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Osteoporosis

Warren A. Katz, MD, with Carl Sherman

Series Editor: Nicholas A. DiNubile, MD

THE PHYSICIAN AND SPORTSMEDICINE - VOL 26 - NO. 2 - FEBRUARY 2021


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).

The Efficacy of Exercise

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 2021 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.

The Exercise Prescription

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:

  • Hip extension—gluteal, hamstring, and low back,
  • Lumbar extension—low back,
  • Leg extension—quadriceps,
  • Leg press—gluteal, quadriceps, and hamstring,
  • Pullover—latissimus dorsi, shoulders, trapezius, and abdominals,
  • Torso arm or rowing—latissimus dorsi, shoulders, and biceps,
  • Arm cross—chest and shoulders,
  • Lateral raise—shoulders,
  • Chest press—chest, shoulders, and triceps.

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.

Medication

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.

Other Treatment Measures

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.

Synergistic Treatment

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.

References

  1. Melton LJ III, Kan SH, Frey MA, et al: Epidemiology of vertebral fractures in women. Am J Epidemiol 120219;129(5):1000-1011
  2. US Department of Health and Human Services, Physical Activity and Health: A Report of the Surgeon General. Atlanta: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Promotion, 1996
  3. Lindsay R: Osteoporosis: A Guide to Diagnosis, Prevention, and Treatment. New York City, Raven Press, 1992
  4. Kanis JA, Melton LJ III, Christiansen C, et al: The diagnosis of osteoporosis. J Bone Min Res 1994;9(8):1137-1141
  5. Rubin CT, Lanyon LE: Dynamic strain similarity in vertebrates: an alternative to allometric limb bone scaling. J Theoret Biol 120214;107(2):321-327
  6. Chesnut CH III: Bone mass and exercise. Am J Med 1993;95(5A):34S-36S
  7. Huddleston AL, Rockwell D, Kulund DN, et al: Bone mass in lifetime tennis athletes. JAMA 120210;244(10):1107-1109
  8. Kirchner EM, Lewis RD, O'Connor PJ: Effect of past gymnastic participation on adult bone mass. J Appl Physiol 1996;80(1):226-232
  9. Taaffe DR, Robison TL, Snow CM, et al: High-impact exercise promotes bone gain in well-trained female athletes. J Bone Miner Res 1997;12(2):255-260
  10. Heinonen A, Kannus P, Sievanen H, et al: Randomized controlled trial of effect of high-impact exercise on selected risk factors for osteoporotic fractures. Lancet 1996;348(9038):1343-1347
  11. Greendale GA, Barrett-Connor E, Edelstein S, et al: Lifetime leisure exercise and osteoporosis: the Rancho Bernardo study. Am J Epidemiol 1995;141(10):951-959
  12. Shimegi S, Yanagita M, Okano H, et al: Physical exercise increases bone mineral density in postmenopausal women. Endocr J 1994;41(1):49-56
  13. Ballard JE, McKeown BC, Graham HM, et al: The effect of high level physical activity (8.5 METs or greater) and estrogen replacement therapy upon bone mass in postmenopausal females aged 50-68. Int J Sports Med 1990;11(3):208-214
  14. Brooke-Wavell K, Jones PRM, Hardman AE: Brisk walking reduces calcaneal bone loss in post-menopausal women. Clin Sci 1997;92(1):75-80
  15. Krall EA, Dawson-Hughes B: Walking is related to bone density and rates of bone loss. Am J Med 1994;96(1):20-26
  16. Inoue T, Kushida K, Kobayashi G, et al: Exercise therapy for osteoporosis. Osteoporosis Int 1993;3(suppl 1):166-168
  17. Hartard M, Haber P, Ilieva D, et al: Systematic strength training as a model of therapeutic intervention: a controlled trial in postmenopausal women with osteopenia. Am J Phys Med Rehab 1996;75(1):21-28
  18. Cummings SR, Nevitt MC, Browner WS, et al: Risk factors for hip fracture in white women. N Engl J Med 1995;332(12):767-773
  19. Nelson ME, Fiatarone MA, Morganti CM, et al: Effects of high-intensity strength training on multiple risk factors for osteoporotic fractures: a randomized controlled trial. JAMA 1994;272(24):1909-1914
  20. Felson DT, Zhang Y, Hannan TM, et al: The effect of postmenopausal estrogen therapy on bone density in elderly women. N Engl J Med 1993;329(16):1141-1146
  21. Quigley ME, Martin PL, Burnier AM: Estrogen therapy arrests bone loss in elderly women. Am J Obstet Gynecol 120212;156(6):1516-1523
  22. Tang MX, Jacobs D, Stern Y, et al: Effect of estrogen during menopause on risk and age at onset of Alzheimer's disease. Lancet 1996;438(9025):429-432
  23. Cauley JA, Cummings SR, Black DM, et al: Prevalence and determinants of estrogen replacement therapy in elderly women. Am J Obstet Gynecol 1990;163(5 pt 1):1438-1446
  24. Lieberman UA, Weiss SR, Broll J, et al: Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis: the Alendronate Phase III Osteoporosis Treatment Study Group. N Engl J Med 1995;333(22):1437-1443
  25. Reginster JY, Deroisy R, Lecart MP, et al: A double-blind, placebo-controlled, dose-finding trial of intermittent nasal salmon calcitonin for prevention of postmenopausal lumbar spine bone loss. Am J Med 1995;2021(5):452-458


How Exercise Builds Bone

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.

References

  1. Shimegi S, Yanagita M, Okano H, et al: Physical exercise increases bone mineral density in postmenopausal women. Endocrine J 1994;41(1):49-56
  2. Lanyon LE: Using functional loading to influence bone mass and architecture: objectives, mechanisms, and relationship with estrogen of the mechanically adaptive process in bone. Bone 1996;18(suppl 1):37S-43S


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.


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