PRACTICAL PERSPECTIVES ON PREVENTION AND TREATMENT OF
OSTEOPOROSIS
From University of Miami Miller School of Medicine’s Advances in Medicine
Bruce R. Troen, MD, Professor of Medicine, University of Miami Miller School of Medicine, and Veterans Affairs Medical
Center, Miami, FL
| Treatment overview: all patients with history of fragility fractures require treatment; evidence shows women with
osteoporosis plus fracture benefit most from treatment; women with osteopenia and men benefit less; medical
options—bisphosphonates; raloxifene; parathyroid hormone (PTH); strontium (not available in United States); all
reduce incidence of vertebral fractures; alendronate, risedronate, zoledronic acid, and estrogen (in some subsets of
women) reduce incidence of hip fractures among community-dwelling women; calcium plus vitamin D supplementation
reduces incidence of vertebral and hip fractures among community-dwelling and institutionalized older
adults
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| World Health Organization (WHO) definitions: osteoporosis—bone mineral density (BMD) ≥2.5 SD below
mean (based on BMD of white women, 30 yr of age); severe osteoporosis—osteoporosis plus fracture
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| Guidelines for densitometry and treatment: although some societies (eg, National Osteoporosis Foundation)
recommend densitometry for postmenopausal women with fractures (to confirm diagnosis of osteoporosis), others
(eg, North American Menopause Society) recommend treatment without BMD testing; speaker’s opinion—
presence of fragility fracture diagnostic for osteoporosis; densitometry unnecessary
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| Clinical significance: osteoporosis results in lost height, kyphosis (which may impair ability to breathe deeply),
and fractures; \>1.5 million osteoporotic fractures each year in United States; vertebral fractures most common, followed
by hip, distal forearm, pelvis, and ribs; risk increases with age (≈33% of women and ≈17% of men suffer hip
fracture by 90 yr of age); hip fracture associated with 12% to 20% excess mortality (twice as high in men); 50% of
patients with hip fracture require long-term care; annual cost, \>$15 billion; up to half of patients with hip fracture
do not receive treatment for osteoporosis
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| Risk factors for osteoporotic fractures: BMD—\>50% of hip fractures occur in patients who do not meet
WHO criteria for osteoporosis; decreases in incidence of fracture (as result of antiosteoporotic therapies)
not fully explained by increases in BMD; other aspects of bone quality important, but not measurable with
densitometry; age—most important risk factor; alternative definition of osteoporosis—disease characterized
by low bone mass, enhanced bone fragility (due to microarchitectural changes), and increased risk for fracture;
risk for fracture—influenced by risk for falls and force of impact, ie, trauma experienced by bone; clinical
risk factors—age; history of fracture as adult; family history of fracture (first-degree relative); low body
weight; current smoking; use of oral steroids \>3 mo; low intake of calcium and vitamin D; early menopause;
dementia (increases risk for falls); frailty; recent falls; impaired vision; low physical activity (weakens
bones and muscles); alcohol overuse (affects osteoblasts)
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 | History of fracture: increases risk for future fracture equally in women and men (equivalent to that of person 10 yr
older without history of fracture); risk remains elevated for 10 yr after fracture, but most subsequent fractures occur
1 to 2 yr after initial fracture (opportunity for intervention)
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| Risk stratification: use clinical risk factors to assess fracture risk; treat patients at high risk; assess BMD of intermediate-risk
patients; consider supplementing vitamin D and calcium even in low-risk patients
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| Biochemical markers: useful for monitoring response to therapy; may enhance compliance; useful for predicting
BMD response to therapy; potentially useful for diagnosis (insufficient evidence); benefits over densitometry—fast
response (3 mo, compared to 1-2 yr for BMD); less expensive; no radiation exposure
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| Indications for densitometry: white women ≥65 yr of age (screening may help reduce risk for fracture; unnecessary
in women with history of fragility fracture); patients with risk factors for osteoporosis (eg, history of corticosteroid
use, low body weight, positive family history, or smoking); postmenopausal women averse to
antiosteoporotic therapy (to encourage compliance); young patients with nontraumatic fractures or evidence of
demineralization; before initiation of corticosteroid therapy; use in monitoring treatment—controversial (speaker
does not recommend)
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| Acute management of osteoporotic fractures: pain management —sufficient analgesia important (especially
