preventing and treating osteoporosis: pharmacologic and nonpharmacologic approaches

S13 The Journal for Nurse Practitioners - JNP June 2009

INTRODUCTIONOsteoporosis, the most common bone disease, is a sys-temic skeletal disorder characterized by reduced bonemass, deteriorating bone strength and architecture, and anincreased risk of fracture.1 Although once perceived to bean inevitable part of aging for women, osteoporosis isnow known to be a preventable disease that affects bothmen and women over a broad age spectrum.The epi-demiology and economic impact of osteoporosis arereviewed elsewhere in this supplement (see Osteoporosis:Background and Overview on page S4).

Prevention of osteoporosis is a lifelong process thatcenters on optimizing bone health. Strategies can beeither nonpharmacologic or pharmacologic. However,once osteoporosis is diagnosed, the only availabletreatment options proven to reduce the risk of frac-tures are pharmacologic agents. As with other diseases,prevention is preferable to treatment in that it canreduce morbidity and health care costs. In osteoporo-sis, if left untreated, certain changes in bone microar-chitecture associated with bone loss are irreversibleafter a certain point as the process of bone resorptioncomes to exceed the synthesis of new bone matrix.2

This paper will discuss the various approaches to pre-venting and treating osteoporosis, emphasizing theindications and contraindications for use, advantagesand limitations, and potential side effects. For abroader discussion of when to implement theseapproaches and in which patients, please refer to Inte-grating Osteoporosis into Clinical Practice, the final paperin this supplement, on page S21.

NONPHARMACOLOGIC APPROACHES FOR PREVENTIONDiet and NutritionGood nutrition is essential to bone health.Adequatecalcium and vitamin D intake over the lifespan are crit-ical to building peak bone mass and may require sup-plementation to reach target levels.The skeleton con-tains 99% of the body’s calcium stores, and when cal-cium intake is insufficient, bone tissue from the skele-ton is resorbed to maintain constant blood levels.3 Rec-ommended calcium intake for patients from childhoodthrough older adulthood is shown in Table 1.4,5 Keep inmind that too much calcium may be as dangerous astoo little: excess intake (> 2000 to 2500 mg daily) mayincrease the risk of developing kidney stones or cardio-

ABSTRACTOsteoporosis is a serious disease that is preventable and treatable. Prevention strategiesinclude a healthy diet, adequate calcium and vitamin D intake (via supplementationif needed), and lifestyle changes (eg, exercise with resistance, avoiding smoking andexcessive alcohol intake). Medications proven to reduce the risk of osteoporoticfractures include hormone therapy, selective estrogen receptor modulators(SERMs), parathyroid hormone, and bisphosphonates. Nurse practitioners (NPs)should evaluate patients for osteoporosis and educate patients on the importance ofbone health. For patients who have osteoporosis, it is important to discuss fracturerisks and potential sequelae.Working with patients to select the proper drug forthem is a crucial part of the clinical decision-making and management process.The importance of continued communication and follow-up are also vital.

Preventing and Treating Osteoporosis:Pharmacologic and Nonpharmacologic ApproachesJulia Chavez, RN, MSN, CFNP

The Journal for Nurse Practitioners - JNP S14www.npjournal.org

vascular disease.3,5 Despite the ready availability of theserecommendations, only an estimated 25% of boys and10% of girls 9 to 17 years of age, and only 50% to 60%of older adults, consume an adequate amount of cal-cium daily.1 Health professionals should investigate theirpatients’ calcium and vitamin D intake during routineoffice and hospital visits.

