- Email: [email protected]
Preventing and Treating Osteoporosis: Pharmacologic and Nonpharmacologic Approaches
Preventing and Treating Osteoporosis: Pharmacologic and Nonpharmacologic Approaches Julia Chavez, RN, MSN, CFNP ABSTRACT Osteoporosis is a serious disease that is preventable and treatable. Prevention strategies include a healthy diet, adequate calcium and vitamin D intake (via supplementation if needed), and lifestyle changes (eg, exercise with resistance, avoiding smoking and excessive alcohol intake). Medications proven to reduce the risk of osteoporotic fractures 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 of bone health. For patients who have osteoporosis, it is important to discuss fracture risks and potential sequelae.Working with patients to select the proper drug for them is a crucial part of the clinical decision-making and management process. The importance of continued communication and follow-up are also vital.
INTRODUCTION Osteoporosis, the most common bone disease, is a systemic skeletal disorder characterized by reduced bone mass, deteriorating bone strength and architecture, and an increased risk of fracture.1 Although once perceived to be an inevitable part of aging for women, osteoporosis is now known to be a preventable disease that affects both men and women over a broad age spectrum.The epidemiology and economic impact of osteoporosis are reviewed elsewhere in this supplement (see Osteoporosis: Background and Overview on page S4). Prevention of osteoporosis is a lifelong process that centers on optimizing bone health. Strategies can be either nonpharmacologic or pharmacologic. However, once osteoporosis is diagnosed, the only available treatment options proven to reduce the risk of fractures are pharmacologic agents. As with other diseases, prevention is preferable to treatment in that it can reduce morbidity and health care costs. In osteoporosis, if left untreated, certain changes in bone microarchitecture associated with bone loss are irreversible after a certain point as the process of bone resorption comes to exceed the synthesis of new bone matrix.2 S13
The Journal for Nurse Practitioners - JNP
This paper will discuss the various approaches to preventing and treating osteoporosis, emphasizing the indications and contraindications for use, advantages and limitations, and potential side effects. For a broader discussion of when to implement these approaches and in which patients, please refer to Integrating Osteoporosis into Clinical Practice, the final paper in this supplement, on page S21. NONPHARMACOLOGIC APPROACHES FOR PREVENTION Diet and Nutrition Good nutrition is essential to bone health. Adequate calcium and vitamin D intake over the lifespan are critical to building peak bone mass and may require supplementation to reach target levels.The skeleton contains 99% of the body’s calcium stores, and when calcium intake is insufficient, bone tissue from the skeleton is resorbed to maintain constant blood levels.3 Recommended calcium intake for patients from childhood through older adulthood is shown in Table 1.4,5 Keep in mind that too much calcium may be as dangerous as too little: excess intake (> 2000 to 2500 mg daily) may increase the risk of developing kidney stones or cardioJune 2009
vascular disease.3,5 Despite the ready availability of these recommendations, only an estimated 25% of boys and 10% of girls 9 to 17 years of age, and only 50% to 60% of older adults, consume an adequate amount of calcium daily.1 Health professionals should investigate their patients’ calcium and vitamin D intake during routine office and hospital visits. To optimize the absorption of calcium, adequate levels of vitamin D are also needed.Vitamin D contributes to calcium absorption, bone health, muscle performance, and balance; in so doing, it reduces morbidity from falling.6 Milk intake is the primary source of vitamin D for most infants and children, unless dairy intake is contraindicated.To ensure that calcium absorption is supported by adequate vitamin D intake, supplementation is needed in infants and children who do not consume sufficient dairy products, as well as in adolescents and adults, because dairy consumption tends to decrease with age.1 The recommended daily intake for vitamin D appears in Table 1.4,5 Older patients with malabsorption (eg, celiac disease) or chronic kidney disease, or who are housebound and have limited exposure to sunlight have an elevated risk of vitamin D insufficiency and may require greater consumption.3 Nutritional factors that may negatively affect calcium levels include a diet that is high in protein, phosphorus, sodium, or caffeine. However, if calcium and vitamin D intake are adequate, these factors are less likely to have clinical relevance.1
Behavioral Modification Smoking and excessive alcohol consumption contribute to bone demineralization. Nurses can play a key role in identifying patients who smoke, or those who drink excessively, and offer behavioral counseling as part of a complete osteoporosis prevention program, especially for patients with other risk factors for osteoporosis. Smoking cessation programs are recommended for all patients who smoke, and alcohol intake should be kept below 3 drinks per day to maintain good bone health and reduce the risk of falling.
Exercise Exercise is another important preventive tool. Resistance and high-impact activities are considered to be the most beneficial.1 Studies have shown that engaging in such exercises (eg, running and weight training) early in life leads to higher peak bone mass. Low-impact exercises, such as walking and bicycle riding, have only a minimal effect on bone mass. Less is known about the effect of exercise begun later in life (eg, during middle age), although it is thought that high-impact physical activity may have a modest preventive effect on the loss of bone mass when combined with adequate calcium and vitamin D intake. Other benefits of exercise, including increased muscle mass, strength, and function, benefit people of all ages. Exercise also helps preserve independence in the elderly and has been shown to reduce falls by up to 25%.1
PHARMACOLOGIC OPTIONS FOR PREVENTION AND TREATMENT Hormone Therapy While not recommended for treatment of established osteoporosis, estrogen therapy (ET), or hormone therapy (HT) could be considered for prevention in postmenopausal women at risk for osteoporosis. However, because of safety concerns with ET/HT (see below), the U.S. Food and Drug Administration (FDA) currently recommends that non-estrogen options be employed before considering prophylactic ET/HT for the prevention of osteoporosis (Table 2).3 The Women’s Health Initiative (WHI) reported that 5 years of HT led to a 35% reduction in the risk of vertebral and hip fractures and a 23% decrease in other osteoporotic fractures.7 Cauley et al found that women who took HT had a reduced risk for fracture at the initial follow-up,
www.npjournal.org
Table 1. National Osteoporosis Foundation Calcium and Vitamin D Recommendations4,5 Calcium (mg daily)
Vitamin D (IU daily)
1-3 years
500
400*
4-8 years
800
400*
9-18 years
1300
400*
19-49 years
1000
400-800
50 years
1200
800-1000
Group Children & Adolescents
Adult Women & Men
Pregnant & Breastfeeding Women 18 years
1300
400-800
19 years
1000
400-800
*National Osteoporosis Foundation does not have specific vitamin D recommendations for these age groups. These are the recommendations of the American Academy of Pediatrics.
