Background People with type 2 diabetes (T2D) are at high risk of fragility fractures; however, there are no randomized controlled trials evaluating the efficacy of anti-osteoporosis drugs as a primary pre-specified endpoint in T2D. Objectives To compare the efficacy of anti-osteoporotic drugs in postmenopausal women with T2D. Design Prospective, randomized, open, blinded endpoint clinical pilot trial. Methods Postmenopausal women (⩾50 years) with T2D (duration ⩾5 years), HbA1c 7-10%, eGFR ⩾45 mL/min/1.73 m2 and prior vertebral (clinical/morphometric), hip, radius, humeral fragility fracture or bone mineral density (BMD) T-score (adjusted for diabetes) at lumbar spine/femoral neck ⩽-2.5 and high FRAX score will be eligible for inclusion. Subjects with secondary causes of osteoporosis, prior exposure to bone-active therapies or history of use of glucocorticoids/pioglitazone/thiazides/canagliflozin will be excluded. Finally, eligible subjects will undergo estimation of serum calcium, phosphate, alkaline phosphatase, parathyroid hormone, 25-hydroxyvitamin D and bone turnover markers (BTMs) (total procollagen type I N-propeptide, β-CTX) along with trabecular bone score (TBS) and high-resolution peripheral quantitative computed tomography (HR-pQCT) of non-dominant hand and leg. After a 2-week run in phase, they will be randomized in a 1:1:1:1 ratio to receive yearly zoledronate, or biannually denosumab or daily teriparatide (in addition to standard of care, i.e., calcium 1000 mg/day and cholecalciferol 1000 IU/day) or only standard of care (control). The primary endpoints will be change in areal BMD and frequency of incident fractures at 18 months. The secondary endpoints will be change in HR-pQCT parameters, TBS and BTMs at 18 months. Adverse events will be recorded for all randomized participants. Ethics The study has been approved by the Institute Ethics Committee. Written informed consent will be obtained from each participant. Discussion The trial is expected to provide information regarding optimal anti-osteoporotic therapy in people with T2D and bone fragility. Registration Prospectively registered in Clinical Trial Registry of India (CTRI/2022/02/039978).

中文翻译：

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唑来膦酸盐、狄诺塞麦或特立帕肽对患有脆性骨折高风险 2 型糖尿病的绝经后女性的疗效：一项开放、盲法终点随机对照试验方案。

背景 2 型糖尿病 (T2D) 患者发生脆性骨折的风险很高；然而，尚无随机对照试验评估抗骨质疏松药物作为 T2D 主要预先指定终点的疗效。目的 比较抗骨质疏松药物对患有 T2D 的绝经后妇女的疗效。设计前瞻性、随机、开放、盲态终点临床试点试验。方法 患有 T2D（持续时间≥5 年）、HbA1c 7-10%、eGFR ≥45 mL/min/1.73 m2 且既往有椎骨（临床/形态测量）、髋部、桡骨、肱骨脆性骨折或骨骼的绝经后妇女（⩾50 岁）腰椎/股骨颈矿物质密度 (BMD) T 分数（针对糖尿病进行调整）⩽-2.5 和高 FRAX 分数将有资格纳入。患有继发性骨质疏松症、既往接受过骨活性治疗或有糖皮质激素/吡格列酮/噻嗪类/卡格列净使用史的受试者将被排除。最后，符合条件的受试者将接受血清钙、磷酸盐、碱性磷酸酶、甲状旁腺激素、25-羟基维生素 D 和骨转换标志物 (BTM)（总前胶原 I 型 N-前肽，β-CTX）以及小梁骨评分 (TBS) 的评估）和非优势手和腿的高分辨率外周定量计算机断层扫描（HR-pQCT）。经过 2 周的阶段性运行后，他们将以 1:1:1:1 的比例随机接受每年一次唑来膦酸治疗，或每两年一次地诺塞麦治疗或每日特立帕肽治疗（除了标准护理，即钙 1000 毫克/天和胆钙化醇 1000 IU/天）或仅标准护理（对照）。主要终点是 18 个月时面积 BMD 的变化和骨折发生频率。次要终点将是 18 个月时 HR-pQCT 参数、TBS 和 BTM 的变化。所有随机参与者的不良事件都将被记录。伦理 该研究已获得研究所伦理委员会的批准。每位参与者都将获得书面知情同意书。讨论 该试验预计将为患有 T2D 和骨脆性的患者提供最佳抗骨质疏松治疗的信息。注册 在印度临床试验注册中心前瞻性注册 (CTRI/2022/02/039978)。