Growth hormone treatment prevents osteoporosis in uremic rats
I. Berger1, G. Piecha1,2,3, R. Rabkin4, N. Kaya1, A. Geldyyev1, D. Sun4, Y. Chen4, N. Koleganova1 and M.-L. Gross1
1Department of Pathology, University of Heidelberg, Heidelberg, Germany, 2Department of Nephrology, Endocrinology and Metabolic Diseases Medical University of Silesia, Katowice, Poland, 3Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany and 4Research Service, Veterans Affairs Palo Alto Health Care System and Department of Medicine, Stanford University, Palo Alto, California, USA
Offprint requests to: Irina Berger, MD, Institute of Pathology, University Heidelberg, Im Neunheimer Feld 220/221, 69120 Heidelberg, Germany. e-mail: Irina_berger@med.uni-heidelberg.de
Summary. Introduction: Growth hormone (GH) is responsible for longitudinal bone growth. GH-receptor in the growth plate was found to be decreased in chronic renal insufficiency. A therapeutic use of GH in chronic renal insufficiency is not established. The current study aims to clarify the effects of GH treatment on bone metabolism in a uremic rat model. Methods: Sprague Dawley rats were subjected to subtotal surgical renal ablation (SNX) or sham operation. SNX rats were randomized into 4 groups: treated with different doses of GH (1.5, 4.0, or 10.0 mg/kg) or vehicle after 10 weeks of uremia and treated for 6 weeks. Bone and renal morphology was evaluated: bone density, thickness of spongiosa, osteoblast surface, osteoid volume, osteoclast quantity, and resorptive volume. Results: GH treatment resulted in a decrease of resorption area and lower number of osteoclasts. Osteoid volume, number of osteoblasts, percentage of active osteoblasts, thickness of the growth plate and mean cortical width increased. GH receptor (GHR) protein expression increased in GH treated rats. IGF-1 expression was decreased in osteoblasts and chondroblasts of SNX-V rats and increased following GH treatment. The TGF-ß expression was down regulated in SNX+V group in osteocytes and chondroblasts as compared to sham operated animals. The down regulation was prevented in treated animals irrespective of the dose given. Conclusions: Treatment with GH in uremic animals increased bone density to the levels of non-uremic controls. Thus GH seems to have a potential of preventing renal osteodystrophy. Histol Histopathol 22, 1231-1239 (2007)
Key words: Osteoporosis, Uremia, Growth hormone
DOI: 10.14670/HH-22.1231