Systemic application of growth hormone for enhancement of secondary and intramembranous fracture healing.
Hormones are known to influence bone metabolism and cellular mechanisms of fracture healing. Recent technologies in molecular biology offer recombinant production of hormones, which makes them applicable for pharmacological use. To investigate the effect of systemic growth hormone (GH) application experiments were performed in micropig animal models. Systemic daily subcutaneous injection of species-specific recombinant GH was investigated in Yucatan micropigs to evaluate the effect on secondary fracture healing in a standardized gap model (1 cm) and on intramembranous bone formation in distraction osteogenesis (DO). Quantitative computed tomography (qCT), biomechanical testing, measurement of systemic insulin-like growth factor 1 (IGF-1) levels as well as histomorphometric analyses were performed to investigate differences in regenerate formation. Systemic GH administration significantly increased the torsional stability of the regenerate in comparison to the contralateral side in both experiments. qCT showed accelerated fracture bridging in the GH-treated animals in bone defect healing, while in DO histomorphometry elicited larger callus areas in the case of GH application. Systemic IGF-1 levels were significantly increased in both GH-treated groups. These experiments show that the systemic administration of recombinant GH accelerates fracture healing in standardized animal models. Clinical studies have now been initiated in order to prove the safety and the effectiveness of this therapeutical option.
Bail
Hermann J
HJ
Clinic for Trauma and Reconstructive Surgery, Charité - Campus Virchow Clinic, Medizinische Fakultät der Humboldt-Universität zu Berlin, Germany. hermann.bail@charite.de
Kolbeck
Stefan
S
Krummrey
Gert
G
Schmidmaier
Gerhard
G
Haas
Norbert P
NP
Raschke
Michael J
MJ
D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000473:pathology; D002146:Bony Callus / Q000473:pathology; D005260:Female; D015200:Fluoroimmunoassay; D017102:Fracture Healing / Q000187:drug effects*; D050723:Fractures, Bone / Q000188:drug therapy / Q000473:pathology; D013006:Growth Hormone / Q000627:therapeutic use*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D013552:Swine; D013556:Swine, Miniature
D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone