Interaction between bone and glucose metabolism [Review]

Abstract

Abstract.Accumulating evidence has shown that bone and glucose metabolism are closely associated with each other. Since the risk of osteoporotic fractures is increased in patients with diabetes mellitus (DM), osteoporosis is recently recognized as one of diabetic complications, called DM-induced bone fragility. Previous studies showed that collagen cross-links of advanced glycation end products (AGEs) and dysfunctions of osteoblast and osteocyte are involved in DMinduced bone fragility. Circulating levels of AGEs and homocysteine are increased in patients with DM, and they directly impair the functions of osteoblast and osteocyte, resulting in decreased bone formation and bone remodeling. On the other hand, bone is recently recognized as an endocrine organ. Previous studies based on in vitro and animal studies showed that osteocalcin, which is specifically expressed in osteoblasts and secreted into the circulation, may regulate glucose homeostasis. Although several clinical studies reported the relationship between osteocalcin and glucose metabolism, further large-scale and intervention studies are necessary to confirm the beneficial effects of osteocalcin on glucose metabolism in human. It has been shown that adenosine monophosphate-activated protein kinase (AMPK), an intracellular energy sensor, is involved in bone metabolism. Adiponectin and metformin stimulate osteocalcin expression and the differentiation of osteoblasts via AMPK activation. Also, AMPK activation protects against oxidative stress-induced apoptosis of osteocytes. These findings suggest that AMPK in osteoblasts and osteocytes may be a therapeutic target for DM-induced bone fragility.

Retinol‐binding protein 4 is positively associated with bone mineral density in patients with type 2 diabetes and osteopenia or osteoporosis

“…Similar studies were also reported in type I diabetes mellitus . It has been recommended that skeleton deterioration and fragility, such as osteoporosis, are also part of diabetic‐related complications …”

Metabolic and bone profile in postmenopausal women with and without type 2 diabetes: a cross-sectional study

“…However, overweight and obese patients present an increased risk of fracture to minimal trauma, such as proximal humerus fracture or ankle [10,24], thus an increased BMI is no longer a protective factor against fragility fractures as it was considered in the past [5,12,23,24]. Thereby, the risk of fracture in diabetic patients is less dependent on the bone quantity (bone mass density), but more on bone quality [12,26,27].…”

D-mannose attenuates bone loss in mice via Treg cell proliferation and gut microbiota-dependent anti-inflammatory effects

“…Although the relationship between D-mannose and bone metabolism is still obscure, accumulating evidences have shown that saccharides, like glucose play a role in bone metabolism. [33][34][35] For example, Kanazawa and colleagues reported that advanced glycation end-products of glucose can increase reactive oxygen species production, impair osteoblast and osteocyte activity, and eventually decrease bone formation. 35 However, as an epimer of D-glucose, D-mannose increased bone formation inversely, which may be associated with other mechanisms.…”