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

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ClinicalTrials.gov Identifier: NCT03051620

Recruitment Status : Completed

First Posted : February 14, 2017

Last Update Posted : August 26, 2019

Sponsor:

Collaborator:

University of Aarhus

Information provided by (Responsible Party):

Anne Sophie Sølling, Aarhus University Hospital

Study Description

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.

Condition or disease	Intervention/treatment
Osteoporosis	Drug: Discontinue 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 Design

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Study Type :	Observational
Actual Enrollment :	136 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Official Title:	Predictive Value of Bone Turnover Markers During Discontinuation With Alendronate
Actual Study Start Date :	February 1, 2017
Actual Primary Completion Date :	January 31, 2019
Actual Study Completion Date :	January 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoporosis

Drug Information available for: Alendronic acid Alendronate sodium

U.S. FDA Resources

Groups and Cohorts

Intervention Details:

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

Outcome Measures

Primary Outcome Measures :

Carboxy-terminal collagen crosslinks (CTX) [ Time Frame: One year ]
To what extent changes in the biochemical bone turnover marker carboxy-terminal collagen crosslinks (CTX) three and six months after stopping alendronate treatment predict changes in total hip BMD after one year.

Secondary Outcome Measures :

Carboxy-terminal collagen crosslinks (CTX) [ Time Frame: One year ]
To what extent baseline CTX (biochemical bone turnover marker carboxy-terminal collagen crosslinks) when stopping alendronate treatment predicts changes in total hip BMD after one year.
Procollagen type I N-terminal propeptide (PINP) [ Time Frame: One year ]
To what extent changes in the biochemical bone turnover marker procollagen type I N-terminal propeptide (PINP) three and six months after stopping alendronate treatment predict changes in total hip BMD after one year.
Ratio CTX/PINP [ Time Frame: One year ]
To what extent changes in the ratio CTX/PINP (biochemical bone turnover markers) 3 and 6 months after stopping alendronate treatment predict changes in total hip BMD after one year.
Bone turnover [ Time Frame: 3, 6, and 12 months. ]
The proportion of the study population in which bone turnover increases to above premenopausal/young adult reference levels after 3, 6, and 12 months.
BMD [ Time Frame: one year ]
The proportion of the study population who loses BMD beyond least significant change in lumbar spine and total hip.

Eligibility Criteria

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Ages Eligible for Study:	50 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

140 patients with osteoporosis stopping treatment with alendronate.

Criteria

Inclusion Criteria:

Postmenopausal women (postmenopausal for at least two years)
Men above 50 years
Treatment for at least five years with alendronat
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 alendronat 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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03051620

Locations

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

Sponsors and Collaborators

Aarhus University Hospital

University of Aarhus

Investigators

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

More Information

Publications:

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.

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.

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.

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.

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.

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.

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Responsible Party:	Anne Sophie Sølling, MD, PhD student, Aarhus University Hospital
ClinicalTrials.gov Identifier:	NCT03051620
Other Study ID Numbers:	2016-003110-27
First Posted:	February 14, 2017 Key Record Dates
Last Update Posted:	August 26, 2019
Last Verified:	August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

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Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Anne Sophie Sølling, Aarhus University Hospital:


Bone turnover markers Alendronate Drug Holiday

Additional relevant MeSH terms:

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Osteoporosis Bone Diseases, Metabolic Bone Diseases Musculoskeletal Diseases	Metabolic Diseases Alendronate Bone Density Conservation Agents Physiological Effects of Drugs

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