The Journal for Nurse Practitioners - JNP
S14
with further reductions seen over time.8 Moreover, the women who took the combined HT also had increased bone mineral density (BMD) that continued to improve during follow-up. Unfortunately, ET/HT has also been associated with serious adverse effects.The WHI investigators reported that, after 5 years of follow-up, HT (estrogen and progesterone) increased the risk of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein phlebitis.7 Factors that were later found to affect these risks included the number of years between menopause and the start of HT, and the use of estrogen alone vs estrogen plus progestin.9,10 The incidence of cardiovascular disease did not increase in women who started HT within 10 years of menopause, and the incidence in breast cancer did not increase over 7.1 years of treatment in women who received estrogen alone.9,10 Oral and IV Bisphosphonates The bisphosphonates, which include alendronate, risedronate, ibandronate, and zoledronic acid, are recommended as first-line options in the management of osteoporosis in postmenopausal women. Alendronate, risedronate, and zoledronic acid are also indicated for treatment to increase bone mass in men with osteoporosis. Bisphosphonates are classified as antiresorptive agents because they inhibit bone resorption directly, thereby reducing net bone turnover, increasing bone mineral density, improving bone strength, and lowering fracture risk.11-14 The indications, dosing, and fracture risk reductions from randomized clinical trials, as provided in the agents’ package inserts, are summarized in Table 2.11-14 Because of the well-documented problem of adherence to and persistence with oral regimens,15 the trend in development of bisphosphonates has been toward formulations that are administered less frequently.The range of options for oral drugs now spans daily, weekly, and monthly, whereas the options for IV include quarterly and once yearly.The range of options allows patients and health care providers to discuss which option best suits the patient’s needs. Alendronate. Alendronate is given orally 10 mg/day or 70 mg once weekly and is now available as a nonproprietary generic.11 The 10-mg daily dose reduced relative risk of spine fractures in postmenopausal women with osteoporosis by 47% and hip fractures by 51%, relative to placebo, over 3 years.11,16 The weekly dose, which is now S15
The Journal for Nurse Practitioners - JNP
more commonly used, has similar efficacy to the daily dose, as demonstrated by showing similar improvements in BMD in a head-to-head trial. Risedronate. Risedronate is given orally in doses ranging from 5 mg/day and 35 mg/week to 150 mg/month.12 The drug reduced the relative risk of spine fractures in postmenopausal women with osteoporosis by up to 49% and non-spine fractures by up to 39% over 3 years.12,17,18 Treatment with daily, weekly, or monthly formulations of risedronate significantly increases BMD.12 Ibandronate. Ibandronate is given 150 mg (orally) once per month, or 3 mg (IV) every 3 months.13 Ibandronate given orally 2.5 mg daily was shown to reduce the relative risk of spine fractures in postmenopausal women with osteoporosis by 52% but did not significantly reduce the risk of non-spine fractures.13,19 The monthly dose was demonstrated to provide BMD increases superior to the daily dose over 1 year, and all marketed doses improve BMD significantly vs placebo.13,20 Zoledronic acid. Zoledronic acid is the first annual treatment for osteoporosis. It is administered by IV at a dose of 5 mg once a year over at least 15 minutes.14 In postmenopausal women with osteoporosis, zoledronic acid reduced the incidence of spine fractures by 70%, hip fractures by 41%, and non-spine fractures by 25%, compared with placebo over 3 years.14,21 In this study, it also significantly increased BMD at the spine and hip. Zoledronic acid is the only bisphosphonate that has been evaluated to prevent future fractures in men and women following surgical repair of a low-trauma hip fracture. Use of IV zoledronic acid reduced the risk of new clinical fractures by 35% and clinical spine fractures by 46%, compared with placebo.22 Bisphosphonate Safety and Tolerability Side-effect profiles are similar for all of the approved bisphosphonates, and the package inserts reflect these similarities.11-14 Numerous large-scale clinical trials and more than a decade of experience in millions of patients in the clinic has led to a well-established safety profile for the class. However, some important considerations should be kept in mind for the class, for the oral agents, and for those administered via IV. For the class as a whole, it is important to remember that serum creatinine should be measured and an estimated creatinine clearance calculated, as no bisphosphonate is recommended to be used in patients with severe June 2009
Table 2. FDA-Approved Drugs for Osteoporosis3,11-14,26,28,29,32 Drug Bisphosphonates Alendronate sodium11 (Fosamax and Fosamax plus D) (generic available)
Indication(s)/ Contraindication(s) Prevention and treatment of postmenopausal osteoporosis Treatment to increase bone mass in men with osteoporosis
3-Year Relative Fracture Risk Reduction
Dosing Prevention: 5 mg/day and 35 mg/week
47%: spine fractures 51%: hip fractures
Treatment: 10 mg/day and 70 mg/week or 70 mg/week with 2800 IU and 5600 IU of vitamin D
Treatment of glucocorticoidinduced osteoporosis Esophageal abnormalities Inability to stand or sit upright for 30 minutes after dosing Hypocalcemia Hypersensitivity Ibandronate sodium13 (Boniva)
Prevention (only oral doses) and treatment of postmenopausal osteoporosis Inability to stand or sit upright for 60 minutes after oral dosing
2.5 mg/day orally
52%: spine fractures
150 mg/month orally 3 mg every 3 months IV over 15-30 seconds
Hypocalcemia Hypersensitivity Risedronate sodium12 (Actonel and Actonel with Calcium)
Prevention and treatment of postmenopausal osteoporosis
5 mg/day and 35 mg/week
49%: spine fractures 39%: non-spine fractures
Prevention and treatment of glucocorticoid-induced osteoporosis Inability to stand or sit upright for 30 minutes after dosing Hypocalcemia Hypersensitivity Zoledronic acid14 (Reclast)
Treatment of postmenopausal osteoporosis Treatment of patients after low-trauma hip fracture Treatment to increase bone mass in men with osteoporosis
5 mg IV infusion over at least 15 minutes once yearly
70%: spine fractures 41%: hip fractures 25%: non-spine fractures In post-hip fracture patients: 35%: all clinical fractures 46%: clinical spine fractures
Treatment and prevention of glucocorticoid-induced osteoporosis Hypocalcemia Hypersensitivity www.npjournal.org
The Journal for Nurse Practitioners - JNP
S16
Table 2. Continued Drug Calcitonin Salmon calcitonin28,29 (Miacalcin, Calcimar, Fortical)
Indication(s)/ Contraindication(s) Treatment of osteoporosis in women >5 years postmenopausal Clinical allergy to salmon calcitonin
Dosing
3-Year Relative Fracture Risk Reduction
200 IU single daily intranasal spray
Increases bone mineral density
Subcutaneous and oral administration also available
Estrogen/Hormone Therapy (ET/HT)* ET3 (Climara, Estrace, Estraderm, Estratab, Ogen, Ortho-Est, Premarin, Vivelle) HT (Activella, Femhrt, Premphase, Prempro)
Prevention of osteoporosis and other symptoms of menopause
Varies by individual brand
35%: vertebral and hip fractures† 23%: other fractures†
60 g/day orally
30%: spine fractures with prior spine fracture
Breast- or estrogendependent carcinoma, abnormal vaginal bleeding, history of thrombosis, liver dysfunction, pregnancy
Estrogen Agonist/Antagonist Raloxifene25 (Evista)
Prevention and treatment of postmenopausal osteoporosis
55%: spine fractures without prior spine fracture
Active or past history of venous thromboembolism
Parathyroid Hormone Teriparatide32 (Forteo)
Treatment of postmenopausal osteoporosis in women at high risk for fracture
20 g/day subcutaneous injection, self-administered
65%: spine fractures 53%: non-spine fractures
Treatment to increase bone mass in men at high risk for fracture Hypersensitivity Patients at increased baseline risk for osteosarcoma
