Paget's Disease of Bone
Paget's Disease of Bone
As PD is characterised by accelerated bone remodelling, measurement of markers of bone turnover are one of the key investigations in management and diagnosis. The performance of a variety of markers of bone formation and bone resorption has been assessed for the diagnosis and monitoring of PD. We assessed seven turnover markers in a trial of patients with active PD treated with ibandronate (n=20) or placebo (n=9). All participants had PD confirmed on plain X-ray and ALP at least twice the upper reference range. Participants were randomised to 6 mg intravenous ibandronate at baseline, or 6 mg ibandronate at baseline and 1 month, or placebo and blood samples were taken at baseline and 6 months. Figure 2 shows that there were substantial differences in the performance of these markers. Of the bone formation markers, total ALP, bone alkaline phosphatase (bALP) and procollagen type-I N-terminal propeptide (PINP) had similar results. At baseline, these markers were elevated in all patients and were highly correlated. With treatment, they declined by 70–80%, and again changes were highly correlated. Of the bone turnover markers, only urine N-telopeptide of type I collagen cross-links (NTx) had similar results to these three bone formation markers. In contrast, osteocalcin, a bone formation marker, and C-telopeptide of type I collagen cross-links (CTx) and free deoxpyridinoline (fDPD), two bone resorption markers, had much lower proportions of abnormal results at baseline and smaller decreases with treatment. Therefore, the best markers appear to be total ALP, bALP, PINP and urine NTx. Of these, urine NTx and bALP have higher interassay and intra-assay coefficients of variation. Because of its widespread availability, low assay variation and low cost, total ALP is the single best marker for clinical use in PD. PINP is more specific and can be useful as second line test when ALP is normal and mild but active PD is suspected, or in patients with other abnormal liver enzyme tests.
(Enlarge Image)
Figure 2.
Performance of bone turnover markers in Paget's disease (PD). The left axis shows the percentage of patients with PD with abnormal bone turnover markers at baseline, and the right axis, the average decrease in marker after treatment with ibandronate. ALP, total serum alkaline phosphatase; bALP, bone alkaline phosphatase; OC, osteocalcin; PINP, procollagen type-I N-terminal propeptide; NTx, urine N-telopeptide of type I collagen cross-links; fDPD, free deoxpyridinoline; β-CTx, C-telopeptide of type I collagen cross-links.
Bone Turnover Markers
As PD is characterised by accelerated bone remodelling, measurement of markers of bone turnover are one of the key investigations in management and diagnosis. The performance of a variety of markers of bone formation and bone resorption has been assessed for the diagnosis and monitoring of PD. We assessed seven turnover markers in a trial of patients with active PD treated with ibandronate (n=20) or placebo (n=9). All participants had PD confirmed on plain X-ray and ALP at least twice the upper reference range. Participants were randomised to 6 mg intravenous ibandronate at baseline, or 6 mg ibandronate at baseline and 1 month, or placebo and blood samples were taken at baseline and 6 months. Figure 2 shows that there were substantial differences in the performance of these markers. Of the bone formation markers, total ALP, bone alkaline phosphatase (bALP) and procollagen type-I N-terminal propeptide (PINP) had similar results. At baseline, these markers were elevated in all patients and were highly correlated. With treatment, they declined by 70–80%, and again changes were highly correlated. Of the bone turnover markers, only urine N-telopeptide of type I collagen cross-links (NTx) had similar results to these three bone formation markers. In contrast, osteocalcin, a bone formation marker, and C-telopeptide of type I collagen cross-links (CTx) and free deoxpyridinoline (fDPD), two bone resorption markers, had much lower proportions of abnormal results at baseline and smaller decreases with treatment. Therefore, the best markers appear to be total ALP, bALP, PINP and urine NTx. Of these, urine NTx and bALP have higher interassay and intra-assay coefficients of variation. Because of its widespread availability, low assay variation and low cost, total ALP is the single best marker for clinical use in PD. PINP is more specific and can be useful as second line test when ALP is normal and mild but active PD is suspected, or in patients with other abnormal liver enzyme tests.
(Enlarge Image)
Figure 2.
Performance of bone turnover markers in Paget's disease (PD). The left axis shows the percentage of patients with PD with abnormal bone turnover markers at baseline, and the right axis, the average decrease in marker after treatment with ibandronate. ALP, total serum alkaline phosphatase; bALP, bone alkaline phosphatase; OC, osteocalcin; PINP, procollagen type-I N-terminal propeptide; NTx, urine N-telopeptide of type I collagen cross-links; fDPD, free deoxpyridinoline; β-CTx, C-telopeptide of type I collagen cross-links.
