bone minerals

bennett exam 1

alendronate brand

fosamax

alendronate (fosamax) class

bisphosphonate

raloxifene brand

evista

raloxifene (evista) class

SERM

ibandronate brand

boniva

ibandronate class

bisphosphonate

risedronate brand

actonel

what can be used for prevention of osteoporosis

calcium and vitamin D supplements + weight bearing exercise

composition of bones

25% organic — osteoblasts, osteoclasts, other cells

75% inorganic — calcium, phos, hydroxyapatite

what can cause malabsorption of calcium, PO4, and vit D

GI or hepatic disease

what can an imbalance of calc and phos cause

bone disease, 2nd hyperparathyroidism, renal osteodystrophy

what vitamin promotes intestinal absorption of calc

vitamin D

what happens to calcium levels in renal disease

conversion to active vit D is impaired → vit D deficiency → increased phos levels → decreased calc levels, increased PTH

what hormones play a role in bone homeostasis

primary regulators — PHT and vit D

secondary regulators — calcitonin, thyroid, estrogen

are calc levels higher intracellularly or extracellularly

extracellularly (plasma)

where is intracellular calc found

in mitochondria and endoplasmic reticulum

is intracellular or extracellular calc more important

intracellular calc

where can calc be found in the body

small intestine (dietary intake)

kidney (filtered then reabsorbed in tubules)

bone and teeth

heart and blood vessels

what are some physiological functions of calc

promotes “proper” resting membrane potential

maintains cardiac function

involved in signal transduction cascade

involved in coag process and cell replication

what oral calc formulation has the highest % of elemental calc

calcium carbonate — 40% elemental calc

what % elemental calcium is in calcium citrate

21% elemental — preferred in high gastric pH, elderly, and use with PPI

which form of oral calcium should be taken with food

calcium carbonate

what are the IV formulations of calc

ca-gluceptate, ca-chloride, ca-gluconate

calcium ADRs

constipation, kidney stones, hypercalcemia, headache, bone pain, coma

what drugs can interact with calcium

iron, tetracyclines, bisphosphonates, quinolones, phenytoin, fluoride, digoxin

phos binding agents mechanism

bind dietary phos in the GI tract → form insoluble aluminum, calc, or magnesium → excreted in feces → decreased phos in the blood

how should phos binding agents be dosed

titrate to achieve correct serum phos without causing hypercalcemia

when should phos binding agents be taken

with meals to increase binding in the gut

what are phos binding agents used for

chronic kidney disease

what are the 4 types of phos binding agents

calc containing, aluminum containing, magnesium containing, iron containing

calc containing phos binding agent ADRs

constipation, hypercalcemia

aluminum containing phos binding agent ADRs

constipation, worsening of anemia (due to accumulation of Al) avoid if possible

magnesium containing phos binding agent ADRs

diarrhea

iron containing phos binding agent ADRs

nausea, diarrhea, constipation, dark/discolored feces, bloating, abdominal pain

lanthanum carbonate brand

fosrenol (phos binding agent)

aluminum carbonate brand

basaljel (phos binding agent)

which phos binding agents should not be taken with calcium citrate

aluminum carbonate and aluminum hydroxide — increased Al absorption

which phos binding agents are 1st line

calcium carbonate, citrate, and acetate

which phos binding agent should not be taken with antacids or sucralfate

calcium citrate

which phos binding agent is 2nd line

sevelamer chloride — does not contain Ca, Al, or Mg

how do inorganic phosphates work

form bone mineralization

when is potassium phosphate used

in patients with low potassium levels

when is sodium phosphate preferred

if patient has hyperkalemia

what strength are inorganic phosphates prescribed in

millimoles

what are the indications for inorganic phosphates

severe hypophosphatemia, hypercalcemia

what stimulates parathyroid hormone release

low blood calc levels

how does PTH work

stimulates osteoclasts (breaks down bones) and kidneys to reabsorb calc and inhibits reabsorption of phos

promotes formation of vit D3

what drug is a PTH analog

teriparatide (forteo) — increases bone formation by stimulating osteoblasts (builds bones)

how is teriparatide formulated/dosed

refrigerated subq injection

if PTH breaks down bones, how does it work to build bones as teriparatide

high levels of PTH → osteoclast bone demineralization

intermittent/bolus of PTH → osteoblast bone growth

“once daily exposure of PTH favors bone anabolism, continuous exposure favors bone catabolism”

teriparatide (forteo)/PTH ADRs

dizziness, tachycardia, leg cramps, hypercalcemia, osteosarcoma, orthostatic hypotension

what is the new formulation of PTH

abaloparatide (tymlos) and palopegteriparatide (yorvipath)

what is palopegteriparatide (yorvipath)

