Alendronate in an Weekly Effervescent Tablet Formulation Following Denosumab Discontinuation (BAD)

251 Hellenic Air Force & VA General Hospital

Status: Completed

Conditions: Postmenopausal Osteoporosis

Treatments: Drug: Binosto 70Mg Effervescent Tablet

Study type: Observational

Funder types: Other

Identifiers

NCT04338529

2550/14-2-20 (Other Identifier)

F076/AD1704/S606/18-2-2020

Details and patient eligibility

About

Discontinuation of denosumab results in a rebound response of bone turnover markers, which rise above baseline at 3 months and remain elevated until reaching again baseline levels approximately 30 months after the last dose. Bone mineral density (BMD) gains are also lost and BMD values reach original baseline values after 1-2 years off-treatment.For the above reasons, current literature recommends that patients who discontinue denosumab should continue to receive either intravenous (iv) or oral (peros) bisphosphonate therapy for some time. The study aims to investigate changes in the BMD of the lumbar spine 12 months after transitioning from denosumab to oral alendronate 70 mg in a weekly effervescent tablet formulation

Full description

Denosumab, a monoclonal antibody against the receptor activator of nuclear factor κ-Β ligand (RANKL), is a potent antiresorptive agent commonly prescribed in patients with postmenopausal osteoporosis. Discontinuation of denosumab results in a rebound response of bone turnover markers, which rise above baseline at 3 months and remain elevated until reaching again baseline levels approximately 30 months after the last dose. Bone mineral density (BMD) gains are also lost and BMD values reach original baseline values after 1-2 years off-treatment, in contrast to bisphosphonates, which remain within the skeleton acting for several months or even years after discontinuation while preserving most of the BMD gains achieved despite the cessation of treatment.

For the above reasons, current literature recommends that patients who discontinue denosumab should continue to receive either intravenous (iv) or oral (peros) bisphosphonate therapy for some time. Due to lack of specifically designed studies, the period of treatment with bisphosphonates after denosumab discontinuation has been arbitrarily proposed to be 1 to 2 years. Preservation of BMD gains after denosumab discontinuation has so far been demonstrated: (a) with one year of alendronate treatment, in a study designed to investigate patients' compliance to treatment, and b) with a single dose of zolendronate 5mg iv in a recent study specifically designed to address this question in which BMD levels remained stable for the next two years.

Preventing bone loss, and the reported high risk of multiple vertebral fractures after discontinuation of denosumab treatment, is a clinical issue of critical importance raising serious concerns to the international scientific community and needs to be addressed. Clinical studies specifically designed to investigate both the efficacy of various bisphosphonates and the optimal duration of their administration in order to avoid the reported adverse effects of denosumab discontinuation are currently lacking.

This study aims to investigate changes in the BMD of the lumbar spine (LS) and femoral neck (FN) 12 months after transitioning from denosumab to oral alendronate 70 mg in a weekly effervescent tablet formulation. Alendronate will be given either for 6 or 12 months following Denosumab discontinuation

Enrollment: 92 patients

Sex: Female

Ages: Under 90 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

i) osteopenic postmenopausal Caucasian women following Dmab treatment ii) assignment to treatment with alendronate in an effervescent tablet formulation following Dmab discontinuation

Exclusion criteria

i) secondary osteoporosis; ii) diseases that could affect bone metabolism iii) medications that could affect bone metabolism iv) chronic kidney disease (stage >3b) and/or liver failure v) neoplastic disease vi) hypersensitivity to alendronate or to any of the excipients vii) abnormalities of the esophagus and other factors which delay esophageal emptying such as stricture or achalasia viii) inability to stand or sit upright for at least 30 minutes ix) hypocalcaemia x) confirmed esophagitis

Trial design

92 participants in 2 patient groups

Group Alendronate 6m

Description:

Postmenopausal Caucasian women who were treated with denosumab and became osteopenic (BMD T-score of \> -2.5 at the LS and the non-dominant FN) and were assigned from their treating physician to receive treatment with alendronate in an effervescent tablet formulation for 6 months and then followed for another 6 months without medication. In case serum P1NP levels are \> 35μg/L and/or serum CTX levels are \> 280 ng/L at 9 months (3 months following alendronate discontinuation) the patients would be strongly advised to restart alendronate treatment.

Treatment:

Drug: Binosto 70Mg Effervescent Tablet

Group Alendronate 12m

Description:

Postmenopausal Caucasian women who were treated with denosumab and became osteopenic (BMD T-score of \> -2.5 at the LS and the non-dominant FN) and were assigned from their treating physician to receive treatment with alendronate in an effervescent tablet formulation for 12 months.

Treatment:

Drug: Binosto 70Mg Effervescent Tablet