Postmenopausal Osteoporosis
Conditions
Keywords
Denosumab, Alendronate, osteoporosis, discontinuation of treatment
Brief summary
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
Detailed 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
Interventions
As discussed in group descriptions
Sponsors
Laikο General Hospital, Athens
424 General Military Hospital
251 Hellenic Air Force & VA General Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
No minimum to 90 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bone Mineral Density LS | 12 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bone Mineral Density FN | 12 months | Changes in the BMD of the femoral neck (FN) of the non-dominant hip 12 months after transitioning from denosumab to oral alendronate 70 mg in a weekly effervescent tablet formulation |
| Serum levels of bone turnover markers (BTMs): P1NP, CTX and TRAP5b | 12 months | Changes in BTMs 12 months after transitioning from denosumab to oral alendronate 70mg in a weekly effervescent tablet formulation. |
| Comparison of Bone Mineral Density LS | 12 months | Comparison of changes in the BMD of the LS after transitioning from denosumab to 12 months versus 6 months of treatment with oral alendronate 70 mg in a weekly effervescent tablet formulation. |
| Comparison of Bone Mineral Density FN | 12 months | Comparison of changes in the BMD of the FN of the non-dominant hip after transitioning from denosumab to 12 months versus 6 months of treatment with oral alendronate 70mg in a weekly effervescent tablet formulation. |
| Comparison of changes in: the serum levels of bone turnover markers (BTMs) P1NP, CTX and TRAP5b; the 24-hours urine levels of calcium | 12 months | Comparison of changes in the levels of serum BTMs and 24hours urine calcium after 12 months versus 6 months treatment with oral alendronate 70mg in a weekly effervescent tablet formulation in patients previously treated with denosumab |
Countries
Greece
Outcome results
None listed