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 theyoung normal mean

Low BMD or BMD between -1 SD andosteopenia -2,5 SD

Osteoporosis BMD is reduced below -2,5 SD

Severe or BMD is reduced below -2,5 SDestablished in the presence of fractureosteoporosis

BMD Classification BMD Classification

BMDOsteopenia

Osteoporosis

-1,0

-2,5

SD

- 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 doesn’t change the shape of the skeleton

Time sequence of bone remodellingTime 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 dalamwaktu lama

A T A U

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

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.

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

o 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 bonemetabolism

The two methods complement each other

MENOPAUSE MENOPAUSE HIGH RISK HIGH RISK

Bone Turnover

Characterized by 2 metabolic processes :

• Formation of new bone by osteoblast• Degradation (resorption) old bone by osteoclast

Risk FactorsRisk Factors

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

Biochemical bone markers for bone formationBiochemical bone markers for bone formationand resorptionand resorption

OSTEOCALCIN

- Synthesized by osteoblast- Its production is dependent upon vitamin K (formation of g-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

CROSSLINK

Free :- Free pyridinoline crosslink (Pyd)- Free deoxypyridinoline crosslink (Dpd)

Peptide :- N-telopeptide (NTx, Osteomark)- C-telopeptide (CTx, Crosslaps)

Osteocalcin DegradationOsteocalcin Degradation

Collagen Crosslink Pyridinoline (PYD), Deoxypyridinoline (DPD)

Sebagai Petanda Resorpsi Tulang (BR)Indeks Kuantitatif untuk Kecepatan Resorpsi Tulang

1. Produk uraian secara proteolitik dari kolagen khas2. tulang oleh aktivitas Oc ke dalam urine3. Tidak di metabolisme lebih lanjut oleh hati4. Tidak dipengaruhi oleh diit

Sensitivitas dan spesifisitas > Hydroxyproline

Crosslink = PYD/Creatinine ratio

Collagen CrosslinksCollagen Crosslinks

Biochemical Structure of Collagen Type 1Biochemical 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 Combination of the assessment of BMD and bone resorption rate to predict hip fracturevrisk in elderly women followed rate to predict hip fracturevrisk in elderly women followed Prospectively for 2 years (The Epidos Study)Prospectively for 2 years (The Epidos Study)

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

Decision tree according to Chestnut IIIDecision tree according to Chestnut III

rendah

high

normal

low

low

high

BMD

Bone Resorption

Marker

Bone Resorpt

ion Marker

Fracture risk

+ + +

Fracture risk+ +

Fracture risk+ +

Fracture risk- -

treatment treatment1)No

treatment2)

treatment3)

Longitudinal Studies of early postMenopausal 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 SDAbove the mean of premenopausalwomen

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.