Therapy of Osteoporosis Flashcards
Osteoporosis is a bone disorder characterized by:
1) Low bone mineral density
2) Impaired bone architecture
3) Compromised bone strength
Risk factors for osteoporosis?
1) Female gender
2) Advanced age
3) Low body weight
4) Systemic oral glucocorticoid therapy
5) Cigarette smoking
6) Alcohol (3 or more drinks/day)
7) Low calcium intake
8) Low physical activity
9) Vitamin D insufficiency and deficiency
Which drugs can cause osteoporosis?
1) Glucocorticoids
2) Proton pump inhibitors (PPIs)
3) Antidepressants
4) Aromatase inhibitors
5) Androgen-Deprivation Therapy (GnRH)
6) Anticonvulsant therapy
7) Furosemide
8) Heparin
9) Thiazolidinediones
10) Canagliflozin (SGLT2 inhibitors)
In people taking glucocorticoids, fracture risk increases before ___ are detected.
Changes in bone mass density
What do glucocorticoids do?
1) Decrease osteocyte and osteoblast function
2) Increase osteocyte and osteoblast apoptosis
3) Increase osteoclast proliferation
4) Decrease osteoclast apoptosis
What do glucocorticoids do in reference to calcium?
1) Decrease calcium absorption
2) Increase urinary calcium excretion
Via alterations in calcium transporters
How do antidepressants cause osteoporosis?
Increased peripheral serotonin levels = Increased osteoclastic activity
How do aromatase inhibitors cause osteoporosis?
Reduce peripheral estrogen levels =
1) Upregulates osteoclast formation
2) Increases the lifespan of osteoclasts
Estrogen deficiency leads to:
1) Increased bone loss
2) Cortical porosity
3) Enlarged resorption areas
How does androgen-deprivation therapy cause osteoporosis?
Increases interleukin-6 (IL-6) = Stimulates osteoclastogenesis.
What do androgen receptors (ARs) on osteoblasts do?
Promote osteoblast differentiation = Decreases bone resorption.
How does Furosemide cause osteoporosis?
Via increased calcium excretion by the kidney
The primary goal of osteoporosis care should be:
Prevention
What should you do to reduce the future incidence of osteoporosis?
Optimize skeletal development and peak bone mass gain in childhood, adolescence, and early adulthood
Once low bone mass or osteoporosis develops, the objective is to:
1) Stabilize bone
2) Improve bone strength and mass
3) Prevent fractures
In patients who have already suffered osteoporotic fractures, the objective is to:
1) Reduce pain and deformity
2) Improve functional capacity
3) Improve quality of life
4) Reduce future falls and fractures
What is the first step in prevention and treatment of osteoporosis?
Adequate intake of calcium and vitamin D
___ is advised in any postmenopausal woman, or man age 50 years and older, presenting with a hip or vertebral fracture or low bone mass.
Prescription therapy
What increases calcium absorption?
1) Carbohydrates
2) Fat
3) Lactose
What decreases calcium absorption?
1) Fiber
2) Wheat bran
3) Phytates (beans)
4) Oxylates (spinach)
5) High-protein diets
6) Caffeine
7) Smoking
What are the 3 main sources of vitamin D?
1) Sunlight
2) Diet
3) Supplements
Vitamin D3 and D2 come from:
1) Oily fish
2) Eggs
3) Fortified dairy products
Inadequate concentrations of which form of vitamin D are common?
25(OH) vitamin D
Low vitamin D concentrations result from:
1) Insufficient intake
2) Dietary fat malabsorption
3) Decreased sun exposure
4) Decreased skin production
5) Decreased liver and renal metabolism of vitamin D
Endogenous synthesis of vitamin D can be decreased by:
Sunscreen use
Darkly pigmented skin can ___(increase/decrease) vitamin D production.
Decrease
When are the troughs and peaks in vitamin D in respect to the seasons?
Troughs: Late winter
Peaks: Late summer
How does alcohol increase the risk for fractures and osteoporosis?
1) Increases bone resorption and decreases bone formation by inhibiting signaling pathways
2) Increasing oxidative stress that results in osteoblast apoptosis
Alcoholics may have:
1) Poor nutrition
2) Decreased calcium absorption
3) Altered vitamin D metabolism
4) Impaired balance
Excessive caffeine consumption may be associated with:
1) Increased calcium excretion
2) Increased rates of bone loss
3) Modestly increased risk for fractures
The effect of smoking on bone mass density is dependent on what?
1) Dose
2) Duration
How does smoking increase the risk of osteoporosis and fractures?
1) Reduces intestinal calcium absorption
2) Increases 25(OH) vitamin D catabolism
How does exercise decrease the risk of falls and fractures?
1) Stabilizes bone density
2) Improves muscle strength, coordination, balance, and mobility.
Lack of physical activity can lead to:
1) Suboptimal loading/straining
2) Decreased stimulation of bone deposition
3) Reduced peak bone mass
All patients who are medically fit should be encouraged to perform:
1) A moderate-intensity weight bearing activity (walking, jogging, golf, and stair climbing) daily.
2) A resistance activity (weight machines, free weights, or elastic bands).
First line osteoporosis treatments?
1) Bisphosphonates
2) Calcium
3) Vitamin D intake
4) Denosumab
Which drugs are first line bisphosphonates?
1) Alendronate
2) Risedronate
3) Zoledronic acid
Which drugs are alternatives for osteoporosis?
1) Ibandronate (Bisphosphonate)
2) Teriparatide (PTH analog)
3) Raloxifene (Selective Estrogen Receptor Modulators (SERMS)
Which drug is last line for osteoporosis?
