Clinical trial NCT05764733: Bone, Exercise, Alendronate, and Caloric Restriction
Official title: The Bone, Exercise, Alendronate, and Caloric Restriction Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Bone Loss
Keywords: Older Adults
Weight Loss
Resistance Training
Osteoporosis
Osteopenia
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2023-03-13
Enrollment: 700
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: This is a 2x2 factorial design.
Primary purpose: PREVENTION

Brief summary: The purpose of this research is to identify strategies that minimize bone loss that occurs when older adults lose weight. Participation in this research will involve up to nine assessment visits and last up to two years.

Detailed description: The main objective of this study is to compare the independent and combined effects of a 12-month intervention of resistance training (RT) plus bone-loading exercises and bisphosphonate use on dietary weight loss (WL)-associated bone loss among older adults, with an indication for WL, and low bone density to explore lasting treatment efficacy. All participants will receive the same group-mediated dietary WL intervention and be randomized to one of four groups. Due to its robust change following dietary WL and clinical utility in predicting fracture, the study's primary outcome is change in total hip areal bone mineral density (aBMD) measured via dual x-ray absorptiometry (DXA). This will be complemented by DXA assessment at other skeletal sites, as well as high resolution peripheral quantitative computed tomography (HR-pQCT) derived compartmental volumetric (v)BMD, trabecular bone microarchitecture, cortical thickness/porosity, and strength at the distal radius and tibia allowing for assessment of intervention effectiveness on novel measures of bone quality.

Eligibility criteria: Inclusion Criteria:

* Community-dwelling
* BMI\>30 kg/m\^2 or BMI 25.0 to \<30 kg/m\^2 plus one risk factor
* Currently receiving routine (annual) dental care
* Pre-existing low bone mass (T-score ≤-1.1 to \>-2.5 at the hip, femoral neck, or lumbar spine (L1-L4))

Exclusion Criteria:

* Weight greater than 450 lbs (DXA limit)
* Resides with someone who is currently participating in BEACON
* Dependent on quad cane or walker; inability to walk independently
* History of mild cognitive impairment or dementia or evidence of cognitive impairment ((score \<20) on Montreal Cognitive Assessment (MoCA))
* Excessive alcohol use (\>21 drinks/week) in the past month; any non-cannabis illicit drug use
* Weight change ≥5% in past 3 months
* Regular participation (\>60 mins per day on \> 3 days/week) in structured strength training program for \>6 months
* Severe arthritis, fracture, chronic injury, or other musculoskeletal disorder that prevents safe exercise participation; joint replacement or other orthopedic surgery in past 6 months or planned in next 12 months; invasive dental procedure (i.e. extraction/implant) in past 6 month or planned in next 12 months
* Osteoporosis (any of the following): Self-reported and on prescription osteoporosis medication; self-reported prior spine, hip, wrist, or shoulder fracture after age 40 (except when caused by trauma or fall from height), including atypical femoral fractures (AFF); or ≥20% for major osteoporotic fracture at screening
* Uncontrolled hypertension (systolic \>180 OR diastolic \>110 mmHg) upon repeated assessments (up to 3 times)
* Uncontrolled type 2 diabetes (HbA1c \>8%); dialysis or abnormal kidney function (eGFR \<45 mL/min/1.73 m2); liver disease or abnormal liver function (ALT levels 2 times above normal); anemia (Hb\<LLN); calcium above or below normal limit; uncontrolled thyroid disease (hypo/hyper) or requiring recent (past 3 months) adjustments in thyroid hormone supplementation or thyroid-stimulating hormone \<LLN or \>10 mIU/ml; vitamin D deficiency (\<20 ng/mL).
* Stroke, heart attack, heart failure hospitalization, or revascularization procedure within the past 6 months; chronic respiratory disease requiring oxygen; PAD diagnosis within the last 12 months; uncontrolled angina; progressive neurological disease; malabsorption disorder; any disease suggesting a life-expectancy \<3 years; bilateral hip replacement; past or planned bariatric surgery; cancer requiring initial treatment within the last 12 months (except non-melanoma skin cancers); major vision or hearing loss; unstable gastric reflux; esophageal stricture, achalasia, or Barrett's esophagus
* Daily use of growth hormones, weight loss medications, oral steroids, or diabetes prescriptions (such as insulin, thiazolidinediones, or canagliflozin); known allergy to bisphosphonates; prior use of oral bisphosphonates for \>3 months within the past 3 years; zoledronic acid within the past 5 years; denosumab use within the past year; anabolic agents for \>3 months in the last year; current use of biotin or strontium; history of 3+ years of antiresorptive therapy
* Unable/unwilling to: provide own transportation to study visits, commit to study protocol (including random assignment), or adhere to data collection visits
* Current participation in another intervention research study; planned out-of-town trip greater than 1 month at a time during the first 6 months of the study; unwilling to provide informed consent, including consent to access personal electronic health records; judged unsuitable for the trial for any reason by research team

Primary outcomes:
measure: Change in total hip areal bone mineral density (aBMD)
timeFrame: from baseline through month 12
Secondary outcomes:
measure: aBMD assessment of the femoral neck
timeFrame: baseline, month 6, month 12
measure: aBMD assessment of the lumbar spine
timeFrame: baseline, month 6, month 12
measure: Tibial Trabecular (Tb) BMD
timeFrame: baseline and month 12
measure: Tibial Cortical (Ct.) BMD
timeFrame: baseline, month 6, month 12
measure: Tibial Trabecular Number (Tb.N)
timeFrame: baseline and month 12
measure: Tibial Cortical Thickness (Ct.Th)
timeFrame: baseline and month 12
Other outcomes:
measure: Tibial Total bone mineral density (Tt.BMD)
timeFrame: baseline and month 12
measure: Tibial Total Area (Tt.Ar)
timeFrame: baseline and month 12
measure: Tibial Trabecular Area (Tb Ar)
timeFrame: baseline and month 12
measure: Tibial Cortical Area (Ct.Ar)
timeFrame: baseline and month 12
measure: Tibial Total Trabecular Volume (Tt.TV)
timeFrame: baseline and month 12
measure: Tibial Trabecular Volume (Tb.TV)
timeFrame: baseline and month 12
measure: Tibial Cortical Volume (Ct.TV)
timeFrame: baseline and month 12
measure: Tibial Cortical Perimeter (Ct.Pm)
timeFrame: baseline and month 12
measure: Tibial Trabecular Bone Volume Fraction (Tb.BV/TV)
timeFrame: baseline and month 12
measure: Tibial Trabecular Thickness (Tb.Th)
timeFrame: baseline and month 12
measure: Tibial Trabecular Separation (Tb.Sp)
timeFrame: baseline and month 12
measure: Tibial Inhomogeneity of Trabecular Network
timeFrame: baseline and month 12
measure: Tibial Cortical Porosity (Ct.Po)
timeFrame: baseline and month 12
measure: Tibial Cortical Pore Diameter (Ct.Po.Dm)
timeFrame: baseline and month 12
measure: Tibial Cortical Pore Volume (Ct.Po.V)
timeFrame: baseline and month 12
measure: Tibial Estimated Failure Load (FL)
timeFrame: baseline and month 12
measure: Tibial Bone Stiffness
timeFrame: baseline and month 12
measure: Bone Formation Assay
timeFrame: baseline, month 6, month 12
measure: Bone Resorption Assay
timeFrame: baseline, month 6, month 12
Locations:
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Winston-Salem
country: United States
facility: Atrium Health Wake Forest Baptist
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Kristen Beavers, PhD
role: PRINCIPAL_INVESTIGATOR
References: