The Role of Sclerostin in Bone in Patients with Diabetes Mellitus
Research type
Research Study
Full title
Does Sclerostin contribute to the pathogenesis of skeletal complications in Diabetic Mellitus?
IRAS ID
139965
Contact name
Ines LH Reichert
Contact email
Sponsor organisation
King's College Hospital NHS Foundation Trust
Research summary
Diabetes Mellitus is detrimental for bone health leading to an increase in fracture risk, delay in fracture repair with a high risk of complications such as infection, non- or mal-union. Our understanding of the mechanisms leading to the loss of bone and its reduced strength in diabetic patients is limited.
We plan to study the role of Sclerostin, a signalling protein highly specific to osteocytes, ie mature bone cells, in diabetic bone. Sclerostin is expressed by osteocytes and has been found to inhibit bone formation in normal bone. Sclerostin levels can be also measured in blood serum. Changes in the production of Sclerostin in diabetic bone may contribute to bone loss and impaired fracture healing.
Charcot osteoarthropathy (COA) is a separate entity of bone and joint disease in patients with severe diabetes and consequent neuropathy. COA leads to devastating consequences for the individual with loss of shape and function of joints, most commonly in foot and ankle. Clinical evidence indicates that diabetic bone is such fragility and poor quality, compared with normal bone, for such changes to occur.
Sclerostin acts as negative regulator of bone formation. Indeed an absence of Sclerostin leads to a significant overgrowth of bone. However in a diabetic patient we would expect the opposite mechanism i.e. pathologically high levels of Sclerostin which may inhibit bone formation.We hypothesise that:
1) hyperglycemia (high blood sugar levels) increases sclerostin production by osteocytes
2) the number of osteocytes and sclerostin levels in bone and blood serum correlate to decreased bone formation activity and impaired fracture repair in diabetic and COA neuropathic diabetic bone.This project will examine the role of sclerostin in the pathogenesis of skeletal complications in patients with Diabetes Mellitus. Human bone biopsies and blood samples from diabetic and COA patients will be investigated and compared to non-diabetic patients.
REC name
London - Bromley Research Ethics Committee
REC reference
14/LO/1483
Date of REC Opinion
28 Oct 2014
REC opinion
Further Information Favourable Opinion