glucocorticoids excessive thyroid hormone diuretics: furosemide cyclosporine, methotrexate,...
TRANSCRIPT
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OSTEOPOROSIS
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RISK FACTORS FOR OSTEOPOROSIS
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MEDICAL DISORDERS AND MEDICATIONSASSOCIATED WITH OSTEOPOROSIS
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MEDICATIONS KNOWN TO CAUSE OR ACCELERATE BONE LOSS Glucocorticoids
Excessive thyroid hormone
Diuretics: Furosemide
Cyclosporine, methotrexate, tacrolimus
Seizure medications: Phenytoin, phenobarbital
Psychotropic: Lithium,
Heparin
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EVALUATION AND TREATMENT OF OSTEOPOROSIS Initial evaluation:
CBC Ca, p, Cr Alkaline phosphatase,
aminotransferases 25-hydroxyvitamin D TSH 24-hour urine for Ca and creatinine
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ASSESSMENT OF BONE DENSITY Osteoporosis diagnosed when a radiograph
shows signs of demineralization or compression fractures of vertebral bodies.
Techniques for evaluating bone mass:
Dual-energy x-ray absorptiometry (DEXA)
Quantitative (CT) of spine.
Ultrasound
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INDICATIONS FOR BMD All postmenopausal women < 65 yr who have one or
more additional risk factors for osteoporosis
All women > 65 yr regardless of additional risk factors
To document reduced bone density in patients with vertebral abnormalities or osteopenia on radiographs
To diagnose low bone mass in glucocorticoid-treated individuals
To document low bone density in patients with asymptomatic primary or secondary hyperparathyroidism
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TREATMENTCalcium:
Goals of therapy for osteoporosis reduce bone resorption and enhance bone formation.
Bone loss occurs when Ca intake and absorption insufficient to balance daily Ca losses.
In absence of kidney stones or an underlying disorder of Ca metabolism,Ca intakes safe.
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Calcium carbonate:
contains 40% elemental Ca
should be taken with meals because of poor absorption in achlorhydric patients in absence of food.
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Calcium citrate:
contains 24% elemental Ca,
better bioavailability and is more absorbed.
absorbed well on an empty stomach in patients with achlorhydria.
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Milk Yogurt Orange juice (with Ca) Cheese Ice cream (1/2 cup) Soy milk (1 cup) Beans (1/2 cup cooked) Dark,green vegetables
(1/2 cup cooked) Almonds Orange (1 medium)
300 mg 250 mg 300 mg 195 to 335 mg 100 mg 300 mg 60 to 80 mg 50 to 135 mg 70 mg 60 mg
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SELECTIVE ESTROGEN RECEPTOR MODULATORS Tamoxifen:
Estrogen antagonist that binds to estrogen receptor
Estrogen-agonist effects on bone
Small increase in bone density of spine over 2 years,
No effect on radial bone density
45% reduction at hip and 29% at spine fracture.
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Raloxifene:
FDA approved for prevention and treatment of
osteoporosis
Estrogen agonist on bone
Antagonist effects on breast and uterus.
Increased BMD in lumbar spine by 2.4%, in hip by 2.4%, in total body 2%
Over 2-year, significant reduction in vertebral fractures
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CALCITONIN a potent inhibitor of osteoclastmediated bone
resorption.
Human and salmon calcitonin available
Salmon calcitonin commonly used because greater potency.
Parenteral calcitonin (100 IU SC or IM three times a week or daily)
Maintain bone density or produce a small increase in bone mass in spine
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Nasal spray calcitonin absorbed through nasal mucosa
Approximately 40% as potent as parenterally administered (50 to 100 IU of injectable calcitonin comparable with 200 IU of nasal spray calcitonin).
Nasal calcitonin (200 IU/day) increases spinal bone density
No effect on proximal femur bone mass;
36% reduction in vertebral fractures over 5 years.
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Adverse effects of parenteral calcitonin:
nauseaflushing
local irritation at injection site
Calcitonin intranasally well tolerated
Rhinitis and nasal dryness and crusting potential side effects.
Calcitonin may beneficial analgesic response in presence of osteoporotic fractures.