To optimize the absorption of calcium, adequatelevels of vitamin D are also needed.Vitamin D con-tributes to calcium absorption, bone health, muscleperformance, and balance; in so doing, it reduces mor-bidity from falling.6 Milk intake is the primary sourceof vitamin D for most infants and children, unless dairyintake is contraindicated.To ensure that calciumabsorption is supported by adequate vitamin D intake,supplementation is needed in infants and children whodo not consume sufficient dairy products, as well as inadolescents and adults, because dairy consumptiontends to decrease with age.1 The recommended dailyintake for vitamin D appears in Table 1.4,5 Olderpatients with malabsorption (eg, celiac disease) orchronic kidney disease, or who are housebound andhave limited exposure to sunlight have an elevated riskof vitamin D insufficiency and may require greaterconsumption.3

Nutritional factors that may negatively affect calciumlevels include a diet that is high in protein, phosphorus,sodium, or caffeine. However, if calcium and vitamin Dintake are adequate, these factors are less likely to haveclinical relevance.1

ExerciseExercise is another important preventive tool. Resis-tance and high-impact activities are considered to bethe most beneficial.1 Studies have shown that engagingin such exercises (eg, running and weight training) earlyin life leads to higher peak bone mass. Low-impactexercises, such as walking and bicycle riding, have onlya minimal effect on bone mass. Less is known about theeffect of exercise begun later in life (eg, during middleage), although it is thought that high-impact physicalactivity may have a modest preventive effect on the lossof bone mass when combined with adequate calciumand vitamin D intake. Other benefits of exercise,including increased muscle mass, strength, and function,benefit people of all ages. Exercise also helps preserveindependence in the elderly and has been shown toreduce falls by up to 25%.1

Behavioral ModificationSmoking and excessive alcohol consumption contributeto bone demineralization. Nurses can play a key role inidentifying patients who smoke, or those who drinkexcessively, and offer behavioral counseling as part of acomplete osteoporosis prevention program, especially forpatients with other risk factors for osteoporosis. Smokingcessation programs are recommended for all patients whosmoke, and alcohol intake should be kept below 3 drinksper day to maintain good bone health and reduce the riskof falling.

PHARMACOLOGIC OPTIONS FOR PREVENTION AND TREATMENTHormone Therapy While not recommended for treatment of establishedosteoporosis, estrogen therapy (ET), or hormone ther-apy (HT) could be considered for prevention in post-menopausal women at risk for osteoporosis. However,because of safety concerns with ET/HT (see below),the U.S. Food and Drug Administration (FDA) cur-rently recommends that non-estrogen options beemployed before considering prophylactic ET/HT forthe prevention of osteoporosis (Table 2).3 The Women’sHealth Initiative (WHI) reported that 5 years of HT ledto a 35% reduction in the risk of vertebral and hip frac-tures and a 23% decrease in other osteoporotic frac-tures.7 Cauley et al found that women who took HThad a reduced risk for fracture at the initial follow-up,

Table 1. National Osteoporosis Foundation Calcium andVitamin D Recommendations4,5

Calcium Vitamin DGroup (mg daily) (IU daily)Children & Adolescents1-3 years 500 400*

4-8 years 800 400*

9-18 years 1300 400*

Adult Women & Men19-49 years 1000 400-800

50 years 1200 800-1000

Pregnant & Breastfeeding Women18 years 1300 400-800

19 years 1000 400-800

*National Osteoporosis Foundation does not have specific vitamin Drecommendations for these age groups. These are therecommendations of the American Academy of Pediatrics.


with further reductions seen over time.8 Moreover, thewomen who took the combined HT also had increasedbone mineral density (BMD) that continued to improveduring follow-up.

Unfortunately, ET/HT has also been associated withserious adverse effects.The WHI investigators reportedthat, after 5 years of follow-up, HT (estrogen and proges-terone) increased the risk of myocardial infarction, stroke,invasive breast cancer, pulmonary emboli, and deep veinphlebitis.7 Factors that were later found to affect theserisks included the number of years between menopauseand the start of HT, and the use of estrogen alone vsestrogen plus progestin.9,10 The incidence of cardiovasculardisease did not increase in women who started HTwithin 10 years of menopause, and the incidence in breastcancer did not increase over 7.1 years of treatment inwomen who received estrogen alone.9,10

