ERG Calcium

1.5 kg

normal adults have how much calcium in the body

phosphate

calcium forms insoluble minerals with many anions: hydroxide, __________, fluoride, carbonate

25000

extracellular calcium concentration is ___________ times higher than intracellular

40

what percent of calcium is protein bound (not freely diffusible)

vitamin D, small intestine

calcium enters the body through intestine by two mechanisms:

- active, ___________ dependent transport in the proximal duodenum

- facilitated diffusion throughout ________ _________

glucocorticoids

drugs like _________ and phenytoin depress intestinal calcium transport

inversely

intestinal calcium absorption efficiency is __________ related to calcium intake

PTH

reabsorption of calcium is highly regulated by _____

Increased, decreased

In the Kidney, when Ca2+ is LOW, there is ____________ Ca2+ reabsorption, and _______________ Pi reabsorption

Increased, increased

In the Intestine , when Ca2+ is LOW, there is ____________ Ca2+ reabsorption, and _______________ Pi reabsorption

increases

when serum Ca2+ is low, PTH secretion __________

decreases

when serum Ca2+ is high, PTH secretion ____________

increased

the effect of PTH in the intestine is ________ Ca absorption

decreased

the effect of PTH in the kidney is ____________ Ca exretion

teriparatide

a short, 34 residue peptide identical to a part of PTH is biologically as active as PTH and called _______

oseteoporosis

what is the main indication of teriparatide and abaloparatide

bone metastasis or skeletal malignancy

teriparatide and abaloparatide should not be used in patients with:

true

true or false: vitamin D is a hormone

photochemical

an essential step in the formation of Vit D3 is a __________ reaction that requires UVB light

liver

to creat biologically active form of vit D, need reaction in the skin, then the __________, and finally in the kidney

gene transcription

vitamin d and its metabolites bind to cytoplasmic/nuclear vitamin D receptors and regulate ______________

increased

vitamin D effect on intestine is that is increases ________ absorption

decreased

effect of vitamin D on kidney is ________ ca excretion

true

true or false: there is no major effect of FGF23 on overall serum Ca decrease in serum phosphate

hypophosphatemia

burosumab is approved to treat X-linked _____________

FGF23

________ is the target of an anti-FGF23 blocking monoclonal antibody

Klotho

FGF23 MOA: binds to FGF receptor with "friend" ___________

calcitonin

32 amino acid peptide hormone

C-cells (parafolicular cells)

tcalcitonin is produced in _______ of the thyroid

opposing

calcitonin has __________ effects to PTH

calcium and phosphate

calcitonin lowers ___________ and ____________ levels by modulating bone remodeling

decreases

the overall net effect of calcitonin is serum calcium _________

salmon calcitonin

this is used for treatment of osteoporosis in women 5 years after menopause when alternative treatments are not suitable (not afirst line med to treat osteoporosis)

hypercalcemia

central nervous depression is a symptom of _____________

hypocalcemia

neuromuscular effects are symtpoms of ___________

diuretics

which med can be used to treat hypercalcemia that increases urine flow and inhibits calcium reabsorption

calcitonin

this is used as an ancillary agent for hypercalcemia

phosphate

when __________ is given intravenously, it brings down free calcium quickly

hypocalcemia

hypoparathyroidism, vitamin D deficiency, chronic kidney disease, and calcium malabsorption are some of the causes of ____________

calcium infusion

what is the acute treatment of hypocalcemia

vitamin D (D3)

this is used as treatment in hypocalcemia in that it increases clacium levels within 24-48 hours

increases, decreases, increases

vitamin D ___________ Ca uptake in the intestine, __________ Ca excretion in the kidney, and __________ solubilization of Ca into serum

bone health

_________ depends on the balanced and continuous interplay of bone resorption and bone deposition

bone remodeling

bones are subjected to a continuous, life-long process of breakdown and renewal called:

Cholecalciferol

Vitamin D3

Ergocalciferol

Vitamin D2

Calcitrol

Vitamin D3

Gene transcription

Vitamin D MOA: Binds to Vit. D receptors and helps in the regulation of _______ _________. (Skin -> Liver -> Kidneys)

Osteosarcoma

PTH's BBW includes increased risk of _____________. (Increased Ca2+ is NOT the cause)

Digoxin

What is the Drug-Drug- Interaction with PTH?

osteoclasts

what cell resorb bone material and generate cavities

preosteoblasts

_________ are derived from marrow stroma and are recruited into the base of the cavity

osteoblasts

preosteoblasts differentiate into __________ and replace the resorbed bone by secreting new bone matrix constituents, such as collagen, osteocalcin, and other proteins

6 months

how long does the completion of a bone remodeling cycle take?

