Denosumab prevents trabecular microstructure deterioration in postmenopausal osteoporosis

Postmenopausal women with low bone mineral density assigned denosumab therapy had less deterioration of trabecular microstructure at the distal tibia compared with women assigned placebo, study findings show.

“Trabecular bone strength is determined by its plate and rod microstructure,” X. Edward Guo, PhD, professor of biomedical engineering and interim chair of the department of biomedical engineering at Columbia University, and colleagues wrote. “Age- and menopause-related microstructural deterioration occurs because of unbalanced and rapid remodeling on the surfaces of plates and rods. The resulting thinning, perforation and loss of connectivity compromise bone strength out of proportion to the bone loss producing this deterioration.”

Guo and colleagues evaluated data from a phase 2 study on 164 postmenopausal women (mean age, 61 years; mean duration since menopause, 13 years) randomly assigned to placebo or denosumab 60 mg (Prolia, Amgen) to determine the effect of therapy on trabecular plate-rod microstructure. They assessed individual trabecular segmentation and whole bone stiffness using finite element analyses at baseline and 12 months.

At baseline, participants had mean BMD T-scores of –2.4 at the lumbar spine and –1.2 at the total hip.

Compared with placebo, the denosumab group had less deterioration or more improvement in all microstructural parameters at the distal tibia and increased trabecular stiffness. Plate number and thickness increased compared with baseline in the denosumab group, and researchers did not observe the increase in rod number and thinning in the denosumab group that they saw in the placebo group. Plate to rod ratio was preserved from baseline to 12 months in the denosumab group, whereas it decreased significantly in the placebo group.

“[Our study] demonstrates the underlying mechanisms how denosumab treatment improves trabecular bone microstructure, therefore reducing the fracture risk in patients,” Guo told Endocrine Today. “It also suggests that the development of new anti-osteoporosis drugs should consider implementation of the advanced imaging modality and imaging analysis technique.” – by Amber Cox

Reference:

Guo XE, et al. Abstract 1033. Presented at: American Society for Bone and Mineral Research Annual Meeting; Sept. 8-11, 2017; Denver.

Disclosure: Guo reports no relevant financial disclosures.