People with diabetes are at greater risk of bone fracture, and certain anti-diabetic drugs further increase this risk, particularly in postmenopausal women. But a new drug candidate could treat both type 2 diabetes and bone disease, expanding the treatment options.
A study co-led by Patrick R. Griffin, a professor on the Florida campus of The Scripps Research Institute (TSRI), and B. Lecka-Czernik, a professor at the University of Toledo, has shown that a new class of drug candidates developed at TSRI increases bone mass by expanding bone formation (deposition of new bone) and bone turnover (a normal process of replacement of old bone).
A proper balance of these two processes is critical to healthy bone maintanence, but diabetes interferes with bone formation.
Reporting on the new development, TSRI said that Griffin and his colleague, TSRI associate professor Theodore Kamenecka, have been investigating molecules that increase sensitivity to insulin (a hormone that regulates blood sugar). Using newly discovered information, the researchers made significant advances in developing a family of drug candidates that target a receptor known as peroxisome proliferator-activated receptors gamma (PPARy), a key regulator of stem cells controlling bone formation and bone resorption and a master regulator of fat.
Existing anti-diabetic drugs known as glitazones (TZDs) target the PPARy protein, but that interaction leads to severe bone loss and increased fractures. Stem cells in the bone marrow can differentiate either into bone cells or fat cells, and the glitazones drive them to fat at the expense of bone.
The new compound, known as SR10171, is designed to avoid this outcome. In animal models treated with the compound, fat formation in the bone marrow was successfully blocked independent of their metabolic state (healthy or diabetic).
“SR10171 improves bone mass regardless of body mass index, normal to obese,” Griffin said. “So you could use such a drug to treat osteoporosis whether patients are diabetic or not.”
The findings have been published in the journal EBioMedicine.