LABORATORY ASPECTS AND CLINICAL SIGNIFICANCE OF BONE TURNOVER MARKERS

Introduction. With an aging population, there is a marked increase in prevalence of metabolic bone diseases, especially osteoporosis. A serious complication of osteoporosis is non-traumatic bone fractures, which significantly impair quality of life and are associated with comorbid conditions and high mortality. Diseases associated with impaired bone remodeling require timely diagnosis, treatment and monitoring. The consequent public health and socioeconomic burden warrant timely diagnosis, treatment and follow-up of these disorders. Knowing the limitations of radiological techniques, biochemical markers of bone turnover measurements come handy since the changes in their levels readily reflect bone physiology. Material and methods. This paper presents a literature review concerning bone turnover biomarkers with the aim of providing comprehensive information on the applicability of these biomarkers for clinical use. A literature search was conducted in the PubMed, MedLine, Scopus and Embase databases from 1987–2019. Keywords used for search: bone turnover, bone formation, bone resorption, bone biomarkers, biochemical markers of bone turnover. We aimed to determine the clinical effectiveness, test accuracy, reliability, reproducibility and cost-effectiveness of bone turnover markers for monitoring the response to osteoporosis treatment, predicting bone loss and fracture risk, diagnostic of osteoporosis, Paget’s disease, renal osteodystrophy, and certain oncological conditions and rheumatic diseases. Results and discussion. Bone turnover markers are a series of protein or protein derivative biomarkers released during bone remodeling by osteoblasts or osteoclasts. Bone biomarkers typically analyzed in high throughput automated routine laboratories are collagen degradation products, reflecting osteoclast activity and collagenous or non-collagenous proteins produced by the osteoblasts. All these markers can be quantitated well from blood samples, serum being the preferred sample of choice. Although assays for urine examination were developed for quite a few markers, blood sampling generally detours the pre-analytic issues usually involving urine sampling. The most commonly used bone resorption and bone formation markers are discussed in this article. Biochemical markers of bone resorption are mainly different fragments of type I collagen, as well as non-collagen proteins that enter the circulation from the bone matrix resorption zone. The main biochemical indicators used in clinical practice as a criterion for bone tissue resorption are pyridinoline, deoxypyridinoline, tartrate-resistant acid phosphatase, and degradation products of type I collagen - C- and N-terminal telopeptide. All the afore mentioned markers have since been superseded by the more sensitive and specific telopeptides of type I collagen, namely the C-terminal telopeptide (CTx). As compared to the bone resorption biomarkers, there is a larger repertoire of biomarkers of bone formation, reflecting osteoblast activity, namely serum bone-specific alkaline phosphatase, osteocalcin and procollagen type I N-terminal propeptide (PINP). Although produced by the osteoblasts, osteocalcin may be defined as a bone turnover marker reflecting both bone formation and bone resorption, since it is also released from the bone matrix during bone resorption. PINP is more extensively described in literature are compared to the other bone formation biomarkers. Conclusion. Biochemical markers of bone turnover reflect bone homeostasis, i.e., the activity of osteoblasts and osteoclasts in both physiological and pathophysiological conditions. Although quite sensitive to a multitude of exogenous and endogenous pre-analytical factors, bone markers are best used in monitoring anti-osteoporosis therapy efficacy and compliance. Combination of bone mineral density measurement by dual energy x-ray absorptiometry with biochemical markers of bone turnover levels, at least one bone resorption and one bone formation marker, may potentially improve early detection of individuals at increased risk for bone loss and eventually non-traumatic bone fracture. Furthermore, they have widespread clinical utility in osteoporosis, renal osteodystrophy, certain oncological conditions and rheumatic diseases