Biochemical Markers for Osteoporosis

Osteoporosis is defined as a disease characterised by low bone mass and micro

architectural deterioration of bone tissue, leading to enhanced bone fragility and a
consequent increase in fracture risk
(anonymous, 1991)
Classification of BMD Levels
Description

Meaning

Normal BMD BMD above -1 SD from the

young normal mean
Low BMD or
osteopenia

BMD between -1 SD and

-2,5 SD

Osteoporosis

BMD is reduced below -2,5 SD

Severe or
BMD is reduced below -2,5 SD
established in the presence of fracture
osteoporosis

BMD Classification

BMD

Osteopen
ia

1,0

Osteoporosis

2,5

S
D

- Modelling and Remodelling

The shape and structure of bone is continually renewed and modified by means of
modelling and remodelling. In both processes modelling and remodelling old bone is
replaced with new bone.
- Modelling :
Takes place mainly during youth
The result of modelling is a change in skeletal shape
- Remodelling :
Takes place primarily in adults
It doesnt change the shape of the skeleton

Time sequence of bone remodelling

Peak Bone Mass

- Is defined as bony tissue in the end of skeletal maturation
- Major determinant of osteoporosis fracture risk
Apakah tulang yang lebih lemah merupakan hasil kehilangan tulang berlebih dalam
waktu lama
ATAU
massa tulang puncak yang tidak cukup ??
Jawabannya : ya atau tidak
o Mayoritas risiko osteoporosis tergantung pada individu yang tidak pernah mencapai
massa tulang puncak dengan kecepatan kehilangan tulang yang normal
osteoporotik
o Kehilangan tulang yang cepat (bone turnover tinggi) mempunyai efek yang besar
pada risiko fraktur

MENOPAUSE HIGH RISK

Can bone densitometry be replaced with a laboratory test ?

o

A laboratory test cannot replace bone densitometry, because the two procedures
provide different types of information perse.

Bone densitometry indicates the current level of bone density at that time.

The laboratory test represents the process of bone reformation and therefore
provides information about a potential imbalance between bone formation and
resorption.

The laboratory parameter also provides information about the kinetics of bone
metabolism
The two methods complement each other

Risk Factors

Bone Turnover
Characterized by 2 metabolic processes :

Formation of new bone by osteoblast

Degradation (resorption) old bone by osteoclast

Biochemical bone markers for bone formation

and resorption

Markers for Bone Formation

Osteocalcin
Bone Specific Alkaline Phosphatase or Isoenzyme Alkaline Phosphatase

Markers for Bone Resorption

Pyridinoline Crosslink
Deoxypyridinoline Crosslink
C-Telopeptida (CTx, Cross Laps)
N-Telopeptida (NTx, Osteomark)

Bone Specific Alkaline Phosphatase

Has low cross reactivity with isoenzyme from the liver

More sensitive compare to total alkaline phosphatase total, to detect increased
bone turnover after menopause

OSTEOCALCIN
-

Synthesized by osteoblast
Its production is dependent upon vitamin K (formation of -Carboxyglutamic
acid residues) and is stimulated by vitamin D3
Osteocalcin level is related to the rate of bone turnover in various disorders of
bone metabolism

Osteocalcin Degradation

CROSSLINK
Free :
Free pyridinoline crosslink (Pyd)
Free deoxypyridinoline crosslink (Dpd)
Peptide :
N-telopeptide (NTx, Osteomark)
C-telopeptide (CTx, Crosslaps)

Collagen Crosslink Pyridinoline (PYD), Deoxypyridinoline (DPD)

Sebagai Petanda Resorpsi Tulang (BR)
Indeks Kuantitatif untuk Kecepatan Resorpsi Tulang
1.
2.
3.
4.

Produk uraian secara proteolitik dari kolagen khas

tulang oleh aktivitas Oc ke dalam urine
Tidak di metabolisme lebih lanjut oleh hati
Tidak dipengaruhi oleh diit

Sensitivitas dan spesifisitas > Hydroxyproline

Crosslink = PYD/Creatinine ratio

Collagen Crosslinks

Biochemical Structure of Collagen Type 1

Clinical Usefulness of Biochemical Bone Markers

Predicting the development of osteoporosis or rates of bone loss

Determining when to start therapy
Determining risk of fracture, and
Monitoring intervention with therapeutic agents (determine therapeutic
effectiveness)

Combination of the assessment of BMD and bone resorption

rate to predict hip fracturevrisk in elderly women followed
Prospectively for 2 years (The Epidos Study)

Decision tree according to Chestnut III

BMD

low
high

Fracture
risk

Bone
Resorp
tion
Marker

renda
h

Fracture
risk

norm
al
Bone
Resorpt
ion
Marker

high

low
Fracture
risk

Fracture
risk

+++

++

--

++

treatment

treatment3)

No
treatment2)

treatment1)

Decision tree according Chestnut III

1)

Or repeat BMD or bone marker within 1 year

2)

Reevaluate in 12 24 months depending upon clinical status

3)

Low BMD is a predictor of fracture risk, independent of marker level

Biochemical Markers

Melengkapi BMD (DEXA) dan memberikan respon lebih cepat

Menawarkan pendekatan yang cost effective untuk mengindentifikasi dan
mengelola penyakit tulang

Bone markers might be used in combination with BMD to improve the prognostic
assessment of post menopausal women i.e. their risk of developing osteporosis and
ultimately fractures

Longitudinal Studies of early post

Menopausal women :
35% lose significant amounts of bone mineral
fast losers
65% lose only a minor amount of bone mineral
normal losers
Fast Loser
One who lose more than 3% of bone mass per annum

Kecepatan kehilangan tulang pada wanita post menopause dapat diukur secara
tidak langsung dengan pengukuran penanda biokimia
Massa tulang yang rendah dan kecepatan kehilangan tulang yang besar
mempunyai peran yang sama besar untuk risiko fraktur di masa depan
Higher baseline levels of bone formation and bone resorption markers baseline
were significantly associated with faster BMD loss, independently of age
Women with an abnormally high bone turnover (bone markers at baseline > 2SD
above the mean of premenopausal woman) had a rate of bone loss that was 2-6x
higher than women with a low turnover according to the marker
High Bone Turnover
Baseline levels of bone markers > 2 SD
Above the mean of premenopausal
women
Rate of bone loss 2-6 x
>> low bone turnover

Clinical Value of Biochemical Parameters

Bone markers display therapy response when determined before and a few
months after start of treatment.
Bone markers reflect therapy response already after 3 months, which is drastically
sooner than the BMD with the waiting period is 2 years to measure therapeutic
response.