IDIM, Instituto de Diagnóstico e Investigaciones Metabólicas, Libertad 836, (P.C:1012), Buenos Aires, Argentina.
Cátedra de Osteología y Metabolismo Mineral, Universidad del Salvador, Buenos Aires, Argentina.
Osteoporos Int. 2018 Jan;29(1):41-47. doi: 10.1007/s00198-017-4242-6. Epub 2017 Oct 3.
We evaluate 38 elderly women who had received long-term denosumab treatment after stopping the drug. Taking into account the gain during treatment and the loss after stopping treatment, they lost 35.5% of the total gain in the spine, 44.6% of the total gain in the femoral neck, and 103.3% in the total hip.
Denosumab (DMAb) is a soluble inhibitor of the receptor activator of nuclear factor-kappaB ligand (RANKL) and, therefore, does not incorporate into the bone matrix. Consistently, DMAb discontinuation is associated with reversal of the effects attained with treatment.
The aim of this study is to assess changes in BMD after a year of discontinuation of DMAb in a group of postmenopausal women treated with DMAb for 7 or 10 years. Secondly, is to evaluate the occurrence of fragility fractures.
Women who had participated in the FREEDOM study and its extension were invited to participate in this follow-up study. BMD at LS and hip and spine X-rays were obtained. Results were compared to the last value obtained while in treatment to assess changes after discontinuation.
Thirty-eight women, mean age: 81 ± 3.4 years completed study procedures; none had received bisphosphonates after stopping DMAb. Mean gap time between DMAb last dose and the follow-up visit was 17 months (range 16-20 months). Bone mineral density (BMD) decreased significantly in all regions: - 8.1% in LS, - 6% in FN, and - 8.4% in TH. Five (5/38, 13.15%) patients had a fragility fracture, one suffered a wrist fracture, and four experienced vertebral fractures. Three patients suffered one vertebral fracture and one of them had two vertebral fractures. Laboratory results showed the following mean values: CTX = 996 ± 307 pg/ml (normal values 550 ± 226 pg/ml); osteocalcin = 55.2 ± 18.6 ng/ml (normal value 42 ng/ml); and 25 OH vitamin D = 23.7 ± 6.9 ng/ml.
Our results describe the rapid bone loss occurring after cessation of denosumab treatment. Further studies are needed to assess if patients have a higher risk of fracture after stopping DMAb and if so, which patients have the highest risk, and assess the role of transitioning to bisphosphonates in the long term.
本研究旨在评估接受地舒单抗（DMAb）治疗 7 年或 10 年的绝经后妇女在停止治疗 1 年后 BMD 的变化。其次，评估脆性骨折的发生情况。
参加 FREEDOM 研究及其扩展的妇女被邀请参加这项随访研究。测量 LS 和髋部及脊柱 X 线的 BMD。将结果与最后一次治疗时获得的数值进行比较，以评估停药后的变化。
38 名女性（平均年龄 81 ± 3.4 岁）完成了研究程序；停药后均未接受双膦酸盐治疗。DMAb 末次剂量与随访时间间隔的平均时间为 17 个月（范围 16-20 个月）。所有部位的骨密度（BMD）均显著下降：LS 下降-8.1%，FN 下降-6%，TH 下降-8.4%。5 例（5/38，13.15%）患者发生脆性骨折，1 例腕部骨折，4 例椎体骨折。3 例患者发生 1 例椎体骨折，其中 1 例发生 2 例椎体骨折。实验室结果显示以下平均值：CTX = 996 ± 307 pg/ml（正常值 550 ± 226 pg/ml）；骨钙素= 55.2 ± 18.6 ng/ml（正常值 42 ng/ml）；25 羟维生素 D = 23.7 ± 6.9 ng/ml。
我们的研究结果描述了停止地舒单抗治疗后迅速发生的骨丢失。需要进一步研究以评估患者停止使用 DMAb 后骨折风险是否增加，如果是，哪些患者的风险最高，并评估在长期使用中过渡到双膦酸盐的作用。
