Assessment of Urinary Bone Markers for Monitoring Treatment of Osteoporosis (Evidence-Based Medicine and Test Utilization) (Clinical Report‪)‬

Extended treatment of an individual patient with a bone-active agent for osteoporosis calls for some evidence that the treatment is working. In the osteoporotic patient, a change of spinal bone density from vertebrae L1 or L2 to L4 has been used to demonstrate a response, but its use has been restricted by the occurrence of deformities in the lumbar spine, particularly in the elderly; by the limited response of bone density to some treatments (1); and because the time to show a significant change may be as long as 2 years or more (2). Changes in measurements of markers of bone resorption and formation, which are often increased in postmenopausal women with osteoporosis, have been proposed as a means of detecting early responses to treatment (3). Groups of patients treated with estrogens or bisphosphonates show significant decreases of these markers (4). Even if the response of a treatment group is statistically significant, this is not useful clinically unless the change in an individual patient is greater than would be expected on the basis of known variability. This degree of change is known in laboratory medicine as the reference change value (RCV) [1] and in the bone marker field and elsewhere as the least (or minimum) significant change or, sometimes, critical difference. It is the minimum change in the quantity that would imply a true biological response. Hereafter in this report it is referred to as RCV. Variation of factors affecting bone turnover, including seasonal variation of vitamin D, may affect bone marker activity (5); they therefore should be followed for as long as possible in patients receiving no bone-active agents. With-in-person variability may also vary among different populations or groups. Intraassay, interassay, and with-in-person variances, and hence RCV, have been reported for several markers.