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CLINICAL BIOCHEMISTRY AND BONES
~ DETAILED STUDY
AARATHILFA G
IST M.SC. ADVANCED
BIOCHEMISTRY
Submitted by-
BONES
 Ossification – Process of bone formation by
osteoblasts
 Growth starts from 6th week after fertilization in
an embryo till 25 years of age
 Grows in thickness throughout life, but after 25,
ossification functions primarily in bone
remodelling and repair
REQUIRMENT
For healthy and normal growth of bones, proper
amount of:
 Vitamin D,C and A
 Minerals like calcium, phosphorus and
magnesium
 Hormones like PTH, GH and Calcitonin
are required
ENZYMOLOGY
 Clinical biology - body fluid, predominantly,
blood as most of the disease conditions are
diagnosed using the ↑ed or ↓ed levels of
enzymes in serum/plasma.
 Plasma functional enzymes are secreted actively
into plasma whereas plasma non- functional
enzymes are increased during disease conditions
ALKALINE PHOSPHATASE
~ BONE PROFILE
ALP
 EC. 3.1.3.1
 Non-specific enzyme hydrolysing aliphatic, aromatic or
heterocyclic compounds.
 Optimum pH – between 9 and 10
 Activator – magnesium and manganese
 Constituent ion – zinc; produced by osteoblasts of bone, and is
associated with calcification process
 Location – cell membranes (ecto-enzyme)
 Function – associated with transport mechanisms in liver, kidney
and intestinal mucosa
 Sialic acid content in ALP iso-enzyme makes it iso-forms due to
its synthesis during post- translational modification
CLINICAL MANIFESTATION
 Normal serum value : 40 – 125 U/L
 Upper normal in children is more, due to ↑ed osteoblastic
activity
 Mild ↑ during pregnancy, due to placental iso-enzyme
production
 Moderate ↑(2 to 3 times) during hepatic disease such as
infective hepatitis, alcoholic hepatitis or hepato cellular
carcinoma; Hodgkin’s lymphoma; congestive cardiac failure
or ulcerative colitis
 Very high level(10-12 times upper limit) during extrahepatic
obstruction (obstructive jaundice) or cholestasis
 Drastically high level(10-25 times upper limit) during bone
diseases such as Paget’s disease, rickets, osteomalacia,
osteoblastoma, hyperparathyroidism
SOURCES FOR HEALTHY BONE
Calcium
ExerciseVitamin D
ROLE OF VITAMIN D AND BONE DISSORDER
CALCITRIOL (1,25- DHCC)
 Biological active form of vitamin D
 7-dehydrocholesterol , an intermediate in cholesterol
biosynthesis, on exposure to sun light is converted to
cholecalciferol (vitamin D3) in the skin. On several
hydroxylation, calcitriol(1,25-
DiHydroxyCholeCalciferol) is synthesised
 Regulates the plasma levels of calcium and phosphate
 Acts at 3 different level – intestine, kidney and bone.
RICKETS
 Due to deficiency of vitamin D in children
 Derived from an old English word ‘wrickken’ means
twist.
 Characterized by bone deformities due to incomplete
mineralization, resulting in soft and pliable bones.
Weight bearing bones are bent to form bow-legs.
 plasma level of calcitriol is decreased and ALP is
elevated
OSTEOMALACIA
 Due to deficiency of vitamin D in adult (adult
rickets)
 Derived from Greek :osteon- bone; malakia –
softness
 Demineralization of bones occurs, increasing
their susceptibility to fracture
 Vitamin D is called as antirachitic vitamin
ROLE OF CALCIUM AND BONE DISSORDER
PARATHYROID HORMONE (PTH)
 Causes demineralization of bone, carried out by
osteoclasts, by stimulating ↑ed activity of enzyme
pyrophosphatase and collagenase resulting in
bone reabsorption
 this leads to an increase in the blood Ca level
 Thus blood calcium level is maintained
associated with alterations in PTH
RENAL OSTEODYSTROPHY
 Observed in patients with chronic renal failure
or with damage to renal tissues causing
impairment in the synthesis of calcitriol
 Thus renal rickets is mainly due to ↓ed synthesis
of calcitriol in kidney
 This does not respond to vit D, thus called as
vitamin D resistant rickets
 Treated by administration of calcitriol
OSTEOPOROSIS
 Characterized by demineralization of bone
resulting in progressive loss of bone mass
 Generally, elderly people (60+ yrs)of both sexes
are at the risk for osteoporosis
 But predominantly occurs in post –menopausal
women.
