MD Meet the Professor-Diabetes

MD-1

PATHOGENESIS OF OSTEOPOROSIS AND OSTEOPOROTIC FRACTURES IN PATIENTS WITH DIABETES

J-F KUO

Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Taiwan, ROC

Both type 1 (T1DM) and 2 diabetes (T2DM) are associated with an increased risk of fracture. Although bone mineral density (BMD) is decreased in T1DM, BMD in T2DM is often normal or even slightly elevated compared with an age-matched control population. On the other hand, bone loss as determined by Dual-energy X-ray absorptiometry (DXA) occurs more rapidly in type 2 diabetic postmenopausal women. Fracture risk in T2DM is higher for a given BMD T-score and age or for a given Fracture Risk Assessment Tool (FRAX) score. Bone strength consists of BMD and bone quality, which suggests that factors other than BMD play a major role in bone quality in diabetes.

The skeletal system seems to be an additional target of diabetes-mediated damage, leading to the development of diabetes- induced osteoporosis. Mechanisms of diabetes- induced bone fragility including low bone turnover, accumulation of advanced glycation end products (non-enzymatic glycosylation of collagen) with micro and macro-architecture alterations (increased cortical porosity) that cause reduced resistance to mechanical stress, pro-inflammatory state with increased oxidative like growth factor 1, loss of incretin effect, increased marrow fat. Complications of DM increase the risk of falls and fracture including peripheral neuropathy, orthostatic hypotension, sarcopenia, risk.

MD-2

PHARMACOLOGIC TREATMENT FOR OSTEOPOROTIC FRACTURES IN PATIENTS WITH DIABETES

JAWL-SHAN HWANG, MD

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital

Osteoporosis and diabetes are two common diseases in developed countries that are related to the aging of population, as well as in Taiwan. Osteoporosis characterized by a decrease in bone mass and deterioration in skeletal microarchitecture, which lead to increased fragility and susceptibility to fractures.

There is clear evidence that type 1 and type 2 diabetic patients have a higher fracture risk than nondiabetic people. However, the risk of osteporotic fractures in these patients does not correspond to low bone mineral density as measured by dual energy X-ray absorptiometry. Actually, the majority of the studies carried out in T2DM patients have shown a BMD normal or paradoxically higher than nondiabetic controls, where fracture risk is increased in patients despite normal or even high bone present, are the cause of reduced bone strength. The parameters that describe the mechanical behavior failure load and energy absorption), while intrinsic properties describe the mechanics of the bone tissue (e.g. failure stress and toughness). Bone mass, structure and intrinsic material properties all contribute to the extrinsic or whole-bone mechanics. Causes of reduced bone tissue mechanics in diabetes may include reduced bone turnover, increased porosity and the accumulation of non-enzymatic collagen cross-links known as advanced glycation end-products. These cross-links form spontaneously through non-enzymatic glycation, and are known to affect bone mechanics directly by reducing extrinsic and intrinsic properties, and indirectly by inhibiting osteoblast function, in particular in combination with high levels of glucose.

In clinical practice, the diagnosis of osteoporosis in diabetic patient needs further investigations beyond the measurement of BMD. Bone health should be considered part of the diabetic management algorithm, and monitored as diligently as are diabetic eye examinations, cholesterol levels or foot care. Currently, not all guidelines include bone health as a part of diabetes care. The general recommendations for the intake of calcium, vitamin D should be applied to the diabetic population. Exercise should be greatly encouraged in patients with diabetes. The focus should be in understanding the pathophysiology of bone fragility in diabetics, so that appropriate therapies directed at the underlying cause of decreased BMD can be used. Further studies need to be conducted to guide clinicians toward appropriate screening and the best possible treatment modalities available for bone fragility in diabetics.