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Title: Denosumab reduces cortical porosity of the proximal femoral shaft in postmenopausal women with osteoporosis
Austin Authors: Zebaze, Roger M D;Libanati, C;McClung, MR;Zanchetta, JR;Kendler, DL;Høiseth, A;Wang, A;Ghasem-Zadeh, Ali ;Seeman, Ego 
Affiliation: Austin Health, University of Melbourne, Heidelberg, Victoria, Australia
Amgen Inc, Thousand Oaks, CA, USA
Oregon Osteoporosis Center, Portland, OR, USA
Instituto de Investigaciones Metabólicas, Buenos Aires, Argentina
University of British Columbia, Vancouver, BC, Canada
Curato Røntgen, Oslo, Norway
Issue Date: Oct-2016 2016-04-15
Publication information: Journal of Bone and Mineral Research 2016; 31(10): 1827-1834
Abstract: Hip fractures account for over half the morbidity, mortality, and cost associated with osteoporosis. Fragility of the proximal femur is the result of rapid and unbalanced bone remodeling events that excavate more bone than they deposit, producing a porous, thinned, and fragile cortex. We hypothesized that the slowing of remodeling during treatment with denosumab allows refilling of the many cavities excavated before treatment now opposed by excavation of fewer new resorption cavities. The resulting net effect is a reduction in cortical porosity and an increase in proximal femur strength. Images were acquired at baseline and 36 months using multidetector CT in 28 women receiving denosumab and 22 women receiving placebo in a substudy of FREEDOM, a randomized, double-blind, placebo-controlled trial involving women with postmenopausal osteoporosis. Porosity was quantified using StrAx1.0 software. Strength was estimated using finite element analysis. At baseline, the higher the serum resorption marker, CTx, the greater the porosity of the total cortex (r = 0.34, p = 0.02), and the higher the porosity, the lower the hip strength (r = -0.31, p = 0.03). By 36 months, denosumab treatment reduced porosity of the total cortex by 3.6% relative to baseline. Reductions in porosity relative to placebo at 36 months were 5.3% in total cortex, 7.9% in compact-appearing cortex, 5.6% in outer transitional zone, and 1.8% in inner transitional zone (all p < 0.01). The improvement in estimated hip integral strength of 7.9% from baseline (p < 0.0001) was associated with the reduction in total porosity (r = -0.41; p = 0.03). In summary, denosumab reduced cortical porosity of the proximal femoral shaft, resulting in increased mineralized matrix volume and improved strength, changes that may contribute to the reduction in hip and nonvertebral fractures reported with denosumab therapy
DOI: 10.1002/jbmr.2855
PubMed URL:
Type: Journal Article
Subjects: Osteoporosis
Appears in Collections:Journal articles

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