Document Detail

Formation of neutralizing antibodies during intranasal synthetic salmon calcitonin treatment of Paget's disease.
MedLine Citation:
PMID:  3410939     Owner:  NLM     Status:  MEDLINE    
Nine patients with Paget's disease were treated with 200 U (15 nmol) synthetic salmon calcitonin (sCT) intranasally (in)/day for 12 months. Five of them had received im or in sCT therapy for 1-4 yr up to 0.5-5 yr before this study. Low titer antibodies to sCT were detected in the serum of three of these five patients, but not in the four patients who had not received prior sCT therapy. After 2 months of in sCT administration, four of the former group, but none of the latter group, had antibodies to sCT. After 12 months of treatment, antibodies to sCT were found in all patients who had received sCT earlier and in three of the four patients who had not. The half-maximal inhibition of [125I]sCT binding ranged from 44-284 pmol/L sCT. In a cultured human breast cancer cell line (T47D) cAMP production was stimulated by sCT (EC50, 70 pmol/L). cAMP production stimulated by sCT (5 pmol/L) was reduced to 6-20% of the control value in the presence of serum from patients which inhibited [125I]sCT binding by more than 50% in a dilution of 1:50 or greater. In patients with lower titer antibodies cAMP production was not inhibited. Serum alkaline phosphatase activity was transiently lowered to 79 +/- 6% (+/- SE) of basal levels in the patients who had earlier received sCT (P greater than 0.1), while sustained reduction to between 66 +/- 2% and 84 +/- 6% of basal levels (P less than 0.05) occurred in the patients who had not been treated with sCT previously. In conclusion, reexposure to sCT of five patients with Paget's disease caused secondary antibody responses and clinical resistance.
F Levy; R Muff; S Dotti-Sigrist; M A Dambacher; J A Fischer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  67     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  1988 Sep 
Date Detail:
Created Date:  1988-09-27     Completed Date:  1988-09-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  541-5     Citation Subset:  AIM; IM    
Department of Orthopedic Surgery, University of Zurich, Switzerland.
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MeSH Terms
Administration, Intranasal
Aged, 80 and over
Alkaline Phosphatase / blood
Antibody Formation*
Calcitonin / administration & dosage,  analogs & derivatives*,  immunology
Calcium / blood
Drug Resistance
Middle Aged
Neutralization Tests
Osteitis Deformans / drug therapy*,  immunology
Reg. No./Substance:
7440-70-2/Calcium; 88433-78-7/calcitonin, salmon, Gly(8)-; 9007-12-9/Calcitonin; EC Phosphatase

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