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.

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

Postmenopausal women