Osteoporosis and Menopause

Information for Patients and Families What is osteoporosis? Osteoporosis is a condition in which bones lose their normal strength, becoming porous and weak. Osteoporosis can affect both men and women, but it tends to occur in women more frequently and at an earlier age. Osteoporosis is caused by an imbalance in a normal process called bone remodeling. During this process, there is a continuous cycle of breakdown and repair, which takes place in all bones throughout life. Special cells called osteoclasts eat away or resorb areas of old, damaged bone. Other cells called osteoblasts then fill in the empty spaces with new bone. Osteoporosis can be caused either by too much resorption of old bone, or too little formation of new bone. The result is a bone that is weaker than normal and may break with a minor injury, or even sponta neously. The most common fractures that occur in women with osteoporosis are fractures of the hip, verte brae (spinal bones and wrist. Hip fractures are the most serious because they need to be repaired surgical ly. Fractures of the vertebrae are called compression fractures because the vertebral bone does not break in two; instead, the bone becomes so weak that it simply collapses on itself. The curvature of the spine seen in many women with osteoporosis is a result of a series of these compression fractures of the verte bral bones. Who gets osteoporosis? A variety of factors can affect your chances of developing osteoporosis. The most common of these socalled risk factors are listed below: Common Risk Factors for Osteoporosis1,2 Female gender Increasing age Menopause Asian or Caucasian heritage Small body build Smoking Inadequate calcium intake Excessive alcohol use Lack of exercise Hyperthyroidism Drugs: long-term use of corticosteroids, certain anticonvulsants Two of the most important risk factors are female sex and increasing age. Women are affected by osteo porosis much more than men in part because they simply live longer than men. Also, women tend to reach a lower peak bone mass than men. Both men and women reach their highest bone mass (and greatest bone strength) at about age 30. After this age, bone strength gradually declines. One way to prevent some of the damage caused by osteoporosis is by ensuring that children and young adults get sufficient exercise and dietary calcium to reach as high a peak bone strength as possible. Lack of estrogen definitely contributes to osteoporosis. This occurs most dramatically at menopause many women experience a period of rapid bone loss, losing 3-5% of their bone strength per year in the first several years after menopause3. However, estrogen deficiency at other times can also lead to osteo porosis. For instance, women who are very athletic or who have eating disorders may go for long periods without menstruating. This can mean that less estrogen is present than normal. For such women, taking
FORM 143918 (February 2004)

estrogen in the form of birth control pills has typically been recommended to prevent osteoporosis, although this has not been proven to be effective. What can be done about osteoporosis? The best approach to osteoporosis is prevention. Once bone loss has occurred, even the best treatments available are not enough to restore completely normal bone strength. Some medications can improve bone density by 10% and possibly more4, but this still does not make the bones as strong as they would have been if good preventive steps had been taken from the beginning. Prevention of osteoporosis The key features of osteoporosis prevention are getting enough calcium and vitamin D (from sun exposure, food or supplements), and keeping up a program of regular exercise. It is also very important to stop smoking if you are a smoker, since smoking increases the risk of osteoporosis significantly. Dietary Calcium Calcium in the diet is used in maintaining normal bone strength. The average American diet contains about 300-500 mg of calcium daily. Adolescent women need a much higher calcium intake of 1300 mg of calcium daily. Women aged 19-50 should have a calcium intake of 1000 mg daily5. The dose should be increased to 1200 mg after age 50. Milk and milk products have the highest natural calcium content, but some foods such as cereals and orange juice are fortified with calcium (extra calcium has been added). Low fat and skim milk contain just as much calcium as regular whole milk. Dietary calcium sources5 8 ounces of plain yogurt 8 ounces of fruit yogurt 8 ounce cup of calcium-fortified orange juice 1-1/2 ounces of cheese 8 ounce cup of milk Approximate calcium content 450 mg 300 mg 300 mg 300 mg 300 mg

Non-dairy sources of calcium include beans, broccoli, bok choy, and canned fish with bones (such as sar dines, salmon or mackerel). Calcium supplements Two widely available calcium supplements are calcium carbonate (Os-Cal, TUMS and others) and calcium citrate (Citracal and others). Calcium citrate is more readily absorbed into the circulation; for this reason, four tablets of Citracal which supply a total of 800 mg of calcium is considered equivalent to 1000 mg of calcium carbonate. Calcium citrate is the preferred form of calcium supplement if you have a history of kidney stones. Calcium may be more readily absorbed when chewed rather than swallowed whole. TUMS tablets are meant to be chewed, and they are actually cheaper than most calcium tablets. A regular-strength TUMS contains 200 mg of calcium, while an extra-strength TUMS contains 300 mg. TUMS-500 tablets contain ing 500 mg of calcium are also available. In choosing calcium tablets, be sure to look for the elemental calciumcontent, not just the number of milligrams of the active ingredient for instance, although a regular strength TUMS tablet contains 500 mg of calcium carbonate,the amount of elemental calcium is only 200 mg.

