Osteoporosis Risk Factors
- Age is the main risk factor for osteoporosis. Aging causes bones to thin and weaken. Although osteoporosis affects mostly postmenopausal women, older men are also at risk.
- Osteoporosis is more common in people who have a small, thin body frame and bone structure.
- Dietary calcium and vitamin D deficiencies are important factors in the risk for osteoporosis.
- Women who smoke, particularly after menopause, have a significantly greater risk of spine and hip fractures than those who do not smoke. Men who smoke also have lower bone density.
- Excessive alcohol consumption increases osteoporosis risk.
- Lack of exercise and a sedentary lifestyle can increase the risk of osteoporosis. Engaging in regular weight-bearing and resistance exercises (such as walking or strength training) can help prevent it.
- Bisphosphonates are the main drugs used for osteoporosis prevention and treatment. Alendronate (Fosamax), risedronate (Actonel), and ibandronate (Boniva) come in pills that are taken by mouth. Zoledronic acid (Reclast) is given by once-yearly injection. Ibandronate is also available as a four-times a year injection. Denosumab (Prolia) is a new type of antiresorptive medication that works differently than bisphosphonates.
- Other types of drugs used for osteoporosis treatment and prevention include raloxifene (Evista), calcitonin, and teriparatide (Forteo).
In 2010, the FDA approved denosumab (Prolia) for treatment of osteoporosis in postmenopausal women who are at high risk for fracture. It may also be considered for women who cannot tolerate or who have not been helped by other osteoporosis treatments. Denosumab is the first biologic drug approved for osteoporosis treatment and prevention of fractures. It is given in a doctor’s office as a twice-yearly injection.
In 2010, the FDA warned that long-term (more than 5 years) use of bisphosphonate drugs may increase the risk for thigh bone fracture.
Osteoporosis is a skeletal disease in which bones become brittle and prone to fracture. In other words, the bone loses density. Bone density is the amount of bone tissue (such as calcium and minerals) in a certain volume of bone. Osteoporosis is diagnosed when bone density has decreased to the point where the risk of fractures is high even without severe stress or injury to the bones.
The skeleton consists of groups of bones which protect and move the body.
The Function of Bones. The skeleton has a dual function:
- It provides structural support for muscles and organs.
- It also serves as a storehouse for the body's calcium and other essential minerals, such as phosphorus and magnesium.
The skeleton holds 99% of the body's calcium. The remaining 1% circulates in the blood and is essential for crucial bodily functions, ranging from muscle contraction to nerve function to blood clotting.
Bone Turnover: the Breakdown and Rebuilding of Bones. Bone tissue is constantly being broken down and reformed again. This turnover is necessary for growth, for repair of minor damage that occurs from everyday stress, and for the maintenance of a properly functioning body. Two essential cells are involved in this process:
- Osteoclast cells are formed from certain blood cells and are responsible for the breakdown, or resorption, of the skeleton. These cells dig holes into the bone and release the small amounts of calcium into the bloodstream that are necessary for other vital functions.
- Osteoblast cells are produced by bone cells and are the bone builders. They rebuild the skeleton, first by filling in the holes with collagen, and then by laying down crystals of calcium and phosphorus.
Each year, about 10 - 30% of the adult skeleton is remodeled in this way. The balance of bone build-up (formation) and break down (resorption) is controlled by a complex mix of hormones and chemical factors. If bone resorption occurs at a greater rate than bone build up, your bone loses density and puts you at risk for osteoporosis.
Until a healthy adult is around age 40, the process of formation and resportion is a nearly perfectly coupled system, with one phase balancing the other. As a person ages, or in the presence of certain conditions, this system breaks down and the two processes become out of sync. Some individuals have a very high turnover rate of bone, some have a very gradual turnover, but the breakdown of bone eventually overtakes the build-up.
In women, estrogen loss after menopause is particularly associated with rapid resorption and loss of bone density. Postmenopausal women are therefore at highest risk for osteoporosis and subsequent fractures.
