Bone Rx

Question 1

What is the average calcium requirements for a young adult? When might excess calcium be recommended?

Answer 1

young adults require 1000mg/d total, 1200-1300mg is recommended in adolescents, teens, and pregnant/lactating women, posted menopausal women and men over the age of 70y

Question 2

What is the active ingredient in vocative, caltrate and TUMS?

Answer 2

calcium carbonate (best taken with food): products marketed for calcium usually advertise the amount of elemental calcium while ant-acid sources of calcium advertise their total calcium carbonate content (40% which is elemental calcium)

Question 3

What are important dosing instructions to remember about calcium citrate?

Answer 3

it usually requires 2 pills to a achieve a 500-600mg dose, does not need to be taken with food

Question 4

What is the recommended daily allowance of vitamin D?

Answer 4

400 to 600 IU/d, those with osteoporosis may need more

not a lot of foods naturally high in vitamin D

Question 5

What is the best natural source of vitamin D?

Answer 5

sun exposure, must be

during summer months, peak during peak sun hours (10-2p), to exposed skin not protected by sunblock, or through a window

Question 6

What are other important bone strategies to talk to your patients about?

Answer 6

walking/impactexercise
stop smoking
care on ice, in cluttered areas and at night w/o the light on

Question 7

What is the MOA of cincalcet?

Answer 7

is a CaSR agonist, can b used to suppress abnormal/unwanated PTH secretion (parathyroid carcinoma), secondary hyperparathryodism due to ESRD)

Question 8

T/F? Almost all filtered calcium is reabsorbed?

Answer 8

true

Question 9

What are the PTH independent and PTH dependent mechanisms of Ca++ reabsorption in the kidney?

Answer 9

PTH independently: passive diffusion in the proximal tubule and in the thick ascending limb driven by voltage gradient created by Na/K/Cl reabsorption

PTH-dependent: PTH dependent calcium reabsorption occurs in the distal convoluted tubule

Question 10

How can loop diuretics be used to block Ca reabsorption?

Answer 10

loop diuretics block the Na/K/Cl transport mechanism (in TAL) but should only be used with adequate volume expansion to avoid impaired renal function

Question 11

What are the sources of cholecalciferol and ergocalciferol?

Answer 11

cholecalciferol is produced in the skin from 7-dehydrocholesterol in UV light and is also found in most supplements

ergocalciferol is produced by irradiating plant sterols and is found in some vitamin D supplements

both forms are readily activated and are equally effective at binding VDR

Question 12

What is calcitriol?

Answer 12

1,25-dihydroxy vitamin D (1, 25-D), the active form of vitamin D

Question 13

Describe how the body metabolizes cholesterol to active vitamin D.

Answer 13

7-dehydrocholesterol is converted by the sun to cholecalciferol

in the liver cholecalciferol is converted in the liver to 25-hyrdoxyvitamin D (storage form)

in the liver 25-D is converted to its active form 1-25-dihydroxyvitamin D

Question 14

When is supplementation of vitamin D indicated?

Answer 14

in vitamin deficiency (OTC or Rx cholecaciferol or ergocalciferol)

in CKD with secondary hyperparathyroidism due to impairment of 1a-hydroxylase (calcitriol or other active analogues are used)

in hypocalcemia due to hypoparathyroidism (calcium and calcitriol is used)

Question 15

What is the lifetime risk of a 50yo to have an osteoporotic fracture? (vertebrae, hip or wrist?)

Answer 15

in women the risk is 40% (18% risk of hip fracture)

in men 13%

Question 16

What are the two major classes of drugs that are used in treating osteoporosis?

Answer 16

antiresorptive agents decrease bone resorption (inhibit osteoclasts): estrogen, SERMs, bisphosphonates, calcitonin, denosumab

anabolic agent- stimulate bone formation

Question 17

How does estrogen improve bone health?

Answer 17

estrogen stimulates maturation of osteoblasts and inhibits the maturation of osteoclasts

it inhibits the expression of RANK-L decreasing osteoclast activity

**due to significant side effects is not considered a first line treatment of osteoporosis

Question 18

What is the mechanism of action of raloxifine?

Answer 18

raloxifine is a selective estrogen receptor modifier and binds to the estrogen with differential effects depending on the tissue:

estrogen like effects at the bone (improving density and preventing further loss)

shows a decrease in vertebral fracture risk of 30-50% but can also cause hot flashes and thromboembolic disease

Question 19

What is the MOA of bisphosphonates?

Answer 19

as bisphophonates are incorporated into the bone matrix, if resorbed by osteoclasts they impair function of the osteoclasts and prevent further bone loss

the induce a small improvement in bone density and prevent further bone loss

Question 20

What are examples of bisphosphonates currently used?

Answer 20

aledronate
risedronate
ibandronate
zoledronic acid

Question 21

What are the possible side effects of bisphophonates?

Answer 21

upper GI symptoms with PO agents

very rare osteonecrosis of the jaw and atypical femoral fractures

Question 22

What is the efficacy of agents aledronate and risedronate?

Answer 22

decrease risk of fracture of all types by about 50%; aledronate is dosed orally per week and resedronate is dosed weekly-monthly

both have a similar side effect profile

Question 23

What is the efficacy of ibandronate? How is it dosed?

Answer 23

anti fracture efficacy demonstrated only for vertebral fractures

it is dosed orally/mo or IV/3mo
side effect profile is similar to other bisphophonates

Question 24

What is the efficacy of zoledronic acid? How is zoledronic acid dosed? What side effects might patients expect?

Answer 24

most potent bisphosphonate with anti fracture efficacy at all sites, vertebral fracture rates decrease by 70%

dosed IV/year or IV/2yrs for prevention

no GI side effects (IV) but up to ⅓ of patients will have an acute phase reaction to their first infusion (fever, myalgias)

Question 25

What are the pharmacological uses of calcitonin?

Answer 25

salmon-derived calcitonin can be used to treat severe hypercalcemia (short-lived effect)
can be used in pain control of acute vertebral compression fracture
is given intranasally or subcutaneously

data suggest possible link to increase cancer risk

Question 26

What is the MOA of denosumab? What is its efficacy and method of dosing?

Answer 26

denosumab is a monoclonal antibody to RANK-L, decreases activation of osteoclasts
has anti fracture efficacy at all sites, and decreases vertebral fractures by 70%

administered by subcutaneous injection dosed every 6mo

Question 27

What is the mechanism of action of teriparatide?

Answer 27

tripartite is a short acting recombinant PTH 1-34

causes pulsatile PTH that induces osteoblastic activity much more than osteoclastic activity, leading to net gains in bone density

Question 28

How is teriparatide dosed? Is it effective?

Answer 28

given as a daily injection and approved for use for 2yrs an can cause mild nausea, dizziness and weakness (osteosarcoma in rats)

it can lead to significant gains in BMD and is shown to decrease vertebral fractures by 65% and non vertebral fractures by 50%— note bon gains are achieved are quickly lost when the drug is stopped, Teriparatide must be followed by an anti-resorptive to maintain improvements

Question 29

How do you know who to treat for osteoporosis?

Answer 29

prevent bone loss in those experiencing rapid bone loss (glucocorticoid treatment)

prevent fractures in those who are at high risk of fracture (elevated by FRAX)