Osteoporosis Drugs Flashcards
Osteocytes signal what 2 types of cells?
Osteoblasts and osteoclasts
What type of cells break down and resorb bone?
Osteoclasts
What type of cells form and deposit bone?
Osteoblasts
What is the primary regulator of osteoclasts?
Osteoblasts
Is bone remodeling resorption or formation dominant?
Resorption dominant (clasts > blasts) (3 weeks to dig pit, 3-4 months for new bone formation)
What is the key for osteoporosis treatment and fracture prevention?
Decreasing bone resorption
What is the progression of a monocyte in bone remodeling? (4 steps)
Monocyte → preosteoclast → osteoclast → bone resorption
What is the progression of stem cells in bone remodeling? (4 steps)
Stem cells → preosteoblasts → osteoblasts → release RANKL and OPG
What has a positive feedback mechanism with osteoclast formation?
RANKL
What inhibits RANKL?
OPG
What 4 things regulate bone remodeling?
PTH, vit D, calcitonin, estrogen
When is PTH release stimulated?
Low serum blood calcium (via calcium sensing receptor, CaSR)
How does PTH increase circulating calcium?
↑ osteoclast activity and # via RANKL
How does vitamin D increase circulating calcium? (2)
↑ intestinal absorption and ↓ renal excretion, stimulates osteoclast activity through RANKL (in combo w/ PTH)
How does calcitonin decrease circulating calcium?
Inhibits osteoclasts to ↓ resorption (also ↓ renal reabsorption)
What stimulates calcitonin release?
High circulating calcium
When does calcitonin contribute to bone maintenance?
Pregnancy and lactation
What does estrogen increase? Decrease?
↓ IL-6 (pro-osteoclast) ↑ OPG (inhibitor of RANKL)
What condition is described as the following: Bone mass is decreased Structural integrity of trabecular bone is impaired Cortical bone becomes more porous and thinner Makes bones weaker/ more likely to fracture
Osteoporosis
How many standard deviations from N is defined as osteoporosis?
2.5
How many standard deviations from N is defined as osteopenia?
1
What leads to a 14% death rate from osteoporosis?
Hip fractures leading to subsequent consequences (another common complication = spinal compression fractures (often unknown to pt))
What is the greatest RF for osteoporosis?
Postmenopausal women
Besides postmenopausal women, what are other less prominent RF’s for osteoporosis? (4)
Long-term glucocorticoid use Thyrotoxicosis Alcoholism Malabsorption syndrome
What is the DOC for osteoporosis? (drug class)
Bisphosphonates
What are other treatment options for osteoporosis besides bisphosphonates (DOC)? (general)
Calcium and vit D (not always enough on their own), HRT- estrogen, SERMs, calcium regulating hormones
What is the MOA for calcium and vit D?
Increase circulating calcium
What is the use for calcium and vit D?
Use in combo for osteoporosis (cannot prevent/ treat osteoporosis alone/ adequate calcium intake needed for any other treatment to work/ vit D must be adequate for optimal absorption of calcium)
What is the preferred route of administration for calcium?
Chewable (not all preparations absorbed equally)
Calcitonin drug class?
Hormone drugs (also includes estrogen and raloxifene)
What is the MAO for calcitonin? (2)
Decrease bone resorption of calcium, antagonizes PTH hormone
What is the use of calcitonin? (2)
Osteoporosis (not 1st line), Paget’s disease
What are the 2 possible routes of administration for calcitonin?
Nasal spray or injection
What are the SEs of calcitonin? (3)
Allergy, rhinitis/ sinusitis (nasal spray), N/V (injection) (salmon calcitonin = more active but cannot use if allergy)
What is the MOA of teriparatide and abaloparatide?
PTH receptor type 1- RG agonist
What is the use for teriparatide and abaloparatide?
Osteoporosis (more osteoblast activity) and formation of new bone (only anabolic drugs for osteoporosis)
What route of adminitration allows Teriparatide to have intermittent effects?
S.C. injection, short t1/2 = peaks in 30 min, gone in 3 hours
What are the SEs of both Teriparatide and Abaloparatide?
Hypercalcemia and hypercalciuria
Teriparatide and Abaloparatide can both cause hypercalcemia and hypercalciuria. What is an additional SE of just Abaloparatide?
Hyperuricemia
Teriparatide and Abaloparatide are contraindicated in what situation?
Osteosarcoma (black label)
What is the MOA for rhPTH?
PTH receptor type 1- R0 agonist
What is the use for rhPTH?
Hypoparathyroidism (more osteoclast activity)
Teriparatide drug class?
PTH drugs
Abaloparatide drug class?
PTH drugs
rhPTH drug class?
PTH drugs
Denosumab drug class?
Rank-ligand inhibitor
What is the MOA for Denosumab? (2)
Inhibits bone resorption, Ab against RANKL = inhibits RANKL
(necessary for formation of mature osteoclasts)
Denosumab is used for the treatment of osteoporosis in what populations?
Men and postmenopausal women with high fracture risk
One of the benefits/ uses of Denosumab is the increase of what?
Bone mass and strength in cortical and trabecular bone
What is the route of admintration for Denosumab?
SC injection q 6 months
What are the contraindications for Denosumab? (3)
Hypocalcemia and pregnancy > IMC
Alendronate drug class?
Bisphosphates
Ibandronate drug class?
Bisphosphates
Risedronate drug class?
Bisphosphates
Zoledronic acid drug class?
Bisphosphates
Route of administration for Alendronate?
Oral
Route of administration for Ibandronate?
Oral/ IV
Route of administration for Risedronate?
Oral
Route of administration for Zoledronic acid?
IV
What is the primary MOA for bisphosphonates?
Substitutes for PO4 in Ca binding (incorporated into bone)
Although not the primary MOA, what drug class involves P-C-P bond analogs of pyrophosphate and inhibition of osteoclast activity and bone resorption?
Bisphosphates
What is the DOC for post-menopausal osteoporosis?
Bisphosphates
When must oral bisphosphates be taken due to very poor absorption?
Taken on empty stomach and seated upright for 30 min after taking (taken daily)
What is the SE for Bisphosphates (all routes of administration)?
Osteonecrosis of the jaw
(will limit bone turnover with each dose = dense bones (non-flexible) = brittle bone)
What is the SE for oral Bisphosphates? (2)
GI sxs/ discomfort, esophageal ulceration
What are the SEs for IV Bisphosphates? (2)
Renal toxicity (if given too fast), N/V
What are the contraindications for oral Bisphosphates? (2)
Inability to stand/ sit upright or esophageal disease
What is the contraindication for IV Bisphosphates?
Renal disease
