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7/30/2019 Mineral Homeostasis Bone
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Bone mineral homeostasisThe main minerals in bone are calcium salts andphosphates.
More than 90% of Ca+2 in the body is in the skeleton,mostly as crystalline hydroxyapatite (ca-phosphatecrystals) which are deposited the osteoid , converting it
into hard bone matrix.
Bone remodeling:
The process of remodeling involves the activity of:
1. Osteoblasts which secretes new bone matrix.2. Osteoclasts which break it down.
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The principal hormone involved in Ca+2 metabolism and
bone remodeling are:
1. Parathyroid hormone.
2. Calcitonin.
3. Vitamin D
And the main target tissues for these hormones are:
a. Bone. b. Kidney. c. Intestine.
These 3 hormones and their target organs maintain
serum calcium levels & bone integrity.
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Parathyroid hormone (PTH)
PTH orparathormone is secreted from parathyroid
gland in response to free Ca+2 concentration
(hypocalcemia).
It maintains serum the plasma Ca+2 by:
1. Mobilizing Ca+2from bone.
2. Promotes its absorption by the kidney.
3. synthesis of calcitriol which Ca+2absorption from the
intestine.
4. PTH promotes phosphate excretion.
So net effects: Ca+2in plasma, phosphate in the plasma.
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The main factors involved in maintaining
the concentration of Ca+2 in the plasma &
the action of drugs
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Calcitonin
Is secreted from specialized C cells found in the thyroidgland.
Actions:
1. Inhibits bone resorption by inhibiting osteoclasts effects.
2. In the kidney, it decrease reabsorption of Ca+2 &phosphate in the proximal tubules.
So net effects: Ca+2in plasma, phosphate in the
plasma.
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Clinical uses of calcitonin
Hypercalcemia.
Osteoporosis.
It is given by injection & can be given intranasally.
A form of calcitonin from salmon is mainly usedbecause of longer half life & high potency.
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Vitamin D
Vitamin D is prehormone ,that is converted in the body in
to number of biologically active metabolites that act as a
true hormone.
Sources of vitamin D:
1.Dietary ergocalciferol(D2).2.Cholecalciferol (D3) generated in the skin from 7-
dehydrocholesterol by the action of ultraviolet radiation.
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Vitamin D synthesis
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Action of vitamin D
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The main action of calcitriol are:
1.Stimulation of absorption of Ca+2 & phosphate
in the intestine.2. Mobilization of Ca+2 from bone.
3.Ca+2 reabsorption in the kidney tubules.
The NET effect: Ca+2, phosphate.
the effect of Ca+2 on bone is complex & is clearly
not confined to mobilising Ca+2!?
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Administration of vitamin D restore bone formation. one
explanation may lie in the fact that calcitriol stimulates the
synthesis of osteocalcin, the vitamin K-dependent Ca+2binding protein of bone matrix.
Clinical uses of vitamin D :
1. Hypocalcemia caused by hypoparathyroidism.
2. Deficiency states :prevention & treatment of various
forms of rickets, osteomalacia & deficiency owing to
malabsorption.
3.In combination with calcium supplementation & hormone
replacement therapy, in postmenopausal osteoporosis.
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Vitamin D Deficiency
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Actions of Parathyroid Hormone (PTH), Vitamin D, on Gut, Bone, and Kidney
PTH Vitamin D
Intestine Increased calcium andphosphate absorption (byincreased 1,25[OH]2D
production)
Increased calcium and phosphateabsorption by 1,25 (OH)2D
Kidney Decreased calcium excretion,increased phosphateexcretion
Calcium and phosphate excretionmay be decreased by 25(OH)D and1,25(OH)2D
1
Bone Calcium and phosphateresorption increased by highdoses.
Increased calcium and phosphateresorption by 1,25(OH)2D; boneformation may be increased by1,25(OH)
2
D
Net effect on serum levels Serum calcium increased,serum phosphate decreased
Serum calcium and phosphate bothincreased
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S/Es:
Excessive intake of vitamin D causes hypercalcemia :
constipation, weakness & fatigue & if persist Ca salts
are deposited in the kidney & cause renal failure &kidney stones.
Other drugs that involved in bone metabolism:
a. Glucocorticoids :
physiological concentrations of glucocorticoids are
required for osteoblast differentiation.
Excessive concentration of glucocorticoids inhibit bone
formation by inhibiting osteoblast differentiation &
osteoclast action.
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b. estrogens:
During the reproductive life in female, estrogens have
important role in maintenance of bone integrity.
They inhibit osteoclast action & oppose bone-resorbing,
Ca+2mobilizing action of PTH.
Withdrawal of estrogen as happens at menopause can lead
to osteoporosis.
Drugs related to estrogens:
Selective estrogen receptor modulator (SERM).Raloxifene
Has an estrogen agonist effect on bone & antagonist
activity on estrogen receptor in mammary tissue & the
uterus.
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Drugs used in bone disorders:
Bisphosphonates
MOA: they bone resorption by inhibiting osteoclasts &
promote apoptosis & indirectly stimulate osteoblastactivity.
Example: alendronate
S/Es: GI disturbances which can be sever. Esophagitiscan also occur.
To prevent this oral preparation are given with sufficientamount of water & with the patient in upright position.
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Clinical uses:
1. prevention or treatment of postmenopausal
osteoporosis.
2. Hypercalcemia due to malignant disease.
Dental consideration:
Concomitant use of salicylates or salicylate- containing
compound with bisphosphonates is not recommended
since an incidence of upper GI adverse effects.
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Fluoride
Accumulated by bones & teeth, stabilize thehydroxyapatite crystals
Effective for prophylaxis of dental caries
Under investigation for the treatment ofosteoporosis
Excess leads to mottling
A/Es N., V., GIT blood loss, arthritis