Bone, Exercise, Alendronate, and Caloric Restriction

Bone Loss Clinical Trial

— BEACON  

Official title:

The Bone, Exercise, Alendronate, and Caloric Restriction Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05764733
• Other study ID #: IRB00077185
• Secondary ID: R01AG074979
• Status: Recruiting
• Phase: Phase 3
• Start date: June 8, 2023
• Est. completion date: April 2027

Study information

• Verified date: February 2024
• Source: Wake Forest University Health Sciences
• Contact: Kristen Beavers, PhD
• Phone: 336-758-5855
• Email: beaverkm[@]wfu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 700
• Est. completion date: April 2027
• Est. primary completion date: April 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bone Loss

Intervention

Drug:
• Bisphosphonate
Medicine used to treat bone problems, called osteopenia or osteoporosis.

Behavioral:
• Resistance Training/Bone-Loading Exercise
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.

Other:
• Placebo
Capsules identical to the active alendronate capsules without any active ingredients with the same dosing and follow up as BIS treatment group.

Locations

Country	Name	City	State
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	Atrium Health Wake Forest Baptist	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Tibial Total bone mineral density (Tt.BMD)	High resolution peripheral quantitative computed tomography (HR-pQCT) acquired; Avg. volumetric BMD [mg/cm3]	baseline and month 12
Other	Tibial Total Area (Tt.Ar)	HR-pQCT acquired; Avg. cross-sectional area (all slices)	baseline and month 12
Other	Tibial Trabecular Area (Tb Ar)	HR-pQCT acquired; Avg. cross-sectional area (all slices)	baseline and month 12
Other	Tibial Cortical Area (Ct.Ar)	HR-pQCT acquired; Avg. cross-sectional area (all slices)	baseline and month 12
Other	Tibial Total Trabecular Volume (Tt.TV)	total Volume in tissue compartments; millimeter (mm)^3	baseline and month 12
Other	Tibial Trabecular Volume (Tb.TV)	Volumes in trabecular compartments; mm^3	baseline and month 12
Other	Tibial Cortical Volume (Ct.TV)	Volumes in cortical compartments; mm^3	baseline and month 12
Other	Tibial Cortical Perimeter (Ct.Pm)	millimeter; Average periosteal perimeter (all slices)	baseline and month 12
Other	Tibial Trabecular Bone Volume Fraction (Tb.BV/TV)	Volume ratio of bone in trabecular compartment percentage	baseline and month 12
Other	Tibial Trabecular Thickness (Tb.Th)	Average thickness of trabeculae in mm	baseline and month 12
Other	Tibial Trabecular Separation (Tb.Sp)	Avg distance between trabeculae in mm	baseline and month 12
Other	Tibial Inhomogeneity of Trabecular Network	Volume ratio of pores in cortical compartment	baseline and month 12
Other	Tibial Cortical Porosity (Ct.Po)	Volume ratio of pores in cortical compartment	baseline and month 12
Other	Tibial Cortical Pore Diameter (Ct.Po.Dm)	Average 3D diameter of pore volumes	baseline and month 12
Other	Tibial Cortical Pore Volume (Ct.Po.V)	Total volume of cortical pores	baseline and month 12
Other	Tibial Estimated Failure Load (FL)	Estimated by calculation of the reaction force at which 7.5% of the elements exceed a local effective strain of 0.7%	baseline and month 12
Other	Tibial Bone Stiffness	Reaction force divided by displacement	baseline and month 12
Other	Bone Formation Assay	Procollagen type I N-propeptide (PINP) is a biomarker of bone formation (mcg/L)	baseline, month 6, month 12
Other	Bone Resorption Assay	C-terminal telopeptide of type I collagen (CTX) is a biomarker of bone resorption (pg/mL)	baseline, month 6, month 12
Primary	Change in total hip areal bone mineral density (aBMD)	Dual X-ray absorptiometry (DXA) derived	from baseline through month 12
Secondary	aBMD assessment of the femoral neck	DXA derived	baseline, month 6, month 12
Secondary	aBMD assessment of the lumbar spine	DXA derived	baseline, month 6, month 12
Secondary	Tibial Trabecular (Tb) BMD	HR-pQCT acquired; Average volumetric BMD [mg/cm3]	baseline and month 12
Secondary	Tibial Cortical (Ct.) BMD	HR-pQCT acquired; Avg. volumetric BMD [mg/cm3]	baseline, month 6, month 12
Secondary	Tibial Trabecular Number (Tb.N)	Average number trabeculae per unit length	baseline and month 12
Secondary	Tibial Cortical Thickness (Ct.Th)	Average thickness of cortical compartment in mm	baseline and month 12