biochemical markers of bone formation and their utility in orthopaedics

1. BIOCHEMICAL MARKERS OF
BONE FORMATION AND
RESORPTION AND THEIR
UTILITY IN ORTHOPAEDICS

2. INTRODUCTION
• Chemicals in serum and urine can serve as
markers for monitoring bone loss, bone
reformation, and the effectiveness of therapy
in patients with osteoporosis. Although not yet
well recognized or readily available, tests for
these markers may prove preferable to
densitometry in some settings or for some
patients. In the future, biochemical markers
may provide important information on fracture
risks as well.

3. HISTORY
• More than 50 years ago, Fuller Albright,the
father of metabolic bone diseases, noted that
postmenopausal women were losing excessive
amounts of calcium in their urine.
• He is credited with introducing the use of
biochemical markers into the clinical arena.

4. CO
The BONE matrix
– 40% organic
• Type 1 collagen (tensile strength)
• Proteoglycans (compressive strength)
• Osteocalcin/Osteonectin
• Growth factors/Cytokines/Osteoid
– 60% inorganic
• Calcium hydroxyapatite
• The cells
– osteo-clast/blast/cyte/progenitor

5. PHYSIOLOGY
• Bone is a reservoir of calcium, calcium En
Masse being required to make &maintain the
skeleton. To be an effective reservoir for the
maintenance of normal blood calcium, calcium
must be able to be incorporated into &
liberated from the bone on short notice.

6. BONE REMODELLING
• Characteristic of the adult skeleton, occurs most often
in skeletal sites rich in trabecular bone, e.g. proximal
femur, calcaneus, and distal radius.
• Remodeling is essential to maintain skeletal
homeostasis, to provide elasticity to bone, and to
produce a steady source of extracellular calcium.
• Takes place in a cyclic fashion at specific sites or
skeletal lacunae in a cycle lasting about 120 days .

7. REMODELLING PROCESS
• Osteoclasts induce
bone degradation
• Activation of surface
osteoblasts

8. BONE TURNOVER
• It is a coupled process of bone formation and bone
resorption
• Takes place throughout the life at different rates
• Before 30yrs bone formation exceeds resorption
• At 30 yrs the skeletal mass is at its peak and both
processes are matched
• Later resorption goes on increasing for the rest of the
life

9. MEDIATORS
• Bone formation is mediated by osteoblasts.
• Bone resorption is mediated by osteoclasts

10. MARKERS

11. OSTEOBLASTIC MARKERS
MarkerMarker Type ofType of
assayassay
Ease of use*Ease of use* BoneBone
specificityspecificity
VariabilityVariability
Total alkalineTotal alkaline
phosphatasephosphatase
ColorimetricColorimetric ++++++++ -- ++++
SkeletalSkeletal
alkalinealkaline
phosphatasephosphatase
ELISAELISA ++++ ++++++ ++
Procollagen-IProcollagen-I
extensionextension
peptidepeptide
RIARIA ++++ ++++++ ++++
OsteocalcinOsteocalcin RIA, ELISARIA, ELISA ++++++ ++++++ ++

12. OSTEOCLASTIC MARKERS
MarkerMarker Type ofType of
assayassay
Ease of use*Ease of use* BoneBone
specificityspecificity
VariabilityVariability
CalciumCalcium AAAA ++++++ -- ++++++
HydroxyHydroxy
prolineproline
ColorimetricColorimetric ++++ ++ ++++++
TotalTotal
pyridinolinespyridinolines
HPLCHPLC ++ ++++ ++++
Free deoxyFree deoxy
pyridinolinepyridinoline
ELISAELISA ++++++ ++++++ ++++
NN-telopeptide-telopeptide ELISAELISA ++++++ ++++++ ++to+++++to+++
CC-telopeptide-telopeptide ELISAELISA ++++ ++++ ++++

13. CALCIUM HOMEOSTASIS
DIETARY CALCIUM
INTESTINAL ABSORPTION
ORGAN PHYSIOLOGY
ENDOCRINE PHYSIOLOGY
DIETARY HABITS,
SUPPLEMENTS
BLOOD CALCIUM
BONE
KIDNEYS
URINE
THE ONLY “IN”
THE PRINCIPLE “OUT”
ORGAN PHYS.
ENDOCRINE PHYS.
ORGAN,
ENDOCRINE

14. CALCIUM, PTH, AND VITAMIN D
FEEDBACK LOOPS
NORMAL BLOOD Ca
RISING BLOOD Ca
FALLING BLOOD Ca
SUPPRESS PTH
STIMULATE PTH
BONE RESORPTION
URINARY LOSS
1,25(OH)2 D PRODUCTION
BONE RESORPTION
URINARY LOSS
1,25(OH)2 D PRODUCTION

15. ALKALINE PHOSPHATASE
• In intestinal mucosa, bone & kidney
• Concentrated in epiphyseal area
• Normal level : 4-13 units/dl (KA).
• Composed of a group of isoenzymes- heat
labile and heat stable

16. HYDROXYPROLINE
• Hypro is an exclusive constituent of collagen
• Excreted in urine in peptide bound form
• Rate of excretion differs with age

17. FACTORS AFFECTING BONE
TURNOVER
• Local factors
• I-GF 1 (somatomedin C)
– increased osteoblast proliferation
• TGF
– increased osteoblast activity
• IL-1
– increased osteoclast activity (myeloma)
• PG’s
– increased bone turnover (#’s/inflammn)
• BMP
– bone formation

18. FACTORS AFFECTING BONE
TURNOVER
• Other hormones
• Oestrogen
– gut – increased ca absorption
– bone - decreased re-sorption
• Glucocorticoids
– gut - decrease ca absorption
– bone - increased re-sorption/decreased formation
• Thyroxine
– stimulates bone formation/resorption
– net resorption

19. FACTORS AFFECTING BONE
TURNOVER
• Other factors
• Local stresses
• Electrical stimulation
• Environmental
– temp
– oxygen levels
– acid/base balance

20. THANK YOU