Primary and Secondary Osteoporosis
Primary osteoporosis is the most common type of osteoporosis. It can be age-related and associated with the postmenopausal decline in estrogen levels, or related to calcium and vitamin D insufficiency.
Secondary osteoporosis is osteoporosis caused by other conditions, such as hormonal imbalances, diseases, or medications (such as corticosteroids or anti-seizure drugs).
Click the icon to see an image of osteoporosis.
Because the patterns of reforming and resorbing bone often vary from patient to patient, doctors believe several different factors account for this problem. Important chemicals (estrogen, testosterone, parathyroid hormone, and vitamin D) and blood factors that affect cell growth are involved with this process. Changes in levels of any of these factors can play a role in the development of osteoporosis.
The Role of Sex Hormones in Bone Breakdown
Although normally associated with women, sex hormones play a role in osteoporosis in both genders, most likely by controlling the development and activity of both osteoclasts (bone breakers) and osteoblasts (bone builders).
Women and Estrogen. A woman experiences a rapid decline in bone density after menopause, when her ovaries stop producing estrogen. Estrogen comes in several forms:
The uterus is a hollow muscular organ located in the female pelvis between the bladder and rectum. The ovaries produce the eggs that travel through the fallopian tubes. Once the egg has left the ovary it can be fertilized and implant itself in the lining of the uterus. The main function of the uterus is to nourish the developing fetus prior to birth.
- The most potent form of estrogen is estradiol. Estradiol deficiency appears to be a very strong factor in the development of osteoporosis.
- The other important but less powerful estrogens are estrone and estriol.
The ovaries produce most of the estrogen in the body, but it can also be formed in other tissues, such as the adrenal glands, body fat, skin, and muscle. After menopause, some amounts of estrogen continue to be manufactured in the adrenals and in peripheral body fat. Even though the adrenals and ovaries have stopped producing estrogens directly, they continue to be a source of the male hormone testosterone, which converts into estradiol.
Estrogen may have an impact on bone density in various ways, including slowing bone breakdown (resorption).
Men and Androgens and Estrogen. In men, the most important androgen (male hormone) is testosterone, which is produced in the testes. Other androgens are produced in the adrenal glands. Androgens are converted to estrogen in various parts of a man’s body, including bone.
Click the icon to see an image of the adrenal glands.
Studies have suggested that the falling levels of estrogen as well as testosterone may contribute to bone loss in elderly men. Both hormones appeared to be integral to bone function in men.
Vitamin D and Parathyroid Hormone Imbalances
Low levels of vitamin D and high levels of parathyroid hormone (PTH) are associated with bone density loss in women after menopause:
- Vitamin D is a vitamin with hormone-like properties. It is essential for the absorption of calcium from the intestines and for normal bone growth. Lower levels result in impaired calcium absorption, which in turn causes an increase in parathyroid hormone (PTH).
- Parathyroid hormone is produced by the parathyroid glands. These are four small glands located on the surface of the thyroid gland. They are the most important regulators of calcium levels in the blood. When calcium levels are low, the glands secrete more PTH, which then increases blood calcium levels. High persistent levels of PTH stimulate bone resorption (bone mineral loss).
Click the icon to see an image of the benefits of vitamin D.
Click the icon to see an image of the sources of vitamin D.
Click the icon to see an image of the parathyroid glands.
Genetic factors may play a role in determining bone density.
Causes of Secondary Osteoporosis
Corticosteroids. Oral corticosteroids (also called steroids or glucocorticoids) can reduce bone mass in both men and women. It is not clear whether inhaled steroids carry the same risks, but some studies indicate that they may cause bone loss when taken at higher doses for long periods of time. (Children on inhaled steroids may have temporary impaired growth, but they do not appear to be at risk for bone loss.)
Diuretics. Diuretics, which are used to treat high blood pressure, have different effects on osteoporosis, depending on the type. Loop diuretics, such as furosemide (Lasix), increase the kidneys’ excretion of calcium, which can lead to thinning bones. Thiazide diuretics, on the other hand, protect against bone loss, but this protective effect ends after use is discontinued.
