Type

Journal Article

Authors

G P Duffy
T C Lee
D Taylor
F J O'Brien
R J McCoy
C M Curtin
L E Mulcahy

Subjects

Medicine & Nursing

Topics
mice bone health care factor kappa b imidazoles bone and bones microinjury nanoscience materials global health bone remodeling bisphosphonate treatment ageing osteocytes osteoclasts bone diseases diphosphonates cellular response treatment response bone density conservation agents osteoblasts osteoporosis bone remodelling anatomy treatment effect osteoclastogenesis osteogenesis basic multicellular unit animals

The effect of bisphosphonate treatment on the biochemical and cellular events during bone remodelling in response to microinjury stimulation. (2015)

Abstract Osteoporosis is one of the most prevalent bone diseases worldwide and is characterised by high levels of bone turnover, a marked loss in bone mass and accumulation of microdamage, which leads to an increased fracture incidence that places a huge burden on global health care systems. Bisphosphonates have been used to treat osteoporosis and have shown great success in conserving bone mass and reducing fracture incidence. In spite of the existing knowledge of the in vivo responses of bone to bisphosphonates, the cellular responses to these drugs have yet to be fully elucidated. In vitro model systems that allow the decoupling of complex highly integrated events, such as bone remodelling, provide a tool whereby these biological processes may be studied in a more simplified context. This study firstly utilised an in vitro model system of bone remodelling and comprising all three major cell types of the bone (osteocytes, osteoclasts and osteoblasts), which was representative of the bone's capacity to sense microdamage and subsequently initiate a basic multicellular unit response. Secondly, this system was used to study the effect of two commonly utilised aminobisphosphonate treatments for osteoporosis, alendronate and zoledronate. We demonstrated that microinjury to osteocyte networks being treated with bisphosphonates modulates receptor activator of nuclear factor kappa-B ligand and osteoprotegerin activity, and subsequently osteoclastogenesis. Furthermore, bisphosphonates increased the osteogenic potential following microinjury. Thus, we have shown for the first time that bisphosphonates act at all three stages of bone remodelling, from microinjury to osteoclastogenesis and ultimately osteogenesis.
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Full list of authors on original publication

G P Duffy, T C Lee, D Taylor, F J O'Brien, R J McCoy, C M Curtin, L E Mulcahy

Experts in our system

1
Garry P Duffy
Royal College of Surgeons in Ireland
Total Publications: 54
 
2
T Clive Lee
Royal College of Surgeons in Ireland
Total Publications: 76
 
3
David Taylor
Trinity College Dublin
Total Publications: 75
 
4
Fergal J O'Brien
Royal College of Surgeons in Ireland
Total Publications: 265
 
5
Ryan J McCoy
Royal College of Surgeons in Ireland
 
6
Caroline M Curtin
Royal College of Surgeons in Ireland
Total Publications: 22