A Clinical Study on the Effect of Discontinuing Alendronate in Postmenopausal Women with Osteoporosis After a Treatment Period Without Fractures (ALEXIS)

The Alendronate Discontinuation Study

The goal of this clinical trial is to study the effects of discontinuation of Alendronate treatment for three years. The participants are postmenopausal women with osteoporosis, who have had a treatment period without fractures. The study will answer:

• What is the rate of fragility fractures during the study? The hypothesis is that discontinuation of Alendronate after a fracture-free period does not raise the 3-year fracture risk.
• Are there predictors of significant bone loss after discontinuation of Alendronate? The hypothesis is that clinical, biochemical, cellular, or molecular characteristics can predict bone loss.

Researchers will compare the outcomes of discontinuation of Alendronate with continuing treatment. Participants will be randomly assigned to a group.

Participants will:

• Either take alendronate once weekly for three years OR discontinue their treatment
• Visit the clinic at 6 and 18 months for blood samples
• Visit the clinic at the start of the study and after 1, 2, and 3 years for bone scans and blood samples.

Study Overview

• Status: Recruiting
• Conditions: Osteoporosis in Post-menopausal Women
• Intervention / Treatment: Drug: Alendronate 70mg weekly

• Study Type: Interventional
• Enrollment (Estimated): 1400
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Pernille Hermann, MD, PhD.; Phone Number: +4523602366; Email: pernille.herman@rsyd.dk
• Study Contact Backup: Name: Lars Folkestad, MD, PhD.; Phone Number: +4529648537; Email: lars.folkestad@rsyd.dk

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Not yet recruiting
    • Aalborg University Hospital
    • Contact: Peter Vestergaard; Phone Number: +4597660000; Email: p.vestergaard@rn.dk
  • Copenhagen, Denmark, 2400
    • Not yet recruiting
    • Bispebjerg Hospital
    • Contact: Pia Eiken; Phone Number: +4525889530; Email: pia.eiken.01@regionh.dk
  • Esbjerg, Denmark, 6700
    • Not yet recruiting
    • Esbjerg og Grindsted Sygehus
    • Contact: Jeppe Gram; Phone Number: +4521338706; Email: svs-forskning@rsyd.dk
  • Herlev, Denmark, 2730
    • Not yet recruiting
    • Copenhagen University Hospital (Herlev)
    • Contact: Jakob Praest Holm; Phone Number: +4538683868; Email: jakob.praest.holm.01@regionh.dk
  • Hillerød, Denmark, 3400
    • Not yet recruiting
    • Nordsjaellands Hospital (Hillerød)
    • Contact: Louise Tjelum; Phone Number: +4520485162; Email: louise.tjelum@regionh.dk
  • Hvidovre, Denmark, 2650
    • Not yet recruiting
    • Hvidovre Hospital
    • Contact: Jens-Erik Bech Jensen; Phone Number: +4540427592; Email: jens-erik.beck-jensen@regionh.dk
  • Odense, Denmark, 5000
    • Recruiting
    • Odense University Hospital
    • Contact: Pernille Hermann, MD, PhD.; Phone Number: +4523602366; Email: pernille.hermann@rsyd.dk
    • Contact: Freja Gram, MD
    • Contact: Lars Folkestad, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Female
• Postmenopausal
• Current treatment with Alendronate
• Alendronate treatment >3 år AND no fracture OR
• Alendronate treatment >5 år AND latest low energy fracture > 3 years ago

Exclusion Criteria:

• T-score < - 3,5 in hip (total hip or femoral neck) or lumbar spine
• Treatment with systemic glucocorticoids, ongoing or within 12 months
• Uncontrolled inflammatory disease
• Active malignancy
• eGFR < 40 mL/min
• Atypical femur fracture (ever)
• OsteoNecrosis of the Jaw (active)
• Unable to give inform consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Discontinuation of Alendronate; Discontinuation of Alendronate treatment	Drug: Alendronate 70mg weekly; The intervention is discontinuation of Alendronate
No Intervention: Control group; The control group will continue Alendronate treatment, but shift to project-sponsored product (70 mg Alendronate weekly)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fragility fractures	Incidence of fragility fractures during the study period	From enrollment to the end of the 3 year study period.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in bone mineral density (BMD)	Changes in lumbar spine and total hip BMD measured by dual energy X-ray arbsorptiometry. The three follow-up scans will be analyzed by a technician blinded to participant allocation, ie this person will not meet the patient and the patient will not be able see the results of the scans until the final study visit.	Baseline, 12, 24 and 36 months
Bone turn over marker (CTX)	Fasting blood samples will be performed during the study period to analyze changes in carboxy-terminal collagen crosslinks (CTX).	Blood samples are performed at baseline, 6, 12, 18, 24, and 36 months.
Bone turn over marker (P1NP)	Fasting blood samples will be performed during the study period to analyze changes in procollagen type I N-terminal propeptide (PINP).	Blood samples are performed at baseline, 6, 12, 18, 24, and 36 months.
Restart Criteria	The proportion of participants meeting restart criteria during the study period. Restart criteria is defined as: Participants experiencing boneloss exceeding 10% from baseline in any region, one clinical vertebral fracture, two low energy fractures (including morphometric vertebral fracture but excluding fractures of scull, fingers or toes) are withdrawn from the study and offered treatment with alendronate or zoledronic acid after new diagnostic work-up.	From enrollment to the end of the study period at 3 years
Adverse Events	At baseline a thoroughly physical examination of the participants and questioning concerning any conditions or diseases will take place. This way the investigators will be able to evaluate possible changes throughout the study. Patients will be interviewed about the occurrence of AEs at each visit from the first trial related activity after the subject has signed the informed consent. Subjects that experience adverse events or develop a disease during the trial period will be managed until the condition is cured or stationary. If this is not the case at the end of the study, subjects will be referred to a relevant physician, e.g. the general practitioner or a specialist, to be followed up.	From enrollment to the end of the 3 year study period.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Osteoclastassay	Osteoclasts differentiation, formation, activity and response to Alendronate in cultures derived from peripheal blood at baseline and 12 months, from a subgroup of 35 from each arm (70 participants in total).	Baseline and 12 months
Molecular bone histology	Iliac crest bone biopsy specimens will be obtained to evaluate the effect of discontinuation of alendronate on cortical and trabecular bone resorption and formation by histomorphometry. These results will be compared with results of bone turnover markers. Biopsies will be obtained of maximum 35 from each treatment group at 12 and 36 months (in totalt 140 participants).	12 and 36 months
Epigenetic analysis	Epigenetic analysis of peripheal blood with focus on the degree of methylation.	Baseline

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Investigators: Principal Investigator: Pernille Hermann, MD, PhD., Odense Universitetshospital / Odense University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2025
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): September 15, 2029

Study Registration Dates

• First Submitted: February 10, 2025
• First Submitted That Met QC Criteria: February 28, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 28, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Osteoporosis; Bone mineral density; Alendronate; Discontinuation; post-menopausal
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Bone Diseases, Metabolic; Osteoporosis; Physiological Effects of Drugs; Bone Density Conservation Agents; Alendronate
• Other Study ID Numbers: CT 2023-510042-24; 2023-510042-24-01 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No