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TZD’s Can Increase Bone Loss in Type 2 Women

Nov 7, 2006

Elderly nursing home patients with type 2 diabetes mellitus have higher bone mass and lower bone turnover than those without diabetes. Harald Dobnig, MD, of the department of internal medicine at the Medical University of Graz in Austria, and colleagues undertook a study of women nursing home patients older than 70 to further examine the bone characteristics and the rates of fracture associated with diabetes in this population.

The study included 583 women with type 2 diabetes and 1,081 women without diabetes for a control group. Bone measurements were taken at the calcaneus, the distal one-third of the radius and the proximal phalanx of the third finger on the nondominant side; for the calcaneus, measurements resulted in a stiffness index combining speed of sound and broadband ultrasound attenuation.

Patients in the diabetes group were slightly younger than those in the control group, and fewer patients in the diabetes group had a diagnosis of osteoporosis (P=.07). Researchers followed patients for an average of 24.7 months, and during this period 378 control patients (35%) and 216 diabetes patients (37%) died.

Diabetic patients had higher age-, weight- and mobility score-adjusted calcaneal stiffness (–0.03 for diabetic patients vs. –0.52 for control patients, P<.0001). Speed of sound measurements at the peripheral radius (–0.49 vs. –0.81, P<.005) and phalanx (–0.65 vs. –0.79, P<.05) also showed higher bone mass in diabetic patients.

Bone turnover was found to be significantly lower in diabetic patients than in control patients. Regression analysis found that in both patient groups, parathyroid hormone was the most important predictor of osteocalcin levels, followed by HbA1c levels. “Independent of serum PTH, patients with higher HbA1c levels had higher calcaneal bone mass and lower bone turnover markers,” the researchers wrote.

The hazard ratio for hip fracture among diabetic patients was 0.90 vs. control patients (95% CI, 0.70-1.34) after adjustment for age and weight. Dobnig stated that, “Although type 2 diabetes mellitus has significant beneficial effects on bone turnover and bone mass, the fracture risk is equal to nondiabetic patients.” “This is likely due to an increase in the risk of falls; these two influences seem to neutralize each other.”

Dobnig noted that PTH appears to play a large role in the mechanisms of lower bone turnover and higher bone mass in diabetic patients. “PTH is down-regulated in long-standing type 2 diabetes,” he said. “For a given serum calcium level, PTH was significantly lower, pointing to a change in the calcium set-point for PTH secretion in diabetics. This, as well as the direct inhibitory effect of glycemia, seem to be the main responsible mechanisms for low bone turnover in this clinical setting.”

Furthermore, they discussed recent findings indicating that the use of thiazolidinediones in treating diabetes may increase bone loss, especially in diabetic women. “TZDs are a relatively new class of oral agents that have rapidly gained wide usage, with an estimated 20 million prescriptions written in 2004,” they wrote. Because of TZDs’ effects on bone and the increased risk of falls, it seems that fracture risk might actually be increased by type 2 diabetes.

“Patients with type 2 diabetes are certainly not protected from fracture and deserve at least the same screening for osteoporosis that is recommended for nondiabetic [patients].”

Journal of Clinical Endocrinology and Metabolism. Nov 2006; Watts NB, D’Alessio DA. Type 2 diabetes, thiazolidinediones: bad to the bone? J Clin Endocrinol Metab. 2006;91:3276-3278.


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