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61 Cards in this Set
- Front
- Back
Describe effects of glucocorticoids on bone density
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They inhibit OB function, decreasing bone density.
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Describe effects of progesterone on bone density
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It inhibits LH/FSH, therefore inhibiting E2, which decreases bone density.
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Describe effects of Aromatase inhibitors on bone density
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They decrease E2, decreasing bone density.
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What Causes Osteoporosis ?
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*Result of a "mismatch" between bone formation and resorption
*Bone becomes abnormally thin and porous i.e. Osteopenia/Osteoporosis *Increasing fragility and risk of fracture |
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Factors that impact bone homeostasis:
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Estrogen
Androgens PTH Vitamin D 1,25 Glucocorticoids Thyroid hormone Insulin Growth Hormone Immobilization Cytokines |
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Symptoms of Osteoporosis:
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*Asymptomatic
*Fracture -Vertebral Fracture 2/3 asymptomatic Height loss --> Kyphosis -Hip Fracture Increase in mortality Disability --> Nursing home -Wrist Fracture Hands out stretched to stop a fall |
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WHO: DEFINITONS of osteoporosis, etc:
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*Normal bone density (T-score >-1)
Within 1 SD of the mean in young adults of the same sex and race *Osteopenia (T-score –1 to-2.5) More than 1 and less than or equal to 2.5 standard deviations below the mean in young adults of the same sex and race *Osteoporosis (T-score < -2.5) More than 2.5 standard deviations below the mean in young adults of the same sex and race Associated with skeletal fragility |
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Most people need 1000-1200 mg daily.
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elemental Ca is what you need
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What effect does Ca intake have on bone density?
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It prevents bone density loss.
Ca + Vit D is even better. |
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Adverse Reactions of Calcium:
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*Safe upper limit for calcium of 2000mg/day
*Related to a high calcium intake -GI symptoms (dyspepsia/constipation) -Hypercalciuria --> kidney stones -Vascular calcifications --> MI or stroke -Other symptoms associated with hypercalcemia *Drug Interaction -Antagonize effects of calcium channel blockers -Decreases the GI absorption of various drugs (e.g. Iron, bisphosphonates) |
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Vitamin D Deficiency:
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Prevalence:
*Overt RARE hypocalcemia hypophosphatemia rickets or osteomalacia *Subclinical COMMON osteoporosis *Contributing factors include reduced cutaneous production and Vitamin D intake |
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-Study showed 50% of women had subclinical Vit D deficiency.
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Vit D levels are inversely proportional to PTH levels.
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Diagnosis and Treatment of Vit D deficiency:
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*Diagnosis
25-OH D: < 20-30 ng/mL *Treatment 1) Ergocalciferol (D2) 50,000 IU q wk 12 wks decreases PTH and improves BMD 2) Calcium intake of 1000-1200 mg a day **Don't need to memorize these numbers** |
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Fracture Risk Reduction:
**Calcium 1200mg and Vitamin D 800IU /day** - BMD: 2.7% increase with treatment versus 4.6% decrease in the placebo group - Fracture: 43% reduction in hip fracture and 34% reduction in non vertebral fracture |
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Dermal Synthesis of Vitamin D:
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*Major source of the Vitamin D
10-15 minutes of sun exposure at least two times per week to the face, arms, hands, or back without sunscreen is equivalent to ingestion of 200 IU/day *Limitations Winter season Northern latitude Cloud cover/ smog Sunscreen (SPF>8) Greater melanin content |
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Discuss Vitamin D Supplements:
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*Maintenance
Cholecalciferol (Vitamin D3) *Vitamin D deficiency or insufficiency Ergocalciferol (Vitamin D2) *Renal failure or hypoparathyroidism Dihydrotachysterol (1-hydroxyvitamin D) Calcitriol (1,25-OHD) *Liver disease Calcidiol (25-hydroxyvitamin D) Calcitriol (1,25-OHD) |
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Adverse Reactions of Vitamin D:
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*Toxicity
-Not associated with sun exposure -Associated with very high oral intake i.e. intake of 25,000-60,000 IU daily for 1-4 months *Toxicity symptoms -Monitor symptoms of hypercalcemia |
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Osteoporosis Risk Assessment:
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Risk factors for osteoporosis: 12
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Personal history of fracture
Fracture in first degree relative Current cigarette smoking Low body weight (127lbs) Oral corticosteroid therapy > 3mo Early estrogen deficiency (< 45) Lifelong low calcium intake Alcoholism (>2 drinks/day) Inadequate physical activity Recurrent falls Dementia Impaired eye sight Poor health/ frailty |
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Meds that put you at risk for osteoporosis: 6
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Glucocorticoids
Progesterone (depo) Aromatase Inhibitors GNRH agonists Anticonvulsants Immunosuppressants |
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Describe effects of GnRH agonists on bone density
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Continuous use decreases LH/FSH, leading to decreased E2 and decreased bone density.
