1 osteoporosis j.b. handler, m.d. physician assistant program university of new england
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Osteoporosis
J.B. Handler, M.D.Physician Assistant ProgramUniversity of New England
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Abbreviations BD- bone density SERM- selective estrogen receptor modulator PTH- parathyroid hormone RA- rheumatoid arthritis SD- standard deviation S/S- sensitivity/specificity CC- creatinine clearance BMD- bone mineral density
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Osteoporosis Osteoporosis is defined as a skeletal
disorder characterized by compromised bone strength predisposing to an increased risk of fracture.
NIH Consensus Development Conference, March 2000
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Osteoporosis Most common metabolic bone disease Decreased bone matrix and mineral
“thin bones”. Women>Men, often asymptomatic early;
later, bones fail structurallyfractures. 20 million cases in USA; 1.5 million
fractures annually- spine, hip. Increased bone resorption, esp. trabecular
bone.
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Bone Density (BD) Increases dramatically in puberty in
response to gonadal steroids. Peaks in young adults (early 20’s) Determinants: age, race, genetics,
gonadal steroids, timing of puberty, exercise, calcium intake and diet.
Genetics: Female offspring of patients with osteoporosis have lower BD.
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Physiologic Bone Loss Begins before menses cease. Accelerated loss in 1st 5-10 yrs
post menopause. Trabecular (cancellous)> Cortical
(compact) bone loss.
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Bone Structure
Images.google.com
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Physiologic Bone Loss Net bone loss over 10 years:
Trabecular: 25-30%Cortical: 10-15%.
Ongoing bone loss after age 60 is slower. Theoretically preventable with estrogen,
and useful in some subsets (hypogonadism, premature menopause) but not a long term option postmenopause risk of side effects. Testosterone in men with hypogonadism.
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Etiologies (increased risk) Sex hormone deficiency: post
menopause; hypogonadism- M&W Excess glucocorticoids (Cushing’s) Hyperparathyroidism- PTH Thyrotoxicosis- bone metabolism Alcoholism, anorexia nervosa, Vit D deficiency. Others
RA, Multiple myeloma, leukemias Genetic disorders (osteogenesis imperfecta),
connective tissue diseases
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Definitions (BD Scores) Osteopenia: bone mineral density
1-2.5 SD below peak bone density Osteoporosis: bone mineral
density >2.5 SD below peak bone density
Peak bone density = young healthy adult of same gender and race
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History, Signs and Symptoms Dietary calcium, Vit D Delayed puberty, hypogonadism,
premature menopause FH of osteoporosis Asymptomatic until fracture (often
spontaneous) Back pain, decrease in height,
kyphosis deformity
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Osteoporosis of Spine
Images.google.com
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Men Have Osteoporosis Too!
It has been estimated that 1 out of 5 people with osteoporosis are men.
Lifetime fracture risk in men may be as high as 15-25% (women=50%).
36% of men with hip fracture die the year following fracture (nearly twice that of women).
Alendronate is approved by the FDA for the treatment of osteoporosis in men.
Cheater!
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Investigative Findings Lab: normal ionized calcium, PO4
Vit D levels (25-hydroxy vit D)- test if low bone density proven; may be lacking (diet/sun).
Where indicated: TSH, cortisol, estradiol, testosterone, PTH.
X-rays: spine, femoral head and neck Bone densitometry: DEXA (dual energy x-
ray absorptiometry) is test of choice- High S/S for detecting/ruling out osteopenia/osteoporosis.
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Bone Densitometry DEXA typically looks at spinal bone
and proximal femur; includes eval of trabecular and cortical bone. Rapid exam time OK for F/U changes in BD; response to
Rx Relatively inexpensive Limited radiation exposure
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DEXA Scores T score: number of SD by which patient
BD differs from peak BD of young healthy adults of same gender/race. Z score: number of SD by which patient BD
differs from age matched individuals of same gender/race; of limited benefit
Initiate Rx: Osteoporosis: BMD > 2.5 SD below peak BD of
young adults. Severe osteopenia: BMD of > 2 SD below peak
of young adults.
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Prevention and Treatment Cannot reverse established
osteoporosis; can BD, fractures, halt progression.
Essential to Rx underlying secondary etiologies or predisposing factors if present.
