GSK response to Nature Medicine article on rosiglitazone and bone in mice

London, UK - The Nature Medicine study adds further context on the possible involvement of thiazolidinediones (TZDs) in osteoclast activity. However, the TZD class of medicines (both rosiglitazone and pioglitazone) has already been widely studied in relation to bone fracture, and fractures have been previously reported in female patients taking this class of drugs. There is a precaution for fracture on the labels of both rosiglitazone and pioglitazone and this information has been widely communicated for both products through dear healthcare professional letters in Europe and the U.S.

The European and U.S. labels for rosiglitazone provide information about the incidence of fractures observed and state that the risk of fracture should be considered in the care of patients, especially female patients, treated with rosiglitazone.

An observational study of TZD effects on bone mineral density for three TZDs used to treat type 2 diabetes (pioglitazone, rosiglitazone and troglitazone) showed a reduction in bone mineral density with all three drugs [J Clin Endocrinol Metab, Sept. 2006, 91(9):3349–3354].

GSK evaluated the rates of bone fractures in a post hoc analysis of the ADOPT (A Diabetes Outcome Progression Trial) data. In ADOPT, more women with bone fractures at peripheral sites (foot, hand and upper arm) were observed in the rosiglitazone group versus those in the metformin or glyburide groups. These peripheral fractures are not typical of those associated with osteoporosis. Prior to this post hoc analysis of the ADOPT data, there were no findings in the rosiglitazone clinical trial database to suggest that people with type 2 diabetes taking rosiglitazone were at increased risk for fractures. In addition, the evidence to date from ADOPT, shows no increase in spine or hip fractures (typically associated with osteoporosis) in patients treated with rosiglitazone.

GSK has a comprehensive pre-clinical and clinical programme to better understand the underlying mechanism of the fractures and the EMEA have agreed that the programme is adequate.

In October 2007, the EMEA completed an overall benefit:risk assessment of rosiglitazone which looked at the bone fracture evidence to date, among other things. The EMEA concluded that the overall benefits outweigh the risks of rosiglitazone. No new additions were recommended to the EU label with respect to bone.