The interpretation of biochemical investigations in the management of metabolic bone disorders

A bone is basically a combination of the organic matrix, inorganic minerals (calcium phosphate), and vitamins that make the structural framework. The two counteracting processes, bone formation and bone resorption, make the bone a metabolically active tissue that undergoes continuous remodeling. The laboratory evaluation of serological and urinary markers is important in the diagnosis of suspected bone disease such as osteoporosis, rickets/osteomalacia, fluorosis, and primary hyperparathyroidism, which are common metabolic bone diseases (MBD), whereas a few rare MBDs include Paget’s disease, fibrous dysplasia, osteogenesis imperfecta, tumor-induced osteomalacia, etc. Calcium and phosphate level in serum and urine reflects the status of metabolism of bone. Markers of one formation include: alkaline phosphatase (ALP), osteocalcin (OCn), and procollagen I peptides: the amino (N-) terminal propeptide (PINP) and the carboxy (C-) terminal propeptide (PICP). Markers of bone resorption include hydroxyproline (OHP), hydroxylysine (HYL), deoxypyridinoline (DPD), pyridinoline (PYD), bone sialoprotein (BSP), osteopontin (OP), tartrate-resistant acid phosphatase 5b (TRAP 5b), carboxy-terminal crosslinked telopeptide of type 1 collagen (CTX-1), amino-terminal crosslinked telopeptide of type 1 collagen (NTX-1), cathepsin K (CTSK), urinary calcium, and acid phosphatase. Novel biochemical markers such as periostin, cathepsins, RANK-L, secreted frizzled-related proteins (sFRP), Wnt inhibitory factor-1 (WIF1), Dickkopfs (Dkk) 1–4, sphingosine-1-phosphate (S1P), sclerostin, fibroblast growth factor (FGF)-23, and miRNA are also the markers of bone metabolism. Biochemical markers of bone metabolism provide a potentially important clinical tool for assessing and monitoring MBD. These markers are quick to appear after any derangement in physiology. Still, we must keep in mind that the characteristics of any marker are at present primarily a function of the assay used for the assessment of the marker. That continued efforts aimed at improving the analysis and interpretation of markers that are known today must continue.