*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 meet the 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
renal impairment (creatinine clearance < 30-35 mL/min).11-14 Patients with known disorders of mineral metabolism should have any deficiencies corrected before therapy with a bisphosphonate is initiated. Adequate daily intake of calcium and vitamin D is important for all patients with osteoporosis and should be strongly recommended for patients on bisphosphonates.The “Precautions” section of all bisphosphonate labels menS17
The Journal for Nurse Practitioners - JNP
tions a possible side effect of severe and occasionally incapacitating bone, joint, or muscle pain; however, such cases are infrequent.11-14 With the oral agents, the most concerning potential side effects are upper GI problems, such as difficulty swallowing, esophageal inflammation, and gastric ulcer.11-13 Patients should also remain upright for 30 to 60 minutes after taking oral bisphosphonates; reclining June 2009
soon after administration may cause esophageal irritation in patients with gastroesophageal reflux.3 Because oral bisphosphonates are poorly absorbed, they must be taken with a glass of plain water (ie, not mineral water) on an empty stomach after an overnight fast. Patients taking alendronate or risedronate also must not consume food, drink, other medications, or nutritional supplements for at least one-half hour after administration. For patients taking ibandronate, the same instructions apply but the recommended waiting time is 1 full hour.23 Because IV bisphosphonates bypass the GI tract and are 100% bioavailable, they pose no risk for upper GI events, and they eliminate the need for the patient to follow complex dosing instructions. However, in some patients, IV bisphosphonates are associated with the occurrence of transient post-dose symptoms, such as arthralgia, headache, myalgia, or fever.These symptoms occur within 3 days of administration, usually resolve within 3 days (but may take 7 to 10 days), and typically occur less often with subsequent doses.14,21 Health care professionals should counsel patients that they may experience these symptoms and that treatment with acetaminophen as needed for up to 72 hours after the infusion can help reduce or prevent symptoms. A rare side effect, osteonecrosis of the jaw (ONJ), has been reported in patients receiving bisphosphonate therapy. However, the vast majority of cases are seen in cancer patients treated with intravenous bisphosphonates for multiple myeloma and breast cancer24,25 and may reflect the immunocompromised state of these patients. In osteoporosis patients taking IV or oral bisphosphonates, it appears that ONJ occurs rarely and may be no more frequent than in the general population or background rate.25 Because media reports have heightened patients’ concerns, it is important to inform osteoporosis patients before they receive bisphosphonate therapy that this potential side effect is very rare, and that the benefits of preventing fractures outweigh the risk of ONJ. Estrogen Agonist/Antagonist Therapy Raloxifene is the only estrogen agonist/antagonist, also known as a selective estrogen receptor modulator (SERM), approved for the prevention and treatment of postmenopausal osteoporosis (Table 2).26 It is taken orally once a day in a 60-mg dose.When given over 3 years, raloxifene reduced the risk of new spine fractures in patients without prior vertebral fractures by 55% and in www.npjournal.org
patients with existing spine fractures by 30%.26,27 Raloxifene has not demonstrated any reductions in risk of nonspine fractures. Raloxifene is contraindicated for patients at risk for deep vein thrombosis or who have had a prior thrombotic event. Moreover, it may exacerbate hot flushes in some women.26 Calcitonin Calcitonin is a naturally occurring hormone that is important in calcium regulation and bone metabolism. Salmon calcitonin is approved for use in women who have been postmenopausal for at least 5 years and is given as an intranasal spray 200 IU/day.28 It has been shown to prevent bone loss in postmenopausal women with osteoporosis.29 However, it is considered to have relatively weak antifracture efficacy compared with the bisphosphonates.30 Thus, it is most appropriate for use in patients for whom the other treatments are contraindicated.Anecdotal clinical experience suggests that the drug may be useful for relief of bone pain resulting from compression fractures.31 Nasal irritation has been reported and patients should alternate nostrils daily.28,29 Patients using calcitonin should be warned not to coat the nostril to reduce irritation, as this will decrease absorption of the drug. Parathyroid Hormone Parathyroid hormone, PTH(1-34) or teriparatide, is an anabolic agent given as a daily, subcutaneous injection to promote bone formation.Teriparatide increases BMD, improves bone strength, and reduces fracture risk. It works by increasing bone formation above that of bone resorption during the period of time known as the “anabolic window.”33 During a 21-month course of treatment, postmenopausal women receiving teriparatide experienced a 65% reduction in the rate of spine fractures and a 53% reduction at nonspinal sites.34 Teriparatide is self-injected subcutaneously every day for a recommended period of 18 to 24 months.32 The safety and efficacy of the drug have not been established beyond 2 years. On discontinuation, the drug should be followed with an antiresorptive agent to sustain or improve the positive changes in BMD. Health professionals should instruct patients on the correct injection technique to ensure proper administration.Teriparatide is available in a dosing pen and must remain refrigerated; if left unrefrigerated for more than 30 minutes, the drug may lose its effectiveness. The Journal for Nurse Practitioners - JNP
S18
Teriparatide is generally well-tolerated. Common side effects include dizziness or heart palpitations; these may last for 10 to 15 minutes after the injection.32,34 Combination Strategies Both bisphosphonates and estrogen inhibit bone resorption, but they may act through different mechanisms.The combination of estrogen and alendronate may increase BMD beyond that of the individual agents.35 Estrogen plus calcitonin,36 estrogen and androgen,37 estrogen plus etidronate,38 and alendronate and raloxifene39 also appear to act synergistically on bone density. Fracture data are not available for these combinations. Patient Preference Patients tend to prefer medications that require less frequent dosing. Monthly or weekly dosing has been shown to be preferred over daily dosing. However, compliance is still suboptimal. Less than 50% of patients are persistent over a 12-month period. If a patient and health care provider decide that an annual IV bisphosphonate is appropriate, the health care provider can choose to refer the patient to an infusion center or to administer the drug in their own clinic if it is set up for infusion capabilities. Additional practical information on zoledronic acid infusion is available at the product website (www.reclast.com). CONCLUSION Osteoporosis is a serious medical problem, one that places a heavy health and economic burden on society, yet the disease itself remains largely preventable.The strategy includes the use of dietary choices, vitamin/mineral supplementation, lifestyle changes, and drug therapy in appropriate patients. These interventions often must remain in place for a lifetime.Antiresorptive agents, estrogen agonists/antagonists, and anabolic agents have been shown to improve BMD and reduce the rate of fractures in postmenopausal women and men with osteoporosis. Health care professionals should be aware of the indications, contraindications, and side-effect profiles for these drugs to best match each patient with the appropriate treatment. In so doing, we can reduce the substantial morbidity and mortality associated with the disease in the years to come. References 1. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA. 2001;285:785-795.