Calcitonin
Antiresorptive therapies include:
1) Calcium
2) Vitamin D
3) Bisphosphonates
4) Denosumab
5) Estrogen agonists/antagonists (Selective estrogen receptor modulators (SERMs))
6) Tissue selective estrogen complexes
7) Calcitonin
8) Estrogen
9) Testosterone
Calcium supplements should be combined with:
Vitamin D
Adverse effects of calcium supplementation?
1) Constipation
2) Gas and cause stomach upset
3) May increase kidney stones
Which drugs decrease calcium absorption?
1) Proton pump inhibitors
2) Fiber laxatives
Calcium can decrease the oral absorption of some drugs including:
1) Iron
2) Tetracyclines
3) Quinolones
4) Bisphosphonates
5) Thyroid supplements
Vitamin D daily maintenance dose?
800-2,000 units daily
___ is the best indicator of total body vitamin D status.
Serum 25(OH) vitamin D
Which drugs can induce vitamin D metabolism?
1) Rifampin
2) Phenytoin
3) Barbiturates
4) Carbamazepine
Vitamin D absorption can be decreased by:
1) Cholestyramine
2) Colestipol
3) Orlistat
4) Mineral oil
___ are indicated for postmenopausal females, males, and glucocorticoid-induced osteoporosis.
Bisphosphonates
Intravenous and oral ___ is indicated only for postmenopausal osteoporosis.
Ibandronate
Bisphosphonates are analogs of:
Pyrophosphate
Intravenous and oral Ibandronate is indicated
only for:
Postmenopausal osteoporosis
What is pyrophosphate?
An endogenous bone resorption inhibitor
What do bisphosphonates do?
Decrease osteoclast:
1) Maturation
2) Number
3) Recruitment
4) Bone adhesion
5) Life span
Bisphosphonates delay formation and dissolution of:
Hydroxyapatite crystals
Bisphosphonates localize to regions of:
Bone resorption
The effect of bisphosphonates is ___-dependent and greatest when?
Dose; in the first year of therapy.
Adverse effects of bisphosphonates?
1) GI complaints (Most common)
a) Heartburn
b) Dyspepsia
c) Esophageal erosion
d) Esophageal ulceration
e) GI bleeding
2) Injection reactions and musculoskeletal pain
3) Fever, flu-like symptoms, myalgias, and arthralgias with IV administration
4) Osteonecrosis of the jaw
5) Atypical subtrochanteric femoral fractures
What alternatives are used if bisphosphonates cause GI upset?
1) IV Ibandronate
2) IV Zoledronic acid
Contraindications for bisphosphonates?
1) Patients with creatinine clearances <30-35 mL/min
2) Patients who have serious GI upset, peptic ulcer disease, or esophageal motility disorders
3) Pregnant patients
How should you take bisphosphonates?
1) Take 180 mL of plain water at least 30-60 minutes before consuming anything
2) Remain upright for at least 30-60 minutes after administration
When can a patient who misses a weekly bisphosphonate dose take it?
The next day
A patient missed a weekly bisphosphonate dose and realized it 3 days later. When can they take it?
Skip that dose and wait for the next weekly dose.
A patient missed a monthly bisphosphonate dose, but the next dose is 7 days away. When can they take it?
Take it now
A patient missed a monthly bisphosphonate dose, but the next dose is 6 days away. When can they take it?
Skip it and wait for the next dose
Before IV bisphosphonates are used, the patient’s serum __ concentration must be normalized.
Calcium
___ should be monitored before each dose of zoledronic acid.
Creatinine clearance
How is the quarterly ibandronate injection given?
Slowly, intravenously over 15 - 30 seconds.
How can Ibandronate be given?
1) Injection
2) Infusion
How do you administer once-yearly zoledronic acid?
Infused over at least 15 minutes with a pump
___ can be given to decrease acute phase reactions in bisphosphonates.
Acetaminophen
Which problem in bisphosphonates causes decreased effectiveness?
Poor adherence (Low patient compliance)
A drug holiday could be considered in postmenopausal women after _ years of oral
bisphosphonates or _ years of intravenous bisphosphonates.
5; 3
What is another therapeutic use for bisphosphonates?
Hypercalcemia associated with malignancy
When is Denosumab indicated?
1) In women and men at high risk of fractures
2) To increase bone mass in men receiving androgen deprivation therapy or LHRH agonists for nonmetastatic prostate cancer
3) In women receiving adjuvant aromatase inhibitor therapy for breast cancer who are at high risk of fractures
What is Flutamide?
Antiandrogens
What is Leuprolide?
LHRH agonist
What is Anastrozole?
Aromatase inhibitor
Denosumab binds to:
RANKL
Denosumab mechanism of action?
Inhibits RANKL binding to its RANK receptor on the surface of osteoclast precursor cells and mature osteoclasts
What does the RANK receptor activate?
Nuclear factor-κb
RANKL/RANK signaling regulates the formation
of:
Multinucleated osteoclasts from their precursors as well as their activation and survival in normal bone remodeling =
1) Inhibits osteoclastogenesis
2) Increases osteoclast apoptosis
Following subcutaneous injection of Denosumab, rapid suppression of bone turnover occurs within:
12 hours
Denosumab’s bone mass density effects are similar to:
Weekly alendronate
Activity of Denosumab dissipates with:
Drug discontinuation
Adverse effects of Denosumab?
1) Dermatitis, eczema, and rashes
2) Marked bone turnover suppression = Muscle, bone, and joint pain and atypical femoral fractures
3) Serious infections including skin infections
4) Hypocalcemia
What should you monitor within 14 days of administering Denosumab if the patient has a ClCr < 30 mL/min?
1) Serum calcium
2) Serum Magnesium
3) Serum Phosphorus
