Degree Name

PhD (Doctor of Philosophy)

Program

Biomedical Sciences

Date of Award

12-2004

Committee Chair or Co-Chairs

Ronald C. Hamdy, Fred E. Hossler

Committee Members

Richard Skalko, Kenneth E. Ferslew, Ellen M. Rasch

Abstract

In the United States, osteoporosis results in about 1.5 million annual fractures, costing approximately $15 billion. Calcitonin is safe and effective in slowing osteoporotic bone loss, but its effect is transient. The current studies were designed to explore the dose-dependent effects of salmon calcitonin on bone turnover in ovariectomized rats and to determine if the decrease in therapeutic effectiveness of calcitonin demonstrated over time with higher doses is due to oversuppression of bone turnover. Doses of 5, 15, & 50 IU/kg BW/day of calcitonin were compared to placebo in 12-week-old ovariectomized and sham-ovariectomized Sprague-Dawley rats for 24 weeks. The spinal bone mineral content (BMC) as measured by DXA in ovariectomized subjects receiving 5 & 15 IU/kg of calcitonin was not significantly different from sham-ovariectomized subjects, while spinal BMC of subjects receiving 50 IU/kg was significantly lower than shamovariectomized subjects (p<0.05). Femoral BMC of ovariectomized subjects was significantly lower than sham-ovariectomized subjects (p<0.05), but no significant differences were noted between treatment groups. Scanning electron microscopy (SEM) demonstrated a decrease in number and density of trabeculae and in cortical thickness when comparing femurs from ovariectomized with sham-ovariectomized subjects. SEM of subjects receiving 50 IU/kg displayed greater bone loss than other groups. No significant differences were noted between groups for levels of urinary helical peptides or serum pyridinoline [ELISA], indicators of bone resorption. Urinary calcium excretion [capillary ion electrophoresis] was significantly higher in subjects receiving 50 IU/kg of calcitonin than other ovariectomized subjects (p<0.05). Serum levels of osteocalcin [RIA], an indicator of bone formation, were significantly higher in subjects receiving 5 IU/kg of calcitonin than control subjects and those receiving 50 IU/kg (p<0.05). Production of antibodies to calcitonin [ELISA] by subjects in this study did not correlate with changes in bone turnover or bone density. The results of this study do not provide evidence higher doses of calcitonin result in oversuppression of bone turnover. However, urinary calcium excretion affected bone resorption in a reverse dose-dependent manner, suggesting the calciuric effect may be responsible for less effective outcomes seen with higher doses of calcitonin.

Document Type

Dissertation - Open Access

Copyright

Copyright by the authors.

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