The enzymatic mechanism of the otospongiotic disease and NaF action on the enzymatic balance.

Extensive research on enzymes led to the discovery of the innermost mechanism of the otospongiotic disease. The authors present the results of multiple correlations made from February 1976 to September 1980 on 648 samples of perilymph taken during stapedectomies performed on otosclerotic patients. We studied microdosages of three selected enzymes--trypsin, alpha 1 antitrypsin, and alpha 2 macroglobulin--in each of the samples and their relationship with cochlear deterioration expressed in dBs of bone conduction decrease in pure-tone audiometry testing. This study allowed us a better knowledge of the enzymatic mechanism of the otospongiotic disease, based on the previously reported trypsin-alpha 1 antitrypsin balance, but in which alpha 2 macroglobulin appears to play a role as essential as that of alpha 1 antitrypsin. This enzymatic mechanism explains NaF efficiency, which is due in fact to a double action: not only direct trypsin inhibition, but also an overall reduction in enzymatic values in the perilymph of otospongiotic/otosclerotic patients. Current studies could lead to the possibility of future NaF replacement by proteinase inhibitors either of microbial origin, under study by Japanese researchers, or even of synthetic origin, which should be investigated. In fact, the role of NaF therapy could already be taken over by diphosphonates currently under study.