S19
The Journal for Nurse Practitioners - JNP
2. Eastell R. Pathogenesis of postmenopausal osteoporosis. In: Favus MJ, Bikle DD, Christakos S, et al, eds. Primer on the metabolic bone diseases and disorders of mineral metabolism. 6th ed. Washington, DC: American Society for Bone and Mineral Research; 2006:259-262. 3. National Osteoporosis Foundation. Clinician’s guide to prevention and treatment of osteoporosis. Available at: http://www.nof.org/professionals/ Clinicians_Guide.htm. Accessed November 2008. 4. Institute of Medicine, Food and Nutrition Board. Dietary reference intakes: calcium, phosphorus, magnesium, vitamin D, and fluoride. Washington, DC: National Academy Press; 1997. 5. National Osteoporosis Foundation. Calcium recommendations. Available at: http://www.nof.org/prevention/calcium2.htm. Accessed November 2008. 6. Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, et al. Effect of vitamin D on falls: a meta-analysis. JAMA. 2004;291:1999-2006. 7. Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. JAMA. 2002;288:321-333. 8. Cauley JA, Robbins J, Chen, Z, et al. Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women’s Health Initiative randomized trial. JAMA. 2003;290:1729-1738. 9. Manson JE, Hsia J, Johnson KC, et al, for the Women’s Health Initiative Investigators. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. 2003;359:523-534. 10. The Women’s Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative Randomized Controlled Trial. JAMA. 2004;291:1701-1712. 11. Fosamax [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; 2008. 12. Actonel [package insert]. Cincinnati, OH: Procter & Gamble Pharmaceuticals, Inc; 2008. 13. Boniva [package insert]. Nutley, NJ: Roche Laboratories Inc; 2006. 14. Reclast [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2008. 15. Seeman E, Compston J, Adachi J, et al. Non-compliance: the achilles’ heel of anti-fracture efficacy. Osteoporos Int. 2007;18:711-719. 16. Black DM, Cummings SR, Karpf DB, et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet. 1996;348:1535-1541. 17. Harris ST, Watts NB, Genant HK, et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. JAMA. 1999;282:1344-1352. 18. Reginster J, Minne HW, Sorensen OH, et al. Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos Int. 2000;11:83-91. 19. Chesnut CH III, Skag A, Christiansen C, et al. Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res. 2004;19:1241-1249. 20. Miller PD, McClung MR, Macovei L, et al. Monthly oral ibandronate therapy in postmenopausal osteoporosis: 1-year results from the MOBILE study. J Bone Miner Res. 2005;20:1315-1322. 21. Black DM, Delmas PD, Eastell R, et al, for the HORIZON Pivotal Fracture Trial. Once yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356:1809-1822. 22. Lyles KW, Colón-Emeric CS, Magaziner JS, et al, for the HORIZON Recurrent Fracture Trial. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007;357:1799-1809. 23. Gertz BJ, Holland SH, Kline WF, et al. Studies of bioavailability of alendronate. Clin Pharmacol Ther. 1995;58:288-298. 24. Ruggiero S, Gralow J, Marx RE, et al. Practical guidelines for the prevention, diagnosis, and treatment of osteonecrosis of the jaw in patients with cancer. J Oncol Pract. 2006;2:7-14. 25. Reid IR. Osteonecrosis of the jaw: who gets it, and why? Bone. 2009;44:4-10. epub ahead of print. 26. Evista [package insert]. Indianapolis, Ind: Eli Lilly and Co; 2007. 27. Ettinger B, Black DM, Mitlak BH, et al, for the Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. JAMA. 1999;282:637-647. 28. Miacalcin [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2006. 29. Chesnut CH III, Silverman S, Andriano K, et al, for the PROOF Study Group. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. Am J Med. 2000;109:267-276. 30. Downs RW, Bell NH, Ettinger MP, et al. Comparison of alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women. J Clin Endocrinol Metab. 2000;85:1783-1788. 31. Francis RM, Aspray TJ, Hide G, Sutcliffe AM, Wilkinson P. Back pain in osteoporotic vertebral fractures. Osteoporos Int. 2008;19:895-903.
June 2009
32. Forteo [package insert]. Indianapolis, IN: Eli Lilly and Co; 2008. 33. Canalis E, Giustina A, Bilezikian JP. Mechanisms of anabolic therapies for osteoporosis. N Engl J Med. 2007;357:905-916. 34. Neer RM, Arnaud CD, Znchetta JR, et al. Effect of parathyroid hormone (134) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001;344:1434-1441. 35. Greenspan SL, Resnick NM, Parker RA. Combination therapy with hormone replacement and alendronate for prevention of bone loss in elderly women: a randomized controlled trial. JAMA. 2003;289:2525-2533. 36. Meschia M, Brincat M, Barbacini P, et al. A clinical trial on the effects of a combination of elcatonin (carbocalcitonin) and conjugated estrogens on vertebral bone mass in early postmenopausal women. Calcif Tissue Int. 1993;53:17-20. 37. Watts NB, Notelovitz M, Timmons MC, et al. Comparison of oral estrogens and estrogens plus androgen on bone mineral density, menopausal symptoms, and lipid-lipoprotein profiles in surgical menopause. Obstet Gynecol. 1995;85:529-537. 38. Wimalawansa SJ. A four-year randomized controlled trial of hormone replacement and bisphosphonate alone or in combination, in women with postmenopausal osteoporosis. Am J Med. 1998;104:219-226. 39. Johnell O, Scheele WH, Lu Y, et al. Additive effects of raloxifene and alendronate on bone density and biochemical markers of bone remodeling in postmenopausal women with osteoporosis. J Clin Endocrinol Metab. 2002;87:985-992.
