Predictive Value of Bone Turnover Markers During Discontinuation With Alendronate

Completed

• Conditions: Osteoporosis

• Registration Number: NCT03051620
• Lead Sponsor: Aarhus University Hospital

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.

Study Timeline

• Study Start: 2017-02-01
• Study First Submitted: 2017-02-07
• Study First Submitted QC: 2017-02-09
• Study First Posted: 2017-02-14
• Primary Completion: 2019-01-31
• Study Completion: 2019-01-31
• Results First Submitted: 2020-11-26
• Status Verified: 2021-03
• Results First Submitted QC: 2021-03-16
• Last Update Submitted: 2021-03-16
• Results First Posted: 2021-03-18
• Last Update Posted: 2021-03-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 142

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Department of Endocrinology and Internal Medicine, Aarhus University Hospital; 🇩🇰 Aarhus, Denmark