drugs affecting the bones and joints - bone health Flashcards
(22 cards)
Nuclear factor kappa B ligand (RANKL)
Helps with activation of the osteoclasts to start the bone remodeling process that is a natural method for the body to replace bone over time
osteoprotegrin (OPG)
a protein that is key in the conversation between osteoblasts and osteoclasts
OPG binds to OPG-ligand
- Prevents the action of osteoclasts
- Stimulates the action of osteoblasts
Balance of OPG and OPG-ligand appears to control bone resorption and growth
- Medications have been developed to affect the balance between these two
osteoporosis
having a bone density 2.5 standard deviations below the average adult peak bone mass
the bone remodeling cycle is initiated by osteoclastic activity
- In response to microfractures and other damage associated with normal wear and tear, osteoclasts are drawn to the damaged area of trabecula, attach to its surface, and resorb the damaged and surrounding bone, creating a resorption pit
- Resorption is accomplished by pseudopodia, which attach tightly to the bone surface and secrete acids and enzymes that dissolve the bone
- Osteoclasts leave and osteoblasts move in, line up to cover the surface of the pit, and form new bone
- RANKL facilitates osteoclast formation
- Monoclonal antibodies modify bone remodeling by reducing RANKL action
bisphosphonates
Bisphosphonates adhere tightly to bone, and by inhibiting osteoclastic activity, are potent inhibitors of both normal and abnormal bone resorption
- Considered first-line treatment for women and men with osteoporosis or at increased risk who have no contraindications
bisphosphonate medications
- Etidronate (Didronel)
- Pamidronate (Aredia) and risedronate (Actonel)
- Alendronate (Fosamax)
- Zoledronic acid (Zometa)
- Ibandronate (Boniva)
etidronate (Didronel)
Reduces both bone resorption and bone formation because formation is coupled with resorption
Pamidronate (Aredia) and risedronate (Actonel)
Inhibit bone resorption without inhibiting bone formation and mineralization
alendronate (Fosamax)
- Highly selective inhibitor of bone resorption
- 100-500 more potent than the other drugs
- Does not interfere with osteoclast recruitment or attachment, but it does inhibit osteoclast activity
zoledronic acid (Zometa)
- Inhibits osteoclastic activity and induces osteoclast apoptosis
- Inhibits the increased osteoclastic activity and skeletal calcium release induced by various stimulatory factors released by tumors
ibandronate (Boniva)
Inhibits osteoclastic activity and reduces bone resorption and turnover based on its affinity for hydroxyapatite, which is part of the mineral matrix of the bone
absolute contraindications for bisphosphonates
o Uncorrected hypocalcemia
o Documented Barrett esophagus
o Renal insufficiency
Raloxifene (Evista)
A SERM approved for preventing and treating postmenopausal osteoporosis
- Reduces the resorption of bone with less risk for CV effects than estrogen
- Also has positive effects on lipid metabolism by decreasing total and LDL cholesterol levels
- Block estrogen binding
- But free serum estrogen remains in the system –> Associated with hot flashes
Guidelines do not recommend raloxifene for primary prevention of osteoporotic fragility fracture in postmenopausal women, but it is used as a second-line drug for secondary therapy
human parathyroid hormone drugs pharmacodynamics
The growth of bone, its response to mechanical stressors, and its role in storage of minerals depends on the proper functioning of circulating hormones that respond to changes in serum calcium and phosphorus levels
- If calcium or phosphorus levels are low -> PTH stimulates osteoclasts to resorb bone
- Calcium and phosphorus are released into the bloodstream
o Estrogens reduce bone resorption stimulated by PTH
o Natural calcitonin balances PTH by shutting down osteoclastic activity and increasing osteoblastic activity in the presence of hypercalcemia
PTH drugs
- Teriparatide (Forteo)
- abaloparatide (Tymlos)
Teriparatide (Forteo) and abaloparatide (Tymlos)
are synthetic injectable PTH analogs derived from recombinant DNA technology
- These drugs stimulate bone formation, especially in the axial skeleton
- Once-daily subcutaneous doses
- Preferential stimulation of osteoblastic activity over osteoclastic activity
Third-line drugs in treating osteoporosis
- Ordered by specialists
- Monitored in primary care
adverse effects of PTH drugs
- Can cause orthostatic hypotension and hypercalcemia
- Have a potential increased risk for osteosarcoma
RANKL inhibitors
Considered second-line therapy
- Used for those who do not respond to bisphosphonate therapy, those who are unable to tolerate bisphosphonates, or cancer patients with bone metastasis
Denosumab (Prolia)
- A human antibody against RANKL
- Inhibits osteoclast survival and function
Romosozumb (Evenity)
One of the newest treatment options for patients with osteoporosis
A monoclonal antibody that works by inhibiting sclerostin
- Allows for an increase in new bone formation while decreasing bone resorption for breakdown
Should only be considered if the patient is unable to tolerate either a bisphosphonate or denosumab and is at very high risk for osteoporosis-related fracture
rational drug selection for all bone health drugs
- Bisphosphonates are first-line therapy for osteoporosis
- Estrogen and SERMs are 2nd line medications for osteoporosis
- Synthetic PTH and RANKL inhibitor drugs have specific indications
- Carry cost issues and possible cancer risks - Calcium, especially when combined with vitamin D, is central to prevention of osteoporosis