Julia Chavez, RN, MSN, CFNP, is an Adult Healthcare Provider at the New Mexico Clinical Research & Osteoporosis Center in Albuquerque, NM. In compliance with national ethical guidelines, the author reports no relationships with business or industry that would pose a conflict of interest. Acknowledgments—The author thanks Eileen O’Connor of BioScience Communications, New York, NY, for her editorial assistance in the preparation of this manuscript. 1555-4155/09/$ see front matter © 2009 American College of Nurse Practitioners doi:10.1016/j.nurpra.2009.03.015
www.npjournal.org
The Journal for Nurse Practitioners - JNP
S20
INTRODUCTION Osteoporosis, the most common bone disease, is a systemic skeletal disorder characterized by reduced bone mass, deteriorating bone strength and architecture, and an increased risk of fracture.1 Although once perceived to be an inevitable part of aging for women, osteoporosis is now known to be a preventable disease that affects both men and women over a broad age spectrum.The epidemiology and economic impact of osteoporosis are reviewed elsewhere in this supplement (see Osteoporosis: Background and Overview on page S4). Prevention of osteoporosis is a lifelong process that centers on optimizing bone health. Strategies can be either nonpharmacologic or pharmacologic. However, once osteoporosis is diagnosed, the only available treatment options proven to reduce the risk of fractures are pharmacologic agents. As with other diseases, prevention is preferable to treatment in that it can reduce morbidity and health care costs. In osteoporosis, if left untreated, certain changes in bone microarchitecture associated with bone loss are irreversible after a certain point as the process of bone resorption comes to exceed the synthesis of new bone matrix.2 S13
The Journal for Nurse Practitioners - JNP
This paper will discuss the various approaches to preventing and treating osteoporosis, emphasizing the indications and contraindications for use, advantages and limitations, and potential side effects. For a broader discussion of when to implement these approaches and in which patients, please refer to Integrating Osteoporosis into Clinical Practice, the final paper in this supplement, on page S21. NONPHARMACOLOGIC APPROACHES FOR PREVENTION Diet and Nutrition Good nutrition is essential to bone health. Adequate calcium and vitamin D intake over the lifespan are critical to building peak bone mass and may require supplementation to reach target levels.The skeleton contains 99% of the body’s calcium stores, and when calcium intake is insufficient, bone tissue from the skeleton is resorbed to maintain constant blood levels.3 Recommended calcium intake for patients from childhood through older adulthood is shown in Table 1.4,5 Keep in mind that too much calcium may be as dangerous as too little: excess intake (> 2000 to 2500 mg daily) may increase the risk of developing kidney stones or cardioJune 2009
vascular disease.3,5 Despite the ready availability of these recommendations, only an estimated 25% of boys and 10% of girls 9 to 17 years of age, and only 50% to 60% of older adults, consume an adequate amount of calcium daily.1 Health professionals should investigate their patients’ calcium and vitamin D intake during routine office and hospital visits. To optimize the absorption of calcium, adequate levels of vitamin D are also needed.Vitamin D contributes to calcium absorption, bone health, muscle performance, and balance; in so doing, it reduces morbidity from falling.6 Milk intake is the primary source of vitamin D for most infants and children, unless dairy intake is contraindicated.To ensure that calcium absorption is supported by adequate vitamin D intake, supplementation is needed in infants and children who do not consume sufficient dairy products, as well as in adolescents and adults, because dairy consumption tends to decrease with age.1 The recommended daily intake for vitamin D appears in Table 1.4,5 Older patients with malabsorption (eg, celiac disease) or chronic kidney disease, or who are housebound and have limited exposure to sunlight have an elevated risk of vitamin D insufficiency and may require greater consumption.3 Nutritional factors that may negatively affect calcium levels include a diet that is high in protein, phosphorus, sodium, or caffeine. However, if calcium and vitamin D intake are adequate, these factors are less likely to have clinical relevance.1
Behavioral Modification Smoking and excessive alcohol consumption contribute to bone demineralization. Nurses can play a key role in identifying patients who smoke, or those who drink excessively, and offer behavioral counseling as part of a complete osteoporosis prevention program, especially for patients with other risk factors for osteoporosis. Smoking cessation programs are recommended for all patients who smoke, and alcohol intake should be kept below 3 drinks per day to maintain good bone health and reduce the risk of falling.
Exercise Exercise is another important preventive tool. Resistance and high-impact activities are considered to be the most beneficial.1 Studies have shown that engaging in such exercises (eg, running and weight training) early in life leads to higher peak bone mass. Low-impact exercises, such as walking and bicycle riding, have only a minimal effect on bone mass. Less is known about the effect of exercise begun later in life (eg, during middle age), although it is thought that high-impact physical activity may have a modest preventive effect on the loss of bone mass when combined with adequate calcium and vitamin D intake. Other benefits of exercise, including increased muscle mass, strength, and function, benefit people of all ages. Exercise also helps preserve independence in the elderly and has been shown to reduce falls by up to 25%.1
PHARMACOLOGIC OPTIONS FOR PREVENTION AND TREATMENT Hormone Therapy While not recommended for treatment of established osteoporosis, estrogen therapy (ET), or hormone therapy (HT) could be considered for prevention in postmenopausal women at risk for osteoporosis. However, because of safety concerns with ET/HT (see below), the U.S. Food and Drug Administration (FDA) currently recommends that non-estrogen options be employed before considering prophylactic ET/HT for the prevention of osteoporosis (Table 2).3 The Women’s Health Initiative (WHI) reported that 5 years of HT led to a 35% reduction in the risk of vertebral and hip fractures and a 23% decrease in other osteoporotic fractures.7 Cauley et al found that women who took HT had a reduced risk for fracture at the initial follow-up,
www.npjournal.org
Table 1. National Osteoporosis Foundation Calcium and Vitamin D Recommendations4,5 Calcium (mg daily)
Vitamin D (IU daily)
1-3 years
500
400*
4-8 years
800
400*
9-18 years
1300
400*
19-49 years
1000
400-800
50 years
1200
800-1000
Group Children & Adolescents
Adult Women & Men
Pregnant & Breastfeeding Women 18 years
1300
400-800
19 years
1000
400-800
*National Osteoporosis Foundation does not have specific vitamin D recommendations for these age groups. These are the recommendations of the American Academy of Pediatrics.