Oral and IV Bisphosphonates The bisphosphonates, which include alendronate, rise-dronate, ibandronate, and zoledronic acid, are recom-mended as first-line options in the management ofosteoporosis in postmenopausal women.Alendronate,risedronate, and zoledronic acid are also indicated fortreatment to increase bone mass in men with osteo-porosis. Bisphosphonates are classified as antiresorptiveagents because they inhibit bone resorption directly,thereby reducing net bone turnover, increasing bonemineral density, improving bone strength, and loweringfracture risk.11-14 The indications, dosing, and fracturerisk reductions from randomized clinical trials, as pro-vided in the agents’ package inserts, are summarized inTable 2.11-14

Because of the well-documented problem of adher-ence to and persistence with oral regimens,15 the trend indevelopment of bisphosphonates has been toward formu-lations that are administered less frequently.The range ofoptions for oral drugs now spans daily, weekly, andmonthly, whereas the options for IV include quarterlyand once yearly.The range of options allows patients andhealth care providers to discuss which option best suitsthe patient’s needs.

Alendronate. Alendronate is given orally 10 mg/dayor 70 mg once weekly and is now available as a nonpro-prietary generic.11 The 10-mg daily dose reduced relativerisk of spine fractures in postmenopausal women withosteoporosis by 47% and hip fractures by 51%, relative toplacebo, over 3 years.11,16 The weekly dose, which is now

more commonly used, has similar efficacy to the dailydose, as demonstrated by showing similar improvementsin BMD in a head-to-head trial.

Risedronate. Risedronate is given orally in dosesranging from 5 mg/day and 35 mg/week to 150mg/month.12 The drug reduced the relative risk ofspine fractures in postmenopausal women with osteo-porosis by up to 49% and non-spine fractures by up to39% over 3 years.12,17,18 Treatment with daily, weekly, ormonthly formulations of risedronate significantlyincreases BMD.12

Ibandronate. Ibandronate is given 150 mg (orally)once per month, or 3 mg (IV) every 3 months.13 Iban-dronate given orally 2.5 mg daily was shown to reducethe relative risk of spine fractures in postmenopausalwomen with osteoporosis by 52% but did not signifi-cantly reduce the risk of non-spine fractures.13,19 Themonthly dose was demonstrated to provide BMDincreases superior to the daily dose over 1 year, and allmarketed doses improve BMD significantly vs placebo.13,20

Zoledronic acid. Zoledronic acid is the first annualtreatment for osteoporosis. It is administered by IV at adose of 5 mg once a year over at least 15 minutes.14 Inpostmenopausal women with osteoporosis, zoledronicacid reduced the incidence of spine fractures by 70%, hipfractures by 41%, and non-spine fractures by 25%, com-pared with placebo over 3 years.14,21 In this study, it alsosignificantly increased BMD at the spine and hip. Zole-dronic acid is the only bisphosphonate that has been eval-uated to prevent future fractures in men and women fol-lowing surgical repair of a low-trauma hip fracture. Useof IV zoledronic acid reduced the risk of new clinicalfractures by 35% and clinical spine fractures by 46%,compared with placebo.22

Bisphosphonate Safety and TolerabilitySide-effect profiles are similar for all of the approved bis-phosphonates, and the package inserts reflect these simi-larities.11-14 Numerous large-scale clinical trials and morethan a decade of experience in millions of patients in theclinic has led to a well-established safety profile for theclass. However, some important considerations should bekept in mind for the class, for the oral agents, and forthose administered via IV.

