Calcium homeostasis Flashcards
Vitamin D stimulates intestinal abs of Ca and P
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PTH and Vit D effect of bone:
Formation via osteoblasts
Resorption via osteoclasts
PTH and Vit D effect on kidney:
Enhance resorption of Calcium
PTH: stimulates renal excretion of P
Vit D: enhances P retention
Fibroblast growth factor effect at kidney:
Stimulates excretion of P, overall decreases serum level
PTH stimulates Vit D activation at kidney
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Vit D and Ca++ inhibit PTH synthesis and release
negative feedback
Fibroblast growth factor inhibits VIt D in kidney
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Calcitonin (synthetic) can reduce serum Ca and P by inhibiting bone resorption
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Vitamin D3 (cholecalciferol)
Modest cost. Efficient
Vitamin D2 (ergocalciferol)
Less efficient than D3, shouldnt be 1st choice
25-Hydroxyvitamin D3 (calcifediol)
DOesnt need hepatic hydroxylation. Best for liver disease
1, 25-dihydroxyvitamin D3 (calcitriol)
Most useful in patients with decreased synthesis of calcitriol (renal disease)
Calicitriol synthesis stimulated by
PTH in the kidney (released in response to hypocalcemia)
Hypophosphatemia also directly stimulates synthesis
Calcitonin stimulated by, MOA
Hypercalcemia
inhibits bone resorption –> decreases Ca++ and PO4
Reduces absorption/increases excretion of Ca++ and PO4
Estrogen MOA
Decreases number and activity of osteoclasts
Increase osteoblast activity
Glucocorticoid MOA on decreasing bone density
Lowers serum Ca++ by inhibiting dietary absorption –> increases PTH in response, increased osteoclast activity
Activates osteoclasts –> increased bone resorption
Suppresses osetoblast activity
RANK ligand is expressed on an osteoblast in response to
Vitamin D3, PTH and interleukins
RANKL interacts with receptor (RANK) on osteoclast
forms mature osteoclasts
Bisphosphonates inhibit bone resorption by osteoclasts
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Estrogen increases production of a decoy molecule that doesnt allow activation of RANK receptor
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Post-menopausal women predisposed to osteoporosis because loss of…
estrogen - which inhibits osteoclasts (normally), so they go un-leashed
Bisphophonate MOA
Bind to sites of bone remodeling
Inhibit osteoclasts by (1)apoptosis and (2)inhibit protein synthesis w/i cell, necessary for function
Bisphosphonates are 1st-line, most effective in preventing and treating osteoporosis
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Alendronate or Risedronate dose, ADR
Bisphosphonates: weekly or monthly PO
Esophagitis, GI upset
Selective Estrogen Receptor Modulator (SERM) in osteoporosis
Prevention and treatment only if patient can’t tolerate a bisphosphonate or is at risk of breast CA (contra of estrogen)
Denosumab MOA
Antibody against RANKL - reduces osteoclast activation and improves BMD
Denosumab use
For tx of patient with high fracture risk
Teriparatide (Forteo) treats osteoporosis by stimulating bone formation. UNIQUE
All other treatments are anti-resorptive agents
Teriparatide MOA
must be given intermittently
increases osteoblastic activity
expensive
Calcitonin Use in Osteoporosis
Treats not prevents
inhibits osteoclastic resorption
Subcutaneously or intranasal
Expensive
Thiazide diuretics in hypercalciuria
Reduces urinary calcium excretion
Hypercalcemia caused by
hyperparathyroidism and/or cancer
Muscle weakness, lethargy
Saline diuresis in hypercalcemia
Frequently dehydrated. Once rehydrated, loop diuretics can be used to increase Ca++ excretion
Bisphosphonates in hypercalcemia
Mainstay of treatment. Potent inhibition of osteoclastic bone resorption
Calcitonin in hypercalcemia
potentially useful - decreases calcium mobilization out of bone
Hypocalcemia causes
hypoparathyroidism, Vit D deficiency, hypomagnesemia
Hypocalcemia TX with Calcium (acute)
Calcium gluconate IV for treatment of severe hypocalcemic tetany
Hypocalcemia TX with Calcium (chronic)
supplements recommended only if can’t be taken in from diet
Vitamin D supplements in hypocalcemia
Improves intestinal Ca++ absorption
supresses bone remodelling
