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Relationships Between GLP-2 and Markers of Bone Turnover Following Feeding

Completed
Conditions
Obesity
Interventions
Other: Study visit procedures
Registration Number
NCT01531907
Lead Sponsor
Sheffield Teaching Hospitals NHS Foundation Trust
Brief Summary

This study has been designed to study differences bone turnover in relation to glucagon-like peptide-2 (GLP-2) following feeding in lean and obese premenopausal women. Given the preliminary evidence that GLP-2 may act directly on osteoclasts, the investigators plan to determine whether GLP2 receptors are expressed in osteoclasts and the effect of GLP-2 on bone resorption.

Hypotheses:

1. Acute responses of GLP-2 and bone resorption markers following feeding are affected by body fat mass.

2. Serum levels of GLP-2 are lower in obese pre-menopausal women and are associated with a reduction in trabecular and/or cortical bone mass

3. GLP-2 has direct actions on osteoclast resorption via a functional receptor

Detailed Description

Study objectives:

1. To determine if differences in baseline serum levels of GLP-2 are related to differences in bone microarchitecture, structure and strength at the distal tibia and distal radius between obese and lean premenopausal females.

2. To determine whether obesity in premenopausal females influences levels of circulating GLP-2 following a standardised glucose meal with a resultant change in markers of bone formation and resorption

3. To test whether GLP-2 directly affects osteoclast function via an identifiable receptor

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
19
Inclusion Criteria
  • Age 25-40
  • Caucasian
  • Premenopausal
  • Able and willing to consent
  • BMI either 18.5-24.9 kg/m2 or ≥30 kg/m2
  • Completion 'The Effects of Obesity on Bone Structure and Strength' study REC ref 10/H1308/61
  • Consented to be approached for future research studies
Exclusion Criteria
  • Fracture less than twelve months prior to recruitment

  • History of any long term immobilization (duration greater than three months)

  • Current pregnancy or trying to conceive Pregnancy or breast feeding less than one year prior to recruitment

  • Diabetes mellitus

  • History of or current conditions known to affect bone metabolism, which may include:

    • Diagnosed skeletal disease or osteoarthritis
    • Chronic renal disease
    • Acute or chronic hepatic disease
    • Hyperparathyroidism or Hyperthyroidism
    • Malabsorption syndromes
    • Diagnosed endocrine disorders
    • Diagnosed diabetes mellitus
    • Clinically significant hypocalcemia or hypercalcemia
    • Diagnosed restrictive eating disorder
  • Current or clinically significant previous use of medications or treatment known to affect bone metabolism, for example:

    • Depot medroxyprogesterone or the combined oral contraceptive pill
    • Glucocorticoid therapy
    • Anti-convulsant therapy
    • Bone treatments (e.g. Bisphosphonates)
  • Alcohol intake of greater than 21 units per week

  • Athlete, defined as an individual participating in competitive sport at amateur or professional level

  • Monogenic and obesity syndromes

  • History of cancer within the past 5 years excluding skin cancer non melanomas

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
ObeseStudy visit proceduresPremenopausal women, 25 - 40 years with BMI of ≥30kg/m2
LeanStudy visit proceduresPremenopausal women, 25 - 40 years with BMI of 18.5-24.9 kg/m2
Primary Outcome Measures
NameTimeMethod
GLP-2 levelsChange at 20, 60 and 120 minutes
Secondary Outcome Measures
NameTimeMethod
Osteocalcin levelsChange at 20, 60 and 120 minutes
β Carboxy-terminal collagen crosslinks (β CTx)levelsChange at 20, 60 and 120 minutes
High-resolution peripheral quantitative computed tomography (HRpQCT)At baseline
Procollagen 1 N-terminal propeptide (P1NP) levelsChange at 20, 60 and 120 minutes
Dual-emission X-ray absorptiometry (DXA)At baseline

Trial Locations

Locations (1)

Academic Unit of Bone Metabolism

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Sheffield, South Yorkshire, United Kingdom

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