with vertebral fractures, which may cause muscle spasm); immobilization—temporary immobilization appropriate
for patients with unstable fractures; mobilization improves healing by preventing deconditioning and improving
calcium balance; physical therapy—especially for patients with muscle spasm; pool therapy supports weight,
builds confidence, and increases mobility; increased muscle strength improves ability to perform activities of daily
living; surgery—avoid delaying surgery for hip fracture; antiosteoporotic therapy—prevents additional fractures
and loss of bone
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| Osteoporosis in men: case—man 69 yr of age; history includes chronic obstructive pulmonary disease, gastroesophageal
reflux disease, benign prostatic hyperplasia, hypertension, lipid abnormalities, and depression; multiple
medications include long-term use of steroids (prednisone, 20 mg qd); epidemiology—\>2 million men in United
States affected; lifetime fracture risk up to 25% in some populations; risk increases with age and matches that of
women 10 yr younger (curve shifted because of higher baseline BMD in men); 20% of hip fractures occur in men;
lifetime risk for vertebral fracture, ≈12% (same as in women); laboratory tests (case)—25-hydroxyvitamin D, 14
ng/mL; testosterone, 166 ng/dL (hypogonadal); low BMD at femur and L3-L4 vertebral body (meets definition for
osteoporosis); etiologies—corticosteroid use; hypogonadism; hypercalciuria with nephrolithiasis; cancer and cancer
therapy; gastrectomy; alcoholism; hyperthyroidism; immobilization
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Treatment Options
| Calcium and vitamin D: study—daily calcium (1200 mg) and vitamin D3 (800 IU) resulted in increased BMD
(by 2.7%) in healthy ambulatory postmenopausal women over 3 yr; BMD decreased 4.6% in control group; supplementation
associated with decreased nonvertebral and hip fractures (32% and 43%, respectively), increased 25-hydroxy
vitamin D levels, and decreased levels of PTH; vitamin D dose—meta-analysis shows daily dose of 700 to
800 IU, but not 400 IU (recommended daily allowance), reduces fractures; vitamin D deficiency—<10 ng/mL (25
nmol/L) considered deficiency; 10 ng/mL to 32 ng/mL now considered “insufficiency”; \>32 ng/mL (80 nmol/L)
considered normal; \>95% of patients with minimal-trauma fractures have 25-hydroxyvitamin D levels <30 ng/
mL, and 50% have levels <15 ng/mL; latitude (in continental United States) does not affect risk for deficiency;
older adults often avoid sun exposure; supplementation—speaker takes 2000 IU/day of vitamin D, and recommends
supplementation (1000 IU/day), even in children; associated with many benefits (evidence suggests association
with decrease in type 1 diabetes in children and type 2 diabetes in adults); inexpensive
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| Bisphosphonates: reduce incidence of fracture; improve BMD; more evidence of benefit with alendronate and
risedronate than with ibandronate (more long-term data necessary); monitoring therapy—speaker prefers total alkaline
phosphatase as marker; important to get baseline level before initiating therapy; significant reductions seen
within 3 mo; if using telopeptides, results seen in 6 wk
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| Parathyroid hormone (teriparatide): daily subcutaneous injections associated with dramatic decrease in vertebral
fractures; anabolic effects; indications—patients who continue to fracture or to lose BMD while on bisphosphonate
therapy; severe osteoporosis (T-value ≤-3.5); fractures plus low BMD; treatment recommendations—daily
20-µg injections (patient must be willing and able); maximum duration, 2 yr (caution based on association with osteosarcoma
in rats); combination therapy with bisphosphonates not recommended (associated with less benefit than
PTH alone); bisphosphonate therapy recommended after completion of PTH therapy to maintain BMD
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| Calcitonin: less effective than other therapies; more difficult to administer; appropriate for patients with painful vertebral
fractures (has analgesic effect)
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| Raloxifene: beneficial, but many patients refuse; associated with extraskeletal effects
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| Zoledronic acid: good option for patients unlikely to be compliant with monthly therapy; intravenous (IV) therapy,
given annually; randomized multicenter clinical trial enrolled women who met WHO criteria for osteoporosis; calcium
and vitamin D supplemented; annual IV infusion (5 mg) associated with reduced incidence of hip (40%), vertebral
(77%), and nonvertebral (25%) fractures; adverse effects—fever (controlled with acetaminophen); myalgia;
flu-like symptoms; most resolved within 3 days and decreased after subsequent infusions; 1 case of osteonecrosis
of jaw (ONJ; resolved with treatment); rarely, serious atrial fibrillation (all but 3 cases resolved easily)
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| Management of comorbidities: limit medications associated with bone resorption; avoid medications that increase
