Efficacy of Zoledronic Acid to Prevent Bone Loss Following Denosumab Discontinuation

Study Overview
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Brief Summary
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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
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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.

Official Title
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Efficacy of a Single Infusion of Zoledronic Acid to Mitigate the Rebound Effect of Rapid Bone Loss Following Denosumab Treatment Discontinuation

Conditions
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Osteopenia, Osteoporosis, Osteoporosis, Postmenopausal, Bone Loss

Intervention / Treatment
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* Drug: Zoledronic acid


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Zoledronic acid|Once-yearly infusion of zoledronic acid following denosumab discontinuation|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in volumetric Bone Mineral Density (BMD)/bone microarchitecture from baseline | High-resolution peripheral computed tomography scan (radius and tibia) will be used to quantify volumetric BMD/bone microarchitecture | Change from Baseline (within 1-month of infusion) to 6-months and 12-months | 
| Change in areal Bone Mineral Density (BMD) from baseline | Dual X-ray absorptiometry scan (lumbar spine, lateral vertebral assessment, and hip) will be used to quantify areal BMD | Change from Baseline (within 1-month of infusion) to 6-months and 12-months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fractures | Any clinically diagnosed fractures will be reported by treating physician | 1 year | 
| MoJo Fracture Risk Questionnaire | An assessment of fracture risk | 1 year |