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Osteoporosis:What to Tell Patients About Prevention and Treatment

Article

Osteoporosis is no longer consideredage- or sex-dependent, although prevalencevaries by sex and race. Postmenopausalwhite women suffer almost75% of all hip fractures and havethe highest age-adjusted rate of fracture.Thanks to progress in our understandingof causes and treatments, thisdisease is largely preventable, and significantimprovements in morbidityand mortality are possible. The beststrategy for prevention and treatmentuses a team approach that involves thepatient, physician, health educators, dietitians,and physical therapists.

Osteoporosis is no longer consideredage- or sex-dependent, although prevalencevaries by sex and race. Postmenopausalwhite women suffer almost75% of all hip fractures and havethe highest age-adjusted rate of fracture.Thanks to progress in our understandingof causes and treatments, thisdisease is largely preventable, and significantimprovements in morbidityand mortality are possible. The beststrategy for prevention and treatmentuses a team approach that involves thepatient, physician, health educators, dietitians,and physical therapists.

In this article we highlight recentrecommendations that are most applicableto clinical practice.

OVERVIEW
More than 25 million Americanshave-or are at imminent risk for--osteoporosis,which is characterized by microarchitecturaldeterioration of bone tissuethat leads to decreased bone massand bone fragility and an increased riskof fracture.1 Low bone density measurementis the best predictor of future fracture.Primary osteoporosis results fromnormal aging processes and decreasedgonadal function; secondary osteoporosis,which accounts for about 5% ofcases, is associated with inactivity, chronicdiseases, nutritional factors, medication(such as glucocorticoids), and otherexternal conditions (Table 1).

 
Table 1 -Risk factors associated with osteoporosis
Personal risk factors
 
Lifestyle

History
 
Medication use

HRT, hormone replacement therapy. *Primary risk factor.

The prevalence of osteoporosis increaseswith age in both sexes. Thiscondition affects 20% of women in their60s, 33.3% of women in their 70s, and70% of women in their 80s. In thecourse of a lifetime, 1 of 2 women willincur a fracture secondary to osteoporosis.By extreme old age, 1 in 6 menwill have had a hip fracture.2 In theyear following a hip fracture, there is a15% to 20% reduction in expected survivalfor both men and women. Qualityof-life issues that affect patients andtheir families include psychologicalreactions, social consequences, functionallimitations, and pain. The societalimpact of this disease is significant,including 432,000 hospital admissions,2.5 million physician visits, and 180,000nursing home admissions annually.2

PREVENTION
Osteoporosis is no longer thoughtto be an inevitable consequence ofaging. Prevention is vastly preferableto treatment. The best foundation forstrong bone tissue is laid in childhood.Healthy habits early in life, such as agood diet, physical activity, and avoidanceof smoking, build strong boneand provide larger stores to draw fromlater in life. Bone mass increases duringchildhood and adolescence andpeaks between 25 and 30 years of age.Once peak bone mass is reached,bone loss must be slowed to preventosteoporosis.

White women have a higher riskof osteoporosis resulting from decreasedbone mass than men or darker-skinned women. After age 30years, women lose bone mass at arate of 0.3% to 0.5% per year. Beginningwith menopause, this rate increasesto 3% to 5% per year for about5 to 7 years. The first 3 years aftermenopause are a key window of timeto educate women about reducingbone loss and to institute strengtheningprograms. Men lose bone massfrom midlife through old age atthe same rate as premenopausalwomen.3,4

When counseling your youngerpatients about exercise, healthy diet,and smoking cessation, use the opportunityto mention osteoporosis. Emphasizethat it is never too early--ortoo late--to implement risk-reductionmeasures.

DIAGNOSIS
Many factors can help identify patientsat risk for osteoporosis. Theseinclude race, genetics, sex, personaland family history, medication use,and lifestyle issues (see Table 1). Therisk increases with cumulative riskfactors.2,5

 
Table 2 – BMD measurement: Which patients to test?
Recommendations from the National Osteoporosis Foundation and the American Medical Association
 

Recommendations from the World Health Organization
 

BMD, bone mineral density; HRT, hormone replacement therapy. Adapted from National Osteoporosis Foundation. Physician's Guide to Prevention and Treatment of Osteoporosis. 19982; Genant HK et al. Osteoporos Int. 199916; American Medical Association. Managing Osteoporosis. 1999.

Regularly review your patient'srelative risk of osteoporosis. Mostguidelines suggest that screening notbe done universally but on an individualbasis according to risk factors(Table 2). Screening is especially importantat menopause, when aggressivepreventive and therapeutic interventionsare most effective.

A history of acute or chronicback pain from thoracic to lumbar vertebraeor loss of height may alert youto initiate the screening process. Osteoporosiscan be far advanced, however,before a patient feels any pain. Althoughboth the history taking andthe physical examination are important,they are not sensitive or specificenough to make or exclude a diagnosisof osteoporosis.

The preferred method of bonedensity measurement is dual-energyx-ray absorptiometry (DEXA), whichmeasures bone mass in the spine,hip, and total body by scanning andfiltering x-rays from a stable source.DEXA scans are accurate (error rate,4% to 8%); precise (error rate, 1% to3%); fast (3 to 10 minutes); and involvelow radiation exposure.5 However,because of its relatively highcost, DEXA is recommended as ascreening tool only for those at greatestrisk for osteoporosis.

Dual photon absorptiometry is aless precise indicator of bone densitythan DEXA. Ultrasound densitometryis promising, though unproved.6 Othermodalities--which are not as commonlyused--include single photonabsorptiometry and quantitative CT.

Specific biochemical markers indicatebone formation and resorption,although these markers are only weaklyassociated with changes in bonemass and do not predict fracture risk.Aminoterminal and cross-linked carboxyterminaltelopeptide levels are elevatedin osteopenic women and moreso in osteopenic men. Aminoterminalpropeptide, osteocalcin, and alkalinephosphatase also are indicators of increasedbone turnover. These and otherresearch tools may eventually beused in diagnosis or for following thecourse of treatment, because they aremore dynamic than scans (althoughreliability is still an issue).7,8 Tests ofbiochemical markers can show withina few months whether bone turnoverhas decreased, whereas significantchanges in nonspinal bone mineraldensity (BMD) may not appear onDEXA scans for at least 2 years.

NONDRUGINTERVENTIONSDiet. Proper nutrition is essentialfor optimal bone health at all ages. Calciumis the most important nutrient forattaining peak bone mass during thedevelopmental years.2 The combinationof calcium and vitamin D reduceship and other nonvertebral fractures. Atypical American diet provides lessthan 700 mg/d of calcium. The recommendeddaily allowances for calciumare listed in Table 3.

 
Table 3 - Recommended calcium intake
Age
 
Dosage (mg/d)

Infants < 6 mo
 
400

Infants 6 mo - 1 y
 
600

Children 1 - 10 y
 
800 - 1200

Young adults 11 - 24 y
 
1200 - 1500

Adults ≥ 25 y
 
1000

Pregnant and breast-feeding women
 
1200 - 1500

Adults > 65 y
 
1500

Postmenopausal women > 50 y not taking hormone replacement therapy
 
1500

Postmenopausal women > 50 y taking hormone replacement therapy
 
1000

Adapted from NIH Consensus Development Panel on Optimal Calcium Intake. JAMA. 1994.

Excellent calcium-rich food choicesinclude low-fat or nonfat milk,cheese, and yogurt. Consumption canbe increased with the use of calciumfortifiednondairy foods, such as orangejuice, rice or soy milk, breakfastcereals, breads, and margarines.Foods such as dark green leafy vegetables,hazelnuts, dried figs, fish withsmall edible bones (such as cannedsalmon or sardines), and tofu processed with calcium sulfate all containsignificant amounts of calcium.9

Calcium supplementation. Whena patient's history and physical examinationsuggest a need for calcium supplementationfor either prevention ortreatment of osteoporosis, recommendan over-the-counter product taken in divideddoses; calcium absorption is optimalwhen no more than 600 mg is ingestedat once. Calcium carbonate isthe most efficient and least expensivesource of calcium.10,11 A good rate of absorptionis also desirable. Chewabletablets are an acceptable choice; absorptionmay be enhanced when calciumis ingested with food.

