Osteoporosis in diabetes mellitus: Possible cellular and molecular mechanisms

Abstract

Osteoporosis, a global age-related health problem in both male and female elderly, insidiously deteriorates the microstructure of bone, particularly at trabecular sites, such as vertebrae, ribs and hips, culminating in fragility fractures, pain and disability. Although osteoporosis is normally associated with senescence and estrogen deficiency, diabetes mellitus (DM), especially type 1 DM, also contributes to and/or aggravates bone loss in osteoporotic patients. This topic highlight article focuses on DM-induced osteoporosis and DM/osteoporosis comorbidity, covering alterations in bone metabolism as well as factors regulating bone growth under diabetic conditions including, insulin, insulin-like growth factor-1 and angiogenesis. Cellular and molecular mechanisms of DM-related bone loss are also discussed. This information provides a foundation for the better understanding of diabetic complications and for development of early screening and prevention of osteoporosis in diabetic patients.

Keywords: Bone remodeling; Bone strength; Diabetes; Fragility fracture; Insulin; Osteoblast; Osteoclast; Osteopenia; Osteoporosis; Pregnancy.

Figure 1

Possible deleterious effects of diabetes mellitus on bone metabolism and bone quality. Diabetes mellitus (DM) increases osteoclast function but decreases osteoblast function, thereby leading to accelerated bone loss, osteopenia and osteoporosis. DM/hyperglycemia induces production of macrophage colony stimulating factor (MCSF), tumor necrosis factor (TNF)-α and receptor activator of nuclear factor-κB ligand (RANKL), all of which are osteoblast-derived activators of osteoclast proliferation and differentiation. Moreover, DM/hyperglycemia suppresses osteoblast proliferation and function, in part, by decreasing runt-related transcription factor (Runx)-2, osteocalcin and osteopontin expressions. Adipogenic differentiation of mesenchymal stem cells is increased as indicated by the overexpression of adipocyte differentiation markers, including peroxisome proliferator-activated receptor (PPAR)-γ, adipocyte fatty acid binding protein (aP2), adipsin and resistin. A decrease in neovascularization may further aggravate bone loss. Bone quality is also reduced as a result of advanced glycation end products (AGE) production, which may eventually result in low-impact or fragility fractures.