Baseline atherosclerosis parameter could assess the risk of bone loss during pioglitazone treatment in type 2 diabetes mellitus.
CONCLUSIONS
We found that serum osteocalcin, femoral bone mineral density (F-BMD), and 1/3R-BMD were decreased during pioglitazone treatment in patients with type 2 diabetes. Moreover, baseline atherosclerosis parameter, serum insulin-like growth factor-I (IGF-I), and urinary N-terminal cross-linked telopeptide of type I collagen (uNTX) values were associated with changes in bone mineral density (BMD). Therefore, these parameters could assess the risk of BMD reduction in patients treated with pioglitazone.


BACKGROUND
The aim of this study was to investigate the effects of pioglitazone or metformin on bone mass and atherosclerosis in patients with type 2 diabetes.


METHODS
A total of 55 Japanese patients were enrolled in this 1-year open-label study and randomized to either pioglitazone (n = 22, 15-30 mg/day) or metformin (n = 23, 500-750 mg/day) groups. BMD at the lumbar spine, femoral neck (F), and one third of the radius (1/3R), bone markers, and atherosclerosis parameters were measured.


RESULTS
In the pioglitazone group, serum osteocalcin significantly decreased at 6 months (p < 0.05), although it almost recovered to baseline level at 12 months. F-BMD significantly decreased at 6 months (p < 0.05), and 1/3R-BMD significantly decreased at 6 and 12 months (p < 0.05), while bone markers or BMD at any site were not changed in the metformin group. Although atherosclerosis parameters were not changed in the pioglitazone group, intima-media thickness (IMT)-mean significantly increased at 6 months (p < 0.05) and plaque score significantly increased at 6 and 12 months (p < 0.01) in the metformin group. In the pioglitazone group, %changes in F-BMD were significantly and negatively correlated with baseline IMT-Max, IMT-mean, and plaque scores (r = -0.61, p < 0.01; r = -0.71, p < 0.01; and r = -0.68, p < 0.01, respectively), and %changes in 1/3R-BMD were significantly and negatively correlated with baseline uNTX and IMT-Max (r = -0.57, p < 0.01 and r = -0.48, p < 0.05, respectively) and positively with IGF-I (r = 0.45, p < 0.05).


CONCLUSIONS
Baseline IMT, uNTX, and IGF-I could assess the risk of BMD reduction in diabetic patients treated with pioglitazone.
Kanazawa
I
I
Department of Internal Medicine 1, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan. ippei.k@med.shimane-u.ac.jp
Yamaguchi
T
T
Yano
S
S
Yamamoto
M
M
Yamauchi
M
M
Kurioka
S
S
Sugimoto
T
T
D000368:Aged; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000378:metabolism / Q000517:prevention & control*; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D003094:Collagen / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005272:Femur Neck / Q000503:physiopathology; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008159:Lumbar Vertebrae / Q000503:physiopathology; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D000077205:Pioglitazone; D011884:Radius / Q000503:physiopathology; D018570:Risk Assessment / Q000379:methods; D045162:Thiazolidinediones / Q000009:adverse effects* / Q000627:therapeutic use; D014463:Ultrasonography
D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; C461299:urinary N-telopeptide of type I collagen, human; D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D008687:Metformin; D000077205:Pioglitazone