MedPath

Preventing Osteoporosis Using Denosumab

Phase 4
Completed
Conditions
Osteoporosis
Osteoporotic Fractures
Osteoporosis, Postmenopausal
Interventions
Drug: Placebo
Dietary Supplement: Calcium and Vitamin D
Registration Number
NCT02753283
Lead Sponsor
Susan L. Greenspan
Brief Summary

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.

Detailed 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
201
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Men DenosumabCalcium and Vitamin DSemi-annual dose for men: denosumab 60 mg semi-annual injection; Vitamin D 800-1000 IU/daily and Calcium approximately 1200 mg/daily (dietary + supplements).
Men Placebo GroupPlaceboSemi-annual for men: placebo saline injection; Vitamin D 800-1000 IU/daily and Calcium approximately1200 mg/daily (dietary + supplements)
Women DenosumabdenosumabSemi-annual dose for women: denosumab 60 mg semi-annual injection; Vitamin D 800-1000 IU/daily and Calcium approximately 1200 mg/daily (dietary + supplements).
Women DenosumabCalcium and Vitamin DSemi-annual dose for women: denosumab 60 mg semi-annual injection; Vitamin D 800-1000 IU/daily and Calcium approximately 1200 mg/daily (dietary + supplements).
Women Placebo GroupPlaceboSemi-annual for women: placebo saline injection; Vitamin D 800-1000 IU/daily and Calcium approximately1200 mg/daily (dietary + supplements).
Women Placebo GroupCalcium and Vitamin DSemi-annual for women: placebo saline injection; Vitamin D 800-1000 IU/daily and Calcium approximately1200 mg/daily (dietary + supplements).
Men DenosumabdenosumabSemi-annual dose for men: denosumab 60 mg semi-annual injection; Vitamin D 800-1000 IU/daily and Calcium approximately 1200 mg/daily (dietary + supplements).
Men Placebo GroupCalcium and Vitamin DSemi-annual for men: placebo saline injection; Vitamin D 800-1000 IU/daily and Calcium approximately1200 mg/daily (dietary + supplements)
Primary Outcome Measures
NameTimeMethod
Bone Density of the Total Hip24 months

Bone Mineral Density (BMD) of the total hip percent change over 24 months as assessed by dual-energy x-ray absorptiometry (DXA)

Bone Density of the Spine24 months

Bone Mineral Density (BMD) of the spine percent change over 24 months as assessed by dual-energy x-ray absorptiometry (DXA)

Secondary Outcome Measures
NameTimeMethod
Distal Radius BMD24 Months

Percent change over 24 months

Femoral Neck BMD24 Months

Percent change over 24 months

TBS24 Months

Trabecular Bone Score (TBS) Percent change over 24 months. This not a scale. Higher values are better.

Trial Locations

Locations (1)

UPMC Senior Communities

🇺🇸

Pittsburgh, Pennsylvania, United States

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