⭐ LECTURE 4: OSTEOPOROSIS Flashcards
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Mother cells
OSTEOPROGENITOR CELLS
immature bone cells and are found on the outer surface of the bone and in the bone cavities
OSTEOBLASTS
Mature bone cells
OSTEOCYTES
Large, phagocytic, multinucleated derivatives of monocytes or monocyte-like cells formed in the bone marrow
OSTEOCLASTS
What are the 2 types of growth in BONE REMODELING?
Linear Growth
Appositional Growth
initiates remote signal by activating the macrophages
ACTIVATION PHASE
will begin once osteoclasts are activated by RANKL and M CSF to release calcium and phosphorus
RESORPTION PHASE
osteoclasts will disappear and will undergo apoptosis
REVERSAL PHASE
bone calcification will begin once collagen molecules are secreted
FORMATION PHASE
Imbalance that occurs in bone resorption and bone formation due to:
-Decrease in bone resorption
-Increase in bone resorption
-Combination of both
OSTEOPOROSIS
What are the signs and symptoms of OSTEOPOROSIS
For menopausal women: lose 25-30% of spongy bone and 10-15% of cortical bone
What are the PRIMARY HORMONES?
PTH, Vitamin D, Fibroblast Growth Factor 23 (FGF23)
What are the SECONDARY HORMONES?
Calcitonin, Glucocorticoids, Estrogen, Prolactin, GH, Insulin, Thyroid Hormone
Albumin is at low level = decrease level in calcium
HYPOALBUMINEMIA
exhibition of Low level of ionization
and in favor of ionization
Acidosis
Disfavors ionization
Disfavors ionization
This primary hormone Promotes bone formation and resorption by stimulating osteoblasts and osteoclasts
PTH
This primary hormone Stimulates intestinal absorption of Ca and phosphate and Promotes bone formation and resorption by stimulating the osteoblasts and osteoclasts
Vitamin D
This primary hormone Stimulates P excretion in the kidney = hypophosphatemia and low levels of 1,25(OH)2D3
Fibroblast growth factor
This secondary hormone Lowers Ca and P and Inhibits osteoclastic bone resorption
Calcitonin
excess PTH promotes?
an increase in bone resorption
low PTH promotes?
an increase in bone formation
What are the common sites for osteoporosis related fracture?
Vertebrae
Hip
Distal radius
WHAT ARE THE AGENTS USED TO INCREASE BONE MINERAL DENSITY
Calcium
Vitamin D
Bisphosphonates
Calcitonin
Estrogen therapy
PTH
Monoclonal antibody
2500 mg/day
MAXIMUM TOLERATED LIMIT
1000 mg/day
CEILING EFFECT
Daily requirement of calcium supplements
800-1500 mg per day
what are the Risks in Calcium Supplements
arterial calcification and cardiovascular disease and hypercalcemia
How many mg of calcium supplements are excreted daily in urine and feces?
300 mg
mimics effects of endogenous calcium
Calcimimetic
Helps prevent bone breakdown and increase in plasma calcium levels associated with excessive PTH release
CINACALCET (SENSIPAR)
Enhance bone formation by increasing the absorption and retention of calcium and phosphate in the body
VITAMIN D AND VITAMIN D ANALOGS
recommended intake of men and women from 51 to 70 yrs old of VITAMIN D AND VITAMIN D ANALOGS
600 IU/day
recommended intake of men and women from > 70 yrs old of VITAMIN D AND VITAMIN D ANALOGS
800 IU/day
Daily adult allowance of VITAMIN D AND VITAMIN D ANALOGS
2000 to 10000 units/day
CALCITRIOL
Calcijex, Rocaltrol
CHOLECALCIFEROL
Replesta, Vitamin D3
ERGOCALCIFEROL
Calciferol, Drisdol
PARICALCITOL
Zeemplar
Absorbed into calcium crystal and blocks excessive bone resorption and formation by inhibiting osteoclast activity
BISPHOSPHONATES
AR/SE of BISPHOSPHONATES
Osteonecrosis of the jaw
Atypical hip fractures
GI disturbances
1st Generation
Oral Bisphosphonates
Etidronate (most common), Medronate, Clodronate, Tiludronate
→ Minimally modified side chain contain a chlorophenyl group
→ Metabolized into a non-hydrolyzable ATP analog that accumulate within osteoclasts and includes apoptosis which account for its antiresorptive effect
→ Least potent
2nd Generation
Oral Bisphosphonates
→ Alendronate (most common), Pamidronate, Ibandronate
→ Contains nitrogen group in the side chain
→ Inhibits bone resorption
→ Antiresorptive activity involves inhibition of multiple steps in the pathway from mevalonate to cholesterol and isoprenoid lipids that are required for the prenylation of proteins that are important for osteoclast function
→ 10-100 times more potent than 1st Gen BP
3rd Generation
IV Bisphosphonates
→ Risedronate and Zoledronate
→ Contain nitrogen atom within heterocyclic ring
→ 10 000 times more potent than 1st Gen BPs
Taken up by the osteoclast
and can Cause cell apoptosis through activation of caspase pathway
NON-NITROGEN CONTAINING BPs
Not metabolized
and Affects protein prenylation of osteoclast by inhibiting farnesyl diphosphate (FPP) synthase (key enzyme of the mevalonate pathway)
NITROGEN CONTAINING BPs
Lower plasma calcium levels in hypercalcemic emergencies
Calcitonin
Promote bone mineralization in women who lack endogenous estrogen production
Estrogen
Able to preferentially activate estrogen receptors
SERM (Selective Estrogen Receptor Modulators)
Activates receptors in bone and blocks receptors in breast and uterine tissues
RALOXIFENE (Evista 60 mg PO)
Monoclonal antibody (MAB)
and Binds to specific receptors (RANK) on osteoclasts → inhibits ability of endogenous chemical to stimulate osteoclast activity → inhibition of osteoclast-induced bone resorption
DENOSUMAB (PROLIA)
Stimulates new bone formation on trabecular and cortical bone surfaces by preferential stimulation of osteoblastic activity over osteoclastic activity
rPARATHYROID HORMONE [rPTH(1-34), TERIPARATIDE]
Synthetic form of human PTH – recombinant human PTH (1-34) analog
TERIPARATIDE (FORTEO)
“Dual action bone agents” (DABA)
STRONTIUM RANELATE
Testosterone replacement therapy increases BMD in hypogonadal men
ANDROGENS
Protease expressed in osteoclasts
Degrades type 1 collagen in organic bone
Inhibit matrix dissolution, decrease bone resorption, and improve BMD in postmenopausal women
CATHEPSIN K INHIBITORS
Increase osteoblast number and promotion of osteoblastic differentiation, leading onto increased bone formation by simvastatin
STATINS
potential new drug for osteoporosis
Echistatin
Calcium-sensing receptor antagonists are new drug class of orally administered agents that stimulate endogenous PTH release and have bone forming action
CALCILYTICS
