Effects of RANKL inhibition on osteotomy healing in a murine model of fibrous dysplasia

Authors

  • A Arif
  • KS Pan
  • LF de Castro
  • V Kram
  • AM Boyce

Abstract

Fibrous dysplasia (FD) is a rare mosaic disorder resulting in expansile fibro-osseous lesions leading to deformities, fractures, and functional impairment. Surgery to prevent and repair deformities and fractures is a mainstay of treatment. RANKL inhibition with denosumab is a promising therapy to reduce lesional activity and increase mineralization; however, the effects of denosumab on FD tissue healing are unknown. To investigate RANKL inhibition effects on osteotomy healing, we compared cortical and trabecular bone repair in FD and WT mice with and without anti-RANKL treatment. Our injury model consisted of a 0.9mm diameter unicortical drill hole between the proximal epiphysis and mid-diaphysis of the tibia, including the periosteal and endosteal surfaces of one cortex and extended 0.3 to 0.5mm into the marrow. Bone microarchitecture analysis was performed using Analyze 14.0 software on micro-CT scans. Volumes of interest (VOI) for the cortical and medullary defects were manually traced. The results demonstrate a significant increase in Bone Volume/Total Volume (BV/TV) and Bone Mineral Density (BMD) in both FD and WT mice treated with anti-RANKL. These findings indicate that anti-RANKL treatment does not impair bone healing but increases density of healing tissue. These pre-clinical data suggest that denosumab treatment in patients with fibrous dysplasia likely does not impair healing from osteotomy procedures and may serve as a useful adjuvant to surgical management.

Scientific Focus Area: Clinical Research

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