Effects of pioglitazone on bone in postmenopausal women with impaired fasting glucose or impaired glucose tolerance: a randomized, double-blind, placebo-controlled study.
BACKGROUND
Meta-analyses of clinical studies have suggested an increased incidence of peripheral fractures in postmenopausal women with type 2 diabetes mellitus taking pioglitazone. The mechanism behind this apparent increase is unknown.


OBJECTIVE
The objective of the study was to examine the effects of pioglitazone on bone mineral density (BMD) and turnover.


METHODS
Twenty-five sites (in the United States) enrolled participants in this randomized, double-blind, placebo-controlled study.


METHODS
Postmenopausal women (n = 156) with impaired fasting glucose or impaired glucose tolerance participated in the study.


METHODS
The intervention consisted of pioglitazone 30 mg/d (n = 78) or placebo (n = 78), increased to 45 mg/d after 1 month, for 12 months of treatment total, followed by 6 months of washout/follow-up.


METHODS
Percentage changes from baseline to month 12 and from month 12 to month18 in BMD in total proximal femur (primary end point), total body, femoral neck, lumbar spine, and radius were measured.


RESULTS
Least squares mean changes from baseline to month 12 in total proximal femur BMD were -0.69% for pioglitazone and -0.14% for placebo (P = .170). No statistically significant between-group differences were observed for any BMD or bone remodeling marker end point. We observed improved glycemic control and insulin sensitivity with pioglitazone treatment. In addition, pioglitazone appeared to increase body fat, which may affect bone density measurements, especially in the lumbar spine. One pioglitazone-treated and three placebo-treated women experienced confirmed fractures. Over 18 months, one pioglitazone-treated (1.3%) and eight placebo-treated women (10.3%) developed overt type 2 diabetes mellitus. The pattern and incidence of adverse events with pioglitazone were consistent with clinical experience with thiazolidinediones.


CONCLUSIONS
Maximal-dose pioglitazone had no effects on BMD or bone turnover, while improving glycemic control as expected, in postmenopausal women with impaired fasting glucose or impaired glucose tolerance.
MD,Michigan Bone and Mineral Clinic, 22201 Moross Road, Suite 260, Detroit, MI 48236-2175. hgbone.md@att.net.
Henry G
HG
Bone
Robert
R
Lindsay
Michael R
MR
McClung
Alfonso T
AT
Perez
Marsha G
MG
Raanan
Robert G
RG
Spanheimer
D050154:Adiposity / Q000187:drug effects; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects*; D001862:Bone Resorption / Q000139:chemically induced*; D001842:Bone and Bones / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D018149:Glucose Intolerance / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D007333:Insulin Resistance; D008875:Middle Aged; D000077205:Pioglitazone; D017698:Postmenopause; D011236:Prediabetic State / Q000097:blood / Q000188:drug therapy*; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
D015415:Biomarkers; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone