Osteoporosis

Question 0

Trabecular

Answer 0

20% of total bone mass.

Vertebrae and ends of long bones

Question 1

Cortical bone

Answer 1

80% of total bone mass

Primarily long bones; outer layer of all bones

Question 2

Osteoblasts

Answer 2

Build bone
Secrete RANKL and osteoprotegrin(which inhibits RANKL)
Have PTH, estrogen, and androgen receptors
Makes bone matrix proteins and are responsible for bone mineralization

Question 3

Osteoclasts

Answer 3

Resorb bone–> takes up or breakdown bone. Bone remodeling
RANKL(stimulates osteoclasts through RANK receptor. RANKL is released by osteoblasts) and mevalonate pathway are essential for activity
Osteoclasts differentiate into multinucleated cells and have finger like projections to increase surface area attached to bone and secrete H+ions to dissolve the bone. Absorb dissolve bone matrix(calcium, phosphate, bisphosphonates…)

Question 4

Osteoid

Answer 4

Collagen, unmineralized bone. What is laid down to build new bone by osteoblasts. Calcium and phosphate are needed to mineralized bone

Question 5

Mineralization

Answer 5

Strength. Deposit of hydroxyapatite

Calcium and phosphate are needed

Question 6

Osteoprotegrin

Answer 6

Soluble decoy receptor for RANKL. Also secreted by osteoblasts
Decreases bone resorption

Question 7

Osteocytes

Answer 7

Sense mechanical strain and send a signal back to osteoblasts to initiate the 1st step of bone remodeling (osteoclasts recruitment and proliferation)
Neither an osteoblasts nor osteoclasts

Question 8

Active vitamin D

Answer 8

Stimulates RANKL. RANKL stimulates osteoclasts. Osteoclasts Resorb bone and free up calcium–> vitamin D increases calcium
Increases calcium absorption from intestines
Increases PTH
Formed after vitamin D is hydroxylated for a second time in the kidney

Question 9

PTH

Answer 9

Increases extracellular calcium
Directly stimulates osteoblasts–> increase RANKL–>activates osteoclasts–>Resorb bone–>increase calcium
Increases calcium reabsorption in kidney. Increase inactive vitD to active calcitriol
Released in response to low calcium
Inhibited by 1,25(OH)2 D (active vitD) via negative feedback

Question 10

Calcitonin

Answer 10

Produced by C-cells (parafollicular cells) of thyroid
Counterbalance for PTH–> calcitonin decreases calcium levels by decreasing reabsorption in kidneys and increasing deposition do calcium in the bone
Inhibits osteoclasts

Question 11

Risk factors for osteoporosis

Answer 11

Menopause: estrogen increases osteoblasts lifespan, suppresses osteoclasts differentiation, decreases bone resorption, inc. calcium absorption, promotes calcitonin biosynthesis, increase vitD receptors on osteoclasts
Low physical activity
Smoking
Chronic diseases-hyperparathyroidism, hyperthyroidism, estrogen deficiency
Medications-glucocorticoids, thyroid replacement therapy

Question 12

Teriparatide (Forteo)

Answer 12

Stimulates bone formation (KEY IS LOW INTERMITTANT DOSING)
Recombinant PTH (PTH causes bone resorption to release calcium into circulation)
Increases mature osteoblasts
Inhibits apoptosis of osteoblasts and osteocytes (*especially offsets glucocorticoid induced osteoporosis)
SEs: hypercalcemia( transient, occurs immediately and stimulates osteoclasts to Resorb bone initially causing spike of calcium), leg cramps, orthostatic hypotension (Ca is needed for vasodilation), and osteosarcoma. Not for use in CrCl <30mls/min
For prevention and Treatment in post menopausal women and osteoporosis in men and GCC induced osteoporosis do not use longer than 2 years

Question 13

Calcitonin-salmon
Miacalcin (nasal spray)
Calcimar or Salmonine (IV)
Fortical

Answer 13

Inhibit bone resorption
Calcitonin analog but with longer half life (inhibits osteoclasts, decrease bone resorption
Treatment in post menopausal women (>5 years) with vertebral fracture

Question 14

Bisphosphonates

Answer 14

Inhibit bone formation:1st line except ibandronate
Bind to hydroxyapatite crystals embed in skeleton (get built into bone itself)–> bone still gets resorbed and bisphosphonates get taken up by osteoclasts and inhibits activity
Dose varies daily or weekly to monthly or yearly
* prevention &osteoporosis in post menopausal women or in men or in GCG Induced osteoporosis
SEs: GI upset, esophagitis, osteonecrosis of jaw, flu like febrile illness, hypocalcemia in vitD deficient pts, atypical bone fractures
Don’t use in CrCl <35mls/min

Question 15

Denosumab (Prolia)

Answer 15

Inhibit bone resorption
Monoclonal antibody to RANKL. Similar MOA to osteoprotegrin.
For high fracture risk pts or for pts who failed bisphosphonates. Treatment in post menopausal women, men on deprivation treatment for prostate cancer and women on aromatse inhibitor treatment for breast cancer

Question 16

Raloxifen (Evista)

Answer 16

Inhibit bone resorption
SERM: estrogen receptor agonist in bone, antagonist in breast and uterus
SEs: hot flashes, DVT, PE– avoid additional estrogen use, d/c 3 days prior to prolonged immobilization
For prevention and Treatment in post menopausal women with high breast cancer risk

Question 17

Non-Nitrogen containing bisphosphonates

Answer 17

Incorporate into ATP and cause apoptosis

Etidronate (Didronel)

Question 18

Nitrogen containing bisphosphonates

Answer 18

Osteoclasts lose ruffled border- not enough surface area to secrete enough H + ions to dissolve bone ( primarily by inhibition of farnesyl pyrophosphate synthase)
Leads to inactivation and possible apoptosis

Question 19

Alendronate sodium

Answer 19

Fosamax

Propyl amine

Question 20

Etidronate disodium

Answer 20

Didronel

Methyl. Least potent

Question 21

Ibandronate sodium

Answer 21

Boniva

Tertiary alkyl amine

Question 22

Risedronate disodium

Answer 22

Actonel or Atelvia
Pyridine fxn group 2nd greatest potency
Only bisphosphonate that can be given without regards to meal

Question 23

Zoledronic Acid

Answer 23

Zometa or Reclast

Histidine functionality. Greatest potency