Efficacy of intranasal human calcitonin in patients with Paget's disease refractory to salmon calcitonin.
OBJECTIVE
A cause for the resistance to intranasal salmon calcitonin (sCT) therapy in patients with Paget's disease is the occurrence of neutralizing antibodies to sCT. As a result, a new formulation of intranasal human calcitonin (hCT) was developed, and the efficacy investigated in patients treated earlier with sCT.


METHODS
Twelve patients with Paget's disease were treated twice daily for 6 months with 1 mg synthetic hCT administered intranasally. Five patients demonstrated low-titer antibodies to sCT, and four of the patients did not respond previously to 1-year therapy with intranasal sCT. The hypocalcemic effect of 3 mg hCT was compared to that of 0.1 mg sCT before and after the intranasal hCT therapy. Serum alkaline phosphatase and the ratio between the urinary excretion of hydroxyproline and creatinine were measured before and during intranasal hCT treatment.


RESULTS
The hypocalcemic response to 3 mg intranasal hCT (-6.60 +/- 0.67%, mean +/- standard error) was similar before and at the end of intranasal hCT therapy (-5.92 +/- 0.80%, p greater than 0.1). Intranasal sCT (0.1 mg) lowered serum calcium less effectively (-2.86 +/- 0.76%) than 3 mg intranasal hCT (p less than 0.05). The presence of low-titer antibodies to sCT did not affect the hypocalcemic response to sCT or hCT. As a result of the 6-month intranasal hCT regimen, serum alkaline phosphatase and urinary hydroxyproline/creatinine ratio were reduced to 62 +/- 5% (p less than 0.001) and 80 +/- 7% (p less than 0.05) respectively, of pretreatment levels. In four patients previously resistant to intranasal sCT therapy because of neutralizing antibodies to sCT, serum alkaline phosphatase was similarly lowered by intranasal hCT to 66 +/- 6% of pretreatment levels (p less than 0.05).


CONCLUSIONS
A new formulation of intranasal hCT effectively lowered serum calcium levels, alkaline phosphatase concentrations, and urinary hydroxyproline excretion in patients with Paget's disease, some of whom were previously resistant to intranasal sCT because of neutralizing antibodies.
Muff
R
R
Department of Orthopedic Surgery, University of Zurich, Switzerland.
Dambacher
M A
MA
Perrenoud
A
A
Simon
C
C
Fischer
J A
JA
D000281:Administration, Intranasal; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D000906:Antibodies / Q000032:analysis; D002116:Calcitonin / Q000008:administration & dosage* / Q000276:immunology; D002118:Calcium / Q000097:blood; D004351:Drug Resistance / Q000276:immunology; D005260:Female; D006801:Humans; D006909:Hydroxyproline / Q000652:urine; D008297:Male; D008875:Middle Aged; D010001:Osteitis Deformans / Q000188:drug therapy* / Q000378:metabolism
D000906:Antibodies; C028815:salmon calcitonin; D002116:Calcitonin; D000469:Alkaline Phosphatase; D006909:Hydroxyproline; D002118:Calcium