falls (eg, benzodiazepines) or cause orthostatic hypotension; correct endocrinopathies; minimize immobilization;
recommend environmental changes that reduce risk for falls
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| Fall-prevention checklist: vision; factors that impair walking and balance (eg, peripheral neuropathy or arthropathy);
postural hypotension; excessive use of tranquilizers, sedatives, hypnotics, or antidepressants; home environments
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Glucocorticoid-Induced Osteoporosis
| Oral bisphosphonates: study data show alendronate and risedronate enhance BMD in setting of glucocorticoid
therapy and are associated with reductions in vertebral fractures (40% with alendronate and 70% with risedronate)
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| Parathyroid hormone: recent study showed PTH superior to alendronate at reducing vertebral, but not nonvertebral
fractures in patients with osteoporosis
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| Treatment indications: initiate antiosteoporotic therapy early in patients receiving oral corticosteroids for ≥3 mo;
assess BMD before initiating corticosteroids; consider alternative to corticosteroid therapy if BMD (T-score) <-1.5;
ensure adequate intake of calcium and vitamin D in all patients; note—thiazide diuretics beneficial (decrease risk
for hip fracture) in patients with hypertension and calciuria by reducing calcium excretion, thus maintaining calcium
homeostasis and bone health; risk stratification—oral bisphosphonate therapy appropriate for patients with
intermediate T-scores and with no history of fracture; PTH therapy preferred for patients with osteoporosis
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Osteonecrosis of the Jaw
| Scope of problem: relatively rare; marked by significant bone resorption and persistent infection; often resistant to
therapy; risk factors—high doses of (usually, IV) bisphosphonates, often for prevention of cancer metastasis;
trauma (especially dental)
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| Oral bisphosphonates: clinical trials had no cases of ONJ in \>100,000 patients in \>3 yr; postmarketing anecdotal
reports show alendronate (≈75 cases) and risedronate (≈10 cases) and led Food and Drug Administration (FDA) to
add cautionary label; estimated risk, 0.0005% of all people taking oral bisphosphonates
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| Mortality risk: deaths per year per 100,000 people—fragility fracture, 2600; anaphylaxis from penicillin exposure,
32; murder, 6; ONJ, 0.7
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| Implications: some dentists unwilling to treat patients on bisphosphonate therapy; educating patients and dental
colleagues about risks and benefits important
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Questions and Answers
| Treatment efficacy (vitamin D vs bisphosphonates): no head-to-head studies; widespread supplementation
with vitamin D likely to reduce total burden of osteoporosis; study in former Yugoslavia showed inhabitants of
dairy-rich regions have significantly lower lifetime risk for hip fracture, compared to general population
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| Treatment in patients with advanced chronic renal failure: avoid cholecalciferol, because renal failure prevents
conversion to active form; consider other agents (eg, paricalcitol, α-calcidol); collaborate with nephrologist to ensure
patient has adequate levels of active hormone; patients on dialysis—bisphosphonate therapy acceptable (oral
therapy preferred), but careful monitoring (eg, for secondary hyperparathyroidism) required; no data on PTH therapy in
this population
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| Proton-pump inhibitors and osteoporosis: reducing acidic environment of stomach decreases calcium absorption;
calcium supplementation important (citrate and maleate forms preferred)
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| Treatment for osteopenic patients: assess clinical risk factors; treat those with frailty or other risk factors
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| Duration of treatment: concerns about long-term treatment come from animal studies (eg, increased risk for microfractures);
study with 7- to 10-yr follow-up found no increase in fracture rate; “drug holiday” may be considered,
but not evidence-based
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| Contraindications to supplementation: calcium—history of stone formation (especially calcium carbonate
stones); hyperparathyroidism; vitamin D—very safe; recent study—calcium supplementation (1200 mg/day) associated
with increased incidence of myocardial infarction; caution warranted until more data available
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Suggested Reading
Bischoff L, Derk CT: Premenopausal osteoporosis. Minerva Med 99:55, 2008; Bischoff-Ferrari HA et al: Fracture
prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 293:2257,
2005; Black DM et al: Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. New Engl J Med
356:1809, 2007; De Nijis RN: Glucocorticoid-induced osteoporosis: a review on pathophysiology and treatment options.
