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.