Biological Effects of Anti-RANKL Antibody and Zoledronic Acid on Growth and Tooth Eruption in Growing Mice

Abstract

The anti-bone resorptive drugs denosumab, an anti-human-RANKL antibody, and zoledronic acid (ZOL), a nitrogen-containing bisphosphonate, have recently been applied for treatment of pediatric patients with bone diseases, though details regarding their effects in growing children have yet to be fully elucidated. In the present study, we administered these anti-resorptive drugs to mice from the age of 1 week and continued once-weekly injections for a total of 7 times. Mice that received the anti-RANKL antibody displayed normal growth and tooth eruption, though osteopetrotic bone volume gain in long and alveolar bones was noted, while there were nearly no osteoclasts and a normal of number osteoblasts observed. In contrast, ZOL significantly delayed body growth, tooth root formation, and tooth eruption, with increased osteoclast and decreased osteoblast numbers. These findings suggest regulation of tooth eruption via osteoblast differentiation by some types of anti-resorptive drugs.

Role of osteoclasts in oral homeostasis and jawbone diseases

“…In contrast, bisphosphonate‐treated mice display delayed tooth root formation and tooth eruption with a significant reduction in the interradicular septum length. These mice exhibit increased osteoclasts and a significant reduction in osteoblast numbers in the alveolar bone 85 . These data suggest that both bone resorption and bone formation are critical for tooth eruption as well as root formation.…”

“…These mice exhibit increased osteoclasts and a significant reduction in osteoblast numbers in the alveolar bone. 85 These data suggest that both bone resorption and bone formation are critical for tooth eruption as well as root formation. 93,94 Clinical studies showed that administration of PGE2 accelerates orthodontic tooth movement without any obvious side effects.…”

“…It has been experimentally demonstrated that removal of the coronal half of the dental follicle inhibits alveolar bone resorption, while removal of the basal half of the dental follicle inhibits alveolar bone formation at the base of the crypt, and both cases result in impaired tooth eruption 84 . Although RANKL is considered to be a key regulator for tooth eruption, the growing mice that received denosumab, an anti‐RANKL antibody, display an osteopetrotic phenotype with normal tooth eruption 85 . These mice exhibit a reduced number of osteoclasts with normal number of osteoblasts in the alveolar bone at 8 weeks of age 85 .…”

“…Although RANKL is considered to be a key regulator for tooth eruption, the growing mice that received denosumab, an anti‐RANKL antibody, display an osteopetrotic phenotype with normal tooth eruption 85 . These mice exhibit a reduced number of osteoclasts with normal number of osteoblasts in the alveolar bone at 8 weeks of age 85 . In contrast, bisphosphonate‐treated mice display delayed tooth root formation and tooth eruption with a significant reduction in the interradicular septum length.…”

“…85 These mice exhibit a reduced number of osteoclasts with normal number of osteoblasts in the alveolar bone at 8 weeks of age. 85 In contrast, bisphosphonate-treated mice display delayed tooth root formation and tooth eruption with a significant reduction in the interradicular septum length. These mice exhibit increased osteoclasts and a significant reduction in osteoblast numbers in the alveolar bone.…”