Internal Medicine Series Editor: Donald M. Christie, Jr, MD
THE PHYSICIAN AND SPORTSMEDICINE - VOL 25 - NO. 11 - NOVEMBER 97
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In Brief: Insufficient estrogen can cause osteoporosis in young female athletes, like the 17-year-old runner described here, as well as in postmenopausal women, whose management is also detailed. The most common technique for diagnosis is dual-energy x-ray absorptiometry. Prevention and treatment depend on a woman's age but may include increased calcium intake, weight gain, weight-bearing and resistance exercise, and estrogen replacement therapy. Alendronate and/or calcitonin may be used as alternatives to estrogen therapy.
Osteoporosis has been defined as "a disease characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk (1)." Although anyone can develop osteoporosis, postmenopausal women and young females with menstrual irregularities are most commonly affected. An estimated 20% of women more than 50 years old have osteoporosis (2,3). Although most studies have focused on women of this age-group, osteoporosis is potentially more deleterious in younger women because they haven't yet attained peak bone mass, and early bone loss therefore can affect the rest of their lives.
Whether patients are younger or older, the social costs of osteoporosis are enormous. The yearly estimated healthcare bill for osteoporotic fractures is between $2 billion and $6 billion (4,5). About 200,000 osteoporosis-related hip fractures occur each year in the United States, and the mortality rate 1 year after fracture is estimated to be as high as 20% (6).
Understanding the pathophysiology of osteoporosis begins with a knowledge of normal bone development. Bone health partially depends on physical stress and on adequate levels of calcium, parathyroid hormone, and estrogen. In normal individuals, bone density increases throughout childhood and adolescence and until about 30 years of age. A longitudinal study (7) in 1992 showed that cortical and trabecular bone mass continues to increase slightly in healthy young women until approximately 28 years of age. Other studies (8-10) show that trabecular bone loss may begin in the third decade, but cortical bone may increase or remain constant until the fifth decade (11).
Following achievement of peak bone mass, some bone loss occurs in both men and women. The average bone loss for women at age 50 is estimated at 7% in the lumbar spine and 16% in the femoral neck (12).
Excessive bone loss most commonly occurs in females who have insufficient levels of estrogen. Rencken et al (13), in a case-control study involving 49 athletes, 17 to 39 years old, showed that the age of menarche predicts lumbar bone mineral density (BMD) in both amenorrheic and eumenorrheic athletes and that delayed menarche predicts lower BMD in amenorrheic athletes. The study also demonstrated that extended periods of amenorrhea can result in decreased bone density at multiple skeletal sites, including weight-bearing sites such as the femoral shaft and tibia. This means that osteoporosis in young athletes (see "Osteoporosis and Stress Fractures in a Young Runner," below) can be more devastating than in older women because it interferes with attainment of peak bone mass.
Besides delayed menarche and amenorrhea, other risk factors for the development of osteoporosis include a family history of osteoporosis, low calcium intake, malnutrition, eating disorders, premature menopause, oligomenorrhea, and prolonged exposure to certain medications, such as corticosteriods, excess thyroid replacement, and phenytoin.
The Scientific Advisory Committee of the National Osteoporosis Foundation (14) recommends screening for osteoporosis in estrogen-deficient women who are considering hormone replacement or other therapy, patients with osteopenia or vertebral abnormalities revealed on radiographs, those who will receive long-term glucocorticoid therapy, and those with asymptomatic primary hyperparathyroidism who would benefit from surgical intervention. We would add to this list patients with multiple risk factors for osteoporosis and those who have fractures with suspected osteoporotic causes.
Patients who may have osteoporosis should receive a screening evaluation to identify reversible causes. This evaluation should include a complete blood count, chemistry panel, sedimentation rate, and thyroid-stimulating hormone assay. In adolescent patients with menstrual irregularities, an evaluation for secondary amenorrhea should also be considered and should include a laboratory examination of estrogen, luteinizing and follicle-stimulating hormones, prolactin, and a urine pregnancy test.
The gold standard for diagnosing osteoporosis is a bone biopsy, an invasive procedure that is usually not necessary because accurate information can be obtained using noninvasive measures. The current diagnostic techniques include quantitative computed tomography, dual-photon absorptiometry, and dual-energy x-ray absorptiometry (DEXA). DEXA scanning is the most widely used technique in the United States today. It has a margin of error of 1% to 2% and exposes the patient to less radiation than a typical chest x-ray. DEXA results are usually reported as a T-score (table 1), the number of standard deviations (SD) below the average BMD for the sex-matched young adult population. Studies have shown that a 1-SD reduction in bone density results in a twofold to threefold increased risk of fracture (15).
| Table 1. Bone Health Diagnostic Categories Based on Bone Density Values Relative to the Young Adult Mean, Reported as T-scores* | |
| Normal | <1 standard deviation (SD) below the mean |
| Osteopenia | 1 to 2.5 SD below the mean |
| Osteoporosis | >2.5 SD below the mean |
| Severe Osteoporosis | >2.5 SD below the mean, plus one or more fragility fractures |
| *World Health Organization: Assessment of Fracture Risk and Its Application to Screening for Postmenopausal Osteoporosis. WHO Technical Report Series No. 843. Geneva, World Health Organization, 1994 | |
Many advances have been made recently in the prevention and treatment of osteoporosis in young athletes as well as postmenopausal women. We now have a better understanding of the role of exercise, calcium intake, estrogen, alendronate, and calcitonin in the management of this condition.
