Osteoporosis is a common problem that causes bones to become abnormally thin, 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 assessment of 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 discusses bone density testing.
OSTEOPOROSIS PREVENTION
Some of the most important treatments for preventing osteoporosis include diet, exercise, and not smoking. These recommendations apply to men and women.
Diet — An optimal diet for preventing or treating osteoporosis includes consuming an adequate number of protein and calories as well as optimal amounts of calcium and vitamin D, which are essential in helping to maintain proper bone formation and density.
Calcium intake — Experts recommend that premenopausal women and men consume at least 1000 mg of calcium per day; this includes calcium in foods and beverages plus calcium supplements. Postmenopausal women should consume 1200 mg of calcium per day (total of diet plus supplements). However, you should not take more than 2000 mg calcium per day, due to the possibility of side effects.
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 kale and broccoli. 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 (236 mL) or yogurt (224 g), 1 oz (28 g) of hard cheese, or 16 oz (448 g) of cottage cheese.
Calcium supplements (calcium carbonate or calcium citrate) may be suggested for women who cannot get enough calcium in their diet. Supplemental calcium doses greater than 500 mg/day should be taken in divided doses (eg, once in morning and evening).
Vitamin D intake — Experts recommend that men over 70 years and postmenopausal women consume 800 international units of vitamin D each day. This dose appears to reduce bone loss and fracture rate in older women and men who have adequate calcium intake (described above). Although the optimal intake has not been clearly established in premenopausal women or in younger men with osteoporosis, 600 international units of vitamin D daily is generally suggested.
Milk supplemented with vitamin D is a primary dietary source of dietary vitamin D; it contains approximately 100 international units per 8 oz (236 mL). Another good source is salmon, with approximately 600 international units per 3.5 oz (98 g) serving. Experts recommend vitamin D supplementation for all patients with osteoporosis whose intake of vitamin D is below 600 to 800 international units per day.
Protein supplements — Protein supplements may be recommended in some people to ensure sufficient protein intake. This may be particularly important for those who have already had an osteoporotic fracture.
Alcohol, caffeine, and salt intake — Drinking alcohol excessively (more than two drinks a day) can increase the risk of fracture due to an increased risk of falling, poor nutrition, etc, so it should be avoided.
Restricting caffeine or salt has not been proven to prevent bone loss in people who consume an adequate amount of calcium.
Exercise — Exercise may decrease fracture risk by improving bone mass in premenopausal women and helping to maintain bone density for women after menopause. Furthermore, exercise may decrease the tendency to fall due to weakness. Physical activity reduces the risk of hip fracture in older women as a result of increased muscle strength. Most experts recommend exercising for at least 30 minutes three times per week.
The benefits of exercise are quickly lost when a person stops exercising. A regular, weightbearing exercise regimen that a person enjoys improves the chances that the person will continue it over the long term.
Smoking — Stopping smoking is strongly recommended for bone health because smoking cigarettes is known to speed 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.
Falls — Falling significantly increases the risk of osteoporotic fractures in older adults. Taking measures to prevent falls can decrease the risk of fractures. Such measures may include the following:
●Removing loose rugs and electrical cords or any other loose items in the home that could lead to tripping, slipping, and falling.
●Providing adequate lighting in all areas inside and around the home, including stairwells and entrance ways.
●Avoiding walking on slippery surfaces, such as ice or wet or polished floors.
●Avoiding walking in unfamiliar areas outside.
●Reviewing drug regimens to replace medications that may increase the risk of falls with those that are less likely to do so.
●Visiting an ophthalmologist or optometrist regularly to optimize vision.
Medications — Prolonged therapy with and/or high doses of certain medications can increase bone loss. The use of these medications should be monitored by a health care 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)
●Certain antiepileptic drugs (eg, phenytoin, carbamazepine, primidone, and phenobarbital)
OSTEOPOROSIS MEDICATIONS
The non-drug measures discussed above can help to reduce bone loss. A medication or hormonal therapy may also be recommended for certain men and women who have or who are at risk for osteoporosis.
Who needs treatment with a medication? — People with the highest risk of fracture are the ones most likely to benefit from drug therapy. In the United States, the National Osteoporosis Foundation (NOF) recommends use of a medication to treat postmenopausal women (and men ≥50 years) with a history of hip or vertebral fracture or with osteoporosis (T-score ≤-2.5).
In addition, the NOF recommends drug therapy for people who have osteopenia (T-score between -1.0 and -2.5) and an estimated 10-year risk of hip or osteoporosis-related fracture ≥3 or ≥20 percent, respectively. The absolute risk of fracture can be calculated using the Fracture Risk Assessment Tool (FRAX) calculator.
However, some people who do not meet these criteria will benefit from a medication to treat osteoporosis or osteopenia. The final decision about use of a medication should be shared between the patient and health care provider.
Treatment in premenopausal women — The relationship between bone density and fracture risk in premenopausal women is not well defined. A premenopausal woman with low bone density may have little increased risk of fracture. Thus, bone density alone should not be used to diagnose osteoporosis in a premenopausal woman; further evaluation is generally recommended.
Bisphosphonates — Bisphosphonates are medications that slow 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 plain (not sparkling) water. The person must then wait:
●At least half an hour (with alendronate and risedronate) before eating or taking any other medications.
●At least one hour (with ibandronate) before eating or taking any other medications.
These dosing instructions help ensure that the drugs will be absorbed and also reduce the risk of side effects and potential complications.
