Preventing Osteoporosis Using Denosumab

Objective:

The long term goal is to improve health, well-being and quality of life in the frail long-term care (LTC) elderly population by reducing fractures. The short term goal is to demonstrate efficacy of the non-bisphosphonate denosumab to improve bone mineral density (BMD), a necessary (but not sufficient) pre-condition of a large fracture reduction trial. The investigators propose to conduct a 2-year, randomized, double-blind, calcium-vitamin D controlled trial to test the efficacy and predictability of the antiresorptive RANK ligand inhibitor, denosumab (60 mg), among a cohort of 212 institutionalized, under-served, frail men and women ≥65 years old in LTC.

Specific Aims:

Aim 1: To evaluate efficacy of denosumab in improving/maintaining bone mineral density. The investigators will measure conventional hip and spine bone mineral density (BMD).

Primary Hypothesis: After 2 years, women and men on denosumab will have greater hip and spine BMD increases.

Inclusion criteria

Ambulatory male and female residents with osteoporosis or low bone mass (at risk for fracture) ages 65 and older will be considered if:

• Reside in long-term care institution (nursing home or assisted living facility); and
• HaveOsteoporosis: (1) by bone density [spine, hip or forearm Bone Mineral Density (BMD) T-score ≤ -2.5]; (2) A previous adult fragility fracture of the spine or hip; or (3) Would be treated based on FRAX® and the National Osteoporosis Foundation (NOF) treatment thresholds of a 10 year risk of ≥ 20% for a major fracture or ≥ 3% for hip fracture suing femoral neck BMD.

Exclusion criteria

• Institutionalized residents with subacute illnesses who are not expected to survive or who will be discharged in < 2 years.
• Non-ambulatory residents (those who cannot stand and pivot with assistance in order to transfer to the DXA table).
• Those currently on therapy (including bisphosphonate, denosumab, or teriparatide) or who have been on a bisphosphonate for > 1year during the previous 2 years because some bisphosphonates are long acting.
• Those with a history of hypocalcemia or contraindication for treatment. We will screen for these conditions by detailed history, chart review, and baseline laboratory analyses.
• Those with vitamin D levels < 25ng/mL will be treated with vitamin D 50,000 IU/wk for 8 weeks; they will be enrolled if the follow-up vitamin D level is 25 ng/mL or more (if after 2 rounds of vitamin D repletion their vitamin D level is not at least 25 ng/mL, they will not be eligible to be randomized into the study).
• Those on dialysis or with stage 5 chronic kidney disease (eGFR<15ml/min) will be excluded at screening.
• Those requiring tooth extraction or oral surgery will not be enrolled until cleared by a dentist.
• Patients will be allowed to continue on glucocorticoids and anticonvulsants because their use is common in this population.
• Those on glucocorticoids and anticonvulsants will be allowed to continue in the study because their use is common in this population.
• Those on hormone replacement therapy (HRT), raloxifene, or prescribed protective hip pads by their Primary Care Physician (PCP) will be allowed to participate and continue on these therapies.
• We will suggest that participants stop long-term calcitonin as it has been discontinued in Europe due to cancer concerns.