The role of exercise in preventing and treating osteoporosis is best summarized by the American College of Sports Medicine position statement (16), which makes five points: (1) Weight-bearing physical activity is essential for developing and maintaining a healthy skeleton; (2) strength exercises may also be beneficial, particularly for non-weight-bearing bones; (3) if sedentary women increase their activity, they may avoid the further loss of bone that inactivity can cause and may even slightly increase bone mass; (4) exercise is not a substitute for postmenopausal hormone replacement therapy; and (5) an optimal exercise program for older women includes activities for improving strength, flexibility, and coordination, since improvement in these areas lessens the likelihood of falls and fractures.
Physical stress is a major stimulus for the remodeling and strengthening of bone. In fact, two studies (17,18) have shown that weight-bearing exercise can increase BMD; women who were 50 or more years old and ran regularly had lumbar spine BMDs between 9.2% and 35% higher than women who did not run.
Though exercise can increase premenopausal women's BMD, this benefit reaches only to a point: Excessive exercise interferes with the hypothalamic-pituitary axis and can lead to a hypoestrogenic state, resulting in a reduction in BMD. In addition, weight-bearing exercise should not be used as a single treatment for osteoporosis in either young or older women. Exercise cannot offset the negative effect of decreased estrogen production on the skeleton of young amenorrheic athletes (13). Likewise, exercise alone has not been shown to prevent the bone loss that occurs after menopause, so it should be used only as an adjuvant treatment for osteoporosis in this age-group.
We recommend that older women get 30 minutes of weight-bearing exercise most days of the week. The vast majority of young women need to exercise more, not less. However, younger women whose high level of exercise may be interfering with their menstrual cycle should seek medical advice regarding the relationship of their physical activities with abnormal menses.
Adequate calcium intake is recommended for both the prevention and treatment of osteoporosis. Recently, the National Institutes of Health released a consensus statement(19) recommending that individuals from 11 to 24 years of age consume 1,200 to 1,500 mg of calcium per day. It also recommended that 25- to 50-year-old women and 50- to 65-year-old women who take estrogen should consume 1,000 mg of calcium per day, and that postmenopausal women who are not taking estrogen and women older than 65 years get 1,500 mg per day. In addition, the statement says that young athletes who have menstrual dysfunction and/or eating disorders should consume 1,200 to 1,500 mg of calcium and 400 to 800 IU of vitamin D per day. Consuming adequate amounts of dairy products can help individuals reach these levels of calcium intake, (for example, 3 cups of milk contain about 900 mg of calcium), but taking supplemental calcium is often necessary as well. Eating other calcium-rich foods (table 2: not shown) can also help.
The importance of estrogen for the development and maintenance of bone health is well-documented. Estrogen replacement therapy in the prevention and treatment of osteoporosis in postmenopausal women is widely accepted, but its effectiveness in treating osteoporosis in adolescent athletes is debatable.
Premenopausal estrogen therapy. Keen and Drinkwater (20) recently reported that previously amenorrheic, younger athletes with osteoporosis who had either regained menses or had been taking hormone replacement for up to 9 years did not significantly improve bone density, suggesting that bone loss is irreversible.
Several other studies, however, suggest the opposite. In a recent retrospective study (21), Cumming demonstrated that eight amenorrheic women, 24 to 34 years old, who took hormone replacement (conjugated equine estrogen 0.625 mg/day, or estradiol transdermal patch, 50 micrograms/day, with medroxyprogesterone acetate 10 mg/day for 14 days per month) had BMD increases of 8% in the lumbar spine and 4% in the femoral neck after 24 to 30 months of hormone replacement therapy, while the control group, who took no hormones, had nonsignificant decreases at each site. In a randomized trial by Hergenroeder et al (22), 14- to 28-year-old amenorrheic females who took oral contraceptive pills (OCPs) for 6 months increased their spinal bone density by 2%, while an amenorrheic control group had a 3% decrease. Gulekli et al (23) found that 17- to 40-year-old amenorrheic women with associated osteopenia treated with either hormone replacement or OCPs for an average of 19 months increased BMD by 3.5%, while controls had a nonsignificant loss of bone mass.
Though the weight of evidence indicates that estrogen increases BMD in young, amenorrheic women, there is no consensus on the amount of estrogen necessary to achieve maximal gains. Furthermore, experts agree that premature adolescent osteoporosis is best prevented by maintaining eumenorrhea. (Of particular note for younger athletes: OCPs, conjugated equine estrogen, and medroxyprogesterone acetate are not banned by the US Olympic Committee or the National Collegiate Athletic Association.)
