title: Parathyroid hormone's enhancement of bones' osteogenic response to loading is affected by ageing in a dose- and time-dependent manner.
abstract: Decreased effectiveness of bones' adaptive response to mechanical loading contributes to age-related bone loss. In young mice, intermittent administration of parathyroid hormone (iPTH) at 20-80μg/kg/day interacts synergistically with artificially applied loading to increase bone mass. Here we report investigations on the effect of different doses and duration of iPTH treatment on mice whose osteogenic response to artificial loading is impaired by age. One group of aged, 19-month-old female C57BL/6 mice was given 0, 25, 50 or 100μg/kg/day iPTH for 4weeks. Histological and μCT analysis of their tibiae revealed potent iPTH dose-related increases in periosteally-enclosed area, cortical area and porosity with decreased cortical thickness. There was practically no effect on trabecular bone. Another group was given a submaximal dose of 50μg/kg/day iPTH or vehicle for 2 or 6weeks with loading of their right tibia three times per week for the final 2weeks. In the trabecular bone of these mice the loading-related increase in BV/TV was abrogated by iPTH primarily by reduction of the increase in trabecular number. In their cortical bone, iPTH treatment time-dependently increased cortical porosity. Loading partially reduced this effect. The osteogenic effects of iPTH and loading on periosteally-enclosed area and cortical area were additive but not synergistic. Thus in aged, unlike young mice, iPTH and loading appear to have separate effects. iPTH alone causes a marked increase in cortical porosity which loading reduces. Both iPTH and loading have positive effects on cortical periosteal bone formation but these are additive rather than synergistic.
authors.affiliation: School of Veterinary Sciences, University of Bristol, Bristol, UK. Electronic address: lee.meakin@bristol.ac.uk.
authors.forename: Lee B
authors.initials: LB
authors.lastname: Meakin
authors.affiliation: School of Veterinary Sciences, University of Bristol, Bristol, UK.
authors.forename: Henry
authors.initials: H
authors.lastname: Todd
authors.affiliation: School of Veterinary Sciences, University of Bristol, Bristol, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Delisser
authors.affiliation: School of Veterinary Sciences, University of Bristol, Bristol, UK; Newlife Birth Defects Research Centre, UCL Great Ormond Street Institute of Child Health, UCL, London, UK.
authors.forename: Gabriel L
authors.initials: GL
authors.lastname: Galea
authors.affiliation: School of Veterinary Sciences, University of Bristol, Bristol, UK; Department of Surgery, Faculty of Veterinary Medicine, Kafr El-Sheikh University, Kafr El-Sheikh, Egypt.
authors.forename: Alaa
authors.initials: A
authors.lastname: Moustafa
authors.affiliation: School of Veterinary Sciences, University of Bristol, Bristol, UK.
authors.forename: Lance E
authors.initials: LE
authors.lastname: Lanyon
authors.affiliation: School of Veterinary Sciences, University of Bristol, Bristol, UK; Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Sara H
authors.initials: SH
authors.lastname: Windahl
authors.affiliation: School of Veterinary Sciences, University of Bristol, Bristol, UK.
authors.forename: Joanna S
authors.initials: JS
authors.lastname: Price
mesh_terms: D000375:Aging; D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects* / Q000502:physiology; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D013314:Stress, Mechanical; D013977:Tibia / Q000187:drug effects / Q000502:physiology*; D016474:Weight-Bearing; D055114:X-Ray Microtomography
chemical_list: D010281:Parathyroid Hormone
keywords: Ageing; Bone; Mechanical loading; Osteoporosis; Parathyroid hormone