In the Journals

Denosumab reduces cortical porosity in women with postmenopausal osteoporosis

Cortical porosity of the proximal femur shaft was reduced in women treated with denosumab therapy, study data show.

The reduced cortical porosity results in increased mineralized matrix volume as well as improved strength, according to the researchers.

Ego Seeman, MD, of the department of endocrinology at Austin Health, University of Melbourne in Australia, and colleagues evaluated data from the FREEDOM study on women with postmenopausal osteoporosis randomly assigned to subcutaneous denosumab (60 mg) every 6 months (n = 28) or placebo (n = 22) for 36 months.

A non-threshold-based segmentation algorithm was used to quantify porosity, and finite element analysis was used to estimate bone strength.

Higher total cortex porosity was found in participants with higher serum C-terminal telopeptide (sCTX; P = .02). Lower areal BMD (P < .01), lower total cortical volumetric BMD (P < .01), thinner cortices (P = .02), lower cortical mass (P < .01) and lower estimated integral strength (P = .03) were found among participants with higher total cortex porosity.

Porosity of all cortical regions decreased from baseline to 36 months in the denosumab group: -3.6% for the total cortex, -6.7% for the compact-appearing cortex, -5.9% for the outer transitional zone and -1.1% for the inner transitional zone (P < .01 for all). However, porosity of all cortical regions remained relatively stable in the placebo group.

Significant differences were found between the denosumab and placebo group for porosity in all cortical regions at 36 months (P < .001 for all). Porosity reduction in the denosumab group was linked with an increased estimated integral strength for total cortex (P = .03), compact-appearing cortex (P = .02) and outer transitional zone (P < .01).

“We confirm and extend reports of ex vivo studies in animal models, and reports in human subjects documenting a reduction of cortical porosity associated with denosumab therapy,” the researchers wrote. “Quantification of cortical porosity of the hip provides a means of assessing fracture risk and the effects of treatment on this important determinant of bone strength. The benefits of denosumab treatment in reducing porosity at this location are relevant to our understanding of the structural basis of the reduced nonvertebral and hip fracture risk observed in clinical trials.” – by Amber Cox

Disclosure: Seeman reports various financial ties with Allergan, Amgen, Asahi, Genzyme, Merck Sharp & Dohme, Sanofi, StraxCorp and Warner-Chilcott and was one of the inventors of the StrAx1.0 algorithm.

Cortical porosity of the proximal femur shaft was reduced in women treated with denosumab therapy, study data show.

The reduced cortical porosity results in increased mineralized matrix volume as well as improved strength, according to the researchers.

Ego Seeman, MD, of the department of endocrinology at Austin Health, University of Melbourne in Australia, and colleagues evaluated data from the FREEDOM study on women with postmenopausal osteoporosis randomly assigned to subcutaneous denosumab (60 mg) every 6 months (n = 28) or placebo (n = 22) for 36 months.

A non-threshold-based segmentation algorithm was used to quantify porosity, and finite element analysis was used to estimate bone strength.

Higher total cortex porosity was found in participants with higher serum C-terminal telopeptide (sCTX; P = .02). Lower areal BMD (P < .01), lower total cortical volumetric BMD (P < .01), thinner cortices (P = .02), lower cortical mass (P < .01) and lower estimated integral strength (P = .03) were found among participants with higher total cortex porosity.

Porosity of all cortical regions decreased from baseline to 36 months in the denosumab group: -3.6% for the total cortex, -6.7% for the compact-appearing cortex, -5.9% for the outer transitional zone and -1.1% for the inner transitional zone (P < .01 for all). However, porosity of all cortical regions remained relatively stable in the placebo group.

Significant differences were found between the denosumab and placebo group for porosity in all cortical regions at 36 months (P < .001 for all). Porosity reduction in the denosumab group was linked with an increased estimated integral strength for total cortex (P = .03), compact-appearing cortex (P = .02) and outer transitional zone (P < .01).

“We confirm and extend reports of ex vivo studies in animal models, and reports in human subjects documenting a reduction of cortical porosity associated with denosumab therapy,” the researchers wrote. “Quantification of cortical porosity of the hip provides a means of assessing fracture risk and the effects of treatment on this important determinant of bone strength. The benefits of denosumab treatment in reducing porosity at this location are relevant to our understanding of the structural basis of the reduced nonvertebral and hip fracture risk observed in clinical trials.” – by Amber Cox

Disclosure: Seeman reports various financial ties with Allergan, Amgen, Asahi, Genzyme, Merck Sharp & Dohme, Sanofi, StraxCorp and Warner-Chilcott and was one of the inventors of the StrAx1.0 algorithm.