Albert S Kim1,2,3, Christian M Girgis3,4,5, Michelle M McDonald6,7. 1. Bone Biology Program, Garvan Institute of Medical Research, Sydney, Australia. 2. Faculty of Medicine UNSW Sydney, St Vincent's Clinical School, Kensington, NSW, Australia. 3. Department of Diabetes and Endocrinology, Westmead Hospital, Westmead, NSW, Australia. 4. Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia. 5. The Westmead Institute for Medical Research, Westmead, NSW, Australia. 6. Bone Biology Program, Garvan Institute of Medical Research, Sydney, Australia. m.mcdonald@garvan.org.au. 7. Faculty of Medicine UNSW Sydney, St Vincent's Clinical School, Kensington, NSW, Australia. m.mcdonald@garvan.org.au.
Abstract
PURPOSE OF REVIEW: Inhibition of receptor activator of nuclear factor kappa-B ligand (RANKL) with denosumab is an effective treatment in a number of conditions including osteoporosis where suppression of bone resorption is desired. However, denosumab discontinuation is associated with rebound increase in bone resorption and subsequent loss in bone mass and a rapid return to baseline fracture risk. We review recent data on the rebound increase in bone resorption following denosumab discontinuation and the potential mechanisms behind this phenomenon. RECENT FINDINGS: Osteoclasts have been considered to be highly specialised cells that undergo apoptosis after fulfilling their function of bone resorption. However, recent studies suggest that osteoclasts are longer lived cells which migrate through vasculature and are capable of undergoing fission into a novel cell type (the osteomorph) and re-fusion in a process termed osteoclast recycling. The life cycle of the osteoclast is more complex than previously appreciated. Osteoclast recycling provides a novel mechanistic framework to examine changes in osteoclast biology in response to treatment of bone diseases and provides an exciting new avenue towards personalised medicine.
PURPOSE OF REVIEW: Inhibition of receptor activator of nuclear factor kappa-B ligand (RANKL) with denosumab is an effective treatment in a number of conditions including osteoporosis where suppression of bone resorption is desired. However, denosumab discontinuation is associated with rebound increase in bone resorption and subsequent loss in bone mass and a rapid return to baseline fracture risk. We review recent data on the rebound increase in bone resorption following denosumab discontinuation and the potential mechanisms behind this phenomenon. RECENT FINDINGS: Osteoclasts have been considered to be highly specialised cells that undergo apoptosis after fulfilling their function of bone resorption. However, recent studies suggest that osteoclasts are longer lived cells which migrate through vasculature and are capable of undergoing fission into a novel cell type (the osteomorph) and re-fusion in a process termed osteoclast recycling. The life cycle of the osteoclast is more complex than previously appreciated. Osteoclast recycling provides a novel mechanistic framework to examine changes in osteoclast biology in response to treatment of bone diseases and provides an exciting new avenue towards personalised medicine.
Authors: N Udagawa; N Takahashi; T Akatsu; H Tanaka; T Sasaki; T Nishihara; T Koga; T J Martin; T Suda Journal: Proc Natl Acad Sci U S A Date: 1990-09 Impact factor: 11.205
Authors: N Takahashi; T Akatsu; N Udagawa; T Sasaki; A Yamaguchi; J M Moseley; T J Martin; T Suda Journal: Endocrinology Date: 1988-11 Impact factor: 4.736
Authors: F H Drake; R A Dodds; I E James; J R Connor; C Debouck; S Richardson; E Lee-Rykaczewski; L Coleman; D Rieman; R Barthlow; G Hastings; M Gowen Journal: J Biol Chem Date: 1996-05-24 Impact factor: 5.157