Act Now To Prevent Fracture

By Irina A. Lidow, NP, and Norma L. Rawlings, NP

Postmenopausal osteoporosis is characterized by low bone mass, microarchitectural deterioration of bone tissue, bone fragility, and susceptibility to fractures.¹ Osteoporosis treatment expenditures in this country top $20 billion annually.² About 60% of that amount is for hospitalization, 30% is for nursing home care, and 10% is for outpatient expenditures.³

Epidemiology of Osteoporosis

An estimated 8 million women in the United States meet World Health Organization criteria on for osteoporosis (Table 1).⁴ According to the National Osteoporosis Foundation, approximately 20% of Caucasian and Asian women older than 50 years have osteoporosis, and another 52% have low bone mass (osteopenia). An estimated 10% of Hispanic women older than 50 have osteoporosis, while 49% have low bone mass. Five percent of African-American women older than 50 have osteoporosis, and 35% have low bone mass.⁴

Despite its worldwide prevalence, less than 30% of all cases of osteoporosis have been diagnosed, and only 1 in 7 U.S. women with osteoporosis receives treatment.¹

Epidemiology of Fractures

Approximately 1.5 million osteoporotic fractures occur in the United States each year.⁴ The presence of osteoporosis and increasing age are the two most important risk factors for fractures.³ The risk of osteoporotic fractures (also called low-trauma fractures) increases continuously as bone mineral density (BMD) declines. These are fractures that occur with trauma that is equivalent to that generated by a fall from a standing height or lower. Relative risk for fractures increases approximately twofold with every one standard deviation decrease in age-adjusted BMD.⁵

Previous fractures are important predictors of future fractures. Women who sustain one vertebral compression have a fivefold increased risk of second fracture, and the risk increases exponentially with the number of preexisting vertebral compressions. One in five women with an existing symptomatic or asymptomatic vertebral deformity will experience a new compression fracture within a year.^3,5

Types of Fractures

Fractures at the spine and hip cause the most significant morbidity and mortality.⁵ After a hip fracture, nearly 16% of patients ages 50 to 55 must recover in an inpatient rehabilitation facility or nursing home.⁵ Between 30% and 50% of older patients must be discharged from hospitals to nursing homes, and many of them become permanent residents. Up to 20% of patients who sustain a hip fracture die within the following year. One year after hip fracture, only 40% of surviving patients regain their prefracture level of mobility, and only 25% regain their prior functional status.^3,5

Vertebral fractures (also called compressions) are the hallmark of osteoporosis.⁵ Vertebral deformities result in thoracic kyphosis, a condition that compromises ambulation. They also increase the risk of falls and produce compensatory lumbar lordosis and back pain. The majority of vertebral compressions do not produce symptoms. Their occurrence may not be realized until years later, when the patient complains of back pain or loss of height. Kyphosis may also result in systemic symptoms such as restrictive lung disease. Decreased mobility of the spine and physical crowding of internal organs causes reduced respiratory capacity and shortness of breath. Pneumonia is also a common problem in patients with multiple vertebral compressions.³

In addition to deformity and disability, vertebral compressions cause depression, social isolation and anxiety. The classic kyphotic deformity makes dressing difficult because clothes fit poorly over the dorsal protuberance. In an attempt to alleviate anxiety, many women withdraw from enjoyable social activities and feel hopeless about their current and future quality of life.³

Pathophysiology

Bone mass increases throughout the first 3 decades of life, reaching its peak around the age of 30. Peak bone mass is primarily determined by genetics, but may be modified by lifestyle practices (exercise, diet, smoking) or concomitant diseases such as hyperthyroidism, type 1 diabetes and chronic obstructive pulmonary disease. The level of peak bone mass achieved at skeletal maturity is a major determinant of bone mass in later life, as well as the subsequent development of osteoporosis.¹

Bone is constantly being remodeled to repair damage that occurs in daily activities. In healthy young adults, the process of bone formation and resorption is balanced. However, at menopause, bone remodeling becomes unbalanced due to loss of the suppressive effects of estrogen on osteoclast activity. The latter results in bone loss at each remodeling site and an increase in the number of remodeling sites.^1,5

The two major types of bone are cortical and trabecular. Cortical bone forms the outer shell of all bones and accounts for 75% of total bone mass. Trabecular bone is concentrated in the vertebral bodies, pelvis and at the end of long bones, and accounts for most of the bone volume. In the early postmenopausal years, accelerated bone loss occurs in the lumbar spine and other areas of high trabecular bone content because of the availability of many metabolically active sites inherited in trabecular bone architecture. Later in life, cortical bone loss increases in the hip and other nonvertebral areas. Women lose an average of 2% of cortical bone and 5% of trabecular bone during the first decade after menopause.^1,5,6

Diagnosis

Who should be evaluated for postmenopausal osteoporosis? All women 65 years and older, all adult women with fractures not caused by severe trauma, and younger postmenopausal women who have one or more risk factors for osteoporotic fractures (Table 2).^1,6

The diagnosis of osteoporosis is made according to BMD results.² BMD is the only index of bone strength that can be easily measured clinically. Dual-energy x-ray absorptiometry (DXA) of the lumbar spine and proximal femur is the gold standard for determining BMD. WHO classification of bone status (Table 1) should not be applied to measurement obtained from other sites.¹

Bone density data are reported as T-scores and Z-scores. T-scores represent the number of standard deviations (SDs) from mean bone density values in normal young adults. Z-scores represent the number of SDs from the normal mean value for age- and sex-matched subjects. Z-scores of -2 or lower should prompt investigation of secondary cause of osteoporosis.¹

Prevention

General principles of osteoporosis prevention apply to women of all ages. Chief among today's preventive measures are adequate calcium intake, regular weight-bearing exercise and avoidance of smoking.

A diet with adequate calcium and vitamin D content is essential to osteoporosis prevention. The National Institutes of Health recommend 1,000 mg of elemental calcium per day for all women ages 25 to 50, and 1,500 mg calcium per day for postmenopausal women. When dietary intake is not sufficient, calcium supplementation is advised to meet recommended daily requirements.

The bioavailability of elemental calcium depends on the source and chemical composition of calcium preparations. The calcium compounds most commonly used in supplements are calcium phosphate, calcium carbonate and calcium citrate.

In choosing calcium supplements, the important considerations are tolerance, availability, cost and lifestyle. Experts generally recommend avoiding calcium from bone meal, dolomite or unrefined oyster shell because these preparations may contain lead or other toxic metals. The better choice is from among well-known brand names with proven reliability.

Whether obtained from the diet or from supplements, calcium is best absorbed by the body when taken several times a day in amounts of 500 mg or less. Calcium carbonate is optimally absorbed when taken with food.

Calcium citrate can be taken any time. The most common side effects of calcium supplementation are intestinal flatulence and constipation. These problems are less likely with calcium citrate. Foods high in oxalates or phytates, such as spinach, beets, nuts, chocolate, tea, wheat bran, beans and peas, as well as foods high in protein and sodium, may interfere with calcium absorption.^1,4,7

The recommended daily intake of vitamin D is 400 IU to 800 IU. Natural sources of vitamin D are sunlight exposure, fish oils, fortified milk, cereals and breads. The ability to produce vitamin D in the skin varies depending on the time of day, season, latitude and the person's skin pigmentation. Aging is associated with a declining ability to manufacture vitamin D. In addition, sunscreen, window glass and clothing markedly diminish the amount of vitamin D produced by the body.

Calcium supplements containing vitamin D may be especially beneficial for homebound or institutionalized older women who don't receive exposure to natural sunlight. However, daily intake of vitamin D should not exceed the recommended 800 IU because high doses of vitamin D may be harmful.^4,7

Selected commercially available calcium and vitamin D preparations are outlined in Table 3.^1,2,6

Another essential prevention strategy against osteoporosis is physical exercise. Regular weight-bearing exercise slows bone loss, promotes mobility, and improves muscle strength and coordination — all of which help prevent falls. Beneficial exercises may include stretching, walking, dancing, running and weight training.¹

Smoking cessation and moderation of alcohol intake are also important in osteoporosis prevention. Cigarette smokers tend to undergo early menopause, have increased catabolism of endogenous estrogen, and sustain more fractures. Several studies have demonstrated that alcohol consumption (defined as 2 ounces to 4 ounces per week) in women 65 years and older is associated with increased BMD and lower fracture risk. In contrast, heavy alcohol consumption (defined as 7 ounces or more per week) is associated with increased risk for falls and hip fractures.^1,6

Treatment Options

The National Osteoporosis Foundation recommends pharmacologic treatment for women who fall into one of three categories:

• T-scores of -2 (as determined by central DXA) and no additional risk factors

• T-scores of -1.5 (as determined by central DXA) with one or more additional risk factors (Table 2)

• history of vertebral or hip fractures.²

Available therapeutic agents include medications that provide antiresorptive therapy (Table 4). The bisphosphonate class includes alendronate (Fosamax), risedronate (Actonel), ibandronate sodium (Boniva) and etidronate (Didronel).

Alendronate is approved by the FDA for the prevention of bone loss in recently menopausal women and the treatment of established postmenopausal osteoporosis. The recommended dose for prevention of bone loss is 5 mg daily or 35 mg weekly. For the treatment of established osteoporosis, the recommended dose is 10 mg daily or 70 mg weekly. Research shows that once-a-week dosing is equally effective to daily dosing for increasing bone density.

Alendronate should be taken with plain water on an empty stomach, at least 30 minutes before the first meal, beverage or oral medications of the day. Taking alendronate with food and any beverage other than plain water will substantially reduce absorption. Alendronate should be taken with 6 to 8 ounces of water, and the patient should remain in an upright position for 30 minutes, to avoid esophageal irritation.¹

Randomized, controlled trails show that alendronate therapy prevents bone loss and increases BMD at the spine and hip by 5% to 10%. Alendronate prevents bone loss at the forearm and reduces the risk of fractures of the spine and nonvertebral sites such as the hip and wrist by 40% to 50%.^1,2

The primary side effects of alendronate are upper gastrointestinal symptoms such as heartburn, substernal discomfort and indigestion.¹

Contraindications to alendronate therapy are hypocalcemia, inability to remain upright for at least 30 minutes, and the presence of esophageal abnormalities that might delay transit of the tablet. Hypocalcemia must be corrected before any bisphosphonate therapy is initiated.¹

The therapeutic efficacy and safety of alendronate have been established for a treatment duration of 7 years. No accelerated bone loss occurs after discontinuation of therapy. Extension studies with alendronate have documented increased BMD for up to 10 years; however, fracture risk reduction during this period has not yet been established.²

Risedronate is approved for the prevention of bone loss in recently menopausal women and treatment of established postmenopausal osteoporosis. The recommended dose for both treatment and prevention is 5 mg daily or 35 mg weekly.

Risedronate should be taken with plain water on an empty stomach, at least 30 minutes before the first meal, beverage or other oral medications of the day. Risedronate should be taken with 6 ounces to 8 ounces of water, and patients should remain in an upright position for 30 minutes, to avoid esophageal irritation.¹

Risedronate increases BMD at the spine and hip, prevents bone loss at the forearm, and reduces the risk of fractures of the spine, hip and other nonvertebral sites by 30% to 50%.^1,2

Side effects and contraindications to risedronate are similar to those associated with alendronate. Data from randomized, controlled clinical trials support the efficacy and safety of risedronate therapy for 5 years. In these trials, bone density continued to increase and fracture incidence remained low for up to 7 years.²

Ibandronate sodium received marketing clearance in March and is the first once-monthly pharmacologic treatment for postmenopausal osteoporosis. In addition to the 150-mg monthly dose, it is available as a 2.5-mg pill for daily dosing. Boniva halts bone loss and increases bone mass, thus reducing fracture risk.⁸ Ibandronate sodium 150 mg should be taken once a month on a designated date with 6 ounces to 8 ounces of water, on an empty stomach. Dosing should be at least 60 minutes before lying down, eating, drinking or taking other medications, including calcium, vitamins or antacids. The side effects and contraindications associated with Boniva are similar to those with alendronate and risedronate. The drug may cause dysphagia, esophagitis and stomach or esophageal ulcers.

Etidronate is approved for the treatment of osteoporosis in several countries but has not been approved by the FDA for this use. In the United States, it is indicated for Paget's disease. Etidronate is an alternative for osteoporotic patients who cannot tolerate other oral bisphosphonates.1 It is given in an intermittent cyclic regiment, 400 mg daily for 14 days, with cycles repeated every 3 months. As with all other bisphosphonates, etidronate should be taken on an empty stomach with 6 to 8 ounces of water only.

Continuous administration of etidronate may impair mineralization of newly formed bone, leading to bone pain and fractures. However, intermittent cyclical administration avoids this problem. Two randomized, controlled trials documented significant increases in spinal bone mass and decreases in vertebral and nonvertebral fractures. Etidronate has no significant side effects, except occasional mild diarrhea.⁹

Salmon calcitonin (Miacalcin) is a nasal spray approved for the treatment of postmenopausal osteoporosis. The recommended dose is 200 IU (one puff) daily. In clinical trials, calcitonin was associated with a 36% decrease in the incidence of new vertebral fractures. Calcitonin did not demonstrate a decrease in nonvertebral fracture risk. The major side effect of nasal calcitonin is nasal discomfort. The optimal duration of therapy has not yet been established.^1,2,6

Selective estrogen receptor modulators (SERMS) are another class of medicines used to treat osteoporosis. Raloxifene (Evista) is approved for prevention of bone loss in recently menopausal women and the treatment of established postmenopausal osteoporosis. The recommended dose is 60 mg daily. In randomized, controlled trails, raloxifene reduced vertebral fracture risk by 30% to 50% and significantly reduced bone resorption. The therapeutic use of raloxifene has not been associated with reduction of nonvertebral fractures, although it increases BMD in the femoral neck by 2.4%. Raloxifene does not stimulate the endometrium, and preliminary results suggest that it is associated with a reduction in the incidence of breast cancer.^1,2,6

The major side effects of raloxifene are vasomotor symptoms (hot flashes, night sweats) and increased risk of deep vein thrombosis and pulmonary embolism. The severity of these is similar to those associated with estrogen. Raloxifene is contraindicated in patients with a history of thromboembolic events.^1,6 Current data support safe and effective use of raloxifene for up to 4 years.²

Other SERMS are tibolone (Livial) and tamoxifen (Nolvadex). Tibolone has demonstrated efficacy in the prevention of postmenopausal bone loss. The effects of tibolone on fracture reduction and the endometrium are now being extensively investigated in several clinical trails.⁶ Tamoxifen has demonstrated a slight but statistically significant reduction in fracture risk. However, side effects such as endometrium stimulation that resulted in hyperplasias and adenocarcinomas limits use of tamoxifen as antiresorptive agent.⁶

Oral and transdermal forms of estrogen and combined estrogen-progestin have been approved by the FDA for the prevention of bone loss in postmenopausal women.¹ The Women's Health Initiative (WHI) confirmed that estrogen used alone or with progestin is effective in reducing the incidence of hip, vertebral and total fractures.^10,11 However, data from these trials also indicated an increased risk of heart attack, stroke, pulmonary emboli and breast cancer when estrogen was used with progestin.^10,11 The results also suggested a small but statistically significant increase in the risk of stroke with estrogen alone.^10,11 In light of these data, hormone therapy solely for osteoporosis prevention is not recommended. Other approved treatments should be considered first.¹

Patient Monitoring

Current clinical guidelines recommend annual assessment of stature and skeletal integrity, along with determination of adherence to recommended prevention or treatment interventions.¹

Serial BMD measures are useful for monitoring changes in bone mass. To be clinically significant, the difference between measurements performed by central DXA must be in the range of 3% to 5%. A lack of change in BMD does not constitute evidence of treatment failure and does not warrant alteration in therapy. A decrease in vertebral BMD greater than 4% to 5% indicates a need to evaluate compliance with therapy.^1,6

No definitive determination about the most effective use of serial BMD measurements has been made. Therefore, the following general guidelines are recommended:

• For patients with a T-score more than -1 in baseline, repeat central DXA in 3 to 5 years.

• For patients in an osteoporosis prevention or treatment program, repeat central DXA every 2 years.^1,6

• Medicare will reimburse providers every 2 years for BMD testings.⁴

Referral to an osteoporosis specialist is appropriate for patients with the following:

• unexpected severity of osteoporosis: very low BMD (T-score below -3 or Z-score below -2 at baseline), osteoporosis despite young age (premenopausal), or fractures in the presence of borderline or normal BMD

• a suspected or known condition that may cause secondary osteoporosis

• failure to respond to antiresorptive therapy.¹ No data has confirmed that combined therapies (for example, bisphosphonates plus raloxifene) have an additive effect on fracture reduction, even though small additional increases in bone density were observed in some studies.^1,6

Fracture Prevention is Primary

In October 2004, U.S. Surgeon General Richard Carmona, MD, issued the first report on the nation's bone health. He warned that without concerted preventive efforts by providers and patients, 50% of all U.S. citizens older than 50 will be at risk for osteoporotic fractures by 2020.¹²

Osteoporosis is associated with significant morbidity, mortality and psychological burden. The primary goal of osteoporosis therapy is to prevent fractures. Current therapies improve bone mass and reduce fracture risk. The challenge for primary care providers is to identify and treat asymptomatic women before low-trauma fractures occur.

References

1. AACE Osteoporosis Guidelines. Endocr Pract. 2003;9(6):544-564.

2. The state of the art in the management of osteoporosis. Interdisciplinary Medicine. 2004;5(5):1-12.

3. Cosman F. The epidemiology of osteoporosis. Managed Care Consult [serial online]. Available at: http://www.princetoncme.com/public/2003-21/reprot99.html. Accessed March 19, 2004.

4. National Osteoporosis Foundation. Disease statistics. Available at: http://www.nof.org/osteoporosis/stats.html. Accessed March 21, 2004.

5. Ettinger MP. Aging bone and osteoporosis: strategies for preventing fractures in the elderly. Arch Intern Med. 2003;163:2237-2246.

6. Osteoporosis. ACOG Practice Bulletin No. 50. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2004;103:203-216.

7. Miller GD, Jarvis JK, McBean LD. The importance of meeting calcium needs with foods J Am Coll Nutr. 2001;20(2 Suppl):168S-185S.

8. Roche Laboratories. Available at: http://www.4boniva.com/about-boniva/default.asp. Accessed July 5, 2005.

9. Orwoll ES, Bliziotes M, eds. Osteoporosis: Pathophysiology and Clinical Management. Totowa, N.J.: Humana Press; 2003.

10. Writing Group for the Women's Health Initiative Investigators. Risk and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. 2002;288:321-333.

11. 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. 2001;291:1701-1712.

12. United States Department of Health and Human Services. By 2020, one in two Americans over age 50 will be at risk for fractures from osteoporosis or low bone mass. News release. http://www.hhs.gov/news/press/2004pres/20041014.html. Accessed July 5, 2005.

Irina Lidow is a women's health nurse practitioner at the Baltimore County Health Department in Baltimore. Norma Rawlings is a women's health nurse practitioner who is an assistant professor at the University of Maryland School of Nursing in Baltimore.