Eastell Richard, Brown Jacques P, Adler Robert A, Lewiecki E Michael, Binkley Neil, Orwoll Eric S, Kendler David, Mitlak Bruce H, Wang Yamei
Department of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield S10 2RX, South Yorkshire, United Kingdom.
Department of Medicine, Centre de recherche du CHU de Québec, Laval University, Quebec, QC G1V 0A6, Canada.
J Bone Miner Res. 2025 Mar 15;40(3):315-322. doi: 10.1093/jbmr/zjaf003.
Early increases in bone turnover markers (BTMs) in response to anabolic therapy correlate with 18-mo BMD increases in postmenopausal women with osteoporosis; however, this relationship has not been assessed in men. In this analysis, the correlation between changes from baseline in fasting intact serum procollagen type I N propeptide (PINP) and serum CTX at 1, 3, 6, and 12 mo and percent increase from baseline in BMD at 12 mo in men from the randomized phase 3 ATOM study (NCT03512262) were evaluated using Pearson's correlation coefficients. The uncoupling index (UI), a measure of the balance between markers of bone formation (PINP) and bone resorption (CTX), with positive UI favoring bone formation, was calculated. Results in men were compared to 12-mo results for women from the ACTIVE study using the z score test after Fisher's Z transformation. In abaloparatide-treated men, PINP increases at 1 mo (r = 0.485), 3 mo (r = 0.614), 6 mo (r = 0.632), and 12 mo (r = 0.521) were highly correlated (p < .0001) with 12-mo LS BMD increases. The mean UI for abaloparatide-treated men was greater than placebo as early as 1 mo (2.26 vs -0.25). At month 3, the mean UI for men was greater (1.32) than for women (0.88) (p < .001). There was a significant correlation between 3-mo UI and LS BMD at 12 mo in both men (r = 0.453; p < .001) and women (r = 0.252; p < .01). UI at months 6 and 12 were also significantly correlated with 12-mo LS BMD in men and women, but the correlation was stronger in men than women. These data support that early changes in BTMs in men treated with abaloparatide are associated with subsequent changes in BMD similar to what has been reported in women.
在骨质疏松症的绝经后女性中，骨转换标志物（BTMs）对合成代谢疗法的早期升高与18个月的骨密度（BMD）增加相关；然而，这种关系尚未在男性中进行评估。在本分析中，使用Pearson相关系数评估了来自随机3期ATOM研究（NCT03512262）的男性在1、3、6和12个月时空腹完整血清I型前胶原N端前肽（PINP）和血清CTX相对于基线的变化与12个月时BMD相对于基线的百分比增加之间的相关性。计算了解偶联指数（UI），这是一种衡量骨形成标志物（PINP）和骨吸收标志物（CTX）之间平衡的指标，UI为正时有利于骨形成。在Fisher Z变换后，使用z分数检验将男性的结果与ACTIVE研究中女性的12个月结果进行比较。在接受阿巴洛肽治疗的男性中，1个月（r = 0.485）、3个月（r = 0.614）、6个月（r = 0.632）和12个月（r = 0.521）时PINP的增加与12个月时腰椎BMD的增加高度相关（p <.0001）。接受阿巴洛肽治疗的男性的平均UI早在1个月时就大于安慰剂组（2.26对 -0.25）。在第3个月时，男性的平均UI（1.32）大于女性（0.88）（p <.001）。在男性（r = 0.453；p <.001）和女性（r = 0.252；p <.01）中，3个月时的UI与12个月时的腰椎BMD之间均存在显著相关性。6个月和12个月时的UI与男性和女性12个月时的腰椎BMD也显著相关，但男性中的相关性强于女性。这些数据支持，接受阿巴洛肽治疗的男性中BTMs的早期变化与随后BMD的变化相关，这与在女性中报道的情况类似。