Contraceptives. Hormonal contraceptives that use progestin without estrogen (such as Depo-Provera injection or other progestin-based contraceptives), can cause loss of bone density. For this reason, the Food and Drug Administration (FDA) recommends that Depo-Provera injections should not be used for longer than 2 years.
Other Medications. Anticonvulsant (anti-seizure) drugs increase the risk for bone loss (as does epilepsy itself). Other drugs that increase the risk for bone loss include the blood-thinning drug heparin, and hormonal drugs that suppress estrogen (such as gonadotropin-releasing hormone agonists and aromatase inhibitors). Proton pump inhibitors (PPIs), which are used to treat gastroesophageal reflux disease (heartburn), may also increase the risk for bone loss and fractures. These drugs include omeprazole (Prilosec), lansoprazole (Prevacid), and esomeprazole (Nexium).
Medical Conditions. Osteoporosis can be secondary to several other conditions, including alcoholism, diabetes, hyperthyroidism, chronic liver or kidney disease, Crohn's disease, celiac disease, scurvy, rheumatoid arthritis, leukemia, cirrhosis, gastrointestinal diseases, vitamin D deficiency, lymphoma, hyperparathyroidism, and rare genetic disorders such as Marfan and Ehlers-Danlos syndrome.
About 10 million adults in the United States have osteoporosis, and another 34 million have low bone mass that places them at risk for developing osteoporosis.
Seventy percent of people with osteoporosis are women. Men start with higher bone density and lose calcium at a slower rate than women, which is why their risk is lower. Nevertheless, older men are also at risk for osteoporosis.
As people age, their risks for osteoporosis increase. Aging causes bones to thin and weaken.
Although adults from all ethnic groups are susceptible to developing osteoporosis, Caucasian and Asian women and men face a comparatively greater risk.
Osteoporosis is more common in people who have a small, thin body frame and bone structure.
People whose parents had a history of fractures may be more likely to have fractures.
Women. Events associated with estrogen deficiencies are the primary risk factors for osteoporosis in women. These include:
- Menopause. Within 5 years after menopause, the risk for fracture increases dramatically. Fractures occurring during this period are more likely to occur in the wrist or spine than the hip, but their occurrence is a strong predictor of later severe osteoporosis and hip fracture.
- Surgical removal of ovaries
- Missing periods for 3 months or longer
- Never having given birth
- Anorexia nervosa, (an eating disorder), or extreme low body weight can affect the body's production of estrogen
Men. Low levels of testosterone increase osteoporosis risk. Certain types of medical conditions (hypogonadism) and treatments (prostate cancer androgen deprivation) can cause testosterone deficiency.
Dietary Factors. Diet plays an important role in preventing and speeding up bone loss in men and women. Calcium and vitamin D deficiencies are important factors in the risk for osteoporosis. Other dietary factors may also be harmful or protective for certain people.
The body requires adequate vitamin D in order to absorb calcium. In the United States, many food sources of calcium such as milk are fortified with vitamin D.
Click the icon to see an image of the sources of calcium.
Exercise. Lack of exercise and a sedentary lifestyle increases the risk for osteoporosis. Conversely, in competitive female athletes, excessive exercise may reduce estrogen levels, causing bone loss. (The eating disorder anorexia nervosa can have a similar effect.) People who are chairbound or bedbound due to medical infirmities and who do not bear weight on the bones are at risk for osteoporosis.
Lack of Sunlight. The photochemical effect of sunlight on the skin is a primary source for vitamin D. Bone formation peaks in the summer and bone breakdown increases in the winter. People who avoid sun exposure to prevent skin cancer may be at risk for vitamin D deficiency, particularly if they are elderly.
Click the icon to see an image of the sources of vitamin D.
Smoking. Women who smoke, particularly after menopause, have a significantly greater chance of spine and hip fractures than those who don't smoke. Men who smoke also have lower bone density.
Alcohol. Excessive consumption of alcoholic beverages can increase the risk for bone loss.
