Osteoporosis Pharmacology Flashcards
Two OTC supplements commonly used that affect calcium regulation
Calcium salts
Vitamin D supplements
Similar in structure and function to human calcitonin synthesized by thyroid, but has a longer half-life and greater potency
Calcitonin-salmon
Effects of calcitonin-salmon on calcium regulation
Inhibits activity of osteoclasts to decrease bone resorption
Inhibits renal tubular resorption of calcium to increase calcium excretion
Clinical applications of calcitonin-salmon
Used for tx of established osteoporosis, but not prevention
Also used in Paget disease of bone
Can treat hypercalcemia but not a preferred target
AEs of calcitonin salmon
Generally very safe
Intranasal dosing can cause dryness and irritation
Parenteral dosing can cause inflammatory reaction at the injection site
Neutralizing antibodies appear in some pts over time
Name the bisphosphonates used to inhibit bone resorption in osteoporosis
Alendronate Risedronate Ibandronate Tiludronate Zolendronic acid
MOA of the bisphosphonates (i.e., alendronate)
Structural analogs of pyrophosphate, a normal constituent of bone
Undergo incorporation into bone, then inhibit bone resorption by decreasing both the number and activity of osteoclasts
Clinical applications of the bisphosphonates
Drugs of first choice for:
Postmenopausal osteoporosis
Osteoporosis in men
Glucocorticoid-induced osteoporosis
Paget disease of bone
Hypercalcemia of malignancy
AEs of the bisphosphonates
Esophagitis +/- ulceration (minimized by taking with glass of water on empty stomach)
Ocular inflammation
Osteonecrosis of the jaw
Atypical femur fractures
Atrial fibrillation
Bisphosphonate most commonly associated with osteonecrosis of the jaw (often occurring after tooth extraction or some other dental procedure in cancer pts), and is also associated with dose-dependent kidney damage and rarely atrial fibrillation
Zolendronic acid
MOA of raloxifene
Selective estrogen receptor modulator (SERM)
Exerts estrogen effects in bone
Anti-estrogenic in breast and uterus
SERM that is not generally used to tx osteoporosis
Tamoxifen
Clinical applications of raloxifene
Due to its estrogen agonist effects on bone, it is used to prevent AND treat postmenopausal osteoporosis
Due to its antiestrogenic effects on the breast, used to reduce the risk for development (but not treat) estrogen-dependent breast cancer
AEs of raloxifene
Increased risk of DVT, PE, and stroke (discontinue in anticipation of prolonged immobilization)
Pregnancy risk category X — leads to many fetal anomalies and fetal death
Can cause hot flashes in women previously asymptomatic
What is the only drug for osteoporosis that increases bone formation?
Teriparatide (PTH 1-34)
[Clinical indications include tx of postmenopausal osteoporosis, osteoporosis in men, and glucocorticoid-induced osteoporosis]
MOA of teriparatide
Truncated (1-34) version of endogenous 1-84 PTH made by recombinant DNA technology that retains the activity of full length PTH
Teriparatide is the only drug that increases bone formation. How does it do this?
Increases bone resorption by osteoclasts and increases bone deposition by osteoblasts
When given continuously, bone resorption by osteoclasts predominates
When given daily using PULSED therapy, osteoblast responses predominate
Monoclonal Ab that is a first-in-class RANKL inhibitor; thus, by binding to RANKL it decreases the formation and function of osteoclasts, decreasing the bone resorption with increased bone mass density and bone strength
Denosumab
Clinical applications of denosumab
Treatment of osteoporosis in postmenopausal women at high risk for fractures
Prevention of skeletal-related events in pts with bone metastases from solid tumors (uses a much higher dosage)
Denosumab should be taken with ____ and ______ to prevent hypocalcemia
Calcium; vitamin D
AEs of teriparatide [not an LO]
Generally well tolerated but AEs include nausea, headache, back pain, and leg cramps
Levels of serum Ca, Mg, and uric acid rise transiently but return to normal over several weeks
AEs of denosumab [not an LO]
In women with osteoporosis, AEs include back pain, pain in extremities, MSK pain, hypercholesterolemia, UTI
In bone mets pts, AEs include fatigue, hypophosphatemia, and nausea
In all pts: delayed fracture healing, increased risk of new fractures, osteonecrosis of the jaw, skin reaction not limited to injection site, and slightly increased risk of severe infections
“Calcimimetic” drug that binds to the calcium-sensing receptors on the parathyroid gland, both increasing their sensitivity to extracellular calcium, and decreasing PTH secretion
Cinacalcet
Clinical applications for cinacalcet
Primary hyperparathyroidism (parathyroid carcinoma)
Secondary hyperparathyroidism due to CKD
T/F: No pharmacotherapy convincingly reverses (or even slows) the joint damage seen in osteoarthritis
True
List dietary supplements used for osteoarthritis despite a lack of evidence of meaningful benefit
Glucosamine
Chondroitin
Dimethyl sulfoxide (DMSO)
S-adenosyl-L-methionine (SAMe)
OTC Herbal remedies used for osteoarthritis that lack both reliable evidence of benefit and consistency in preparation
Devil’s claw
Stinging nettle
Rose hips
Avocado soybean unsaponifiables
_______ is utilized to treat the pain of noninflammatory osteoarthritis
Acetaminophen
_______ are used to treat inflammatory osteoarthritis, or non-inflammatory OA that is refractory to acetaminophen
NSAIDs
Topical treatments utilized to treat pain of osteoarthritis
Topical NSAID: 1% diclofenec gel
Capsaicin
Osteoarthritis pain that is resistant to acetaminophen, NSAIDs, or capsaicin, may be treated with what other options?
Opioid analgesics
Intra-articular hyaluronans
Glucosamine and chondroitin compounds (safe to use even if lack of benefit)
Challenges associated with antibiotic treatment of osteomyelitis
Canaliculi are big enough for bacteria, but too small for white cells, so the antibiotic needs to penetrate in there or the bone needs to be destroyed to get at them
Blood flow may also be compromised
Effective oral antibiotics used to tx osteomyelitis
Clindamycin
Rifampin
Trimethoprim-sulfamethoxazole
Fluoroquinolones
