A cohort study of thiazolidinediones and fractures in older adults with diabetes.
BACKGROUND
Thiazolidenediones (TZDs) are selective ligands of peroxisome-proliferator-activated receptor-gamma and have been shown to reduce bone mineral density. Recent results from several randomized controlled trials find an increased risk of fracture with TZDs compared with other oral antidiabetic agents.


OBJECTIVE
The aim of the study was to determine the association between TZD use and fracture risk among older adults with diabetes.


METHODS
We conducted a cohort study.


METHODS
Medicare beneficiaries with at least one diagnosis of diabetes initiating monotherapy for an oral hypoglycemic agent participated in the study.


RESULTS
We measured the incidence of fracture within the cohort.


RESULTS
Among the 20,964 patients with diabetes eligible for this study, 686 (3.3%) experienced a fracture during the median follow-up of approximately 10 months. Although not statistically significant, patients using only a TZD were more likely to experience a fracture than those using metformin (adjusted relative risk, 1.31; 95% confidence interval, 0.98-1.77; P = 0.071) or a sulfonylurea (adjusted relative risk, 1.21; 95% confidence interval, 0.94-1.55; P = 0.12). Each individual TZD was associated with an increased risk, with confidence intervals overlapping unity, compared with both metformin and sulfonylureas. The adjusted risk of any fracture associated with TZD use compared with metformin was elevated for non-insulin-using patients, women and men. If TZD use is associated with fractures, the number needed for one excess fracture when comparing TZD users to sulfonylurea users was 200, and the number was 111 when comparing TZDs with metformin.


CONCLUSIONS
As has been found with other analyses, our data suggest that TZDs may be associated with an increased risk of fractures compared with oral sulfonylureas and metformin.
Solomon
Daniel H
DH
Division of Rheumatology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. dsolomon@partners.org
Cadarette
Suzanne M
SM
Choudhry
Niteesh K
NK
Canning
Claire
C
Levin
Raisa
R
Stürmer
Til
T
D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000188:drug therapy*; D005260:Female; D050723:Fractures, Bone / Q000139:chemically induced*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D008297:Male; D008687:Metformin / Q000009:adverse effects; D012306:Risk; D013453:Sulfonylurea Compounds / Q000009:adverse effects; D045162:Thiazolidinediones / Q000009:adverse effects*
D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D008687:Metformin