Postmenopausal estrogen therapy. Estrogen is the only drug with US Food and Drug Administration (FDA) approval for the prevention of postmenopausal osteoporosis. Further, two recent double-blind, placebo-controlled clinical trials document the effectiveness of estrogen replacement therapy for the treatment of postmenopausal osteoporosis.
The Postmenopausal Estrogen/Progestin Interventions Trial (24) followed postmenopausal women assigned to receive either estrogen replacement therapy or a placebo for 36 months. Comparisons of the subjects' baseline and final BMDs showed that the placebo group lost an average of 1.8% in the spine and 1.7% in the hip, while the women who received estrogen replacement therapy increased their BMD by 3.5% to 5% in the spine and 1.7% in the hip. In addition, this study showed that women who followed a regimen of conjugated equine estrogen plus continuous medroxyprogesterone acetate had greater increases in spinal BMD (5% average) than those who took other estrogen regimens (3.8% average).
Another study (25) showed that women who were treated with unopposed ethinyl estradiol--the estrogen widely used for contraception--for 2 years had no increase in bone mass. However, when ethinyl estradiol was given in continuous combination with norethindrone acetate, dose-dependent increases in spinal bone mass occurred, suggesting that norethindrone acetate may have a positive effect on bone density. This trial also found that ethinyl estradiol and norethindrone decreased serum lipids. However, the combination of conjugated equine estrogen and medroxyprogesterone acetate has even more favorable effects on lipid profiles.
These trials suggest that conjugated equine estrogen (0.625 mg/day) with medroxyprogesterone (2.5 mg/day) is the treatment of choice for postmenopausal osteoporosis patients who have a uterus. Most experts still recommend conjugated equine estrogen alone (0.625 mg/day) for patients without a uterus (25).
Reduced fracture risk. Estrogen not only increases BMD, but also reduces the risk of osteoporotic fractures. In a recent study (26), patients who began estrogen replacement therapy soon after menopause and continued taking estrogen for 5 years had a lower risk of hip and wrist fractures than women who did not have replacement therapy (relative risk, 0.29). Patients who had previously been taking estrogen replacement--some for as long as 10 years--but were not currently using estrogen had no significant decrease in their risk of fracture. A second study (27) showed that the duration of exposure to estrogen (years of menstruation plus postmenopausal estrogen use) was associated with higher BMD and a reduced incidence of atraumatic fractures. Estrogen therapy that is initiated at the time of menopause and is continued into later life results in the greatest increases in bone density. However, even when it is started after age 60, estrogen replacement also results in some increased BMD and reduced fracture risk (28).
Encouraging estrogen use. Despite estrogen therapy's positive effects on bones, only 15% to 20% of eligible women currently receive this preventive care, partly because of fear that estrogen replacement increases the risk of breast cancer. Recent studies (29,30) have yielded conflicting results; but experts conclude (31) that the estrogen regimens that have been shown to protect against osteoporosis and cardiovascular disease are not currently associated with any clear increase in the risk of breast cancer. In addition, estrogen therapy for women who have a uterus does not appear to increase their risk of endometrial cancer if they also take progestins (25).
Estrogen therapy also benefits patients' heart health. A 1991 report from the Nurses' Health Study (32) showed that women taking estrogen replacement decreased their risk of myocardial infarction and cardiac death by 44% and of overall mortality by 11% relative to women who had never been treated with estrogen.
Risk/benefit counseling. Women who are considering hormone replacement should receive information about the risks and benefits of this therapy. A 50-year-old woman, for example, may expect the following risks with and without estrogen replacement therapy (33):
Thus, the cardiovascular benefits of estrogen replacement should encourage women to begin this therapy.
Two studies may also be useful in counseling patients. Grady et al (34) concluded that most postmenopausal women who use estrogen could increase their life expectancy by 1 or 2 years; exceptions are those with a history of breast cancer or with a first-degree relative who has had premenopausal breast cancer. More recently, Col et al (35) concluded that hormone therapy should extend the life of women who have at least one risk factor for cornonary heart disease, even if they also have first-degree relatives with breast cancer. However, these authors do not recommend hormone replacement for women who have no risk factors for coronary heart disease or hip fracture, but have two first-degree relatives with breast cancer.
Postmenopausal patients who have a contraindication to estrogen replacement therapy should be treated with alendronate. Alendronate is a bisphosphonate that inhibits osteoclastic activity and is approved for the treatment of postmenopausal osteoporosis. It has been shown to increase BMD and reduce fracture risk. A recent trial (36) showed that alendronate, 10 mg/day for 2 years, increased BMD in the hip by 5% and in the spine by 7%. A second trial (37) found that 10 mg/day for 3 years reduced the risk of vertebral fractures by 48%. In addition, this study demonstrated that alendronate also reduced the loss of height and the progression of vertebral deformities often associated with osteoporosis in postmenopausal women. Results from the Fracture Intervention Trial (38) showed that the same dose of alendronate reduced the number of fractures in the hip and wrist by 50% and also decreased new vertebral fractures. Though alendronate is highly effective in increasing BMD and decreasing risk of fracture, its gastrointestinal side effects include nausea, abdominal pain, and dyspepsia.
Alendronate can be used to treat younger women who have severe osteoporosis and who do not respond to estrogen. However, few physicians are willing to prescribe alendronate to women of childbearing age because of the potential teratogenicity to a fetus; those who do, do so with great caution and only along with adequate birth control.
In the authors' estimation, only patients with a contraindication to estrogen and alendronate should be treated initially with nasal calcitonin. Calcitonin-salmon is an antiresorptive agent that targets osteoclasts directly and has recently been approved by the FDA in the form of a nasal spray (200 IU/day) for the treatment of postmenopausal osteoporosis. However, the efficacy of calcitonin in reducing the risk of osteoporotic fractures is uncertain. A recent study(39) suggests that moderately osteoporotic women who take calcitonin increase their lumbar spine BMD in a dose-dependent fashion and reduce the incidence of new fractures by two-thirds relative to moderately osteoporotic women who take calcium alone. However, this and other studies(40,41) do not demonstrate that calcitonin unequivocally reduces vertebral and nonvertebral fractures among patients with premature or postmenopausal osteoporosis. Hence, in spite of nasal calcitonin's favorable side-effect profile, the authors suggest that alendronate and estrogen are more effective treatments for postmenopausal osteoporosis.
New therapies for osteoporosis are currently being developed. Raloxifene, a tamoxifen derivative, is one of the most promising drugs on the horizon. Preliminary research indicates that this drug may yield the same benefits as estrogen for osteoporosis and cardiovascular diseases without increasing the risk of breast cancer.
Meanwhile, the state-of-the-art treatment of postmenopausal osteoporosis is still estrogen replacement therapy during menopause and beyond. Patients for whom estrogen therapy is condraindicated should be treated with alendronate. Those with a contraindication to estrogen and alendronate should be prescribed nasal calcitonin. Additionally, all patients should receive adequate amounts of calcium, vitamin D, and weight-bearing exercise.
Adolescent athletes and premenopausal women can avoid osteoporosis if they maintain eumenorrhea, adequate calcium intake, and appropriate weight-bearing exercise. Premature osteoporosis is usually related to low estrogen and menstrual dysfunction; these conditions can often be alleviated if the patients decrease their energy expenditure, gain weight, and/or replace estrogen with oral contraceptives or through standard estrogen replacement therapy. Estrogen therapy in adolescents is complicated by the fact that current research has not answered the question of how much estrogen is sufficient to reverse premature osteoporosis. In addition, it may not be easy to convince young athletes to take oral contraceptives or to follow estrogen replacement therapy regimens for their bone health.
A 17-year-old cross-country runner presented with right foot pain that had begun 3 weeks earlier at the start of the season. Her pain came on after running less than 1 mile and at times when walking barefoot. She had been running about 35 miles per week for the past 8 to 10 weeks. She denied any acute right foot or ankle injury but reported a stress fracture of the left tibia the previous year.
She was 5'2'', weighed 100 lb, and had oligomenorrhea. She had pain on palpation over the shaft of the first metatarsal but none over the second through fifth metatarsals and no soft-tissue swelling of the foot. Her gait showed mild hyperpronation. Right foot radiographs revealed no bony abnormalities, but a bone scan showed increased uptake in the first metatarsal and cuboid. Given her past stress fracture and the unusual location of the present fracture, an evaluation for osteoporosis was undertaken.
Results of tests, including a complete blood count, chemistry panel, and thyroid-stimulating hormone assay, were all within normal limits. Dual-energy x-ray absorptiometry revealed a T-score (table 1) of -2.59 for the spine and -1.69 for the hip, both diagnostic of osteoporosis. A sports psychologist and a nutritionist were consulted and agreed that the patient had an eating disorder.
She was treated with oral contraceptives, supplemental calcium, vitamin D, avoidance of weight bearing, and counseling. Her stress fracture healed over the next 6 weeks, but she did not return to competition until the next cross-country season. She has continued to be treated with oral contraceptives and calcium supplements and is being followed by an eating disorder specialist.
This case demonstrates that a seemingly healthy young woman can have significant osteoporosis. Physicians and trainers must recognize that multiple or unusual stress fractures can be "red flags" for osteoporosis.
Dr Erickson completed a residency in internal medicine at St Joseph's Hospital in Phoenix and is a primary care sports medicine fellow at Ball Memorial Hospital/Central Indiana Sports Medicine in Muncie, Indiana. He is a member of the American Medical Society for Sports Medicine (AMSSM). Dr Sevier is the program director of the Sports Medicine Fellowship in Muncie. Dr Christie practices internal medicine and sports medicine at the Community Health Plan in Poughkeepsie, New York. He is a fellow of the American College of Physicians, and a member of the editorial board of The Physician and Sportsmedicine. Drs Sevier and Christie are board certified in internal medicine, charter members of the AMSSM, and fellows of the American College of Sports Medicine. All three hold certificates of added qualification in sports medicine. Address correspondence to Steven Erickson, MD, Ball Memorial Hospital, Central Indiana Sports Medicine, 100 N Tillotson, Muncie, IN 47304; e-mail correspondence to smerickson@compuserve.com.
