title: Equol but not genistein improves early metaphyseal fracture healing in osteoporotic rats.
abstract: Healing of predominantly metaphyseal fractures in postmenopausal osteoporosis is delayed and comparatively poor. Hormone replacement therapy could improve fracture healing, but, because of its potential side effects, natural alternatives are more appealing. The aim of this study was to determine if the soy metabolite equol and the native isoflavone genistein, in comparison to 17beta-estradiol, improve metaphyseal fracture healing in ovariectomy-induced osteoporotic bone of the rat. Forty-eight 12-week-old female rats developed severe osteoporosis ten weeks after ovariectomy. After metaphyseal tibial osteotomy and standardized stable internal fixation, changes in callus morphology were evaluated biomechanically, qualitatively and quantitatively in fluorochrome-labeled histological sections and microradiographs in ovariectomized rats (C) and under standardized 17beta-estradiol (E), equol (EQ) and genistein (G) supplemented rats over a period of five weeks. Estrogen and equol were able to improve the elasticity of callus formation significantly in postmenopausal osteoporotic bone (stiffness of C: 121.40 +/- 47.08 N/mm, E: 147.90 +/- 39.38 N/mm, EQ: 167.8 +/- 59.90 N/mm). The effects of estrogen were more anabolic than those of equol and were visible in changes to the trabecular bone (N.Nd of E: 6.47 +/- 7.68, EQ: 4.25 +/- 3.96). However, in terms of the whole body, equol seemed to induce less of an adverse reaction than estrogen (body weight of C: 342.20 +/- 19.91 g, E: 280.25 +/- 12.05 g, EQ: 308.75 +/- 24.28 g). Genistein as an osteoclast inhibitor influenced callus stiffness (G: 144.50 +/- 61.52 N/mm) and negatively impacted trabecular structure (N.Nd of G: 0.59 +/- 1.01) in severely osteoporotic bones. Estrogen and equol were able to improve fracture healing in ovariectomy-induced osteoporotic bones, and the extent of callus formation played only a minor role. Genistein rather negatively influenced fracture healing. The metaphyseal osteotomy model in ovariectomized rats allows an accurate study of the therapeutic effects of antiosteoporotic substances on the fracture healing process.
authors.affiliation: Department of Trauma and Reconstructive Surgery, Georg-August-University of Goettingen, Goettingen, Germany. leilakolios@med.uni-goettingen.de
authors.forename: Leila
authors.initials: L
authors.lastname: Kolios
authors.forename: Stephan
authors.initials: S
authors.lastname: Sehmisch
authors.forename: Florian
authors.initials: F
authors.lastname: Daub
authors.forename: Thomas
authors.initials: T
authors.lastname: Rack
authors.forename: Mohammed
authors.initials: M
authors.lastname: Tezval
authors.forename: Klaus Michael
authors.initials: KM
authors.lastname: Stuermer
authors.forename: Ewa Klara
authors.initials: EK
authors.lastname: Stuermer
mesh_terms: D000818:Animals; D002146:Bony Callus / Q000187:drug effects; D004195:Disease Models, Animal; D004548:Elasticity; D060754:Equol; D004958:Estradiol / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004967:Estrogens / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D017102:Fracture Healing / Q000187:drug effects*; D019833:Genistein / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007529:Isoflavones / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D010010:Osteoclasts / Q000187:drug effects; D010024:Osteoporosis / Q000188:drug therapy* / Q000473:pathology; D010052:Ovariectomy; D048789:Phytoestrogens / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008517:Phytotherapy; D010936:Plant Extracts / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013025:Glycine max / Q000737:chemistry; D013977:Tibia / Q000187:drug effects / Q000473:pathology
chemical_list: C007610:4',7-dihydroxy-3,4-dihydroisoflavone; D004967:Estrogens; D007529:Isoflavones; D048789:Phytoestrogens; D010936:Plant Extracts; D004958:Estradiol; D060754:Equol; D019833:Genistein