40 + HRT；n = 122），中位治疗时间为13.8个月。每组中约一半的患者在随机分组前接受了至少12个月的HRT预处理。患者每天口服补充1000mg钙和400 - 1200IU维生素D。通过双能X线吸收法（DXA）测量骨密度。
与单独使用HRT相比，在研究终点时，TPTD40 + HRT组的脊柱骨密度显著增加（p < 0.001）（14%对3%）、全髋骨密度（5.2%对1.6%）和股骨颈骨密度（5.2%对2%）。联合治疗组全身和桡骨远端1/3处的骨密度较高，而桡骨远端1/3处的骨密度较低，HRT组则无此情况。与HRT组相比，接受TPTD40 + HRT的女性血清骨特异性碱性磷酸酶和尿N-端肽/Cr显著增加（p < 0.01）。在随机分组患者以及未接受预处理或接受过HRT预处理的患者亚组中，骨密度和骨标志物的情况相似。患者对两种治疗的耐受性都很好。TPTD40 + HRT组恶心和腿部抽筋的报告更频繁。
在抗吸收药物HRT基础上加用促骨形成药物特立帕肽，可使骨密度增加幅度超过单独使用HRT。特立帕肽加用至HRT时的不良反应与单独使用特立帕肽时描述的不良反应相似。无论特立帕肽是与HRT同时开始使用还是在HRT使用至少1年后开始使用，相对于单独使用HRT的增量增加相似。