Vitamin D. This nutrient facilitatesthe absorption of calcium.11 Theminimum recommended dosage is400 IU/d. This amount can be attainedin the following ways:

  • Exposure to sunlight for 10 to 15minutes 3 times a week.
  • Consumption of foods such as milk,egg yolks, or fortified foods.
  • Ingestion of a multivitamin.

The recommended dosage is1000 IU/d for persons aged 19 to 50years and 1200 IU/d for those 51 yearsand older.12 Pharmacologic doses of vitaminD have been used to preventand treat glucocorticoid-induced osteoporosis.13 Studies emphasize thatmany elderly persons may have subclinicalvitamin D deficiency becauseof inadequate sun exposure, suboptimalabsorption, or decreased conversionof nutritional precursors evenwith adequate sun exposure.

Exercise. Prevention and managementof osteoporosis includes anexercise program individually tailoredto maintain bone density and slow therate of bone loss with minimum risk.Exercise early in life contributes tohigher peak bone mass, although it hasonly a modest effect on slowing the decreasein BMD and does not decreasefracture rates.4 Exercise improves musclecoordination, mobility, and balance;it reduces the incidence of falls by 25%.Exercise also improves function anddelays loss of independence. Ideally, patientsshould exercise on most days, alternatingactivities to maximize resultsand lessen recovery time from anystress associated with exercise. Encouragepatients to choose activitiesthey enjoy; this promotes consistency.9

A comprehensive exercise programincludes a balance of aerobic,strengthening, and flexibility activities.14 A combination of activities forstrengthening bones includes weightbearingexercises, such as running,walking, skating, and tennis. To avoidimpact-loading the spine, patients withosteoporosis should avoid such activitiesas jumping, high-impact aerobics,and running.

Muscle strength training (resistancetraining) also strengthens bone.Specific exercises (such as leg press,calf raises, knee curl, quadriceps extension,back extension, lateral pulldown, bent-over row, biceps curl, tricepsextension wrist curl, and shouldershrugs) should be included tostrengthen legs, hips, back, arms,wrists, shoulders, and neck. Excessivespinal flexion (such as in sit-ups, toetouches,and crunches and on rowingmachines) and abduction and adductionof the leg can be harmful.

Smoking cessation. Bone healthis one more reason to recommendsmoking cessation: smokers have 5times the relative risk of osteoporosisof nonsmokers.15

Fall prevention. A propensity tofall may be a more important risk factorfor fracture than commonly recognized.Environmental conditions thatincrease the risk of falls include hazardssuch as slippery floors, unsafebathrooms, area rugs, obstacles in theliving space, and inappropriate shoes.Medical conditions that contribute torisk include postural hypotension or alteredsensorium secondary to medicationuse, impaired vision, muscle weakness,poor coordination, and lack ofagility. Review patients' medications,especially sedatives and hypnotics, andscreen for alcohol abuse.

Advise patients at risk for fractureto do a safety assessment of theirhome. They may wish to consider installingsafety bars and handrails, re-moving area rugs and potential obstacles,ensuring adequacy of lighting,and repairing cracked sidewalks. Garmentswith hip padding offer extraprotection to patients at very high riskfor falls.

DRUG THERAPY
Guidelines such as those of the NationalOsteoporosis Foundation (NOF)can be helpful in making the decisionto initiate drug therapy.2 The NOF recommendstreatment of women withT-scores below --2 without--or --1.5with--other risk factors for osteoporoticfracture. However, some patients, suchas those older than 70 years with multiplerisk factors, may need treatmenteven without BMD testing. Consider osteoporosistreatment in all women whopresent with postmenopausal vertebraland hip fractures.2

The World Health Organization(WHO) recommends offering treatmentto patients with a T-score of lessthan --2.5, to postmenopausal womenwith a T-score between --1 and --2.5,and to other patients with a T-score between--1 and --2.5 and additional riskfactors.16 The WHO has determinedthat the use of bone-active drugs at thetime of first fracture or for the treatmentof high-risk patients, includingthose with low BMD, is a cost-effectiveintervention.

