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

• Osteocalcin levels [ Time Frame: Change at 20, 60 and 120 minutes ] [ Designated as safety issue: No ]
• β Carboxy-terminal collagen crosslinks (β CTx)levels [ Time Frame: Change at 20, 60 and 120 minutes ] [ Designated as safety issue: No ]
• Procollagen 1 N-terminal propeptide (P1NP) levels [ Time Frame: Change at 20, 60 and 120 minutes ] [ Designated as safety issue: No ]
• High-resolution peripheral quantitative computed tomography (HRpQCT) [ Time Frame: At baseline ] [ Designated as safety issue: No ]
• Dual-emission X-ray absorptiometry (DXA) [ Time Frame: At baseline ] [ Designated as safety issue: No ]

• Osteocalcin levels [ Time Frame: Up to 120 minutes ] [ Designated as safety issue: No ]
• β Carboxy-terminal collagen crosslinks (β CTx)levels [ Time Frame: Up to 120 minutes ] [ Designated as safety issue: No ]
• Procollagen 1 N-terminal propeptide (P1NP) levels [ Time Frame: Up to 120 minutes ] [ Designated as safety issue: No ]
• High-resolution peripheral quantitative computed tomography (HRpQCT) [ Time Frame: At baseline ] [ Designated as safety issue: No ]
• Dual-emission X-ray absorptiometry (DXA) [ Time Frame: At baseline ] [ Designated as safety issue: No ]

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

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

The investigators will recruit healthy pre-menopausal, Caucasian female participants 25-40 years and divide them into two groups, obese and lean according to their Body Mass Index. Participants will be identified and approached from a study group of obese and lean participants previously recruited for the 'The Effects of Obesity on Bone Structure and Strength - Fat and Bone Study (FAB)' study (REC ref 10/H1308/61) conducted at the Academic Unit of Bone Metabolism (AUBM) in Sheffield. Participants from this study have been selected as some of the scan and neuromuscular function data generated from this study will be reused as explained below. Body Mass Index ≥30 kg/m2 will be used to define obesity with BMI for lean participants defined as 18.5-24.9 kg/m2. Thirty participants will be recruited, 15 obese and 15 lean. Participants will be matched for age, and where possible height.

• Obese
  Premenopausal women, 25 - 40 years with BMI of ≥30kg/m2
  Intervention: Other: Study visit procedures
• Lean
  Premenopausal women, 25 - 40 years with BMI of 18.5-24.9 kg/m2
  Intervention: Other: Study visit procedures

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