Study on the Intervention Effect of Denosumab on High-Risk Patients With Osteoporotic Fractures in Type 2 Diabetes

Overview

This study will conduct a randomized controlled trial targeting patients with type 2 diabetes and a high risk of fractures. The aim is to evaluate the intervention effect of denosumab combined with edilossobulin on patients with a high risk of osteoporotic fractures due to type 2 diabetes, as well as its impact on bone density, bone turnover indicators, the risk of new fractures, and the risk of hypocalcemia. This will provide scientific evidence for clinical diagnosis and treatment, and offer important clinical research evidence for formulating national health policies.

Interventions

• Drug Denosumab treatment in type 2 diabetes mellitus (T2DM) with osteoporosis patients
  1. Antihyperglycemic drug therapy: Follow the Chinese Diabetes Treatment Guidelines and clinical practice standards. Adjust the antihyperglycemic regimen based on blood glucose levels, with a target HbA1c of below 7.5%. 2. Denosumab treatment: Administer 60 mg of denosumab via subcutaneous injection every six months for a total treatment period of one year.
• Drug Denosumab combined with eldecalcitol treatment in type 2 diabetes mellitus (T2DM) with osteoporosis patients
  1. Antihyperglycemic drug therapy: Follow the Chinese Diabetes Treatment Guidelines and clinical practice standards. Adjust the antihyperglycemic regimen based on blood glucose levels, with a target HbA1c of below 7.5%. 2. Denosumab injection (Mai Lishu), 60 mg subcutaneous injection, once every six months, combined with eldecalcitol soft capsules (Gai Sheng Yuan), 0.75 μg/capsule, take one capsule orally once daily, for one year of treatment.

Primary outcome measures

• change rate of lumbar bone density [Time frame: 12 months of treatment]

Secondary outcome measures (6)

• Incidence of osteoporotic fractures [Time frame: 12 months of treatment]
• Change rate of bone density in the femoral neck and total hip [Time frame: 12 months of treatment]
• Change rate of serum levels of β-CTX [Time frame: 6 months of treatment]
• Change rate of serum levels of β-CTX [Time frame: 12 months of treatment]
• Change rate of serum levels of PINP [Time frame: 6 months of treatment]
• Change rate of serum levels of PINP [Time frame: 12 months of treatment]

Eligibility criteria

Inclusion criteria

• Confirmed diagnosis of type 2 diabetes (based on the "China Guidelines for the Prevention and Treatment of Diabetes (2024 Edition)").
• Males aged ≥50 years; females aged ≥45 years and postmenopausal for more than 2 years.
• Duration of diabetes >10 years; or presence of at least one of the following conditions: ①diabetic retinopathy; ②urine albumin-to-creatinine ratio (UACR)≥ 30 mg/g; ③estimated glomerular filtration rate (eGFR)<60 mL/min/1.73 m²; ④coronary atherosclerotic heart disease; ⑤ischemic stroke; ⑥transient ischemic attack; ⑦ atherosclerosis of the carotid, cerebral, or lower-extremity arteries with ≥50% luminal stenosis.
• Glycated hemoglobin (HbA1c) ≤ 8.0 % measured within 1 month
• History of hip or vertebral fragility fractures; or history of fragility fractures at other sites (excluding the skull, feet, and hands) with a T-score of <-1.0 at the femoral neck, total hip, or any L1-L4 site; or a T-score of <-2.0 at the femoral neck, total hip, or any L1-L4 site.
• In the BMD measurement at lumbar vertebrae L1-L4, at least two or more vertebral bodies must meet the evaluable criteria.
• Signed informed consent form, willing to participate in the study

Exclusion criteria

• Diseases that cause secondary osteoporosis: a. Various metabolic bone diseases, such as osteomalacia, primary hyperparathyroidism, osteogenesis imperfecta, Paget's disease, etc.; b. Cushing's syndrome; c. Hyperprolactinemia; d. Others;
• Malignant tumors within the past 5 years, except for those expected to be cured after treatment (e.g., completely resected in situ basal cell or squamous cell carcinoma of the skin, cervical cancer, or ductal carcinoma of the breast);
• Received intravenous bisphosphonate treatment within the past 2 years or oral bisphosphonate treatment within the past 1 year;
• History or current diagnosis of osteomyelitis or osteonecrosis of the jaw; unhealed dental or oral surgical wounds; acute dental or jaw conditions requiring oral surgery; planned to undergo invasive dental surgery during the study period;
• Received denosumab, teriparatide, or romosozumab treatment within the past 6 months;
• Continuous use of calcitonin for more than 3 months within the past year;
• Use of glucocorticoids (equivalent to>5 mg/day prednisone) for more than 10 days within the past 6 weeks;
• 25-hydroxyvitamin D<10ng/mL;
• Active infections requiring systemic treatment;
• Uncontrolled comorbidities, including New York Heart Association (NYHA) functional class III or above heart failure, severe arrhythmias, severe hepatic insufficiency (alanine aminotransferase or aspartate aminotransferase>3 times the upper limit of normal), severe renal insufficiency (eGFR<30 ml/min/1.73 m²);
• Hypocalcemia, hypercalcemia, or hypercalciuria (Note: hypercalciuria is defined as a urinary calcium/creatinine ratio > 0.5 mg/mg, or 24-hour urinary calcium > 7.5 mmol).;
• Allergy to the study drug;
• Currently participating in other clinical trials of drugs;
• Subjects deemed unsuitable for enrollment in this study by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

China · 4 centers

• Peking Union Medical College Hospital — Beijing
• Huai'an First People's Hospital — Huai'an
• Jiangxi Provincial People's Hospital — Jiangxi
• Kunshan Hospital of Traditional Chinese Medicine — Kunshan

Identifiers

NCT: NCT07063797 · 2024ZD0532204

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