Clinical trial NCT04338529: Alendronate in an Weekly Effervescent Tablet Formulation Following Denosumab Discontinuation
Official title: Alendronate in an Weekly Effervescent Tablet Formulation for Preservation of Bone Mass After Denosumab Discontinuation in Postmenopausal Women with Low Bone Mass. an Observational Study (Binosto After Denosumab - the BAD Study)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Postmenopausal Osteoporosis
Keywords: Denosumab
Alendronate
osteoporosis
discontinuation of treatment
Lead sponsor: 251 Hellenic Air Force & VA General Hospital
Sponsor class: OTHER
Collaborators: name: Laikο General Hospital, Athens
name: 424 General Military Hospital
First posted: 2020-04-08
Enrollment: 92
Sex: FEMALE
Maximum age (years): 90
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will include 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 either 6 months (Group 6, n=46) and then followed for another 6 months without medication, or 12 months of continuous treatment with alendronate (Group 12, n=46). As this is an observational study, patients could be either referred from their treating physicians or could be actually followed by the investigators themselves in case the investigator is the treating physician

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

Eligibility criteria: 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

Primary outcomes:
measure: Bone Mineral Density LS
timeFrame: 12 months
Secondary outcomes:
measure: Bone Mineral Density FN
timeFrame: 12 months
measure: Serum levels of bone turnover markers (BTMs): P1NP, CTX and TRAP5b
timeFrame: 12 months
measure: Comparison of Bone Mineral Density LS
timeFrame: 12 months
measure: Comparison of Bone Mineral Density FN
timeFrame: 12 months
measure: Comparison of changes in: the serum levels of bone turnover markers (BTMs) P1NP, CTX and TRAP5b; the 24-hours urine levels of calcium
timeFrame: 12 months
Other outcomes:
Locations:
city: Athens
country: Greece
facility: 251 Hellenic Air Force & VA General Hospital
state: Attiki
Study officials:
affiliation: LAIKO General Hospital, Athens, Greece
name: Maria Yavropoulou, MD, PhD
role: STUDY_CHAIR
affiliation: 251 Hellenic Airforce Gen. Hospital, Athens, Greece
name: Polyzois Makras, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: 424 Gen. Military Hospital Thessaloniki, Greece
name: Athanasios D Anastasilakis, MD, PhD
role: STUDY_DIRECTOR
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