Short-term treatment with troglitazone decreases bone turnover in patientswith type 2 diabetes mellitus

Poorly controlled type 2 or non-insulin dependent diabetes mellitus (NIDDM) patients exhibit high bone turnover, which decelerate with treatment accor ding to the degree of improvement in glycemic control. In adults, higher bo ne turnover results in rapid bone loss. Therefore, deceleration of bone tur nover is beneficial for bone. Troglitazone (Tro), a new anti-diabetic drug, is a thiazolidinedione (TZD) which promotes adipocyte differentiation by a ctivating peroxisome proliferator activated receptor gamma (PPAR gamma). Be cause, in the bone marrow, adipocytes and osteoblasts originate in common m esenchymal stem cells that are also essential for osteoclastogenesis, TZDs may directly affect bone metabolism. Thus, we examined the effects of Tro o n metabolic bone markers in type 2 DM patients. Tro (400 mg/day) was admini stered to 33 type 2 DM patients for four weeks. The day before and four wee ks after starting Tro, serum and urine samples were collected after overnig ht fasting. Metabolic bone markers and glycemic indices were assessed. As b one resorption markers, urinary free and total deoxypyridinoline as well as urinary collagen type I C-terminal telopeptide were measured; as bone form ation markers, serum bone type and total alkaline phosphatase (BALP and ALP ) levels along with osteocalcin (OC) were used. No significant changes in f asting plasma glucose or HbA1c levels were observed in our short-term treat ment with Tro. All the bone resorption markers, BALP and ALP were significa ntly decreased. OC was not significantly changed. The discrepant changes of OC from all the other metabolic bone markers suggest limitation of the use of OC as a reliable bone formation marker in diabetics. Our results that T ro decreased metabolic bone markers before significantly improving glucose metabolism suggest that it has direct effects on bone and decreased bone tu rnover. TZDs may spare bone mass in NIDDM subjects through its dual effects on glucose and bone metabolism.