Risk Factors in Children and Adolescents
The maximum density that bones achieve during the growing years is a major factor in whether a person goes on to develop osteoporosis. People, usually women, who never develop adequate peak bone mass in early life are at high risk for osteoporosis later on. Children at risk for low peak bone mass include those who are:
- Born prematurely
- Have anorexia nervosa
- Have delayed puberty or abnormal absence of menstrual periods
Although to a large extent genetics predict bone health, exercise and good nutrition during the first three decades of life (when peak bone mass is reached) are still excellent safeguards against osteoporosis (and countless other health problems).
Bone density loss from osteoporosis is a major cause of disability and death in the elderly, mostly due to subsequent fractures. The lifetime risk of spinal fracture in women is about one in three, and for hip fracture is one in six. Women at highest risk for fractures are those with low bone density plus a history of fractures, particularly low-trauma fractures.
Click the icon to see an animation about osteoporosis.
Osteoporosis causes more than 1.5 million fractures annually. About 50% of women and 25% of men over age 50 will suffer an osteoporosis-related fracture during their lifetime. Spinal vertebreal fractures are the most common type of osteoporosis-related fracture, followed by hip fractures, wrist fractures, and other types of broken bones. About 80% of these fractures occur after relatively minor falls or accidents.
Click the icon to see an image of a compression fracture.
Click the icon to see an image of a hip fracture.
Risk Factors for Fracture and Falling. In addition to low bone density, falling is the primary risk factor for fractures. Additional risk factors for fracture are those that increase the risk for falling. They include:
- Having chronic medical problems (emphysema, heart disease, stroke, arthritis, and depression), the risk increasing with multiple health problems
- Taking multiple medications (especially tranquilizers and antidepressants)
- Poor physical function, importantly slow gait and reduced muscle strength. Inactivity that results in weak thigh muscles and poor balance particularly puts any older person at risk for fracture and particularly those with low bone density.
- Poor concentration or mental impairment
- Impaired vision
- Hazardous environment (such as the presence of throw rugs in the house)
Mortality after Fracture
Hip fractures can increase the risk of death in both men and women. Complications of hip fractures include hospital-acquired infections and blood clots in the lungs.
Many people confuse osteoporosis with arthritis and mistakenly believe it is safe to wait for symptoms such as swelling and joint pain to occur before seeing a doctor. However, arthritis is entirely different from osteoporosis. Osteoporosis is quite advanced before symptoms appear.
All too often, osteoporosis becomes apparent in dramatic fashion: A fracture of a vertebra (backbone), hip, forearm, or any bony site if sufficient bone mass is lost. These fractures frequently occur after apparently minor trauma, such as bending over, lifting, jumping, or falling from the standing position.
Pain, disfigurement, and debilitation are common in the latter stages of the disease. Early spinal compression fractures may go undetected for a long time, but after a large percentage of calcium has been lost, the vertebrae in the spine start to collapse, gradually causing a stooped posture called kyphosis, or a "dowager’s hump." Although this is usually painless, patients may lose as much as 6 inches in height.
Click the icon to see an image of osteoporosis.
Candidates for Bone Density Testing
Because osteoporosis can occur with few symptoms, testing is important. Bone density testing is recommended for:
- All women over age 65
- Postmenopausal women under age 65 with one or more risk factors for osteoporosis
- All men over age 70
- Men ages 50 - 70 with one or more risk factors for osteoporosis
- Any man or woman over age 50 who has suffered a fracture
Risk factors that may indicate a need for bone mineral density testing include:
- Long-term use of medications associated with low bone mass or bone loss such as corticosteroids, some anti-seizure medications, Depo-Provera, thyroid hormone, or aromatase inhibitors. Long-term use of corticosteroids (more than 5 mg/day for more than 3 months) is a specific risk factor.
- History of treatment for prostate cancer or breast cancer
- History of medical conditions such as diabetes, thyroid imbalances, estrogen or testosterone deficiencies, early menopause, anorexia nervosa, rheumatoid arthritis
- Significant loss of height
- Significant recent weight loss or low body mass index (BMI less than 21)
- History of hip fracture in parent
- Excessive alcohol use
Tests Used for Measuring Bone Density
Central DXA. The standard technique for determining bone density is a form of bone densitometry called dual-energy x-ray absorptiometry (DXA). DXA is simple and painless and takes 2 - 4 minutes. The machine measures bone density by detecting the extent to which bones absorb photons that are generated by very low-level x-rays. (Photons are atomic particles with no charge.) Measurements of bone mineral density are generally given as the average concentrations of calcium in areas that are scanned.
