The Effect of Semaglutide on Bone Turnover in Patients With Increased Risk of Bone Fracture

Study Overview
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Brief Summary
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The hypothesis for this study is that the GLP-1Ra Semaglutide has a positive effect on the balance between build-up and degradation as well as the strength of the bones in men and women aged 40-85 years at increased risk of bone fractures. Treatment involves injection of Semaglutide 1.34 mg/ml once a week or corresponding volume of placebo once a week for 52 weeks. The effect will be measured by bone markers in blood samples, bone scans, bone tissue tests (bone biopsy), and direct bone strength measured by microindentation at the start and end of the study.

Official Title
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The Effect of Semaglutide (Ozempic) on Bone Turnover in Patients With Increased Fracture Risk: a Randomized Placebo-controlled Clinical Trial

Conditions
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Osteopenia

Intervention / Treatment
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* Drug: Ozempic
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: T-score <-1 in hip or lower back, assessed by DXA scan and / or Low-energy fracture within the last 3 years Exclusion Criteria: T-score <-2.5 in hip or lower back, assessed by DXA scan, although these individuals may be included if they prefer to participate or are not candidates for conventional therapy, e.g., by eGFR <35 or adverse reaction (influenza-like symptoms, allergic reaction, etc.) to, e.g., bisphosphonate therapy Diabetes type 1 and 2 Heart failure similar to NYHA Class IV Primary hyperparathyroidism Vitamin D deficiency (<25 nM) (re-test after substitution acceptable) Known disorders affecting bone metabolism, e.g., uncontrolled thyrotoxicosis, severe renal impairment (eGFR <20) or liver function (baseline phosphatase higher than twice upper limit (105 U/L)), rheumatism, celiac disease, hypogonadism, severe COPD, hypopituitarism, Cushing's disease Antiresorptive or bone anabolic drugs for the last 12 months Use of anabolic steroids in the previous year History of pancreatitis Allergy to the medicines used Inability to give informed consent BMI <20 kg / m2

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Semaglutide<br>Ozempic 1 mg (or highest tolerated dose) s.c. once weekly for 52 weeks (incl. titration) | Drug: Ozempic<br>* 2 mg prefilled pen for subcutaneous injection, 0.25 mg for two weeks then 0.5 mg for two weeks and then 1 mg for another 48 weeks.<br>|
| Placebo Comparator: Placebo<br>Placebo (saline) 1 mg (or highest tolerated dose) s.c. once weekly for 52 weeks (incl. titration) | Drug: Placebo<br>* 2 mg prefilled pen for subcutaneous injection, 0.25 mg for two weeks then 0.5 mg for two weeks and then 1 mg for another 48 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Procollagen type 1 N-terminal propeptide (P1NP) | Percentage changes in bone formation marker P1NP from baseline and after 12 months | Baseline and 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Collagen 1 cross link C-terminal telopeptide (CTX) | Changes in bone resorption marker CTX from baseline and after 12 months | Baseline and 52 weeks | 
| Tartrate-resistant acid phosphatase (TRAP) | Changes in bone resorption marker TRAP from baseline and after 12 months | Baseline and 52 weeks | 
| Osteocalcin | Changes in bone formation marker osteocalcin from baseline and after 12 months | Baseline and 52 weeks | 
| Bone specific alkaline phosphatase (BALP) | Changes in bone formation marker BALP from baseline and after 12 months | Baseline and 52 weeks | 
| BMSi | Changes in direct bone strength measured by microindentation from baseline and after 12 months | Baseline and 52 weeks | 
| Bone mineral density (BMD) | Changes in BMD (total hip, femoral neck and lumbar spine (L1-4)) assessed by DXA scans from baseline and after 12 months | Baseline and 52 weeks | 
| Estimated bone strength | Changes in estimated bone strength assessed by finite elemental analysis (HR-pQCT scan) from baseline and after 12 months | Baseline and 52 weeks | 
| Total volumetric BMD | Changes in total volumetric BMD (mg/cm^3) assessed by HR-pQCT scan of distal tibia and radius | Baseline and 52 weeks | 
| Trabecular volumetric BMD | Changes in trabecular volumetric BMD (mg/cm^3) assessed by HR-pQCT scan of distal tibia and radius | Baseline and 52 weeks | 
| Cortical volumetric BMD | Changes in cortical volumetric BMD (mg/cm^3) assessed by HR-pQCT scan of distal tibia and radius | Baseline and 52 weeks | 
| Bone volume | Changes in trabecular bone volume pr total volume (BV/TV) assessed by HR-pQCT scan of distal tibia and radius | Baseline and 52 weeks | 
| Trabecular thickness | Changes in trabecular thickness (mm) assessed by HR-pQCT scan of distal tibia and radius | Baseline and 52 weeks | 
| Cortical thickness | Changes in cortical thickness (mm) assessed by HR-pQCT scan of distal tibia and radius | Baseline and 52 weeks | 
| Cortical porosity | Changes in cortical porosity assessed by HR-pQCT scan of tibia and radius | Baseline and 52 weeks | 
| Bone formation rate | Changes in bone formation rate (BRF/BS, µm^3/µm^2 per day), the volume of mineralized bone made per unit surface of bone per year | 52 weeks |