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.
Female
Postmenopausal
Current treatment with Alendronate
Alendronate treatment >3 år AND no fracture OR
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
Parallel
Alendronate 70mg weekly
DrugThe intervention is discontinuation of Alendronate
Fragility fractures
Incidence of fragility fractures during the study period
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.
Bone turn over marker (CTX)
Fasting blood samples will be performed during the study period to analyze changes in carboxy-terminal collagen crosslinks (CTX).
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).
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.
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).
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).
Epigenetic analysis
Epigenetic analysis of peripheal blood with focus on the degree of methylation.
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