When to screen: All patients at risk for osteoporosis* including postmenopause (see Table in CMDT- Chap 26-10).
*+FH, malnourished, alcoholism, renal failure, etc.
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Treatment Tailored to underlying etiology (if
other than post-menopause). Bisphosphonates SERMS Calcitonin Vitamin D; Calcium PTH (synthetic analog)
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Estrogen Replacement Use in patients with hypogonadism or premature
menopause for prevention. Inhibits osteoclastic bone resorption. Prevents bone loss, fractures. Problems (dose related): risk breast Ca, risk
endometrial cancer (if not coupled with progestins), thromboembolic events, in coronary events (when combined with progesterone).
If used postmenopause (controversial)- low dose topical Rx preferred for short term use only. Consider SERMs for long term use.
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Bisphosphonates Inhibit osteoclastic bone resorption;
bone density, fractures (vertebral and elsewhere).
Excreted in urine: Requires dose adjustment if CC< 35mL/min- Caution- severe renal insufficiency.
Commonly used as initial Rx.
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Bisphosphonates Alendronate (Fosomax): Take 30”
before AM meal with 8 oz H20, remaining upright for 30” minutes to prevent esophagitis.Dose: 70 mg po weeklyGI side effects: gastritis, esophagitis
Risedronate (Actonel): less GI side effects Single weekly dose: 35mg po before am meal. Similar instructions as above.
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Bisphosphonates Ibandronate (new): 150mg po q monthly IV forms available: Pamidronate (q3mos)
and Zoledronic Acid (given 1-2x year- expensive). For patients who cannot tolerate oral forms.
Side effects: muscle, bone, joint pain. Dental concerns: non-healing jaw post tooth extraction. Dental care important for patients on bisphosphonates.
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SERMS Selective Estrogen Receptor Modulators-
agonist/antagonist effects on estrogen receptors.
Alternative to estrogen in post-menopausal woman with risk of adverse effects; decrease bone loss, bone density (less than estrogen), vertebral fractures.
For treatment and prevention (woman at risk and osteopenia) of osteoporosis post-menopause.
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SERMS Raloxifene (Evista) 60 mgs po/daily:
increases bone density but less than estrogen; blocks estrogen effects on breast and uterus. Does not cause endometrial
hyperplasia, cancer or uterine bleeding. ’s incidence of breast cancer; risk of
thromboembolism (like estrogen). Increases hot flashes
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Calcitonin Nasal spray (salmon calcitonin)- inhibits
osteoclast action, bone density (2-3% over time): 1 inhalation daily (200 IU).side effects: rhinitis, epistaxis. Accelerates Ca absorption by bones.
Results: decreases fractures and bone pain.
Parenteral forms available.
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Calcium and Vitamin D Diet: Need adequate Ca, protein & Vit D
Intake and GI absorbtion of Ca with age Vit D levels useful in determining need
Osteoporosis/osteopenia or high risk individuals: supplement Vit D and Ca (replacement doses of Ca if not adequate per diet).
Help arrest bone loss, especially Vit D Recent concerns in older women (>70).
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Calcium and Vitamin D Vit D2- 400-600 IU daily Calcium: Dietary Ca or supplements to
maintain recommended daily amounts (1200 mg/d for men/women 51 y/o & over); ideally via diet- milk/dairy. Ca supplements beyond RDA may increase risk of MI and stroke, especially in women > 70 or with CHD.
Caution: patient on thiazide diuretics or glucocorticoids- hypercalcemia can occur.
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PTH and Ca Homeostasis
Normal actions: Stimulates osteoclasts and osteoblasts (bone remodeling). Osteoclastic activity predominates physiologicallyCa homeostasis
Paradoxical (anabolic) effects when synthetic PTH given as intermittent (20mcg/d daily) sub-cut injection; results in: Osteoblastic predominancenew bone
formation. Mechanism of this action not known.
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Teriparatide
Synthetic analog of PTH (Forteo) Targets bone formation For Rx of severe osteoporosis Administered by daily injection for up to
2 year period. Significant BD (10-13%), fractures (50-
70%, especially of spine);
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Lifestyle Healthy diet Weight bearing exercise Fall precautions, especially in elderly