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Abstract：
BACKGROUND: The comparative effectiveness of denosumab and zoledronic acid for adult patients with osteogenesis imperfecta (OI) has not been established.
OBJECTIVE: To evaluate the efficacy and safety of denosumab and zoledronic acid in adult patients with OI.
METHODS: This was a prospective, open-label study. Patients were randomized to receive denosumab 60 mg every 6 months or zoledronic acid 5 mg once for 12 months. Pathogenic mutations of OI were identified by next-generation sequencing and confirmed by Sanger sequencing. Percentage changes in the areal bone mineral density (aBMD), trabecular bone score (TBS), and bone turnover biomarkers (BTMs) from baseline to 6 and 12 months of treatment, as well as safety, were evaluated.
RESULTS: A total of 51 adults with OI (denosumab: 25, zoledronic acid: 26) were included, of whom 49 patients had identified pathogenic mutations. At 12 months, aBMD at the lumbar spine and total hip significantly increased by 4.34% (P = .005) and 1.45% (P = .023) in the denosumab group and by 4.92% (P = .006) and 2.02% (P = .016) in the zoledronic acid group, respectively. TBS showed an increasing trend by 1.39% and 2.70% in denosumab and zoledronic acid groups, respectively. Serum levels of β-isomerized carboxy-telopeptide of type I collagen and alkaline phosphatase markedly decreased after denosumab treatment. Percentage changes in aBMD, TBS, and BTMs during the treatment were similar between the 2 groups. Patients with OI with milder phenotypes showed a significantly higher increase in the TBS after 12 months of denosumab treatment than those with more severe phenotypes (P = .030). During the study period, the denosumab group had fewer adverse events than the zoledronic acid group.
CONCLUSIONS: Denosumab effectively increases aBMD in adults with OI, with similar efficacy to zoledronic acid. Long-term and large-sample studies are needed to confirm the antifracture efficacy and safety of denosumab in adult patients with OI.
OBJECTIVE: To evaluate the efficacy and safety of denosumab and zoledronic acid in adult patients with OI.
METHODS: This was a prospective, open-label study. Patients were randomized to receive denosumab 60 mg every 6 months or zoledronic acid 5 mg once for 12 months. Pathogenic mutations of OI were identified by next-generation sequencing and confirmed by Sanger sequencing. Percentage changes in the areal bone mineral density (aBMD), trabecular bone score (TBS), and bone turnover biomarkers (BTMs) from baseline to 6 and 12 months of treatment, as well as safety, were evaluated.
RESULTS: A total of 51 adults with OI (denosumab: 25, zoledronic acid: 26) were included, of whom 49 patients had identified pathogenic mutations. At 12 months, aBMD at the lumbar spine and total hip significantly increased by 4.34% (P = .005) and 1.45% (P = .023) in the denosumab group and by 4.92% (P = .006) and 2.02% (P = .016) in the zoledronic acid group, respectively. TBS showed an increasing trend by 1.39% and 2.70% in denosumab and zoledronic acid groups, respectively. Serum levels of β-isomerized carboxy-telopeptide of type I collagen and alkaline phosphatase markedly decreased after denosumab treatment. Percentage changes in aBMD, TBS, and BTMs during the treatment were similar between the 2 groups. Patients with OI with milder phenotypes showed a significantly higher increase in the TBS after 12 months of denosumab treatment than those with more severe phenotypes (P = .030). During the study period, the denosumab group had fewer adverse events than the zoledronic acid group.
CONCLUSIONS: Denosumab effectively increases aBMD in adults with OI, with similar efficacy to zoledronic acid. Long-term and large-sample studies are needed to confirm the antifracture efficacy and safety of denosumab in adult patients with OI.
摘要：
目的：评价地诺塞马和唑来膦酸治疗成人OI的疗效和安全性。
方法：这是一个前瞻性的，开放标签研究。患者随机接受denosumab60mg每6个月或唑来膦酸5mg一次，为期12个月。通过下一代测序鉴定OI的致病突变，并通过Sanger测序确认。区域骨矿物质密度（aBMD）的百分比变化，骨小梁评分（TBS）和骨转换生物标志物（BTMs）从基线到6和12个月的治疗，以及安全,进行了评估。
结果：共纳入51例OI成人（地诺塞马：25，唑来膦酸：26），其中49例患者已鉴定出致病性突变。12个月时,denosumab组腰椎和全髋关节的aBMD分别增加4.34%(P=0.005)和1.45%(P=0.023)，唑来膦酸组分别增加4.92%(P=0.006)和2.02%(P=0.016)，分别。在地诺单抗和唑来膦酸组中,TBS分别为1.39%和2.70%,分别。denosumab治疗后血清β-CTX和ALP水平显着降低。aBMD的百分比变化，两组治疗期间的TBS和BTM相似。Denosumab治疗12个月后，表型较温和的OI患者的TBS增加明显高于表型较严重的患者（P=0.030）。在学习期间,地诺单抗组的不良事件少于唑来膦酸组。
结论：Denosumab有效增加OI成人的aBMD，与唑来膦酸功效相似。需要长期和大样本研究来确认denosumab在成年OI患者中的抗骨折功效和安全性。
方法：这是一个前瞻性的，开放标签研究。患者随机接受denosumab60mg每6个月或唑来膦酸5mg一次，为期12个月。通过下一代测序鉴定OI的致病突变，并通过Sanger测序确认。区域骨矿物质密度（aBMD）的百分比变化，骨小梁评分（TBS）和骨转换生物标志物（BTMs）从基线到6和12个月的治疗，以及安全,进行了评估。
结果：共纳入51例OI成人（地诺塞马：25，唑来膦酸：26），其中49例患者已鉴定出致病性突变。12个月时,denosumab组腰椎和全髋关节的aBMD分别增加4.34%(P=0.005)和1.45%(P=0.023)，唑来膦酸组分别增加4.92%(P=0.006)和2.02%(P=0.016)，分别。在地诺单抗和唑来膦酸组中,TBS分别为1.39%和2.70%,分别。denosumab治疗后血清β-CTX和ALP水平显着降低。aBMD的百分比变化，两组治疗期间的TBS和BTM相似。Denosumab治疗12个月后，表型较温和的OI患者的TBS增加明显高于表型较严重的患者（P=0.030）。在学习期间,地诺单抗组的不良事件少于唑来膦酸组。
结论：Denosumab有效增加OI成人的aBMD，与唑来膦酸功效相似。需要长期和大样本研究来确认denosumab在成年OI患者中的抗骨折功效和安全性。
