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Endocrine II - Exam 2 > Agents for Bone Mineralization (Waller) - SRS > Flashcards

Agents for Bone Mineralization (Waller) - SRS Flashcards

1
Q

What are the minerals used in tx of bone issues?

A

Calcium

Phosphate

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2
Q

What are the hormones used in treatment of bone diseases?

A

Calcitonin

Teriparatide

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3
Q

What are the Vitamin D, metabolites and analogs used in Rx o’ bone diseases?

6 with three bolds

A
  1. Calcipotriene
  2. Calcitriol
  3. Cholecalciferol (Vitamin D3)
  4. Doxercalciferol
  5. Ergocalciferol (Vitamin D2)
  6. Paricalcitol
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4
Q

What is the selective estrogen receptor modulator (SERMs) we learned (or should have)?

A

Raloxifene

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5
Q

What are the bisphosphonate drugs we studied?

7 with one bold

A
  1. Alendronate (Fosamax)
  2. Etidronate
  3. Ibandronate (Boniva)
  4. Pamidronate
  5. Risedronate (Actonel)
  6. Tiludronate
  7. Zoledronic acid (Reclast, Zometa)
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6
Q

What is the calcium receptor agonist we learned?

Not bold

A

Cincalcet

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7
Q

What are the “other” drugs we learned for the rx of bone disease?

3 with one bold

A
  1. Denosumab (Prolia)
  2. Estrogens
  3. Glucocorticoids
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8
Q

Describe the MOA of Teriparatide!

A

Synthetic recombinant human parathyroid hormone (1-34) Continuous administration of PTH causes bone demineralization and osteopenia, however intermittent (once per day administration sub q promotes bone growth.

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9
Q

In what patients would you consider using teriparatide? 4

A

Women with…

  1. history of osteoporotic fracture
  2. multiple risk factors for fracture
  3. failed on other drug therapies.
  4. Men with hypogonadal osteoporosis
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10
Q

What are the ADR’s associated with Teriparatide? (6)

A
  1. Orthostatic hypotension
  2. hypercalcemia
  3. dizziness
  4. nausea
  5. hyperuricemia
  6. angina
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11
Q

In what situations is teriparatide contraindicated?

(1 major thing with 4 examples)

A

Patients at increased risk of osteosarcoma including…

  1. Paget’s disease
  2. Unexplicably elevated alkaline phosphatase
  3. Open epiphyses
  4. with prior radiation therapy involving the skeleton
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12
Q

What are cholecalciferol and ergocalciferol?

A

Cholecalciferol = Vitamin D3

Ergocalciferol = Vitamin D2

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13
Q

Describe generally the locations in which the steps of Vitamin D3 biotransformation is carried out.

A
  1. First in the skin by UV light
  2. Then in the liver by hydroxylation
  3. Finally in the kidney
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14
Q

What impact does calcitriol have on bone related minerals?

A

Increases intestinal absorption of Calcium and phosphate.

Increases renal retention of calcium and phosphate.

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15
Q

How does calcitriol increase bone turnover? (3)

A
  1. Promoting the recruitment of osteoclast precursor cells to resorption sites.
  2. Promoting the development of differentiated functions that characterize mature osteoclasts.
  3. Inducing the synthesis of several proteins that regulate the bone mineralization process, such as RANK ligand and osteocalcin.
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16
Q

What is the MOA of the vitamin D analogs?

A
  1. MOA: increases intestinal absorption of Ca2+ and PO43- as well as bone turnover.
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17
Q

What are four therapeutic indications for the use of vitamin D analogs?

A
  1. Nutritional and metabolic Rickets
  2. Osteomalacia
  3. Hypoparathyroidism
  4. osteoporosis
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18
Q

What are the ADR’s associated with the vitamin D analogs? Which are serious? (bolded)

A
  1. Arrhythmias
  2. Pancreatitis
  3. hypercalcemia with/without hyperphosphatemia
  4. Nausea
  5. Vomiting
  6. Constipation
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19
Q

What are the principle effects of calcitonin?

A

Decreases serum calcium and phosphate by actions on bone and kidney.

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20
Q

In what disorders would the use of calcitonin be indicated?

A

Disorders of increased skeletal remodeling

  1. Pagets
  2. Osteoporosis
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21
Q

What are the ADRs associated with calcitonin?

