CALCIUM METABOLISM: VITAMIN D-PARATHYROID-CALCITONIN ROLE (Rickets,Osteoporosis,Renal Osteodystrophy) Prevention Dr.Sandeep C Agrawal Agrasen Hospital Gondia India Metabolic Bone Diseases:phosphorus,magnesium and other minerals ,Calcium and vitamin D rich diets,Sunlight exposure,vitamin D synthesis,Osteoporosis prevention and diet

1. Dr.Sandeep Agrawal
Consultant Orthopedic Surgeon
MS,DNB
Agrasen Hospital
Gondia
Maharashtra
India
drsandeep123@gmail.com
09960122234
CALCIUM METABOLISM:
VITAMIN D-PARATHYROID-CALCITONIN
ROLE
(Rickets,Osteoporosis,Renal
Osteodystrophy)
Prevention

2. NORMAL VALUES
Total body calcium – 1100 g {27.5
mol / L}
99 % in bones
Plasma calcium : 9 – 11 mg / dL
{5 m Eq / L or 2.5
mmol / L}
Ionized calcium – 50 % {1.2 mmol /
L}
Protein bound – 41 % {1.0 mmol / L}
Complexed with anions – 9 % {0.2
mmol / L}

3. 3

4. • PRINCIPLE ORGAN
SYSTEMS
• GUT, BONE, KIDNEYS
– HORMONES
• PARATHYROID HORMONE
(PTH), VITAMIN
D,CALCITONIN
BLOOD CALCIUM
REGULATION

5. GLOMERULAR
FILTRATE
250 mmol
DIET
25mmol (1000 mg)
GIT
FECES
22.5mmol
ABSORPTION
15 mmol
SECRETION
12.5 mmol
REABSORPTION
247.5
mmol
ECF
35 mmol
URINE
2.5 mmol
BONE
EXCHANGEABLE
100 mmol
STABLE
27,200 mmol
RAPID
EXCHANGE
500 mmol
REABSORPTION
7.5 mmol

6. 1. Rapid phase – osteolysis by
osteocytes
2. Slow phase – by osteoclasts

7. CALCIUM PHYSIOLOGY:
BLOOD CALCIUM
CALCIUM FLUX INTO AND OUT OF
BLOOD:
“IN” FACTORS: INTESTINAL
ABSORPTION, BONE RESORPTION
“OUT” FACTORS: RENAL EXCRETION,
BONE FORMATION (Ca INCORPATION INTO
BONE)
BALANCE BETWEEN “IN” AND “OUT”
FACTORS
ORGAN PHYSIOLOGY OF GUT, BONE,
AND KIDNEY
HORMONE FUNCTION OF PTH AND
VITMAMIN D
1. Neutral
– normal healthy adults
– daily intake & excretion same
– bone entry & exit same
2. Positive
– growing children
– intestinal absorption > excretion
– bone entry > bone exit
3. Negative
– pregnant & lactating women
- intestinal absorption < excretion
– bone entry < bone exit
“CALCIUM
BALANCE”

8. 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

11. 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

12. FUNCTIONS OF CALCIUM
Blood coagulation
Muscle contraction
Transmission of nerve impulses
Formation of skeleton ,etc.
FREE IONIZED CALCIUM

13. CALCIUM IN GIT
• 30 – 80 % of ingested calcium is absorbed
• Actively transported out of the intestinal cells with
the help of
Ca 2+ dependent ATPase
• Increased plasma calcium – decreased absorption
from the gut
• Decreased by phosphates and oxalates and alkalis
• Increased by high protein diet
1,25 Vitamin D3

15. CALCIUM IN KIDNEYS
• 98 % - 99 % is reabsorbed
60 % in PCT
40 % in Ascending limb of LOH
Distal tubule
PARATHYROID HORMONE

16. RECOMMENDED DAILY INTAKE OF
VITAMIN D
ESTIMATED DAILY CALCIUM
INTAKES

20. Calcium Citrate

23. NORMAL VALUES
• Total body phosphate – 500 to 800 g.
• 85 – 90 % in skeleton
• Plasma phosphate – 12 mg / dL
2/3rd – organic
1/3rd – inorganic {Pi}
ex. PO4
3- , HPO4
2-, H2PO4
2-
FUNCTIONS
ATPase , c AMP , 2-3, DPG
Phosphorylation and Dephosphorylation
PHOSPHATE METABOLISM