For the class as a whole, it is important to rememberthat serum creatinine should be measured and an esti-mated creatinine clearance calculated, as no bisphospho-nate is recommended to be used in patients with severe


Table 2. FDA-Approved Drugs for Osteoporosis3,11-14,26,28,29,32

Indication(s)/ 3-Year Relative Fracture Drug Contraindication(s) Dosing Risk ReductionBisphosphonatesAlendronate sodium11

(Fosamax and Fosamaxplus D) (generic available)

Prevention and treatment ofpostmenopausalosteoporosis

Treatment to increase bonemass in men withosteoporosis

Treatment of glucocorticoid-induced osteoporosis

Esophageal abnormalities

Inability to stand or sit uprightfor 30 minutes after dosing

Hypocalcemia

Hypersensitivity

Prevention: 5 mg/day and35 mg/week

Treatment: 10 mg/day and70 mg/week or 70 mg/weekwith 2800 IU and 5600 IU ofvitamin D

47%: spine fractures

51%: hip fractures

Ibandronate sodium13

(Boniva)Prevention (only oral doses)and treatment ofpostmenopausalosteoporosis

Inability to stand or situpright for 60 minutes afteroral dosing

Hypocalcemia

Hypersensitivity

2.5 mg/day orally

150 mg/month orally

3 mg every 3 months IVover 15-30 seconds


Risedronate sodium12

(Actonel and Actonel with Calcium)

Prevention and treatment ofpostmenopausalosteoporosis

Prevention and treatment ofglucocorticoid-inducedosteoporosis

Inability to stand or sit uprightfor 30 minutes after dosing

Hypocalcemia

Hypersensitivity

5 mg/day and 35 mg/week 49%: spine fractures

39%: non-spine fractures

Zoledronic acid14

(Reclast)Treatment ofpostmenopausalosteoporosis

Treatment of patients afterlow-trauma hip fracture

Treatment to increase bonemass in men withosteoporosis

Treatment and prevention ofglucocorticoid-inducedosteoporosis

Hypocalcemia

Hypersensitivity

5 mg IV infusion over atleast 15 minutes onceyearly


41%: hip fractures

25%: non-spine fractures

In post-hip fracture patients:

35%: all clinical fractures

46%: clinical spine fractures


renal impairment (creatinine clearance < 30-35mL/min).11-14 Patients with known disorders of mineralmetabolism should have any deficiencies correctedbefore therapy with a bisphosphonate is initiated.Ade-quate daily intake of calcium and vitamin D is importantfor all patients with osteoporosis and should be stronglyrecommended for patients on bisphosphonates.The“Precautions” section of all bisphosphonate labels men-

tions a possible side effect of severe and occasionallyincapacitating bone, joint, or muscle pain; however, suchcases are infrequent.11-14

With the oral agents, the most concerning poten-tial side effects are upper GI problems, such as diffi-culty swallowing, esophageal inflammation, and gastriculcer.11-13 Patients should also remain upright for 30 to60 minutes after taking oral bisphosphonates; reclining

Table 2. Continued

Indication(s)/ 3-Year Relative Fracture Drug Contraindication(s) Dosing Risk ReductionCalcitoninSalmon calcitonin28,29

(Miacalcin, Calcimar,Fortical)

Treatment of osteoporosisin women >5 yearspostmenopausal

Clinical allergy to salmoncalcitonin

200 IU single dailyintranasal spray

Subcutaneous and oraladministration alsoavailable

Increases bone mineraldensity

Estrogen/Hormone Therapy(ET/HT)*ET3

(Climara, Estrace,Estraderm, Estratab, Ogen,Ortho-Est, Premarin, Vivelle)HT (Activella, Femhrt,Premphase, Prempro)

Prevention of osteoporosisand other symptoms ofmenopause

Breast- or estrogen-dependent carcinoma,abnormal vaginal bleeding,history of thrombosis, liverdysfunction, pregnancy