The Journal for Nurse Practitioners - JNP
S14
with further reductions seen over time.8 Moreover, the women who took the combined HT also had increased bone mineral density (BMD) that continued to improve during follow-up. Unfortunately, ET/HT has also been associated with serious adverse effects.The WHI investigators reported that, after 5 years of follow-up, HT (estrogen and progesterone) increased the risk of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein phlebitis.7 Factors that were later found to affect these risks included the number of years between menopause and the start of HT, and the use of estrogen alone vs estrogen plus progestin.9,10 The incidence of cardiovascular disease did not increase in women who started HT within 10 years of menopause, and the incidence in breast cancer did not increase over 7.1 years of treatment in women who received estrogen alone.9,10 Oral and IV Bisphosphonates The bisphosphonates, which include alendronate, risedronate, ibandronate, and zoledronic acid, are recommended as first-line options in the management of osteoporosis in postmenopausal women. Alendronate, risedronate, and zoledronic acid are also indicated for treatment to increase bone mass in men with osteoporosis. Bisphosphonates are classified as antiresorptive agents because they inhibit bone resorption directly, thereby reducing net bone turnover, increasing bone mineral density, improving bone strength, and lowering fracture risk.11-14 The indications, dosing, and fracture risk reductions from randomized clinical trials, as provided in the agents’ package inserts, are summarized in Table 2.11-14 Because of the well-documented problem of adherence to and persistence with oral regimens,15 the trend in development of bisphosphonates has been toward formulations that are administered less frequently.The range of options for oral drugs now spans daily, weekly, and monthly, whereas the options for IV include quarterly and once yearly.The range of options allows patients and health care providers to discuss which option best suits the patient’s needs. Alendronate. Alendronate is given orally 10 mg/day or 70 mg once weekly and is now available as a nonproprietary generic.11 The 10-mg daily dose reduced relative risk of spine fractures in postmenopausal women with osteoporosis by 47% and hip fractures by 51%, relative to placebo, over 3 years.11,16 The weekly dose, which is now S15
The Journal for Nurse Practitioners - JNP
more commonly used, has similar efficacy to the daily dose, as demonstrated by showing similar improvements in BMD in a head-to-head trial. Risedronate. Risedronate is given orally in doses ranging from 5 mg/day and 35 mg/week to 150 mg/month.12 The drug reduced the relative risk of spine fractures in postmenopausal women with osteoporosis by up to 49% and non-spine fractures by up to 39% over 3 years.12,17,18 Treatment with daily, weekly, or monthly formulations of risedronate significantly increases BMD.12 Ibandronate. Ibandronate is given 150 mg (orally) once per month, or 3 mg (IV) every 3 months.13 Ibandronate given orally 2.5 mg daily was shown to reduce the relative risk of spine fractures in postmenopausal women with osteoporosis by 52% but did not significantly reduce the risk of non-spine fractures.13,19 The monthly dose was demonstrated to provide BMD increases superior to the daily dose over 1 year, and all marketed doses improve BMD significantly vs placebo.13,20 Zoledronic acid. Zoledronic acid is the first annual treatment for osteoporosis. It is administered by IV at a dose of 5 mg once a year over at least 15 minutes.14 In postmenopausal women with osteoporosis, zoledronic acid reduced the incidence of spine fractures by 70%, hip fractures by 41%, and non-spine fractures by 25%, compared with placebo over 3 years.14,21 In this study, it also significantly increased BMD at the spine and hip. Zoledronic acid is the only bisphosphonate that has been evaluated to prevent future fractures in men and women following surgical repair of a low-trauma hip fracture. Use of IV zoledronic acid reduced the risk of new clinical fractures by 35% and clinical spine fractures by 46%, compared with placebo.22 Bisphosphonate Safety and Tolerability Side-effect profiles are similar for all of the approved bisphosphonates, and the package inserts reflect these similarities.11-14 Numerous large-scale clinical trials and more than a decade of experience in millions of patients in the clinic has led to a well-established safety profile for the class. However, some important considerations should be kept in mind for the class, for the oral agents, and for those administered via IV. For the class as a whole, it is important to remember that serum creatinine should be measured and an estimated creatinine clearance calculated, as no bisphosphonate is recommended to be used in patients with severe June 2009
Table 2. FDA-Approved Drugs for Osteoporosis3,11-14,26,28,29,32 Drug Bisphosphonates Alendronate sodium11 (Fosamax and Fosamax plus D) (generic available)
Indication(s)/ Contraindication(s) Prevention and treatment of postmenopausal osteoporosis Treatment to increase bone mass in men with osteoporosis
3-Year Relative Fracture Risk Reduction
Dosing Prevention: 5 mg/day and 35 mg/week
47%: spine fractures 51%: hip fractures
Treatment: 10 mg/day and 70 mg/week or 70 mg/week with 2800 IU and 5600 IU of vitamin D
Treatment of glucocorticoidinduced osteoporosis Esophageal abnormalities Inability to stand or sit upright for 30 minutes after dosing Hypocalcemia Hypersensitivity Ibandronate sodium13 (Boniva)
Prevention (only oral doses) and treatment of postmenopausal osteoporosis Inability to stand or sit upright for 60 minutes after oral dosing
2.5 mg/day orally
52%: spine fractures
150 mg/month orally 3 mg every 3 months IV over 15-30 seconds
Hypocalcemia Hypersensitivity Risedronate sodium12 (Actonel and Actonel with Calcium)
Prevention and treatment of postmenopausal osteoporosis
5 mg/day and 35 mg/week
49%: spine fractures 39%: non-spine fractures
Prevention and treatment of glucocorticoid-induced osteoporosis Inability to stand or sit upright for 30 minutes after dosing Hypocalcemia Hypersensitivity Zoledronic acid14 (Reclast)
Treatment of postmenopausal osteoporosis Treatment of patients after low-trauma hip fracture Treatment to increase bone mass in men with osteoporosis
5 mg IV infusion over at least 15 minutes once yearly
70%: spine fractures 41%: hip fractures 25%: non-spine fractures In post-hip fracture patients: 35%: all clinical fractures 46%: clinical spine fractures
Treatment and prevention of glucocorticoid-induced osteoporosis Hypocalcemia Hypersensitivity www.npjournal.org
The Journal for Nurse Practitioners - JNP
S16
Table 2. Continued Drug Calcitonin Salmon calcitonin28,29 (Miacalcin, Calcimar, Fortical)
Indication(s)/ Contraindication(s) Treatment of osteoporosis in women >5 years postmenopausal Clinical allergy to salmon calcitonin
Dosing
3-Year Relative Fracture Risk Reduction
200 IU single daily intranasal spray
Increases bone mineral density
Subcutaneous and oral administration also available
Estrogen/Hormone Therapy (ET/HT)* ET3 (Climara, Estrace, Estraderm, Estratab, Ogen, Ortho-Est, Premarin, Vivelle) HT (Activella, Femhrt, Premphase, Prempro)
Prevention of osteoporosis and other symptoms of menopause
Varies by individual brand
35%: vertebral and hip fractures† 23%: other fractures†
60 g/day orally
30%: spine fractures with prior spine fracture
Breast- or estrogendependent carcinoma, abnormal vaginal bleeding, history of thrombosis, liver dysfunction, pregnancy
Estrogen Agonist/Antagonist Raloxifene25 (Evista)
Prevention and treatment of postmenopausal osteoporosis
55%: spine fractures without prior spine fracture
Active or past history of venous thromboembolism
Parathyroid Hormone Teriparatide32 (Forteo)
Treatment of postmenopausal osteoporosis in women at high risk for fracture
20 g/day subcutaneous injection, self-administered
65%: spine fractures 53%: non-spine fractures
Treatment to increase bone mass in men at high risk for fracture Hypersensitivity Patients at increased baseline risk for osteosarcoma
