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The best evidence for the use of bone turnover markers in clinical medicine is in the monitoring of the treatment for osteoporosis (Figure 9.1). This approach is useful if care is taken to minimize interindividual variability. This can be done if the blood and urine samples are collected in the morning. For example, the blood sample should be taken between 08:00 and 10:00 in the fasting state, and the urine collection between 07:00 and 09:00. Variability can be further reduced by obtaining markers on two occasions before starting therapy. The average of the two marker results is then calculated and forms a baseline to calculate the change in markers after treatment is started. Follow-up measurements can then

Figure 9.1 NTx was measured in the second morning void urine sample in 49 patient with osteoporosis (Bainbridge et al., 2000 [87]) on two occasions at baseline (B1 and B2) and then after 4, 7 and 10 months on treatment with HRT or bisphosphonates. Note that NTx does vary before starting treatment, and that there is an early and marked decrease in NTx after starting treatment such that the maximum effect is seen by 4 months in most patients. Note that NTx is in the lower half of the premenopausal reference range in most subjects after 10 months of treatment.

Figure 9.1 NTx was measured in the second morning void urine sample in 49 patient with osteoporosis (Bainbridge et al., 2000 [87]) on two occasions at baseline (B1 and B2) and then after 4, 7 and 10 months on treatment with HRT or bisphosphonates. Note that NTx does vary before starting treatment, and that there is an early and marked decrease in NTx after starting treatment such that the maximum effect is seen by 4 months in most patients. Note that NTx is in the lower half of the premenopausal reference range in most subjects after 10 months of treatment.

be made 3-6 months after starting therapy, and the average of these taken to compare with the baseline value. A decrease of more than 20-30% in a serum marker or of more than 40-60% in a urine marker would then indicate a response. It is also desirable to suppress the bone marker level into the normal reference range. Figure 9.1 shows the results of antiresorptive therapy in patients with osteoporosis. Note that there is variability in the two baseline measurements. The effect of treatment is rapid and the bone turnover level decreases to the lower half of the reference range for premenopausal women in most cases. This early sign of response assures a positive outcome in over one-half of patients. This test is useful when carried out in conjunction with follow-up measurements of lumbar spine BMD.

It is likely that bone turnover markers will eventually be used to predict future fracture risk so that patients who require treatment can be better managed. The best way to use markers for predicting fracture risk, however, has not yet been determined.

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