Clinical trial NCT03051620: Predictive Value of Bone Turnover Markers During Discontinuation With Alendronate
Official title: Predictive Value of Bone Turnover Markers During Discontinuation With Alendronate
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Osteoporosis
Keywords: Bone turnover markers
Alendronate
Drug Holiday
Lead sponsor: Aarhus University Hospital
Sponsor class: OTHER
Collaborators: name: University of Aarhus
First posted: 2017-02-14
Enrollment: 142
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 140 patients with osteoporosis stopping treatment with alendronate.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: Baseline and one year after baseline
Secondary outcomes:
measure: Percent Change in Bone Turnover Markers Measured Three and Six Months After Stopping Alendronate Treatment and BMD After One and Two Years
timeFrame: one and two years after baseline
measure: Number of Participants in Which CTX Increased Above the Least Significant Change
timeFrame: From baseline to month 24
measure: The Number of Participants Who Lost BMD Beyond the Least Significant Change (LSC) at the Lumbar Spine and Total Hip.
timeFrame: from baseline to month 24
measure: If Baseline Bone Turnover Markers at the Time of Alendronate Discontinuation Predict Changes in BMD After One and Two Years.
timeFrame: Changes in TH BMD after one and two years.
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Department of Endocrinology and Internal Medicine, Aarhus University Hospital
Study officials:
affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark
name: Bente L Langdahl, MD PhD DMSc
role: STUDY_DIRECTOR
References:
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citation: Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR, Felsenberg D, Gagel RF, Gilsanz V, Guise T, Koka S, McCauley LK, McGowan J, McKee MD, Mohla S, Pendrys DG, Raisz LG, Ruggiero SL, Shafer DM, Shum L, Silverman SL, Van Poznak CH, Watts N, Woo SB, Shane E; American Society for Bone and Mineral Research. Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2007 Oct;22(10):1479-91. doi: 10.1359/jbmr.0707onj.
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citation: Schwartz AV, Bauer DC, Cummings SR, Cauley JA, Ensrud KE, Palermo L, Wallace RB, Hochberg MC, Feldstein AC, Lombardi A, Black DM; FLEX Research Group. Efficacy of continued alendronate for fractures in women with and without prevalent vertebral fracture: the FLEX trial. J Bone Miner Res. 2010 May;25(5):976-82. doi: 10.1002/jbmr.11.
citation: Solling AS, Harslof T, Bruun NH, Langdahl B. The predictive value of bone turnover markers during discontinuation of alendronate: the PROSA study. Osteoporos Int. 2021 Aug;32(8):1557-1566. doi: 10.1007/s00198-021-05835-4. Epub 2021 Jan 30.