*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 meet the 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
renal impairment (creatinine clearance < 30-35 mL/min).11-14 Patients with known disorders of mineral metabolism should have any deficiencies corrected before therapy with a bisphosphonate is initiated. Adequate daily intake of calcium and vitamin D is important for all patients with osteoporosis and should be strongly recommended for patients on bisphosphonates.The “Precautions” section of all bisphosphonate labels menS17
The Journal for Nurse Practitioners - JNP
tions a possible side effect of severe and occasionally incapacitating bone, joint, or muscle pain; however, such cases are infrequent.11-14 With the oral agents, the most concerning potential side effects are upper GI problems, such as difficulty swallowing, esophageal inflammation, and gastric ulcer.11-13 Patients should also remain upright for 30 to 60 minutes after taking oral bisphosphonates; reclining June 2009
soon after administration may cause esophageal irritation in patients with gastroesophageal reflux.3 Because oral bisphosphonates are poorly absorbed, they must be taken with a glass of plain water (ie, not mineral water) on an empty stomach after an overnight fast. Patients taking alendronate or risedronate also must not consume food, drink, other medications, or nutritional supplements for at least one-half hour after administration. For patients taking ibandronate, the same instructions apply but the recommended waiting time is 1 full hour.23 Because IV bisphosphonates bypass the GI tract and are 100% bioavailable, they pose no risk for upper GI events, and they eliminate the need for the patient to follow complex dosing instructions. However, in some patients, IV bisphosphonates are associated with the occurrence of transient post-dose symptoms, such as arthralgia, headache, myalgia, or fever.These symptoms occur within 3 days of administration, usually resolve within 3 days (but may take 7 to 10 days), and typically occur less often with subsequent doses.14,21 Health care professionals should counsel patients that they may experience these symptoms and that treatment with acetaminophen as needed for up to 72 hours after the infusion can help reduce or prevent symptoms. A rare side effect, osteonecrosis of the jaw (ONJ), has been reported in patients receiving bisphosphonate therapy. However, the vast majority of cases are seen in cancer patients treated with intravenous bisphosphonates for multiple myeloma and breast cancer24,25 and may reflect the immunocompromised state of these patients. In osteoporosis patients taking IV or oral bisphosphonates, it appears that ONJ occurs rarely and may be no more frequent than in the general population or background rate.25 Because media reports have heightened patients’ concerns, it is important to inform osteoporosis patients before they receive bisphosphonate therapy that this potential side effect is very rare, and that the benefits of preventing fractures outweigh the risk of ONJ. Estrogen Agonist/Antagonist Therapy Raloxifene is the only estrogen agonist/antagonist, also known as a selective estrogen receptor modulator (SERM), approved for the prevention and treatment of postmenopausal osteoporosis (Table 2).26 It is taken orally once a day in a 60-mg dose.When given over 3 years, raloxifene reduced the risk of new spine fractures in patients without prior vertebral fractures by 55% and in www.npjournal.org
patients with existing spine fractures by 30%.26,27 Raloxifene has not demonstrated any reductions in risk of nonspine fractures. Raloxifene is contraindicated for patients at risk for deep vein thrombosis or who have had a prior thrombotic event. Moreover, it may exacerbate hot flushes in some women.26 Calcitonin Calcitonin is a naturally occurring hormone that is important in calcium regulation and bone metabolism. Salmon calcitonin is approved for use in women who have been postmenopausal for at least 5 years and is given as an intranasal spray 200 IU/day.28 It has been shown to prevent bone loss in postmenopausal women with osteoporosis.29 However, it is considered to have relatively weak antifracture efficacy compared with the bisphosphonates.30 Thus, it is most appropriate for use in patients for whom the other treatments are contraindicated.Anecdotal clinical experience suggests that the drug may be useful for relief of bone pain resulting from compression fractures.31 Nasal irritation has been reported and patients should alternate nostrils daily.28,29 Patients using calcitonin should be warned not to coat the nostril to reduce irritation, as this will decrease absorption of the drug. Parathyroid Hormone Parathyroid hormone, PTH(1-34) or teriparatide, is an anabolic agent given as a daily, subcutaneous injection to promote bone formation.Teriparatide increases BMD, improves bone strength, and reduces fracture risk. It works by increasing bone formation above that of bone resorption during the period of time known as the “anabolic window.”33 During a 21-month course of treatment, postmenopausal women receiving teriparatide experienced a 65% reduction in the rate of spine fractures and a 53% reduction at nonspinal sites.34 Teriparatide is self-injected subcutaneously every day for a recommended period of 18 to 24 months.32 The safety and efficacy of the drug have not been established beyond 2 years. On discontinuation, the drug should be followed with an antiresorptive agent to sustain or improve the positive changes in BMD. Health professionals should instruct patients on the correct injection technique to ensure proper administration.Teriparatide is available in a dosing pen and must remain refrigerated; if left unrefrigerated for more than 30 minutes, the drug may lose its effectiveness. The Journal for Nurse Practitioners - JNP
S18
Teriparatide is generally well-tolerated. Common side effects include dizziness or heart palpitations; these may last for 10 to 15 minutes after the injection.32,34 Combination Strategies Both bisphosphonates and estrogen inhibit bone resorption, but they may act through different mechanisms.The combination of estrogen and alendronate may increase BMD beyond that of the individual agents.35 Estrogen plus calcitonin,36 estrogen and androgen,37 estrogen plus etidronate,38 and alendronate and raloxifene39 also appear to act synergistically on bone density. Fracture data are not available for these combinations. Patient Preference Patients tend to prefer medications that require less frequent dosing. Monthly or weekly dosing has been shown to be preferred over daily dosing. However, compliance is still suboptimal. Less than 50% of patients are persistent over a 12-month period. If a patient and health care provider decide that an annual IV bisphosphonate is appropriate, the health care provider can choose to refer the patient to an infusion center or to administer the drug in their own clinic if it is set up for infusion capabilities. Additional practical information on zoledronic acid infusion is available at the product website (www.reclast.com). CONCLUSION Osteoporosis is a serious medical problem, one that places a heavy health and economic burden on society, yet the disease itself remains largely preventable.The strategy includes the use of dietary choices, vitamin/mineral supplementation, lifestyle changes, and drug therapy in appropriate patients. These interventions often must remain in place for a lifetime.Antiresorptive agents, estrogen agonists/antagonists, and anabolic agents have been shown to improve BMD and reduce the rate of fractures in postmenopausal women and men with osteoporosis. Health care professionals should be aware of the indications, contraindications, and side-effect profiles for these drugs to best match each patient with the appropriate treatment. In so doing, we can reduce the substantial morbidity and mortality associated with the disease in the years to come. References 1. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA. 2001;285:785-795.
