A SINGLE MEASUREMENT OF BIOCHEMICAL MARKERS OF BONE TURNOVER HAS LIMITED UTILITY IN THE INDIVIDUAL PERSON

Biochemical markers of bone turnover are used to estimate the rate of bone loss in the individual osteoporotic patient. During recent years it has become increasingly clear that the biological variability of bi ochemical bone markers has to be taken into consideration in the evalu ation of their usefulness in the clinical setting. Eleven premenopausa l, 8 perimenopausal and 11 postmenopausal healthy women were included. We assessed the analytical and the biological components of variation for a number of resorptive and formative bone markers: u-hydroxyproli ne, u-pyridinoline, and u-deoxypyridinoline together with u-calcium an d u-creatinine, s-total alkaline phosphatases and s-osteocalcin. Blood and urine samples were collected five times with 7-day intervals. Uri nary parameters were expressed as outputs and corrected for creatinine in fasting night urines and second void fasting morning urines. The a bsolute values differed with a tendency towards increasing values in t he postmenopausal women, but the biological variations in relation to menopausal status were not different. The biological variability was m uch higher for the urinary resorptive markers than for the formative m arkers in the blood. The critical difference expressing the difference needed between two serial results from the same person to be signific ant at a 5% level was 15% for s-alkaline phosphatases, 18% for s-osteo calcin, and lowest in the second void fasting morning urines with valu es of 28% and 34% for u-pyridinoline/creatinine and u-deoxypyridinolin e/creatinine, and 50 % and 112 % for u-hydroxyproline/creatinine and u -calcium/creatinine, respectively. The index of individuality, denotin g the individual variation divided by the variation between subjects, was in the range from 0.19 for s-alkaline phosphatases to 1.23 for u-h ydroxyproline/minute in second void fasting morning urine making the u se of conventional reference intervals difficult. Low indices, however , indicate high test performance and offer the possibility of stratifi cation of persons within a range. The number of samples required to de termine the true individual mean value +/-5% for the single person, ra nged from 5 for s-total alkaline phosphatases, 6 for s-osteocalcin, 23 for u-deoxypyridinoline/creatinine in the fasting morning urine to ov er two hundred for u-calcium analytes; It is concluded that, due to hi gh biological variation, a single measurement of biochemical markers o f bone turnover is of limited utility in the individual person. We rec ommend that routine clinical use of biochemical markers should be rest ricted until further evidence justifies it.