 This results in frequent bone fractures
 The ability to produce calcitriol from vit D is ↓ed with age,
particularly in postmenopausal women
 Immobilized or sedentary individuals tend to decrease bone
mass while those on regular exercise tend to increase bone
mass
 Deficiency of sex hormone(women) has been implicated in
the development of osteoporosis
 Estrogen administration along with calcium
supplimentation (in combination with vit D)to
postmenopausal women reduces the risk factor
 Higher dietary intake of Ca (<1.5g/day) is recommended for
elderly people
OSTEOPETROSIS
 Known as marble bone disease
 Characterized by ↑ed bone density, due to
inability to resorb bone
 Mostly observed in association with renal
tubular acidosis ( due to defect in the enzyme
carbonic anhydrase) and cerebral calcification
ROLE OF REMODELLING AND BONE DISSORDER
PAGET’S DISEASE
 A chronic condition which interferes with the
body’s normal bone remodelling process
 This can cause the affected bones to become
fragile and misshapen
 Most commonly occurs in pelvis, skull, spine and
legs
Complications includes:
 Age : 40+yrs
 Sex: Men are affected more
 Family history
 Fractures and deformities(Lathyrism)
 Osteoarthritis
 Neurological problems
 Heart failure
 Bone carcinoma
 Hearing loss
Single site of bone is affected –
monostotic paget’s disease
Multiple sites of bone are affected
– polystotic paget’s disease
Bisphosphonate – medication also
used in osteoporosis- are the
mainstay of treatment
In several cases, surgery may be
necessary
CLINICAL BIOCHEMISTRY OF BONE
CLINICAL BIOCHEMISTRY OF BONE
CLINICAL BIOCHEMISTRY OF BONE
CLINICAL BIOCHEMISTRY OF BONE

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CLINICAL BIOCHEMISTRY OF BONE

  • 1. CLINICAL BIOCHEMISTRY AND BONES ~ DETAILED STUDY
  • 2. AARATHILFA G IST M.SC. ADVANCED BIOCHEMISTRY Submitted by-
  • 3. BONES  Ossification – Process of bone formation by osteoblasts  Growth starts from 6th week after fertilization in an embryo till 25 years of age  Grows in thickness throughout life, but after 25, ossification functions primarily in bone remodelling and repair
  • 4. REQUIRMENT For healthy and normal growth of bones, proper amount of:  Vitamin D,C and A  Minerals like calcium, phosphorus and magnesium  Hormones like PTH, GH and Calcitonin are required
  • 5.
  • 6. ENZYMOLOGY  Clinical biology - body fluid, predominantly, blood as most of the disease conditions are diagnosed using the ↑ed or ↓ed levels of enzymes in serum/plasma.  Plasma functional enzymes are secreted actively into plasma whereas plasma non- functional enzymes are increased during disease conditions
  • 8. ALP  EC. 3.1.3.1  Non-specific enzyme hydrolysing aliphatic, aromatic or heterocyclic compounds.  Optimum pH – between 9 and 10  Activator – magnesium and manganese  Constituent ion – zinc; produced by osteoblasts of bone, and is associated with calcification process  Location – cell membranes (ecto-enzyme)  Function – associated with transport mechanisms in liver, kidney and intestinal mucosa  Sialic acid content in ALP iso-enzyme makes it iso-forms due to its synthesis during post- translational modification
  • 9. CLINICAL MANIFESTATION  Normal serum value : 40 – 125 U/L  Upper normal in children is more, due to ↑ed osteoblastic activity  Mild ↑ during pregnancy, due to placental iso-enzyme production  Moderate ↑(2 to 3 times) during hepatic disease such as infective hepatitis, alcoholic hepatitis or hepato cellular carcinoma; Hodgkin’s lymphoma; congestive cardiac failure or ulcerative colitis  Very high level(10-12 times upper limit) during extrahepatic obstruction (obstructive jaundice) or cholestasis  Drastically high level(10-25 times upper limit) during bone diseases such as Paget’s disease, rickets, osteomalacia, osteoblastoma, hyperparathyroidism
  • 10. SOURCES FOR HEALTHY BONE Calcium ExerciseVitamin D
  • 11. ROLE OF VITAMIN D AND BONE DISSORDER
  • 12. CALCITRIOL (1,25- DHCC)  Biological active form of vitamin D  7-dehydrocholesterol , an intermediate in cholesterol biosynthesis, on exposure to sun light is converted to cholecalciferol (vitamin D3) in the skin. On several hydroxylation, calcitriol(1,25- DiHydroxyCholeCalciferol) is synthesised  Regulates the plasma levels of calcium and phosphate  Acts at 3 different level – intestine, kidney and bone.