Series Editor: Nicholas A. DiNubile, MD
THE PHYSICIAN AND SPORTSMEDICINE - VOL 26 - NO. 2 - FEBRUARY 98
For patients who have osteoporosis, exercise is an essential part of treatment. Just as regular workouts build muscle, they also maintain and may even increase bone strength. By strengthening your muscles and bones and improving your balance, exercise can reduce the risk of falls and resulting fractures. Exercise works well with estrogen or other medications that increase bone density and strength. Exercise, medication, and proper diet combat osteoporosis more effectively together than any one treatment alone could do. Remember that you're never too old to exercise.
Here are some tips on how to start a program of weight-bearing exercise and resistance training that will benefit your bones and muscles and also help your general health.
For most people who have osteoporosis, brisk walking is ideal. It can be done anywhere, requires no special equipment, and carries minimal risk of injury. If walking is too difficult or painful for you, workouts on a stationary exercise cycle are a good alternative.
The full benefits of walking come from a regular schedule--at least 15 to 20 minutes 3 to 4 days per week. But if you haven't been active for years, you may need to start modestly. Start at whatever level is comfortable for you. Five-minute walks are fine at first, but try increasing their length by 1 minute every other time until you reach the optimal exercise level.
Walk briskly enough to become slightly short of breath. A little puffing shows that you're working your body hard enough to improve your fitness. If you have certain lung, heart, or other medical conditions, you should consult your doctor about a safe level of activity.
Lifting weights or using strength-training machines strengthens bones all over your body, especially if you exercise all of the major muscle groups in your legs, arms, and trunk. Following a program designed by your doctor or a physical therapist is important. Joining a gym or fitness facility is a good way to begin because there you may have access to trainers who can advise you on proper technique.
Strength training is a slow process, so start at a low level and build up gradually over several months. For each exercise, select weights or set the machine so the muscle being trained becomes fatigued after 10 to 15 repetitions. As muscles strengthen, gradually add more weight. But don't increase the weight more than 10% per week, since larger increases can raise your risk of injury. Remember to lift with good form, and don't sacrifice good form to lift more weight.
Remember: This information is not intended as a substitute for medical treatment. Before starting an exercise program, consult a physician.
Dr Katz is chief of rheumatology at the University of Pennsylvania Health System Presbyterian Medicine Center and the director of Physician Strategic Planning and Development and a professor of medicine at the University of Pennsylvania School of Medicine in Philadelphia. He codirects the Philadephia Osteoporosis Center and the Osteoporosis Center at Main Line Health and Fitness, and is board director of the National Osteoporosis Institute and president of Medical Consultant Services. Mr Sherman is a New York City freelance writer. Dr DiNubile is an orthopedic surgeon in private practice in Havertown, Pennsylvania, specializing in sports medicine and arthroscopy. He is the director of Sports Medicine and Wellness at the Crozer-Keystone Healthplex in Springfield, Pennsylvania; a clinical assistant professor in the department of orthopedic surgery at the University of Pennsylvania in Philadelphia; the orthopedic consultant to the Philadelphia 76ers basketball team and the Pennsylvania Ballet; and a member of the editorial board of The Physician and Sportsmedicine.
Series Editor: Nicholas A. DiNubile, MD
THE PHYSICIAN AND SPORTSMEDICINE - VOL 26 - NO. 2 - FEBRUARY 98
In Brief: Physical activity promotes increases in bone mineral density or reductions in bone loss in young, premenopausal, and postmenopausal women, making exercise a key strategy for preventing and treating osteoporosis. Alongside weight-bearing exercise and resistance training, treatment may also include therapy with estrogen, alendronate, or calcitonin, adequate calcium and vitamin D intake, and measures to prevent falls.
Osteoporosis is a metabolic bone disease characterized by a loss of bone mass and disturbance of bone architecture. The loss of calcium and the alteration of bone structure combine to weaken bone in patients who have osteoporosis. This condition affects about 25 million Americans, 80% of them women, and is responsible for 1.5 million fractures per year (1). A half million of these fractures occur in the thoracic and lumbar vertebrae and often result in a deformed, hunched posture that is associated with chronic back pain and poor self-image. Another quarter million fractures annually are hip fractures that result in a 15% to 20% mortality rate and a high incidence of disability (2). Overall, the direct and indirect annual cost of osteoporosis is estimated at $18 billion per year (3).
Osteoporosis is the culmination of a process that typically begins in the third and fourth decades of life, but starts earlier in certain patients, such as athletes who have the triad of disordered eating, amenorrhea, and osteoporosis. In women, bone mass decreases approximately 1% per year from age 40 through menopause; after menopause and the loss of estrogen, bone loss and deterioration accelerate markedly for about 10 years and then level off. Though the average woman loses 15% of bone mass within 5 years of menopause (with prolonged bedrest, the loss can increase to 40%), not all women develop osteoporosis according to the World Health Organization (WHO) definition. The WHO proposes (4) that women are osteoporotic if they have bone densities more than 2.5 standard deviations (SD) below the mean density for young adults. However, it is important to emphasize that the risk of osteoporosis is actually a continuum that begins at less than 2.5 SD from that mean.