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Describe effects of anticonvulsants on bone density
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Blocks activation of Vit D to 1,25OH active form
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Describe effects of immunosuppressants on bone density
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Cause direct bone breakdown
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Medical conditions that put you at risk for osteoporosis:
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Hypogonadism [decreased testosterone]
Anorexia [decreased LH/FSH, E2] Hyperparathyroidism [increased bone resorption] CRF [no Vit D] Thyrotoxicosis [direct effect on bone] IBS/Malabsorption/Sprue [decreased Vit D] Immobilization Multiple Myeloma HIV/DM/RA |
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Who should undergo testing for osteoporosis?
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Who should be treated for osteoporosis?
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*know these 3 treatment recommendations*
1000-1200mg Ca 800-1000 IU Vit D |
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What hx = automatic osteoporosis diagnosis?
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Hx of a fragility fx
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Effects of estrogen on bone density:
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*estrogen maintains bone density; prevents bone loss.
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Risks of HRT?
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CHD
Stroke Pulmonary embolism Breast Cancer, Colon cancer |
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Selective Estrogen Receptor Modulators (SERMS):
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*SERMS:
-Triphenylethylenes: Clomiphene / Tamoxifen -Benzothiophenes: Raloxifene *Mixed agonist and antagonist activity *Raloxifene Estrogen action inhibited --> Breast / Uterus* Estrogen action retained --> Skeleton / Lipids* Indications: prevention and treatment of osteoporosis Dose: 60mg oral every day Side Effect – hot flashes, leg cramps, thrombosis [* decreased Ca risk compared to HRT] |
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Pharma effects of estrogen vs. Raloxifene vs. Tamoxifen:
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Efficacy limitations of SERMS?
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-They've been shown to reduce vertebral fxs; but NOT hip fxs.
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Calcitonin:
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*Produced by parafollicular cells of the thyroid
*Physiologic antagonist to PTH *Stimulated by high calcium levels -Inhibits osteoclast formation and function -Increases renal calcium excretion by decreasing tubular reabsorption. |
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Describe calcitonin's role in osteoporosis prevention and treatment:
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*Osteoporosis: prevention and treatment
-Intranasal 200 units (1 spray)/day -IM/SQ 100 units/every other day -Effect: Increase BMD and decrease spine fracture (NOT HIP) *Side effects: -Intranasal: rhinitis, epistaxis -SQ/IM: nausea, vomiting, facial flushing, allergic reaction, develop anti-calcitonin antibodies and become resistant to therapy |
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HOW DO bisphosphanates work?
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-Inhibit OC function
-INCREASE BONE DENSITY -DECREASE ALL INCIDENCES OF FX IN HIP, SPINE, WRIST. |
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4 BISPHOSPHANATE AGENTS:
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Alendronate - Oral
Residronate - Oral Ibandronate - Oral or IV Zolendronate - IV |
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SEs of bisphosphanates:
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*GI Symptoms
-Esophagitis -Ulcers [pill lodges in esophagus; pts must drink with full glass of H2O and not lie down after taking pill] *Transient acute phase reaction with IV -Myalgias -Arthralgia -Fever *Hypocalcemia *Atrial Fibrillation *Osteonecrosis of jaw *Atypical fractures (?) |
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Denosumab:
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Osteoclasts express RANK
Osteoblasts express RANKL RANKL/RANK stimulates osteoclastogenesis *Denosumab Humanized monoclonal antibody Anti-RANKL Inhibit RANKL/RANK signaling Decrease bone resorption. *Blocks RANKL --> No OC activation* |
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Results of the FREEDOM trial:
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-good fx reduction
-infections are a problem -possible neoplasms |
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Counterintuitive usage of PTH to increase bone formation:
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*daily injections increase bone formation*
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Recombinant Human Parathyroid Hormone:
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*osteosarcoma is the big one*
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Indications and CIS for using rPTH in osteoporosis therapy:
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*Failed/intolerant of therapies
*Limited to 2 years |
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Therapies and their fx reduction abilities:
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Overall chart summarizing BMD effects, fx effects, and SEs of all osteoporosis treatments.
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First line bisphosphanate:
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Alendronate b/c it's oral.
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If you see low BMD in forearm as compared to spine and hip, think:
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hyperparathyroidism
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You pick osteoporosis drugs based on:
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the SE profiles of the drugs.
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