calcitonin and Weight-Gain

The study was designed to determine, by histomorphometric techniques, bone changes as a function of time during long-term treatment with salmon calcitonin (CT) and after withdrawal of the hormone in ovariectomized (OVX) rats. Groups of OVX rats were treated with vehicle alone or CT on alternate days for 30, 60, or 90 days. Additional groups of sham-operated control rats were treated with vehicle alone. Rats from each of the three groups were sacrificed at each time point. All treatments in the remaining rats were then terminated at 90 days, followed by sacrifice of rats from each group at 30 and 60 days after withdrawal of vehicle or CT treatment. The proximal tibia from each animal was processed undecalcified for quantitative bone histomorphometry. Compared with control rats, the proximal tibiae of vehicle-treated OVX rats were characterized by cancellous osteopenia and significant increases in osteoclast surface, osteoblast surface, mineralizing surface, mineral apposition rate, and bone formation rate. CT treatment of OVX rats partially prevented cancellous bone loss by approximately 50% and significantly decreased most of the above indices of bone turnover relative to vehicle-treated OVX rats. However, soon after withdrawal of CT, OVX rats previously treated with the hormone exhibited rapid loss of cancellous bone associated with increased bone turnover. These results in an animal model of estrogen depletion suggest that early postmenopausal women who are withdrawn from prophylactic CT treatment may be at high risk for subsequent bone loss.

Topics: Animals; Bone and Bones; Calcitonin; Calcium; Female; Osteoclasts; Ovariectomy; Rats; Rats, Sprague-Dawley; Time Factors; Weight Gain

Studies were carried out to determine whether monolithic depot formulations, prepared using lactide:glycolide copolymers, could be used to administer salmon calcitonin (sCT) to rats in vivo. Formulations containing 2, 5, or 10% (w/w) sCT were administered subcutaneously to female Wistar strain rats. Release of sCT was determined by measurement of peptide in plasma using a specific radioimmunoassay and by measurement of residual sCT in the depots after recovery at postmortem. Plasma calcium concentrations and cumulative weight gain of the animals were used to measure pharmacological effects of the released sCT. Release of sCT from the depots was controlled by the copolymer and was sustained for periods up to 10 days. However, the release of sCT from the depots did not significantly alter plasma calcium concentrations, and effects on cumulative weight gain were small and transient. Peptide loading of the formulations was shown to modify sCT release. Maximal release of sCT from depots containing 10% peptide occurred over a 7 to 14-day period postadministration, with 5% sCT release occurred between days 11 and 14, and with 2% sCT, the period of maximal release was between days 11 and 18. Release of peptide from the depots was essentially complete by 21 days postadministration irrespective of the peptide loading. These data suggest that lactide:glycolide copolymer depots may have application for the convenient clinical administration of sCT in metabolic bone diseases.

Topics: Animals; Calcitonin; Calcium; Delayed-Action Preparations; Drug Implants; Female; Lactic Acid; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Radioimmunoassay; Rats; Rats, Wistar; Weight Gain