Hormone replacement therapy(HRT). Formulations containing estrogenalone or estrogen plus progestinmay be administered orally or transdermally.They decrease bone loss,increase bone density in the hip andspine, and decrease the risk of spinefractures in postmenopausal women.17,18Increased BMD can be sustained ifHRT is started at menopause or withinthe first few postmenopausal years19,20and continued into very late life.21

Absolute contraindications toHRT include a history of breast canceror other estrogen-dependent malignancy,abnormal vaginal bleeding, andthromboembolic conditions. Relativecontraindications include migraine, astrong family history of breast cancer,uterine neoplasia (benign or malignant),hypertriglyceridemia, and liverdisease.21

Selective estrogen receptor modulators(SERMs). These agents weredeveloped to mimic the beneficial effectsof estrogen on the bone, heart,and CNS while avoiding its adverse effectson the uterus and breasts.22,23SERMs do not relieve menopausalsymptoms, such as hot flashes, andmay sometimes worsen them. Theymay be associated with muscle crampingand thrombophlebitis. Contraindicationsinclude pregnancy and activeor past venous thromboembolism.23

A large, prospective randomizedtrial examined the effects of the SERMraloxifene on the risk of vertebral fracturesin women who met the WHO criteriafor osteoporosis. Compared withplacebo, a 3-year regimen of 60 mg/dof raloxifene was associated with a relativerisk of 0.7 for vertebral fractureincidence.24 There was no difference inthe incidence of nonvertebral fracturesbetween the placebo and raloxifenegroups.

HRT continues to be the costeffectiveagent of choice to decreasebone loss, but SERMs are an optionfor women who cannot or do not wishto use HRT.

Calcitonin. This hormone inhibitsosteoclastic bone resorption; itsrelease is primarily controlled by circulatinglevels of ionized calcium. Itmay be of most value in women withlow BMD who are not candidates forHRT and who are more than 5 yearspostmenopausal.

The recommended dosage ofsalmon calcitonin nasal spray is 200IU/d. A recent study concluded thatthis agent decreased the risk of newvertebral fractures by 33% in postmenopausalwomen with osteoporosis.25 In some trials, calcitonin reducedpain and/or analgesia consumptionin this group.26 Adverseeffects include nausea, runny nose,and rhinitis.

Bisphosphonates. These agentsinhibit bone resorption and increasespine and hip density through a mechanismthat is not fully understood. Thebisphosphonates alendronate and risedronatehave been shown to decreasevertebral fracture risk by 30% to 48%in women with established osteoporosis.27,28 These drugs also stimulate osteoblasticactivity.29,30 Alendronate hasalso been found beneficial for menwith osteoporosis.31

Alendronate and risedronate decreasethe risk of subsequent nonvertebralfractures in postmenopausalwomen with osteoporosis and in adultswith glucocorticoid-induced osteoporosiswho have suffered an initialfracture resulting from aging and estrogendeficiency.28 The recommendeddosage of alendronate is 5 mg/d forosteoporosis prevention and 10 mg/dfor treatment. It is also available in aformulation that can be taken weekly;dosages are 35 mg once weekly forprevention and 70 mg once weekly fortreatment. The recommended dosageof risedronate is 5 mg/d.

Bisphosphonates must be takenwith plain water at least half an hourbefore the first food, beverage, or medicationof the day because of poor absorptionand the risk of esophageal injury.These drugs are not recommendedfor patients with severe renalimpairment or hypocalcemia.28 Calciumand antacids interfere with the absorptionof bisphosphonates.

References:

