Monday, October 15, 2007

Osteoporosis prevention and treatment

INTRODUCTION — Osteoporosis is a common skeletal disorder that causes a decrease in bone mass and density, causing bones to become abnormally thin (osteopenic), weakened, and easily broken (fractured). Women are at a higher risk for osteoporosis after menopause due to lower levels of estrogen, a female hormone that helps to maintain bone mass.

Fortunately, preventive treatments are available that can help to maintain or increase bone density. For those already affected by osteoporosis, prompt diagnosis of bone loss and fracture risk are essential because therapies are available that can slow further loss of bone or increase bone density.

This topic review discusses the therapies available for the prevention and treatment of osteoporosis. A separate topic review is available about the causes, diagnosis, and screening measures for osteoporosis. (See "Patient information: Osteoporosis causes, diagnosis, and screening").

NON-DRUG PREVENTION AND TREATMENT — The non-drug therapy of osteoporosis includes three major components: diet, exercise, and smoking cessation. These recommendations apply to men and women.

Diet — An optimal diet for the prevention or treatment of osteoporosis includes an adequate intake of calories as well as calcium and vitamin D, both of which are essential in helping to maintain proper bone formation and density.

Calcium intake — Experts recommend that daily elemental calcium intake (total of diet plus supplement) be at least 1000 mg for premenopausal women and men, and 1500 mg in postmenopausal women who do not take estrogen. However, the total daily calcium intake should not routinely exceed 2000 mg due to the possibility of adverse effects. (See "Patient information: Calcium for bone health").

The main dietary sources of calcium include milk and other dairy products, such as cottage cheese, yogurt, or hard cheese, and green vegetables, such as spinach and broccoli (show table 1). A rough method of estimating dietary calcium intake is to multiply the number of dairy servings consumed each day by 300 mg. One serving is 8 oz of milk or yogurt, 1 oz of hard cheese, or 16 oz of cottage cheese.

Calcium supplements (calcium carbonate or calcium citrate) may be suggested if a person cannot get enough calcium in their diet (show figure 1). Calcium doses greater than 500 mg/day should be taken in divided doses (eg, once in morning and evening). The daily intake recommendations given above always apply to "elemental calcium". Use caution when reading the labels of calcium supplements and be sure to note the amount of elemental calcium contained per serving, as many products give the calcium content per two pills.

Vitamin D intake — Experts also recommend 800 International Units (IU) of vitamin D each day. This dose appears to reduce bone loss and fracture rate in older women and men when there is adequate calcium intake (described above).

Milk is the primary dietary source of dietary vitamin D, containing approximately 100 IU per cup. Experts recommend vitamin D supplementation for all patients with osteoporosis whose intake of vitamin D is below 400 IU per day. This can be found in a daily multivitamin or a calcium/vitamin D supplement. Vitamin D is available separately in 400 IU supplements.

Protein supplements — Protein supplements may also be recommended for some patients to ensure sufficient protein intake. This may be particularly important for those who have already had osteoporotic fractures.

Alcohol, caffeine, and salt intake — A healthcare provider may also recommend limiting alcohol consumption, since high alcohol intake may increase the risk of fracture due to an increased risk of falling, poor nutrition, etc. It is not clear if restricting caffeine or salt is helpful; these measures have not been proven to prevent bone loss in those who have a sufficient intake of calcium.

Exercise — A person who has or wants to prevent osteoporosis should exercise for at least 30 minutes three times per week. Any weight-bearing exercise regimen is appropriate (eg, walking). However, exercises that could increase the risk of falling should be avoided.

Weight-bearing exercises can improve bone mass in premenopausal women and help to maintain bone density for women after menopause. Physical activity reduces the risk of hip fracture in older women as a result of increased muscle strength.

The benefits of exercise are quickly lost if a person stop exercising. A regular, weight-bearing exercise regimen that a person genuinely enjoys improves the chances of continuing to follow the routine over the long term. (See "Patient information: Exercise").

Smoking cessation — Smoking cessation is strongly recommended for patients at risk for osteoporosis because smoking cigarettes is known to accelerate bone loss. One study suggested that women who smoke one pack per day throughout adulthood have a 5 to 10 percent reduction in bone density by menopause, resulting in an increased risk of fracture. (See "Patient information: Smoking cessation").

