Bone fragility in type 2 diabetes mellitus

Abstract

The number of patients with osteoporosis or type 2 diabetes mellitus (T2DM) is increasing in aging and westernized societies. Both disorders predispose elderly people to disabling conditions by causing fractures and vascular complications, respectively. Recent animal studies have shown that administration of osteocalcin, which is specifically secreted from osteoblasts, can increase insulin secretion and ameliorate hyperglycemia, obesity, and high triglyceride levels in mice fed a high-fat diet. Moreover, several studies have shown that antagonism of Wnt signaling by oxidative stress contributes to the development of osteoporosis, as well as insulin resistance and hyperlipidemia. Thus, bone metabolism and glucose/fat metabolism seem to be etiologically related to each other. Meta-analyses of multiple clinical studies in humans have shown that hip fracture risk of T2DM patients is increased by 1.4-1.7-fold, although bone mineral density (BMD) is not diminished. Vertebral fracture risk of T2DM patients is also increased, and BMD is not sensitive enough to assess the risk. These findings suggest that bone fragility in T2DM, which is not reflected by BMD, depends on bone quality deterioration rather than bone mass reduction. Thus, surrogate markers are needed to replace the insensitivity of BMD in assessing fracture risks of T2DM patients. Pentosidine, the endogenous secretory receptor for advanced glycation endproducts, and insulin-like growth factor-I seem to be such candidates, although further studies are required to clarify whether or not these markers could predict the occurrence of new fractures of T2DM patients in a prospective fashion.

Keywords: Fracture risk; Osteocalcin; Osteoporosis; Type 2 diabetes mellitus; Wnt signaling.

Figure 1

When osteocalcin was administered to obese mice, it increased insulin secretion, and decreased blood glucose level, fat mass, and triglyceride level. In humans, serum carboxylated and uncarboxylated osteocalcin levels were positively correlated with insulin sensitivity and adiponectin level, whereas they were negatively correlated with blood glucose level, fat mass, and atherosclerosis index. Thus, osteoporosis and diabetes are pathophysiologically related to each other through osteocalcin (OC) action in mice and humans.

Figure 2

Distribution of bone mineral density in subjects with and without vertebral fractures (black dots and open circles, respectively) as a function of age. BMD: Bone mineral density; T2DM: Type 2 diabetes mellitus.