Bone Marker Measurements in Diagnosing and Managing Osteoporosis
1. BABCOCK UNIVERSITY
SCHOOL OF PUBLIC AND ALLIED HEALTH
DEPARTMENT OF MEDICAL LABORATORY SCIENCE
2015/2016 SEMINAR PRESENTATION ON:
THE UTILITY OF BONE MARKERS MEASUREMENT IN THE
DIAGNOSIS AND MANAGEMENT OF OSTEOPOROSIS
BY
OMOVIYE, EMMANUEL O. 11/1909
FEBRUARY 18, 2016.
1
3. Outline
• Bone: definition
• Structure and functions of bone
• Formation and resorption of bone
• Osteoporosis
• Diagnostic bone markers in osteoporosis
• Conclusion
• Selected references 3
4. 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
5. Bone: Structure and Function
Bone
Structure
Extracellular
matrix
Cellular
constituents
Function
Mechanical Synthetic Metabolic
5
6. Bone: Formation and Resorption
• Metabolically active and constantly being repaired and remodelled
throughout an individuals lifetime.
• Formation involves actively synthesizing osteoblasts while its
resorption involves multinucleated osteoclasts. (Vasikaran et al.,
2008).
• Osteoporosis occurs when bone resorption is the more active.
(Wheater et al., 2013). 6
7. Osteoporosis
• 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).
• Risk factors: Age, hormonal disturbances, genetic, lifestyle, drugs
and some diseases like hyperthyroidism.
• Results in substantial morbidity and an estimated health cost >
$14billion annually (McCormick, 2007). 7
8. Osteoporosis: Epidemiology
• Prevalence: 30% in women living in developed countries.
• Age and Sex: 3 in 5 women > 65 years and 1 in 5 men > 75
years.
• Race: predominant among Caucasians and Asians.
• Genetics: studies suggest a significant genetic component.
• Geography: most common in developed countries.
(McCormick, 2007).
9. 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
Annualincidencex1000
1 500 000
Annual incidence
all ages
513 000
annual estimate
women 29+
228 000
annual estimate
women 30+
(Vasikaran, 2006)
9
10. Vertebrae
Hip
Wrist
50 60 70 80
40
30
20
10
Age (Years)
Annualincidenceper1000
women
Incidence of
Osteoporotic Fractures in European Women
(Burch et al., 2014)
11. Diagnostic Tools in Osteoporosis
• Bone Mineral Density (BMD) scanning using dual-energy X-
ray absorptiometry (DXA) is the WHO standard for
diagnosis of osteoporosis (McCormick, 2007).
• DXA measures the amount of bone mineral in bone tissue.
• BMD is used in cliinical medicine as an indirect indicator of
osteoporosis.
• Poor sensitivity of DXA means that potential fractures will
be missed if it is used alone (Wheater et al., 2013). 11
12. Limitations of BMD measurements in the
Diagnosis of Osteoporosis
• Changes in bone metabolism after therapy are detectable
only after about 2 years.
• Limited access to the technology.
• It is relatively expensive.
• The exposure to radiation although small, is best avoided.
• Bone biomarkers offer an alternative monitoring strategy.
(Burch et al., 2014)
12
13. Diagnostic Bone Markers in Osteoporosis
• Specifically derived biomarkers that reflect both bone
formation by osteoblasts and resorption by osteoclasts.
• Include both enzymes and peptides derived from cellular and
non-cellular compartments of bone.
• May be measured in synovial fluid, blood or urine.
• Techniques for their measurements are abundant .
• Classified as bone formation and resorption markers.
(Seibel, 2005). 13
14. Diagnostic Bone Markers in Osteoporosis
• Detect metabolic changes in bone after about 3-6 months
(McCormick, 2007).
• Relatively cheap compared with DXA (Wheater et al., 2013).
• No exposure to radiation.
• Helpful tools in the diagnostic, prognostic and therapeutic
assessment of osteoporosis.
14
17. Bone Alkaline Phosphatase (BALP)
• Total alkaline phosphatase has several isoforms in serum
(Liver, bone, placental, intestine, spleen and kidney).
• 40–50% of the total alkaline phosphatase activity arises from
the bone as a result of osteoblast activity (Siebel, 2005).
• Residual low cross-reactivity (16%) with liver ALP limits its use
in patients with liver disease (Yang and Grey 2006). 17
18. Bone Alkaline Phosphatase (BALP): Assays
• Immunoradiometric assay (IRMA).
• Enzyme-linked immunosorbent assay (ELISA).
• 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
19. Osteocalcin
• A non collagenous matrix protein.
• Detected using enzyme linked immunosorbent assays (ELISA)
or radioimmunoassays (RIA).
• It is tissue specific, widely available (Eapen et al., 2008).
• Heterogeneity of the fragments in the serum is thought to
limit its use (Burch et.al., 2014).
• May be affected by use of warfarin (Yang and Grey 2006).
21. Carboxy-terminal telopeptide cross-linked
type 1 collagen (CTX)
• Peptide fragments from the carboxy-terminal end of type 1
collagen produced during osteoclastic resorption.
• Detected in urine or serum using enzyme linked
immunosorbent assay (ELISA).
• More accurate when monitoring the response to specific
treatments (e.g. with bisphosphonates) (Burch et al.,2014).21
22. Amino-terminal telopeptide cross-linked
type I collagen (NTX)
• Peptide fragments from the amino terminal end of
type 1 collagen produced during osteoclastic
resorption.
• Detected in the urine or serum with competitive
inhibition ELISA or chemiluminescence assay.
• It is non-invasive and may be preferred by patients
(Yang and Grey, 2006). 22
23. Conclusion
• 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.
• They show more rapid changes soon after initiating
treatment, hence are better tools in the prognosis and
monitoring of patients receiving antiresorptive therapy.
23
24. 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: 97–102.
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): 119–125.
Wheater G., Elshahaly M., Tuck S.P., 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):561–568.
