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1. Calcium & Phosphate Metabolism
INDIAN DENTAL ACADEMY
Leader in continuing Dental Education

2. Contents
Introduction
Sources
Requirements
Distribution
Absorption
Excretion
Functions
Regulation of calcium & phosphate metabolism
Associated disorders
Periodontal considerations

3. Sources of calcium & phophorus
Calcium:
Milk & milk products
Eggs
Meat
Leafy vegetables
Fruits
Nuts
Ragi
Phosphorus
Same as calcium
More in cereals & pulses

4. RDA
Calcium:
Adult 500-800 mg/day
In pregnancy 1500 mg/day
Lactating mothers 2000 mg/day
New born and Infants 360 mg/day
Children 800 mg/day
Phosphorus
Adults 500-800 mg/day
Pregnant/lactating 1200 mg/day
Adolscents 1200 mg/day
Infants 240 mg/day

5. Distribution of Calcium & phosphorus
Calcium:
Total body calcium : 1100-1200 gms Plasma Ca levels: 9-11 mg/dl
99% Bone & teeth
1%: 0.9% soft tissue, 0.1% ECF

6. Daily Calcium Balance

7. Phosphorus:
Total body phosphorus: 500-800 mg
85% bone, 15% Liver, pancreas, brain
Plasma phosphate: 2.5-4.5 mg/dl
Organic form: 0.5-1 mg/dl
Inorganic form: 3-4 mg/dl in adults
5-6 mg/dl in children

8. Absorption of calcium & phosphate
Calcium : 40% absorption
Factors influencing absorption:
1. Influencing mucosal cells
2. Influencing solubility of calcium
Factors influencing mucosal cells:
1. Vit D
2. Body calcium Stores
3. Pregnancy & growth
4. Growth hormone

9. Factors influencing availability of Ca in gut
1. pH
2. Amount of dietary calcium and phosphorus
3. Phytic acid & phytates
4. Oxalates
5. Fat
6. Proteins
7. Carbohydrates
8. Bile salts

10. Absorption of phosphate:
Factors increasing Ca absorption also increase phosphate absorption
Occurs in Duodenum
Small Intestine

11. Calcium absorption
Factors favoring:
1. PTH
2. Vit D
3. High protein diet
4. Acidic pH
5. Negative Cal balance
6. Pregnancy, lactation, growth
7. Carbohydrates
Factors negating:
1. Oxalates, phytates
2. Excess lipid
3. Excess phosphate
4. Corticosteroids
5. Thyroid hormone
6. Alkaline pH
7. High body stores

12. Phosphate absorption
Factors favouring:
1. Low calcium diet
2. PTH
3. Vit D
4. Growth hormone
Factors negating:
1. High Ca diet
2. Vit D deficiency
3. Antacids

13. Excretion of calcium & phosphate:
1. Faeces: most of unabsorbed calcium constitutes fecal calcium
2. Urine: under full body control
maintenance of homeostasis
Ca in urine decreases with increased phosphate intake
High phosphate diet serum Pi PTH→ ↑ → ↑
↓
reabsorption of Ca from kidney
Plasma phosphate threshold value
Urine phosphate proportional to plasma phosphate
Threshold value:- 2-2.4 mg/dl

14. Functions of calcium & phosphorus
Calcium:
1. Major component of skeleton, bone & teeth
2. Cell membrane stabilization
3. Maintenance of nerve excitability & muscle contraction
4. Skeletal & smooth muscle contraction
5. Neurotransmitter release
6. Activation of enzymes
7. Secretion of hormones
8. Blood coagulation

15. Functions of phosphorus:
1. Formn of bone, teeth- hydroxyapatite
2. Essential components: Nucleoproteins
phospholipids
power molecules: ATP, NADPH, GTP
3. Reguln of blood pH & urine pH
4. Intermediate in fat & carbohydrate metabolism
5. Deamination & transamination of amino acids
6. Regulation of glycolysis

16. Regulation of Calcium, Phosphate Metabolism
• Organ systems that play an import role in Ca2+
metabolism
– Skeleton
– GI tract
– Kidney
• Hormones
– Parathyroid hormone (PTH)
– Calcitonin (CT)
– Vitamin D (1,25 dihydroxycholecalciferol)
– Parathyroid hormone related protein (PTHrP)

17. Overview of Calcium-Phosphate Regulation

18. Parathyroid Hormone
secreted by the parathyroid glands
polypeptide containing 84 amino acids.
Overall effect : increase Ca conc in plasma
Lowers plasma phosphate concentration
Regulation of PTH Secretion:
Extracellular Ca ( Ca conc <7 mg/dl)
Ca2+ also regulates transcription
High levels of Vit D inhibit transcription

19. Calcium Sensing Receptor (CaSR)
•Parathyroid chief cells contain a Ca2+
sensing receptor (CaSR)
•There are two paradoxes
-The receptor responds to decreasing concentrations of agonist
-Low extracellular Ca2+
increases intracellular Ca2+
-Also found in thyroid C cells (calcitonin), kidney, and brain

