MedPath

Bone, Exercise, Alendronate, and Caloric Restriction

Phase 3
Recruiting
Conditions
Bone Loss
Interventions
Drug: Bisphosphonate
Other: Placebo
Behavioral: Resistance Training/Bone-Loading Exercise
Registration Number
NCT05764733
Lead Sponsor
Wake Forest University Health Sciences
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
700
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
FACTORIAL
Arm && Interventions
GroupInterventionDescription
No RT + BISBisphosphonateNo Resistance Training + 70 mg/weekly dose alendronate
Resistance Training (RT) + Bisphosphonate (BIS)BisphosphonateProgressive Resistance Training (RT) and Bone-Loading Exercise + 70 mg/weekly dose alendronate
No RT + Placebo (PL)PlaceboNo Resistance Training + Weekly Placebo
RT + PLResistance Training/Bone-Loading ExerciseProgressive RT and Bone-Loading Exercise + Weekly Placebo
RT + PLPlaceboProgressive RT and Bone-Loading Exercise + Weekly Placebo
Resistance Training (RT) + Bisphosphonate (BIS)Resistance Training/Bone-Loading ExerciseProgressive Resistance Training (RT) and Bone-Loading Exercise + 70 mg/weekly dose alendronate
Primary Outcome Measures
NameTimeMethod
Change in total hip areal bone mineral density (aBMD)from baseline through month 12

Dual X-ray absorptiometry (DXA) derived

Secondary Outcome Measures
NameTimeMethod
Tibial Cortical (Ct.) BMDbaseline, month 6, month 12

HR-pQCT acquired; Avg. volumetric BMD \[mg/cm3\]

Tibial Cortical Thickness (Ct.Th)baseline and month 12

Average thickness of cortical compartment in mm

aBMD assessment of the femoral neckbaseline, month 6, month 12

DXA derived

Tibial Trabecular Number (Tb.N)baseline and month 12

Average number trabeculae per unit length

aBMD assessment of the lumbar spinebaseline, month 6, month 12

DXA derived

Tibial Trabecular (Tb) BMDbaseline and month 12

HR-pQCT acquired; Average volumetric BMD \[mg/cm3\]

Trial Locations

Locations (2)

University of Colorado Anschutz Medical Campus

🇺🇸

Aurora, Colorado, United States

Atrium Health Wake Forest Baptist

🇺🇸

Winston-Salem, North Carolina, United States

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