If your diet contains the usual average calcium content of 300-500 mg a day, and you choose not to sup plement this by consuming more milk products, you could get your recommended daily amount of 1000 1200 mg of calcium by taking 2-3 extra-strength TUMS a day. No more than 500 mg of a calcium supple ment should be taken at one time. Vitamin D Vitamin D is made in skin upon exposure to sunlight, and about 20 minutes per day is all that is necessary until old age (when a supplement is needed). Women who prefer to avoid sun exposure can take vitamin D as a supplement to ensure proper absorption of calcium. The usual recommended daily amount of vita min D is 400 international units (IU); some studies have used 800 IU daily. Most multiple vitamins contain 400 IU of vitamin D in each tablet, and milk is typically fortified with vitamin D as well. Taking more than 800 IU of vitamin D (or an excess of calcium) may have side effects. Exercise Weight-bearing exercise such as walking, climbing stairs, jogging or weight-lifting helps to maintain the normal balance in bone remodeling and thus helps to preserve normal bone strength. Non-weight bearing exercise such as swimming or bicycling is less helpful for osteoporosis prevention, although it is very helpful for cardiovascular fitness. In addition, physical conditioning and balance training may be helpful in minimizing the risk of falling6. A variety of simple precautions in the home are advisable for those who have difficulty with balance or limit ed mobility7: Ensure that stairways are well-lit and in good repair Install hand rails where appropriate Install grab-bars in shower or bath Use non-skid mat, bath/shower chair Avoid use of throw rugs; secure carpet edges to floor Store frequently used items at eye level or below Consider using raised, cushioned toilet seat

How do I know if I have osteoporosis? Osteoporosis is defined in terms of a loss of bone density compared to the average value for young adults. Some degree of bone loss is considered normal with age, but when bone density falls below a certain level, bone fractures become more likely. Evidence of osteoporosis is sometimes apparent on ordinary X-rays. Osteoporotic bones may appear more transparent than normal bones, or compression fractures of the spine may be seen. Osteoporosis must be fairly advanced to be detected in this way. Earlier diagnosis can be achieved through bone density scans. The method currently recommended is called DEXA (dual energy x-ray absorptiometry). Does everyone need to have a bone density scan? No but it may be advisable depending on your individ ual situation. All postmenopausal women should be checked at age 65 if not yet screened. Repeating a measurement in 3 to 5 years can be helpful in selected cases. Medications for osteoporosis Current medications for osteoporosis include hormone replacement therapy, raloxifene, alendronate, rise dronate, etidronate, pamidronate, calcitonin and parathyroid hormone. Not all of these medicines are actually approved by the Food and Drug Administration (FDA) for osteoporosis. All are most effective when used with proper amounts of calcium and vitamin D. Insurance companies variably cover the cost of these medicines even if you have a prescription medicine benefit; some insurance companies require your physician to obtain authorization for the newer medicines before coverage is considered.

Hormone replacement (HRT) HRT refers to the use of two hormones, estrogen and progesterone, which are normally manufactured by the ovaries before menopause. After menopause, the production of these hormones drops dramatically. HRT restores at a lower level the hormone balance that exists before menopause, and has been used to prevent osteoporosis. Although for many years it was felt that estrogen therapy reduces the rate of osteoporosis-related fractures by about 50%4, there were no well-controlled studies supporting this assumption. In 2002, the Womens Health Initiative (WHI) study did demonstrate a reduced risk of fracture from HRT, although other risks outweighed this benefit. This included the risk of heart disease. For years HRT was thought to prevent heart disease, since before menopause, women have a much lower rate of heart disease than do men of the same age. After menopause, the rate of heart disease in women rises rapidly, and ultimately 50% of women, like men, die of heart disease. Epidemiological studies suggested that estrogen treatment was able to reduce a womans risk of developing heart disease by as much as 50%4.Yet cross-sectional data can be (and was) misleading, and randomized, double-blind clinical trials have unfortunately shown just the opposite. Users of HRT mainly have an increased risk of heart attack, especially during the first year of use 8,9. Estrogen has also been thought to have a number of other benefits. Some research suggested that it might reduce the risk of Alzheimers disease, but the risk of dementia actually increased in a substudy of the WHI. Colon cancer and diabetes risks do fall with HRT, but such benefits were less common than the risks of heart attack, stroke, blood clots and breast cancer in the WHI. Finally, HRT increases the risk of gall stones and can cause nuisance effects problems that may be uncomfortable but not dangerous, and disappear when the medicine is stopped. The most common such effect is vaginal bleeding, which can resemble a period,although it is not usually accompanied by as many symptoms as true menstruation. Other possible side effects include breast swelling and tenderness, nausea, skin problems, headaches and bloating. These symptoms occur in 5-10% of women who use hormone replacement, but they generally become less noticeable or disappear after the first few months. The increase in breast cancer in the WHI confirms an important study that has shown that when proges terone is used along with estrogen, breast cancer risk increases substantially 9,10. The risk of breast cancer rises in proportion to the length of time HRT is used. In the general population, an average womans life time risk of developing breast cancer is about 12%, high enough to make use of HRT problematic on that basis alone. If estrogen is used without progesterone, it can overstimulate the growth of the lining of the uterus (endometrium) and lead to cancer of the uterus. Since this was discovered, the standard prescrip tion for postmenopausal hormone replacement has included progesterone as well as estrogen. Progesterone counteracts the stimulatory effects of estrogen on the uterus, and with the combination of estrogen and progesterone there is no increased risk of cancer of the uterus. Only women who have had a hysterectomy (removal of the uterus) are prescribed estrogen alone, without progesterone. Thus, on balance there are far better options than estrogen for prevention and treatment of osteoporosis Raloxifene (Evista) Raloxifene is the second of a class of medications called selective estrogen receptor modulators (SERMs). It has effects which that estrogen in some tissues, and that oppose estrogen in others11,12. Raloxifene, like estrogen, reduces bone resorption and lowers the risk of fracture, although it is unknown as to whether hip fracture risk falls. Raloxifene improves cholesterol profiles without causing an increase in blood levels of C-reactive protein, a risk factor for heart disease that is significantly increased by estrogen. There is no information yet as to whether raloxifene influences the risk of heart disease or Alzheimers disease. The drug lacks some benefits of estrogen in that it does not help with menopause-related symptoms such as vaginal dryness or urinary

