Reginster J Y, Deroisy R, Lecart M P, Sarlet N, Zegels B, Jupsin I, de Longueville M, Franchimont P
Centre Universitaire d'Investigation du Métabolisme Osseux et du Cartilage Articulaire (CIMOCA), Université de Liège, Belgium.
Am J Med. 1995 May;98(5):452-8. doi: 10.1016/S0002-9343(99)80344-1.
Nasal administration of salmon calcitonin (SCT) has been suggested for preventing trabecular bone loss during the first years following the menopause, but no conclusive evidence has appeared about the minimal effective dose. Since nasal calcitonin is highly expensive, it makes sense to define this dose.
We performed a double-blind, placebo-controlled, randomized, single-center study with a 3-arm parallel-group design. The subjects were 251 healthy women who had experienced natural menopause within the past 6 to 72 months and were not affected by any diseases or treatments that interfere with calcium metabolism. They were randomly allocated in groups of 6 to receive intranasal SCT 50 IU (n = 84), SCT 200 IU (n = 84), or placebo (n = 83). All treatments were given on 5 consecutive days per week. Statistical analysis was based on two populations: intention-to-treat (IT) and valid completers (VC). The main assessments performed were bone mineral density of the lumbar spine (LSBMD) and biochemical parameters reflecting bone turnover (serum alkaline phosphatase, urinary calcium/creatinine, and hydroxyproline/creatinine ratios).
Changes over the treatment period were comparable in the IT and VC populations. In the group receiving the placebo, LSBMD decreased from baseline to end point by a mean of 6.28% (95% confidence interval [CI] -7.69 to -4.89) in the IT population and 6.98% (95% CI -8.86 to -5.11) in the VC population (P = 0.0001, end LSBMD versus baseline LSBMD). LSBMD increased slightly with the 50-IU/d dose of SCT, by 0.82% (95% CI -0.26 to 1.89) in the IT population, and 0.51% (95% CI -0.69 to 1.72) in the VC (P = NS, versus baseline). Subjects who received SCT 200 IU/d experienced significant increases of 2.03% (95% CI 0.92 to 3.15) in the IT population and 2.26% (95% CI 1.01 to 3.51) in the VC (both P = 0.001). The difference between the evolution of the combined groups receiving nasal SCT and the group treated with the placebo was highly significant (P = 0.0001). No significant changes were recorded in biochemical parameters reflecting bone turnover.
SCT 50 IU/d administered nasally and intermittently appears to prevent lumbar bone loss in nonobese early postmenopausal women.
有人提出经鼻给予鲑鱼降钙素（SCT）可预防绝经后最初几年的小梁骨丢失，但关于最小有效剂量尚无确凿证据。由于鼻用降钙素价格昂贵，确定该剂量是有意义的。
我们进行了一项双盲、安慰剂对照、随机、单中心研究，采用三臂平行组设计。受试者为251名健康女性，她们在过去6至72个月内经历了自然绝经，且未受任何干扰钙代谢的疾病或治疗影响。她们被随机分成每组6人，分别接受鼻内给予50 IU SCT（n = 84）、200 IU SCT（n = 84）或安慰剂（n = 83）。所有治疗每周连续给药5天。统计分析基于两个总体：意向性治疗（IT）和有效完成者（VC）。主要进行的评估是腰椎骨密度（LSBMD）和反映骨转换的生化参数（血清碱性磷酸酶、尿钙/肌酐和羟脯氨酸/肌酐比值）。
治疗期间IT和VC总体的变化具有可比性。在接受安慰剂的组中，IT总体的LSBMD从基线到终点平均下降6.28%（95%置信区间[CI] -7.69至-4.89），VC总体下降6.98%（95% CI -8.86至-5.11）（P = 0.0001，终点LSBMD与基线LSBMD相比）。50 IU/d剂量的SCT使LSBMD略有增加，IT总体增加0.82%（95% CI -0.26至1.89），VC总体增加0.51%（95% CI -0.69至1.72）（P =无统计学意义，与基线相比）。接受200 IU/d SCT的受试者，IT总体显著增加2.03%（95% CI 0.92至3.15），VC总体增加2.26%（95% CI 1.01至3.51）（两者P = 0.001）。接受鼻内SCT的联合组与接受安慰剂治疗组的变化差异非常显著（P = 0.0001）。反映骨转换的生化参数未记录到显著变化。
经鼻间歇性给予50 IU/d的SCT似乎可预防非肥胖绝经后早期妇女的腰椎骨丢失。
