Preventing Osteoporosis Using Denosumab (PROUD)

Susan L. Greenspan

Status and phase: Completed; Phase 4

Conditions: Osteoporosis; Osteoporotic Fractures; Osteoporosis, Postmenopausal

Treatments: Drug: Placebo; Drug: denosumab; Dietary Supplement: Calcium and Vitamin D

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02753283

STUDY19050268

1R01AG052123-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

The purpose of this research study is to find out if denosumab (Prolia®), an injection given in the arm under the skin every 6 months, works to treat bone loss and prevent it from worsening in older men and women (ages 65 and older) who have osteoporosis and reside in long-term care (LTC) facilities.

Full description

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.

Enrollment: 201 patients

Sex: All

Ages: 65+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

201 participants in 4 patient groups, including a placebo group

Women Denosumab

Experimental group

Description:

Semi-annual dose for women: denosumab 60 mg semi-annual injection; Vitamin D 800-1000 IU/daily and Calcium approximately 1200 mg/daily (dietary + supplements).

Treatment:

Dietary Supplement: Calcium and Vitamin D

Drug: denosumab

Women Placebo Group

Placebo Comparator group

Description:

Semi-annual for women: placebo saline injection; Vitamin D 800-1000 IU/daily and Calcium approximately1200 mg/daily (dietary + supplements).

Treatment:

Dietary Supplement: Calcium and Vitamin D

Drug: Placebo

Men Denosumab

Experimental group

Description:

Semi-annual dose for men: denosumab 60 mg semi-annual injection; Vitamin D 800-1000 IU/daily and Calcium approximately 1200 mg/daily (dietary + supplements).

Treatment:

Dietary Supplement: Calcium and Vitamin D

Drug: denosumab

Men Placebo Group

Placebo Comparator group

Description:

Semi-annual for men: placebo saline injection; Vitamin D 800-1000 IU/daily and Calcium approximately1200 mg/daily (dietary + supplements)

Treatment:

Dietary Supplement: Calcium and Vitamin D

Drug: Placebo