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BISPHOSPHONATES
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Alendronate (Fosamax) is FDA approved for prevention and treatment of osteoporosis.
Alendronate (10 mg/day) produces:
8.8% and 7.8% increase in bone density in spine and femoral trochanter
Alendronate (70 mg) most commonly used dose for treatment of osteoporosis.
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Adverse effects of bisphosphonates:
GI symptoms:stomach painesophagitis
Myalgias and arthralgias,
Osteonecrosis of jaw
Subtrochanteric fractures
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Risedronate:
Increased bone mass
Reduced risk of new vertebral fractures
Significant reduction in risk of hip fracture
Approved for prevention and treatment of osteoporosis(35 mg once a week)
Risedronate well tolerated even in patients with mild GI symptoms.
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Ibandronate:
Approved for treatment and prevention of osteoporosis.
Vertebral fractures reduce about 50%.
150 mg/month
Intravenous ibandronate in a dose of 3 mg every 3 months
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Zoledronic acid approved for treatment and prevention of osteoporosis.
5 mg once a year by intravenous infusion,
Risk of vertebral fractures reduce 68%, hip fractures 40%
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Side effects:
arthralgias and myalagias;
Patients should have serum Ca and 25-OHD levels monitored and replaced to NL levels before treatment.
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RANK LIGAND INHIBITOR Denosumab (Prolia):
Monoclonal antibody that against RANKL
Approved for treatment of osteoporosis.
60 mg subcutaneously every 6 months for 36 months
Vertebral fractures reduce 68%, hip fractures 40%,
Well tolerated,
Adverse events: skin infection
Before treatment Ca and 25-OHD should be checked and replaced if needed up to normal levels.
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PARATHYROID HORMONE PTH significantly increase bone mass in
spine,
Fortéo approved for treatment of osteoporosis.
20 μg/day for 21 months.
Lumbar spine bone mass increased between 9% and 13% ,
Hip bone mass increased slightly.
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Risk of new vertebral fractures reduce nearly 70%.
Fortéo is given daily injection.
Individual may experience headache, nausea, flushing with initiation of treatment, but these side effects become less severe after few weeks.
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PTH:
Stimulates new bone formation
Increases bone mass
Reduces new vertebral and nonvertebral fractures
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Subcutaneous injection daily for 18 to 24 months.
Other routes of administration:
intranasalskin patch.
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VITAMIN D Physiologic doses of vitamin D
important to NL bone mineralization.
Individuals 50 years of age and older should take at least 600 to 1000 IU of vitamin D daily
Low vit D levels increase risk of bone loss and fracture.
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Low 25-OHD levels during the winter and spring associated with decreases in bone density.
Daily treatment with 700 IU of cholecalciferol and 500 mg of Ca carbonate reduced rate of bone loss in:
femoral neck, spine,
total body Decreased incidence of nonvertebral fractures by
50%.
Patients require a vit D intake that in 25-OHD level of at least 30 ng/mL.
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RECOMMENDATIONS FOR PREVENTION OF GLUCOCORTICOID-INDUCED OSTEOPOROSIS Patients starting GC therapy at a dose equivalent to
prednisone ≥5 mg/day for 3 mo or longer should:
Modify risk factors for osteoporosis (stop smoking, decrease alcohol consumption)
Start regular weight-bearing physical exercise
Initiate intake of Ca (total 1500 mg/day) and vit D(400-800 I U/day)
BMD to predict risk of fracture and bone loss
Initiate bisphosphonate therapy (alendronate 5 mg/day or 35 mg/wk, or risedronate 5 mg/day or 35 mg/wk)
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TREATMENT If T-score is < −1:
Risk factor modification including reducing risk of falls
Regular weight-bearing physical exercises
Ca and vit D supplementation
Bisphosphonate therapy (alendronate 10 mg/day or 70 mg/wk,or risedronate 5 mg/day or 35 mg/wk);
If bisphosphonates contraindicated or not tolerated, calcitonin as second-line agent, intravenous bisphosphonate (pamidronate or zolendronate), parathyroid hormone
Repeat BMD measurement annually or biannually