HDCN Article Review/Hyperlink

Urena P, Hruby M, Ferreira A, Ang KS, de Vernejoul MC

Plasma total versus bone alkaline phosphatase as markers of bone turnover in hemodialysis patients

J Am Soc Nephrol (Mar) 7:506-512 1996

The authors investigated whether bone specific alkaline phosphatase could differentiate patients with high bone turnover from those with low turnover. Evaluation of 42 chronic hemodialysis patients included plasma determinations of intact parathyroid hormone (IRMA- Nichols assay), total alkaline phosphatase (automated method), and bone specific alkaline phosphatase (IRMA, Ostase-Hypritech, Belgium), as well as a transiliac bone biopsy for quantitative histomorphometry.

Patients were separated into groups according to type of bone disease observed on biopsy; high turnover, normal or low-turnover, and adynamic. Thirty-two patients had a high turnover lesion, while 1 had adynamic bone disease and 9 had normal or low turnover lesion. Those with high turnover had significantly higher plasma bone alkaline phosphatase and PTH levels than those with normal or low turnover disease whereas total alkaline phosphatase was not significantly different between the 2 groups. Bone formation and resorption were highly correlated with all the biochemical parameters, however, bone alkaline phosphatase was better correlated with bone formation rate than the total alkaline phosphatase and PTH. Plasma bone alkaline phosphatase level greater than 20 ng/mL had the best sensitivity, specificity and predictability for the diagnosis of high turnover bone disease. The combination of a bone alkaline phosphatase greater than 20 ng/mL and PTH greater than 200 pg/mL essentially excluded patients with normal or low turnover bone disease.

Comment: Despite the improvement of PTH assays and the development of newer markers of bone formation and resorption, many patients still require bone biopsy for diagnosis of their bone disorder and help direct therapy. The recent development of monoclonal antibodies against bone-specific alkaline phosphatase has resulted in the development of sensitive immunoassays for bone-specific alkaline phosphatase which has been demonstrated to be a more reliable marker of bone turnover than total alkaline phosphatase.

Utilizing a newly developed IRMA assay for bone alkaline phosphatase the authors demonstrated increased specificity and sensitivity of this marker for differentiating high from low turnover in a group of dialysis patients. Although bone alkaline phosphatase may become useful for clinical use, its widespread application could not be justified from this study. Only 10 of the patients evaluated had normal or low turnover. Of these 10, 7 had IRMA PTH levels less 150 pg/mL, levels in which vitamin D therapy is usually initiated and a biopsy would generally not be indicated as these patients would have normal or decreased bone turnover. As indicated by a recent report by Malluche and colleagues