Varies by individual brand 35%: vertebral and hipfractures†

23%: other fractures†

Estrogen Agonist/Antagonist Raloxifene25

(Evista)Prevention and treatment ofpostmenopausalosteoporosis

Active or past history ofvenous thromboembolism

60 �g/day orally 30%: spine fractures withprior spine fracture

55%: spine fractures withoutprior spine fracture

Parathyroid HormoneTeriparatide32

(Forteo)Treatment ofpostmenopausalosteoporosis in women athigh risk for fracture

Treatment to increase bonemass in men at high risk for fracture

Hypersensitivity

Patients at increasedbaseline risk forosteosarcoma

20 �g/day subcutaneousinjection, self-administered

65%: spine fractures53%: non-spine fractures

*Because of the potential risks associated with ET/HT, these agents should be used at the lowest effective doses and for the shortest duration to meetthe objectives of treatment. The FDA recommends using approved non-estrogen treatments when prevention of osteoporosis is the sole concern. †Findings for conjugated estrogens/medroxyprogesterone acetate from the WHI.7


soon after administration may cause esophageal irrita-tion in patients with gastroesophageal reflux.3 Becauseoral bisphosphonates are poorly absorbed, they mustbe taken with a glass of plain water (ie, not mineralwater) on an empty stomach after an overnight fast.Patients taking alendronate or risedronate also mustnot consume food, drink, other medications, or nutri-tional supplements for at least one-half hour afteradministration. For patients taking ibandronate, thesame instructions apply but the recommended waitingtime is 1 full hour.23

Because IV bisphosphonates bypass the GI tract andare 100% bioavailable, they pose no risk for upper GIevents, and they eliminate the need for the patient to fol-low complex dosing instructions. However, in somepatients, IV bisphosphonates are associated with theoccurrence of transient post-dose symptoms, such asarthralgia, headache, myalgia, or fever.These symptomsoccur within 3 days of administration, usually resolvewithin 3 days (but may take 7 to 10 days), and typicallyoccur less often with subsequent doses.14,21 Health careprofessionals should counsel patients that they may expe-rience these symptoms and that treatment with acetamin-ophen as needed for up to 72 hours after the infusion canhelp reduce or prevent symptoms.

A rare side effect, osteonecrosis of the jaw (ONJ), hasbeen reported in patients receiving bisphosphonate ther-apy. However, the vast majority of cases are seen in cancerpatients treated with intravenous bisphosphonates formultiple myeloma and breast cancer24,25 and may reflectthe immunocompromised state of these patients. Inosteoporosis patients taking IV or oral bisphosphonates, itappears that ONJ occurs rarely and may be no more fre-quent than in the general population or backgroundrate.25 Because media reports have heightened patients’concerns, it is important to inform osteoporosis patientsbefore they receive bisphosphonate therapy that thispotential side effect is very rare, and that the benefits ofpreventing fractures outweigh the risk of ONJ.

Estrogen Agonist/Antagonist Therapy Raloxifene is the only estrogen agonist/antagonist, alsoknown as a selective estrogen receptor modulator(SERM), approved for the prevention and treatment ofpostmenopausal osteoporosis (Table 2).26 It is taken orallyonce a day in a 60-mg dose.When given over 3 years,raloxifene reduced the risk of new spine fractures inpatients without prior vertebral fractures by 55% and in

patients with existing spine fractures by 30%.26,27 Ralox-ifene has not demonstrated any reductions in risk of non-spine fractures.

Raloxifene is contraindicated for patients at risk fordeep vein thrombosis or who have had a prior throm-botic event. Moreover, it may exacerbate hot flushes insome women.26

Calcitonin Calcitonin is a naturally occurring hormone that isimportant in calcium regulation and bone metabolism.Salmon calcitonin is approved for use in women whohave been postmenopausal for at least 5 years and is givenas an intranasal spray 200 IU/day.28 It has been shown toprevent bone loss in postmenopausal women with osteo-porosis.29 However, it is considered to have relatively weakantifracture efficacy compared with the bisphosphonates.30

Thus, it is most appropriate for use in patients for whomthe other treatments are contraindicated.Anecdotal clini-cal experience suggests that the drug may be useful forrelief of bone pain resulting from compression fractures.31

Nasal irritation has been reported and patients shouldalternate nostrils daily.28,29 Patients using calcitonin shouldbe warned not to coat the nostril to reduce irritation, asthis will decrease absorption of the drug.

