title: Poor histological healing of a femoral fracture following 12 months of oestrogen deficiency in rats.
abstract: CONCLUSIONS
  Fractures in post-menopausal osteoporosis cause significant morbidity; however, animal models for post-menopausal fracture healing lack the effect of ageing. Therefore, we developed a model using aged animals with chronic oestrogen deficiency, which demonstrates inferior fracture repair (decreased healing histologically, bone mineral density and content and strength). This novel model may help develop molecular strategies for osteoporotic fracture repair.
  
  
  BACKGROUND
  The femur is susceptible to damage by both systemic conditions such as osteoporosis and locally by traumatic injury. The capacity for fracture repair decreases with age, while the risk of fracture increases. As studies of osteoporotic fracture healing in rats traditionally use a period of 3 months or less of oestrogen deficiency prior to fracturing, we aimed to establish a osteoporosis model in rats with chronic oestrogen deficiency by 12 months to better mimic human female osteoporosis.
  
  
  METHODS
  Seventy female Sprague-Dawley rats (10 weeks old) were ovariectomised or sham operated and housed for 12 months. The right femur was fractured by way of an open osteotomy and fixed with an intramedullary Kirschner wire. Animals were sacrificed at 1, 3 and 6 weeks for radiography, dual-energy X-ray absorptiometry, tensile testing and histology.
  
  
  RESULTS
  Bone mineral density and bone mineral content were lower by 60 and 63 %, respectively, (p < 0.05) in the bilaterally ovariectomized (OVX) groups than those in the sham groups at 6 weeks in the right fractured femurs. Maximum breaking force of the OVX group was lower than that of the sham group, with the greatest difference seen at 6 weeks following osteotomy. Histologically, the OVX groups demonstrated a delay in cellular differentiation within the fracture callus and the presence of bone resorption. The sham animals had a superior histological healing pattern with an Allen score of 4 at 6 weeks compared to a score of 1 for the OVX groups (p < 0.01).
  
  
  CONCLUSIONS
  Long-term ovariectomy has a deleterious effect on fracture healing in a rodent model.
authors.affiliation: Surgical & Orthopaedic Research Laboratory, Prince of Wales Clinical School, University of New South Wales, Level 1, Clinical Sciences Bldg, Barker Street, Randwick, NSW, 2031, Sydney, Australia, rema.oliver@unsw.edu.au.
authors.forename: R A
authors.initials: RA
authors.lastname: Oliver
authors.forename: Y
authors.initials: Y
authors.lastname: Yu
authors.forename: G
authors.initials: G
authors.lastname: Yee
authors.forename: A K
authors.initials: AK
authors.lastname: Low
authors.forename: A D
authors.initials: AD
authors.lastname: Diwan
authors.forename: W R
authors.initials: WR
authors.lastname: Walsh
mesh_terms: D015502:Absorptiometry, Photon; D000375:Aging / Q000473:pathology / Q000502:physiology; D000818:Animals; D015519:Bone Density / Q000502:physiology; D002146:Bony Callus / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D017102:Fracture Healing / Q000502:physiology*; D010024:Osteoporosis / Q000503:physiopathology; D058866:Osteoporotic Fractures / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical
chemical_list: D004967:Estrogens
references.citation: Calcif Tissue Int. 1985 May;37(3):324-8
references.pmid: 3926284
references.citation: Chin J Traumatol. 2003 Jun;6(3):160-6
references.pmid: 12749788
references.citation: Obstet Gynecol. 1976 Sep;48(3):351-2
references.pmid: 948380
references.citation: J Bone Miner Res. 2000 Feb;15(2):342-51
references.pmid: 10703937
references.citation: Bone. 2001 Jan;28(1):80-6
references.pmid: 11165946
references.citation: Clin Orthop Relat Res. 2000 Mar;(372):139-50
references.pmid: 10738423
references.citation: Proc Soc Exp Biol Med. 1992 Jun;200(2):165-70
references.pmid: 1374563
references.citation: Calcif Tissue Int. 1989 Dec;45(6):360-6
references.pmid: 2509027
references.citation: J Steroid Biochem Mol Biol. 1999 Mar;68(5-6):197-202
references.pmid: 10416834
references.citation: Clin Orthop Relat Res. 1982 Jan-Feb;(162):288-97
references.pmid: 7067226
references.citation: J Bone Miner Res. 2002 Dec;17(12):2237-46
references.pmid: 12469918
references.citation: J Orthop Res. 1984;2(1):97-101
references.pmid: 6491805
references.citation: Bone. 2009 May;44(5):893-8
references.pmid: 19442605
references.citation: Clin Rheumatol. 2007 Mar;26(3):380-4
references.pmid: 16944072
references.citation: Am J Epidemiol. 1997 May 1;145(9):804-9
references.pmid: 9143210
references.citation: BMJ. 2006 Dec 16;333(7581):1251-6
references.pmid: 17170416
references.citation: Can J Surg. 1970 Oct;13(4):415-20
references.pmid: 5506099
references.citation: Postgrad Med J. 2002 Sep;78(923):526-32
references.pmid: 12357012
references.citation: Clin Orthop Relat Res. 1990 Apr;(253):287-96
references.pmid: 2317984
references.citation: Bone Miner. 1991 Dec;15(3):175-91
references.pmid: 1773131
references.citation: Acta Orthop Scand. 1991 Oct;62(5):471-5
references.pmid: 1950495
references.citation: Bone. 1997 Mar;20(3):207-12
references.pmid: 9071470
references.citation: Clin Orthop Relat Res. 1997 Sep;(342):218-27
references.pmid: 9308544
references.citation: Spine (Phila Pa 1976). 2008 Feb 1;33(3):242-9
references.pmid: 18303455
references.citation: J Orthop Res. 2001 May;19(3):428-35
references.pmid: 11398856
references.citation: Acta Orthop Scand. 1980 Aug;51(4):595-600
references.pmid: 7446048
references.citation: Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12190-3
references.pmid: 1465458
references.citation: Bone. 1994 Jul-Aug;15(4):377-86
references.pmid: 7917575
references.citation: Acta Endocrinol (Copenh). 1975 Nov;80(3):603-12
references.pmid: 1242573