Markers of bone health

Bone turnover markers (BTM) are compounds that are released during the process of bone remodelling. The concentrations of BTMs in serum or plasma serve as indicators of the dynamic balance between bone resorption and formation. Disruptions in this balance may arise from aging, metabolic bone diseases, alterations in mobility, therapeutic interventions and other pathological or physiological conditions.

Osteoporosis is the most common disease affecting bone remodelling and is characterised by loss of bone mass and increased fracture risk, particularly in the elderly population. Further bone metabolic diseases include Paget’s disease, hypophosphatasia, osteomalacia, metastatic cancers, fibrous dysplasia, primary hyperparathyroidism and chronic kidney disease-mineral bone disorder (CKD-MBD).

The key markers of bone resorption are cross-linked collagen type I fragments (CTX-1) and tartrate-resistant acid phosphatase 5b (TRAcP5b). Markers of bone formation include procollagen I N-propeptide (PINP), osteocalcin and bone-specific alkaline phosphatase (BALP).

Osteoporosis therapy monitoring

Since bone turnover is a dynamic process, the levels of BTMs change rapidly following initiation of therapy, for example in osteoporosis, enabling early assessment of treatment effectiveness and patient adherence. BTM analysis serves as an early indicator of therapy outcome, since bone density measurement typically detects changes only after around one year of therapy. Additionally, BTM testing is minimally invasive, cost-effective and well-suited for serial monitoring over time. Beta-CTX-1 and PINP are the recommended markers for managing patients with osteoporosis, while TRAcP5b and BALP are advised for osteoporosis patients with kidney disease, as their levels are not influenced by renal retention.

Bone disease diagnostics

BTMs are also useful for diagnostic assessment of endocrine bone disorders such as Paget’s disease, hypophosphatasia and osteomalacia. Paget’s disease is the second most prevalent metabolic bone disorder after osteoporosis and is characterised by excessive bone resorption and unstructured bone formation. Hypophosphatasia is a rare inherited disorder resulting in defective mineralisation of bone and teeth due to an enzyme deficiency. Osteomalacia manifests with softened bones and is primarily caused by vitamin D deficiency. BTM analysis provides insight into the altered bone remodelling processes in these diseases, supporting diagnosis and monitoring.

Importance of calcium metabolism

Bone serves as a critical reservoir of calcium, and disturbances in calcium homeostasis can compromise bone integrity. Elevated levels of parathyroid hormone (PTH) stimulate excessive bone resorption to release calcium, thereby increasing the risk of fractures, osteopenia and osteoporosis. Deficiencies in vitamin D metabolites lead to lower calcium uptake from the intestine, resulting in poorly mineralised and fracture-prone bones. Biochemical markers that are useful for assessing calcium metabolic disorders include intact PTH, calcitonin, 25-OH vitamin D and 1,25 dihydroxy vitamin D.

Standardised laboratory analysis

Euroimmun and Immunodiagnostics Systems (both part of Revvity) offer a comprehensive range of fully automated chemiluminescence immunoassays (ChLIA) and enzyme-linked immunoassays (ELISA) for quantitative measurement of BTMs and calcium homeostasis markers in patient serum or plasma.

The ChLIA range includes CTX-1, TRAcP5b, intact PINP, osteocalcin, BALP, intact PTH, 25-OH vitamin D, and 1,25 dihydroxy vitamin D. The ELISA range covers CTX-1, TRAcP5b, osteocalcin, BALP, intact PTH, calcitonin, 25-OH vitamin D, and 1,25 dihydroxy vitamin D. The assays provide highly standardised measurements and are backed up by extensive scientific studies.

The assays can be fully automated on established analytical instruments, accommodating a wide range of laboratory throughput requirements. IDS ChLIA platforms provide rapid turnaround times, high degree of walkaway operation and random-access capabilities. Furthermore, assays from other diagnostic specialties can be processed in parallel, allowing exceptional flexibility and efficiency in routine laboratory workflows.

References available at  https://www.euroimmunblog.com/high-quality-diagnostics-osteoporosis-bone-disorders/