A Clinical Study on the Effect of Discontinuing Alendronate in Postmenopausal Women With Osteoporosis After a Treatment Period Without Fractures

Incidence of fragility fractures during the study period

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.

Fasting blood samples will be performed during the study period to analyze changes in carboxy-terminal collagen crosslinks (CTX).

Fasting blood samples will be performed during the study period to analyze changes in procollagen type I N-terminal propeptide (PINP).

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low energy fractures (including morphometric vertebral fracture but excluding fractures of scull, fingers or toes) are withdrawn from the study and offered treatment with alendronate or zoledronic acid after new diagnostic work-up.

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.

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).

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 of peripheal blood with focus on the degree of methylation.