title: Effect of human parathyroid hormone hPTH (1-34) applied at different regimes on fracture healing and muscle in ovariectomized and healthy rats.
abstract: Three experiments were conducted to investigate the effect of intermittent administration of parathyroid hormone (PTH) (1-34) applied at different regimes on fracture healing and muscle in healthy and ovariectomized (Ovx at 3 months of age) rats. Five-month old rats underwent bilateral transverse metaphyseal osteotomy of tibia and were divided into groups (12 rats each). In Exp 1, Ovx rats were either treated with PTH (7x/w, 1-35d), with oral estradiol-17beta-benzoate (0.4 mg/kg BW, 1-35d) or untreated. In Exp. 2, there were 3 groups: healthy untreated or treated with PTH (5x/w, 1-35d or 7-35d). In Exp. 3, there were 7 groups: healthy, Ovx, "healthy PTH 5x/w 7-35d", "Ovx PTH 5x/w 7-35d, 14-35d or 14-28d", "Ovx PTH every other day 7-35d". Single dosage of PTH was 40 microg/kg BW. After 35 days of healing one tibia was analyzed by computed tomographical, biomechanical, histological analyses. The other tibia was used in analyses of Alp, Oc, Trap 1, Igf-1, Rankl, Opg genes (Exp.2, 3). Serum Oc and Alp were measured. Body, uterus weight was recorded. M. gastrocnemius was analyzed for weight (Exp. 2), fiber size and mitochondrial respiratory activity (MRA) (Exp.3). Estrogen enhanced uterus weight, prevented body increase, however, did not improve bone healing in Ovx rats (Exp. 1). PTH administration from days 1 and 7 improved bone parameters in all rats regardless of the application frequency (7, 5x/w or every other day) (Exp. 1, stiffness Ovx: 118+13 N/mm, Ovx PTH: 250+/-20 N/mm) being more effective in healthy rats (Exp. 3, stiffness improvement Healthy: 59 to 174 N/mm, Ovx: 52 to 98 N/mm). Serum Oc level was elevated in PTH treated rats. Application from day 14 proved to be less effective (Exp. 3). PTH had no effect (P>0.05) on body, uterus and muscle weight, muscle fiber size, MRA and expression of bone markers. PTH promoted bone healing in Ovx and healthy rats, when it is applied during early stage of healing without having any adverse systemic effect. In perspective, PTH may represent a treatment for enhancement of fracture healing. The findings need to be confirmed by follow-up studies on other animals.
authors.affiliation: Department of Trauma Surgery and Reconstructive Surgery, University of Goettingen, Robert-Koch 40, 37075 Goettingen, Germany. komrakova@yahoo.com
authors.forename: Marina
authors.initials: M
authors.lastname: Komrakova
authors.forename: Ewa K
authors.initials: EK
authors.lastname: Stuermer
authors.forename: Carsten
authors.initials: C
authors.lastname: Werner
authors.forename: Michael
authors.initials: M
authors.lastname: Wicke
authors.forename: Leila
authors.initials: L
authors.lastname: Kolios
authors.forename: Stephan
authors.initials: S
authors.lastname: Sehmisch
authors.forename: Mohammad
authors.initials: M
authors.lastname: Tezval
authors.forename: Florian
authors.initials: F
authors.lastname: Daub
authors.forename: Timo
authors.initials: T
authors.lastname: Martens
authors.forename: Peter
authors.initials: P
authors.lastname: Witzenhausen
authors.forename: Christian
authors.initials: C
authors.lastname: Dullin
authors.forename: Klaus M
authors.initials: KM
authors.lastname: Stuermer
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D005260:Female; D017102:Fracture Healing / Q000187:drug effects*; D006801:Humans; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009929:Organ Size; D010027:Osteotomy; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D019379:Teriparatide / Q000494:pharmacology*; D013977:Tibia / Q000187:drug effects / Q000473:pathology / Q000502:physiology
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D019379:Teriparatide