Association of pioglitazone treatment with decreased bone mineral density in obese premenopausal patients with polycystic ovary syndrome: a randomized, placebo-controlled trial.
OBJECTIVE
Our objective was to investigate the effect of pioglitazone on bone mineral density (BMD) and bone turnover markers in polycystic ovary syndrome (PCOS).


METHODS
We conducted a randomized, placebo-controlled study at an outpatient clinic at a university hospital.


METHODS
Thirty premenopausal patients with PCOS and 14 age- and weight-matched healthy females participated.


METHODS
Pioglitazone (30 mg/d) or placebo was given for 16 wk.


METHODS
Measurements of BMD [hip (neck and total) and lumbar spine (L2-L4)], bone metabolic parameters [alkaline phosphatase (ALP), 25-hydroxyvitamin D, C-telopeptide of type I collagen (ICTP), osteocalcin, and PTH], endocrine profiles (testosterone, estradiol, and insulin), and body composition (waist to hip ratio, body mass index, and whole-body dual-energy x-ray absorptiometry scans) were performed.


RESULTS
Patients with PCOS had significantly higher levels of ICTP, fasting insulin, and testosterone than controls, whereas no differences were measured in ALP, PTH, body composition, or BMD. Pioglitazone treatment was followed by reduced BMD [geometric means (-2 to +2 sd)]: lumbar spine 1.140 (0.964-1.348) vs. 1.127 (0.948-1.341) g/cm(2) (average decline 1.1%) and femoral neck 0.966 (0.767-1.217) vs. 0.952 (0.760-1.192) g/cm(2) (average decline 1.4%), both P < 0.05. Both ALP and PTH decreased significantly during pioglitazone treatment, whereas no significant changes were measured in 25-hydroxyvitamin D, ICTP, osteocalcin, sex hormones, and body composition.


CONCLUSIONS
Pioglitazone treatment was followed by decreased lumbar and hip BMD and decreased measures of bone turnover in a premenopausal study population relatively protected from bone mineral loss.
Glintborg
Dorte
D
Department of Endocrinology and Metabolism, Odense University Hospital, Kløvervaenget 6, Odense C, Denmark. dorte.glintborg@dadlnet.dk
Andersen
Marianne
M
Hagen
Claus
C
Heickendorff
Lene
L
Hermann
Anne Pernille
AP
D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D001823:Body Composition / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D007328:Insulin / Q000097:blood; D009765:Obesity / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists; D000077205:Pioglitazone; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy* / Q000378:metabolism; D017697:Premenopause; D045162:Thiazolidinediones / Q000009:adverse effects*
D012739:Gonadal Steroid Hormones; D007004:Hypoglycemic Agents; D007328:Insulin; D047495:PPAR gamma; D045162:Thiazolidinediones; D000469:Alkaline Phosphatase; D000077205:Pioglitazone