A
  1. Nausea
  2. Hand swelling
  3. urticaria
  4. intestinal cramping (rare)
22
Q

Glucocorticoids antagonize vitamin D stimulated intestinal calcium transport, stimulate renal calcium excretion, and block bone formation. The ultimate effect: decrease in total body calcium stores.

What are three indications for the use of these drugs within the context of calcium disorders? (3)

A

Managing hypercalcemia in…

  1. Lymphoma
  2. Sarcoidosis (and other noncaseating granulomatous diseases)
  3. Vitamin D intoxication
23
Q

What impact does prolonged exposure to glucocorticoids have on adults? Children?

A

Adults = osteoporosis

Children = Stunted skeletal muscle development

24
Q

Estrogens prevent accelerated bone loss during the immediate post-menopausal perio and at least transiently increase bone in post-menopausal women. What is the prevailing hypothesis on how this works?

A

estrogens reduce bone-resorbing action of PTH.

25
Q

What type of drug is Raloxifene?

A

Selective estrogen receptor modulator (SERM)

26
Q

What indication would point you towards using raloxifene?

A

Treatment and prevention of post menopausal osteoporosis

27
Q

Raloxifene, a selective estrogen receptor modulator (SERM), serves as a partial agonist in bone but does not stimulate endometrial proliferation in post-menopausal women. What are the important ADRs to know for this drug?

A
  1. Hot flashes
  2. Leg cramps
  3. thromboembolism (increased risk of DVT and PE by 3X)
28
Q

In what situations would the use of raloxifene be contraindicated?

A

In women with active or past history of…

  1. Venous thromboembolism
  2. coronary heart disease
  3. risk factors for major coronary events such as stroke
29
Q

What type of drug is alendronate?

A

Bisphosphonate

30
Q

Knowing alerndronate is a analog of pyrophosphate in which P-O-P bond replaced with non-hydrolyzable P-C-P bond, what is the MOA of Alendronate? (5 components)

A
  1. Their structure responsible for chelating Ca2+, which gives these agents a strong affinity for bone.
  2. Concentrate at sites of active bone remodeling; incorporated into bone until the bone is remodeled and the bisphosphonate is released back into the acid medium.
  3. Decreases the formation and dissolution of hydroxyapatite crystals within and outside the skeletal system.
  4. Directly inhibits osteoclasts.
  5. Some of the newer agents appear to increase bone mineral density. May be a result of other cellular effects including inhibition of 1,25(OH)2D production and intestinal calcium transport.
31
Q

What should be done when the patient takes alendronate and other bisphosphonates?

A

Take on an empty stomach to maximize bioavailability.

Take with a full glass of water and remain upright for 30 minutes to minimize ADRs.

32
Q

What are the ADRs associated with the bisphosphonates?

(some pretty good fodder for TQs here)

A
  1. Osteonecrosis of the jaw (very rare; more frequent with high intravenous doses of zoledronate used to control bone metastases and cancer induced hypercalcemia).
  2. Subtrochanteric femur fractures due to over-suppression of bone turnover.
  3. Esophageal and gastric irritation
33
Q

What is the MOA of Denosumab?

A

This fully human monoclonal antibody binds and prevents the action of RANKL.

  1. Mimics the effects of osteoprotegerin, reducing binding of RANKL to RANK and blocking osteoclast formation and activation (osteoclastogenesis).
34
Q

How/how often is Denosumab administered?

A

Sub Q every 6 months

35
Q

What are two therapeutic indications for the use of denosumab?

A
  1. Post-menopausal osteoporosis
  2. Cancers (such as prostate and breast)
36
Q

Denosumab is generally well tolerated, but three concerns about its use linger. What are they?

A
  1. A number of cells in the immune system also express RANKL suggesting there could be an increased risk of infection associated with use.
  2. Because suppression of bone turnover is similar to potent bisphosphonates, risk of osteonecrosis of the jaw and subtrochanteric fractures may be increased (although this has not been reported in clinical trials leading up to FDA approval).
  3. Can lead to transient hypocalcemia, especially in patients with marked bone loss (and bone hunger) or compromised calcium regulatory mechanisms including chronic kidney disease and vitamin D deficiency.
37
Q

What is the MOA of calcimimetics?

A

Activates CaSR, which is widely distributed but has greatest concentration in parathyroid gland. Activation leads to inhibition of PTH secretion.

38
Q

What are the main features of hypocalcemia? (give 5)

A
  1. Tetany
  2. paresthesias
  3. laryngospasm
  4. muscle cramps
  5. seizures
39
Q

What are the main features of hypercalcemia?

A
  1. Painful bones
  2. Renal stones
  3. Abdominal Groans
  4. Psychic moans
40
Q

What are the five components of the treatment approach to hypercalcemia?

A
  1. Saline diuresis +/- furosemide
  2. Bisphosphonates
  3. Calcitonin
  4. Phosphate
  5. Glucocorticoids
41
Q

What are the two primary components of the treatment approach to hypocalcemia?

A
  1. Calcium IV, IM, or PO
  2. Vitamin D, calcitriol when rapid action required (raises serum Ca2+ within 24-48 hours).
42
Q

Osteoporosis is defined as abnormal loss of bone predisposing patient to fractures. Most common in post-menopausal women but also occurs in men. It is commonly associated with loss of gonadal function (i.e., menopause), but may also occur as an adverse effect of long-term glucocorticoid use, manifestation of endocrine disease (i.e., thyrotoxicosis), malabsorption syndrome, as a consequence of alcohol abuse or cigarette smoking, or without obvious cause (idiopathic).

What are the six main treatment options?

A
  1. Bisphosphonates
  2. SERMs
  3. Calcium and vitamin D supplementation
  4. Teriparatide
  5. Calcitonin
  6. Denosumab
43
Q

Post-menopausal osteoporosis due to reduced estrogen production and may be treated with estrogen, however concerns abound that decrease physicians enthusiasm about using this approach.

What are these concerns?

A

Estrogen increases the risk of breast cancer and fails to reduce (may actually increase) heart disease has reduced enthusiasm for estrogen therapy.

44
Q

A 57 year old man presents with pain in his shins, thighs, pelvis and clavicles. On PE you find that these areas feel warm to the touch. You order labs and recieve the following

Serum calcium: 9.8 mg/dL

Serum PTH: 25 mg/dL

Alkaline Phosphatase = 931 mg/dL

What are the approved first line treatment options for this condition?

A

Calcitonin and bisphosphonates (Alendronate, etidronate, risedronate, and tiludronate all are approved).

45
Q

Using the bisphonates and calcitonin to treat pagets disease has what common results?

A
  1. Often, patients who respond well initially to calcitonin lose response.
  2. Long-term (months to years) remission may be expected in patients who respond to bisphosphonates.
46
Q

Treatment of Paget’s disease with bisphosphonates should not exceed how long?

When can it be repeated if needed?

A

Not more than 6 months.

Can repeat after 6 months if needed.

47
Q

The patient from a few questions ago with Pagets comes back to your office complaining that he has had nausea and intestinal cramping. He also has a new rash on his torso. On PE you observe that he is not wearing a ring, but has a wedding band tan line. On further questioning he reports that recently his wedding band no longer fits him.

What medication is causing this patients problems?

A

Calcitonin - ADRs include…

  1. Nausea
  2. Urticaria
  3. intestinal cramping
  4. hand swelling
48
Q

Your 55 y/o recently post-menopausal patient comes to you complaining of hot flashes and leg cramps.

What medication is likely responsible?

What other ADR does this medication predispose her to?

A

Raloxifene, ADRs include…

  1. Hot flashes
  2. Leg cramps
  3. Thromboembolism
49
Q

The patient you were treating for Pagets just can’t catch a break. They come back to you with a subtrochanteric femur fracture after their grandchild bumped into them. Why did this happen?

A

Bisphosphonate use is associated with subtrochanteric femur fractures d/t over-suppression of bone turnover.

50
Q

Your Paget patient presents to your office with reports of trouble voiding his bladder and repeated urination attempts at night. He reports an unintentional 8lb weight loss over the past two months. You find a positive Lloyds sign on the left. You order labs and find that his serum calcium is 25 mg/dL. Bone scan shows the usual pagets deposition pattern but with the additional appearance of lytic lesions in the spine.

In order to control the spread of the bone metastasis and cancer induced hypercalcemia you change his Alendronate to what drug?

What do you need to be sure to tell the patient about risk wise?

A

Zolendronate

Zolendronate

  1. Osteonecrosis of the jaw (very rare; more frequent with high intravenous doses of zoledronate used to control bone metastases and cancer induced hypercalcemia).
51
Q

MOA for estrogen in bone diseases?

A

Prevents maturation of osteoclast precursors to mature osteoclasts

Endocrine II - Exam 2 (16 decks)

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