Elecsys® bone marker panelOptimal patient management starts in the laboratory

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Elecsys® 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.

Complete solution for osteoporosis

The most complete bone metabolism panel on a single platform

What does Roche offer? What does it detect? What is its clinical value?Elecsys β-CrossLaps/serum (CTx) Degradation products of type I collagen during

bone resorptionAid in the assessment of bone resorption rate, monitoring anti-resorptive therapies such as bisphosphonates

Elecsys total P1NP(Procollagen 1 N-terminal peptide)

Degradation products of type I collagen during bone formation

Aid in the assessment of bone formation rate, monitoring anabolic therapy for osteoporosis and Paget‘s disease

Elecsys N-MID Osteocalcin Non-collagenous protein in bone matrix, synthesized by osteoblasts during bone formation

Aid in the assessment of bone turnover, monitoring antiresorptive therapies in osteoporosis

Elecsys Vitamin D total II Both hydroxyforms of vitamin D2 and D3 Aid in the assessment of vitamin D sufficiency

Elecsys PTH (Parathyroid hormone) Parathyroid hormone secreted by parathyroid glands Differential diagnosis of hypercalcemia/hypocalcemia and hyperparathyroidism

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Complete solution for osteoporosis Bone turnover and calcium markers

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, subse-quently, enhanced bone resorption.

The bone remodelling markers CTX-1, P1NP and OC, together with calcium-related markers PTH and 25(OH)D, provide complemen-tary information on bone turnover, which can be useful to monitor the efficacy of treatments and to predict fracture risk.

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. Elecsys® 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.

Complementary information from bone-related cycles

Calcium cycle Bone remodelling cycle

1,25(OH)2D

Calcium homeostasis

↑ Ca2+ resorption

Lining cells

Quiescence

FormationResorption

Reversal

P1NP

OC

↓ Ca2+ excretion

PTH25(OH)D

Ca2+ too low

↑ PTH secretionCTX-1

Osteoclast• Apoptosis• Removal

Mineralisation

Matrix synthesis

Osteoblast• Recruitment• Differentiation• Activation

Osteoclast• Recruitment• Differentiation• Activation

↑ dietary Ca2+ absorption

Osteoblast

Preosteoclast

VDR-RXR

RANKL

RANK

Osteoclast

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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 monthsafter the start of therapy - much earlier than BMD – and helpidentify cases of non-adherence and non-response to therapy.7

• Positive BTMs results reassure the patient about long-termtherapy efficacy and can potentially increase adherence.8,9

• BTMs can be used to predict fragility fracture risk and identifypeople at risk of losing bone mass.10,11

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

In line with the latest recommendations

Figure 2: Bone turnover markers and vitamin D testing in the management of osteoporotic patients.

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 withvitamin D deficiency and low bone mineral density.16-19

• In order to ensure effective vitamin D supplementation for theprevention of falls and fractures, 25(OH)D levels should bemeasured at baseline and after 3 months of supplementation,and dose should be adjusted as needed.13,15

A panel of bone markers for optimal patient management

Diagnosis of osteoporosis

Start anti-osteoporosis therapyMeasure baseline value b-CrossLaps – anti-resorptive therapytotal P1NP – anabolic therapy

Bone marker monitoring with total P1NP or b-CrossLaps after 3 months

Significant decrease with b-CrossLaps (>30 %)20 in anti-resorptive therapy

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 compli-ance, increase supplement dose

Significant increase with total P1NP (>20 %)21 in anabolic therapy

No significant increase with total P1NP in anabolic therapy

No significant decrease with b-CrossLaps in anti-resorptive therapy

25(OH)D baseline test

Start vitamin D supplementation

25(OH)D monitoring after 3 months

Optimal 25(OH)D levels reached

Insufficient 25(OH)D levels

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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

Optimal solution for your clinicians and your laboratory

Fulfilling the requirements for accurate therapy monitoring

The Elecsys® 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.

Excellent precision• Reliable results with optimized

reproducibility enabling clinical decision in follow-up

• Precise especially at lowconcentrations

Proven consistency• High lot-to-lot consistency ensuring accurate long term

patient monitoring • Minimal variability from

lot to lot (<±5 %)

High efficiency• All requested tests from the one

sample on the one platform• Consolidation of all bone related

markers improves turnaround time

Complete flexibility• All systems, all sample types, one consistent result• Standardized lab reporting across facilities

Maximum convenience• Cost, labour and time savings

through optimized workflow • Long on-board stability for

cost-effective reagent usage

Elecsys®

bone marker panel

High precision for reliable patient follow-up upon treatment and supplementation

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“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

Your most complete bone marker panel

Technical specifications for proven performance

Elecsys b-CrossLaps/serum

Elecsys total P1NP

Elecsys N-MID Osteocalcin

Elecsys Vitamin D total II

Elecsys PTH

Between-run precision cobas e 411 analyzer

3.8 % at 0.488 ng/mL2.8 % at 2.35 ng/mL3.8 % at 4.62 ng/mL

2.3 % at 57.2 ng/mL2.2 % at 527 ng/mL3.3 % at 1140 ng/mL

3.1 % at 12.2 ng/mL3.0 % at 35.6 ng/mL3.3 % at 169 ng/mL

5.2 % at 20.8 ng/mLor 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/mLor 2.83 pmol/L3.9 % at 52.5 pg/mLor 5.56 pmol/L3.0 % at 261 pg/mLor 27.7 pmol/L

Between-run precision cobas e 601 module

1.8 % at 0.502 ng/mL1.7 % at 2.37 ng/mL2.4 % 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/mL2.0 % at 34.5 ng/mL2.3 % at 160 ng/mL

5.9 % at 21.1 ng/mLor 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/mLor 2.32 pmol/L2.5 % at 35.0 pg/mLor 3.71 pmol/L2.8 % at 123 pg/mLor 13.04 pmol/L

Sample type Serum, plasma (lithium heparin, K3- and K2-EDTA)

Serum, plasma (lithium heparin, K3-EDTA)

Serum, plasma (lithium heparin, K3-EDTA)

Serum, plasma (lithium heparin, K3- and K2-EDTA)

Serum, plasma (K3-EDTA)

Sample volume 50 µL 20 µL 20 µL 20 µL 50 µLMeasuring range 0.010 – 6.00 ng/mL 5 – 1200 µg/L

or ng/mL0.500 – 300 ng/mL 3.00 – 100 ng/mL or

7.50 – 250 nmol/L1.20 – 5,00 pg/mL or 0.127 – 530 pmol/L

Incubation time 18 minutes 18 minutes 18 minutes 27 minutes 18 minutesCalibration frequency 8 weeks 4 weeks 12 weeks 12 weeks 12 weeksStability after opening

12 weeks 8 weeks 12 weeks 8 weeks 12 weeks

Order Information

Reagent kit 11972308122 03141071190 12149133122 07464215190 11972103122Calibrator set 11972316122 03141080190 11972111122 07464240190 11972219122QC (PreciControl Varia)

05618860190 05618860190 05618860190 05618860190

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QC (PreciControl Vitamin D total II)

07464266190

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 andreagents for less training and more staff flexibility

• Consistency of patient results due to a universal reagentconcept

cobas® modular platformFlexible configurations for tailor made solutions

cobas 8000 modular analyzer series Large volume

>100 configurations

cobas 6000 analyzer series Mid volume

7 configurations

cobas 4000 analyzer series Low volume

3 configurations

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Not for distribution in the USA.

COBAS, COBAS E, LIFE NEEDS ANSWERS and ELECSYS are trademarks of Roche.

©2017 Roche

Roche Diagnostics International LtdCH-6343 RotkreuzSwitzerlandwww.cobas.com

References1 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 post-

menopausal 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.

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