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What are the five Classes of bone drugs?
- Selective Estrogen Receptor Modulators
- Parathyroid hormone
What is the general action of all drugs that treat osteoporosis?
Increase bone mineral density
Salmon Calcitonin (Miacalcin) is what type of molecule?
32 amino acid peptide
What is the action of Salmon Calcitonin (Miacalcin)?
- Decreases osteoclast attachment to bone, life span and numbers
- Inhibits bone resorption.
What is the route of administration of Salmon Calcitonin (Miacalcin)?
SQ or as a nasal spray
(True/False) Salmon Calcitonin (Miacalcin) is more potent and has a long duration of action due to greater metabolic resistance than Human Calcitonin and has an analgesic effect.
What are the Adverse effects of Salmon Calcitonin (Miacalcin)?
- Nasal irritation/ulceration, nausea, flushing, injection site reactions
- long term - increase cancer rates
What is the Therapeutic use of Salmon Calcitonin (Miacalcin)?
- Osteoporosis: increases bone density
- Limited effectiveness: 2nd line drug.
Why is potency an issue with Calcitonin?
Only a small amount is absorbed
Bisphosphonates have what activity?
- Incorporated into bone and inhibit osteoclast function (make hydrogen ions, and collagenase), metabolic activity and proliferation
- Inhibit farnesyl diphosphate synthase = block the production of farnesyl groups
- Prevent protein prenylation
What drugs are in the Bisphosphonate class?
- Alendronate (Fosamax)
- Risedronate (Actonel)
- Ibandronate (Boniva)
- Zoledronic acid (Reclast)
What percent of Bisphosphonates are absorbed?
What effects Bisphosphonate absorption and how should you counsel patients to take them?
- Reduced by food
- Take before breakfast with water only
What are the Adverse effects of Bisphosphonates?
- Musculoskeletal pain
- gastric irritation/ulcer
- osteonecrosis of the jaw
- femur fractures
- hypocalcemia (iv)
What are the Therapeutic uses of Bisphosphonates?
- #1 = Osteoporosis
- Increase bone density
- Reduce fractures
How are Bisphosphonates administered?
- Daily, intermittent (weekly or monthly at higher doses)
- Oral (usually but can be IV)
- Take standing or sitting (not lying = encourages esophageal ulceration)
What is unique about Zoledronic acid (Reclast)?
Given annually IV
Why can Bisphosphonates be given at long intervals like annually, weekly or monthly?
They bind to the bone and stay for a long period of time
What is the Selective Estrogen receptor modulator?
What is the MOA of Raloxifene (SERM)?
- Stimulate estrogen receptors on osteoblasts to inhibit production of interleukin-6 (IL-6)
- Stimulates estrogen receptors in bone
- Inhibits estrogen receptors in breast and uterus
- Can inhibit or stimulate receptors on other tissues
- Action decreases:
- Osteoclast formation
- Bone resorption
What are the Therapeutic uses of Raloxifene (SERM)?
- Postmenopausal osteoporosis
- Increases bone density
- Reduces fractures
- Decreases LDL cholesterol
- Reduced risk of breast cancer
What are the adverse effects of Raloxifene (SERM)?
- Blood clots, deep vein thrombosis, stroke death
- Hot flashes, leg cramps, peripheral edema (by inhibiting the effects of estrogen)
What type of drug is Teriparatide (Forteo)?
Recombinant Parathyroid Hormone (1-34) Fragment
What is the MOA of Teriparatide (Forteo)?
- Anabolic agent that increases bone remodeling
- Stimulates osteoblasts and bone formation > bone resorption.
What are the Adverse Effects of Teriparatide (Forteo)?
- Orthostatic hypotension, leg cramps, joint pain
- Hypercalcemia (increases serum Ca)
- Osteosarcoma in animals
What are the Use of Teriparatide (Forteo)?
Severe or refractory osteoporosis when other drugs haven’t worked
How is Teriparatide (Forteo) administered?
- Daily subcutaneous injections for 18- 4 months
- Then replaced by another drug like a Bisphosphonate
What are the positive effects of Teriparatide (Forteo)?
Increases bone density, decreases fractures.
Is Teriparatide (Forteo) very effective at reducing risk of fractures?
Denosumab (Prolia) has what action?
- Binds receptor activator of nuclear factor kappa-beta ligand (RANKL), which prevents RANK receptor stimulation of osteoclasts
- Decreases osteoclasts and bone resorption
What is Denosumab (Prolia) contraindicated in?
Hypocalcemia (causes this)
What are the Adverse Effects of Denosumab (Prolia)?
- Dermatitis, rash (b/c and antibody)
- Possible osteonecrosis of the jaw and femur fractures
- Back and musculoskeletal pain
What is Denosumab (Prolia) used for?
High risk osteoporosis
How is Denosumab (Prolia) given?
- SQ once every 6 months
- Given with Ca and vitamin D
What is the end effect of taking Denosumab (Prolia)?
- Decreased fractures
- Increased bone mineral density
What type of molecule is Denosumab (Prolia)?
What is the RDA for Ca?
What is the UL for Ca?
What is the RDA for Vit D?
What is the UL for Vit D?
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