Denosumab (DMAb) significantly improves bone strength at the hip, estimated by FEA from QCT scans, from baseline (B/L) and vs placebo (Pbo) (Keaveny ASBMR 2010). We determined the extent and distribution of mass and thickness changes at the proximal femur, a key skeletal site for fracture risk, using a novel cortical bone mapping technique on the same serial QCT scans. A FREEDOM substudy included 80 women who underwent hip QCT scanning at B/L and months 12, 24 and 36 during DMAb (60 mg Q6M) or Pbo treatment. For each femur, distributions of cortical mass and thickness were measured in a blinded-to-treatment manner. Each individual femur was registered to an average femur, then distributed measures were transferred to this surface. The significance of DMAb or Pbo effects at each time point, vs B/L and between treatments, was calculated using statistical parametric mapping. In DMAb-treated women, cortical mass increased progressively over time, reaching a difference vs Pbo of 5.4% at 3 years (P<0.0001) (Table). Approximately one-third of this increase was attributed to an increase in cortical density of 21.2±7.7 mg/cm3 (P<0.0001), compared with no change in Pbo-treated subjects (P=0.58). Cortical thickness was also significantly increased with DMAb, which may represent in-filling of the cortical compartment, while average cortical mass and thickness decreased with Pbo. The distribution of increases in cortical mass with DMAb was significant over an increasingly large area of the proximal femur. In postmenopausal women with osteoporosis, DMAb significantly and progressively increased cortical mass and thickness in regions of the proximal femur associated with hip fracture.
|Mean change in cortical mass, % baseline (confidence)||DMAb (N=45)*||P vs B/L||Pbo (N=35)*||P vs B/L||P DMAb vs Pbo|
|12 months||2.38 (0.50)||<0.05||−0.31 (0.88)||NS||<0.0001|
|24 months||3.01 (0.66)||<0.05||−1.31 (0.84)||<0.05||<0.0001|
|36 months||4.18 (0.53)||<0.05||−1.20 (0.90)||<0.05||<0.0001|
|*Not all subjects had scans at each study time point.|
18 - 21 May 2013
European Calcified Tissue Society