The skeletal effects of pioglitazone in type 2 diabetes or impaired glucose tolerance: a randomized controlled trial.
OBJECTIVE
Preclinical studies, observational studies, and clinical trials suggest that thiazolidinediones (TZDs) reduce bone mineral density (BMD) and increase fracture risk. Most of the evidence on the skeletal effects of TZDs is from studies of rosiglitazone. We set out to investigate the magnitude and etiology of the adverse skeletal effects of pioglitazone.


METHODS
Double-blind, randomized controlled trial.


BACKGROUND
AUSTRALIA NEW ZEALAND CLINICAL TRIALS REGISTRY, ACTR.ORG.AU IDENTIFIER: ACTRN12607000610437, date of registration 28/11/07.


METHODS
A total of 86 people with type 2 diabetes mellitus (T2DM) or impaired glucose tolerance (IGT), median age 64 years, were randomized to receive either pioglitazone 30 mg/day or placebo for 1 year, in addition to their usual diabetes treatments. The primary outcome was change in lumbar spine BMD; secondary outcomes included changes in BMD at other sites and in biochemical markers of bone turnover.


RESULTS
Change in spine BMD was not altered by treatment with pioglitazone (Ptreatment×time=0.5). After 1 year, the mean (95% CI) between-groups difference in lumbar spine BMD was -0.7% (-2.1, 0.7). Pioglitazone increased bone loss at the proximal femur (Ptreatment×time=0.03). After 12 months, the between-groups difference in total hip BMD was -1.2% (-2.1, 0.2). Pioglitazone did not alter change in BMD at other skeletal sites, nor did it affect changes in the levels of either of the biochemical markers of bone turnover, procollagen type 1 N-terminal propeptide, or β-C-terminal telopeptide of type 1 collagen.


CONCLUSIONS
Over 1 year, treatment with pioglitazone 30 mg/day did not produce consistent effects on either BMD or bone turnover in people with T2DM or IGT. The mechanism(s) by which pioglitazone increases fracture risk in T2DM is unclear.
Department of Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Andrew
A
Grey
Mark
M
Bolland
Sheryl
S
Fenwick
Anne
A
Horne
Greg
G
Gamble
Paul L
PL
Drury
Ian R
IR
Reid
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000009:adverse effects; D016723:Bone Remodeling / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D050723:Fractures, Bone / Q000139:chemically induced; D018149:Glucose Intolerance / Q000188:drug therapy*; D006801:Humans; D008159:Lumbar Vertebrae / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D012306:Risk; D013131:Spine / Q000187:drug effects; D045162:Thiazolidinediones / Q000009:adverse effects*
D050071:Bone Density Conservation Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone