Reducing Hip Fracture Risk in Patients Confined to Long-Term Care Facilities: A Review of Clinical Data
Murray J. Favus, MD

Hip fracture is a debilitating complication of osteoporosis and is a significant source of health care resource utilization among patients confined to long-term care facilities. Strategies aimed at the prevention of hip fracture can provide substantial reductions in morbidity and cost. Prevention strategies include targeted intervention techniques, pharmacotherapy, nutrition therapy, and exercise. (Annals of Long-Term Care 1998;6[10]:315-322)

Osteoporosis is recognized as an important public health problem because of the significant morbidity and mortality associated with its complications. Fractures of the proximal femur (hip) cause hospitalization and disability for approximately 300,000 persons annually.1 Expenditures for hip fractures are estimated at nearly $9 billion each year.2,3 Hip fractures account for more than half of all osteoporosis-related hospital admissions among women 45 years and older.4

Nursing home care accounts for a significant proportion of health care expenditures for patients with skeletal fractures secondary to osteoporosis. Nearly half of all postmenopausal women who sustain hip fractures caused by osteoporosis are discharged to nursing homes after hospitalization.5 According to a recent prevalence-based cost-of-illness study reported by the National Osteoporosis Foundation,6 health care expenditures attributable to osteoporotic fractures (hip and other sites) were approximately $13.8 billion in 1995, of which roughly $3.9 billion was spent on nursing home care. Significant savings in health care cost and resource utilization could be achieved through the identification of risk factors and the implementation of measures that reduce the risk of osteoporotic fractures in those who are confined to long-term care facilities.

Epidemiology of Osteoporosis-Related Fracture

In patients with osteoporosis, the incidence of both hip and vertebral fracture increases exponentially with age. The lifetime risk of a clinically diagnosed hip or vertebral fracture has been estimated to be as high as 17.5% and 15.6%, respectively, in 50-year-old white women (Table I).7 In women between the ages of 60 and 90, the apparent incidence of hip fracture increases fifty-fold and that of vertebral fracture roughly twenty-fold.8

Numerous risk factors for osteoporosis have been identified. Recognition of risk factors can aid in establishing a diagnosis. Female gender and increasing age are the most important risk factors because of the fall in estrogen levels after menopause.9,10 The sudden and nearly complete loss of estrogen after surgical menopause can have a cataclysmic effect on bone mass.9 These risk factors were evaluated in a recent prospective study of 9516 white women age 65 years or older who were followed at four-month intervals for an average of 4.1 years.11 In multivariate age-adjusted analyses, a maternal history of hip fracture doubled the risk, and this increase in risk remained significant after adjustment for bone density. Women who had gained weight since the age of 25 had a lower risk. Others at high risk included those who met the following criteria:

* Had suffered previous fractures of any type after the age of 50 years.

* Were tall at the age of 25 years.

* Rated their own health as fair or poor.

* Had previous hyperthyroidism.

* Had been treated with long-acting benzodiazepines or anticonvulsant drugs.

* Ingested large amounts of caffeine.

* Spent fewer than 4 hours per day on their feet.

Unfortunately, routine clinical observation of risk factors has not been shown to assist in identifying individual hip fracture risk.12 Risk factors for osteoporosis account for only about one third of the variability in bone mass and are not useful for identifying which patients are likely to have low bone mineral density (BMD).12-14 In order to definitively identify women with low bone mass, direct measurement of BMD is required.14

Bone Mass and the Risk of Fracture

Bone mass is a major determinant of bone strength. Prospective studies have shown that, as bone density decreases, the risk of fracture increases.15,16 Measurement of bone mass at any skeletal site is of value in ascertaining the risk of fracture, although measurement at a site of potential fracture (eg, hip, wrist, or spine) may provide the best prediction.16 Wrist or forearm measurements are weaker predictors of hip fracture than hip BMD. Forearm measurements are also less predictive of spine fractures than spine BMD. Table II lists the most common clinical circumstances in which BMD assessments should be performed. BMD measurement in conjunction with existing risk factors provides the clinician with direction for therapeutic intervention. However, the decision to intervene with pharmacotherapy should be based on a global patient profile and not solely on BMD measurement.17

According to recent guidelines established by the American Association of Clinical Endocrinologists,17 measurement of BMD at any skeletal site is useful for assessment of fracture risk, although it is recommended that the first measurement be performed at the hip. The hip is also a good site for baseline and follow-up BMD when the measurements are accessible and affordable and therapeutic intervention is planned.

Densitometric Screening

The measurement of BMD can be performed safely and accurately by a number of densitometric methods (Table III). Those most widely used today are as follows: single-energy x-ray absorptiometry (SXA), dual-energy x-ray absorptiometry (DXA), quantitative computed tomography (QCT), and quantitative ultrasound (QUS), which was recently approved for marketing by the Food and Drug Administration (FDA).

