In vitro detection of neutralizing antibodies after treatment of Paget's disease of bone with nasal salmon calcitonin.

To elucidate the biologic relevance of circulating sCT antibodies, an in vitro bioassay system for the detection of neutralizing antibodies was developed utilizing the human breast carcinoma cell line T47D. We reasoned that the inhibition of the dose-dependent cAMP response to sCT in the T47D assay system by anti-sCT antibodies could be used to determine the in vivo relevance of these antibodies. In this report the clinical course of nine patients with Paget's disease of bone treated with intranasal sCT was correlated with the presence of 125I-sCT binding and neutralizing antibodies. Of these seven patients, four were found to have neutralizing antibodies; the appearance of the antibodies coincided with the development of resistance. One of these patients was subsequently treated with human calcitonin and revealed a good response to the treatment. There was no clinical resistance observed in the three patients with 125I-sCT binding antibodies but no neutralizing antibodies; no resistance was observed in two patients without 125I-sCT binding or neutralizing antibodies. We conclude that this new technique to determine the biologic relevance of circulating anti-sCT antibodies may be an useful adjunct for determining the cause of resistance in patients treated with sCT.