Lifestyle Intervention to Improve Bone Quality

Study Overview
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Brief Summary
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Obese older adults will be randomized to participate in either healthy lifestyle intervention or behavioral diet and exercise intervention for one year. This study aims to determine the effects of Lifestyle intervention on bone microarchitecture, bone strength, bone material properties, and the mechanism behind it.

Detailed Description
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Previous studies had suggested that lifestyle therapy (diet plus exercise) resulting in weight loss in elderly population improves physical function, cardio metabolic risk factors, and cognition/quality of life, but a major complication is loss of BMD. The addition of exercise to diet-induced weight loss attenuated but did not eliminate weight-loss-induced reduction of BMD. Moreover, while long-term maintenance of weight loss and physical function was feasible, sustained lifestyle change led to continued loss of hip BMD, which might predict hip fractures. Although similar BMD loss with weight loss has been observed in younger populations, BMD loss in older adults might be of particular concern because of aggravation of age-related bone loss. Moreover, the belief that obesity protects against fractures has now been challenged by studies demonstrating that obesity is associated with poor bone quality and ankle and leg fractures.Because of previous lack of options to assess bone quality in vivo, there has been little or no scientific study of the possibility that lifestyle therapy in obese older adults improves bone quality. This study represents an unprecedented opportunity to prove the hypothesis that lifestyle therapy intervention improves bone quality and thus, may confer a protective rather than adverse effect on bone health. This will be the first randomized controlled trial (RCT) to comprehensively assess bone quality using novel techniques in response to lifestyle therapy in obese older adults, with major ramifications with regards to defining optimal treatment strategies for this increasingly high-risk older population.

Official Title
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Does Lifestyle Intervention Improve Bone Quality in Obese Older Adults?

Conditions
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Aging, Obesity

Intervention / Treatment
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* Behavioral: Healthy Lifestyle Intervention
* Behavioral: Lifestyle Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 65 - 85 years • BMI 30 - 40 kg/m2 • Stable body weight (±2 kg) during the past 6 months • Sedentary (regular exercise <1 h/wk. or <2 x/wk. for the last 6 months) • Willing to provide informed consent Exclusion Criteria: Failure to provide informed consent. Any major chronic diseases, or any condition that would interfere with exercise or dietary restriction, in which exercise or dietary restrictions are contraindicated, or that would interfere with interpretation of results Cardiopulmonary disease (e.g. recent myocardial infarction, unstable angina, stroke) or unstable disease (e.g., New York Heart Class III or IV congestive heart failure, severe pulmonary disease requiring steroid pills or the use of supplemental oxygen ) that would contraindicate exercise or dietary restriction Severe orthopedic (e.g. awaiting joint replacement) and/or neuromuscular (e.g. multiple sclerosis, amyotrophic lateral sclerosis, active rheumatoid arthritis) disease or impairments that would contraindicate participation in exercise Other significant co-morbid disease that would impair ability to participate in the exercise-based intervention (e.g. renal failure on hemodialysis, severe psychiatric disorder [e.g. bipolar, schizophrenia], excess alcohol use [more than14 drinks per week]) Severe visual or hearing impairments that would interfere with following directions Significant cognitive impairment, defined as a known diagnosis of dementia or positive screening test for dementia using the Mini-Mental State Exam score less than 24) Uncontrolled hypertension (BP>160/90 mm Hg) History of malignancy during the past 5 years (except non-melanoma skin cancers) Current use of bone acting drugs (e.g. use of estrogen, or androgen containing compound, raloxifene, calcitonin, parathyroid hormone during the past year or bisphosphonates during the last two years) Osteoporosis (T-score -2.5 and below on hip or spine scan) or history of fragility fractures - Diabetes mellitus requiring insulin for treatment or with a fasting blood glucose of >140 mg/dl, and/or HbA1c >8.5% (Those excluded from the study because of fasting blood glucose of >140 mg/dl or HbA1c>8.5% will be referred to their primary care provider for follow-up and appropriate treatment). Terminal illness with life expectancy less than 12 months, as determined by a physician Use of any drugs or natural products designed to induce weight loss within past three months. Positive exercise stress test for ischemia