24. Phosphate is found in ATP, DNA, RNA, cAMP, 2,3-DPG,
many proteins. Phosphorylation and
dephosphorylation of proteins are involved in the
regulation of cell function – bone - buffer
Inorganic phosphate in the plasma is mainly in two
forms: HPO4- (1.05 mmol/L) and H2PO4- (0.26
mmol/L)
pH of the ECF becomes more acidic, Relative increase
in H2PO4- and a decrease in HPO4- and viceversa.
Decreasing level of phosphate in ECF from far below
normal does not cause major immediate effects on the
body. In contrast, even slight increases or decreases of
calcium ion in ECF can cause extreme immediate
physiologic effects.
chronic hypocalcemia or hypophosphatemia greatly
decreases bone mineralization

25. BONE SALTS
• Salts of calcium and phosphate.
HYDROXYAPATITE
Ca10(PO4)6. (OH)2
400 Å long
10 – 30 Å thick
100 Å wide
Ca / P ratio – 1.3 to 2.0
Other salts:
Mg2+, Na+ , K+ ions conjugated
to bone crystals.

26. BONE:
3 mg of PO4 enters and is again
reabsorbed.
KIDNEYS:
85 % - 90 % of filtered Pi is reabsorbed by
Active Transport in PCT
PTH
Overflow
mechanism
Phosphorus

27. G I T
• Absorbed in duodenum and small intestine by Active transport and passive
diffusion.
• Absorption is linear to dietary intake.

28. VITAMIN D PHYSIOLOGYFORMATION OF VITAMIN
D3

29. – 25-HYDROXYLASE
FUNCTIONS
CONSTITUTIVELY
WITHOUT INPUT FROM
BLOOD CALCIUM
STATUS OR PTH
– 25(OH)VITAMIN D IS THE
BEST SCREENING TEST
FOR VITAMIN D
ADEQUACY
VITAMIN D RESISTANT RICKETS:
mutations in the gene coding for the
enzyme
1 α HYDROXYLASE

30. calcium homeostasis
absorption of Ca and P
in the small intestine
Role of vitamin D
normal mineralization of
bone
reabsorption Ca and P
in the renal tubule

33. • THE COUPLED PROCESS OF BONE
TURNOVER CAN BE MEASURED BY:
– MARKERS OF OSTEOBLAST METABOLISM
• SERUM BONE-SPECIFIC ALKALINE PHOSPHATASE
• SERUM OSTEOCALCIN
– MARKERS OF OSTEOCLAST METABOLISM
• URINE PRODUCTS OF BONE COLLAGEN BREAKDOWN
– HYDROXYPROLINE
– N-TELOPEPTIDES
– PYRIDINIUM CROSSLINKS
MEASUREMENT OF BONE
TURNOVER

34. Vitamin D
Intake of vitamin D3 can increase many times and
yet the concentration of 25-
hydroxycholecalciferol remains nearly normal -
prevents excessive action of vitamin D
conserves the vitamin D stored in the liver for
future use. Once it is converted, it persists in the
body for only a few weeks, whereas in the
vitamin D form, it can be stored in the liver for
many months.

35. When the plasma calcium concentration is too high, the
formation of 1,25-dihydroxycholecalciferol is greatly depressed
– decreases the absorption of calcium from the intestines, the
bones, and the renal tubules.
z

36. Serum 25(OH)D (calcidiol)
vitamin D - Normal potential
deficiency-insufficiecy adverse
effects
0 25 50 75 125 nmol/L
** 1 nmol/L = 0.4 ng/mL
≥50 nmol/L
(≥20 ng/mL)
>125 nmol/L
(>50 ng/mL)

37. • EXCESSIVE INTAKE OF VITAMIN D
– RELATIVELY HARD TO DO IF ALL RELEVANT ORGAN
SYSTEMS ARE FUNCTIONING PROPERLY; GENERALLY
REQUIRES PRESCRIPTION STRENGTH VITAMIN D,
PARTICULARLY 1,25(OH)2D (CALCITRIOL)
• EXCESSIVE PRODUCTION OF 1,25(OH)2D
– EXTRA-RENAL 1-HYDROXYLATION OF 25(OH)VITAMIN
D BY AN ENZYME WITH 1-HYDROXYLASE ACTIVITY,
WHICH IS DISTINCT FROM RENAL ENZYME
• USUALLY ASSOCIATED WITH GRANULOMAS (MACROPHAGES)
OR ABNORMAL LYMPHOID TISSUE (B CELL LYMPHOMA)
• NOT REGULATED BY PTH OR CALCIUM
HYPERVITAMINOSIS D