The utility of screening for osteoporosis by measuring BMD has been studied by several investigators,18-21 all of whom reported increases in fracture risk with decreasing BMD. In a review of studies of subjects without signs or symptoms of osteoporosis, Melton et al18 determined that densitometric screening tests can accurately measure BMD, and the results can be used to estimate the risk of fracture. For hip fracture alone, the risk has been shown to increase 1.9 times for each 0.1 g/cm2 decrease in radial bone mass.19 The value of measuring BMD at a nonhip site to predict the risk of hip fracture has been confirmed in other trials.22-25 It appears that large-scale densitometric testing of women over age 65 would facilitate the identification of those at greatest risk of hip fracture. However, the costs and benefits of a testing program based on measurement of BMD in the general population have yet to be formally assessed.

In the long-term care facility, the patient population is inherently considered to be at greater risk of osteoporotic fracture than the general population. In this setting, the use of densitometric assessment techniques may be of value. Although BMD measurements can be useful tools in the diagnosis of osteoporosis, testing is often not an option for patients confined to long-term care facilities due to costs, accessibility, and lack of evidence supporting widespread use. In such cases, strategies targeted at fracture and disease prevention should be implemented (Table IV). The quality of supporting evidence for diagnostic strategies and therapeutic interventions is summarized in Table V.26

Hip Fracture Prevention Strategies

Hip fracture prevention strategies include the use of targeted intervention, pharmacotherapy, nutrition therapy, and exercise.

Targeted Intervention

The Yale University Fragility and Injuries Cooperative Studies of Intervention Techniques (FICSIT) trials have tested a broad range of intervention strategies to reduce the risk of fall-related and other injuries by improving physical capacities.27 These strategies include optimizing healthful behaviors and increasing the safety of living environments of persons residing in long-term care facilities. When elderly members of a health maintenance organization were randomly assigned to receive either targeted intervention (Table IV) or purely social visits, significantly fewer members who received targeted therapy (35% versus 47%) sustained a fall in the ensuing 12 months.27,28

Pharmacotherapy

Pharmacologic therapy for osteoporosis is aimed at preventing further bone loss and decreasing the risk of future fracture. Additional goals include the relief of symptoms associated with fractures and skeletal deformities and the maximization of physical function. Drugs with the potential to treat osteoporosis (Table VI) can be categorized into those that decrease bone resorption and those that increase bone formation. Antiresorptive agents include estrogen, bisphosphonates, calcitonin, raloxifene, esterified estrogens, and calcium. These agents work best when bone turnover is increased, and their effect is greater on trabecular bone than on cortical bone. Agents that increase bone formation are currently being investigated for use in individuals with osteoporosis.

Based on the results of numerous randomized, controlled trials, pharmacologic therapy appears to be effective in reducing fracture risk in the elderly. A recent study of elderly nursing home residents found that the combination of vitamin D3 and calcium reduced the risk of hip fracture by 27%.29 The findings of Chapuy and colleagues29 are encouraging, but it is important to note that vitamin D supplementation of foods is not yet practiced in France. Therefore, the results may not be applicable to elderly nursing home populations in the United States. Other studies have suggested that estrogen30and bisphosphonates31-33 may continue to be effective in reducing fracture risk in women older than 65 years of age.

Agents currently approved for marketing by the FDA specifically for the treatment of osteoporosis include estrogen therapy (with or without medroxyprogesterone acetate), alendronate, and calcitonin. In patients five years postmenopausal, these antiresorptive agents differ widely in their capacity to increase spinal bone mass. They commonly result in bone mineral content increases that range from 2% to 10%,17 and only estrogen and alendronate cause increases in BMD in the proximal femur. Estrogen and alendronate also are indicated for the prevention of osteoporosis, as are raloxifene (a selective estrogen receptor modulator [SERM]) and, more recently, low-dose esterified estrogens.

Estrogen. Estrogen inhibits osteoclastic bone resorption. It prevents both cortical and trabecular bone loss in estrogen-deficient individuals and can be administered either orally or topically. Randomized, controlled trials of estrogen replacement therapy in postmenopausal women with established osteoporosis have revealed beneficial effects on bone density and future fracture incidence.30 Unfortunately, there are significant side effects associated with estrogen replacement therapy. These effects include endometrial hyperplasia, irregular vaginal bleeding, cholelithiasis, fluid retention, abdominal pain, and headache.17 The most controversial aspect of estrogen replacement therapy is its association with an increased risk of endometrial and breast cancers.9