Minerva Med 99:23, 2008; Doggrell SA: New horizons for zoledronic acid: results of the HORIZON trials in
postmenopausal women with osteoporosis and after hip fracture. Expert Opin Pharmacother 9:663, 2008; Eisman JA
et al: Efficacy and tolerability of intravenous ibandronate injections in postmenopausal osteoporosis: 2-year results
from the DIVA study. J Rheumatol Feb 1, 2008 [Epub ahead of print]; Grant BT et al: Outcomes of placing dental
implants in patients taking oral bisphosphonates: a review of 115 cases. J Oral Maxillofac Surg 66:223, 2008; Majumdar
SR et al: Multifaceted intervention to improve diagnosis and treatment of osteoporosis in patients with recent
wrist fracture: a randomized controlled trial. CMAJ 178:569, 2008; Olszynski WP, Davison KS: Alendronate for the
treatment of osteoporosis in men. Expert Opin Pharmacother 9:491, 2008; Reid DM et al: A comparison of the effect
of alendronate and risedronate on bone mineral density in postmenopausal women with osteoporosis: 24-month results
from FACTS-International. Int J Clin Pract 62:575, 2008; Reginster JY et al: Role of biochemical markers of bone
turnover as prognostic indicator of successful osteoporosis therapy. Bone Feb 15, 2008 [Epub ahead of print]; Stroup
J et al: Teriparatide in the treatment of osteoporosis. Am J Health Syst Pharm 65:532, 2008; Thomas SK et al: Individual
nutrition therapy and exercise regime: a controlled trial of injured, vulnerable elderly (INTERACTIVE trial).
BMC Geriatr 8:4, 2008; van Helden S et al: Bone and fall-related fracture risks in women and men with a recent
clinical fracture. J Bone Joint Surg Am 90:241, 2008; Wainwright SA et al: Hip fracture in women without osteoporosis.
J Clin Endocrinol Metab 90:2787, 2005.
Educational Objectives
| The goal of this program is to improve prevention and treatment of osteoporosis and osteoporotic fractures. After
hearing and assimilating this program, the clinician will be better able to:
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| 1. Risk-stratify patients based on clinical risk factors for osteoporosis.
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| 2. Compare the risks for osteoporosis and fracture between men and women.
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| 3. Implement evidence-based treatments for patients with osteoporosis.
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| 4. Educate patients about calcium and vitamin D supplementation for reducing risk for osteoporosis and fracture.
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| 5. Discuss the risk factors and clinical relevance of osteonecrosis of the jaw, as it relates to bisphosphonate therapy.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the
planning committee to disclose relevant financial relationships within the past 12 months that might create any personal
conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes
quality in health care and not a proprietary business or commercial interest. For this program, Dr. Troen and the planning
committee reported nothing to disclose.
Acknowledgments
Dr. Troen was recorded at Advances in Medicine, presented by University of Miami, Miller School of Medicine, and
held January 13-18, 2008, in Miami Beach, FL. The Audio-Digest Foundation thanks Dr. Troen and the University of
Miami Miller School of Medicine for their cooperation in the production of this program.
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