20. Actions of Parathyroid Hormone
1. Action on bone:
2 main effects:
1. Fast Ca efflux from labile pool to plasma
2. Stimulation of bone dissolution (Long term effect)
Acts on an osteoblast cell
membrane receptor
↑ cell permeability to calcium.
The increase in cytosolic calcium
activates a pump that drives
calcium from the bone to the
ECF. The pump is enhanced by
1,25 (OH)2D3

22. PTH and Osteoblastogenesis

23. Osteoclast Mediated Bone Resorption

24. PTH and Kidney
Action on kidney:
1. enhances reabsorption of calcium from distal tubules.
2. reduces the uptake of phosphate in the proximal tubules of the
kidney
3. Enhances activity of 1 Hydroxylaseα → ↑ Vit D

25. PTHrP; Parathyroid Hormone related Protein
• shares the same N-terminal end as parathyroid hormone and it
therefore can bind to the same receptor
• plays a role in the development of hypercalcemia of malignancy
– Some lung cancers are associated with hypercalcemia
– Other cancers can be associated with hypercalcemia
• Aids in normal mammary gland development and lactation as well as
placental transfer of calcium
• May be important in fetal development

26. Disorders of PTH secretion
Hyperparathyroidism:
characterized by hypercalcemia, hypercalcuria, hypophosphatemia, and
hyperphosphaturia
Etiology:
1. Primary hyperparathyroidism : dysfunction in the parathyroid glands
themselves
2. Secondary hyperparathyroidism : resistance to the actions of PTH,
usually due to chronic renal failure.
3. Tertiary: rare forms caused by long lasting disorders of the calcium
feedback control system.

27. Primary hyperparathyroidism:
Cause: benign parathyroid adenoma
multiple endocrine neoplasia
C/F:
Complications:
osteitis fibrosa cystica, osteoporosis, osteomalacia, and arthritis.
Rx: surgical removal

30. Secondary hyperparathyroidism:
Cause: renal failure Vit D, phosphate↓ ↑
Insoluble calcium phosphate forms
Tertiary hyperparathyroidism:
hyperparathyroidism can not be corrected by medication
basis of treatment is still prevention in chronic renal failure

31. Pseudohypoparathyroidism
• Symptoms and signs
– Hypocalcemia
– Hyperphosphatemia
– Characteristic physical appearance: short stature, round face,
short thick neck, obesity, shortening of the metacarpals
• Resistance to parathyroid hormone
• The patients have normal parathyroid glands, but they fail to respond
to parathyroid hormone or PTH injections
• Symptoms begin in children of about 8 years
– Tetany and seizures
– Hypoplasia of dentin or enamel and delay or absence of eruption
occurs in 50% of people with the disorder

32. Pseudohypoparathyroidism

33. Hypoparathyroidism
Signs
Hypocalcemia : tremor, tetany and, eventually, convulsions.
Causes
Accidental surgical removal
Autoimmune invasion most common non-surgical cause. It can occur as
part of autoimmune polyendocrine syndromes.
Hemochromatosis.
Absence or dysfunction of the parathyroid glands is one of the
components of chromosome 22q11 microdeletion syndrome
Idiopathic (of unknown cause), occasionally familial
Rx: calcium and Vitamin D3 supplementation , Teriparatide

34. Vitamin D
Intake: average daily intake of vitamin D – 500 IU
recommended intake is 400 IU/day
(1 mg of vitamin D3 = 40 000 IU).

35. Vitamin D Metabolism

36. Vit D regulation

37. Actions of Vit D:
1. Intestine

38. Action on bone:

39. Action on Kidney:
1. Weakly stimulates renal Ca reabsorption
2. Stimulates transport of Ca into skeletal and cardiac muscle

40. Vit D deficiency
Rickets/Osteomalacia
Causes: Inadequate intake and absence of sunlight
defective mineralization of the bone matrix
A deficiency of renal 1 -hydroxylase produces renal ricketsα
Sex linked gene on the X chromosome
Renal tubular defect of phosphate resorption
Teeth may be hypoplastic and eruption may be retarded

43. Calcitonin
• Product of parafollicular C cells of the thyroid
• Acts to lower plasma Ca conc
• Action on bone: deactivation of osteoclast
promotion of phosphate entry into bone
• Action on kidney: Ca excretion↑
small in urinary phosphate excretion↑

44. Other hormones
1. GH: absorption from small intestine↑
2. Insulin: favors bone formation, imp during fetal development
3. Prolactin: favors hydroxylation of Vit D
4. Anabolic hormones: stimulate growth, act on cartilage
5. Estrogen: primarily retard bone resorption, promote positive Ca
balance, induce 1 hydroxylaseα
6. Thyroxine: Ca mobilisation osteoporosis↑ →
7. Glucocorticoids:
- ↓ Ca & Phosphate absorption in small intestine
- ↑ renal Ca excretion
- Inhibit osteoclast diffrentiation Ca levels PTH→ ↓ → ↑

45. Disorders of calcium &phosphate metabolism
Hypercalcemia
Hypocalcemia
hyperphosphatemia
Hypophosphatemia

46. Hypercalcemia
Causes:
1. primary hyperparathyroidism
2. malignancy
3. Granulomatous diseases:
- sarcoidosis, TB
4. Endocrinopathies:
- Hyperthyroidism
- Adrenal Insufficiency
5. Medications
- Thiazide diuretics
- Lithium
- Vit D
- Milk alkali syndrome

