Exam 3: L26 Osteoporosis Flashcards
What are the major cell types involved in bone remodeling?
Osteoblasts, Osteoclasts, Osteocytes
Osteoblasts form and deposit bone, osteoclasts break down and resorb bone, and osteocytes signal the activity of both.
How do osteoblasts regulate osteoclast function?
By releasing RANK Ligand (RANKL) and interleukin-6 (IL-6)
RANKL stimulates osteoclast differentiation and activity, while osteoprotegerin (OPG) limits RANKL’s effects.
What is the definition of osteoporosis?
A bone disease where the amount of bone is decreased and structural integrity of trabecular bone is impaired
Osteoporosis results in weaker bones that are more likely to fracture.
What are the major hormones regulating bone remodeling?
Parathyroid Hormone (PTH), Vitamin D, Calcitonin, Estrogen
These hormones influence bone resorption and formation.
What is the main reason most osteoporosis drugs target resorption?
Because human bone remodeling is resorption dominant
It takes longer to fill resorption pits than to create them.
What role does estrogen play in the treatment of postmenopausal osteoporosis?
Increases osteoblast’s production of OPG and causes apoptosis of osteoclasts
This reduces osteoclast differentiation and activity, hence protecting bone density.
Which drugs have anabolic actions on bone?
Teriparatide, Abaloparatide, rhPTH (1-84)
These drugs stimulate bone formation.
What are the primary therapeutic agents for treating osteoporosis?
Calcium, Vitamin D, Hormones, Denosumab, Romosozumab, Bisphosphonates, Cinacalcet
Each category has specific drugs with unique mechanisms of action.
What is the mechanism of action of calcium in osteoporosis treatment?
Inhibition of PTH secretion and altering bone mineral properties
Adequate calcium is necessary for optimal bone health.
What are the three primary forms of Vitamin D?
Cholecalciferol (D3), Ergocalciferol (D2), Calcitriol
Calcitriol is the most active form of Vitamin D.
How does Vitamin D affect calcium levels in the body?
Increases intestinal absorption, decreases renal excretion
It works in conjunction with PTH to regulate calcium levels.
What are the adverse effects of calcium supplements?
Can inhibit iron absorption, affect thyroid medication absorption
It is important to space out the intake of calcium and iron.
What is the mechanism of action of calcitonin?
Inhibits bone resorption by osteoclasts
It antagonizes the actions of parathyroid hormone.
What are the indications for teriparatide and abaloparatide?
Treatment of osteoporosis by stimulating bone formation
These drugs are not recommended for cumulative use beyond 2 years.
What is the significance of RANK Ligand in bone remodeling?
Stimulates osteoclast differentiation and activity
It is a critical factor released by osteoblasts.
What indicates severe osteoporosis?
Osteoporosis with a fracture
It signifies a significant decrease in bone density and structural integrity.
What are the risk factors for developing osteoporosis?
Post-menopausal status, long-term glucocorticoid use, thyrotoxicosis, alcoholism, malabsorption syndrome
These factors can contribute to decreased bone density.
What is the role of sclerostin in bone remodeling?
Inhibits the WNT signaling pathway, reducing osteoblast activity
This leads to a shift toward bone resorption.
What is the recommended daily intake of elemental calcium for adults?
1,000 to 1,500 mg/day
This includes both dietary sources and supplements.
True or False: Osteopenia is always a bad condition that requires treatment.
False
Osteopenia can be part of the normal remodeling cycle and does not always require osteoporosis drugs.
What is the primary effect of estrogen on bone density?
Increases bone mineral density (BMD) and strength
This is achieved through various mechanisms including reducing osteoclast activity.
What is the affinity of PTH (1-34, aka teriparatide) for the RG conformation?
12X affinity
This refers to the increased activity of teriparatide when administered via daily injections.
How does PTHrP (1-34, aka abaloparatide) compare in affinity to PTH (1-34) for the RG conformation?
1600X affinity
This indicates a significantly greater affinity for the RG conformation than the R0 conformation.
