Clinical trial NCT05405894: Efficacy of Zoledronic Acid to Prevent Bone Loss Following Denosumab Discontinuation
Official title: Efficacy of a Single Infusion of Zoledronic Acid to Mitigate the Rebound Effect of Rapid Bone Loss Following Denosumab Treatment Discontinuation
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Osteoporosis
Osteoporosis, Postmenopausal
Osteopenia
Bone Loss
Lead sponsor: University of Calgary
Sponsor class: OTHER
First posted: 2022-06-06
Enrollment: 20
Sex: FEMALE
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 focuses on post-menopausal, osteoporotic females, anticipating or preparing to transition off active denosumab treatment, for which they have received at least 2 prior injections, via a transition to once-yearly infusion of zoledronic acid.

Brief summary: This two-year observational, open-label clinical trial will evaluate the efficacy of a once-yearly infusion of zoledronic acid after denosumab discontinuation to maintain tissue mineral density and bone microarchitecture using high-resolution peripheral quantitative computed tomography (HR-pQCT) among post-menopausal women with osteoporosis.

Detailed description: As part of an observational study, twenty female osteoporosis patients looking to transition off denosumab therapy will be recruited from the David Hanley Osteoporosis Centre and affiliated primary care physicians in Calgary. The decision to stop denosumab will be made in accordance with standard clinical care and fully separate from the present study. Approximately 6-8 months after the patients' final denosumab injection, patients will receive a single infusion of zoledronic acid (5 mg/100mL) as part of their routine standard of care. The 6-8 month time frame corresponds with the recommended duration between subsequent denosumab injections. Concurrent with zoledronic acid treatment (within one month before or after infusion), patients will visit to the McCaig Institute for Bone and Joint Health to receive a baseline dual X-ray absorptiometry scan (lumbar spine, lateral vertebral assessment, and hip) and a high-resolution peripheral computed tomography scan (radius and tibia) to quantify areal BMD and volumetric BMD/bone microarchitecture, respectively. They will also complete the MoJo Fracture Risk Questionnaire. Patients will return for repeat scanning and questionnaire administrations to monitor potential changes to bone at 6 and 12 months after baseline. Any fracture events during the 12-month time frame will be logged in consultation with the patients' physician as documented through routine clinical follow-up. Researchers may contact participants to repeat scanning and questionnaire administration at the 24-month time point, if participants agree to this contact within the informed consent.

Eligibility criteria: Inclusion Criteria:

* Post-menopausal females with osteoporosis
* Anticipating or preparing to transition off active denosumab treatment for osteoporosis with the use of a once-yearly infusion of zoledronic acid
* Received at least 2 injections of denosumab treatment
* Had a recent test (within 6 months) of serum creatine, calcium and phosphate

Exclusion Criteria:

* Any person for whom zoledronic acid would be considered contraindicated
* Pre-menopausal females
* Any person with significant chronic kidney disease (eGFR \< 50 ml/m2 at time of osteoporosis clinical assessment)
* Any person with previous adverse reactions or allergy to bisphosphonate therapies
* Any person with non-corrected hypocalcaemia
* Any person currently taking, and unable to discontinue the use of, prohibited medications including: ZOMETA, other bisphosphonate therapies, calcitonin, aminoglycosides, loop diuretics and agiogenesis inhibitors
* Any person with other history, condition, therapy, or uncontrolled intercurrent illness, which could in the opinion of the Qualified Medical Investigator affect compliance with study requirements or which would make the participant unsuitable for this study
* Any person with simultaneous participation in another interventional clinical study (e.g., Phase 1-3 clinical studies) or treatment with any investigational medicinal product within 30 days prior to screening visit

Primary outcomes:
measure: Change in volumetric Bone Mineral Density (BMD)/bone microarchitecture from baseline
timeFrame: Change from Baseline (within 1-month of infusion) to 6-months and 12-months
measure: Change in areal Bone Mineral Density (BMD) from baseline
timeFrame: Change from Baseline (within 1-month of infusion) to 6-months and 12-months
Secondary outcomes:
measure: Fractures
timeFrame: 1 year
measure: MoJo Fracture Risk Questionnaire
timeFrame: 1 year
Other outcomes:
measure: Optional further assessment of change in volumetric Bone Mineral Density (BMD)/bone microarchitecture from baseline
timeFrame: Change from Baseline to 24-months
measure: Optional further assessment of change in areal Bone Mineral Density (BMD) from baseline
timeFrame: Change from Baseline to 24-months
Locations:
city: Calgary
country: Canada
facility: University of Calgary, McCaig Institute for Bone and Joint Health
state: Alberta
Study officials:
affiliation: University of Calgary
name: William Brent Edwards, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Solling AS, Harslof T, Langdahl B. Treatment with Zoledronate Subsequent to Denosumab in Osteoporosis: a Randomized Trial. J Bone Miner Res. 2020 Oct;35(10):1858-1870. doi: 10.1002/jbmr.4098. Epub 2020 Jul 12.
citation: Anastasilakis AD, Polyzos SA, Makras P, Aubry-Rozier B, Kaouri S, Lamy O. Clinical Features of 24 Patients With Rebound-Associated Vertebral Fractures After Denosumab Discontinuation: Systematic Review and Additional Cases. J Bone Miner Res. 2017 Jun;32(6):1291-1296. doi: 10.1002/jbmr.3110. Epub 2017 Mar 13.