Alendronate. Alendronate belongs to a group of compounds known as bisphosphonates. These compounds are synthetic pyrophosphate analogues that bind strongly to hydroxyapatite crystals, the form of calcium in bone. Like calcitonin, bisphosphonates inhibit osteoclastic bone resorption. Early bisphosphonates, such as etidronate, have been shown to inhibit bone formation at dose levels that inhibit bone resorption,34,35 but more recent compounds such as alendronate have little or no deleterious effect on bone formation.36

A three-year, large-scale, multicenter, randomized, placebo-controlled clinical trial reported by Lieberman et al33 demonstrated that, compared with placebo, alendronate therapy in women with postmenopausal osteoporosis results in a significant, progressive increase in bone mineral density at all skeletal sites. Overall, treatment with alendronate was associated with a 48% reduction in the number of women with new vertebral fractures, a decreased progression of vertebral deformities, and a reduced loss of height. Similar results were obtained in other studies.31,32 The most common side effects of alendronate therapy are gastrointestinal symptoms, including abdominal pain, nausea, constipation, and diarrhea. These effects are generally mild and self-limiting in nature.

One of the two studies that will make up the Fracture Intervention Trial (FIT) was designed to determine the effect of alendronate on the frequencies of vertebral and nonvertebral (including hip) fractures in postmenopausal women with low BMD.31 This investigation was carried out in women with and without vertebral fractures at baseline. The published report presents the results in women with at least one vertebral fracture at baseline (ie, those at high risk for subsequent fracture).

In this study, 2027 women were randomly assigned to receive either alendronate (n = 1022) or placebo (n = 1005) and were followed for 36 months. Based on follow-up radiographs, 8% of the women who received alendronate had one or more new vertebral fractures, compared with 15% of the women who received placebo. This represents a relative risk reduction of 48%. Similarly, clinically apparent fractures were noted in 2% of women who received alendronate, versus 5% of women who received placebo. The relative risk of hip fracture was determined to be 14% among women who received alendronate, versus 18% among those who received placebo.

Unlike the study reported by Lieberman et al,33 the FIT has the statistical power necessary to demonstrate a significant effect on nonvertebral fractures. The mean percentage changes in BMD from baseline in women receiving alendronate versus placebo are depicted in the Figure. The effect of alendronate on fracture risk in women without existing vertebral fractures will be investigated in the other part of the FIT.

In the long-term care facility, treatment with alendronate may reduce substantially the risk of fractures, including hip fractures, and thereby reduce the costly and disabling consequences of osteoporosis in women at high risk of fracture. Alendronate should be taken on an empty stomach, at least half an hour before breakfast, and with 6 to 8 ounces of water. To be most effective, it should not be taken simultaneously with any other medication. To reduce upper gastrointestinal irritation, the patient should remain upright for a half hour after swallowing the tablet. These dosing instructions require careful planning of medication administration in a long-term care facility.

Calcitonin. Calcitonin, which has a direct inhibitory action on osteoclasts, has been used for many years in the treatment of osteoporosis. Side effects include nausea and facial flushing. The cost and the inconvenience are the drawbacks to subcutaneous calcitonin therapy. However, an intranasal formulation of calcitonin was approved by the FDA in 1995 for the treatment of osteoporosis. Data on fracture incidence in patients receiving the intranasal formulation are limited. Raloxifene. Raloxifene recently gained FDA approval for the prevention of osteoporosis. Raloxifene mimics the action of estrogen in bone without stimulating the tissues of the breast and endometrium. Its mechanism of action is unclear but is thought to be due to its selective estrogen-agonist properties on bone in the absence of endogenous estrogens. In one recent randomized placebo-controlled study, raloxifene was shown to stimulate modest increases in BMD and to lower serum concentrations of total and low-density lipoprotein cholesterol, without stimulating the endometrium.37 The side effects associated with raloxifene therapy are mild. The most commonly reported adverse experience is resumption of hot flashes. Increases in the frequency of deep-vein thrombosis have also been associated with raloxifene therapy.

Esterified Estrogens. These plant-based estrogens are the latest drugs to gain FDA approval for the prevention of osteoporosis. Esterified estrogens are synthesized from plant sources and deliver estrone to target tissues during menopause.38 A two-year, prospective, randomized, placebo-controlled double-blind study by Genant and colleagues39 was conducted to determine the role of esterified estrogens (at doses of 0.3, 0.625, and 1.25 mg per day) in the prevention of postmenopausal osteoporosis. Esterified estrogens, at all doses, were shown to produce increases in the BMD of the lumbar spine, compared with baseline and placebo. Esterified estrogens were also shown to cause positive changes in the lipid profiles of study participants. Although positive lipid changes were apparent in all groups, the effects appear to be dose related.