S19
The Journal for Nurse Practitioners - JNP
2. Eastell R. Pathogenesis of postmenopausal osteoporosis. In: Favus MJ, Bikle DD, Christakos S, et al, eds. Primer on the metabolic bone diseases and disorders of mineral metabolism. 6th ed. Washington, DC: American Society for Bone and Mineral Research; 2006:259-262. 3. National Osteoporosis Foundation. Clinician’s guide to prevention and treatment of osteoporosis. Available at: http://www.nof.org/professionals/ Clinicians_Guide.htm. Accessed November 2008. 4. Institute of Medicine, Food and Nutrition Board. Dietary reference intakes: calcium, phosphorus, magnesium, vitamin D, and fluoride. Washington, DC: National Academy Press; 1997. 5. National Osteoporosis Foundation. Calcium recommendations. Available at: http://www.nof.org/prevention/calcium2.htm. Accessed November 2008. 6. Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, et al. Effect of vitamin D on falls: a meta-analysis. JAMA. 2004;291:1999-2006. 7. Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. JAMA. 2002;288:321-333. 8. Cauley JA, Robbins J, Chen, Z, et al. Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women’s Health Initiative randomized trial. JAMA. 2003;290:1729-1738. 9. Manson JE, Hsia J, Johnson KC, et al, for the Women’s Health Initiative Investigators. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. 2003;359:523-534. 10. The Women’s Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative Randomized Controlled Trial. JAMA. 2004;291:1701-1712. 11. Fosamax [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; 2008. 12. Actonel [package insert]. Cincinnati, OH: Procter & Gamble Pharmaceuticals, Inc; 2008. 13. Boniva [package insert]. Nutley, NJ: Roche Laboratories Inc; 2006. 14. Reclast [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2008. 15. Seeman E, Compston J, Adachi J, et al. Non-compliance: the achilles’ heel of anti-fracture efficacy. Osteoporos Int. 2007;18:711-719. 16. Black DM, Cummings SR, Karpf DB, et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet. 1996;348:1535-1541. 17. Harris ST, Watts NB, Genant HK, et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. JAMA. 1999;282:1344-1352. 18. Reginster J, Minne HW, Sorensen OH, et al. Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos Int. 2000;11:83-91. 19. Chesnut CH III, Skag A, Christiansen C, et al. Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res. 2004;19:1241-1249. 20. Miller PD, McClung MR, Macovei L, et al. Monthly oral ibandronate therapy in postmenopausal osteoporosis: 1-year results from the MOBILE study. J Bone Miner Res. 2005;20:1315-1322. 21. Black DM, Delmas PD, Eastell R, et al, for the HORIZON Pivotal Fracture Trial. Once yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356:1809-1822. 22. Lyles KW, Colón-Emeric CS, Magaziner JS, et al, for the HORIZON Recurrent Fracture Trial. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007;357:1799-1809. 23. Gertz BJ, Holland SH, Kline WF, et al. Studies of bioavailability of alendronate. Clin Pharmacol Ther. 1995;58:288-298. 24. Ruggiero S, Gralow J, Marx RE, et al. Practical guidelines for the prevention, diagnosis, and treatment of osteonecrosis of the jaw in patients with cancer. J Oncol Pract. 2006;2:7-14. 25. Reid IR. Osteonecrosis of the jaw: who gets it, and why? Bone. 2009;44:4-10. epub ahead of print. 26. Evista [package insert]. Indianapolis, Ind: Eli Lilly and Co; 2007. 27. Ettinger B, Black DM, Mitlak BH, et al, for the Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. JAMA. 1999;282:637-647. 28. Miacalcin [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2006. 29. Chesnut CH III, Silverman S, Andriano K, et al, for the PROOF Study Group. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. Am J Med. 2000;109:267-276. 30. Downs RW, Bell NH, Ettinger MP, et al. Comparison of alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women. J Clin Endocrinol Metab. 2000;85:1783-1788. 31. Francis RM, Aspray TJ, Hide G, Sutcliffe AM, Wilkinson P. Back pain in osteoporotic vertebral fractures. Osteoporos Int. 2008;19:895-903.
June 2009
32. Forteo [package insert]. Indianapolis, IN: Eli Lilly and Co; 2008. 33. Canalis E, Giustina A, Bilezikian JP. Mechanisms of anabolic therapies for osteoporosis. N Engl J Med. 2007;357:905-916. 34. Neer RM, Arnaud CD, Znchetta JR, et al. Effect of parathyroid hormone (134) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001;344:1434-1441. 35. Greenspan SL, Resnick NM, Parker RA. Combination therapy with hormone replacement and alendronate for prevention of bone loss in elderly women: a randomized controlled trial. JAMA. 2003;289:2525-2533. 36. Meschia M, Brincat M, Barbacini P, et al. A clinical trial on the effects of a combination of elcatonin (carbocalcitonin) and conjugated estrogens on vertebral bone mass in early postmenopausal women. Calcif Tissue Int. 1993;53:17-20. 37. Watts NB, Notelovitz M, Timmons MC, et al. Comparison of oral estrogens and estrogens plus androgen on bone mineral density, menopausal symptoms, and lipid-lipoprotein profiles in surgical menopause. Obstet Gynecol. 1995;85:529-537. 38. Wimalawansa SJ. A four-year randomized controlled trial of hormone replacement and bisphosphonate alone or in combination, in women with postmenopausal osteoporosis. Am J Med. 1998;104:219-226. 39. Johnell O, Scheele WH, Lu Y, et al. Additive effects of raloxifene and alendronate on bone density and biochemical markers of bone remodeling in postmenopausal women with osteoporosis. J Clin Endocrinol Metab. 2002;87:985-992.
Julia Chavez, RN, MSN, CFNP, is an Adult Healthcare Provider at the New Mexico Clinical Research & Osteoporosis Center in Albuquerque, NM. In compliance with national ethical guidelines, the author reports no relationships with business or industry that would pose a conflict of interest. Acknowledgments—The author thanks Eileen O’Connor of BioScience Communications, New York, NY, for her editorial assistance in the preparation of this manuscript. 1555-4155/09/$ see front matter © 2009 American College of Nurse Practitioners doi:10.1016/j.nurpra.2009.03.015
www.npjournal.org
The Journal for Nurse Practitioners - JNP
S20