Chapter 73 RAT Material Flashcards
Define osteoporosis
Disease characterized by low bone density, impaired tone architecture, and weakened bone strength
Explain the pathophysiology of osteoporosis
It depends on sex,age, diet, genetics, and presence of secondary causes. (endocrine, GI, Inflammatory, chronic illness, immobility/disuse, genetic)
Female (Postmenopausal) - estrogen deficiency results in increased osteoclast activity
Male - decreased testosterone causes bone loss
Age - accelerated bone turnover rate and reduced osteoblasts
Identify risk factors associated with osteoporosis
Female
Advanced Age
Race/ethnicity
Smoking
Alcohol (3 more drinks a day)
Low bone density
Low calcium intake
Low vitamin D
Low body weight or BMI
Recent falls
Cognitive impairment
Impaired vision
History of fragility fracture
Past or present systemic oral glucorticoid use
What are the tools to assess patients for osteoporosis
WHO fracture risk assessment (FRAX)
Peripheral Dual-Energy X-ray Absorptiometry (pDXA)
Central Dual-Energy X-ray Absorptiometry (DXA)
Vertebral Fracture Assessment (VFA)
What is FRAX and when can it be used? When should it not be used?
It is using risk factors to predict the percent probability of a person fracturing in the next 10 years. Can be used when patients do not have access to DXA
It should not be used for patients ALREADY on therapy for osteoporosis
What is pDXA? cDXA? Which one is more popular and why? When should pDXA not be used? When should cDXA not be used?
pDXA measures small bones such as fingers and hands to assess for any fractures and predict risk. cDXA measures the hip and spine for fractures.
pDXA is more common because it is cheap, easy to use, portable, and fast. Used in health fairs and community pharmacies
pDXA should not be used in patients that are already at high risk. Should be referred for cDXA
cDXA should not be used in the absence of suspected risk factors of osteoporosis in children, postmenopausal women, and men younger than 50.
When using cDXA, what parameters are provided in a BMD report? What are they and what are they useful for?
Actual bone density - serial monitoring of therapy response
T-score - number of standard deviations from the mean of the reference population regarding BMD (healthy, young 20-29 YO, SEX-MATCHED, WHITE)
Z-score - same as T-score except race is considered
What is VFA?
It is a measure of vertebral fractures. Recommended for males >70 and females >80
What are the recommendations for calcium and vitamin D supplementation
???
What are some non-pharmacological options to prevent and treat osteoporosis?
Good Diet:
- calcium
- vitamin D
- vitamin K
- low caffeine and alcohol
Other
- no smoking
- exercise
- fall prevention (hip protectors)
What are some pharmacological options to prevent and treat osteoporosis?
Nutritional Supplements - Vitamin D and Calcium
Bisphosphonates
- Risendronate
- Alendronate
- Ibandronate
- Zoledronic acid
RANK ligand inhibitor
- Denosumab
Estrogen agonist antagonist
- Raloxifene
Recombinant human parathyroidhormone(PTH 1–34 units)
- Teriparatide
Calcitonin
- Calcitonin
When would you consider pharmacological options? What are first line agents for these situations? Alternative? Last line?
If the patient presents with a low trauma fracture (in the hip or vertebrae
-OR-
cDXA reveals patient has osteoporosis or has a high risk score (Tscore <-2.5) or can be considered when score is -1.1 to -2.5
First Line: Alendronate, risendronate, zoledronic acid, and denosumab
Alternative: Ibandronate, teriparatide, and raloxifene
Last Line: intranasal calcitonin
What is the overall mechanism that these drugs try to achieve?
Antiresorption (reduce breakdown of bone)
Calcium
Mechanism -
Benefit -
Adverse events -
CI/DDI -
Monitoring -
Calcium
Mechanism - increases BMD but less than Rx drugs
Benefit - prevents osteoporosis
Adverse events - CONSTIPATION, KIDNEY STONES (R)
CI/DDI - PPIs (lansoprazole, etc.)
Monitoring - dietary intake, constipation
Vitamin D
Mechanism -
Benefit -
Adverse events -
CI/DDI -
Monitoring -
Vitamin D
Mechanism - increase Ca++ concentration
Benefit - increases intestinal Ca++ absorption
Adverse events - Hypercalcemia (weakness, cardiac rhythm disturbance, headache, etc.), hypercalciuria
CI/DDI - Rifampin, anticonvulsants, BARs
Monitoring - serum 25(OH) vitamin D concentration
Bisphosphonates
Mechanism -
Benefit -
Adverse events -
CI/DDI -
Monitoring -
Bisphosphonates
Mechanism - mimics pyrophosphate and decreases osteoclast activity
Benefit - fracture risk reductions (usually seen first to 6-12 months during therapy)
Adverse events - musculoskeletal pain, nausea, dyspepsia, GI perforation (R), severe pain (R)
CI/DDI - dont take at same time with other drugs at same time (poor bioavailability) –> must taken 30min after 6 oz of water and normal Ca++ levels
–CRCL <30mL/min or hypocalcemia
Monitoring - bone density, fractures, serum calcium
Denosumab
Mechanism -
Benefit -
Adverse events -
CI/DDI -
Monitoring -
Denosumab
Mechanism - RANK ligand inhibitor -> less osteoclast formation
Benefit - Good for men having androgen-deprivation therapy for prostate cancer or women having aromatase inhibitor therapy for breast cancer.
Adverse events - Flatulence, eczema, cellulitis, infection
CI/DDI - PREGNANCY X
Monitoring - bone density, fractures, serum calcium
Raloxifene
Mechanism -
Benefit -
Adverse events -
CI/DDI -
Monitoring -
Raloxifene
Mechanism - estrogen agonists actions in bone and antagonist actions on breast and uterine tissue
Benefit - Good for PM osteoporosis prevention and treatment and good for reduction of risk in invasive breast cancer (also effects mostly the vertebrae)
Adverse events - Hot flushes (common), leg pain (common), spasms, venous thromboembolism
CI/DDI - Highly protein bound drugs like WARFARIN, and BARs decrease serum conc., PREGNANCY X and VTE history or active X
Monitoring - blood clots, hot flush, bone density, fractures
Calcitonin
Mechanism -
Benefit -
Adverse events -
CI/DDI -
Monitoring -
Calcitonin
Mechanism - endogenous hormone that decreases Ca++ when too high
Benefit - good for osteoporosis women that are at least 5 years past menopause
Adverse events - rhinitis, epistaxis
CI/DDI - Lithium
Monitoring - Bone density, fractures
Teriparatide
Mechanism -
Benefit -
Adverse events -
CI/DDI -
Monitoring -
Teriparatide
Mechanism - Has 34 AA structure of PTH ==> increases bone formation, bone remodeling rate, and osteoblast number and activity
Benefit - reduces non + verterbral fractures in postmenopausal women, no data for men or glucocorticoid users doe
Adverse events - nausea, headache, orthostasis with first few injections
CI/DDI - avoid in patients with osteosarcoma
Monitoring - Ca++ trough conc. after 1 month therapy
