Relationship between biochemical markers of bone turnover and bone scintigraphic indices in assessment of Paget's disease activity

Abstract

Objective. To evaluate the relationship between biochemical markers of bone turnover and bone scan indices of disease activity, as well as to analyze their variations based on skeletal involvement, in Paget's disease. Methods. Serum samples were obtained from 51 patients with Paget's disease to determine the levels of total alkaline phosphatase (total AP), bone alkaline phosphatase (bone AP), propeptide carboxyterminal of type I procollagen (PICP), propeptide aminoterminal of type I procollagen (PINP), osteocalcin, tartrate‐resistant acid phosphatase, and telopeptide carboxyterminal of type I collagen. Urine samples were analyzed for levels of hydroxyproline (HYP), pyridinoline (PYR), deoxypyridinoline (DPYR), C‐terminal telopeptide of type I collagen (CTx), and N‐terminal telopeptide of type I collagen (NTx). In addition, 2 semiquantitative scintigraphic indices, disease activity (AI) and disease extent (EI), were obtained. Pagetic skeletal locations were evaluated individually, with special attention to skull involvement. Results. All biochemical markers correlated with the AI and the EI. Serum PINP, bone AP, and total AP showed the highest proportions of increased values among the bone formation markers (94%, 82%, and 76%, respectively). Among the bone resorption markers, urinary NTx showed the highest proportion of increased values in patients with Paget's disease (96%), compared with PYR (69%), DPYR (71%), CTx (65%), and HYP (64%). In patients with mild disease activity, serum PINP was the marker with the highest proportion of increased values (71%). In contrast, serum PICP and urinary CTx were the most discriminative markers for skull involvement. Except for higher values for most of the biochemical markers of bone turnover in flat bones, no major differences in other skeletal locations were observed. Conclusion. The determination of serum PINP as a marker of bone formation and urinary NTx as a marker of bone resorption provided the best biochemical profile to ascertain the extent and activity of Paget's disease. In patients with skull involvement, serum PICP and urinary CTx were shown to be the most discriminative markers.

Measurement of urinary excretion of nonisomerized and ?-isomerized forms of type I collagen breakdown products to monitor the effects of the bisphosphonate zoledronate in Paget's disease

“…Before treatment, patients with Paget's disease were characterized by a marked increase in bone formation, as assessed by serum BAP and PICP, and bone resorption rates, as assessed by urinary excretion of free D-Pyr, NTX, aCTX, and PCTX. Among markers of bone resorption, urinary NTX and aCTX were the most sensitive, which is consistent with the findings of recent studies in Paget's disease that compared urinary NTX with other markers of bone resorption, including hydroxyproline, serum tartrate-resistant acid phosphatase, and PCTX, but not aCTX (5,20,21). The greater sensitivity of urinary NTX and aCTX, 2 type I collagen crosslinked peptides, compared with free D-Pyr could be related to the increased fraction of peptide-bound crosslinks in states of high bone turnover (22), which may be partly due to a rate-limiting step in their renal degradation to free crosslinks (23).…”

Biochemical Markers of Bone Turnover in Camurati–Engelmann Disease: A Report on Four Cases in One Family

“…The reasons for these discrepancies are not known. However, they could be related to the extent of bone lesion, generally much more marked in PDD, since the pagetic patients with the most extended and active disease usually show the highest BGP values [19].…”

Paget disease of bone

“…For example, the level of alkaline phosphatase in the serum, which reflects osteoblast activity, and N-telopeptide of type I collagen in the urine, which is released during bone resorption and reflects osteoclast activity, can both be markedly elevated (up to 10-to 20-fold) in patients with PD (44). Because bone resorption and formation remain coupled in PD, there is a high correlation between the levels of bone resorption and bone formation markers in Paget patients.…”