Endocrine Abstracts (2002) 3 P175

Abnormal collagen morphology and decreased bone strength in growth hormone deficient rats

M Lange1, K Qvortrup2, OL Svendsen1, A Flyvbjerg3, J Nowak4, K Olgaard1, MM Petersen5 & U Feldt-Rasmussen1


1Department of Endocrinology and Nephrology, Rigshospitalet, Copenhagen, Denmark; 2Department of Medical Anatomy B, University of Copenhagen, Copenhagen, Denmark; 3Department of Diabetes and Endocrinology, Aarhus Kommunehospital, Aarhus, Denmark; 4Novo Nordisk A/S, Maaloev, Denmark; 5Department of Orthopaedic Surgery, Rigshopitalet, Denmark.


Patients with growth hormone deficiency (GHD) have increased risk of bone fractures. Despite a well-known decrease in bone mineral density (BMD) and content (BMC) in these patients, these changes in bone mineralization cannot explain the increase in fracture rate alone. The purpose of this study was to evaluate collagen morphology in cortical bone from GHD rats in order to provide a further explanation for the increased fracture rate seen in GHD patients.

Methods: 5 male Dw-4 rats with isolated growth hormone deficiency were examined at age 12 weeks. 5 healthy Lewis rats acted as age-matched controls. The animals were examined for 1) bone mineralization by DEXA and ash weight/bone volume 2) fracture strength 3) and insulin-like growth factor I (IGF-I). Furthermore, the right femurs were demineralised and cortical bone was examined by scanning and transmission electron microscopy.

Results: Significant decrease was found in IGF-I, fracture strength and DEXA derived BMD/BMC in GHD rats compared to controls. No difference was found in ash weight/bone volume. Electron microscopy showed significant decrease in the number and significant increase in the diameter of collagen micro-fibrils in GHD rats compared to controls.

Conclusion: We have shown that collagen morphology in bone is markedly altered in rats with isolated GHD. Whether similar conditions are present in humans need to be explored. The changes, however, provide a possible explanation for the increase in fracture rate in GHD patients.

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