BIOLOGICAL VARIATION IN BONE-DERIVED BIOCHEMICAL MARKERS IN SERUM

Analytical, within-subject and between-subject components of variation have been determined for total alkaline phosphatase (ALP) and its bon e isoform, osteocalcin, and tartrate-resistant acid phosphatase (TR-AC P) in serum specimens from a cohort of 10 healthy subjects over a 1-mo nth period. From these data, we have calculated the desirable analytic al imprecisions, the indices of individuality, the critical difference s for significant change detection, and the number of specimens requir ed to estimate the homeostatic setpoint of an individual. For total AL P and its bone isoform, most of the observed variability was biologic, whereas osteocalcin and TR-ACP also had relatively high analytical va riability. Total and bone ALP were also the parameters showing the low est within-subject variability, whereas TR-ACP showed the lowest inter individual fluctuation. Osteocalcin and bone ALP had marked individual ity, showing that the use of population-based reference limits is inad equate for their interpretation. The applicable differences required f or two results to be significantly different (p less than or equal to 0.05) are bone ALP:20%; osteocalcin:29%; and TR-ACP:35%. The results d emonstrate that the biochemical markers of bone turnover studied are o f limited use to screen for metabolic bone disorders, but can be usefu l adjuncts for monitoring groups of patients in longitudinal studies.