PTH prodrug for chronic hypoparathyroidism in adults — for continuous PTH exposure (unlike the PTH to treat osteoporosis)

vitamin D3 mechanism

promotes absorption of calc in the GI tract and stimulates kidneys to reabsorb calc

where are vitamin D receptors located

small intestine, hematopoietic cells, epidermal cells, lymphocytes, pancreatic islets, and neurons

where does vit D synthesis begin

in the skin with cholesterol as a precursor

where does the conversion of vit D2 to D3 occur

in the liver

what is the active form of vit D

1,25 (OH)2D3 — calcitriol)

indications for 1,25 vit D3

rickets or osteomalacia, hypocalcemia, CKD, secondary hyperparathyroidism

1,25 vit D3 ADRs

hypercalcemia, headache, edema

what are the 4 types of vit D on the market

calcitriol

ergocalciferol

doxercalciferol

paricalcitol

which form of vit D is activated in the liver and kidney

ergocalciferol → calcifediol

which form of vit D is a prodrug that is activated in the liver

doxercalciferol

bisphosphonate mechanisms

inhibits osteoclast proliferation/activity/lifespan (stops breakdown of bones) and decreases bone resorption (breaking down of old bone)

what do bisphosphonates mimic

pyrophosphate

what is pyrophosphate

normal constitutent of bone that binds to hydroxyapatite portion of the bone

what are the PO forms of 2nd gen bisphosphonates

alendronate, ibandronate, risedronate

what is the IV formulation of 2nd gen bisphosphonates

pamidronate

what is the IV formulation of 3rd gen bisphosphonates

zoledronic acid, zoledronate

what are the 3rd gen bisphosphonates indicated for

treatment of hypercalcemia in cancer patients

what is the difference in potencies between the 1st, 2nd, and 3rd gen bisphosphonates

2nd gen — 100x more potent than 1st gen

3rd gen — 1000x more potent than 1st gen

bisphosphonate ADRs

severe joint/bone/muscle pain, esophageal erosion, jaw osteonecrosis, atypical femur fracture, esophageal cancer

what is the max length of time a patient can use a bisphosphonate

max of 2 years

how does raloxifene work

estrogen antagonist on breast tissue and endometrium

estrogen agonist on bone

raloxifene (SERM) ADRs

hot flash

raloxifene (SERM) boxed warning

increased DVT/PE risk, increased risk of death from stroke in women with or at risk for CHD

calcitonin mechanism

inhibits osteoclast-induced bone resorption via Gs mediated cAMP — inhibits renal tubular cell resorption of Ca — maintains bone mineral homeostasis

calcitonin intranasal spray brand name

miacalcin

calcitonin ADRs

hypocalcemia, increased risk of cancer

how is calcitonin given

intranasal — 200 IU daily

SC or IM — 100 IU q other day

what is the relationship between calcitonin levels and calcium levels

increased calcium → increased calcitonin

what is calcitonin used for

post-menopausal women with osteoporosis, pagets, hypercalcemia

calcimimetic mechanism

blocks PTH secretion by enhancing the sensitivity of the calc sensing receptor (CaR)

what drugs are calcimimetics

cinaclet (sensipar)

etelcalcetide (parsabiv)

calcimimetic indications

secondary hyperparathyroidism in CKD

hypercalcemia associated with PTH carcinoma

calcimimetic ADRs

hypocalcemia, prolonged QT/ventricular arrhythmias

RANKL antagonist mechanism

binds RANKL to prevent interaction between RANKL and RANK → decrease osteoclast and bone resorption → increase bone mass

what is RANKL

protein involved in the formation, function, and survival of osteoclasts

what drugs are RANKL antagonists

denosumab (prolia, xgeva)

what are RANKL antagonists used for

increase bone mass in men and women with high risk of fractures

postmenopausal women with osteoporosis at high risk of fracture

which RANKL antagonist is given subq every 6 months

prolia — for osteoporosis

which RANKL antagonist is given subq every month

xgeva — cancer-related bone disorders

RANKL antagonist ADRs

back pain, hypocalcemia

hypocalcemia must be corrected before giving the drug

prolia (RANKL antagonist) boxed warning

severe hypocalcemia in advanced CKD (GFR <30) and on dialysis

evenity mechanism

inhibit sclerostin → promote bone formation

sclerostin blocks bone formation

how is evenity given

subq monthly for up to 12 months

evenity contraindication

hypocalcemia

evenity boxed warning

increased risk of heart attack or stroke

evenity indication

treatment of postmenopausal women with history of osteoporosis fracture or multiple risk factors

what are disorder of the structure of bone

osteoporosis, secondary osteoporosis

osteopenia

osteomalacia (rickets, pagets)