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Selected Extraskeletal Effects of Systemic Treatment with Basic Fibroblast Growth Factor in Ovariectomized Rats
1 Departments of Pathobiology Correspondence: Address correspondence to: Heather L. Wamsley, University of Florida, College of Veterinary Medicine, Veterinary Medical Teaching Hospital, Clinical Pathology Service, 2015 SW 16th Av, Box 100103C, Gainesville, Florida 32610, USA; e-mail:wamsleyh{at}mail.vetmed.ufl.edu Basic fibroblast growth factor (bFGF) is a pleiotropic mitogen with a potent bone-forming effect, rendering it a potential osteoporosis therapy. This study examined selected extraskeletal effects of bFGF in ovariectomized rats, a well-established model of human postmenopausal osteopenia, to more fully characterize side effects associated with bFGF treatment. Five-month-old, osteopenic, ovariectomized rats were injected subcutaneously with vehicle or bFGF (1 mg/kg) daily for 3 weeks. Hematologic and biochemical analyses were performed; and kidneys, livers, and proximal tibiae were examined histologically and histomorphometrically. bFGF administration resulted in anemia that was due to a shift toward granulocyte production in the bone marrow. Increased granulocyte production was also observed in the liver of bFGF-treated rats, which exhibited a markedly increased number and area of hematopoietic foci. bFGF administration also caused mild glomerular hypertrophy that was not attended by significant biochemical evidence of glomerular dysfunction. The bone anabolic effect of subcutaneous bFGF administration was confirmed in the proximal tibia, and was associated with a significant decrease in urine fractional excretion of calcium in bFGF-treated rats. Though bFGF strongly stimulates bone formation at osteopenic skeletal sites, its extraskeletal effects may restrict the long-term use of bFGF in its current form as an osteoporosis therapy.
Key Words: Basic fibroblast growth factor • fibroblast growth factor-2 • anemia • myeloid hyperplasia • granulocytic hyperplasia • extramedullary hematopoiesis • glomerular hypertrophy • systemic effects • rats • bone Abbreviations: bFGF, basic fibroblast growth factor (fibroblast growth factor-2) • °C, Celsius • EP, prostaglandin E receptor • g, gram • h, hour • IQR, interquartile range • IV, intravenous • kg, kilogram • G:E, granulocytic-to-erythroid ratio • mg, milligram • OVX, ovariectomized • PGE2, prostaglandin E2 • SC, subcutaneous
Toxicologic Pathology, Vol. 33, No. 5,
577-583 (2005) This article has been cited by other articles:
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