Brown J P, Roux C, Ho P R, Bolognese M A, Hall J, Bone H G, Bonnick S, van den Bergh J P, Ferreira I, Dakin P, Wagman R B, Recknor C
CHU de Québec Research Centre and Laval University, Room S-763, 2705 Laurier Boulevard, Quebec City, QC, G1V 4G2, Canada,
Osteoporos Int. 2014 Jul;25(7):1953-61. doi: 10.1007/s00198-014-2692-7. Epub 2014 Mar 28.
Managing osteoporotic patients suboptimally adherent to bisphosphonates (BPs) is difficult. Such patients who remained at higher risk for fracture (≥1 risk factor) were transitioned to denosumab or a monthly oral BP. Denosumab-treated subjects had significantly greater increases in bone mineral density and decreases in bone turnover in this 12-month study.
A clinical need exists to manage patients who are suboptimally adherent to oral BPs and remain at higher risk for fracture. Here, we compare the effects on bone mineral density (BMD) and bone turnover of transitioning such patients to denosumab or monthly oral BP (ibandronate or risedronate).
In two previous multicenter, open-label studies, postmenopausal women ≥55 years previously treated with, though suboptimally adherent to, a daily or weekly BP were randomized to denosumab 60 mg subcutaneously every 6 months (N = 852) or oral BP 150 mg monthly (N = 851) for 12 months. In this combined post-hoc analysis, a subset of higher risk subjects was identified, and the percentage changes from baseline in BMD and serum C-telopeptide of type I collagen (sCTX-1) were assessed.
In the overall population, denosumab was associated with greater gains in BMD at 12 months than monthly oral BP at the total hip, femoral neck, and lumbar spine (p < 0.0001 for all). In higher risk subjects, denosumab led to greater gains in BMD than oral BPs at the total hip (2.2 vs 0.8 %), femoral neck (1.8 vs 0.3 %), and lumbar spine (3.7 vs 1.4 %) (p < 0.0001 for all). Denosumab also led to greater decreases in sCTX-1 in the overall population and higher risk subjects at months 1 and 6 (p < 0.0001 for both). Adverse events and serious adverse events were generally similar between treatment groups.
Transitioning to denosumab was well tolerated and more effective in increasing BMD and reducing bone turnover than cycling to a monthly oral BP treatment in subjects who remained at higher fracture risk despite suboptimal BP treatment.
对双膦酸盐（BP）治疗依从性欠佳的骨质疏松症患者进行管理颇具难度。此类骨折风险较高（≥1个风险因素）的患者转而接受地诺单抗或每月一次的口服BP治疗。在这项为期12个月的研究中，接受地诺单抗治疗的受试者骨矿物质密度显著增加，骨转换率降低。
对于口服BP治疗依从性欠佳且骨折风险较高的患者，临床管理存在需求。在此，我们比较了将此类患者转而接受地诺单抗或每月一次口服BP（伊班膦酸钠或利塞膦酸钠）治疗对骨矿物质密度（BMD）和骨转换的影响。
在之前两项多中心、开放标签研究中，年龄≥55岁、既往接受过每日或每周BP治疗但依从性欠佳的绝经后女性被随机分为两组，一组每6个月皮下注射60mg地诺单抗（N = 852），另一组每月口服150mg BP（N = 851），为期12个月。在这项合并的事后分析中，确定了一组高风险受试者，并评估了BMD和血清I型胶原C端肽（sCTX-1）相对于基线的百分比变化。
在总体人群中，12个月时地诺单抗组全髋关节、股骨颈和腰椎部位BMD的增加幅度大于每月口服BP组（所有部位p < 0.0001）。在高风险受试者中，地诺单抗组全髋关节（分别为2.2%对0.8%）、股骨颈（1.8%对0.3%）和腰椎（3.7%对1.4%）部位BMD的增加幅度大于口服BP组（所有部位p < 0.0001）。在第1个月和第6个月时，地诺单抗组总体人群和高风险受试者的sCTX-1降低幅度也更大（两者p < 0.0001）。治疗组之间的不良事件和严重不良事件总体相似。
对于尽管BP治疗依从性欠佳但骨折风险仍然较高的受试者，转而接受地诺单抗治疗耐受性良好，在增加BMD和降低骨转换方面比改为每月一次口服BP治疗更有效。