RANK ligand

osteoblasts and several other cell types express a cell surface protein called ______________

ODF (Osteoclast differentiation factor)

RANKL is also known as ______.

osteoclast

activation of RANK by RANKL leads to __________ formation

osteoprotegerin (OPG)

osteoblasts produce an inhibitor of RANK-signaling called ____________ which is closely related to RANK and binds to RANKL and thus blocks RANKL from activating RANK

Suppresses, decreases

OPG _________ osteoclast activity and thus ____________ bone degradation

stimulates

OFD __________ osteoclast activity

formation, resorption

RANK ligand acts on RANK and promotes osteoclast __________ and subsequent _________ of bone matrix

sclerostin

__________ is a small protein that regulates bone strength

sclerosteosis (van buchem disease)

a defect in the sclerostin gene leads to non-functional sclerostin and results in ________

larger, stronger

patients with van buchem disease have _________ and _______ bones than normal

reducing

the main effect of estrogen is _________ bone remodeling, likely via its effects on osteocytes (inhibits bone reabsorption)

antagonize

glucocorticosteroids __________ vitamin D stimulated intestinal calcium

decreased

glucocorticosteroids overall effect is _________ serum calcium

Glucocorticosteroids

MOA: antagonize Vit. D calcium transport and stimulate Ca2+ renal excretion => suppresses bone formation

hypercalcemia

glucocorticoids are therapeutically useful in reversing __________

osteoporosis

_______ is a bone disease that occurs when the body loses too much bone, makes too little bone, or both

bisphosphonates

these drugs localize to sites of bone resportion, thus have greatest effects on osteoclasts

hydroxyapatite

bisphosphonates interfere with formation and dissolution of ________ crystals within the skeletal systen

geranyl, farnesyl

the nitrogen containing BPs inhibit ___________ and _________ pyrophosphate transferases, which are important enzymes for osteoclast survival

bisphosphonates

adynamic bone, renal failure, atypical bone fractures, and osteonecrosis of the jaw are some of the side efects of ________-

denosumab

this is a fully human monoclonal antibody that binds specifically to RANK ligand (similar MOA to OPG)

romosozumab

this drug targets sclerostin and reduces its effective concentration and stimulation of its receptor; it sitmualtes bone formation, rather than slowing bone loss

estrogens

________ can increase bone formation in postmenopausal women transiently

venous thromboembolism and death from stroke

what are the serious black ox warning of using estrogen receptor modulators like raloxifene for osteoporosis

rickets

this is the softening and weakening of bones usually caused by nutritional vitamin D deficiency

paget's disease

this disease is excessive bone remodeling and bone deposition in certain areas of the body and the bone material is softer and weaker

increases, decreases, increases

PTH __________ serum Ca in the intestine, ___________ Ca exretion in the kidney, and ________ solubilization of Ca into serum at high doses

Ca and P

vitamin D increases __________ serum levels

neutral, increases, decreased

FGF23 has a ________ effect on Ca in the intestine, ________ P excretion in the kidney, and ___________ bone mineralization

decreases, increases, blocks

calcitonin ___________ Ca uptake in the intestine, ___________ Ca excretion in the kidney, and _________ bone desorption

Ca, P

PTH increases serum __ levels and decreases serum ___ levels

P

FGF23 decreases ___ serum levels

teriparatide and abaloparatide

what are the 2 PTH drugs

PTH and calcitonin

which drug subclasses bind to its receptor and use G-protein coupled signaling

vitamin D and calcitonin

what 2 things do you use to treat osteoporosis and hypercalcemia

raloxifene (SERM)

what drug reduces bone resportion without breast or endometrial cancer risk in the use of osteoporosis

calcitriol

what drug increases calcium levels in the use of rickets and vitamin D deficiency

denosumab

this drug binds to RANKL and blocks activation of RANK, it reduces bone resportion to treat osteoporosis

bisphosphonates

this drug reduces osteoclast activity, inhibiting farnesyl pyrophosphate synthesis to reduce bone resportion

romosozumab

this drug binds sclerostin and stimulates bone deposition

Oral and empty stomach

How should N-containing Biophosphonates be taken?

True

(True/False) Biophosphonates accumulate and embed themselves into bones

Osteoporosis and Paget's Disease

What Indications do Biophosphonates treat?

Rickets and Vit. D deficiency

What two indications does Vitamin D treat?