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Biochemical Assessment of Paget's Disease of Bone
Author(s) -
Shankar Subramanian,
Hosking David J
Publication year - 2006
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.06s204
Subject(s) - pyridinoline , n terminal telopeptide , bone remodeling , type i collagen , bone resorption , alkaline phosphatase , endocrinology , medicine , chemistry , osteocalcin , procollagen peptidase , deoxypyridinoline , resorption , bone disease , hydroxyproline , paget's disease of bone , osteoporosis , biochemistry , disease , enzyme
Biochemical measurements of bone turnover provide an objective assessment of disease activity and the response to treatment. Alkaline phosphatase is the best characterized of the bone turnover markers and reflects the extent and activity of Paget's disease. However, in addition to bone‐specific alkaline phosphatase (Bone ALP), there is also osteocalcin (OC) and procollagen type 1 N‐terminal propeptide (P1NP) as formation markers. A variety of telopeptides (C‐terminal telopeptide of type I collagen, [CTX], N‐telopeptide of type I collagen [NTX]) or cross‐link breakdown products of type 1 collagen can be used to assess bone resorption. Total alkaline phosphatase (Total ALP), Bone ALP, and P1NP all perform similarly in diagnosis and in evaluating the response to treatment, but the general availability, low interassay variation, and inexpensiveness of Total ALP makes it the best test for routine use. Measurement of the biological variability of the different markers in stable, untreated Paget's disease indicates how great a change (critical difference) is needed to define a true alteration in disease activity. Bone ALP, P1NP, and NTX show the highest therapy induced change/critical difference ratio during antiresorptive treatment. Some of the resorption markers show more complex changes in response to treatment. Pyridinoline (PYD) or deoxypyridinoline (DPD) cross‐links of type 1 collagen are excreted in urine either as free or as peptide bound moieties, but it is the latter which decrease by the greatest amount in response to bisphosphonate therapy. Newly formed type 1 collagen contains an aspartyl‐glycine motif (αCTX), which undergoes spontaneous isoaspartyl formation to βCTX as the bone ages. In untreated Paget's disease, the αCTX is raised proportionately more (16‐fold) than βCTX (3‐fold) and decreases in response to bisphosphonate therapy to a greater extent than βCTX (measured in the sCTX assay). As bisphosphonates have become more potent, the aim of treatment has shifted toward the achievement of a rate of bone turnover in the lower part of the reference range. This is important because the duration of remission of disease activity is strongly determined by the post treatment nadir bone turnover.