Effect of Vitamin D and Denosumab on Bone Remodelling in Women With Postmenopausal Osteoporosis

Study Overview
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Brief Summary
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Denosumab is a monoclonal antibody against RANKL ligand, which is used as an alternative treatment for osteoporosis in patients who have a poor response to first-line antiresorptive therapy. However, discontinuation of denosumab produces a rapid increase in bone turnover, bone loss and potentially increased risk of multiple vertebral fractures.

Detailed Description
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76 postmenopausal women from the climacteric clinic of the regional hospital 1o de Octubre of the Institute of Security and Social Services for State Workers (ISSSTE) were firstly considered, of which 23 presented elimination criteria and only 55 who had received denosumab therapy for an average of 2.5 years without a significant improvement in hip and lumbar spine T-scores were enrolled. First, a general medical evaluation was performed. Serum levels of vitamin D were analysed to find the prevalence of hypovitaminosis D. A bone mineral density test was done to calculate hip and lumbar spine T-scores. Then, vitamin D was administrated daily for one year at a dose of 4,000 IU and the studies were repeated after one year. Statistical analysis was performed using PAST 3.0 and GraphPad Prism 8.4.3. software. The arithmetic median (µ) and standard deviation (S.D.) were calculated using Excel-Word. Graphics were constructed with GraphPad Prism 8.4.3 and tables with Excel Word. Categorical variables were analysed with chi-squared or Fisher exact test depending on the number of participants in each cell. Normality was determined using the Shapiro-Wilk test. To compare two paired samples, the Wilcoxon signed-rank test was utilized. The assigned α value for this study was <0.05. In all cases, if a Montecarlo permutation was available, the exact p-value was taken instead of the raw p-value.

Official Title
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Vitamin D Improves Osteoporosis in Postmenopausal Women With Denosumab Failure

Conditions
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Hypovitaminosis D, Osteoporosis, Postmenopausal, Menopause

Intervention / Treatment
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* Drug: Cholecalciferol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of postmenopausal osteoporosis or osteopenia in treatment with denosumab 60mg every six months plus calcium carbonate 1.2g/day + vitamin D 800IU/day. Diagnosis of hypovitaminosis D, with serum cholecalciferol values <30ng/dL. Exclusion Criteria: Incomplete clinical records or clinical records. Age over 90 years. Diagnosis of secondary (hereditary) osteoporosis. History of prolonged use of steroids. Lack of adherence to medical treatment. Diagnosis of cancer. Diagnosis of depression. Diagnosis of Celiac disease or with the presence of alterations in intestinal absorption. Allergies to any of the medications administered.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: 76 participants were considered from the climacteric clinic of the regional hospital 1o de Octubre of the Institute of Security and Social Services for State Workers (ISSSTE), of which 23 presented elimination criteria, and 55 were included in the study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D 4000 IU<br>4000 IU of vitamin D were administrated once a day orally and calcium carbonate 1.2 g a day in a single dose. | Drug: Cholecalciferol<br>* 4000 IU were administrated once a day for 3 months.<br>* Other names: Histofil®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with hip T-score improvement at 12 months | It refers to the number of participants who improved their hip T-score at three months after treatment. | 12 months | 
| Number of participants with lumbar spine T-score improvement at 12 months | It refers to the number of participants who improved their lumbar spine T-score at three months after treatment. | 12 months | 
| Number of participants with osteoporosis of the hip at 12 months | It refers to the number of participants that present a hip T-score above -2.5 three months after treatment. | 12 months | 
| Number of participants with osteoporosis of the lumbar spine at 12 months | It refers to the number of participants that present a lumbar spine T-score greater than -2.5 three months after treatment. | 12 months | 
| Number of participants with osteopenia on the hip at 12 months | It refers to the number of participants that present a hip T-score from -1 to -2.4 three months after treatment. | 12 months | 
| Number of participants with osteopenia of the lumbar spine at 12 months | It refers to the number of participants that present a lumbar spine T-score from -1 to -2.4 three months after treatment. | 12 months | 
| Number of participants with normal hip T-score at 12 months | It refers to the number of participants that present a hip T-score below -1 three months after treatment. | 12 months | 
| Number of participants with normal lumbar spine T-score at 12 months | It refers to the number of participants that present a lumbar spine T-score below -1 three months after treatment. | 12 months | 
| Number of participants with improvement in serum levels of vitamin D at 12 months | Improvement in serum levels of 25-hydroxy vitamin D [25(OH)D] was considered when serum vitamin D levels increased concerning baseline levels. | 12 months | 
| Number of participants with clinical remission of hypovitaminosis D at 12 months | Remission of hypovitaminosis D was considered when serum levels of 25-hydroxy vitamin D [25(OH)D] were above 29 pg/ml. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with vitamin D sufficiency at 12 months | It refers to the number of participants who reached serum levels of vitamin D above 29 pg/ml after three months of treatment. | 12 months | 
| Number of participants with vitamin D insufficiency at 12 months | It refers to the number of participants who reached serum levels of vitamin D of 21 to 29 pg/ml after three months of treatment. | 12 months | 
| Number of participants with vitamin D deficiency at 12 months | It refers to the number of participants who reached serum levels of vitamin D less than 20 pg/ml after three months of treatment. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin D, Postmenopausal Osteoporosis, Denosumab, Hypovitaminosis D, Osteoporosis, Osteopenia