incontinence, and it may cause leg cramps or worsen hot flashes. Its advantages over estrogen are that it does not stimulate breast or uterine tissues, while use of the first SERM, tamoxifen, can lead to bleeding or cancer of the uterus. Most importantly, raloxifene does not cause breast swelling or tenderness, and either delays or prevents breast cancer. Also, while estrogen may make migraine headaches worse, raloxifene does not. Alendronate (Fosamax), risedronate (Actonel), etidronate (Didronel) and pamidronate (Aredia) Alendronate, risedronate and etidronate belong to a class of drugs called bisphosphonates. These drugs mainly act by reducing bone resorption. However, at high concentrations etidronate can actually interfere with bone formation. Because of this, etidronate has not been widely used for osteoporosis. Alendronate was approved for treatment of osteoporosis in late 1995. It has also been approved at a lower dose for prevention of osteoporosis. It can increase the bone density of the spine by about 9%, and reduce the risk of a vertebral fracture by 48%13. Alendronate can be given as a single 10 mg tablet every morning, but it is usually taken as a 70 mg tablet once weekly. This should be taken at least half an hour before eat ing or taking any other medicines (including calcium). It should be avoided in conditions marked by low blood levels of calcium or severe kidney disease. The drug causes few side effects; some women experience stomach upset or irritation of the esophagus (the tube that brings food from the mouth to the stomach). It is very important to take the medicine properly in order to avoid this problem; be sure to take the medi cine with a full 8 ounce glass of water, and do not lie down again afterward for at least 30 minutes and until food has ultimately been ingested. Let your physician know if you have any stomach upset or heart burn after starting the medicine. Because it is a relatively new drug, there is little information about alendronates long-term safety, or how long it should be used. One potential source of concern is that alendronate remains present in bone for years, and it is unknown whether this could cause side effects later. Safety data dating 10 years has fortu nately been reassuring. Risedronate is similar to alendronate and is generally taken as a 35 mg tablet once weekly or a 5 mg tablet daily using the same precautions as for alendronate. This drug is priced slightly less expensively than alen dronate and may have an anti-arthritic effect. For patients who cannot tolerate the gastrointestinal side effects of the oral bisphosphonates but who would significantly benefit from their use, pamidronate can be infused once every 3 months. This drug is not FDA-approved for osteoporosis and these infusions, while helpful, are not covered by most forms of health insurance including Medicare. Calcitonin (Miacalcin) Calcitonin is a hormone that is normally produced by the thyroid gland (a gland in the neck). It cannot be given by mouth because it is destroyed by normal digestion. Until 1995, calcitonin was only available in the form of injections. Since 1995, most patients have used a nasal spray that permits enough medication to be absorbed into the circulation to reach the skeleton. Calcitonin also acts by reducing bone resorption. Unlike bisphosphonates, it does not remain stored in bone, but is rapidly cleared out of the body and appears safe for long-term use. Its main advantage over other drugs for osteoporosis is that it has a pain-relieving effect, especially when used after an osteoporo sis-related vertebral compression fracture. Unfortunately, it is less effective than either hormone replace ment or the bisphosphonates. In general, it produces only a very slight gain in bone density of about 2%. It may reduce the risk of vertebral fracture by up to two-thirds14, although the evidence demonstrating this is less impressive than with the other alternatives. Calcitonin is approved only for treatment of osteoporo sis, not for prevention.

