Formation of Antibodies to Synthetic Human Calcitonin During Treatment of Paget's Disease

Abstract

Low-titre antibodies to synthetic human calcitonin (hCT) were detected in a 69-year-old woman suffering from Paget's disease who was treated for 16 months with hCT and the diphosphonate EHDP. Levels of antibody were highest between 10 and 18 months after commencement of therapy, slowly decreased after completion of treatment and were later no longer measurable. There was no immunological response to a single re-injection of hCT 14 months after discontinuation of therapy. Formation of antibodies to hCT in man is a very rare event, this being the first recorded case of an immune response to synthetic human calcitonin, whereas synthetic salmon calcitonin induces an immune response in a high percentage (up to 78 %) of the patients treated with this hormone.

Calcitonin in Osteoporosis

“…This notion has been corroborated by the results of the PROOF study, where calcitonin-binding antibodies were found in up to 34% of treated subjects, but without any correlation between their presence and skeletal response [51]. Notably, circulating antibodies that can neutralize the biologic activity of calcitonin have been also found in subjects treated with human calcitonin, although the finding is occasional [129,131,132]. Interestingly, significantly fewer antibodies were detected in subjects taking oral recombinant salmon calcitonin relative to intranasal salmon calcitonin (6.5% vs. 32.5%), even though the percentage of neutralizing antibodies among antibody-positive individuals was similar in the two groups, about 70% [30].…”

Formation of neutralizing antibodies during intranasal synthetic salmon calcitonin treatment of postmenopausal osteoporosis

“…In a single patient with Paget's disease, low titer antibodies to hCT were previously recognized [23]. In some patients treated earlier with salmon or porcine CT, clinical responsiveness was restored with the homologous synthetic hCT administered by nasal spray or intramuscularly [10][11][12][13][14][15].…”

Paget's disease of bone

“…The suppression of disease activity does not persist for very long, even with the continuation of the drug. Antibodies develop in around 30-60% of the patients (32,33). Side effects occur in approximately 10% of the patients and include nauseas, a metallic taste and flushing.…”