Osteoporosis/Calcium and Bone disorder Drugs Flashcards
What are the non-pharmacologic treatments for osteoporosis?
Calcium and Vitamin D (Target: 25OH vitamin D > 30)
Antiresorptives include all of the following classes of drugs except:
A. Biologic
B. Hormones
C. SERM (Selective Estrogen Receptor Modulator)
D. Bisphosphonates
E. Anabolic
E. Anabolic (teriparatide)
All the others work against catabolism by osteoclasts
Raloxifene is a _____
SERM
Alendronate is a _____
Bisphosphonate, Oral
Risedronate is a _____
Bisphosphonate, Oral
Ibandronate is a _____
Bisphosphonate, Oral or IV
Zoledronic acid is a _____
Bisphosphonate, IV
Denosumab is a _____ agent used in osteoporosis treatment
Biologic
What two hormones can be used as antiresorptive/anticatabolic osteoporosis meds?
Calcitonin and Estrogen
True or False: Raloxifene is a more potent antiresorptive than denosumab and bisphosphonates
False
Raloxifene is an _____ in bone and an ______ in breast tissue
agonist, antagonist
*In bone, inhibits osteoclasts - improve BMD, decrease fracture risk
In breast, reduces risk of breast cancer
Side effects of Raloxifene include which two of the following: A. DVT B. Headaches C. Hot flushes D. Palpitations E. Thickening of endometrium
A. DVT and C. Hot flushes
*Raloxifene is neutral on cardiovascualar/endometrium
Bisphosphonates work in treating osteoporosis by
Impair osteoclast function
Decrease osteoclast differentiation and increase apoptosis
Overall effect - Increase BMD and decrease fracture risk
Side effects of bisphosphonates include all of the following except: A. Flu-like symptoms w/ IV use B. Hyponatremia C. Hypocalcemia D. Bone and muscle pain E. Esophagitis w/ oral use
B. Nope
*E. avoid oral use in patients with upper GI disease, Barret’s esophagus
Bisphosphonates are contraindicated in patients with creatinine clearance ___
Less than 30
What are the two potential long-term side effects of bisphosphonates?
Atypical subtrochanteric fractures
Osteonecrosis of the jaw
Basis of atypical subtrochanteric fractures and bisphosphonate use
Use of bisphosphonates decreases rate of bone turnover that is necessary for repair of daily wear and tear -> accumulation of microcracks in the bone -> transverse/short oblique fractures with little/no trauma
It takes a median of 7 years for subtrochanteric fractures to occur in bisphosphonate use. What can be done to prevent this?
Give the patient “drug holidays” every 4-5 years
What is osteonecrosis of the jaw?
Area of exposed necrotic bone +/- infection
- more common with IV bisphosphonates, usually after invasive dental procedures
- avoid invasive dental procedures, be hygienic!
Potential mechanism of osteonecrosis
Decreased jaw bone turn over -> accumulation of microcracks
Antiangiogenic effects of bisphosphonates -> necrosis
Invasive dental work -> microbes track into bone
Denosumab mechanism of action
Binds to RANKL (released by osteoblast) to prevent it from binding RANK receptor on osteoclasts ->prevent osteoclast differentiation/maturation
Denosumab is administered by
Subcutaneous injection every 6 months
Side effects of denosumab
Hypocalcemia
Possible increase in infections/neoplastic effects
Concern for subtrochanteric fractures and ONJ
True or False: Denosumab does not have any renal restrictions and can be used in patients with creatinine clearance
True
True or False: Calcitonin is not a potent antiresorptive, but can provide some relief of acute pain in vertebral fractures
True
Estrogen is not recommended as treatment of osteoporosis, why?
Side effects! Breast cancer and cardiovascular disease
Teriparatide is human recombinant PTH1-34, who does it differ from antiresorptives?
It’s the only current anabolic drug. Induce differentiation/maturation of osteoblasts, increase function, reduce apoptosis.
Teriparatide is administered daily by
Subcutaneous injection
*money money money, expensive, so only for severe cases or if other treatments fail or patient contraindicated
Side effects of Teriparatide
Increase uric acid - gout attacks
Hypercalcemia - small, rare
Osteosarcoma concern - 2 year lifetime Tx limit
Teriparatide is contraindicated in
Patients with high risk of osteosarcoma: kids, Paget, prior radiation
Patients with cancer in last 5 years
Patients with elevated PTH
Cessation of teriparatide results in loss of gains in BMD, what can be done to minimize this?
Follow-up with antiresorptives
Signs and Symptoms of hypercalcemia
CNS: fatigue, lethargy, depression
Neuromuscular: weakness
Cardiovascular: HTN, bradycardia, Short QT
Renal: polyuria, fluid depletion, kidney stoens
GI: nausea, vomiting, constipation, anorexia
Cinacalcet is a
calcimimetic
- mimics calcium, binds CaSR on parathyroid cells, decrease PTH secretion -> decrease serum calcium
- used in cases of very high calcium in primary hyperparathyroidism
Main side effect of cinacalcet
nausea
Symptoms and Signs of hypocalcemia
Neuromuscular: parasthesias (fingers/around mouth), tetany, seizures, confusion/fatigue/depression
Cardiac: Prolonged QT
PE: carpopedal spasm and Chvostek’s sign
If PTH is low, serum phosphrus will be ____
High. PTH is needed to promote renal P excretion
If PTH is low, urine calcium is ____
High. PTH needed to promote renal calcium reabsorption
List 4 causes of PTH elevation with low serum calcium
Poor calcium intake Vitamin D deficiency PTH resistance (pseudohypoparathyroidism) Vitamin D resistance