Debilitating bone loss is not inevitable. The physiologic processes that cause osteoporosis occur over much of a patient's lifespan and are amenable to interventions. However, physicians' awareness of osteoporosis risk factors such as loss of height, family history, and premature menopause must be sufficient to prompt testing of patients' bone mineral density (BMD) by dual energy x-ray absorptiometry. Such testing can help determine who is eligible for osteoporosis interventions, including medication, dietary measures, and exercise. One of the most important prevention and treatment strategies is adequate weight-bearing and resistance exercise, which can help build bones (see Highlights item, "Exercise Prevents BMD Loss in Women," page 16).
Findings in young populations. Many studies have shown that exercise increases bone density and calcification. Wolff observed as early as 1892 that bone's form follows its function, so that activity and load-bearing influence the overall shape, size, and thickness of bone (see "How Exercise Builds Bone," below) (5). This concept is dramatically illustrated by the consequences of inactivity. Disuse of the musculoskeletal system in people confined to bed leads to rapid bone loss (6). Even young, healthy, male astronauts--who seem to be unlikely candidates for the disease--may develop osteoporosis after relatively brief periods of weightlessness. On the other hand, dramatic evidence of the effects of load-bearing is seen in the cortical thickening in the dominant arms of tennis players (7).
Many other studies have demonstrated the osteogenic capacity of exercise. In one study (8), BMD is reported to be higher in athletic young adults than in their sedentary peers. In another study (9), female gymnasts (mean age, 18) had higher baseline lumbar spine and femoral neck BMDs and greater increases in those BMDs over 12 months than age-matched swimmers or nonathletes. Lumbar spine BMD changes for gymnasts, swimmers, and nonathletes were +2.3%, -0.3%, and -0.4%, respectively; femoral neck changes were +5.0%, -0.6%, and +2.0%, respectively. And in a randomized, controlled trial (10) involving 98 healthy, sedentary, 35- to 45-year-old women, those who participated in 18 months of three weekly sessions of progressive high-impact training had significantly greater increases in femoral neck BMD than sedentary controls (+1.6% vs -0.2%, respectively). "If done on a regular basis, this type of exercise may help decrease the risk of osteoporotic fractures in later life," the authors concluded.
Lifelong benefits. Regular exercise contributes to the prevention of osteoporosis by helping patients attain peak bone mass at physical maturity and then maintain bone health as they age. The benefit of lifelong exercise was suggested by the Rancho Bernardo study (11), which involved 1,014 women and 689 men (mean age, 73) who reported what their exercise habits had been during their teenage years, at ages 30 and 50, and in the year prior to the study. The results showed a significant positive association between exercise and BMD of the hip, and an association of "borderline significance" with spine BMD. Exercise had no effect on fracture rates, however.
Evidence in postmenopausal women. Regular exercise appears to have a similar bone-preserving effect in women after menopause--the time when bone loss accelerates and osteoporosis is more likely to become a danger. A study (12) of 25 women, 49 to 61 years old, found that those who jogged or played volleyball had significantly greater lumbar spine BMD than those who had no regular physical activity. Other researchers (13) found that 5 to 10 months of physical activity increased the BMD in postmenopausal women. In postmenopausal osteoporosis patients, however, exercise should not be seen as a substitute for estrogen replacement or other therapy.
Of particular interest is the positive effect of walking on bone loss in this population. One study (14) examined the effects of brisk walking for 20 to 50 minutes per day on 84 previously sedentary, 60- to 70-year-old women; half of the women exercised and half served as controls. After 12 months, spinal and calcaneal BMDs remained constant in the walking group, but declined in the control group. Though the femoral neck BMD increased in both the walking and control groups, the change in the walkers correlated with the amount of walking they did.
Activities such as walking appear to benefit not just weight-bearing bones, but the skeletal system as a whole. A 12-month trial (15) involving 239 postmenopausal women showed that those who walked more than 7.5 miles weekly had higher average BMD of the whole body, trunk, and legs than those who walked less than a mile per week. Walking was also associated with significantly slower bone loss in the legs over the course of the year. "These results strongly support the widely held belief that walking is a beneficial form of physical activity for maintaining skeletal integrity," the authors concluded.
Another review (16) summarized several experimental and clinical studies and concluded that weight-bearing exercise apparently has a favorable influence on non-weight-bearing as well as weight-bearing bone in postmenopausal women. Such exercise seems to prevent further loss of bone in osteoporosis, although it is unlikely to increase bone mass, the authors said.
