acid-phosphatase and galactosylhydroxylysine

Bone remodelling is a process by which bone grows and turns over. This process involves a series of highly regulated steps that depend on the interaction of two cell lineages, the osteoclasts and the osteoblasts. Information on metabolic activity of bone tissue are achieved with the determination, in blood and in urine, of biochemical products derived from the activity of this cells. The ability to determine bone turnover with biochemical markers has been enhanced considerably in recent years with the development of new assays for more sensitive and specific markers. These new markers can now replace the outdated and non-specific markers of bone remodeling such as serum total alkaline phosphatase (ALP) and urinary hydroxyproline (Hyp) determination. Biochemical markers of bone turnover can be classified according to the process that underlie in markers of bone formation, products of the osteoblast activity [bone ALP, osteocalcin (OC), procollagene I C- and N-terminal propeptides] and markers of bone resorption, products of the osteocalst activity [pyridinuim crosslinks, collagen I C- and N-terminal telopeptides (CTX-I and NTX-I), tartrate resistent acid phosphatase (TRACP) isoform 5b]. The interpretation of laboratory results should always include the consideration of potential sources of variability. Variation in the results of biochemical markers of bone metabolism can compromise their ability to characterize disorders of bone metabolism. Variation can be categorized into pre-analytical, analytical and biological sources. However, the determination of biochemical markers of bone turnover offers many advantages in clinical practice, since they are non-invasive, can be repeated often, and major changes occur in a short time.

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers; Bone and Bones; Bone Remodeling; Bone Resorption; Humans; Hydroxylysine; Hydroxyproline; Isoenzymes; Osteoblasts; Osteocalcin; Osteoclasts; Osteogenesis; Procollagen; Tartrate-Resistant Acid Phosphatase

Despite these potential problems, biochemical bone markers are the single most sensitive method for monitoring acute changes in bone metabolism. For example, subcutaneous injections of recombinant human insulin-like growth factor I cause a measurable increase in both procollagen and urinary DPD in as little as 1 day. Similarly, it is possible to measure a significant decrease in bone formation as determined by decreases in serum levels of ALP, OC, and C-PCP within 12 hours after the beginning of a PTH infusion study. Additionally, an increase in DPD/cr was determined within 24 hours of the start of bed rest. These changes, seen within 24 hours, are far earlier than could be detected by any other method of monitoring bone metabolism. Thus, biochemical assays have opened a new era where changes in bone metabolism can be detected in hours to days. This acute detectability should be especially helpful to the development of new drugs and the optimization of the use of approved drugs. Accordingly, definite dose-response studies can now be done in a reasonable time. For osteoporosis therapy there are reasons to consider cyclic drug administration, such as avoiding drug resistance (PTH or calcitonin), avoiding overtreatment (bisphosphonates), or avoiding a possible mineralization defect (fluoride). By using biochemical assays, we can determine the optimum amount of "on time" and "off time" in cyclic therapy. Of the bone formation assays, ALP, OC, and PCP, we recommend for routine use the OC assay because of its high discriminant power and because it has been better characterized, in terms of clinical application, than the PCP assays and the ALP IRMA. If, however, the serum cannot be drawn at a specific time in all patients to be studied, we recommend the ALP assay because, unlike the OC assay, it shows no diurnal variation. Of the bone resorption assays, HYP, TRAP, GHYL, and PYD/DPD, we recommend the urine PYD/DPD assay (adjusted for creatinine) because it is commercially available and because, along with the urine GHYL assay, it is the most sensitive bone resorption assay. Established guidelines for the use of assays in patient care is not yet available, largely because of the large intrapatient variation seen with most assays. Once this problem is resolved, it should be possible to apply biochemical assays to routine clinical practice. For example, if the patient has a urine DPD/cr (indicating a high bone resorption rate), the patient would be selected for anti

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone Development; Bone Resorption; Humans; Hydroxylysine; Hydroxyproline; Osteocalcin; Procollagen; Reproducibility of Results