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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.

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

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