bone marker panel Optimal patient management starts in the laboratory
Complete solution for osteoporosis The most complete bone metabolism panel on a single platform bone marker assays are important diagnostic aids in the evaluation and management of osteoporosis and other bone-related diseases, providing a more complete picture of bone metabolism and health than bone mineral densitometry (BMD) alone. What does Roche offer? What does it detect? What is its clinical value? β-crosslaps/serum (CTx) Degradation products of type I collagen during bone resorption Aid in the assessment of bone resorption rate, monitoring anti-resorptive therapies such as bisphosphonates total P1NP (Procollagen 1 N-terminal peptide) N-MID Osteocalcin Degradation products of type I collagen during bone formation Non-collagenous protein in bone matrix, synthesized by osteoblasts during bone formation Aid in the assessment of bone formation rate, monitoring anabolic therapy for osteoporosis and Paget s disease Aid in the assessment of bone turnover, monitoring antiresorptive therapies in osteoporosis Vitamin D total II Both hydroxyforms of vitamin D2 and D3 Aid in the assessment of vitamin D sufficiency PTH (Parathyroid hormone) Parathyroid hormone secreted by parathyroid glands Differential diagnosis of hypercalcemia/hypocalcemia and hyperparathyroidism
Bone turnover and calcium markers Complementary information from bone-related cycles Bone is a dynamic tissue that undergoes continuous remodelling (turnover) through a process of bone dissolution (resorption, by osteoclasts) followed by new bone replacement (formation, by osteoblasts). In young adults, resorption and formation are in balance but this balance is disturbed during menopause, causing an increase in remodelling events that lead to bone loss and, ultimately, a high risk of bone fractures. Markers of bone resorption are mostly degradation products of type I collagen such as the carboxyl-terminal cross-linked telopeptides of type I collagen (CTX-1). Among the most sensitive markers of bone formation rate are the procollagen type I N-terminal propeptide (P1NP) and osteocalcin (OC). Age-related bone loss is also accelerated by impaired calcium intake and low levels of 25-hydroxyvitamin D (25(OH)D). Reduced production of a major precursor of vitamin D in the skin and reduced synthesis of 1,25(OH)2D, the active vitamin D metabolite, in the kidneys contribute to lower calcium absorption, which leads to increased secretion of parathyroid hormone (PTH) and, subsequently, enhanced bone resorption. The bone remodelling markers CTX-1, P1NP and OC, together with calcium-related markers PTH and 25(OH)D, provide complementary information on bone turnover, which can be useful to monitor the efficacy of treatments and to predict fracture risk. Calcium cycle Bone remodelling cycle Ca 2+ excretion PTH Ca 2+ too low dietary Ca 2+ absorption 25(OH)D PTH secretion 1,25(OH)2D Calcium homeostasis Osteoblast VDR-RXR Preosteoclast RANKL RANK Osteoclast Ca 2+ resorption Osteoclast Recruitment Differentiation Activation Resorption Osteoclast Apoptosis Removal Lining cells Quiescence CTX-1 Reversal Mineralisation Formation P1NP OC Matrix synthesis Osteoblast Recruitment Differentiation Activation Figure 1: In the bone remodelling cycle, CTX-1 is released following bone resorption, and P1NP and OC are released following bone formation. In the calcium cycle, PTH stimulates conversion of 25(OH)D to 1,25(OH)2D in the kidneys. This restores serum calcium homeostasis by increasing bone calcium mobilisation (through VDR/RXR modulation of RANKL in osteoblasts and subsequent osteoclast differentiation), increasing dietary calcium absorption in the small intestine, and decreasing calcium excretion in the kidneys. bone marker assays shown in green boxes. RANK/L: receptor activator of nuclear factor-kappa B/ligand; VDR-RXR: vitamin D receptor/retinoic acid X receptor.
In line with the latest recommendations A panel of bone markers for optimal patient management The use of bone turnover markers (BTMs) in monitoring patient therapy is supported by several guidelines. 1-6 BTMs provide information about effectiveness as early as 3 months after the start of therapy - much earlier than BMD and help identify cases of non-adherence and non-response to therapy. 7 Positive BTMs results reassure the patient about long-term therapy efficacy and can potentially increase adherence. 8,9 BTMs can be used to predict fragility fracture risk and identify people at risk of losing bone mass. 10,11 Vitamin D testing is also recommended in populations with, or at risk of, osteoporosis. 13-15 The risk of falls and fractures is increased in patients with vitamin D deficiency and low bone mineral density. 16-19 In order to ensure effective vitamin D supplementation for the prevention of falls and fractures, 25(OH)D levels should be measured at baseline and after 3 months of supplementation, and dose should be adjusted as needed. 13,15 Serum P1NP and serum CTX have been recently recommended as reference markers to be used in clinical studies to further expand the international experience of BTMs applications in clinical practice. 1,12 Diagnosis of osteoporosis 25(OH)D baseline test Start anti-osteoporosis therapy Measure baseline value b-crosslaps anti-resorptive therapy total P1NP anabolic therapy Start vitamin D supplementation Bone marker monitoring with total P1NP or b-crosslaps after 3 months 25(OH)D monitoring after 3 months Significant decrease with b-crosslaps (>30 %) 20 in antiresorptive therapy Significant increase with total P1NP (>20 %) 21 in anabolic therapy No significant decrease with b-crosslaps in antiresorptive therapy No significant increase with total P1NP in anabolic therapy Optimal 25(OH)D levels reached Insufficient 25(OH)D levels Maintain therapeutic regimen, continue monitoring every e.g. 6 12 months Ask about compliance, gastro-intestinal side effects, change therapy if necessary Maintain optimal levels with supplementation (lower dose) Check compliance, increase supplement dose Figure 2: Bone turnover markers and vitamin D testing in the management of osteoporotic patients.
