A single measurement of biochemical markers of bone turnover has limited utility in the individual person

Abstract

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 biochemical bone markers has to be taken into consideration in the evaluation of their usefulness in the clinical setting. Eleven premenopausal, 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-hydroxyproline, u-pyridinoline, and u-deoxypyridinoline together with u-calcium and u-creatinine, s-total alkaline phosphatases and s-osteocalcin. Blood and urine samples were collected five times with 7-day intervals. Urinary parameters were expressed as outputs and corrected for creatinine in fasting night urines and second void fasting morning urines. The absolute values differed with a tendency towards increasing values in the postmenopausal women, but the biological variations in relation to menopausal status were not different. The biological variability was much higher for the urinary resorptive markers than for the formative markers in the blood. The critical difference expressing the difference needed between two serial results from the same person to be significant at a 5% level was 15% for s-alkaline phosphatases, 18% for s-osteocalcin, and lowest in the second void fasting morning urines with values of 28% and 34% for u-pyridinoline/creatinine and u-deoxypyridinoline/creatinine, and 50% and 112% for u-hydroxyproline/creatinine and u-calcium/creatinine, respectively. The index of individuality, denoting 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-hydroxyproline/minute in second void fasting morning urine making the use of conventional reference intervals difficult. Low indices, however, indicate high test performance and offer the possibility of stratification of persons within a range. The number of samples required to determine the true individual mean value +/- 5% for the single person, ranged from 5 for s-total alkaline phosphatases, 6 for s-osteocalcin, 23 for u-deoxypyridinoline/creatinine in the fasting morning urine to over two hundred for u-calcium analytes. It is concluded that, due to high biological variation, a single measurement of biochemical markers of bone turnover is of limited utility in the individual person. We recommend that routine clinical use of biochemical markers should be restricted until further evidence justifies it.

Changes in biochemical markers of bone metabolism and BMD during the first year after a hip fracture

“…Similar to what others have found, BMD was not correlated to bone markers (Cheng et al 1996). Osteoporosis is probably a heterogeneous disorder, which would explain the great interindividual variation in biochemical bone markers, besides the intra-individual variability (Beck Jensen et al 1997). They are therefore unsuitable for prediction of bone loss in the individual patient.…”

Involvement of bone-specific alkaline phosphatase and procollagen I carboxy-terminal propeptide as predictors of early fracture risk in Chinese children with juvenile osteoporosis: An interventional clinical trial

“…Due to high intraindividual and interindividual variability and large discrepancy in normal values of bone biochemical markers, it is difficult to (Jensen et al, 1997a;Jensen et al, 1997b). In addition to this, there is a large variability between analytical methods and standard from laboratory to laboratory (Jensen et al, 1997a;Jensen et al, 1997b). Authors have concluded that large biological variability in the biochemical markers of bone turnover make them unsuitable for diagnosis for prediction of future bone loss in individual patients (Jensen et al, 1997a;Jensen et al, 1997b).…”

“…We also assessed whether plasma levels of BSAP and PIPC could be used as predictors of early bone fracture in children. Due to high intraindividual and interindividual variability and large discrepancy in normal values of bone biochemical markers, it is difficult to (Jensen et al, 1997a;Jensen et al, 1997b). In addition to this, there is a large variability between analytical methods and standard from laboratory to laboratory (Jensen et al, 1997a;Jensen et al, 1997b).…”

“…In addition to this, there is a large variability between analytical methods and standard from laboratory to laboratory (Jensen et al, 1997a;Jensen et al, 1997b). Authors have concluded that large biological variability in the biochemical markers of bone turnover make them unsuitable for diagnosis for prediction of future bone loss in individual patients (Jensen et al, 1997a;Jensen et al, 1997b). In this trial, we have used standardized method and performed all the assessment at single laboratory in order to avoid any confounding variables.…”

Quantitative Measurements of Bone Remodeling Using 99mTc-Methylene Diphosphonate Bone Scans and Blood Sampling

“…A simpler and more widely used technique for studying bone remodeling is the measurement of biochemical markers of bone resorption and bone formation in serum or urine (8)(9)(10). However, the variability of biochemical marker measurements limits their use in individual patients (11,12). Also, they measure bone turnover throughout the whole skeleton and are unable to make regional measurements-for example at sites of predominantly trabecular (spine, pelvis) or cortical bone (long bones).…”