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 85 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lifestyle intervention Group<br>Behavioral therapy for weight loss and Exercise Training | Behavioral: Lifestyle Intervention<br>* The lifestyle modification will be achieved by group behavior therapy sessions designed to have older adults acquire positive weight-control skills/attitudes, and practice weight-maintenance skills.Participants will attend weekly group sessions (10-15 persons), which will last  75-90 minutes. Visit frequency will be decreased to every 2 wks. from 6 to 12 mos. to prevent treatment fatigue. A balanced diet will be prescribed to provide a deficit of 500-750 kcal/day from daily energy requirement. The exercise sessions are of  90 min duration ( 15 min warm-up of flexibility exercise, followed by  30 min of aerobic exercise, and after a brief rest period,  30 min of resistance training, and finally  15 min balance exercise) conducted three times weekly supervised at our exercise facility for one year. Aerobic exercises consist of treadmill, stationary cycling, and stair climbing.<br>|
| Active Comparator: Healthy lifestyle intervention Group<br>Group education sessions that focus on diet exercise and social support. | Behavioral: Healthy Lifestyle Intervention<br>* Participants in the this group will receive group educational sessions that focus on diet, exercise, and social support once a month throughout the study. The sessions will provide an opportunity for participants to discuss issues related to living with obesity and aging.Participants will also attend regular scheduled clinic visits for assessment of outcomes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cortical thickness | Assessed by using high-resolution peripheral computed tomography (HR-pQCT) | Change from baseline at 12 months | 
| Change in femoral bone strength | Assessed by using finite element analyses (FEA) of quantitative computed tomography (QCT) | Change from baseline at 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in bone material strength | Assessed by using microindentation testing | Change from baseline at 12 months | 
| Change in lower extremity strength | Assessed by using a Biodex dynamometer | Change from baseline at 12 months | 
| Change in physical performance test | assessed by using the objective physical performance test | Change from baseline at 12 months | 
| Change in gait speed | as measured by completing the time to walk a certain distance | Change from baseline at 12 months | 
| Change in handgrip strength | Measured by hydraulic hand dynamometer | Change from baseline at 12 months | 
| Change in trabecular thickness | Assessed by using HR-pQCT | Change from baseline at 12 months | 
| Change in areal bone mineral density (BMD) | Assessed by using dual-energy x-ray absorptiometry | Change from baseline at 12 months | 
| Change in trabecular number | Assessed by using HR-pQCT | Change from baseline at 12 month | 
| Change in total volumetric BMD | Assessed by using HR-pQCT | Change from baseline at 12 months | 
| Change in cortical volumetric BMD | Assessed by using HR-pQCT | Change from baseline at 12 months | 
| Change in trabecular volumetric BMD | Assessed by using HR-pQCT | Change from baseline at 12 months | 
| Change in stiffness | Assessed by using HR-pQCT | Change from baseline at 12 months | 
| Change in trabecular separation | Assessed by using HR-pQCT | Change from baseline at 12 months | 
| Change in micro-finite element analyses strength | Assessed by using HR-pQCT | Change from baseline at 12 months | 
| Change in cortical porosity | Assessed by using HR-pQCT | Change from baseline at 12 months | 
| Change in general quality of life | Assessed by using the Short Form-36 questionnaire | Change from baseline at 12 months | 
| Change in obesity specific quality of life | Assessed by using the Impact of weight on quality of life short form (IWQOL-Lite) questionnaire | Change from baseline at 12 months | 
| Change in mood | Assessed by using a mood scale questionnaire | Change from baseline at 12 months | 
| Change in composite cognitive z-score | Using cognitive instrument testing | Change from baseline at 12 months | 
| Change in cardio metabolic risk factors | Assessed by measuring metabolic syndrome components | Change from baseline at 12 months | 
| Change in word list fluency | Assessed by using cognitive instrument testing | Change from baseline at 12 months | 
| Change in Ray Auditory verbal learning test | Assessed by using cognitive instrument testing | Change from baseline at 12 months | 
| Change in blood pressure | Assessed by usingSphygmomanometer | Change from baseline at 12 months | 
| Change in biochemical marker for bone turnover and bone metabolism | Assessed by using enzyme linked immunosorbent assay and radioimmunoassay | Change from baseline at 12 months | 
| Change in central volumetric BMD | Assessed by using CT scan at the spine and hip | Change from baseline at 12 months | 
| Change in waist circumference | Assessed by using tape measurement | Change from baseline at 12 months | 
| Change in lean mass | Assessed by using dual-energy x-ray absorptiometry | Change from baseline at 12 months | 
| Change in fat mass | Assessed by using dual-energy x-ray absorptiometry | Change from baseline at 12 months | 
| Change in visceral fat | Assessed by using dual-energy x-ray absorptiometry | Change from baseline at 12 months | 
| Change in physical activity using accelerometer | Assessed by using an accelerometer | Change from baseline at 12 months | 
| Change in body weight | Assessed by using weighing scale | Change from baseline at 12 months | 
| Change in sclerostin | Assessed by using enzyme linked immunoassay | Change from baseline at 12 months | 
| Change in wnt signaling pathways | Assessed by measurements of circulating levels of Wnt 5a and Sfrp5 | Change from baseline at 12 months | 
| Change in total body mass | Assessed byusing dual energy x-ray absorptiometry | Change from baseline at 12 months | 
| Change in hormones | Assessed by usingenzyme link immunoassay | Change from baseline at 12 months | 
| Change in thigh mass | Assessed by using CT scan | Change from baseline at 12 months | 
| Change in circulating cytokines | Assessed by using enzyme linked immunoassay | Change from baseline at 12 months | 
| Change in adipocytokines | Assessed by using enzyme linked immunoassay | Change from baseline at 12 months | 
| Change in total volumetric BMD | Assessed by using QCT Pro software | Change from baseline at 12 months | 
| Change in cortical trabecular BMD | Assessed by using QCT Pro software | Change from baseline at 12 months | 
| Change in aerobic capacity | Assessed by using indirect calorimetry during graded treadmill test | Change from baseline at 12 months |