38. Parathyroid Hormone

39. ACTIONS OF PTH
I. Increases calcium and phosphate
absorption from the bones
II. Decreases excretion of calcium by the
kidneys
III. Increases the excretion of phosphate by
the kidneys
IV. Increases intestinal absorption of calcium
and phosphate.
INCREASED PLASMA CALCIUM

40. Calcidiol PTH
(25-hydroxy
vitamin D)

41. Parathyroid Hormone

42. PTH - Kidneys
1. PTH causes rapid loss of phosphate in urine owing to
the effect of the hormone to diminish proximal tubular
reabsorption of phosphate ions.
PHOSPHATURIC ACTION
2.PTH increases renal tubular reabsorption of Ca.
3. increases reabsorption of Mg ions and H ions
4.decreases reabsorption of Na, K and amino acid
No PTH - continual loss of Ca into the urine would
eventually deplete both the ECF and the bones

47. • STIMULUS : Increased plasma calcium
Others: β adrenergic agonists, dopamine
and estrogen, GASTRIN, CCK, glucagon..
• ACTIONS:
Decreases absorptive action of osteoclasts
Deposits exchangeable Ca in bone salts
Decreases the formation of osteoclasts
• CLINICAL USE:
Used in the treatment of
PAGET’S DISEASE.
CALCITONIN

48. RICKETS

49. RICKETS

50.  Rickets leads to
cupping and to a
brush−like
appearance of the
epiphyseal ends on
radiograms.
 Radiographs of the
knee of a 3.6-year-
old girl with
hypophosphatemia
depict severe
fraying of the
metaphysis.
N Active Rickets recovery

51. RENAL OSTEODYSTROHY

53. 53
OSTEOPOROSIS

54. • SKELETAL MASS IN
HUMAN REACHES A
PEAK AT ABOUT
AGE 30
– BEFORE 30 :
– SKELETAL MASS
INCREASING..
– BONE FORMATION
EXCEEDS BONE
RESORPTION.
– AT 30:
– TWO PROCESSES ARE
EXACTLY MATCHED
– AFTER 30:
– SKELETAL MASS IS
LOST FOR THE REST
OF LIFE

55. Normal bone has the appearance of a honeycomb
matrix (left). Under a microscope, osteoporotic
bone (right) looks more porous.

57. • Bone mineral density (BMD) is the current measure
(major determinant) of fracture risk. (Not DEXA)
WHO criteria
• Mean for age
– T score: 0
• Osteopenia
– T score: -1.0~-
2.5
• Osteoporosis
– T score < -2.5
Incidence of Fem neck fx (A) and
Intertrochanteric fx (B) by BMD
Osteoporosis

58. What keeps bones healthy
Regular exercise
Adequate amounts of calcium
Adequate amounts of vitamin D, which is very essential for
absorbing calcium

59. TOP CALCIUM SOURCES
1

63. TESTS AND DIAGNOSIS
Osteopenia refers to mild bone loss that isn't severe enough to be called
osteoporosis, but that increases the risk of osteoporosis.
The best screening test is dual energy X-ray absorptiometry (DEXA) –
measures the density of bones in the spine, hip and wrist and it's used to
accurately follow changes in these bones over time.
Ultrasound
Quantitative CT scanning
Dual energy X-ray absorptiometry

66. ThanksPersistence in your presentations, this is one secret to success. After my first
presentation, I got up
and did it again. Even though I was scared to death, I did it again. So
preparation in all areas of life
is so vital to your success. Don’t be lazy in preparing; don’t be lazy in
laying the groundwork that
will make all of the difference in how your life turns out.
What you may be lacking in are the strong feelings
about what you want and what you want to do.
Let these strong feelings help you take a second
look at your life. After all, you’ve only got one life,
at least on this planet. So why not make it an
adventure in achievement? Why not discover what
all
you can do and what all you can have? Why not
now take the Challenge to Succeed!
First you need to succeed to survive. We must take the seasons and learn how to
use them with
the seed, the soil and the rain of opportunity to learn how to sustain ourselves and
our family.
But then second is to then succeed to flourish in every part of your life today than
yesterday, in
our speech, our language, our health, everything we can possibility think of.

67. This presentation is for doctors and students in general.
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