Effects in osteoporosis patients. Once significant bone has been lost, a number of studies suggest that an exercise program can halt or even reverse bone loss. One controlled trial (17) involved 31 postmenopausal women who had lost at least 30% of their bone mass. Half participated in a progressive strength-training regimen for 6 months. During the trial, BMDs did not change in the exercise group, but fell significantly in the control group. It is likely that as strength training programs for older people become more standardized, evidence will show that such training prevents bone loss.
Preventing falls. While bone loss and disruption is the central process in osteoporosis, the clinical problem is fracture. A recent review (18) cites a number of studies that show a decline in fracture risk with exercise, particularly walking. Specifically, investigators (19) suggest that exercise may reduce the risk of fractures by preventing falls. Increases in muscle mass and strength and improvements in balance, gait, and reaction time are exercise-related outcomes that appear to reduce the propensity for falls. Exercise has been shown to improve these outcomes even in quite elderly individuals.
Optimal osteoporosis management involves a multimodal program, but exercise is a key element for almost every patient (see the Patient Adviser, "Exercise for Osteoporosis,"). Because weight-bearing aerobic exercise and resistance exercise have been shown to be helpful, both are generally recommended. The exercise program ideally is integrated into the patient's overall healthcare in order to minimize any negative impact of exercise load on the cardiovascular and respiratory systems.
Weight-bearing aerobic exercise. Brisk walking is almost always the weight-bearing exercise of choice. A treadmill can be helpful, particularly for those who have not exercised in the past. For the few who have real difficulty walking, exercise on a cycle ergometer is an alternative. Low-impact aerobic workouts are suitable for most patients, but high-impact exercise places too great a stress on those who have weakened bone.
Elderly patients who are unaccustomed to physical activity should avoid running because of the risk of falls and possible injury to the spine and weight-bearing bone due to impact. Elderly patients who have osteoporosis should also avoid rowing machines; the maximal forward bending required in the use of these machines may cause low-back sprain and vertebral compression fractures in those at risk.
Intensity and duration. For general health reasons, walking or other weight-bearing exercises should raise the heart rate enough to improve aerobic conditioning. Ultimately, patients should walk or participate in comparable activity at this level for at least 15 to 20 minutes three to four times a week. (No one has shown that longer or more frequent exercise improves the effect on osteoporosis.)
Some patients, though, may need some time to reach this goal. Individuals who have been sedentary most of their lives--a substantial proportion of osteoporosis patients--should begin with very short, low-level exercise. Five minutes a day is likely to be well tolerated, while a more ambitious program virtually ensures noncompliance. Most patients can increase their exercise gradually--about 1 minute every other session-until they approach the target length. Another option is to break the exercise period into several shorter bouts spread throughout the day.
For most osteoporotic patients, walking or similar aerobic exercise needn't be supervised. However, older, frail patients and those with concomitant medical problems such as diabetes mellitus, cardiovascular or lung disease, or arthritis, may need the assistance of a physical therapist in designing or participating in an exercise program.
Resistance training. The other component of an exercise prescription, resistance training, should involve all major muscle groups so that it will affect the bones of the upper body as well as the legs. Following is a list of recommended exercises and the muscle groups that they affect:
Ideally, such exercise should initially be supervised and done on machines in a fitness center or gym. Good form is critical, and movements should be slow and controlled. Loads should be set to induce muscle fatigue after 10 to 15 repetitions and should be increased gradually.
Exercise for nonosteoporotic patients. Exercise programs to prevent osteoporosis are similar to but less restricted than those used to treat the condition. Patients who have no bone loss or other medical contraindications can run, do high-impact aerobics, or use rowing machines if they so desire. Excessive exercise is a concern for only a few people. In some female athletes, for example, excessive exercise together with disordered eating can result in menstrual dysfunction, osteoporosis, and an increased risk of stress fractures.
Though exercise is an important part of the osteoporosis prescription, medication is also a necessary complement for almost all postmenopausal patients who have osteoporosis. Rarely should one be used without the other; exceptions would include patients for whom osteoporosis drugs or exercise may be contraindicated. The situation is less clear-cut for premenopausal women and for male patients. Published data on the role of medication in preventing and treating osteoporosis in men and premenopausal women are lacking; however, it is common clinical practice to prescribe appropriate medication for these patients according to the same BMD criteria as are used for postmenopausal women.
Estrogen. Estrogen remains the drug of choice for postmenopausal patients because estrogen loss at menopause increases bone remodeling and subsequent bone loss. The processes involved can be reversed by hormone replacement therapy, which can be used for both prevention and treatment and has been shown to increase bone mineral density and reduce fracture incidence. Data from the Framingham study (20) revealed that women younger than 75 years of age who had had 7 years of hormone replacement therapy had significantly greater in BMD at the wrist and hip (11.5%) than women who had never used estrogen. In another study (21), women over 64 years old who were current estrogen users had 60% fewer wrist fractures and 40% fewer nonspinal fractures than those who had never used estrogen. In addition, long-term estrogen use can reduce the risk of cardiovascular disease in women and may help prevent Alzheimer's disease (22). However, compliance with hormone replacement therapy tends to be poor; a year after starting therapy, only 29% of women continue to take the medication (23).
