Denosumab and Osteoporotic Vertebral Compression Fracture

Study Overview
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Brief Summary
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This study aimed to investigate the effect of denosumab on bone mineral density(BMD), bone turnover markers(BTMs), functional status, secondary fracture rate, and adverse effects in osteoporotic vertebral compression fracture (OVCF) patients after vertebroplasty during a 12-month follow-up period.

Detailed Description
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We performed a single-center, placebo-controlled, randomized clinical trial in the Department of Spinal Surgery located at the First Affiliated Hospital of Southern University of Science and Technology (Shenzhen People's Hospital). All patients underwent vertebroplasty and randomly received denosumab treatment or placebo control after surgery. The BMDs (lumbar, total hip, and femoral neck) and BTMs were assessed at baseline, 6, and 12 months post-operation. The visual analog scale (VAS) score for back pain, and function status questionnaires, including EuroQol five-dimension (EQ-5D), the Quality of Life Questionnaire of the European Foundation for Osteoporosis-31 (QUALEFFO-31), and the Roland-Morris Disability Functioning Questionnaire (RMDQ),secondary fracture rate, and adverse effects in OVCF patients after vertebroplasty during a 12-month follow-up period.

Official Title
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Denosumab Protects Bone Loss and Function in Patients With Osteoporotic Vertebral Compression Fracture After Percutaneous Vertebroplasty: a Randomized Placebo-controlled Clinical Trial

Conditions
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Osteoporotic Vertebral Compression Fracture

Intervention / Treatment
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* Drug: Denosumab 60 mg/ml [Prolia]
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be age between 50 and 90 years old X-ray diagnosis of 1 or 2 segment vertebral compression fractures from T4 to L5 Bone mineral density T value less than -1 via dual-energy X-ray A recent fracture history less than 6 weeks MRI show bone marrow edema of fractured vertebrae low back pain, local paravertebral tenderness Exclusion Criteria: Must be able to have no intervertebral fissure Must be able to have no infection Must be able to have no malignancy Must be able to have no neurological dysfunction Must be able to have no previous use of anti-osteoporosis drugs Must be able to have no inability to perform magnetic resonance imaging Must be able to have no prior back open surgery Must be able to have no other established contraindications for elective surgery

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 90 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Denosumab<br>Denosumab 60 mg were injected subcutaneously every 6 months (Q6M) | Drug: Denosumab 60 mg/ml [Prolia]<br>* denosumab subcutaneously every 6 months (Q6M)<br>* Other names: Denosumab;|
| Placebo Comparator: Placebo<br>Equal volume of saline (0.9%) as placebo were injected subcutaneously every 6 months (Q6M) | Drug: Placebo<br>* placebo subcutaneously every 6 months (Q6M)<br>* Other names: equal volume of saline (0.9%);|

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) | Bone formation marker, P1NP were determined at baseline, 6 and 12 months after surgery. | up to 12 months | 
| C-terminal cross-linked type 1 collagen terminal peptide (CTX) | Bone resorption marker, CTX were determined at baseline, 6 and 12 months after surgery | up to 12 months | 
| Lumbar bone mineral density(BMD) | Lumbar vertebral (L1 to L4, except the surgery segment) BMD were determined at baseline, 6 and 12 months via dual-energy X-ray. | up to 12 months | 
| Total hip BMD | Total hip BMD were determined at baseline, 6 and 12 months via dual-energy X-ray. | up to 12 months | 
| Femoral neck BMD | Femoral neck BMD were determined at baseline, 6 and 12 month via dual-energy X-ray | up to 12 months | 
| Visual analog scale (VAS) back | The VAS score for back pain were determined at baseline, 6 and 12 month. Use a ruler about 10cm long, one side is marked with 0 and the other 10 respectively. A score of 0 indicates no pain, 10 indicates the most unbearable pain. | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Roland-Morris Disability Questionnaire | The Roland-Morris Disability Questionnaire is scored by 24 adding up the number of items checked yes on different low back pain-related daily activity disabilities. Total scores range from 0 to 24, with higher scores 24 indicating a higher level of disability related to low back pain and lowest 0 represents no back pain. | up to 12 month | 
| The QUALEFFO-31 Questionnaire | The Quality of Life Questionnaire of the European Foundation for Osteoporosis-31 (QUALEFFO-31), which contains three domains including pain, physical function, and mental function. This scale is assessed on a scale of 0 to 100, with 0 indicating the highest QoL and 100 the lowest. | up to 12 month | 
| The EQ-5D Questionnaire | The EQ-5D questionnaire evaluates health status consisting five dimensions: mobility, self-care, performance of usual activities, pain or discomfort, and anxiety or depression. After conversion, the index was between 0 and 1.0 (minimum score: 0, indicating worst health state; full score:1.0, indicating full health). | up to 12 month | 
| Secondary fracture rate | Secondary fracture rate containing vertebral fracture and non-vertebral fracture was assessed at 12 month after surgery. The lowest score was 0, the highest score was 100%. The lower score 0 represents no secondary fracture. | up to 12 month | 
| Adverse events | The main adverse events including deep venous thrombosis, pneumonia, acute renal failure, pulmonary embolism, myocardial infarction, influenza, transfer to intensive care unit, joint pain, headache, nausea, osteonecrosis of the jaw, atypical femoral fracture and rash. | up to 12 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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denosumab, vertebroplasty