Type 2 diabetes and bone disease

Robert Josse (Toronto, Canada) discussed new concepts of skeletal homeostasis and its disorders in a symposium addressing the relationship of type 2 diabetes, and in particular that of thiazolidinedione (TZD) treatment, to bone disease. Remodeling is the process of combined osteoclast and osteoblast activity that optimizes bone structure to improve strength and mechanical function and repair microdamage, fulfills metabolic functions, and acts as an important source of growth factors. The basic multicellular units of bone contain osteoclasts that excavate bone, mononuclear cells that remove cellular debris, and osteoblasts that replace the removed bone. Receptor activator of nuclear factor-κB (RANK) ligand is a transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds RANK and osteoprotegerin and plays an important role in regulating osteoclast differentiation and activation, whereas the Wnt (related to a gene controlling wing forming in fruit flies) system controls osteoblast activity with complex signals linking osteoblasts and osteoclasts (1). An LDL receptor–related protein (LRP)5 mutation is associated with increased bone mass. The LRP5/Wnt signaling pathway increases activity of the multifunctional protein β-catenin that participates in cell adhesion and nuclear signaling and is inhibited by an osteocyte product sclerostin (defects in this are associated with sclerositis) and by the antagonist Dickkopf (DKK) proteins. DKK1 is a myeloblast product that helps explain the failure of multiple myeloma lesions to show activity on bone scan.

Osteoporosis may be caused by increased osteoclast or decreased osteoblast activity, compromising bone strength, which Josse suggested be seen as an integrated measure of bone density and bone quality, recognizing that standard bone density measurement fails to assess the latter component. Bones break when the applied …