Osteoporosis
Conditions
Keywords
Bone turnover markers, Alendronate, Drug Holiday
Brief summary
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
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.
Interventions
DRUGDiscontinue alendronate
136 patients with osteoporosis stopping treatment with alendronate.
Sponsors
University of Aarhus
Aarhus University Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Baseline and one year after baseline | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Bone Turnover Markers Measured Three and Six Months After Stopping Alendronate Treatment and BMD After One and Two Years | one and two years after baseline | 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. |
| Number of Participants in Which CTX Increased Above the Least Significant Change | From baseline to month 24 | 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%. |
| The Number of Participants Who Lost BMD Beyond the Least Significant Change (LSC) at the Lumbar Spine and Total Hip. | from baseline to month 24 | the number of patients who lost BMD beyond the LSC at the lumbar spine (\>3%) and total hip (\>5%) |
| If Baseline Bone Turnover Markers at the Time of Alendronate Discontinuation Predict Changes in BMD After One and Two Years. | Changes in TH 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. |
Countries
Denmark
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Study Population Postmenopausal women and men | 142 |
| Total | 142 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 6 |
| Overall Study | n=124 enrolled in extension (all completed) | 12 |
Baseline characteristics
| Characteristic | Study Population |
|---|---|
| Age, Continuous | 68 years STANDARD_DEVIATION 6 |
| Baseline CTX | 0.21 ug/L STANDARD_DEVIATION 0.1 |
| Baseline PINP | 28 ug/L STANDARD_DEVIATION 9.5 |
| Bone mineral density (BMD) lumbar spine | 0.806 g/cm3 STANDARD_DEVIATION 0.09 |
| Bone mineral density (BMD) total hip | 0.780 g/cm3 STANDARD_DEVIATION 0.09 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 142 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Sex: Female, Male Female | 122 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 142 |
| other Total, other adverse events | 68 / 142 |
| serious Total, serious adverse events | 7 / 142 |
Outcome results
Primary
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.
Time frame: Baseline and one year after baseline
Population: None of the ROC curves investigating the ability of change in CTX to predict BMD loss beyond LSC at any site at month 12 at the individual level had AUC above 60% meaning that it was not possible to identify a specific cut-off value that could predict significant bone loss at the individual level.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Population | 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. | Mean change in TH BMD from baseline to month 12 | 1.14 percentage change | Standard Deviation 0.14 |
| Study Population | 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. | Mean change in CTX from baseline to month 3 | 49 percentage change | Standard Deviation 43 |
| Study Population | 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. | Mean change in CTX from baseline to month 6 | 64 percentage change | Standard Deviation 62 |
Secondary
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.
Time frame: Changes in TH BMD after one and two years.
Population: None of the ROC curves investigating the ability of baseline bone turnover markers to predict BMD loss beyond LSC at any site at month 12 or month 24 at the individual level had AUC above 60% meaning that it was not possible to identify a specific cut-off value that could predict significant bone loss at the individual level.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Population | If Baseline Bone Turnover Markers at the Time of Alendronate Discontinuation Predict Changes in BMD After One and Two Years. | Mean change in TH BMD after one year | -1.14 percentage change | Standard Deviation 0.14 |
| Study Population | If Baseline Bone Turnover Markers at the Time of Alendronate Discontinuation Predict Changes in BMD After One and Two Years. | Mean change in TH BMD after two years | -2.65 percentage change | Standard Deviation 0.39 |
Secondary
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%.
Time frame: From baseline to month 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study Population | Number of Participants in Which CTX Increased Above the Least Significant Change | 85 participants |
Secondary
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.
Time frame: one and two years after baseline
Population: None of the ROC curves investigating the ability of change in bone turnover markers to predict BMD loss beyond LSC at any site at month 12 or month 24 at the individual level had AUC above 60% meaning that it was not possible to identify a specific cut-off value that could predict significant bone loss at the individual level.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Population | Percent Change in Bone Turnover Markers Measured Three and Six Months After Stopping Alendronate Treatment and BMD After One and Two Years | Mean change in PINP from baseline to month 3 | 36 percentage change | Standard Deviation 40 |
| Study Population | Percent Change in Bone Turnover Markers Measured Three and Six Months After Stopping Alendronate Treatment and BMD After One and Two Years | Mean change in PINP from baseline to month 6 | 54 percentage change | Standard Deviation 45 |
| Study Population | Percent Change in Bone Turnover Markers Measured Three and Six Months After Stopping Alendronate Treatment and BMD After One and Two Years | Mean change in TH BMD from baseline to month 12 | -1.14 percentage change | Standard Deviation 0.14 |
| Study Population | Percent Change in Bone Turnover Markers Measured Three and Six Months After Stopping Alendronate Treatment and BMD After One and Two Years | Mean change in TH BMD from baseline to month 24 | -2.65 percentage change | Standard Deviation 0.39 |
Secondary
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%)
Time frame: from baseline to month 24
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Study Population | The Number of Participants Who Lost BMD Beyond the Least Significant Change (LSC) at the Lumbar Spine and Total Hip. | Spine | 21 participants |
| Study Population | The Number of Participants Who Lost BMD Beyond the Least Significant Change (LSC) at the Lumbar Spine and Total Hip. | Total hip | 26 participants |