Fulfilling the requirements for accurate therapy monitoring High precision for reliable patient follow-up upon treatment and supplementation Monitoring patients at different time points requires precise testing regimes. To ensure that the changes observed in the bone marker levels are due to an actual response to treatment and supplementation, it is essential to minimize: biological variability: BTMs should be measured in serum instead of urine, samples drawn in the morning from fasting patients; analytical variability: assays with high precision should be used. 1 The bone marker panel was developed to perform with high precision and consistency from lot to lot, to provide clinicians with reliable results for guiding patients management. Optimal solution for your clinicians and your laboratory Excellent precision Reliable results with optimized reproducibility enabling clinical decision in follow-up Precise especially at low concentrations High efficiency All requested tests from the one sample on the one platform Consolidation of all bone related markers improves turnaround time bone marker panel Proven consistency High lot-to-lot consistency ensuring accurate long term patient monitoring Minimal variability from lot to lot (<±5 %) Maximum convenience Cost, labour and time savings through optimized workflow Long on-board stability for cost-effective reagent usage Complete flexibility All systems, all sample types, one consistent result Standardized lab reporting across facilities
Your most complete bone marker panel Technical specifications for proven performance b-crosslaps/serum total P1NP N-MID Osteocalcin Vitamin D total II PTH Between-run precision cobas e 411 analyzer 3.8 % at 0.488 ng/ml 2.8 % at 2.35 ng/ml 3.8 % at 4.62 ng/ml 2.3 % at 57.2 ng/ml 2.2 % at 527 ng/ml 3.3 % at 1140 ng/ml 3.1 % at 12.2 ng/ml 3.0 % at 35.6 ng/ml 3.3 % at 169 ng/ml 5.2 % at 20.8 ng/ml or 52.0 nmol/l 5.6 % at 25.6 ng/ml or 64.0 nmol/l 2.6 % at 92.6 ng/ml or 232 nmol/l 6.5 % at 26.7 pg/ml or 2.83 pmol/l 3.9 % at 52.5 pg/ml or 5.56 pmol/l 3.0 % at 261 pg/ml or 27.7 pmol/l Between-run precision cobas e 601 module 1.8 % at 0.502 ng/ml 1.7 % at 2.37 ng/ml 2.4 % at 4.64 ng/ml 2.5 % at 57.9 ng/ml 2.3 % at 496 ng/ml 3.4 % at 1,09 ng/ml 2.0 % at 12.0 ng/ml 2.0 % at 34.5 ng/ml 2.3 % at 160 ng/ml 5.9 % at 21.1 ng/ml or 52.8 nmol/l 4.9 % at 24.9 ng/ml or 62.3 nmol/l 3.8 % at 94.3 ng/ml or 236 nmol/l 3.4 % at 21.9 pg/ml or 2.32 pmol/l 2.5 % at 35.0 pg/ml or 3.71 pmol/l 2.8 % at 123 pg/ml or 13.04 pmol/l Sample type (lithium heparin, K3- and K2-EDTA) (lithium heparin, K3-EDTA) (lithium heparin, K3-EDTA) (lithium heparin, K3- and K2-EDTA) (K3-EDTA) Sample volume 50 µl 20 µl 20 µl 20 µl 50 µl Measuring range 0.010 6.00 ng/ml 5 1200 µg/l or ng/ml 0.500 300 ng/ml 3.00 100 ng/ml or 7.50 250 nmol/l 1.20 5,00 pg/ml or 0.127 530 pmol/l Incubation time 18 minutes 18 minutes 18 minutes 27 minutes 18 minutes Calibration frequency 8 weeks 4 weeks 12 weeks 12 weeks 12 weeks Stability after opening 12 weeks 8 weeks 12 weeks 8 weeks 12 weeks Order Information Reagent kit 11972308122 03141071190 12149133122 07464215190 11972103122 Calibrator set 11972316122 03141080190 11972111122 07464240190 11972219122 QC (PreciControl 05618860190 05618860190 05618860190 05618860190 Varia) QC (PreciControl Vitamin D total II) 07464266190 Initially, samples were sent away to a referral laboratory but when our workload escalated, we decided to bring the assay in-house in order to achieve savings. The rapid turnaround time allows for timely decision making and improved patient care, especially for those who are on vitamin D supplementation. William Ellis Principle BMS, Kingston Hospital London, UK
