重组人甲状旁腺激素(1-34)和依降钙素治疗原发性骨质疏松症的随机对照研究

Effect of recombinant human parathyroid hormone( 1-34 ) and elcatonin in the treatment of primary osteoporosis: a randomized controlled trial

目的评价重组人甲状旁腺激素(1-34)[rhPTH(1-34)]治疗原发性骨质疏松症(OP)的疗效和安全性,并与依降钙素进行对比。方法 60例原发性OP患者按3:1被随机分入rhPTH(1-34)组(PTH组)和依降钙素组(CT组)。PTH组予rhPTH(1-34)20μg每日1次皮下注射,连续用药18月。CT组予益钙宁20U每周1次肌肉注射,连续用药12月。受试前检测腰2-4椎体(L2-4)和股骨颈骨密度(BMD)、血钙、血磷、尿钙、血清骨特异性碱性磷酸酶(BSAP)、尿Ⅰ型胶原交基C端肽(CTX-I),治疗后6、12、18月复查上述指标。结果与基线时比较,PTH组L2-4BMD在治疗6、12、18月时显著升高,股骨颈BMD在18月时显著升高,BSAP在6、12月时均显著升高,CTX-I校正值在6、12、18月时均显著升高;CT组L2-4BMD在治疗12月前升高,股骨颈BMD在12、18月时升高,BSAP12、18月时均显著下降,CTX-I校正值治疗前后无统计学差异。两组比较,PTH组患者在6、12月和18月时L2-4的BMD增长值和增长率均高于CT组。但CT组在治疗12月时股骨颈BMD增长值高于PTH组,不良反应:两组差异无统计学意义;PTH组有一过性高钙血症。结论 rhPTH(1-34)治疗原发性OP安全有效,对改善椎体BMD起效时间、增长速度和增长幅度均优于依降钙素,但改善股骨颈BMD较依降钙素起效更慢,增长幅度更小。

Objective To evaluate the clinical efficacy and safety of recombinant human parathyroid hormone （1-34） [ rhPTH （1-34） ] in the treatment of osteoporosis （ OP）, and to compare that with the efficacy of elcatonin. Methods A total of 60 patients with primary OP were randomly divided into 2 groups： rhPTH （1-34） group （PTH group） and elcatonin group （CT group）, with the ratio of 3：1. Patients in PTH group received a daily subcutaneous injection of 20μg rhPTH （1-34） for 18 months, while patients in CT group received a weekly intramuscular injection of 20U elcatonin for 12 months. The bone mineral density （BMD） of the lumbar vertebrae 2-4 （L2~） and the femoral neck, blood calcium and phosphorus, urinary calcium, serum bone specific alkaline phosphatase （BSAP）, and urinary c-terminal telopeptides of type I collagen （CTX-I） were detected before the treatment and at the 6^th month, the 12th month, and the 18^th month after the treatment. Results Compared with those at the baseline, BMD of L2-4 in PTH group increased significantly at the 6^th , the 12^th , and the 18th month after the treatment. BMD of the femoral neck increased significantly at the 18^th month after the treatment, while BSAP increased significantly at the 6^th month and the 12＇h month after the treatment, and the correction value of CTX-I increased significantly at the 6^th month, the 12^th month, and the 18th month. In CT group, BMD of the L224 increased significantly at the 12^th month. BMD of the femoral neck increased significantly at the 12^th month and the 18th month, while BSAP decreased significantly at the 12^th month and the 18^th month, and no significant difference of the correction value of CTX-I before and after the treatment was observed. The comparison between 2 groups showed that the improvement of BMD of the LE2-4 and growth rate at the 6th month, the 12^th month, and the 18^th month in PTHgroup were higher than that in CT group. However, the increase of BMD of the femoral neck and growth rate at the 12^th month and the 18th month in CT group were higher than that in PTH group. There was no significant difference of the rate of adverse events between 2 groups. Nevertheless, there was a transient hypercalcemia in PTH group. Conclusion The application of rhPTH （1-34） is safe and effective in the treatment of primary OP. It is superior to calcitonin on improving BMD of the Vertebrae in onset time, growth rate, and growth range, but inferior to calcitonin on improving BMD of the femoral neck.