title: Abnormal bone collagen morphology and decreased bone strength in growth hormone-deficient rats.
abstract: Patients with growth hormone deficiency (GHD) have an increased risk of bone fractures. In these patients, the well-described decrease in bone mineral density (BMD) and content (BMC) may, however, not alone explain the increase in fracture rate. Accordingly, the aim of this study was to evaluate collagen morphology and bone mineralisation in cortical bone as well as bone strength in GHD rats to try to clarify the explanation for the increased fracture rate. The Dw-4 rat was used as a model for GHD. This strain of rats has an autosomal recessive disorder, reducing GH synthesis to approximately 10% and growth rate to approximately 40-50% when compared to normal control rats. Five male Dw-4 rats were examined at age 12 weeks and five healthy Lewis rats served as age-matched controls. The animals were examined for (1) bone mineral status by dual energy X-ray absorptometry (DXA) and ash weight/bone volume, (2) biomechanical properties, (3) serum insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3), and (4) collagen morphology of cortical bone from the right femurs was examined by scanning and transmission electron microscopy. A significant decrease was found in serum IGF-I, IGFBP-3 and biomechanical properties in GHD rats compared to controls (P < 0.009). While DXA-derived BMD was decreased, no significant difference was found in ash weight/bone volume. Electron microscopy showed a significant decrease in the number and a significant increase in the diameter of collagen microfibrils in GHD rats as compared to their controls (P < 0.009). In conclusion, we report for the first time that collagen morphology in bone is markedly altered in rats with isolated GHD. Whether similar conditions are present in GHD patients need further investigations. The changes described, however, may provide a co-explanation for the increased fracture rate in GHD.
authors.affiliation: Department of Endocrinology and Nephrology, Rigshospitalet, Copenhagen, Denmark. mlange@rh.dk
authors.forename: Martin
authors.initials: M
authors.lastname: Lange
authors.forename: Klaus
authors.initials: K
authors.lastname: Qvortrup
authors.forename: Ole Lander
authors.initials: OL
authors.lastname: Svendsen
authors.forename: Allan
authors.initials: A
authors.lastname: Flyvbjerg
authors.forename: Jette
authors.initials: J
authors.lastname: Nowak
authors.forename: Michael M
authors.initials: MM
authors.lastname: Petersen
authors.forename: Klaus
authors.initials: K
authors.lastname: ØLgaard
authors.forename: Ulla
authors.initials: U
authors.lastname: Feldt-Rasmussen
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000648:ultrastructure*; D003094:Collagen / Q000648:ultrastructure*; D005109:Extracellular Matrix / Q000648:ultrastructure; D005260:Female; D024022:Fibrillar Collagens / Q000648:ultrastructure; D013006:Growth Hormone / Q000172:deficiency*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D051381:Rats
chemical_list: D024022:Fibrillar Collagens; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D003094:Collagen