Preventing falls — Repeated falling may significantly increase the risk of osteoporotic fractures in the elderly. Taking measures to prevent falls can decrease the risk of fractures. Such measures may include the following: Remove loose rugs and electrical cords or any other loose items in your home that could lead to tripping, slipping, and falling. Ensure that there is adequate lighting in all areas inside and around the home, including stairwells and entrance ways. Avoid walking on ice, wet or polished floors, or other potentially slippery surfaces. Avoid walking in unfamiliar areas outside.

Because certain drugs may increase the risk of falls, drug regimens should be reviewed on a regular basis. In some cases, the healthcare provider may decide to substitute one medication with an alternative that has a lower risk of causing falls. In addition, people with poor vision should see an eye specialist (eg, optomotrist or ophthamologist) for corrective lenses (glasses).

Hip pads — A person with osteoporosis who falls on their hip but has a substantial amount of muscle or fat padding over the hips has a lower risk of fracture than a person who has little padding. Hip pads (external hip protectors) are designed to reduce the risk of fracture when an elderly person falls. Results of studies that used hip pads have shown mixed results. For people who are willing to wear them on a consistent basis, hip pads may be of benefit in preventing fractures related to an accidental fall.

Medication monitoring — Prolonged therapy with and/or high doses of certain medications that increase bone loss should be monitored closely by a healthcare provider and decreased or discontinued when possible. Such medications include the following: Glucocorticoid medications (eg, prednisone) Heparin, a medication used to prevent and treat abnormal blood clotting (ie, anticoagulant) Vitamin A and certain synthetic retinoids (eg, etretinate) Certain antiepileptic drugs (eg, phenytoin, carbamazepine, primidone, phenobarbital, and valproate)

MEDICATIONS — The non-drug measures discussed above can help to reduce bone loss. For certain men and for premenopausal women who have or who are at risk for osteoporosis, drug or hormonal therapies may also be recommended.

However, the relationship between bone density and fracture risk in premenopausal women is not well defined. A premenopausal woman with low bone density may have no increased risk of fracture. Thus, bone density alone should not be used to define osteoporosis in a premenopausal woman, but instead indicates the need for further evaluation. (See "Patient information: Osteoporosis causes, diagnosis, and screening").

Bisphosphonates — Bisphosphonates inhibit the breakdown and removal of bone (ie, resorption). They are widely used for the prevention and treatment of osteoporosis in postmenopausal women.

These drugs need to be taken first thing in the morning on an empty stomach with a full 8 oz glass of water. The person must then wait at least half an hour (with alendronate (Fosamax®) and risedronate (Actonel®)) or one hour (with ibandronate (Boniva®)) before eating or taking any other medications. These dosing instructions help to reduce the risk of side effects and potential complications.

Side effects of bisphosphonates — Most people who take bisphosphonates for prevention or treatment of osteoporosis do not have any serious side effects related to the medication. However, it is important to closely follow the instructions for taking the medication; lying down or eating sooner than 30 minutes after a dose increases the risk of stomach upset.

There has been concern about a risk of bisphosphonates in people who require invasive dental work. A problem known as avascular necrosis or osteonecrosis of the jaw has rarely developed in a small number of people who used bisphosphonates. The risk of this problem is small in people who take bisphosphonates for osteoporosis prevention and treatment. However, there is a slightly higher risk of this problem when higher doses of bisphosphonates are given into vein during cancer treatment.

Most experts do not think that it is necessary to stop bisphosphonates before invasive dental work (eg, tooth extraction or implant) unless the treatment has been given into a vein. In this case, the patient should consult their healthcare provider for a specific recommendation.

Bisphosphonates are not recommended for premenopausal women who could become pregnant because of the unknown effects on a developing fetus.

Alendronate — Alendronate (Fosamax®) reduces vertebral and nonvertebral fractures, and decreases the loss of height associated with vertebral fractures. The dose for treatment is 10 mg per day, and the dose for prevention is 5 mg per day. Alendronate is usually taken as a weekly 70 or 35 mg pill.

