3 months vs 12 months of romosozumab for postmenopausal osteoporosis (LIDA): an open-label, non-inferiority, randomised controlled trial.

The most recently introduced osteoporosis medication is romosozumab, a monoclonal antibody with a unique mechanism of action that increases bone mineral density (BMD) more than other agents by both stimulating new bone formation and inhibiting resorption.

最新引入的骨质疏松症药物是罗莫索单抗，这是一种具有独特作用机制的单克隆抗体，通过刺激新骨形成和抑制骨吸收，比其他药物更能增加骨矿物质密度（BMD）。

The drug's stimulation of bone formation, however, wanes after several months.

然而，该药物刺激骨形成的效应在几个月后会减弱。

The use of romosozumab is limited by cost, the inconvenience of monthly clinic-administered injections, and its cardiovascular risk profile.

罗莫佐单抗的使用受到成本、每月需在诊所进行注射的不便以及其心血管风险特征的限制。

In this trial, we aimed to test the hypothesis that a shorter course of romosozumab might be equally effective as the standard regimen.

在这项试验中，我们的目标是检验一个假设，即较短疗程的罗莫佐单抗可能与标准方案同样有效。

Methods

We did a 12-month, prospective, open-label, randomised, controlled, non-inferiority trial of 50 postmenopausal women at high risk of fracture.

我们进行了一项为期12个月的前瞻性、开放标签、随机、对照、非劣效试验，共有50名高骨折风险的绝经后妇女参与。

The study was done at a single academic medical centre in the USA.

该研究在美国的一家学术医疗中心进行。

Participants were randomly assigned to receive 3 months of romosozumab (210 mg by subcutaneous injection, monthly) followed by 9 months of denosumab (60 mg by subcutaneous injection, every 6 months; 3-month ROMO group) or 12 months of romosozumab (12-month ROMO group).

参与者被随机分配接受3个月的罗莫索珠单抗（210毫克，皮下注射，每月一次）治疗，随后接受9个月的地诺塞麦（60毫克，皮下注射，每六个月一次；3个月ROMO组），或者接受12个月的罗莫索珠单抗（12个月ROMO组）。

The primary endpoint was the percentage change in total hip BMD.

主要终点是髋部总体骨密度（BMD）的百分比变化。

The non-inferiority threshold was set at 2%.

非劣效性阈值设定为2%。

The trial was registered at ClinicalTrials.gov, NCT05010590.

该试验已在ClinicalTrials.gov注册，注册号为NCT05010590。

Results

Between March 2, 2022, and May 2, 2023, we screened 188 participants.

在2022年3月2日至2023年5月2日期间，我们筛选了188名参与者。

Of those, 102 (54%) were ineligible and 36 (19%) declined to participate.

在这些患者中，有102名（54%）不符合条件，另有36名（19%）拒绝参与。

We randomly assigned 50 participants to either the 3-month ROMO group (24 [48%] participants) or the 12-month ROMO group (26 [52%] participants).

我们随机将50名参与者分配到3个月ROMO组（24名，占48%）或12个月ROMO组（26名，占52%）。

Study participants completing at least one post-baseline visit were included in the analysis (modified intention-to-treatanalysis).

完成至少一次基线后随访的研究参与者被纳入分析（修改后的意向治疗分析）。

The mean age of participants was 69·6 years (SD 4·5).

参与者的平均年龄为69.6岁（标准差4.5岁）。

The mean 12-month change in total hip BMD was 5·7% (SD 3·3) in the 3-month romosozumab group and 6·0% (3·2) in the 12-month romosozumab group, meeting the prespecified non-inferiority threshold.

在为期3个月的罗莫索珠单抗组中，12个月髋部骨密度（BMD）的平均变化为5.7%（标准差3.3），而在为期12个月的罗莫索珠单抗组中，这一变化为6.0%（标准差3.2），达到了预先设定的非劣效性阈值。

Adverse events (back pain, cough, fatigue, headache, joint pain, muscle cramps, muscle pain, palpitations, paraesthesia, reaction at injection site, rhinorrhoea, skin rash, and swelling) were balanced between groups.

两组之间的不良事件（背痛、咳嗽、疲劳、头痛、关节痛、肌肉痉挛、肌肉痛、心悸、感觉异常、注射部位反应、流鼻涕、皮疹和肿胀）是平衡的。

interpretation

In postmenopausal women at high risk of fracture, 3 months of romosozumab followed by 9 months of denosumab was non-inferior to 12 months of romosozumab in increasing total hip BMD.

在高骨折风险的绝经后妇女中，3个月的罗莫索珠单抗后接9个月的地舒伐单抗治疗，在增加总髋关节骨密度方面，与12个月的罗莫索珠单抗治疗相比，具有非劣效性。

Given the expense, injection burden, and potential adverse effects of romosozumab, this abbreviated approach could broaden access to this uniquely effective therapy.

鉴于罗莫索珠单抗的费用、注射负担以及潜在的不良反应，这种简化的治疗方案可能会扩大对这种独特有效疗法的可及性。

funding

US National Institute of Arthritis and Musculoskeletal and Skin Diseases and US National Center for Advancing Translational Science.

美国国家关节炎、肌肉骨骼和皮肤病研究所以及美国国家转化科学促进中心。