Estrogen therapy can cause side effects that may result in absolute and relative contraindications. Side effects include increased risk of cholelithiasis, bloating and fluid retention, breast fullness and tenderness, and irregular postmenopausal bleeding. Replacement therapy may be associated with an increased risk of certain cancers. The incidence of endometrial cancer increases with estrogen therapy, but there is no increased risk with short-term use, and concurrent use of progestin significantly decreases this risk. Though recent evidence regarding the association of hormone use with increased breast cancer risk is contradictory, the risk of breast cancer may be increased among some populations of estrogen users.
Alendronate, calcitonin, and raloxiphene. Alternatives to estrogen replacement therapy include alendronate, a bisphosphonate, and intranasal calcitonin, both approved by the US Food and Drug Administration. These drugs increase bone density and reduce the risk of fracture by inhibiting bone breakdown by osteoclasts. They may also be better tolerated by some patients than estrogen.
Alendronate is taken orally on an empty stomach at a dose of 10 mg daily (24). Calcitonin is available in subcutaneous and intranasal forms, but the latter is preferred; one puff daily in one nostril is recommended (25). Alendronate may cause dyspepsia in patients predisposed to the condition. Intranasal calcitonin may induce rhinorrhea or epistaxis.
Raloxiphene is an estrogen analogue that is scheduled to be released this year. It promises to be as effective as estrogen at improving BMD, but without causing estrogen's complications.
All drugs have the potential for unwanted side effects. Because most patients are unable to tolerate hormone replacement therapy or even comply with its proper use, the use of bisphosphonates, calcitonins, and newer estrogen analogues become important therapeutic options.
Diet. Nutrition is important in preventing and treating osteoporosis. Attaining optimal bone mass requires adequate nutrition, especially calcium intake, beginning in adolescence. Unfortunately, most American teenagers, especially girls, consume inadequate amounts of calcium. Though studies are few, an adequate daily intake of calcium (at least 1,200 mg) and vitamin D (400 IU) is essential to maximize the building of new bone. Patients should be encouraged to get as much of these nutrients as possible from dietary sources--such as dairy products and dark green vegetables--but most will also need supplements. These guidelines for calcium and vitamin D are applicable to patients of any age, but nursing home residents may require more vitamin D (800 IU daily).
Safety precautions. Prevention of falls demands more than exercise alone. For elderly patients, especially, studies have shown that systematic fall-prevention programs reduce the risk of fractures. Patients and their families should be aware of and correct household hazards, such as dim lighting, loose carpeting, and scattered toys and shoes. Correction of vision and hearing deficits also helps elderly persons maintain equilibrium. If patients take tranquilizers or sleeping medications, they should be cautioned about possible dizziness. The use of protective trochanteric pads in high-risk patients has shown much promise.
Exercise dovetails with all of the other approaches to managing osteoporosis. It augments the effectiveness of medication and diet in maintaining bone integrity. Muscle strengthening and walking improve support and stability to reduce falls and fractures. For individuals of all ages, exercise should be the keystone of osteoporosis prevention and treatment.
Although the evidence that exercise prevents and combats osteoporosis is substantial, how it does so is far from clear. Both mechanical and hormonal processes appear to be involved (1). One explanation of the way bone responds to exercise is the "error strain distribution hypothesis (2)."
According to this theory, bone cells sense the mechanical strain induced by weight-bearing or resistance exercise. The cells then communicate load imbalances with each other on a local level. In vitro, mechanical strain causes a cellular influx of calcium ions, followed by production of prostaglandin and nitric oxide, increased enzyme activity, and the release of growth hormones; these changes may trigger bone remodeling. The theory suggests that such changes also occur in vivo.
The author acknowledges the assistance of Roger Schwab, director of Main Line Health and Fitness in Bryn Mawr, Pennsylvania, and author of the book The Strength of a Woman.
Dr. Katz has served as an independent consultant to Merck & Co., Inc.
Dr Katz is chief of rheumatology at the University of Pennsylvania Health System Presbyterian Medicine Center and the director of Physician Strategic Planning and Development and a professor of medicine at the University of Pennsylvania School of Medicine in Philadelphia. He codirects the Philadephia Osteoporosis Center and the Osteoporosis Center at Main Line Health and Fitness, and is board director of the National Osteoporosis Institute and president of Medical Consultant Services. Mr Sherman is a New York City freelance writer. Dr DiNubile is an orthopedic surgeon in private practice in Havertown, Pennsylvania, specializing in sports medicine and arthroscopy. He is the director of Sports Medicine and Wellness at the Crozer-Keystone Healthplex in Springfield, Pennsylvania; a clinical assistant professor in the department of orthopedic surgery at the University of Pennsylvania in Philadelphia; the orthopedic consultant to the Philadelphia 76ers basketball team and the Pennsylvania Ballet; and a member of the editorial board of The Physician and Sportsmedicine. Address correspondence to Warren A. Katz, MD, Medical Arts Bldg, Suite 107, 39th and Market St, Philadelphia, PA 19104.