title: Enoxaparin prevents steroid-related avascular necrosis of the femoral head.
abstract: Nontraumatic osteonecrosis of the femoral head is still a challenging problem in orthopedic surgery. It is responsible for 10% of the 500,000 hip replacement surgeries in the USA and affects relatively young, active patients in particular. Main reasons for nontraumatic osteonecrosis are glucocorticoid use, alcoholism, thrombophilia, and hypofibrinolysis (Glueck et al., 1997; Orth and Anagnostakos, 2013). One pathomechanism of steroid-induced osteonecrosis is thought to be impaired blood flow to the femoral head caused by increased thrombus formation and vasoconstriction. To investigate the preventive effect of enoxaparin on steroid-related osteonecrosis, we used male New Zealand white rabbits. Osteonecrosis was induced by methylprednisolone-injection (1 × 20 mg/kg body weight). Control animals were treated with phosphate-buffered saline. Treatment consisted of an injection of 11.7 mg/kg body weight of enoxaparin per day (Clexane) in addition to methylprednisolone. Four weeks after methylprednisolone-injection the animals were sacrificed. Histology (hematoxylin-eosin and Ladewig staining) was performed, and empty lacunae and histological signs of osteonecrosis were quantified. Histomorphometry revealed a significant increase in empty lacunae and necrotic changed osteocytes in glucocorticoid-treated animals as compared with the glucocorticoid- and Clexane-treated animals and with the control group. No significant difference was detected between the glucocorticoid and Clexane group and the control group. This finding suggests that cotreatment with enoxaparin has the potential to prevent steroid-associated osteonecrosis.
authors.affiliation: Department of Anatomy and Cell Biology, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Beckmann
authors.affiliation: Department of Anatomy and Cell Biology, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany.
authors.forename: Hayfaa
authors.initials: H
authors.lastname: Shaheen
authors.affiliation: Department of Anatomy and Cell Biology, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany.
authors.forename: Nisreen
authors.initials: N
authors.lastname: Kweider
authors.affiliation: Department of Oral and Maxillofacial Surgery, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany.
authors.forename: Alireza
authors.initials: A
authors.lastname: Ghassemi
authors.affiliation: Department of Anatomy and Cell Biology, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany.
authors.forename: Athanassios
authors.initials: A
authors.lastname: Fragoulis
authors.affiliation: Department of Pathology, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany.
authors.forename: Benita
authors.initials: B
authors.lastname: Hermanns-Sachweh
authors.affiliation: Department of Anatomy and Cell Biology, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pufe
authors.affiliation: Department of Anatomy and Cell Biology, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany.
authors.forename: Mamed
authors.initials: M
authors.lastname: Kadyrov
authors.affiliation: Department of Orthopedic and Trauma Surgery, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany ; Department of Orthopaedic and Spine Surgery, AGAPLESION EV. BATHILDISKRANKENHAUS gemeinnützige GmbH, Maulbeerallee 4, 31812 Bad Pyrmont, Germany.
authors.forename: Wolf
authors.initials: W
authors.lastname: Drescher
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology*; D018890:Chemoprevention; D017984:Enoxaparin / Q000008:administration & dosage / Q000494:pharmacology*; D005271:Femur Head Necrosis / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D010011:Osteocytes / Q000378:metabolism / Q000473:pathology; D011817:Rabbits; D013256:Steroids / Q000009:adverse effects*
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D013256:Steroids
references.citation: Clin Orthop Relat Res. 1997 Jan;(334):43-56
references.pmid: 9005895
references.citation: Pathol Res Pract. 2005;200(11-12):807-11
references.pmid: 15792124
references.citation: Haematologica. 2008 Oct;93(10):1570-4
references.pmid: 18698082
references.citation: Vet Pathol. 2003 Jul;40(4):345-54
references.pmid: 12824505
references.citation: Pharmacology. 2002 May;65(1):32-7
references.pmid: 11901299
references.citation: Proc Natl Acad Sci U S A. 1990 Sep;87(18):6974-8
references.pmid: 2169616
references.citation: J Bone Joint Surg Am. 2006 May;88(5):1117-32
references.pmid: 16651589
references.citation: Arthritis Res Ther. 2010;12(3):R124
references.pmid: 20579363
references.citation: J Bone Joint Surg Am. 1995 Mar;77(3):459-74
references.pmid: 7890797
references.citation: Arthritis. 2012;2012:601763
references.pmid: 23243507
references.citation: Orthop Rev (Pavia). 2012 May 9;4(2):e17
references.pmid: 22802985
references.citation: Ann Intern Med. 1957 May;46(5):831-51
references.pmid: 13411894
references.citation: J Orthop Res. 2008 Jan;26(1):91-5
references.pmid: 17787012
references.citation: Acta Orthop. 2011 Feb;82(1):42-9
references.pmid: 21281264
references.citation: FASEB J. 2011 Oct;25(10):3366-76
references.pmid: 21705669
references.citation: Arthritis Rheum. 1997 Nov;40(11):2055-64
references.pmid: 9365096
references.citation: Orthopedics. 2013 Apr;36(4):290-300
references.pmid: 23590772
references.citation: Clin Orthop Relat Res. 2005 Jun;(435):164-70
references.pmid: 15930934
references.citation: Clin Appl Thromb Hemost. 2013 Sep;19(5):499-503
references.pmid: 22696591
references.citation: Theor Biol Med Model. 2005 Jul 05;2:24
references.pmid: 15996271
references.citation: Future Med Chem. 2012 Mar;4(3):289-96
references.pmid: 22393937
references.citation: Curr Vasc Pharmacol. 2004 Jan;2(1):1-12
references.pmid: 15320828
references.citation: J Orthop Res. 2004 May;22(3):501-8
references.pmid: 15099627
references.citation: J Orthop Res. 2009 Feb;27(2):169-75
references.pmid: 18683891
references.citation: J Bone Joint Surg Br. 1999 Mar;81(2):328-32
references.pmid: 10204945
references.citation: Orthop Clin North Am. 1985 Oct;16(4):595-633
references.pmid: 3903602
references.citation: Bone. 2008 Sep;43(3):561-6
references.pmid: 18572010