47. C/F
Polyurea Lethargy Impaired renal function
Polydipsia Anorexia hypertension
Renal calculi Depression ectopic calcification of
Drowsiness arterial walls, corneal
calcifications
Skeletal and radiologic changes:
-early stages demineralization & subperiosteal erosions in phalanges
- Pepper pot appeareance in lat ceph
- Nephrocalcinosis
- Soft tissue changes
- Ostetis fibrosa cystica

48. Management:
Initial therapy: fluids and diuretics
hydration, increasing salt intake, and forced diuresis
Additional therapy: bisphosphonates and calcitonin

49. Hypocalcemia
Causes:
1. Hypothyroidism
2. Hypoalbuminaria
- Idiopathic
- Surgical
- Transient, post op
- Magnesium defiency
3. Pseudohypoparathyroidism
4. Vit D disorders
Hyperphosphatemia
- Renal Insuffiency
5. Acute pancreatitis

50. C/F:-
Perioral tingling and parasthesia,earliest symptom of hypocalcemia.
Tetany, carpopedal spasm are seen.
latent tetany :
Trousseau sign
Chvostek's sign Tendon reflexes are depressed
life threatening complications
Laryngospasm
cardiac arrhythmias

51. Management
Two ampoules of intravenous calcium gluconate 10% is given slowly
in a period of 10 minutes, or if the hypocalcemia is severe, calcium
chloride is given instead.
Maintenance doses of both calcium and vitamin-D (often as 1,25-
(OH)2-D3, i.e. calcitriol)) are often necessary to prevent further
decline

52. Hypophosphatemia
Seen when plasma phosphate level less than 0.4 mmol/l
C/F: muscle pain & weakness
respiratory muscle weakness
cardiac arrythmias
confusion, convulsion, coma
hypercalciurea
Causes
- Vit D defiency - oral absorption (Antacids)↓
- Malabsorption - phosphate removal
- ↑ CHO metabolism & insulin Haemedialysis

53. Hyperphosphatemia
Causes: 1. Increased intake
Excessive parenteral administration of phosphate
Milk-alkali syndrome
Vitamin D intoxication
2. Decreased excretion
Renal failure, acute or chronic
Hypoparathyroidism
Pseudohypoparathyroidism
3. Shift of phosphate from intracellular to extracellular space
Rhabdomyolysis
Tumor lysis
Acute hemolysis

54. C/f:
muscle cramps, tetany
joint pain, pruritus, or rash
fatigue, shortness of breath, anorexia, nausea, vomiting, and sleep
disturbances
Management:
phosphate binders, diet restrictions, volume repletion with saline
coupled with forced diuresis

55. Hypophosphatasia:
Defienciency of Alk phosphatase
Types: Infantile - severe rickets, hypercalcemia, bone abnormalities,
failure to thrive
Childhood - Infections, growth retardation↑
Adult – spontaeneous #
Oral findings: premature exfoliation of teeth
Hypocalcification of teeth & large pulp chambers
Rx: Vit D – partial improvement
High doses of phosphate – 0.25-0.75 gms QID

56. Pathologic calcifications
Dystrophic calcification:
Not dependent on blood Ca but local conditions
Seen in fibromas, pulps, BV walls
Metastatic calcification
Occurs in undamaged tissue
↑ blood CA
Hyperparathyroidism
Hypervitaminosis D
Mainly in kidneys, lungs, gastric mucosa

57. Osteoporosis
Osteoporosis is characterized by a significant reduction in bone
mineral density compared with age- and sex-matched norms
There is a decrease in both bone mineral and bone matrix
Women lose 50% of their trabecular bone and 30 % of their cortical
bone
30% of all postmenapausal women will sustain an osteoporotic
fracture as will 1/6th
of all men

58. Normal and Osteoporotic Bone

60. FDA Approved Rx’s for Osteoporosis
Bisphosphonates (alendronate and risedronate)
Calcitonin,
Parathyroid hormone
Raloxifene
Teriparatide, a form of parathyroid hormone, is a newly approved
osteoporosis medication. It is the first osteoporosis medication to
increase the rate of bone formation in the bone remodeling cycle

61. Periodontal considerations
Plaque: Inorganic component predominantly calcium & phosphate
Calculus
Osteoporosis:
Von Vowren (1983) : attachement loss in osteoporotic women↑
Wactawski wende & colleagues (1996) : found relationship between
alveolar crestal bone height and skeletal osteopenia
Dietary Ca: Nishida et al (2000) NHANES III
Using multiple logistic regression analysis, a reln found
btwn lower levels of dietary Ca & risk for periodontal disease↑
Calcium and periodontitis Clinical effect of calcium medication
Erik Uhrbom Journal of Clinical Periodontology 1984: 11: 230-241

62. References
Oral physiology & biochemistry : Jenkins
Textbook of physiology : Guyton
Essentials of medical pharmacology : KD Tripathi
Net references