Comparative Antiresorptive Efficacy Discontinuation of Denosumab

Study Overview
=================
Brief Summary
-----------------
Osteoporosis remains a significant healthcare burden for the United States. Current FDA-approved osteoporosis treatments include teriparatide, abaloparatide, bisphosphonates, denosumab, and raloxifene. Denosumab is a fully human monoclonal antibody that specifically binds to receptor activator of nuclear factor kappa-B ligand (RANKL). Denosumab potently suppresses osteoclastic activity but bone turnover rapidly normalizes and bone turnover marker levels can rebound above baseline levels after the drug is discontinued. This study will help us determine the optimal duration and relative efficacy of two oral antiresorptive medications that are FDA-approved for treatment of postmenopausal osteoporosis (alendronate and raloxifene) in preventing the rebound increase in bone turnover that occurs after denosumab discontinuation.

Official Title
-----------------
Comparative Antiresorptive Efficacy of Alendronate or Raloxifene Following Discontinuation of Denosumab

Conditions
-----------------
Osteoporosis, Postmenopausal, Osteoporosis

Intervention / Treatment
-----------------
* Drug: denosumab
* Drug: alendronate
* Drug: raloxifene


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: women aged 45+ postmenopausal osteoporotic with high risk of fracture as per National Osteoporosis Foundation guidelines Exclusion Criteria: no significant previous use of bone health modifying treatments hip fracture within one year of enrollment known congenital or acquired bone disease other than osteoporosis significant renal disease, liver disease, cardiopulmonary disease, or psychiatric disease abnormal calcium or parathyroid hormone level serum vitamin D <20 ng/dL anemia (hematocrit <32%) history of malignancy (except non-melanoma skin carcinoma) excessive alcohol use or substance abuse extensive dental work involving extraction or dental implant within the past 6 months or in the upcoming 12 months known contraindications to denosumab, alendronate, or raloxifene

Ages Eligible for Study
-----------------
Minimum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Denosumab and Raloxifene<br>denosumab and raloxifene | Drug: denosumab<br>* denosumab 60 milligrams subcutaneously every 6 months<br>* Other names: Prolia;Drug: raloxifene<br>* raloxifene 60 milligrams daily<br>* Other names: Evista;|
| Active Comparator: Denosumab and Alendronate<br>denosumab and alendronate | Drug: denosumab<br>* denosumab 60 milligrams subcutaneously every 6 months<br>* Other names: Prolia;Drug: alendronate<br>* alendronate 70 milligrams weekly<br>* Other names: Fosamax;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum c-telopeptide (CTX) | Change in serum CTX between month 12 and month 18 | Month 12 to 18 months | 
| Bone mineral density (BMD) | Change in PA spine BMD between month 24 and month 36 | Month 24 to 36 months |