Efficacy of intranasal human calcitonin in patients with Paget's disease refractory to salmon calcitonin

PURPOSE: 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. PATIENTS AND 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 [+ or -] 0.67%, mean [+ or -] standard error) was similar before and at the end of intranasal hCT therapy -5.92 [+ or -] 0.80%, p >0.1). Intranasal sCT (0.1 mg) lowered serum calcium less effectively -2.86 [+ or -] 0.76%) than 3 mg intranasal hCT (p CONCLUSION: 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.
Paget's disease is a skeletal disease of the elderly involving chronic inflammation of the bones, leading to thickening and softening of the bones and bowing of the long bones. Calcitonin is a hormone of the thyroid gland that regulates bone and calcium metabolism. Calcitonin obtained from salmon is given intranasally or through the nose to treat Paget's disease. However, some patients may become unresponsive to treatment with salmon calcitonin (sCT). This resistance may result from the production of antibodies, or immune proteins, that specifically bind and inactivate the sCT. Hence human calcitonin (hCT) was developed to avoid activating immune mechanisms. The effectiveness of hCT in treating Paget's disease was assessed in 12 patients treated twice daily for six months with one milligram (mg) of intranasal hCT. The reduction of calcium in the blood was similar before and at the end of treatment with intranasal hCT. A dose of 0.1 mg sCT was less effective than three mg hCT in lowering blood calcium levels. A low concentration of antibodies to sCT did not alter the response to sCT or hCT. Treatment with hCT for six months was associated with a decrease in blood levels of the enzyme alkaline phosphatase to 62 percent of levels before treatment, and decreased urinary excretion of hydroxyproline. The new formulation hCT was effective in lowering serum alkaline phosphatase levels in four patients, who were resistant to treatment with sCT. These findings show that hCT is effective in decreasing blood calcium and alkaline phosphatase levels and the urinary excretion of hydroxyproline in patients with Paget's disease, including those patients who are resistant to treatment with sCT. (Consumer Summary produced by Reliance Medical Information, Inc.)