BONE ALKALINE-PHOSPHATASE IN RHEUMATOID-ARTHRITIS - A LONGITUDINAL-STUDY

Objective. To determine whether the raised total alkaline phosphatase (TAP) found in patients with active rheumatoid arthritis (RA) is deriv ed primarily from an increase of the bone or liver isoenzyme, and to e valuate the treatment effect of steroids and disease modifying antirhe umatic drugs (DMARD) on bone alkaline phosphatase (BAP) in serial anal yses. Methods. 58 patients with RA were treated with the DMARD gold so dium thiomalate (n = 22), D-penicillamine (n = 18), or sulfasalazine ( n = 18) over a 24 week period with regular assessment of disease activ ity and measurement of BAP using a newly developed specific double mon oclonal radioimmunometric assay. Results. In the RA group as a whole, BAP correlated with TAP at all time points (e.g., Week 0 r(s) = 0.50, p <0.0001). In contrast, no correlation was found between the intraind ividual change of BAP and TAP between-Weeks 4 and 24. TAP was correlat ed with disease activity (assessed by plasma viscosity r(s) = 0.33, p <0.02 for the whole RA group and r(s) = 0.48, p <0.0002 for intraindiv idual change from Weeks 4 to 24). Similarly, gamma-glutamyltranspeptid ase was correlated with disease activity (r(s) = 0.56: p <0.0001, and r = 0.50, p <0.0001, respectively). In contrast, BAP was not correlate d with disease activity. Low dose steroids and the 3 DMARD studied had no significant effect on the time course of BAP. Conclusion. In the m ajority of patients with active RA, any increase of TAP is not mirrore d by an increase of BAP This supports the hypothesis that inflammatory reactions result in an increase in the plasma concentration of the me mbrane bound enzymes of the hepatobiliary system, including gamma-glut amyltranspeptidase and the liver isoenzyme of alkaline phosphatase, wh ich is Likely to be responsible, at least in part, for the increase of TAP. Since BAP is not correlated with disease. activity, BAP measurem ents are not useful in monitoring response to treatment.