The most striking observation is that there was no reported increase in the incidence of endometrial hyperplasia among subjects receiving 0.3 mg per day of esterified estrogens. The most commonly reported adverse events that resulted in discontinuation of therapy were headaches and vaginal bleeding, which also appear to be dose dependent.39 This study demonstrates that low-dose (0.3 mg per day) therapy with esterified estrogens can improve patients' BMD and lipid profiles without causing endometrial hyperplasia, a precursor of endometrial cancer. Therapy with this drug offers patients with an intact uterus protection against osteoporosis and cardiovascular disease without increasing the risk of endometrial cancer.

Nutrition Therapy

The effects of calcium and vitamin D have been studied to determine their potential relationships to bone mass.

Calcium. Dietary calcium may have a protective effect with regard to fracture risk, although the role of dietary calcium in the attainment of peak bone mass is controversial. Holbrook et al40 performed diet surveys of 957 subjects ages 50 to 79. This population was followed prospectively for 12 years for hip fracture. The age-adjusted risk of fracture was inversely associated with dietary calcium.

Looker et al41 followed a population of 4342 men and postmenopausal women who were not taking estrogen replacement therapy. The risk of hip fracture was 50% lower among patients in the highest quartile of calcium, although these results were not statistically significant. Calcium supplementation is an inexpensive, low-risk intervention. Most experts recommend that all patients with osteoporosis receive calcium carbonate to achieve a calcium intake between 1.0 g and 1.5 g per day.28

Vitamin D. Bone quality may be influenced by vitamin D deficiency, which is common in elderly persons, especially those who are institutionalized and those who have sustained hip fractures.18,42 Low-dose vitamin D supplementation in elderly persons suppresses parathyroid function and reduces bone loss.18,42

The combined use of vitamin D3 and calcium has recently been shown in a randomized, double-blind, placebo-controlled study to decrease the risk of hip fracture.29 In this trial, the effect of combination therapy with vitamin D3 and calcium on hip fracture incidence was studied in 3270 elderly women living in French nursing homes. After only 18 months, the intervention group showed a 26% reduction in the incidence of hip fractures without experiencing any unfavorable side effects. The results of this study support the routine use of vitamin D and calcium supplements for elderly people confined to nursing homes. The optimal dose and formulation of vitamin D has not been established. An intake of 10 µg (400 IU) per day is widely accepted in the United States as a minimum daily requirement.28

Exercise

Weight-bearing exercise, such as walking and weightlifting, is important in the maintenance of bone mass,43 especially in postmenopausal women.44 Conversely, immobility can cause rapid bone loss.36 Exercise prescriptions for elderly patients must minimize adverse events resulting from coexisting conditions such as cardiovascular disease and degenerative joint disease.

Role of Outcomes Research

In addition to data from randomized, controlled clinical trials, strategies for the prevention of hip fractures in patients with osteoporosis will probably arise from the use of outcomes research.14,45 Outcomes research denotes the use of retrospective analysis of medical records or the prospective monitoring of clinical practice and recording of outcomes for the purpose of comparing alternate therapies.14

Historically, claims data have been used for the assessment of health outcomes. Although this method is controversial, the use of claims data affords the availability of resource utilization information for economic analyses.45,46 The analysis of claims data may, therefore, play an important role in determining the most cost-effective prevention and treatment strategies in patients with osteoporosis.

Summary

Hip fracture is a debilitating complication of osteoporosis that places an enormous burden on health care resource utilization. As the U.S. population ages over the next 50 years, the magnitude of this problem can be expected to increase substantially. Nearly $4 billion is spent annually on the care of patients with osteoporotic hip fractures in nursing homes alone. Because the costs and clinical consequences of osteoporosis increase dramatically once hip fracture has occurred, a primary goal for nursing home medical directors and interdisciplinary teams should be the prevention of fracture.

The prevention of fracture starts with the recognition of risk factors that can aid in establishing the diagnosis of osteoporosis. Densitometric techniques such as DXA are useful for screening patients who are considered to be at high risk for fracture, as well as for monitoring the results of therapy. Hip fracture prevention strategies include: targeted intervention; pharmacotherapy with estrogen, alendronate, calcitonin, raloxifene, or esterified estrogens; nutrition therapy with calcium and vitamin D supplements; and, if possible, an exercise regimen.

Prevention strategies for osteoporotic hip fractures will clearly become a major issue for managed care medicine in the long-term care facility in the coming years. Ongoing, large-scale clinical trials, cost-effectiveness assessments, and outcomes analyses should provide more definitive answers as to the most appropriate approaches to the prevention of hip fracture in patients with osteoporosis.

About the Author

Dr. Favus is Professor of Medicine, Director of the Bone Program, and Director of the General Clinical Research Center at the University of Chicago. Address for correspondence: Murray J. Favus, MD, University of Chicago, 5841 S Maryland Ave, MC 5100, Chicago, IL 60637.

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Annals of Long-Term Care - ISSN: 1524-7929 - Volume 6 - Issue 09 - September 1998