Bone strength is influenced by cortical thickness, area, mass and porosity, all of which contribute to nonvertebral fracture risk. Cortical porosity is one parameter of structural decay associated with bone fragility. This is caused by unbalanced and accelerated remodelling of Haversian units which enlarge, coalesce and fragment the cortex. Antiresorptive therapies will limit progression of cortical porosity; reducing existing porosity would be a goal for those already at increased risk of fracture. Using multi-detector computed tomography (MDCT) hip images from FREEDOM, a 3-year, randomized, double-blind trial in which postmenopausal women with osteoporosis received placebo (Pbo) or 60 mg denosumab (DMAb) every 6 months, we previously reported that hip cortical mass and thickness improved over 3 years of DMAb administration. We postulated that this could be explained by infilling of porosity in the inner cortical region adjacent to the medullary canal. For this analysis, percentage porosity in both the compact and the trabecularized (outer and inner transitional zones) cortical volumes of the subtrochanter region were measured at baseline and year 3 based on a subset of the same MDCT hip images (Pbo, n=22 and DMAb, n=28) using StrAx1.0 Software (Zebaze et al., Bone 2013). At baseline, 72% volume was occupied by porosity in the inner transitional zone adjacent to the medullary compartment, 37% in the outer transitional zone, and 29% in the compact-appearing cortex. Cortical porosity was positively correlated with serum CTX (P=0.017) and negatively correlated with hip strength estimated using finite element analysis (P=0.027). At year 3, DMAb reduced cortical porosity compared with baseline and Pbo across the entire cortex and in each compartment, reaching treatment effect improvements (DMAbPbo) of −1.8% (inner transitional zone), −5.6% (outer transitional zone) and −7.9% (compact-appearing cortex; all P<0.001). This is the first report of the response of hip porosity in vivo to pharmacological therapy. Reductions in cortical porosity equate to increased mineralized bone matrix and both are relevant to strength. This improvement in cortical bone parameters is likely to contribute to the observed significant reductions in hip and nonvertebral fractures associated with DMAb administration.
17 May 2014 - 20 May 2014