The Effects of Obesity on Bone Structure and Strength

NCT02629185 | Completed

• 1 other identifier: STH15688
• Study Type: observational
• Target: 258
• Locations: 1 country
• Sites: 1

Brief Summary

High body weight is protective against hip and spine fracture, but has been found to increase the risk of humerus, foot and ankle fracture. Increasing understanding of the actions of adipokines on bone suggests that there may be complex effects on different aspects of bone geometry and microarchitecture and that these effects may vary depending on whether adipokines act directly on bone cells or through the central nervous system and between cortical and trabecular compartments. Previous research is limited by the use of areal dual-energy x-ray absorptiometry (DXA) scans which may be inaccurate in obese populations due to increased body thickness. The aim of this study is to investigate the effect of obesity on bone mineral density, bone geometry, bone microarchitecture and bone strength of the hip, lumbar spine, distal radius and tibia. This is an observational, cross-sectional study of normal weight and obese individuals matched by age, gender, height, postcode and smoking. The total number of subjects will be 240; men and premenopausal women ages 25 to 40 years and men and postmenopausal women ages 55 to 75 years. DXA, high-resolution peripheral computed tomography (HR-pQCT), quantitative computed tomography (QCT) and finite element analysis will be used to assess bone structure and strength. Biochemical markers of bone turnover and hormones related to bone metabolism will also be measured in order to identify potential mediators of the effects of obesity on bone structure and strength. A sub-study has been included to evaluate the interaction of fracture risk and cardiovascular risk in obese and non-obese individuals. There is evidence of an interaction between bone mineral density (BMD) and cardiovascular risk and test the hypothesis that there are common pathways linking BMD and cardiovascular risk, including fat secretion of inflammatory cytokines e.g. interleukin-1 and adipokines e.g. leptin and adiponectin. Ultrasound based assessments of vascular function will be used to assess cardiac risk and relate these measures to bone density. Obese individuals have lower circulating levels of 25OHD. This may be due to poor nutritional intake, reduced sunlight exposure or the vitamin D being stored in fat tissue. The investigators will measure levels of 25OHD in lean, overweight and obese men and women to examine whether 25(OH)D is related to age or gender and whether low 25OHD in obesity affects bone health in subsets of lean, overweight and obese participants of different ages.

Conditions

Osteoporosis; Obesity

Keywords

Bone; Vitamin D; Cardiovascular

Outcome Measures

Primary Outcomes (1)

• mean difference in DXA hip BMD between normal weight and obese

  one measurement at study entry (cross-sectional study)

Secondary Outcomes (6)

• mean difference in other BMD measures between normal weight and obese

  one measurement at study entry (cross-sectional study)

• mean difference in bone microarchitecture measures between normal weight and obese

  one measurement at study entry (cross-sectional study)

• mean difference in biochemical bone turnover markers between normal weight and obese

  one measurement at study entry (cross-sectional study)

• mean difference in hormones between normal weight and obese

  one measurement at study entry (cross-sectional study)

• mean difference in cardiovascular risk measures between normal weight and obese

  one measurement at study entry (cross-sectional study)

Study Arms (3)

normal weight

BMI 18.5 to 25.0 Healthy men and women ages 25-40 and 55-75

overweight

BMI 25.0 to 30.0 Healthy men and women ages 25-40 and 55-75

obese

BMI over 30.0 Healthy men and women ages 25-40 and 55-75

Eligibility Criteria

• Age: 25 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Healthy Caucasians Recruited from South Yorkshire, UK

You may qualify if:

• Caucasian
• BMI of 18.5 kg/m2 or above
• Ages 25 to 40 years (and premenopausal if female) or 55 to 75 years (and postmenopausal (at least 5 years since last menstrual period) if female)
• Sufficiently mobile to undergo scanning
• Able to remain motionless for the duration of the scans
• Able and willing to participate in the study and provide written informed consent

You may not qualify if:

• Previous orthopaedic surgery or fractures which preclude imaging at all sites
• History of any long term immobilization (duration greater than three months)
• High trauma fracture or low trauma fracture less than one year prior to recruitment
• Current pregnancy or trying to conceive
• Delivery of last child less than one year prior to recruitment
• Breast feeding less than one year prior to recruitment
• Pre-diagnosed diabetes mellitus
• History of or current conditions known to affect bone metabolism including:
• Diagnosed skeletal disease
• Osteoarthritis at study measurement sites
• Chronic renal disease
• Malabsorption syndromes
• Diagnosed endocrine disorders
• Hypocalcemia or hypercalcemia
• Diagnosed restrictive eating disorder

Sponsors & Collaborators

• Sheffield Teaching Hospitals NHS Foundation Trust: lead
• University of Sheffield: collaborator
• National Osteoporosis Society: collaborator
• Orthopaedic Research UK: collaborator

Study Sites (1)

University of Sheffield

Sheffield, S10 2TN, United Kingdom

Location

Related Publications (1)

• Evans AL, Paggiosi MA, Eastell R, Walsh JS. Bone density, microstructure and strength in obese and normal weight men and women in younger and older adulthood. J Bone Miner Res. 2015 May;30(5):920-8. doi: 10.1002/jbmr.2407.

  PMID: 25400253 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Serum, plasma, urine, DNA

MeSH Terms

Conditions

Osteoporosis; Obesity

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Jennifer S Walsh, MBChB PhD

  University of Sheffield

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: ECOLOGIC OR COMMUNITY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2015
• First Posted: December 14, 2015
• Study Start: September 1, 2010
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: December 14, 2015

Record last verified: 2015-12

Locations

GB (1)