An enteric-coated, delayed-release formulation of risedronate is also available. Unlike immediate-release risedronate and other oral bisphosphonates, delayed-release risedronate is taken immediately after breakfast and with at least 4 ounces of water.
Patients should remain upright (sitting or standing) for at least 30 minutes after taking any oral bisphosphonate to minimize the risk of reflux.
Side effects of bisphosphonates — Most people who take bisphosphonates 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 the recommended time after a dose increases the risk of stomach upset.
There has been concern about use of bisphosphonates in people who require invasive dental work. A problem known as avascular necrosis or osteonecrosis of the jaw has developed in people who used bisphosphonates. The risk of this problem is very 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 a vein during cancer treatment.
Experts do not think that it is necessary for most people to stop bisphosphonates (when they are taking them for the treatment of osteoporosis) before invasive dental work (eg, tooth extraction or implant). However, people who take a bisphosphonate as part of a treatment for cancer should consult their doctor before having invasive dental work.
Alendronate — Alendronate (brand name: Fosamax) reduces vertebral and hip fractures, and decreases the loss of height associated with vertebral fractures. It is available as a pill that is taken once per day or once per week.
Risedronate — Risedronate reduces the risk of both vertebral and hip fractures. Risedronate (sample brand name: Actonel) is approved for both prevention and treatment of osteoporosis. It can be taken once per day, once per week, or once per month.
Ibandronate — Although ibandronate reduces the risk of bone loss and spine fractures, there is no proof that it reduces the risk of hip fractures. Ibandronate (brand name: Boniva) can be used for prevention and treatment of osteoporosis. It is available as a pill that is taken once per day or once per month. It is also available as an injection that is given into a vein once every three months.
Zoledronic acid — A once-yearly, intravenous dose of zoledronic acid (sample brand name: Reclast) is also available for the treatment of osteoporosis. This medication is given into a vein over 15 minutes and is usually well tolerated. Yearly intravenous zoledronic acid can improve bone density, decrease the risk of spine and hip fractures, and decrease the risk of recurrent fractures in high-risk patients with recent hip fracture.
Side effects of zoledronic acid can include flu-like symptoms within 24 to 72 hours of the first dose. This may include a low-grade fever and muscle and joint pain. Treatment with a fever-reducing medication (acetaminophen) generally improves the symptoms. Subsequent doses typically cause milder symptoms.
Intravenous zoledronic acid is an appealing alternative for people who cannot tolerate oral bisphosphonates or who prefer a once yearly to a monthly, weekly, or daily regimen. However, the ideal duration of therapy and long-term safety (>3 years) have not been established.
“Estrogen-like” medications — Certain medications, known as selective estrogen receptor modulators (SERMs), produce some estrogen-like effects in the bone. These medications provide protection against postmenopausal bone loss. In addition, SERMs decrease the risk of breast cancer in women who are at high risk. Currently available SERMs include raloxifene (brand name: Evista) and tamoxifen. Raloxifene 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. Tamoxifen is usually given to women with breast cancer to reduce the risk of recurrence, or to women who have never had breast cancer but are at high risk of developing it.
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 women who took estrogen alone.
Estrogen had the additional advantage of controlling menopausal symptoms. However, the WHI found that estrogen plus progestin does not reduce the risk of coronary artery disease and slightly increases the risk of breast cancer, stroke, and blood clots. The details of the WHI are discussed elsewhere.
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, and those women are usually protected against bone loss and so do not need to consider additional drugs to prevent bone loss.
Estrogen may be an appropriate treatment for prevention of osteoporosis in young women whose ovaries do not make estrogen. This treatment may be given as a skin patch or orally, such as a birth control pill.
Denosumab — Denosumab (brand name: Prolia) is an antibody directed against a factor (RANKL) involved in the formation of cells that break down bone. Denosumab improves bone mineral density and reduces fracture in postmenopausal women with osteoporosis. It is administered as an injection under the skin once every six months. Although denosumab is generally well tolerated, side effects can include skin infections (cellulitis) and eczema. A mild transient lowering of blood calcium levels has also been reported, but this is not usually a problem in patients with good kidney function, who are taking enough calcium and vitamin D.
Because it is a newer drug and there are no long-term safety data, denosumab is usually reserved for patients who are intolerant of or unresponsive to oral and/or intravenous bisphosphonates. Denosumab should not be given to patients with low blood calcium until it is corrected.
Parathyroid hormone — PTH is unique in that it is the only medication that works by stimulating bone formation. The other medications described above work by reducing bone 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, is approved for the treatment of severe osteoporosis for two years. It is more effective at building spine bone density and reducing spine fracture risk than any other treatment. Because it requires a daily injection and is expensive, it is usually reserved for patients with severe hip or spine osteoporosis (T-score <-2.5 and an osteoporosis-related fracture). It is not recommended for premenopausal women.
Calcitonin — Calcitonin is a hormone produced by the thyroid gland that, together with parathyroid hormone (PTH), helps to regulate calcium concentrations in the body. Other drugs are usually recommended in preference to calcitonin because other available drugs (eg, bisphosphonates) are more effective for the prevention of bone loss and reduction of fracture risk. In addition, there is concern about the long-term use of calcitonin for osteoporosis and an increase in cancer rates. However, due to its pain-relieving (analgesic) effects, calcitonin may be suggested as short-term 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).
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.
MONITORING RESPONSE TO TREATMENT
Testing may be recommended to monitor a person’s response to osteoporosis therapy. This may include measurement of bone mineral density (dual-energy x-ray absorptiometry [DXA] scan) or laboratory tests that indicate bone turnover (ie, rate of new bone formation and breakdown).
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