Clinical trial NCT02753283: Preventing Osteoporosis Using Denosumab
Official title: Sustaining Skeletal Health in Frail Elderly
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Osteoporosis, Postmenopausal
Osteoporosis
Osteoporotic Fractures
Keywords: Bone loss
Frail Geriatric Patients
Nursing Home Patients
Long-term Care Patients
Osteoporosis
Osteoporotic Fractures
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute on Aging (NIA)
First posted: 2016-04-27
Enrollment: 201
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Bone Density of the Total Hip
timeFrame: 24 months
measure: Bone Density of the Spine
timeFrame: 24 months
Secondary outcomes:
measure: Distal Radius BMD
timeFrame: 24 Months
measure: Femoral Neck BMD
timeFrame: 24 Months
measure: TBS
timeFrame: 24 Months
Other outcomes:
measure: CTX
timeFrame: 12 Months
measure: P1NP
timeFrame: 12 Months
Locations:
city: Pittsburgh
country: United States
facility: UPMC Senior Communities
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Susan L Greenspan, MD
role: PRINCIPAL_INVESTIGATOR
References: