OMOVIYE EMMANUELseminar Bone Markers - Copy

BABCOCK UNIVERSITY

SCHOOL OF PUBLIC AND ALLIED HEALTH

DEPARTMENT OF MEDICAL LABORATORY SCIENCE

20152016 SEMINAR PRESENTATION ON

THE UTILITY OF BONE MARKERS MEASUREMENT IN THE

DIAGNOSIS AND MANAGEMENT OF OSTEOPOROSIS

BY

OMOVIYE EMMANUEL O 111909

FEBRUARY 18 2016 1

Summary as presented

2

Outline

bull Bone definition

bull Structure and functions of bone

bull Formation and resorption of bone

bull Osteoporosis

bull Diagnostic bone markers in osteoporosis

bull Conclusion

bull Selected references 3

Bone definition

A specialized mineralized connective tissue that consists of a mainly organic collagen matrix and a mineral phase together with bone cells (Vasikaran et al 2008)

4

Bone Structure and Function

Bone

Structure

Extracellular matrix

Cellular constituents

Function

Mechanical Synthetic Metabolic

5

Bone Formation and Resorption

bull Metabolically active and constantly being repaired and remodelled

throughout an individuals lifetime

bull Formation involves actively synthesizing osteoblasts while its

resorption involves multinucleated osteoclasts (Vasikaran et al

2008)

bull Osteoporosis occurs when bone resorption is the more active

(Wheater et al 2013) 6

Osteoporosis

bull A systemic skeletal disease characterized by low bone mass and

micro-architectural deterioration of bone tissue with a

consequent increase in bone fragility and susceptibility to

fractures (Burch et al 2014)

bull Risk factors Age hormonal disturbances genetic lifestyle drugs

and some diseases like hyperthyroidism

bull Results in substantial morbidity and an estimated health cost gt

$14billion annually (McCormick 2007)

7

Osteoporosis Epidemiology

bull Prevalence 30 in women living in developed countries

bull Age and Sex 3 in 5 women gt 65 years and 1 in 5 men gt 75

years

bull Race predominant among Caucasians and Asians

bull Genetics studies suggest a significant genetic component

bull Geography most common in developed countries

(McCormick 2007)

Osteoporotic Fractures Comparison with Other Diseases

184 300 750 000

vertebral

250 000 other sites

250 000 forearm

250 000 hip

0

500

1000

1500

2000

Osteoporotic Fractures

Heart Attack

Stroke Breast Cancer

An

nu

al in

cid

ence

x 1

00

0

1 500 000

Annual incidence all ages

513 000

annual estimate women 29+

228 000


(Vasikaran 2006)

9

Vertebrae

Hip

Wrist

50 60 70 80

40

30

20

10

Age (Years)

An

nu

al in

cid

en

ce p

er

10

00

w

om

en

Incidence of Osteoporotic Fractures in European Women

(Burch et al 2014)

Diagnostic Tools in Osteoporosis

bull Bone Mineral Density (BMD) scanning using dual-energy X-

ray absorptiometry (DXA) is the WHO standard for

diagnosis of osteoporosis (McCormick 2007)

bull DXA measures the amount of bone mineral in bone tissue

bull BMD is used in cliinical medicine as an indirect indicator of

osteoporosis

bull Poor sensitivity of DXA means that potential fractures will

be missed if it is used alone (Wheater et al 2013)

11

Limitations of BMD measurements in the Diagnosis of Osteoporosis

bull Changes in bone metabolism after therapy are detectable

only after about 2 years

bull Limited access to the technology

bull It is relatively expensive

bull The exposure to radiation although small is best avoided

bull Bone biomarkers offer an alternative monitoring strategy

(Burch et al 2014)

12

Diagnostic Bone Markers in Osteoporosis

bull Specifically derived biomarkers that reflect both bone formation by osteoblasts and resorption by osteoclasts

bull Include both enzymes and peptides derived from cellular and non-cellular compartments of bone

bull May be measured in synovial fluid blood or urine

bull Techniques for their measurements are abundant

bull Classified as bone formation and resorption markers (Seibel 2005) 13


bull Detect metabolic changes in bone after about 3-6 months

(McCormick 2007)

bull Relatively cheap compared with DXA (Wheater et al 2013)

bull No exposure to radiation

bull Helpful tools in the diagnostic prognostic and therapeutic

assessment of osteoporosis

14


15

Markers of Bone Formation

16

Bone Alkaline Phosphatase (BALP)

bull Total alkaline phosphatase has several isoforms in serum

(Liver bone placental intestine spleen and kidney)

bull 40ndash50 of the total alkaline phosphatase activity arises from

the bone as a result of osteoblast activity (Siebel 2005)

bull Residual low cross-reactivity (16) with liver ALP limits its use

in patients with liver disease (Yang and Grey 2006) 17

Bone Alkaline Phosphatase (BALP) Assays

bull Immunoradiometric assay (IRMA)

bull Enzyme-linked immunosorbent assay (ELISA)

bull Ease of measurement cost efficiency and higher

specificity in detecting small changes makes BALP a

good marker for bone formation (Burch et al

2008) 18

Osteocalcin

bull A non collagenous matrix protein

bull Detected using enzyme linked immunosorbent assays (ELISA) or radioimmunoassays (RIA)

bull It is tissue specific widely available (Eapen et al 2008)

bull Heterogeneity of the fragments in the serum is thought to limit its use (Burch etal 2014)

bull May be affected by use of warfarin (Yang and Grey 2006)

Markers of Bone Resorption

20

Carboxy-terminal telopeptide cross-linked type 1 collagen (CTX)

bull Peptide fragments from the carboxy-terminal end of type 1

collagen produced during osteoclastic resorption

bull Detected in urine or serum using enzyme linked

immunosorbent assay (ELISA)

bull More accurate when monitoring the response to specific

treatments (eg with bisphosphonates) (Burch et al2014) 21

Amino-terminal telopeptide cross-linked type I collagen (NTX)

bull Peptide fragments from the amino terminal end of

type 1 collagen produced during osteoclastic

resorption

bull Detected in the urine or serum with competitive

inhibition ELISA or chemiluminescence assay

bull It is non-invasive and may be preferred by patients

(Yang and Grey 2006) 22

Conclusion

bull The biomarkers of bone metabolism are helpful tools to

detect the dynamics of the metabolic imbalance itself

and thus complement the static measures of bone

bull They show more rapid changes soon after initiating

treatment hence are better tools in the prognosis and

monitoring of patients receiving antiresorptive therapy 23

Selected References

Burch J Rice S Yang H Neilson A Stirk L Francis R Holloway P Selby P and Craig D (2014) Systematic review of the use of bone turnover markers for monitoring the response to osteoporosis treatment the secondary prevention of fractures and primary prevention of fractures in high-risk groups Health Technology Assessment 18 (11) 2-28

Eapen E Grey V Don-Wauchope A and Atkinson SA (2008) Bone Health in Childhood Usefulness of Biochemical Biomarkers eJIFCC 19 (2) 221-227

McCormick RK (2007) Osteoporosis Integrating Biomarkers and Other Diagnostic Correlates into the Management of Bone Fragility Alt Med Rev 12 (2) 469-478

Seibel MJ (2005) Biochemical markers of bone turnover part I biochemistry and variability Clin Biochem Rev 26 97ndash102

Vasikaran SD Glendenning P and Morris HA (2006) The Role of Biochemical Markers of Bone Turnover in Osteoporosis Management in Clinical Practice Clin Biochem Rev 27(3) 119ndash125

Wheater G Elshahaly M Tuck SP Datta HK and Van-Laar JM (2013) The clinical utility of bone marker measurements in osteoporosis J of Trans Med 11(201) 111-121

Yang L and Grey V (2006) Pediatric reference intervals for bone markers Clin Biochem 39(6)561ndash568

Thank you for listening

25

Summary as presented

2

Outline




bull Osteoporosis


bull Conclusion


Bone definition


4


Bone

Structure



Function


5






2008)



Osteoporosis









7




years




(McCormick 2007)


184 300 750 000

vertebral

250 000 other sites

250 000 forearm

250 000 hip

0

500

1000

1500

2000


Heart Attack


An

nu

al in

cid

ence

x 1

00

0

1 500 000


513 000


228 000


(Vasikaran 2006)

9

Vertebrae

Hip

Wrist

50 60 70 80

40

30

20

10

Age (Years)

An

nu

al in

cid

en

ce p

er

10

00

w

om

en


(Burch et al 2014)







osteoporosis



11








(Burch et al 2014)

12









(McCormick 2007)





14


15


16














2008) 18

Osteocalcin







20











resorption





Conclusion







Selected References









25

Outline




bull Osteoporosis


bull Conclusion


Bone definition


4


Bone

Structure



Function


5






2008)



Osteoporosis









7




years




(McCormick 2007)


184 300 750 000

vertebral

250 000 other sites

250 000 forearm

250 000 hip

0

500

1000

1500

2000


Heart Attack


An

nu

al in

cid

ence

x 1

00

0

1 500 000


513 000


228 000


(Vasikaran 2006)

9

Vertebrae

Hip

Wrist

50 60 70 80

40

30

20

10

Age (Years)

An

nu

al in

cid

en

ce p

er

10

00

w

om

en


(Burch et al 2014)







osteoporosis



11








(Burch et al 2014)

12









(McCormick 2007)





14


15


16














2008) 18

Osteocalcin







20











resorption





Conclusion







Selected References









25

Bone definition


4


Bone

Structure



Function


5






2008)



Osteoporosis









7




years




(McCormick 2007)


184 300 750 000

vertebral

250 000 other sites

250 000 forearm

250 000 hip

0

500

1000

1500

2000


Heart Attack


An

nu

al in

cid

ence

x 1

00

0

1 500 000


513 000


228 000


(Vasikaran 2006)

9

Vertebrae

Hip

Wrist

50 60 70 80

40

30

20

10

Age (Years)

An

nu

al in

cid

en

ce p

er

10

00

w

om

en


(Burch et al 2014)







osteoporosis



11








(Burch et al 2014)

12









(McCormick 2007)





14


15


16














2008) 18

Osteocalcin







20











resorption





Conclusion







Selected References









25


Bone

Structure



Function


5






2008)



Osteoporosis









7




years




(McCormick 2007)


184 300 750 000

vertebral

250 000 other sites

250 000 forearm

250 000 hip

0

500

1000

1500

2000


Heart Attack


An

nu

al in

cid

ence

x 1

00

0

1 500 000


513 000


228 000


(Vasikaran 2006)

9

Vertebrae

Hip

Wrist

50 60 70 80

40

30

20

10

Age (Years)

An

nu

al in

cid

en

ce p

er

10

00

w

om

en


(Burch et al 2014)







osteoporosis



11








(Burch et al 2014)

12









(McCormick 2007)





14


15


16














2008) 18

Osteocalcin







20











resorption





Conclusion







Selected References









25






2008)



Osteoporosis









7




years




(McCormick 2007)


184 300 750 000

vertebral

250 000 other sites

250 000 forearm

250 000 hip

0

500

1000

1500

2000


Heart Attack


An

nu

al in

cid

ence

x 1

00

0

1 500 000


513 000


228 000


(Vasikaran 2006)

9

Vertebrae

Hip

Wrist

50 60 70 80

40

30

20

10

Age (Years)

An

nu

al in

cid

en

ce p

er

10

00

w

om

en


(Burch et al 2014)







osteoporosis



11








(Burch et al 2014)

12









(McCormick 2007)





14


15


16














2008) 18

Osteocalcin







20











resorption





Conclusion







Selected References









25

Osteoporosis









7




years




(McCormick 2007)


184 300 750 000

vertebral

250 000 other sites

250 000 forearm

250 000 hip

0

500

1000

1500

2000


Heart Attack


An

nu

al in

cid

ence

x 1

00

0

1 500 000


513 000


228 000


(Vasikaran 2006)

9

Vertebrae

Hip

Wrist

50 60 70 80

40

30

20

10

Age (Years)

An

nu

al in

cid

en

ce p

er

10

00

w

om

en


(Burch et al 2014)







osteoporosis



11








(Burch et al 2014)

12









(McCormick 2007)





14


15


16














2008) 18

Osteocalcin







20











resorption





Conclusion







Selected References









25




years




(McCormick 2007)


184 300 750 000

vertebral

250 000 other sites

250 000 forearm

250 000 hip

0

500

1000

1500

2000


Heart Attack


An

nu

al in

cid

ence

x 1

00

0

1 500 000


513 000


228 000


(Vasikaran 2006)

9

Vertebrae

Hip

Wrist

50 60 70 80

40

30

20

10

Age (Years)

An

nu

al in

cid

en

ce p

er

10

00

w

om

en


(Burch et al 2014)







osteoporosis



11








(Burch et al 2014)

12









(McCormick 2007)





14


15


16














2008) 18

Osteocalcin







20











resorption





Conclusion







Selected References









25


184 300 750 000

vertebral

250 000 other sites

250 000 forearm

250 000 hip

0

500

1000

1500

2000


Heart Attack


An

nu

al in

cid

ence

x 1

00

0

1 500 000


513 000


228 000


(Vasikaran 2006)

9

Vertebrae

Hip

Wrist

50 60 70 80

40

30

20

10

Age (Years)

An

nu

al in

cid

en

ce p

er

10

00

w

om

en


(Burch et al 2014)







osteoporosis



11








(Burch et al 2014)

12









(McCormick 2007)





14


15


16














2008) 18

Osteocalcin







20











resorption





Conclusion







Selected References









25

Vertebrae

Hip

Wrist

50 60 70 80

40

30

20

10

Age (Years)

An

nu

al in

cid

en

ce p

er

10

00

w

om

en


(Burch et al 2014)







osteoporosis



11








(Burch et al 2014)

12









(McCormick 2007)





14


15


16














2008) 18

Osteocalcin







20











resorption





Conclusion







Selected References









25







osteoporosis



11








(Burch et al 2014)

12









(McCormick 2007)





14


15


16














2008) 18

Osteocalcin







20











resorption





Conclusion







Selected References









25








(Burch et al 2014)

12









(McCormick 2007)





14


15


16














2008) 18

Osteocalcin







20











resorption





Conclusion







Selected References









25









(McCormick 2007)





14


15


16














2008) 18

Osteocalcin







20











resorption





Conclusion







Selected References









25


15


16














2008) 18

Osteocalcin







20











resorption





Conclusion







Selected References









25


16














2008) 18

Osteocalcin







20











resorption





Conclusion







Selected References









25














2008) 18

Osteocalcin







20











resorption





Conclusion







Selected References









25

Osteocalcin







20











resorption





Conclusion







Selected References









25


20











resorption





Conclusion







Selected References









25











resorption





Conclusion







Selected References









25

Conclusion







Selected References









25

Selected References









25


25

OMOVIYE EMMANUELseminar Bone Markers - Copy

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