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Frontiers of Medicine

Front Med    2013, Vol. 7 Issue (1) : 81-90     DOI: 10.1007/s11684-013-0243-9
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Impact of diabetes and its treatments on skeletal diseases
Wenbo Yan1, Xin Li2()
1. Department of Biology and Chemistry, Nyack College, Room B001, 361 Broadway, New York, NY 10013, USA; 2. Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, Room 901D Dental Center, 345 E. 24th St., New York, NY 10010, USA
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Abstract

Diabetes mellitus is an enormous menace to public health globally. This chronic disease of metabolism will adversely affect the skeleton if not controlled. Both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) are associated with an increased risk of osteoporosis and fragility fractures. Bone mineral density is reduced in T1DM, whereas patients with T2DM have normal or slightly higher bone density, suggesting impaired bone quality is involved. Detrimental effects of T1DM on the skeleton are more severe than T2DM, probably because of the lack of osteo-anabolic effects of insulin and other pancreatic hormones. In both T1DM and T2DM, low bone quality could be caused by various means, including but not limited to hyperglycemia, accumulation of advanced glycosylation end products (AGEs), decreased serum levels of osteocalcin and parathyroid hormone. Risk for osteoarthritis is also elevated in diabetic population. How diabetes accelerates the deterioration of cartilage remains largely unknown. Hyperglycemia and glucose derived AGEs could contribute to the development of osteoarthritis. Moreover, it is recognized that oral antidiabetic medicines affect bone metabolism and turnover as well. Insulin is shown to have anabolic effects on bone and hyperinsulinemia may help to explain the slightly higher bone density in patients with T2DM. Thiazolidinediones can promote bone loss and osteoporotic fractures by suppressing osteoblastogenesis and enhancing osteoclastogenesis. Metformin favors bone formation by stimulating osteoblast differentiation and protecting them against diabetic conditions such as hyperglycemia. Better knowledge of how diabetic conditions and its treatments influence skeletal tissues is in great need in view of the growing and aging population of patients with diabetes mellitus.

Keywords diabetes      bone      osteoporosis      osteoarthritis     
Corresponding Authors: Li Xin,Email:xl15@nyu.edu   
Issue Date: 05 March 2013
 Cite this article:   
Wenbo Yan,Xin Li. Impact of diabetes and its treatments on skeletal diseases[J]. Front Med, 2013, 7(1): 81-90.
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http://journal.hep.com.cn/fmd/EN/10.1007/s11684-013-0243-9
http://journal.hep.com.cn/fmd/EN/Y2013/V7/I1/81
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Fig.1  Possible mechanisms through which diabetic conditions increase the risk of osteoporotic fractures. Diabetic conditions common among both T1DM and T2DM patients can exert detrimental effects on skeletal tissues which will compromise bone quality. The impaired bone quality will reduce bone strength and therefore increase osteoporotic fracture risk. In addition to the above depicted factors, the lack of insulin and other bone anabolic hormones from the pancreas also contribute to impaired osteogenesis and decreased bone mass observed in T1DM patients. AGEs, advanced glycosylation end products; PTH, parathyroid hormone; MSC, mesenchymal stem cell; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus.
Fig.1  Possible mechanisms through which diabetic conditions increase the risk of osteoporotic fractures. Diabetic conditions common among both T1DM and T2DM patients can exert detrimental effects on skeletal tissues which will compromise bone quality. The impaired bone quality will reduce bone strength and therefore increase osteoporotic fracture risk. In addition to the above depicted factors, the lack of insulin and other bone anabolic hormones from the pancreas also contribute to impaired osteogenesis and decreased bone mass observed in T1DM patients. AGEs, advanced glycosylation end products; PTH, parathyroid hormone; MSC, mesenchymal stem cell; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus.
Fig.2  Diabetic conditions increase the risk of osteoarthritis. Diabetic conditions such as elevated blood glucose and blood AGEs levels have been suggested to compromise not only the quantity but also the quality of the cartilage tissues. This will increase the risk of developing osteoarthritis. DM, diabetes mellitus; AGEs, advanced glycosylation end products.
Fig.2  Diabetic conditions increase the risk of osteoarthritis. Diabetic conditions such as elevated blood glucose and blood AGEs levels have been suggested to compromise not only the quantity but also the quality of the cartilage tissues. This will increase the risk of developing osteoarthritis. DM, diabetes mellitus; AGEs, advanced glycosylation end products.
TreatmentsEffects on bone
Insulin (+)Stabilization of BMD and decrease in bone resorption;Prevention of osteopenia/osteoporosis
Thiazolidinediones (–)Suppressed bone formation (inhibited oesteoblastogenesis)Elevated bone resorption (enhanced osteoclastogenesis)
Metformin (+)Elevated bone formation (enhanced oesteoblastogenesis)Suppressed bone resorption (inhibited osteoclastogenesis)Protection of osteoblasts against hyperglycemia
Tab.1  Effects of diabetic treatments on bones
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