Risedronate — Risedronate (Actonel®) is also approved for both prevention and treatment of osteoporosis at a dose of 5 mg/day (or as a single 35 mg once-weekly pill). Like alendronate, it reduces the risk of both vertebral and hip fractures.

Ibandronate — Ibandronate (Boniva®) can be used for prevention and treatment of osteoporosis at a dose of 150 mg once monthly. A monthly reminder can be sent by phone, mail, or email from the manufacturer. Although Boniva reduces the risk of bone loss and spine fractures, there is no proof that it reduces the risk of hip fractures.

Other new bisphosphonates are being studied, including single yearly intravenous infusions of zoledronic acid, which might be an effective treatment for postmenopausal osteoporosis.

"Estrogen-like" medications — Certain medications, known as selective estrogen receptor modulators (SERMs) produce some estrogen-like effects in the bone that provides protection against postmenopausal bone loss. In addition, SERMS also decrease the risk of breast cancer in women who are at high risk. Currently available SERMs include raloxifene (Evista®) and tamoxifen. Raloxifene (Evista) can be used for the prevention and treatment of osteoporosis in postmenopausal women, although it may be less effective in preventing bone loss than bisphosphonates or estrogen. (See "Patient information: Tamoxifen and raloxifene for the prevention of breast cancer").

SERMs are not recommended for premenopausal women.

Estrogen/progestin therapy — In the past, estrogen or estrogen-progestin therapy was considered the best way to prevent postmenopausal osteoporosis and was often used for treatment. Data from the Women's Health Initiative (WHI), a large clinical trial, found that combined estrogen-progestin treatment reduced hip and vertebral fracture risk by 34 percent. A similar reduction in fracture risk was seen in the WHI trial of estrogen alone.

Estrogen had the additional advantages of controlling menopausal symptoms. However, the WHI found that estrogen plus progestin does not reduce the risk of coronary heart disease, and slightly increases the risk of breast cancer, stroke, and blood clots. The details of the WHI are discussed elsewhere. (See "Patient information: Postmenopausal hormone therapy").

Thus, estrogen is not recommended for the treatment or prevention of osteoporosis in postmenopausal women. However, some postmenopausal women continue to use estrogen, including women with persistent menopausal symptoms and those who cannot tolerate other types of osteoporosis treatment.

Estrogen may be an appropriate treatment for prevention of osteoporosis in young women with amenorrhea (absence of menses). This is often accomplished with a birth control pill. (See "Patient information: Menstrual cycle disorders (Absent and irregular periods)").

Calcitonin — Calcitonin is a hormone produced by the thyroid gland that, together with parathyroid hormone, helps to regulate calcium concentrations in the body. Synthetic calcitonin is sometimes recommended as a treatment for osteoporosis. Calcitonin may be administered via nasal spray or injection (subcutaneous salmon calcitonin). Nasal administration is typically preferred due to ease of use and because the injections tend to cause more nausea and flushing.

Other drugs are usually recommended before calcitonin because it is not clear if calcitonin increases bone density and decreases the fracture rate outside the spine. However, due to its pain-relieving (analgesic) effects, calcitonin may be suggested as a first-line therapy for those who have a sudden, intense (acute) onset of pain due to vertebral fractures. The treatment regimen is typically changed once the acute pain subsides or if the pain fails to subside over a prolonged period (eg, four weeks).

Parathyroid hormone (PTH) — PTH is produced by the parathyroid glands and stimulates both bone resorption and new bone formation. Intermittent administration stimulates formation more than resorption. Clinical trials suggest that PTH therapy is effective in both the prevention and treatment of osteoporosis in postmenopausal women and in men.

A PTH preparation called Forteo®, given by daily injection for two years, is approved for the treatment of severe osteoporosis. It is more effective at building spine bone density than any other treatment, although it is unclear if it also prevents fracture better than other treatments (specifically, the bisphosphonates). Because it requires daily injection and is expensive, it is usually reserved for patients with very severe hip or spine osteoporosis. It is not recommended for premenopausal women.

Monitoring response to hormonal or drug therapy — Testing may be recommended to monitor a patient's response to osteoporosis therapy. This may include measurement of bone mineral density or laboratory tests that indicate bone turnover (ie, rate of new bone formation and breakdown).