cobas modular platform Flexible configurations for tailor made solutions With the cobas 4000, 6000 analyzer series and cobas 8000 modular analyzer series, Roche has developed a platform concept based on a common architecture that delivers tailor-made solutions for diverse workload and testing requirements. The cobas platform is designed to reduce the complexity of laboratory operation and provide efficient and compatible solutions for network cooperation. Flexible and intelligent solutions Multiple configurations with tailor-made solutions for higher efficiency and productivity Consolidation of clinical chemistry and immunochemistry with more than 200 parameters for cost and workflow improvements Future sustainability through easy adaptation to changing throughput and parameter needs Consistency of interaction with hardware, software and reagents for less training and more staff flexibility Consistency of patient results due to a universal reagent concept cobas 8000 modular analyzer series Large volume >100 configurations <c 502> <e 602> <c 701> <c 702> <e 801> cobas 6000 analyzer series Mid volume 7 configurations <c 501> <e 601> cobas 4000 analyzer series Low volume 3 configurations <c 311> <e 411>
References 1 Vasikaran, S., et al. (2011). Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int 22(2), 391-420. 2 Delmas, P.D., et al. (2000). The use of biochemical markers of bone turnover in osteoporosis. Osteoporos Int 6: 2-17. 3 Bergmann, P., et al. (2009). Evidence-based guidelines for the use of biochemical markers of bone turnover in the selection and monitoring of bisphosphonate treatment in osteoporosis: a consensus document of the Belgian Bone Club. Int J Clin Pract 63, 19 26. 4 Brown, J.P., et al. (2009). Bone turnover markers in the management of postmenopausal osteoporosis. Clin Biochem 42, 929 942. 5 National Osteoporosis Foundation (2008). Clinician s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation. 6 Nishizawa, Y., et al. (2013). Guidelines for the use of bone metabolic markers in the diagnosis and treatment of osteoporosis (2012 edition). J Bone Miner Metab 31(1), 1-15. 7 Lewiecki, E.M. (2010). Monitoring pharmacological therapy for osteoporosis. Rev Endocr Metab Disord 11, 261-273. 8 Delmas, P.D., et al. (2007). Effect of monitoring bone turnover markers on persistence with risedronate treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab 92, 1296 1304. 9 Clowes, J.A., et al. (2004). The impact of monitoring on adherence and persistence with antiresorptive treatment for postmenopausal osteoporosis: a randomized controlled trial. J Clin Endocrinol Metab 89, 1117 1123. 10 Garnero, P., et al. (1996). Markers of bone resorption predict hip fracture in elderly women: the EPIDOS prospective study. J Bone Miner Res 11, 1531 8. 11 Lee, J., et al. (2012). Current recommendations for laboratory testing and use of bone turnover markers in management of osteoporosis. Ann Lab Med 32, 105-112. 12 Bauer, D., et al. (2012). National Bone Health Alliance bone turnover marker project: current practices and the need for US harmonization, standardization, and common reference ranges. Osteoporos Int 23, 2425-2433. 13 Dawson-Hughes, B., et al. (2010). IOF position statement: vitamin D recommendations for older adults. Osteoporos Int 21(7), 1151-1154. 14 Holick, M.F., et al. (2011). Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96(7), 1911-1930. 15 Souberbielle, J.C., et al. (2010). Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: recommendations for clinical practice. Autoimmun Rev 9(11), 709-715. 16 Pfeifer, M., et al. (2009). Effects of a long-term vitamin D and calcium supplementation on falls and parameters of muscle function in community-dwelling older individuals. Osteoporos Int 20(2), 315-322. 17 Bischoff-Ferrari, H.A., et al. (2009). Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ 339, b3692. 18 Bischoff-Ferrari, H.A., et al. (2009). Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med 169(6), 551-561. 19 Bergman, G.J., et al. (2010). Efficacy of vitamin D3 supplementation in preventing fractures in elderly women: a meta-analysis. Curr Med Res Opin 26(5), 1193-1201. 20 Garnero, P., et al. (2001). Evaluation of a fully automated serum assay for C-Terminal Cross-Linking Telopeptide of Type I Collagen in Osteoporosis. Clin Chem 47(4), 694-702. 21 Garnero, P., et al. (2008). Evaluation of a fully automated serum assay for total N-terminal propeptide of type I collagen in postmenopausal osteoporosis. Clin Chem 54(1), 188-96. Not for distribution in the USA. COBAS, COBAS E, LIFE NEEDS ANSWERS and ELECSYS are trademarks of Roche. 2017 Roche Roche Diagnostics International Ltd CH-6343 Rotkreuz Switzerland www.cobas.com