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2. National Osteoporosis Foundation. Physician’sGuide to Prevention and Treatment of Osteoporosis.Washington, DC: National Osteoporosis Foundation;1998:1-29.
3. Lambing CL. Osteoporosis prevention, detection,and treatment. Postgrad Med. 2000;107:37-41.
4. National Institutes of Health. Consensus DevelopmentConference Statement: Osteoporosis Prevention,Diagnosis, and Therapy. Bethesda, Md: NIH; 2000:1-29.
5. Scientific Advisory Board, Osteoporosis Societyof Canada. Clinical practice guidelines. Available at:www.osteoporosis.ca. Accessed April 2, 2002.
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7. Scariano JK, Glew RH, Bou-Serhal CE, et al.Serum levels of cross linked N-telopeptides andaminoterminal propeptides of type I collagen indicatelow bone mineral density in elderly women.Bone. 1998;23:471-477.
8. Chandani AK, Scariano JK, Glew RH, et al.Bone mineral density and serum levels of aminoterminalpropeptides and cross linked N-telopeptidesof type I collagen in elderly men. Bone. 2000;26:513-518.
9. Bonnick SL. The Osteoporosis Handbook. Dallas:Taylor Publishing Company; 1994.
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12. Institute of Medicine. Dietary Reference Intakes.Washington, DC: National Academy Press, Foodand Nutrition Board; 1998.
13. Hahn TJ. Steroid and drug induced osteopenia.In: Favues MJ, ed. Primer on Metabolic Bone Diseasesand Disorders of Mineral Metabolism. Kelseyville, Calif:American Society for Bone and Mineral Research;1990:158-162.
14. Preisinger E, Alacamlioglu Y, Pils K, et al. Exercisetherapy for osteoporosis: results of a randomizedcontrolled trial. Br J Sports Med. 1996;30:209-212.
15. Ullom-Minich P. Prevention of osteoporosis andfractures. Am Fam Physician. 1999;60:194-202.
16. Genant HK, Cooper C, Poor G, et al. Interimreport and recommendations of the World HealthOrganization Task-Force for Osteoporosis. OsteoporosInt. 1999;10:259-264.
17. Gibaldi M. Prevention and treatment of osteoporosis:does the future belong to hormone replacementtherapy? J Clin Pharmacol. 1997;37:1087-1099.
18. Lufkin EG, Wahner HW, O’Fallon WM, et al.Treatment of postmenopausal osteoporosis withtransdermal estrogen. Ann Intern Med. 1992;117:1-9.
19. Torgerson DJ, Bell-Syer SEM. Hormone replacementtherapy and prevention of nonvertebral fractures:a meta-analysis of randomized trials. JAMA.2001;285:2891-2897.
20. Grady D, Cummings SR. Postmenopausal hormonetherapy for prevention of fractures: how goodis the evidence? JAMA. 2001;285:2909-2910.
21. Hulley S, Grady D, Bush T, et al, for the Heartand Estrogen/progestin Replacement Study (HERS)Research Group. Randomized trial of estrogen plusprogesterone for secondary prevention of coronaryheart disease in postmenopausal women. JAMA.1998;280:605-613.
22. Ashworth LE. Focus on raloxifene. A selectiveestrogen receptor modulator for prevention of osteoporosisin postmenopausal women. Formulary. 1993;33:305-317.
23. Delmas PD, Bjarnason NH, Mitlak BH, et al.Effects of raloxifene on bone mineral density, serumcholesterol concentrations, and uterine endometriumin postmenopausal women. N Engl J Med. 1997;337:1641-1647.
24. Ettinger B, Black DM, Mitlak BH, et al, for theMultiple Outcomes of Raloxifene Evaluation (MORE)investigators. Reduction of vertebral fracture risk inpostmenopausal women with osteoporosis treatedwith raloxifene: results from a 3-year randomizedclinical trial. JAMA. 1999;282:637-645.
25. Chesnut CH, Silverman S, Andriano K, et al, forthe Prevent Recurrence of Osteoporotic FracturesStudy. A randomized trial of nasal spray salmon calcitoninin postmenopausal women with establishedosteoporosis. Am J Med. 2000;109:267-276.
26. Plosker GL, McTavish D. Intranasal salcatonin(salmon calcitonin): a review of its pharmacologicalproperties and role in the management of postmenopausalosteoporosis. Drugs Aging. 1996;8:378-400.
27. Liberman LA, Weiss SR, Broll J, et al. Effect oforal alendronate on bone mineral density and theincidence of fractures in postmenopausal osteoporosis.N Engl J Med. 1995;333:1437-1443.
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29. Ettinger B, Pressman A, Schein J. Clinic visitsand hospital admissions for care of acid relatedupper gastrointestinal disorders in women usingalendronate for osteoporosis. Am J Managed Care.1998;4:1377-1382.
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