Markers
Felicity Stokes
Senior Clinical Biochemist
Royal Liverpool & Broadgreen University Hospital Trust
Talk Outline
Introduction to bone
Metabolic bone disease
Osteoporosis
Osteomalacia/Rickets
Pagets disease
Renal Osteodystrophy
Bone disease of malignancy
Assessment of bone Bone Markers
Analysis
Clinical Utility
Bone: Structure and Function
Function
Structural support to body, mechanical
Protection of organs and bone marrow
Reservoir of calcium and phosphate for
homeostasis
Bone: Structure and Function
Microscopic Structure:
Extracellular organic matrix (~35%)
collagen (~90%) & proteins
Hydroxyapatite crystals (~60%)
(Ca
10
(PO
4
)
6
(OH)
2
)
Cells (<5%)
osteoblasts and osteoclasts, osteocytes, bone lining cells
Macroscopic Structure:
Cortical bone
(80% of skeleton) 80 90% mineralised
Mechanical/ protective
Trabecular bone (spongy bone)
(20% of skeleton) 15 25% mineralised
Metabolically active
Hydroxyapatite crystals become
incorporated into extracellular matrix
Bone goes through a period of resting.
Recruitment of osteoblasts, which produce structural and
enzymatic proteins to form new extracellular matrix
Multi-nucleated osteoclasts excavating
resorption pit. Release H
+
and enzymes
to degrade extracellular bone matrix.
Resting
Resorption
Formation
Mineralisation
osteoclasts
osteocytes
osteoblasts
Many growth factors, cytokines & hormones determine whether formation or resorption take
place
RANK, RANKL and Osteoprotegerin (OPG)
RANK
RANKL
OPG
RANKL > OPG
OPG > RANKL
RANKL
Receptor activator of nuclear
factor B ligand
RANK
Receptor activator of nuclear
factor B
Bone Mineral Density (BMD)
Bone mass (BMD) with age up to 20 30 years (peak bone mass)
After this bone mass gradually decreases
Adult BMD is determined by peak bone mass AND rate of loss
Genetic Environmental
Factors that affect BMD
Decreased sex hormones (eg.
During menopause) causes
increased loss
May determine
peak bone mass
Age
Diet
Physical activity
Calcium intake
Sex hormones
Drugs steroids
cyclosporin
anticonvulsants
Metabolic Bone Disease
Osteoporosis
Pagets disease
Osteomalacia
Renal Osteodystrophy
Metabolic bone disease of malignancy
Osteoporosis
Most prevalent metabolic bone disease in developed
countries
Ageing population reaching epidemic levels
Major cause of morbidity and mortality
Low bone mass
Increases the risk of fragility fractures
(esp. hip, wrist & spine)
Diagnosis
Dual-energy X-ray Absorptiometry (DEXA scan)
to measure spine or hip BMD
T score < -2.5 Osteoporosis
T score -1 to -2.5 Osteopaenia
T score = number of SDs below BMD of a
young adult
Clinical Manifestations
May be silent until fracture
Height loss
Pain
Fracture
Causes
Primary causes genetic
Secondary causes
Secondary causes of Osteoporosis
Endocrine disorders Drugs
1 and 2 hypogonadism Alcohol
Thyrotoxicosis Glucocorticoids
Hyperparathyroidism Heparin
Cushings syndrome Aromatase inhibitors
Hyperprolactinoma GnRH analogs
Malignant disease Other Causes
Myelomatosis Malabsorption
Leukaemia Gastrectomy
Lymphoma Chronic liver disease
Mastocytosis CKD
Transplantation
Connective Tissue Disorders Rheumtoid arthritis
Osteogenesis imperfecta Immobilisation
Marfans syndrome
Homocysteinura
Investigation of 2 causes
FBC, ESR and SPE Multiple Myeloma
Calcium profile Ca
2+
/PO
4
-
/Vit D deficiency
PTH if high Ca
2+
Hyperparathyroidism
TFTs Hyperthyroidism
LFTs Alcohol excess
Anti-TTG ab Coeliac disease
Risk Factors
Aim is to identify patients at high risk of
osteoporotic fracture
Assess BMD + risk factors
Age (> 65 years)
Previous fracture
Strong family history of fracture
Glucocorticoid therapy
Smoking
Alcohol abuse
Secondary Osteoporosis, eg. RA
The FRAX