A bone density scan measures the density of bone in a person. The lower the density of a bone the higher the risk of fractures. A bone density test, along with a patient's medical history, is a useful aid in evaluating the probability of a fracture and whether any preventative treatment is needed. A bone density scan has the advantage of being painless and exposing the patient to only a small amount of radiation.
Central DXA measures the bone mineral density at the hip, upper thigh bone (femoral neck), and spine.
Click the icon to see an image of a hip fracture.
Other Tests. Other tests may be used, but they are not usually as accurate as DXA. They include ultrasound techniques, DXA of the wrist, heels, fingers, or leg (peripheral DXA) and quantitative computed tomography (QCT) scan.
Screening tests using these technologies are sometimes given at health fairs or other non-medical settings. These screening tests typically measure peripheral bone density in the heels, fingers, or leg bones. The results of these tests may vary from DXA measurements of spine and hip. While these peripheral tests may help indicate who requires further BMD testing, a central DXA test is required to diagnose osteoporosis and to monitor treatment response.
Diagnosing Osteoporosis and Predicting the Risk for Fracture
Osteoporosis is diagnosed when bone density has decreased to the point where fractures will happen with mild stress, the so-called fracture threshold. This is determined by measuring bone density and comparing the results with the norm, which is defined as the average bone mineral density in the hipbones of a healthy 30-year-old adult.
The doctor then uses this comparison to determine the standard deviation (SD) from this norm. Standard deviation results are given as Z and T scores:
- The T score gives the standard deviation of the patient in relationship to the norm in young adults. Doctors often use the T-score and other risk factors to determine the risk for fracture.
- The Z score gives the standard deviation of the patient in relationship to the norm in the patient’s own age group and body size. Z scores may be used for diagnosing osteoporosis in younger men and women. They are not normally used for postmenopaual women or for men age 50 and older.
Results of T-scores indicate:
- Higher than -1 indicates normal bone density.
- Between -1 and -2.5 indicates low bone density (osteopenia).
- A score of -2.5 or lower indicates a diagnosis of osteoporosis.
The lower the T-score, the lower the bone density, and the greater the risk for fracture. In general, doctors recommend beginning medication when T-scores are -2.5 or below. Patients who have other risk factors may need to begin medication when they have osteopenia (scores between -1 and -2.5). Osteopenia is considered a precursor to osteoporosis.
In certain cases, your doctor may recommend that you have a blood test to measure your vitamin D levels. A standard test measures 25-hydroxyvitamin D, also called 25(OH)D. Depending on the results, your doctor may recommend you take vitamin D supplements.
Healthy lifestyle habits, including adequate intake of calcium and vitamin D, are important for preventing osteoporosis and are also a useful accompaniment to medical treatment.
Calcium and Vitamin D
A combination of calcium and vitamin D can reduce the risk of osteoporosis. (For strong bones, people need enough of both calcium and vitamin D.) The National Osteoporosis Foundation (NOF) recommends:
- Adults under age 50 should have 1,000 mg of calcium and 400 - 800 IU of vitamin D daily.
- Adults age 50 and older should have 1,200 mg of calcium and 800 - 1,000 IU of vitamin D daily.
Dietary Sources. Good dietary sources of calcium include:
- Milk, yogurt, and other dairy products
- Dark green vegetables such as collard greens, kale, and broccoli
- Sardines and salmon with bones
- Calcium-fortified foods and beverages such as cereals, orange juice, soymilk
Certain types of foods can interfere with calcium absorption. These include foods high in oxalate (such as spinach and beet greens) or phytate (peas, pinto beans, navy beans, wheat bran). Diets high in animal protein, sodium, or caffeine may also interfere with calcium absorption.
