Department of Musculoskeletal Regenerative Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Osaka, Suita 565-0871, Japan; Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, Suita 565-0871, Japan.
Department of Orthopaedic Surgery, Osaka Rosai Hospital, 1179-3 Nagasone-cho, Sakai, Kita-ku 591-8025, Japan.
Joint Bone Spine. 2021 Oct;88(5):105219. doi: 10.1016/j.jbspin.2021.105219. Epub 2021 May 19.
To investigate the effects of prior treatment and determine the predictors of a 12-month treatment response of romosozumab (ROMO) in 148 patients with postmenopausal osteoporosis.
In this prospective, observational, and multicenter study, treatment naïve patients (Naïve; n=50) or patients previously treated with bisphosphonates (BP; n=37) or denosumab (DMAb; n=45) or teriparatide (TPTD; n=16) (mean age, 75.0 years; T-scores of the lumbar spine [LS] -3.2 and total hip [TH] -2.6) were switched to ROMO due to insufficient effects of prior treatment. Bone mineral density (BMD) and serum bone turnover markers were evaluated for 12 months.
At 12 months, changes in LS BMD were Naïve (18.2%), BP (10.2%), DMAb (6.4%), and TPTD (11.2%) (P<0.001 between groups) and changes in TH BMD were Naïve (5.6%), BP (3.3%), DMAb (0.6%), and TPTD (4.4%) (P<0.01 between groups), respectively. In all groups, the LS BMD significantly increased from baseline at 6 and 12 months, although only the DMAb group failed to obtain a significant increase in TH BMD during 12-month treatment. Mean values of N-terminal type I procollagen propeptide (PINP; μg/L) from baseline → 1 month → 12 months were Naïve (67.9 → 134.1 → 51.0), BP (32. 2 → 81.7 → 40.9), DMAb (30.4 → 56.2 → 75.3), and TPTD (97.4 → 105.1 → 37.1), and those of isoform 5b of tartrate-resistant acid phosphatase (TRACP-5b; mU/dL) were Naïve (500.4 → 283.8 → 267.1), BP (273.4 → 203.1 → 242.0), DMAb (220.3 → 246.1 → 304.8), and TPTD (446.6 → 305.1 → 235.7), respectively. Multiple regression analysis revealed that the significant predictors of BMD change at 12 months were difference of prior treatment (r=-2.8, P<0.001) and value of PINP at 1 month (r=0.04, P<0.01) for LS, and difference of prior treatment (r=-1.3, P<0.05) and percentage change of TRACP-5b at 1 month (r=-0.06, P<0.05) for TH.
The early effects of ROMO on LS and TH BMD increase at 12 months were significantly affected by the difference of prior treatment and are predicted by the early change in bone turnover markers.
探讨既往治疗的影响，并确定 148 例绝经后骨质疏松症患者使用罗莫佐单抗（ROMO）治疗 12 个月的治疗反应的预测因素。
在这项前瞻性、观察性和多中心研究中，由于先前治疗效果不佳，治疗初治患者（初治组；n=50）或先前接受过双膦酸盐（BP）治疗的患者（n=37）、地舒单抗（DMAb；n=45）或特立帕肽（TPTD；n=16）治疗的患者（平均年龄 75.0 岁；腰椎（LS）骨密度 T 评分-3.2，全髋（TH）骨密度 T 评分-2.6）被转换为 ROMO。在 12 个月时评估骨矿物质密度（BMD）和血清骨转换标志物。
12 个月时，LS BMD 变化在初治组（18.2%）、BP 组（10.2%）、DMAb 组（6.4%）和 TPTD 组（11.2%）（各组间 P<0.001），TH BMD 变化在初治组（5.6%）、BP 组（3.3%）、DMAb 组（0.6%）和 TPTD 组（4.4%）（各组间 P<0.01）。在所有组中，LS BMD 在 6 个月和 12 个月时均较基线显著增加，尽管仅 DMAb 组在 12 个月治疗期间未能使 TH BMD 显著增加。N 端 I 型原胶原肽（PINP）的平均值从基线到 1 个月到 12 个月在初治组（67.9→134.1→51.0）、BP 组（32.2→81.7→40.9）、DMAb 组（30.4→56.2→75.3）和 TPTD 组（97.4→105.1→37.1），抗酒石酸酸性磷酸酶 5b 同工酶（TRACP-5b）的平均值在初治组（500.4→283.8→267.1）、BP 组（273.4→203.1→242.0）、DMAb 组（220.3→246.1→304.8）和 TPTD 组（446.6→305.1→235.7）。多元回归分析显示，12 个月时 BMD 变化的显著预测因素是既往治疗的差异（r=-2.8，P<0.001）和 1 个月时 PINP 值（r=0.04，P<0.01）LS，以及既往治疗的差异（r=-1.3，P<0.05）和 1 个月时 TRACP-5b 的百分比变化（r=-0.06，P<0.05）TH。
ROMO 对 LS 和 TH BMD 的早期影响在 12 个月时显著受既往治疗差异的影响，并由骨转换标志物的早期变化预测。
