Estrogen and raloxifene improve metaphyseal fracture healing in the early phase of osteoporosis. A new fracture-healing model at the tibia in rat.
BACKGROUND
Fracture healing in osteoporosis is delayed. Quality and speed of fracture healing in osteoporotic fractures are crucial with regard to the outcome of patients. The question arises whether established antiosteoporotic drugs can further improve fracture healing.


METHODS
Osteoporosis manifests predominantly in the metaphyseal bone. Nevertheless, an established metaphyseal fracture model is lacking. A standardized metaphyseal fracture-healing model with stable plate fixation was developed for rat tibiae. The healing process was analyzed by biomechanical, gene expression, and histomorphometric methods in ovariectomized (OVX) and sham-operated rats (SHAM), compared to standardized estrogen (E)- and raloxifene (R)-supplemented diets.


RESULTS
Estrogen and raloxifene improved the biomechanical properties of bone healing compared to OVX (Yield load: SHAM = 63.1 +/- 20.8N, E = 60.8 +/- 17.9N, R = 44.7+/-17.5N, OVX = 32:5 +/- 22.0N). Estrogen vs OVX was significant based on a denser trabecular network. Raloxifene greatly induced total callus formation ((R = 5.3 +/- 0.9 mm2, E = 4.7 +/- 0.5 mm2, SHAM = 4.51 +/- 0.61 mm2, OVX =4.1 +/- 0.6 mm2), whereas estrogen mainly enhanced new endosteal bone formation. There was no correlation between the gene expression (osteocalcin, collagen1alpha1, IGF-1, tartrate-resistant phosphatase) in the callus and the morphology and quality of callus formation.


CONCLUSIONS
Raloxifene and estrogen improve fracture healing in osteoporotic bone significantly with regard to callus formation, resistance, and elasticity. The biomechanically stable metaphyseal osteotomy model with T-plate fixation presented here has proven to be appropriate to investigate fracture healing in osteoporosis.
Stuermer
E K
EK
Department of Trauma Surgery, Plastic and Reconstructive Surgery, Georg-August-University of Goettingen, Robert-Koch-Str. 40, 37099, Göttingen, Germany. e.k.stuermer@med.uni-goettingen.de
Sehmisch
S
S
Rack
T
T
Wenda
E
E
Seidlova-Wuttke
D
D
Tezval
M
M
Wuttke
W
W
Frosch
K H
KH
Stuermer
K M
KM
D000704:Analysis of Variance; D000818:Animals; D001696:Biomechanical Phenomena; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005456:Fluorescent Dyes; D005593:Fracture Fixation, Internal; D017102:Fracture Healing / Q000187:drug effects; D008852:Microradiography; D010024:Osteoporosis / Q000150:complications*; D010027:Osteotomy; D010052:Ovariectomy; D020849:Raloxifene Hydrochloride / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013978:Tibial Fractures / Q000000981:diagnostic imaging / Q000209:etiology / Q000628:therapy*
D050071:Bone Density Conservation Agents; D005456:Fluorescent Dyes; C074283:estradiol 3-benzoate; D020849:Raloxifene Hydrochloride; D004958:Estradiol