Predictive Value of Bone Turnover Markers During Discontinuation With Alendronate

Osteoporosis Clinical Trial

— PROSA  

Official title:

Predictive Value of Bone Turnover Markers During Discontinuation With Alendronate

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03051620
• Other study ID #: 2016-003110-27
• Status: Completed
• Start date: February 1, 2017
• Est. completion date: January 31, 2019

Study information

• Verified date: March 2021
• Source: Aarhus University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 142
• Est. completion date: January 31, 2019
• Est. primary completion date: January 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Osteoporosis

Intervention

Drug:
• Discontinue alendronate
136 patients with osteoporosis stopping treatment with alendronate.

Locations

Country	Name	City	State
Denmark	Department of Endocrinology and Internal Medicine, Aarhus University Hospital	Aarhus

Sponsors (2)

Lead Sponsor	Collaborator
Aarhus University Hospital	University of Aarhus

Country where clinical trial is conducted

Denmark, 

References & Publications (6)

Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, Bauer DC, Genant HK, Haskell WL, Marcus R, Ott SM, Torner JC, Quandt SA, Reiss TF, Ensrud KE. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet. 1996 Dec 7;348(9041):1535-41. — View Citation

Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, Satterfield S, Wallace RB, Bauer DC, Palermo L, Wehren LE, Lombardi A, Santora AC, Cummings SR; FLEX Research Group. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA. 2006 Dec 27;296(24):2927-38. — View 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. — View Citation

Liberman UA, Weiss SR, Bröll J, Minne HW, Quan H, Bell NH, Rodriguez-Portales J, Downs RW Jr, Dequeker J, Favus M. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group. N Engl J Med. 1995 Nov 30;333(22):1437-43. — View 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. — View Citation

Shane E, Burr D, Ebeling PR, Abrahamsen B, Adler RA, Brown TD, Cheung AM, Cosman F, Curtis JR, Dell R, Dempster D, Einhorn TA, Genant HK, Geusens P, Klaushofer K, Koval K, Lane JM, McKiernan F, McKinney R, Ng A, Nieves J, O'Keefe R, Papapoulos S, Sen HT, van der Meulen MC, Weinstein RS, Whyte M; American Society for Bone and Mineral Research. Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2010 Nov;25(11):2267-94. doi: 10.1002/jbmr.253. Erratum in: J Bone Miner Res. 2011 Aug;26(8):1987. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline and one year after baseline
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.	one and two years after baseline
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%.	From baseline to month 24
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%)	from baseline to month 24
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.	Changes in TH BMD after one and two years.