Reduction of fracture risk with denosumab among women with osteoporosis with or without need for treatment according to DVO 2009 guideline

Summary

Data from the FREEDOM trial showed that denosumab 60 mg given subcutaneously every six months to postmenopausal women with osteoporosis reduces the relative risk for new vertebral fractures by 68 %, for nonvertebral fractures by 20 % and for hip fractures by 40 % at 36 months compared with placebo (1). Here we present results of a post hoc analysis to assess the proportion of the FREEDOM population at need for a specific osteoporosis treatment in accordance to DVO guideline (10-year risk for vertebral and hip fractures > 30 %), and the effect of denosumab on fracture risk in patients above or below this threshold for a specific osteoporosis treatment as defined by DVO. Participants of the FREEDOM trial were classified as “recommended for treatment” and “no need for treatment” based on the captured risk factors defined by the DVO guideline. Accordingly, 81 % or 6,323 out of 7,808 patients were classified as “recommended for treatment” according to DVO guideline (denosumab: 80.5 %; placebo: 81.4 %). Relative risk reductions for new vertebral (67 %, p < 0.0001), non-vertebral (23%, p = 0.0051), and hip fractures (41 %, p = 0.0353) in the subgroup of patients “recommended for treatment” were similar to the above-mentioned risk reductions in the entire FREEDOM population. In the subgroup of patients classified as “no need for treatment' ” according to DVO guideline, denosumab reduced the relative risk for new vertebral fractures by 75 % vs. placebo (p = 0.0004). The respective number of non-vertebral and hip fractures showed no significant differences between treatment groups. The relative risk for the combined endpoint of new vertebral and/or hip fractures after 36 months was reduced by 64 % (p < 0.0001) in the entire population, by 62 % (p < 0.0001) in the “recommended for treatment” group, and by 73 % (p = 0.0005) in the “no need for treatment” group, respectively. A sensitivity analysis (adjusting for an additional risk factor which might not have been captured, equivalent to a T-score shift by + 0.5) did not significantly change the results. This analysis comprised that the majority of the FREEDOM patients fulfilled the DVO criterion for a specific osteoporosis treatment and that the fracture risk reductions shown with denosumab could be expected in daily practice when applying the DVO guideline. The marked risk reduction for new vertebral fractures and for the combined endpoint of new vertebral and/or hip fractures with denosumab in the “no need for treatment” group according to DVO guideline is a striking result that should be further analyzed.

Keywords

Osteoporosis - fracture risk - DVO guideline - denosumab

• Literatur

• 1 Cummings SR, San Martin J, McClung MR. et al. Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis. N Engl J Med 2009; 361: 756-765.
• 2 Dachverband Osteologie e. V. DVO-Leitlinie 2009 zur Prophylaxe, Diagnostik und Therapie der Osteoporose bei Erwachsenen – Langfassung. Osteologie 2009; 18: 304-328.
• 3 Boonen S, Adachi JD, Man Z. et al. Treatment with Denosumab Reduces the Incidence of New Vertebral and Hip Fractures in Postmenopausal Women at High Risk. J Clin Endocrinol Metab 2011; 96: 1727-1736.
• 4 Gail M, Simon R. Testing for qualitative interactions between treatment effects and patients subsets. Biometrics 1985; 41: 361-372.