Predictive Value of Bone Turnover Markers During Discontinuation With Alendronate

Study Overview
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Brief Summary
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The study is a cohort study comprising 136 patients with osteoporosis stopping treatment with alendronate. The study will contribute with new knowledge about biochemical markers of bone turnover as predictors of bone loss after stopping treatment with alendronate.

Detailed Description
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Background: Osteoporosis increases the risk of fractures. Alendronate reduces the risk of both vertebral- and hip fractures by approximately 50%. It has, however, become evident that long-term anti-resorptive may lead to serious side effects such as atypical femoral fractures or osteonecrosis of the jaw. The alendronate extension study (FLEX) showed that despite stopping treatment after five years the anti-fracture efficacy regarding non-vertebral and radiological vertebral fractures persists for an additional five years in patients with bone mineral density (BMD) T-score > -2.5 at the femoral neck, no fractures during treatment, and no previous vertebral fracture. It is therefore now clinical practice, that treatment is discontinued after five years in patients that fulfil these criteria. Based on the alendronate extension study it was assumed, that bone turnover monitored by biochemical markers would stay suppressed for years after stopping treatment, however, other studies have demonstrated that there is a great variability in the change in bone turnover markers seen after stopping treatment with alendronate in a real-life setting. Aim: To investigate the predictive value of markers of bone turnover on bone loss 12 months after stopping alendronate therapy. Methods: The study is a cohort study comprising 136 patients with osteoporosis stopping treatment with alendronate. Perspectives: The study will contribute with new knowledge about biochemical markers of bone turnover as predictors of bone loss after stopping treatment with alendronate. It will thus be possible to identify patients who will experience a decrease in BMD during treatment break, and for this particular group of patients treatment can be re-initiated earlier so further loss of bone will be avoided. On the other hand, the biochemical markers of bone turnover could also shed light on who can tolerate treatment break, thereby avoid long-term treatment with alendronate, which may be associated with serious side effects. Finally, the use of blood samples rather than DXA will reduce the use of X-rays.

Official Title
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Predictive Value of Bone Turnover Markers During Discontinuation With Alendronate

Conditions
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Osteoporosis

Intervention / Treatment
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* Drug: Discontinue alendronate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal women (postmenopausal for at least two years) Men above 50 years Treatment for at least five years with alendronate BMD T-score total hip > -2.5 BMD T-score lumbar spine (L1-L4) > -4 Exclusion Criteria: Any low-energy fracture within the previous five years during alendronate treatment (not including fingers, toes, or skull) Low-energy vertebral fracture at any time Low-energy hip fracture at any time Ongoing treatment with glucocorticoids Metabolic bone disease Hormone replacement therapy Cancer Other conditions affecting bone metabolism

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Discontinue alendronate|136 patients with osteoporosis stopping treatment with alendronate.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| If Carboxy-terminal Collagen Crosslinks (CTX) Three and Six Months After Stopping Alendronate Predicted TH BMD (Total Hip BMD) Loss Above the Least Significant Change at Month 12 at the Individual Level. | We constructed receiver operating characteristic (ROC) curves to evaluate if carboxy-terminal collagen crosslinks (CTX) three and six months after stopping alendronate predicted TH BMD loss above the least significant change (LSC) at month 12 at the individual level. | Baseline and one year after baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Bone Turnover Markers Measured Three and Six Months After Stopping Alendronate Treatment and BMD After One and Two Years | We constructed receiver operating characteristic (ROC) curves to evaluate if changes in p-CTX or p-PINP measured three and six months after stopping alendronate predicted TH BMD loss above the least significant change at month 12 and/or month 24 at the individual level. | one and two years after baseline | 
| Number of Participants in Which CTX Increased Above the Least Significant Change | Number of participants in which CTX increased above the least significant change. The Department of Clinical Biochemistry, Rigshospitalet, Glostrup, Denmark provided the the least significant change for p-CTX > 30%. | From baseline to month 24 | 
| The Number of Participants Who Lost BMD Beyond the Least Significant Change (LSC) at the Lumbar Spine and Total Hip. | the number of patients who lost BMD beyond the LSC at the lumbar spine (>3%) and total hip (>5%) | from baseline to month 24 | 
| If Baseline Bone Turnover Markers at the Time of Alendronate Discontinuation Predict Changes in BMD After One and Two Years. | We constructed receiver operating characteristic (ROC) curves to evaluate if baseline p-CTX or baseline p-PINP at the time of alendronate discontinuation predicted TH BMD loss above the least significant change at month 12 and/or month 24 at the individual level. | Changes in TH BMD after one and two years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bone turnover markers, Alendronate, Drug Holiday