Trupti Nagendra Prasad, Sanjay Kumar Bhadada, Veenu Singla, Neelam Aggarwal, Sant Ram, Uttam Chand Saini, Ashok Kumar, Rimesh Pal
{"title":"唑来膦酸盐、替诺沙单抗或特立帕肽治疗绝经后2型糖尿病脆性骨折高危妇女的疗效：一项开放、盲终点随机对照试验方案。","authors":"Trupti Nagendra Prasad, Sanjay Kumar Bhadada, Veenu Singla, Neelam Aggarwal, Sant Ram, Uttam Chand Saini, Ashok Kumar, Rimesh Pal","doi":"10.1177/20420188231207516","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>To compare the efficacy of anti-osteoporotic drugs in postmenopausal women with T2D.</p><p><strong>Design: </strong>Prospective, randomized, open, blinded endpoint clinical pilot trial.</p><p><strong>Methods: </strong>Postmenopausal women (⩾50 years) with T2D (duration ⩾5 years), HbA1c 7-10%, eGFR ⩾45 mL/min/1.73 m<sup>2</sup> and prior vertebral (clinical/morphometric), hip, radius, humeral fragility fracture <i>or</i> bone mineral density (BMD) T-score (adjusted for diabetes) at lumbar spine/femoral neck ⩽-2.5 <i>and</i> 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.</p><p><strong>Ethics: </strong>The study has been approved by the Institute Ethics Committee. Written informed consent will be obtained from each participant.</p><p><strong>Discussion: </strong>The trial is expected to provide information regarding optimal anti-osteoporotic therapy in people with T2D and bone fragility.</p><p><strong>Registration: </strong>Prospectively registered in Clinical Trial Registry of India (CTRI/2022/02/039978).</p>","PeriodicalId":22998,"journal":{"name":"Therapeutic Advances in Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":3.9000,"publicationDate":"2023-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/85/ae/10.1177_20420188231207516.PMC10590540.pdf","citationCount":"0","resultStr":"{\"title\":\"Efficacy of zoledronate, denosumab or teriparatide in postmenopausal women with type 2 diabetes mellitus at high risk of fragility fractures: protocol of an open, blinded endpoint randomized controlled pilot trial.\",\"authors\":\"Trupti Nagendra Prasad, Sanjay Kumar Bhadada, Veenu Singla, Neelam Aggarwal, Sant Ram, Uttam Chand Saini, Ashok Kumar, Rimesh Pal\",\"doi\":\"10.1177/20420188231207516\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>To compare the efficacy of anti-osteoporotic drugs in postmenopausal women with T2D.</p><p><strong>Design: </strong>Prospective, randomized, open, blinded endpoint clinical pilot trial.</p><p><strong>Methods: </strong>Postmenopausal women (⩾50 years) with T2D (duration ⩾5 years), HbA1c 7-10%, eGFR ⩾45 mL/min/1.73 m<sup>2</sup> and prior vertebral (clinical/morphometric), hip, radius, humeral fragility fracture <i>or</i> bone mineral density (BMD) T-score (adjusted for diabetes) at lumbar spine/femoral neck ⩽-2.5 <i>and</i> high FRAX score will be eligible for inclusion. 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Efficacy of zoledronate, denosumab or teriparatide in postmenopausal women with type 2 diabetes mellitus at high risk of fragility fractures: protocol of an open, blinded endpoint randomized controlled pilot trial.
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).
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Therapeutic Advances in Endocrinology and Metabolism delivers the highest quality peer-reviewed articles, reviews, and scholarly comment on pioneering efforts and innovative studies across all areas of endocrinology and metabolism.
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