Mineral Homeostasis Bone

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
http://www.thachers.org/images/Tibial.jpg


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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

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Mineral Homeostasis Bone