Testing is typically done before treatment begins to get a baseline measurement. Laboratory testing may be repeated three months after treatment begins, while bone density testing may be repeated after two years.

SUMMARY Osteoporosis causes bones to become abnormally thin (osteopenic), weakened, and easily broken. This condition can be treated and prevented with diet, exercise, and stopping smoking. Calcium and vitamin D can prevent and treat thinning bones. The main dietary sources of calcium include milk and other dairy products, such as cottage cheese, yogurt, or hard cheese, and green vegetables, such as spinach and broccoli (show table 1). Milk is the primary source of dietary vitamin D, containing approximately 100 IU per cup. Calcium and vitamin D can also be taken as a supplement (eg, in a pill, show figure 1). A total of at least 1000 mg of calcium per day is recommended for premenopausal women and men. Women after menopause should consume 1500 mg calcium per day if they do not take estrogen. Experts also recommend 800 International Units (IU) of vitamin D each day. Exercise can help to prevent and treat thinning bones. Exercise should be done for at least 30 minutes three times per week. Any weight-bearing exercise regimen is appropriate (eg, walking). Smoking cigarettes can cause bones to become thinner and weaker. Stopping smoking can reduce this risk. Falling can cause fractures in the elderly. Preventing falls can lower the risk of fractures. Some medications can cause bone thinning. Such medications include glucocorticoid medications (eg, prednisone), heparin, vitamin A and certain synthetic retinoids (eg, etretinate), and certain antiepileptic drugs (eg, phenytoin, carbamazepine, primidone, phenobarbital, and valproate). You should talk to your provider about the risk of bone thinning if you take one of these medications (see "Medication monitoring" above). There are several medications that help prevent osteoporosis in women after menopause. We think alendronate (Fosamax®), risedronate (Actonel®), or raloxifene (Evista) are the best medications for prevention (see "Bisphosphonates" above). Alendronate (Fosamax®) or risedronate (Actonel®) are recommended to treat women after menopause who have osteoporosis (see "Bisphosphonates" above). Parathyroid hormone (Forteo®) is another medication that can be used to treat osteoporosis. We recommend this medication for men or postmenopausal women with severe hip or spine osteoporosis (see "Parathyroid hormone (PTH)" above). Hormone replacement (eg, estrogen, progesterone) is not usually recommended to prevent osteoporosis in women after menopause. Hormone therapy is recommended for some young women who do not have a monthly menstrual period (see "Estrogen/progestin therapy" above). A bone density test may be recommend to monitor how the bones respond to osteoporosis treatment. For postmenopausal women, a bone density test is usually done two years after treatment starts.

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine

(www.nlm.nih.gov/medlineplus/healthtopics.html)
Osteoporosis and Related Bone Diseases National Resource Center (ORBD-NRC)

Toll-free: (800) 624-BONE (2663)
TTY: (202) 466-4315
E-mail: orbdnrc@nof.org
(www.osteo.org)
National Osteoporosis Foundation

Phone: (202) 223-2226
E-mail: patientinfo@nof.org
(www.nof.org)
National Women's Health Resource Center (NWHRC)

Toll-free: (877) 986-9472
E-mail: ddiamant@healthywomen.org
(www.healthywomen.org)
Osteoporosis Society of Canada

Phone: (416) 696-2663 x 294
(www.osteoporosis.ca/)
The Hormone Foundation

(www.hormone.org/public/osteoporosis.cfm, available in English, Spanish, French, Italian, German, and Portuguese)

[1-5]


Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Delmas, PD, Bjarnason, NH, Mitlak, BH, et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 1997; 337:1641.
2. Rossouw, JE, Anderson, GL, Prentice, RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002; 288:321.
3. Fulton, JP. New guidelines for the prevention and treatment of osteoporosis. National Osteoporosis Foundation. Med Health R I 1999; 82:110.
4. Gregg, EW, Cauley, JA, Seeley, DG, et al. Physical activity and osteoporotic fracture risk in older women. Ann Intern Med 1998; 129:81.
5. NIH Consensus Development Panel on Optimal Calcium Intake. Optimal calcium intake. JAMA 1994; 272:1942.

No comments: