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 derived primarily from an increase of the bone or liver isoenzyme, and to evaluate the treatment effect of steroids and disease modifying antirheumatic drugs (DMARD) on bone alkaline phosphatase (BAP) in serial analyses.


METHODS
58 patients with RA were treated with the DMARD gold sodium thiomalate (n = 22), D-penicillamine (n = 18), or sulfasalazine (n = 18) over a 24 week period with regular assessment of disease activity and measurement of BAP using a newly developed specific double monoclonal radioimmunometric assay.


RESULTS
In the RA group as a whole, BAP correlated with TAP at all time points (e.g., Week 0 rs = 0.50, p < 0.0001). In contrast, no correlation was found between the intraindividual change of BAP and TAP between Weeks 4 and 24. TAP was correlated with disease activity (assessed by plasma viscosity rs = 0.33, p < 0.02 for the whole RA group and rs = 0.48, p < 0.0002 for intraindividual change from Weeks 4 to 24). Similarly, gamma-glutamyltranspeptidase was correlated with disease activity (rs = 0.56, p < 0.0001, and rs = 0.50, p < 0.0001, respectively). In contrast, BAP was not correlated with disease activity. Low dose steroids and the 3 DMARD studied had no significant effect on the time course of BAP.


CONCLUSIONS
In the majority of patients with active RA, any increase of TAP is not mirrored by an increase of BAP. This supports the hypothesis that inflammatory reactions result in an increase in the plasma concentration of the membrane bound enzymes of the hepatobiliary system, including gamma-glutamyltranspeptidase and the liver isoenzyme of alkaline phosphatase, which is likely to be responsible, at least in part, for the increase of TAP. Since BAP is not correlated with disease activity, BAP measurements are not useful in monitoring response to treatment.
Beyeler
C
C
Department of Rheumatology, University of Berne, Switzerland.
Banks
R
R
Thompson
D
D
Forbes
M A
MA
Cooper
E H
EH
Bird
H A
HA
D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D001842:Bone and Bones / Q000201:enzymology*; D005260:Female; D006052:Gold Sodium Thiomalate / Q000627:therapeutic use; D006801:Humans; D015592:Immunoradiometric Assay; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010396:Penicillamine / Q000627:therapeutic use; D012460:Sulfasalazine / Q000627:therapeutic use; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D006052:Gold Sodium Thiomalate; D012460:Sulfasalazine; D005723:gamma-Glutamyltransferase; D000469:Alkaline Phosphatase; D010396:Penicillamine