Bone, Exercise, Alendronate, and Caloric Restriction

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Bone, Exercise, Alendronate, and Caloric Restriction Trial

Conditions
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Bone Loss

Intervention / Treatment
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* Drug: Bisphosphonate
* Behavioral: Resistance Training/Bone-Loading Exercise
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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); FRAX 10-year risk scores ≥3% for hip fracture 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

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: This is a 2x2 factorial design.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Resistance Training (RT) + Bisphosphonate (BIS)<br>Progressive Resistance Training (RT) and Bone-Loading Exercise + 70 mg/weekly dose alendronate | Drug: Bisphosphonate<br>* Medicine used to treat bone problems, called osteopenia or osteoporosis.<br>Behavioral: Resistance Training/Bone-Loading Exercise<br>* Exercise in small groups three days per week under the supervision of exercise physiologists. Heart rate and blood pressure will be measured before and after each session and participants will warm-up by walking or cycling for five minutes at a slow pace. All RT exercises will be conducted on machines which accommodate different body sizes and allow small increments in resistance, both important considerations for low functioning older adults with obesity.<br>|
| Experimental: No RT + BIS<br>No Resistance Training + 70 mg/weekly dose alendronate | Drug: Bisphosphonate<br>* Medicine used to treat bone problems, called osteopenia or osteoporosis.<br>|
| Active Comparator: No RT + Placebo (PL)<br>No Resistance Training + Weekly Placebo | Other: Placebo<br>* Capsules identical to the active alendronate capsules without any active ingredients with the same dosing and follow up as BIS treatment group.<br>|
| Active Comparator: RT + PL<br>Progressive RT and Bone-Loading Exercise + Weekly Placebo | Behavioral: Resistance Training/Bone-Loading Exercise<br>* Exercise in small groups three days per week under the supervision of exercise physiologists. Heart rate and blood pressure will be measured before and after each session and participants will warm-up by walking or cycling for five minutes at a slow pace. All RT exercises will be conducted on machines which accommodate different body sizes and allow small increments in resistance, both important considerations for low functioning older adults with obesity.<br>Other: Placebo<br>* Capsules identical to the active alendronate capsules without any active ingredients with the same dosing and follow up as BIS treatment group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in total hip areal bone mineral density (aBMD) | Dual X-ray absorptiometry (DXA) derived | from baseline through month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| aBMD assessment of the femoral neck | DXA derived | baseline, month 6, month 12 | 
| aBMD assessment of the lumbar spine | DXA derived | baseline, month 6, month 12 | 
| Tibial Trabecular (Tb) BMD | HR-pQCT acquired; Average volumetric BMD [mg/cm3] | baseline and month 12 | 
| Tibial Cortical (Ct.) BMD | HR-pQCT acquired; Avg. volumetric BMD [mg/cm3] | baseline, month 6, month 12 | 
| Tibial Trabecular Number (Tb.N) | Average number trabeculae per unit length | baseline and month 12 | 
| Tibial Cortical Thickness (Ct.Th) | Average thickness of cortical compartment in mm | baseline and month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Older Adults, Weight Loss, Resistance Training, Osteoporosis, Osteopenia