Which conformation does rhPTH (1-84) tend to bind more stably?
R0 conformation
rhPTH (1-84) binds to both conformations but is more stable with R0.
What are the therapeutic effects of PTHR1-RG activation?
- Reduce bone turnover
- Stimulate the formation of new bone
- Increase bone mass
- Increase skeletal mass and number of osteoblasts and osteoclasts
- Increase bone strength
- Reduce incidence of new vertebral and nonvertebral fractures
These effects are significant for osteoporosis treatment.
What is a primary indication for the use of PTHR1-R0 activation with rhPTH (1-84)?
Treatment of hypoparathyroidism
This is given twice a day and is for patients not controlled with calcium and vitamin D supplements.
What is the pharmacokinetics of teriparatide when injected subcutaneously?
- Serum concentration peaks 30 minutes after administration
- Effects are gone within 3 hours
This allows for intermittent effects on the PTH receptor.
What are some common adverse effects associated with PTH treatments?
- Increases serum calcium
- Decreases serum phosphorous
- Hypercalcemia
- Hypercalciuria
- Injection site reactions
- Dizziness
- Nausea
- Headache
- Arthralgia
- Leg muscle cramps
Abaloparatide can also lead to hyperuricemia.
What is the black box warning for PTH treatments?
Osteosarcoma
Increased incidence observed in rats, but no evidence in over 300,000 human trials.
What is Denosumab (Prolia®) used for?
Treatment of osteoporosis in postmenopausal women and men at high risk for fractures
It is an alternative first-line treatment for those unable to tolerate bisphosphonates.
What is the mechanism of action for Denosumab?
Inhibits bone resorption by blocking RANK-Ligand
RANK-Ligand is necessary for the formation of mature osteoclasts.
What are the pharmacokinetics of Denosumab?
Subcutaneous injection, once every 6 months
There is no limit to the duration of Denosumab treatment.
What are some adverse effects of Denosumab?
- Hypocalcemia (2%)
- Risk of severe hypocalcemia in advanced CKD
- Serious cellulitis (0.4%)
- Eczema (10%)
- Bone and back pain
- Atypical fractures
- Osteonecrosis of the jaw (2% in high doses)
This side effect was not observed in osteoporosis studies.
What are the absolute contraindications for Denosumab?
- Hypocalcemia
- Pregnancy
Denosumab is teratogenic.
What is Romosozumab (Evenity®) indicated for?
Osteoporosis treatment in postmenopausal women at high risk for fractures
It is used for up to one year or 12 doses.
What is the mechanism of action of Romosozumab?
Humanized monoclonal antibody against sclerostin
This increases bone formation and decreases bone resorption.
What are the common adverse effects of Romosozumab?
- Arthralgia
- Headache
- Serious cardiovascular events
These should be monitored during treatment.
What are the FDA-approved bisphosphonates for osteoporosis?
- Alendronate (Fosamax®)
- Risedronate (Actonel®)
- Ibandronate (Boniva®)
- Zoledronic Acid (Zometa®, Reclast®)
These drugs are analogs of pyrophosphate.
What is the mechanism of action of bisphosphonates?
Inhibits osteoclast activity and bone resorption
They bind to calcium salts, blocking hydroxyapatite formation.
What are some adverse effects associated with oral bisphosphonate administration?
- Abdominal pain
- Heartburn
- Upper GI irritation
- Esophageal ulceration
- Constipation
- Diarrhea
- Flatulence
Patients must remain upright for 30-60 minutes to reduce GI irritation.
What should patients not take with oral bisphosphonates?
Calcium
Calcium inhibits the absorption of the medication.
What is the mechanism of action for Cinacalcet (Sensipar®)?
Oral calcimimetic drug that binds to the calcium sensing receptor
This blocks PTH release.
What are the adverse effects of Cinacalcet?
- Nausea
- Vomiting
- Anorexia
- Constipation
- Dehydration
- Hypocalcemia
- Hypercalcemia
- Asthenia
- Bone fractures
Hypocalcemia occurs in 66-80% of cases.
