绝经后骨质疏松症女性中，通过组织厚度校正的骨小梁骨评分评估地舒单抗对骨微结构的长期影响：来自 FREEDOM 及其开放标签扩展的结果。

Long-term effect of denosumab on bone microarchitecture as assessed by tissue thickness-adjusted trabecular bone score in postmenopausal women with osteoporosis: results from FREEDOM and its open-label extension.

机构信息

Interdiciplinary Center of Bone Diseases, Lausanne University Hospital and Lausanne University, Av. Pierre Decker 4, 1011, Lausanne, Switzerland.

Amgen Inc., Thousand Oaks, CA, USA.

出版信息

Osteoporos Int. 2023 Jun;34(6):1075-1084. doi: 10.1007/s00198-023-06708-8. Epub 2023 Mar 2.

UNLABELLED

In postmenopausal women with osteoporosis, up to 10 years of denosumab treatment significantly and continuously improved bone microarchitecture assessed by tissue thickness-adjusted trabecular bone score, independently of bone mineral density. Long-term denosumab treatment decreased the number of high fracture-risk patients and shifted more patients to lower fracture-risk categories.

PURPOSE

To investigate the long-term effect of denosumab on bone microarchitecture assessed by tissue thickness-adjusted trabecular bone score (TBS) in post-hoc subgroup analysis of FREEDOM and open-label extension (OLE).

METHODS

Postmenopausal women with lumbar spine (LS) or total hip BMD T-score <-2.5 and ≥-4.0 who completed the FREEDOM DXA substudy and continued in OLE were included. Patients received either denosumab 60 mg subcutaneously every 6 months for 3 years and same-dose open-label denosumab for 7 years (long-term denosumab; n=150) or placebo for 3 years and open-label denosumab for 7 years (crossover denosumab; n=129). BMD and TBS were assessed on LS DXA scans at FREEDOM baseline, month 1, and years 1-6, 8, and 10.

RESULTS

In long-term denosumab group, continued increases from baseline to years 4, 5, 6, 8, and 10 in BMD (11.6%, 13.7%, 15.5%, 18.5%, and 22.4%) and TBS (3.2%, 2.9%, 4.1%, 3.6%, and 4.7%) were observed (all P < 0.0001). Long-term denosumab treatment decreased the proportion of patients at high fracture-risk (according to TBS and BMD T-score) from baseline up to year 10 (93.7 to 40.4%), resulting in increases in the proportions at medium-risk (6.3 to 53.9%) and low-risk (0 to 5.7%) (P < 0.0001). Similar responses were observed in crossover denosumab group. Changes in BMD and TBS were poorly correlated during denosumab treatment.

CONCLUSION

In postmenopausal women with osteoporosis, up to 10 years of denosumab significantly and continuously improved bone microarchitecture assessed by TBS, independently of BMD, and shifted more patients to lower fracture-risk categories.

未注明

在患有骨质疏松症的绝经后妇女中，长达 10 年的地舒单抗治疗可显著且持续地改善骨微结构，这通过组织厚度调整的骨小梁骨评分（TBS）来评估，与骨密度无关。长期使用地舒单抗可减少高骨折风险患者的数量，并使更多患者转移到低骨折风险类别。

目的

在 FREEDOM 和开放标签扩展（OLE）的事后亚组分析中，研究地舒单抗对骨微结构的长期影响，通过 TBS 进行评估。

方法

纳入腰椎（LS）或全髋骨密度 T 评分 <-2.5 且≥-4.0 且完成 FREEDOM DXA 子研究并继续接受 OLE 的绝经后妇女。患者接受地舒单抗 60mg 皮下注射，每 6 个月一次，持续 3 年，然后接受 7 年相同剂量的开放标签地舒单抗（长期地舒单抗；n=150）或安慰剂治疗 3 年，然后接受 7 年开放标签地舒单抗（交叉地舒单抗；n=129）。在 FREEDOM 基线、第 1 个月以及第 1、2、3、4、5、6、8 和 10 年时，通过 LS DXA 扫描评估骨密度和 TBS。

结果

在长期地舒单抗组中，从基线到第 4、5、6、8 和 10 年，骨密度（11.6%、13.7%、15.5%、18.5%和 22.4%）和 TBS（3.2%、2.9%、4.1%、3.6%和 4.7%）持续增加（均 P < 0.0001）。长期地舒单抗治疗可降低高骨折风险（根据 TBS 和骨密度 T 评分）患者的比例，从基线到第 10 年，从 93.7%降至 40.4%，导致中风险（6.3%至 53.9%）和低风险（0%至 5.7%）的比例增加（P < 0.0001）。在交叉地舒单抗组中也观察到类似的反应。在地舒单抗治疗期间，骨密度和 TBS 的变化相关性较差。