The clinical utility of bone marker measurements in osteoporosis

Abstract

Osteoporosis is characterised by low bone mass and structural deterioration of bone tissue, resulting in increased fragility and susceptibility to fracture. Osteoporotic fractures are a significant cause of morbidity and mortality. Direct medical costs from such fractures in the UK are currently estimated at over two billion pounds per year, resulting in a substantial healthcare burden that is expected to rise exponentially due to increasing life expectancy. Currently bone mineral density is the WHO standard for diagnosis of osteoporosis, but poor sensitivity means that potential fractures will be missed if it is used alone. During the past decade considerable progress has been made in the identification and characterisation of specific biomarkers to aid the management of metabolic bone disease. Technological developments have greatly enhanced assay performance producing reliable, rapid, non-invasive cost effective assays with improved sensitivity and specificity. We now have a greater understanding of the need to regulate pre-analytical sample collection to minimise the effects of biological variation. However, bone turnover markers (BTMs) still have limited clinical utility. It is not routinely recommended to use BTMs to select those at risk of fractures, but baseline measurements of resorption markers are useful before commencement of anti-resorptive treatment and can be checked 3–6 months later to monitor response and adherence to treatment. Similarly, formation markers can be used to monitor bone forming agents. BTMs may also be useful when monitoring patients during treatment holidays and aid in the decision as to when therapy should be recommenced. Recent recommendations by the Bone Marker Standards Working Group propose to standardise research and include a specific marker of bone resorption (CTX) and bone formation (P1NP) in all future studies. It is hoped that improved research in turn will lead to optimised markers for the clinical management of osteoporosis and other bone diseases.

Bone remodeling markers and bone metastases: From cancer research to clinical implications

“…It should be used in less than three freeze/ thaw cycles. 23 Urine NTX-I has been the preferred marker in the clinical setting as, in comparison with serum CTX-I, it is less sensitive to the circadian rhythm, it is not affected by food intake and it avoids blood withdrawal. 23 …”

“…Urine samples must be collected without preservatives, and DYP and DPD are stable at 2-8 1C up to 7 days or at À 20 1C for longer storage. 23 The samples should be protected from light, as PYD and DPD are sensitive to UV light, resulting in lower concentrations. 10 NTX-I NTX-I is usually quantified in urine, by ELISA, using a monoclonal antibody against the a-2 isoform (bone-derived peptide).…”

“…BALP in serum is stable at 2-8 1C for up to 5 days or at À 20 1C for longer storage. 23 OC OC can be quantified by RIA, ELISA or chemiluminescense immunoassays. Assays that detect the intact OC or large N-terminal fragments are the most reproducible; however, the use of this marker is limited owing to high variability.…”

Diagnostic performance of osteocalcin measurements in patients with endogenous Cushing’s syndrome

“…2 BTMs do not control skeletal metabolism and are not disease specific; these markers simply reflect the entire skeleton remodeling regardless of the underlining cause. 7 In clinical practice on individual patients, BTMs could be used to evaluate the effectiveness of treatment with antiresorptive or anabolic compounds and patient adherence to therapy. [8][9][10][11] Nevertheless, many researchers have demonstrated a statistically significant reduction in OC levels in patients receiving glucocorticoid therapy 12,13 and in patients with endogenous hypercortisolism.…”

Bone markers and osteoporosis therapy

“…The aging process is associated with bone loss even before the menopause sets in, suggesting that factors related to cellular aging, apart from estrogen deficiency, are important (6). In assessing the dynamics of bone loss and, with therapy, bone gain, bone resorption and bone formation markers can be used, alone or together (7). In clinical practice, for reasons of cost, sometimes a single marker will be used.…”