Calcitonin has few side effects; some irritation of the nose may occur. It is given in the form of one spray in the nose per day. It is one of the most expensive of the treatment options currently available. Parathyroid hormone (PTH, Forteo) Parathyroid, a hormone produced by 4 small glands in the neck, is involved in bone and mineral metabo lism. When given as a daily injection, this agent powerfully stimulates new bone growth and reduces frac ture risk15. It is FDA-approved for use for 2 years, and is the only actual bone-building agent available. Anti-resorptive drugs should be stopped when PTH is used. Studies show it may in some people actually restore bone density to normal levels. This is the most expensive osteoporosis treatment (about $20 per day, or $7,500 per year). Long-term side effects are unknown, and some rats developed bone cancer when given huge doses. For now, PTH is mainly prescribed when osteoporotic fractures occur despite anti resorptive therapy. Hip pads Hip pads are worn under clothing and have been shown to reduce the risk of hip fracture by up to 80% and to reduce the risk of pelvic fracture in frail, elderly people16. These protectors cost about $80 and can be obtained at medical supply stores, including the Mayo Clinic store (800-963-6468). They are generally not covered by medical insurance but they are a relatively inexpensive way of providing protection without taking any risk. Hip pads do have a bulky appearance and are problematic for people who have urinary urgency. Summary Osteoporosis is a common condition that can lead to painful and potentially dangerous fractures of bones in the wrist, spine and hip. The best treatmentis really prevention. This should start at a young age, as maintaining good calcium intake and exercise habits in young adulthood may help build bone strength to a higher level, reducing the effects of future bone loss. All postmenopausal women should educate them selves regarding the actions that can be taken to prevent bone fracture later in life. Where to find more information In addition to the references listed below, you can find more information about osteoporosis through: Community Health Resource Center Palo Alto Medical Foundation 795 El Camino Real Palo Alto, CA 94301 Phone: (650) 614-3200 Family Health Resource Center PAMF Fremont Center 3200 Kearney Street Fremont, CA 94538 Phone: (510) 623-2231 National Osteoporosis Foundation 1150 - 17th Street NW, Suite 500 Washington, DC 20036-4603 Phone: (202) 223-2226 FAX: (202) 223-2237 Internet: www.nof.org

References 1. Gambert SR and others. Osteoporosis: Clinical features, prevention and treatment. Endocrinology and Metabolism Clinics of North America, June 1995; 24: 317-371. 2. Lufkin EG, Zilkoski M. Diagnosis and management of osteoporosis. American Family Physician Monograph #1, 1996. 3. Ott SM. Estrogen therapy for osteoporosis even in the elderly (editorial). Ann Intern Medicine, 1992; 117: 86-87. 4. Riggs BL, Melton LJ. The prevention and treatment of osteoporosis. N Engl J Med, 1992; 327: 620-627. 5. www.nap.edu/html/dri_calcium/tables.html 6. Province MA, Hadley EC et al. The effects of exercise on falls in elderly patients. JAMA, 1995; 273: 1341-1347. 7. Tinetti ME, Speechley M. Prevention of falls among the elderly. N Engl J Med, 1989; 320: 1055-1059. 8. Hulley S, Grady D, Bush T et al., for the Heart and Estrogen/Progestin Replacement Study (HERS) Research Group. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA, 1998; 280: 605-613. 9. Writing Group for the Womens Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy post-menopausal women: principal results from the Womens Health Initiative randomized controlled trial. JAMA, 2002; 288: 321-333. Schairer C, Lubin J, Troisis R et al. Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. JAMA 2000; 283: 485-491. 10. Willett WC, Colditz G, Stampfer M. Postmenopausal estrogens opposed, unopposed, or none of the above. JAMA, 2000; 283: 534-535. 11. Fuleihan GE. Tissue-specific estrogens the promise for the future (Editorial). N Engl J Med, 1997: 1686-1687. 12. Delmas PD, Bjornason NH, et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in post-menopausal women. N Engl J Med, 1997; 337: 1641-1647. 13. Liberman UA and others. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. N Engl J Med, 1995; 333: 1437-1443. 14. Overgaard K and others. Effect of salmon calcitonin given intranasally on bone mass and fracture rates in established osteoporosis: a dose-response study. British Medical Journal, 1992; 305: 556-561. 15. Neer RM, Arnaud CD, Zanchetta JR et al. Effect of Parathyroid Hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med, 2001; 344: 1434. 16. Kannus P, Parkkari J, Niemi S et al. Prevention of hip fracture in elderly people with use of a hip protector. N Engl J Med, 2000; 343: 1506-1513.