Evaluation of Alendronate Sodium Monohydrate on Bone and Glycemic Markers in Type 1 and Type 2 Diabetes Mellitus with Osteopenia/Osteoporosis

The primary objective of this study is to investigate the effect of **Alendronate** on bone markers and glycemic markers in patients with **Diabetes Mellitus** and **Osteopenia/Osteoporosis**. This is clinically relevant as it aims to elucidate the potential benefits of Alendronate, a bisphosphonate, in managing bone health and glycemic control in diabetic patients, which could inform treatment strategies and improve patient outcomes.

Secondary objectives include:

• Comparing type 1 and type 2 diabetes in the context of bone health.
• Evaluating different methods of assessing bone status in diabetic patients.

The clinical trial involves participants diagnosed with **Diabetes Mellitus** and **Osteopenia/Osteoporosis**. The study population includes both male and female subjects aged 50 years and older. Participants are required to have maintained the same medical diabetes treatment for the past six months, with permissible dose adjustments, and must have an HbA1c level of at least 6.7% during this period. The body mass index (BMI) of participants ranges from 19 to 35, and they must have a DXA T-score between -3.5 and -0.5. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the effect of **Alendronate** on bone and glycemic markers in patients with **Diabetes Mellitus** and **Osteopenia/Osteoporosis**. This is a randomized, double-blind, controlled trial involving the administration of Alendronate Teva 70 mg tablets and a placebo. The trial is expected to span approximately 14 years, with an estimated recruitment start date of June 1, 2013, and an estimated end date of January 1, 2027. Participants will be randomly assigned to receive either the active treatment or placebo, with neither the participants nor the investigators aware of the group assignments, ensuring the double-blind nature of the study.

The study will include several key visits: an initial screening visit, multiple follow-up visits, and an end-of-study visit. During the screening visit, eligibility will be assessed based on criteria such as age (≥ 50 years), stable diabetes treatment, and specific **HbA1c** and **DXA T-score** levels. Follow-up visits will occur at regular intervals to monitor primary endpoints, including HbA1c and bone mineral density (BMD), as well as secondary endpoints like insulin levels, plasma glucose, and various biochemical markers. The end-of-study visit will involve a comprehensive assessment of all study parameters and the collection of final data.

Participant involvement is expected to last up to 24 months, with conditions for early termination including significant adverse events, non-compliance with study procedures, or withdrawal of consent. The trial aims to provide valuable insights into the impact of antiresorptive treatment on bone and glycemic health in this patient population, contributing to the understanding of therapeutic strategies for managing these conditions.

The clinical trial involves the administration of **Alendronate Sodium Monohydrate**, marketed under the name Alendronat Teva 70 mg tabletter. This experimental medication is provided in the form of a tablet and is intended for oral administration. The dosage regimen specifies a maximum daily dose of 10 mg, with a total maximum dose of 3650 mg over the course of the treatment period. The treatment duration is set for a maximum of 24 months. The tablets are encapsulated in gelatin capsules by the Hospital Pharmacy to facilitate administration. The active substance, Alendronate Sodium Monohydrate, is of chemical origin and is classified under the ATC code M05BA04, which corresponds to Alendronic Acid. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.

The study also includes a **placebo** control, identified as Placebo 8 mm with scoreline. This placebo is utilized to provide a comparator treatment against the experimental medication. The placebo is designed to mimic the appearance of the active medication but does not contain any active pharmaceutical ingredients. The use of a placebo is critical in maintaining the integrity of the trial by allowing for the assessment of the true efficacy and safety of the experimental treatment. The placebo administration schedule will mirror that of the active treatment to ensure consistency in the trial protocol.

Efficacy in this clinical trial will be assessed by evaluating both primary and secondary endpoints. The primary endpoints include **HbA1c** and Bone Mineral Density (BMD), which will be measured to determine the effect of Alendronate on bone markers and glycemic markers in patients with Diabetes Mellitus (type 1 and type 2). Secondary endpoints encompass a comprehensive range of biomarkers and physiological parameters, including insulin, plasma glucose, HOMA-IR, hs-CRP, AGE markers, lipids, adiponectin, PTH, 25 and 1,25 vitamin D, bone-specific alkaline phosphatase, FSH, LH, testosterone/estradiol, creatinine, GFR, FGF23, sclerostin, osteocalcin, ucOC, P1NP, PICP, CTX, osteoprotegerin, RANKL, and pentosidine. Additionally, urine albumin/creatinine ratio and urine bone markers will be evaluated, alongside HRpQCT scan results and analysis results from fat tissue, muscle tissue, and bone biopsies. A lifestyle questionnaire, including diet and physical activity, will also be utilized to gather relevant data.