Bagger Yu Z, Tankó László B, Alexandersen Peter, Karsdal Morten A, Olson Melvin, Mindeholm Linda, Azria Moïse, Christiansen Claus
Center for Clinical and Basic Research, Ballerup Byvej 222, DK-2750 Ballerup, Denmark.
Bone. 2005 Sep;37(3):425-30. doi: 10.1016/j.bone.2005.04.032.
To assess the efficacy of 3 months of oral salmon calcitonin (sCT) on cartilage degradation as estimated by the changes in the urinary excretion of C-terminal telopeptide of collagen type II (CTX-II), and to investigate whether the response of oral sCT to urinary CTX-II depends on the baseline level of cartilage turnover.
This was a randomized, double blind, placebo-controlled clinical setting including 152 Danish postmenopausal women aged 55-85. The subjects received treatment with the different doses of sCT (0.15, 0.4, 1.0, or 2.5 mg) combined with Eligen technology-based carrier molecule (200 mg), or placebo for 3 months. The efficacy parameter was the changes in the 24-h excretion of urinary CTX-I/II corrected for creatinine excretion at month 3.
sCT induced a significant dose-dependent decrease in 24-h urinary CTX-II excretion. Similar dose-dependent responses were found in 24-h urinary CTX-I. When stratifying the study population into tertiles of baseline urinary CTX-II, the present osteoarthritic symptoms and definite cases of osteoarthritis (OA) were significantly more frequent in women in the highest tertile of CTX-II (mean 391 +/- 18 ng/mmol). Women who received 1.0 mg of sCT and had the highest cartilage turnover presented the greatest decrease in urinary CTX-II after 3 months of treatment.
In addition to its pronounced effect on bone resorption, this novel oral sCT formulation may also reduce cartilage degradation and thereby provide therapeutic benefit in terms of chondroprotection. Women with high cartilage turnover are more likely to benefit from oral sCT treatment.
通过II型胶原C端肽(CTX-II)尿排泄量的变化评估口服鲑鱼降钙素(sCT)3个月对软骨降解的疗效,并研究口服sCT对尿CTX-II的反应是否取决于软骨转换的基线水平。
这是一项随机、双盲、安慰剂对照的临床研究,纳入152名年龄在55 - 85岁的丹麦绝经后女性。受试者接受不同剂量的sCT(0.15、0.4、1.0或2.5毫克)与基于Eligen技术的载体分子(200毫克)联合治疗,或接受安慰剂治疗3个月。疗效参数为第3个月时校正肌酐排泄后的24小时尿CTX-I/II排泄量的变化。
sCT导致24小时尿CTX-II排泄量显著呈剂量依赖性下降。在24小时尿CTX-I中也发现了类似的剂量依赖性反应。将研究人群按基线尿CTX-II三分位数分层时,CTX-II最高三分位数的女性中,目前的骨关节炎症状和确诊的骨关节炎(OA)病例明显更常见(平均391 +/- 18纳克/毫摩尔)。接受1.0毫克sCT且软骨转换率最高的女性在治疗3个月后尿CTX-II下降幅度最大。
除了对骨吸收有显著作用外,这种新型口服sCT制剂还可能减少软骨降解,从而在软骨保护方面提供治疗益处。软骨转换率高的女性更有可能从口服sCT治疗中获益。