Osteoporosis is a major health problem worldwide, and is projected to increase exponentially due to the aging of the population. The absolute fracture risk in individual subjects is calculated by the use of algorithms which include bone mineral density (BMD), age, gender, history of prior fracture and other risk factors. This review describes the laboratory investigations into osteoporosis which include serum calcium, phosphate, creatinine, alkaline phosphatase and 25-hydroxyvitamin D and, additionally in men, testosterone. Parathyroid hormone (PTH) is measured in patients with abnormal serum calcium to determine its cause. Other laboratory investigations such as thyroid function testing, screening for multiple myeloma, and screening for Cushing's syndrome, are performed if indicated. Measurement of bone turnover markers (BTMs) is currently not included in algorithms for fracture risk calculations due to the lack of data. However, BTMs may be useful for monitoring osteoporosis treatment. Further studies of the reference BTMs serum carboxy terminal telopeptide of collagen type I (s-CTX) and serum procollagen type I N-terminal propeptide (s-PINP) in fracture risk prediction and in monitoring various treatments for osteoporosis may help expedite their inclusion in routine clinical practice.
Algorithms ; Biological Markers/*blood ; Clinical Laboratory Techniques ; Collagen Type I/blood ; Fractures, Bone/prevention & control ; Humans ; Osteoporosis/*diagnosis ; Peptide Fragments/blood ; Peptides/blood ; Procollagen/blood

This erratum is being published to correct the errors in sequence of references and in insertion of wrong references on page 112.

Functional reference limits describe key changes in the physiological relationship between a pair of physiologically related components. Statistically, this can be represented by a significant change in the curvature of a mathematical function or curve (e.g., an observed plateau). The point at which the statistical relationship changes significantly is the point of curvature inflection and can be mathematically modeled from the relationship between the interrelated biomarkers. Conceptually, they reside between reference intervals, which describe the statistical boundaries of a single biomarker within the reference population, and clinical decision limits that are often linked to the risk of morbidity or mortality and set as thresholds. Functional reference limits provide important physiological and pathophysiological insights that can aid laboratory result interpretation. Laboratory professionals are in a unique position to harness data from laboratory information systems to derive clinically relevant values. Increasing research on and reporting of functional reference limits in the literature will enhance their contribution to laboratory medicine and widen the evidence base used in clinical decision limits, which are currently almost exclusively contributed to by clinical trials. Their inclusion in laboratory reports will enhance the intellectual value of laboratory professionals in clinical care beyond the statistical boundaries of a healthy reference population and pave the way to them being considered in shaping clinical decision limits. This review provides an overview of the concepts related to functional reference limits, clinical examples of their use, and the impetus to include them in laboratory reports.

Bone-turnover marker (BTM) measurements in the blood or urine reflect the bone-remodeling rate and may be useful for studying and clinically managing metabolic bone diseases.Substantial evidence supporting the diagnostic use of BTMs has accumulated in recent years, together with the publication of several guidelines. Most clinical trials and observational and reference-interval studies have been performed in the Northern Hemisphere and have mainly involved Caucasian populations. This review focuses on the available data for populations from the Asia-Pacific region and offers guidance for using BTMs as diagnostic biomarkers in these populations. The procollagen I N-terminal propeptide and β-isomerized C-terminal telopeptide of type-I collagen (measured in plasma) are reference BTMs used for investigating osteoporosis in clinical settings. Premenopausal reference intervals (established for use with Asia-Pacific populations) and reference change values and treatment targets (used to monitor osteoporosis treatment) help guide the management of osteoporosis. Measuring BTMs that are not affected by renal failure, such as the bone-specific isoenzyme alkaline phosphatase and tartrate-resistant acid phosphatase 5b, may be advantageous for patients with advanced chronic kidney disease. Further studies of the use of BTMs in individuals with metabolic bone disease, coupled with the harmonization of commercial assays to provide equivalent results, will further enhance their clinical applications.