  • 13. RICKETS  Due to deficiency of vitamin D in children  Derived from an old English word ‘wrickken’ means twist.  Characterized by bone deformities due to incomplete mineralization, resulting in soft and pliable bones. Weight bearing bones are bent to form bow-legs.  plasma level of calcitriol is decreased and ALP is elevated
  • 14.
  • 15. OSTEOMALACIA  Due to deficiency of vitamin D in adult (adult rickets)  Derived from Greek :osteon- bone; malakia – softness  Demineralization of bones occurs, increasing their susceptibility to fracture  Vitamin D is called as antirachitic vitamin
  • 16.
  • 17. ROLE OF CALCIUM AND BONE DISSORDER
  • 18. PARATHYROID HORMONE (PTH)  Causes demineralization of bone, carried out by osteoclasts, by stimulating ↑ed activity of enzyme pyrophosphatase and collagenase resulting in bone reabsorption  this leads to an increase in the blood Ca level  Thus blood calcium level is maintained associated with alterations in PTH
  • 19. RENAL OSTEODYSTROPHY  Observed in patients with chronic renal failure or with damage to renal tissues causing impairment in the synthesis of calcitriol  Thus renal rickets is mainly due to ↓ed synthesis of calcitriol in kidney  This does not respond to vit D, thus called as vitamin D resistant rickets  Treated by administration of calcitriol
  • 20.
  • 21. OSTEOPOROSIS  Characterized by demineralization of bone resulting in progressive loss of bone mass  Generally, elderly people (60+ yrs)of both sexes are at the risk for osteoporosis  But predominantly occurs in post –menopausal women.  This results in frequent bone fractures
  • 22.
  • 23.  The ability to produce calcitriol from vit D is ↓ed with age, particularly in postmenopausal women  Immobilized or sedentary individuals tend to decrease bone mass while those on regular exercise tend to increase bone mass  Deficiency of sex hormone(women) has been implicated in the development of osteoporosis  Estrogen administration along with calcium supplimentation (in combination with vit D)to postmenopausal women reduces the risk factor  Higher dietary intake of Ca (<1.5g/day) is recommended for elderly people
  • 24.
  • 25. OSTEOPETROSIS  Known as marble bone disease  Characterized by ↑ed bone density, due to inability to resorb bone  Mostly observed in association with renal tubular acidosis ( due to defect in the enzyme carbonic anhydrase) and cerebral calcification
  • 26.
  • 27. ROLE OF REMODELLING AND BONE DISSORDER
  • 28. PAGET’S DISEASE  A chronic condition which interferes with the body’s normal bone remodelling process  This can cause the affected bones to become fragile and misshapen  Most commonly occurs in pelvis, skull, spine and legs
  • 29.
  • 30. Complications includes:  Age : 40+yrs  Sex: Men are affected more  Family history  Fractures and deformities(Lathyrism)  Osteoarthritis  Neurological problems  Heart failure  Bone carcinoma  Hearing loss
  • 31. Single site of bone is affected – monostotic paget’s disease Multiple sites of bone are affected – polystotic paget’s disease Bisphosphonate – medication also used in osteoporosis- are the mainstay of treatment In several cases, surgery may be necessary

Editor's Notes

  1. Ectoenzyme- enzymes found outside of (or on the outer surface of )a cell
  2. Bone disease – pre beta ALP