Decrease in serum leptin by troglitazone is associated with preventing bone loss in type 2 diabetic patients.
The thiazolidinedione (TZD) class of antidiabetic drugs has been shown to inhibit the formation of bone-resorbing osteoclasts in vitro and to decrease bone resorption markers in vivo. These drugs also inhibit the expression of leptin in adipocytes. Less leptin can be associated with higher bone mass, based on analyses of mice deficient in leptin action. Effects of 1-year treatment with troglitazone, a member of the TZDs, on bone mineral density (BMD) and bone metabolism were examined in 25 Japanese type 2 diabetic patients. Glucose metabolism was improved, whereas body mass index and percent body fat did not change throughout the study. The percent change of BMD was negatively correlated with that of serum leptin, whereas it was not associated with changes of bone metabolic markers, type I collagen N-telopeptide (NTx), bone alkaline phosphatase (ALP), body mass index, or HbA1c. Serum leptin decreased in 68% of subjects (responders) after 1-month treatment and was consistently lower than the basal level throughout the treatment. Percent changes of BMD were significantly higher in the responders than in the nonresponders and in nondiabetic subjects at 6 and 12 months. NTx and bone ALP decreased at 1 month but increased thereafter in either group of patients. Thus, it is suggested that the decrease in serum leptin with no reduction in body fat mass by troglitazone is associated with preventing bone loss in type 2 diabetic patients. Hence, TZDs may have an advantage for diabetic patients who have risk factors for osteoporosis.
Division of Endocrinology, Department of Medicine, University of Tokyo School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Sumiyo
S
Watanabe
Yasuhiro
Y
Takeuchi
Seiji
S
Fukumoto
Hiroko
H
Fujita
Tadasumi
T
Nakano
Toshiro
T
Fujita
D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism; D015519:Bone Density; D002839:Chromans / Q000627:therapeutic use*; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D024042:Collagen Type I; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D020738:Leptin / Q000097:blood*; D008159:Lumbar Vertebrae / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D010455:Peptides / Q000187:drug effects / Q000378:metabolism; D011446:Prospective Studies; D045162:Thiazolidinediones / Q000627:therapeutic use*; D000077288:Troglitazone
D000469:Alkaline Phosphatase; D002839:Chromans; D003094:Collagen; D024042:Collagen Type I; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D020738:Leptin; D010455:Peptides; D045162:Thiazolidinediones; D000077288:Troglitazone; C052929:collagen type I trimeric cross-linked peptide