Predictive Value of Bone Turnover Markers During Discontinuation With Alendronate (PROSA)

March 16, 2021 updated by: Anne Sophie Sølling, Aarhus University Hospital
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Actual)

142

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Aarhus, Denmark, 8000
        • Department of Endocrinology and Internal Medicine, Aarhus University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

140 patients with osteoporosis stopping treatment with alendronate.

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

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.
Time Frame: 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.
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
Time Frame: 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.
one and two years after baseline
Number of Participants in Which CTX Increased Above the Least Significant Change
Time Frame: 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%.
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.
Time Frame: from baseline to month 24
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.
Time Frame: 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.
Changes in TH BMD after one and two years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Aarhus University Hospital

Collaborators

University of Aarhus

Investigators

  • Study Director: Bente L Langdahl, MD PhD DMSc, Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2017

Primary Completion (Actual)

January 31, 2019

Study Completion (Actual)

January 31, 2019

Study Registration Dates

First Submitted

February 7, 2017

First Submitted That Met QC Criteria

February 9, 2017

First Posted (Actual)

February 14, 2017

Study Record Updates

Last Update Posted (Actual)

March 18, 2021

Last Update Submitted That Met QC Criteria

March 16, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016-003110-27

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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