BIOCHEMICAL MARKERS OF BONE
FORMATION AND RESORPTION
AND THEIR UTILITY IN
ORTHOPAEDICS
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.
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.
COThe 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
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.
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 .
REMODELLING PROCESS
• Osteoclasts induce bone degradation
• Activation of surface osteoblasts
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
MEDIATORS
• Bone formation is mediated by osteoblasts.
• Bone resorption is mediated by osteoclasts
MARKERS
OSTEOBLASTIC MARKERS
MarkerMarker Type of Type of assayassay
Ease of use*Ease of use* Bone Bone specificityspecificity
VariabilityVariability
Total alkaline Total alkaline phosphatase phosphatase
Colorimetric Colorimetric ++++++++ -- ++++
Skeletal Skeletal alkaline alkaline phosphatase phosphatase
ELISA ELISA ++++ ++++++ ++
Procollagen-I Procollagen-I extension extension peptide peptide
RIA RIA ++++ ++++++ ++++
Osteocalcin Osteocalcin RIA, ELISA RIA, ELISA ++++++ ++++++ ++
OSTEOCLASTIC MARKERS
MarkerMarker Type of Type of assayassay
Ease of use*Ease of use* Bone Bone specificityspecificity
VariabilityVariability
Calcium Calcium AAAA ++++++ -- ++++++
Hydroxy Hydroxy proline proline
ColorimetricColorimetric ++++ ++ ++++++
Total Total pyridinolines pyridinolines
HPLC HPLC ++ ++++ ++++
Free deoxyFree deoxypyridinoline pyridinoline
ELISAELISA ++++++ ++++++ ++++
NN-telopeptide -telopeptide ELISAELISA ++++++ ++++++ ++to+++++to+++
CC-telopeptide -telopeptide ELISAELISA ++++ ++++ ++++
CALCIUM HOMEOSTASIS
DIETARY CALCIUM
INTESTINAL ABSORPTIONORGAN PHYSIOLOGY
ENDOCRINE PHYSIOLOGY
DIETARY HABITS,
SUPPLEMENTS BLOOD CALCIUM
BONE
KIDNEYS
URINE
THE ONLY “IN”
THE PRINCIPLE “OUT”
ORGAN PHYS.
ENDOCRINE PHYS.
ORGAN, ENDOCRINE
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
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
HYDROXYPROLINE
• Hypro is an exclusive constituent of collagen• Excreted in urine in peptide bound form• Rate of excretion differs with age
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
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
FACTORS AFFECTING BONE TURNOVER
• Other factors• Local stresses• Electrical stimulation• Environmental– temp– oxygen levels– acid/base balance
THANK YOU
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