Parathyroid HormoneParathyroid hormone, PTH(1-34) or teriparatide, is ananabolic agent given as a daily, subcutaneous injectionto promote bone formation.Teriparatide increasesBMD, improves bone strength, and reduces fracturerisk. It works by increasing bone formation above thatof bone resorption during the period of time knownas the “anabolic window.”33 During a 21-month courseof treatment, postmenopausal women receiving teri-paratide experienced a 65% reduction in the rate ofspine fractures and a 53% reduction at nonspinal sites.34

Teriparatide is self-injected subcutaneously everyday for a recommended period of 18 to 24 months.32

The safety and efficacy of the drug have not beenestablished beyond 2 years. On discontinuation, thedrug should be followed with an antiresorptive agentto sustain or improve the positive changes in BMD.Health professionals should instruct patients on thecorrect injection technique to ensure proper adminis-tration.Teriparatide is available in a dosing pen andmust remain refrigerated; if left unrefrigerated for morethan 30 minutes, the drug may lose its effectiveness.


Teriparatide is generally well-tolerated. Common sideeffects include dizziness or heart palpitations; these maylast for 10 to 15 minutes after the injection.32,34

Combination StrategiesBoth bisphosphonates and estrogen inhibit bone resorp-tion, but they may act through different mechanisms.Thecombination of estrogen and alendronate may increaseBMD beyond that of the individual agents.35 Estrogenplus calcitonin,36 estrogen and androgen,37 estrogen plusetidronate,38 and alendronate and raloxifene39 also appearto act synergistically on bone density. Fracture data arenot available for these combinations.

Patient PreferencePatients tend to prefer medications that require less fre-quent dosing. Monthly or weekly dosing has beenshown to be preferred over daily dosing. However,compliance is still suboptimal. Less than 50% of patientsare persistent over a 12-month period. If a patient andhealth care provider decide that an annual IV bisphos-phonate is appropriate, the health care provider canchoose to refer the patient to an infusion center or toadminister the drug in their own clinic if it is set up forinfusion capabilities.Additional practical informationon zoledronic acid infusion is available at the productwebsite (www.reclast.com).

CONCLUSIONOsteoporosis is a serious medical problem,one that places aheavy health and economic burden on society, yet the dis-ease itself remains largely preventable.The strategy includesthe use of dietary choices, vitamin/mineral supplementation,lifestyle changes, and drug therapy in appropriate patients.These interventions often must remain in place for a life-time.Antiresorptive agents, estrogen agonists/antagonists, andanabolic agents have been shown to improve BMD andreduce the rate of fractures in postmenopausal women andmen with osteoporosis.Health care professionals should beaware of the indications, contraindications, and side-effectprofiles for these drugs to best match each patient with theappropriate treatment. In so doing,we can reduce the sub-stantial morbidity and mortality associated with the diseasein the years to come.

References

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39. Johnell O, Scheele WH, Lu Y, et al. Additive effects of raloxifene andalendronate on bone density and biochemical markers of bone remodelingin postmenopausal women with osteoporosis. J Clin Endocrinol Metab.2002;87:985-992.

Julia Chavez, RN, MSN, CFNP, is an Adult HealthcareProvider at the New Mexico Clinical Research & OsteoporosisCenter in Albuquerque, NM. In compliance with national ethi-cal guidelines, the author reports no relationships with businessor industry that would pose a conflict of interest.

Acknowledgments—The author thanks Eileen O’Connor ofBioScience Communications,New York,NY, for her edito-rial assistance in the preparation of this manuscript.

1555-4155/09/$ see front matter© 2009 American College of Nurse Practitionersdoi:10.1016/j.nurpra.2009.03.015

preventing and treating osteoporosis: pharmacologic and nonpharmacologic approaches

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