Skeletal Endocrine Laboratory

Lab head: Dr Tara Brennan-Speranza
Location: Room N350, Anderson Stuart Building, F13


The structural and cellular basis of skeletal and muscle fragility in type II diabetes mellitus

Primary supervisor: Tara Speranza

Patients with T2DM have hyperglycemia and normal to high bone mineral density (BMD). This is

usually associated with reduced fracture risk, yet patients with T2DM have a higher incidence of

fragility fractures and an increased overall fracture risk. The increase in fractures in patients with

T2DM is independent of factors such as age, sex, BMI, tendency to fall and visual impairment. This

implies the increased fracture risk is driven by compromised bone quality. The aim of the current

study is to test this hypothesis in mice and elucidate the specific mechanisms of action. Few rodent

studies have assessed the total effects of hyperglycemia on the skeleton.

Mice will be allocated to a normal chow or a high fat (60%) diet. Insulin sensitivity and glucose

tolerance will be monitored. The effects of hyperglycemia on the skeleton will be tested by

analysing microarchitecture using uCT methods, histologically via fluorescent calcein staining for

dynamic histomorphometry and for immunohistochemical analysis of the incorporation of AGE

products: CML and pentosidine. Lastly, the molecular pathways for the basis of these findings will

be analysed via qRT-PCR and western blotting to analyse the sclerostin content in bone and

BMP7/Smad1/5/8 pathway.

Discipline: Physiology
Keywords: Bone health, Diabetes, Animal Models