Summary
In this study, serum levels of classical serum markers of bone formation [carboxyterminal propeptide of procollagen type I (S-PICP), bone Gla protein (S-BGP)], and total alkaline phosphatase (S-AP)) were related to the calcium kinetic index of whole skeletal mineralization rate (m) by regression analysis in a variety of metabolic bone diseases. For each disease, the regression coefficient (r) as well as the fraction: standard error of estimate/mean dependent variable (SEE/Y) were determined. In a group of 19 normals, only the regression of S-PICP on m reached significance (r=0,53, P<0.02, SEE/Y=0.44), whereas regressions of S-AP and S-BGP on m were nonsignificant. In a pooled material of high-and low-turnover bone diseases without mineralization defects or spinal fracture [myxedema, thyrotoxicosis, and primary hyperparathyroidism (n=48)], a highly significant positive regression of S-PICP on m was demonstrable (r=0.50, SEE/Y=0.63, P<0.001). The regression coefficients obtained for S-BGP and S-AP were 0.74 (P<0.001, SEE/Y=0.41) and 0.42 (P<0.01, SEE/Y=0.55), respectively. When analyzing individual diseases in this group, significant differences among the three markers were detectable. In a group of 52 osteoporotics, S-PICP correlated significantly to m (r=0.49, P<0.001, SEE/Y=0.50). Corresponding r-values for S-BGP and S-AP were 0.21 (NS) and 0.48 (P<0.001, SEE/Y=0.61), respectively.
Patients with histologically proven osteomalacia revealed no correlation between S-PICP and m. S-BGP and S-AP were, however. significantly correlated to m [r=0.92 (SEE/Y=0.46) and r=0.82 (SEE/Y=0.57), respectively], indicating that S-BGP and S-AP reflect mineralization activity, whereas S-PICP reflects matrix formation only. In order to study cellular production of the three formative markers, organ level production rate was normalized for bone turnover by division with m. For each marker, the fraction (bone marker concentration/m) was calculated and the means compared with normal controls. S-PICP/m was found to be lower than normal in primary hyperparathyroidism (P<0.01) and thyrotoxicosis (P<0.001). S-AP/m was elevated in myxedema (P<0.05), osteoporosis (P<0.001), and osteomalacia (P<0.01). S-BGP/m only deviated significantly from normal in osteomalacia (P<0.001).
In conclusion, we found S-BGP to be a reliable marker of organ level mineralization rate in all diseases studied, whereas the regressions of S-AP and S-PICP revealed disease-specific discrepancies. This study also revealed significant alterations in the osteoblastic production rate of the three formative markers at the level of individual osteoblasts that have to be taken into account when comparing bone marker concentrations with other indices reflecting bone formation (e.g., calcium kinetics and histomorphometry).
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Charles, P., Hasling, C., Risteli, L. et al. Assessment of bone formation by biochemical markers in metabolic bone disease: Separation between osteoblastic activity at the cell and tissue level. Calcif Tissue Int 51, 406–411 (1992). https://doi.org/10.1007/BF00296671
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DOI: https://doi.org/10.1007/BF00296671