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The Link Between Diabetes and Bone Density/Osteoporosis

Apr 22, 2002

Fifty years since it was demonstrated that diabetes is associated with loss of bone mass. It has been more than 50 years and since that time, the relationship between osteopenia and type 1 diabetes has become well established, while the effects of type 2 diabetes on bone metabolism have remained less clear. One recent study[1] demonstrated a greater than 12-fold higher risk for hip fractures in women with type 1 diabetes compared with the general population. Women with type 2 diabetes had a still significant but much smaller 1.7-fold increase in risk. Patients with type 2 diabetes taking insulin had a greater risk than patients taking oral agents or than patients not on pharmacotherapy, suggesting that the severity of the metabolic abnormalities might be related to the subsequent risk of fracture.

Interpretation of fracture data as a surrogate measure for bone metabolism is particularly difficult in patients with long-standing diabetes,[2] because visual and neurologic complications can predispose patients to accidents resulting in an increased fracture risk not necessarily dependent on bone density alone. Other factors that make studies difficult to interpret include the presence of diabetic renal disease, autonomic and other neuropathic changes that could contribute to a loss of bone mineral,[3] and a low level of physical activity related to diabetic complications. Also, women with diabetes are much less likely to be on estrogen replacement therapy.

The metabolic factors could contribute to the apparent abnormalities of bone metabolism in diabetes are found in animal models of insulin-deficient diabetes, both decreased bone growth and formation have been demonstrated, along with reduced numbers of osteoblasts. Human studies using histomorphometry have demonstrated similar results.[4] Levels of osteocalcin, a serum marker of bone formation, are often depressed in patients with diabetes, while markers of bone resorption have most often been found to be normal or minimally depressed in both type 1 and type 2 patients. Some recent studies[5,6] demonstrate a significant increase in serum markers of both bone resorption and formation with improved glycemic control, especially when the initial HgbA1C is greater than 10%. These findings suggest that a reduced rate of bone formation occurs in both forms of diabetes during periods of poor glycemic control, which is not accompanied by a proportional reduction in the rate of bone resorption.

Insulin has anabolic effects on bone, and it is tempting to hypothesize that abnormal insulin levels contribute to abnormalities of bone metabolism. Nevertheless, it has been difficult to correlate changes in the concentration of insulin with changes seen in markers of bone turnover. Other growth factors such as insulin-like growth factor 1 (IGF-1), which may depend in part on insulin, may have a stronger correlation with improved bone formation as the metabolic state is normalized.[7]

While there is evidence for both an increased fracture rate and abnormal bone density in both forms of diabetes, the magnitude of risk is clearly greater for patients with classic type 1 disease. Differences between type 1 and type 2 diabetes are probably influenced by the much greater body weight typical of the latter, because obesity per se is associated with increased bone density. Also, patients with type 1 diabetes may go through more frequent episodes of profound insulin deficiency and metabolic acidosis at an early age, when peak bone mass is being determined. A greater peak bone mineral density would be anticipated for patients with type 2 diabetes, whose disease generally starts later in life and who tend to be overweight. It is even possible that a low rate of bone turnover might help protect the skeleton from the development of overt osteoporosis in some older patients.

In summary, it is clear that there is an increased risk for low bone mineral density and particularly for bone fractures in patients with type 1 and, to a lesser extent, type 2 diabetes. These abnormalities may be related at least in part to prolonged periods of poor metabolic control and might be decreased by more aggressive treatment regimens. In particular, aggressive prevention of periods of severe metabolic decompensation may be beneficial. Certainly women with diabetes need to pay special attention to the prevention of osteoporosis by maintaining an adequate calcium and vitamin D intake. This will often require calcium supplementation, which may need to be started at an early age while peak bone mass is still developing. To the extent that diabetes contributes to bone mineral loss by decreased bone turnover, therapies that act solely through reductions in bone resorption, such as the bisphosphonates, may have a complex effect on the bone mineralization.. Finally, physicians need to remember that interventions in the home to prevent accidents for patients with poor vision, sensory and motor neuropathy, and orthostatic hypotension may well contribute more to reducing the risk for serious fractures than any metabolic intervention.

1. Nicodemus KC, Folsom AR. Type 1 and type 2 diabetes and incidence of hip fractures in postmenopausal women. Diabetes Care. 2001;24:1192-1197.

2. Ivers RQ, Cumming RG, Mitchell P, Peduto AJ. Diabetes and the risk of fracture. Diabetes Care. 2001;24:1198-1203.

3. Rix M, Andreassen H, Eskildsen P. Impact of peripheral neuropathy on bone density in patients with type 1 diabetes. Diabetes Care. 1999;22:827-831.

4. SeinoY, Ishida H. Diabetic osteopenia: Pathophysiology and clinical aspects. Diabetes Metab Rev. 1995;11:21-35.

5. Sayinalp S , Gedik O, Koray Z. Increasing serum osteocalcin after glycemic control in diabetic men. Calcif Tissue Int. 1995;57:422-425.

6. Krakauer JC, McKenna MJ, Buderer NF, Rao DS, Whitehouse FW, Parfitt AM. Bone loss and bone turnover in diabetes. Diabetes. 1995;44:775-782.

7. Rosato MT, Schneider SH, Shapses SA. Bone turnover and insulin-like growth factor I levels increase after improved glycemic control in non-insulin dependent diabetes mellitus. Calcif Tissue Int. 1998;63:107-111.