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Current sulfonylurea, TZD use increases fracture risk in type 2 diabetes
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Patients with type 2 diabetes prescribed a sulfonylurea or thiazolidinedione drug in the past 90 days are more like to sustain a fracture, but there appears to be no long-term effect on fracture risk with either drug class, according to a recent analysis.
“The results emphasize what previous studies also have shown — that TZDs increase fracture risk and should, in terms of bone health, be avoided,” Jakob Starup-Linde, MD, PhD, of the department of endocrinology and internal medicine at Aarhus University Hospital in Denmark, told Endocrine Today. “Furthermore, the results suggest that current use of sulfonylureas increases the risk for fracture in patients with diabetes. This is important, as a treatment shift to other glucose-lowering drugs, such as DPP-IV inhibitors, [glucagon-like peptide-1] receptor agonists or insulin, may be possible in many patients.”
Starup-Linde and colleagues analyzed data from 5,244 patients with type 2 diabetes who sustained a hip fracture after diagnosis; participants were identified through the Danish National Patient Registry and drug reimbursement information from the Register of Medicinal Product Statistics. Beginning in January 1996, researchers followed the cohort from time of diabetes diagnosis to time of fracture, death or until Dec. 31, 2011 (mean follow-up time, 5.5 years). The primary exposure was glucose-lowering drugs; primary endpoint was hip fracture.
Researchers found that current use of sulfonylureas (within the last 90 days) increased the risk for hip fracture in all models (HR = 1.64; 95% CI, 1.54-1.75); however, ever use of sulfonylureas was not associated with an increased risk for fracture. Use of sulfonylureas within the last 90 days was also associated with an increased risk for any fracture (HR = 1.44; 95% CI, 1.39-1.49), major osteoporotic fracture (HR = 1.54; 95% CI, 1.47-1.62), vertebral fracture (HR = 1.47; 95% CI, 1.24-1.74) and forearm fracture (HR = 1.55; 95% CI, 1.43-1.69).
“There is no preclinical evidence of detrimental effects of sulfonylureas on bone cells, and hypoglycemia seems to be the most likely explanation for an increased risk for fracture,” the researchers wrote. “However, sulfonylureas appear not to have any major long-term effect on fracture risk.”
Current use of TZDs also was associated with an increased risk for hip fracture (HR = 2.07; 95% CI, 1.39-3.07), whereas ever use was not associated with an increased risk.
Use of TZDs within the last 90 days also was associated with an increased risk for any fracture (HR = 3.01; 95% CI, 2.65-3.43), major osteoporotic fracture (HR = 3.71; 95% CI, 3.07-4.49), vertebral fracture (HR = 4.53; 95% CI, 2.27-9.05) and forearm fracture (HR = 4.89; 95% CI, 3.58-6.65).
“Discrepancies between results of clinical trials and the present observational study may be due to low power in the clinical trials or the fact that glucose-lowering drugs are not used at random,” the researchers wrote. “Rather, the clinical decision to prescribe one of these drugs most likely relies on several factors that may influence fracture risk, such as compliance, socioeconomic factors, ability to administer the drug, etc. More research on the relationship between hypoglycemia, falls and fractures in patients with diabetes is needed.” – by Regina Schaffer
For more information:
Jakob Starup-Linde, MD, PhD, can be reached at the department of endocrinology and internal medicine at Aarhus University Hospital, Tage Hansens-Gade 2, 8000 Aarhus C, Denmark; email: jakob.linde@auh.rm.dk.
Disclosure: One of the researchers reports being on an advisory panel for Novo Nordisk. Starup-Linde reports no relevant financial disclosures.
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