Dietary sources of vitamin D include:
- Fatty fish such as salmon, mackerel, and tuna
- Egg yolks
- Vitamin D-fortified milk, orange juice, soymilk, or cereals
However, many Americans do not get enough vitamin D solely from diet or exposure to sunlight.
Supplements. Adults who consume adequate amounts of calcium in their diets may not need to take a calcium supplement. But they may require vitamin D supplements, particularly if they do not get enough exposure to sunlight. Vitamin D is made in the skin using energy from the ultraviolet rays in sunlight. Because sun exposure increases the risk for skin cancer and premature skin aging, many Americans restrict their sunlight exposure. People's vitamin D levels decline as they age.
Calcium and vitamin D supplements can be taken as separate supplements or as a combination supplement. If separate preparations are used, they do not need to be taken at the same time.
- Calcium supplements include calcium carbonate (Caltrate, Os-Cal, Tums), calcium citrate (Citracal), calcium gluconate, and calcium lactate. Although each kind provides calcium, they all have different calcium concentrations, absorption capabilities, and other actions.
- Vitamin D is available either as D2 (ergocalciferol) or D3 (cholecalciferol). They work equally well for bone health.
Both calcium and vitamin D supplements may increase the risks for kidney stones. If you have a history of kidney stones, discuss with your doctor whether these supplements are appropriate for you.
Calcium supplements can also have other side effects and drug interactions:
- Some people may experience gas, bloating, or constipation. These effects can usually be relieved by increasing fluid and fiber consumption.
- Calcium supplements can interfere with the actions of certain medications such as tetracycline antibiotics, thyroid hormone, and proton pump inhibitors. Iron supplements should not be taken at the same time as calcium supplements.
Exercise is very important for slowing the progression of osteoporosis. Although mild exercise does not protect bones, moderate exercise (more than 3 days a week for more than a total of 90 minutes a week) reduces the risk for osteoporosis and fracture in both older men and women. Exercise should be regular and life-long. Before beginning any strenuous exercise program, older patients or those who have serious medical conditions should talk to their doctors.
Specific exercises may be better than others:
- Weight-bearing exercise applies tension to muscle and bone and, in young people, can increase bone density by as much as 2 - 8% a year. In premenopausal women these exercises are very protective. Careful weight training is also very beneficial for middle-aged and older people, especially women.
- Regular brisk long walks improve bone density and mobility. Most older individuals should avoid high-impact aerobic exercises (step aerobics), which increase the risk for osteoporotic fractures. Although low-impact aerobic exercises such as swimming and bicycling do not increase bone density, they are excellent for cardiovascular fitness and should be part of a regular regimen.
- Exercises specifically targeted to strengthen the back may help prevent fractures later on in life and can be beneficial in improving posture and reducing kyphosis (hunchback), even in people with existing severe conditions.
- Low-impact exercises that improve concentration, balance, and strength, particularly yoga and tai chi, may help to decrease the risk of falling.
Exercise plays an important role in the retention of bone density in the aging person. Studies show that exercises requiring muscles to pull on bones cause the bones to retain and possibly gain density.
Click the icon to see an image of osteoporosis.
Other Lifestyle Factors
Other lifestyle changes that can help prevent osteoporosis include:
- Limit alcohol consumption. Excessive drinking is associated with brittle bones.
- Limit caffeine consumption. Caffeine may interfere with the body’s ability to absorb calcium.
- Quit smoking. The risk for osteoporosis from cigarette smoking appears to diminish after quitting.
Preventing Falls and Fractures
An important component in reducing the risk for fractures is preventing falls. Risk factors for falling include:
- Slow walking
- Inability to walk in a straight line
- Certain medications (such as tranquilizers and sleeping pills)
- Low blood pressure when rising in the morning
- Poor vision
Recommendations for preventing falls or fractures from falls in elderly people include:
- Exercise to maintain strength and balance if there are no conflicting medical conditions.
- Do not use loose rugs on the floors.
- Move any obstructions to walking, such as loose cords or very low pieces of furniture, away from traveled areas.
- Rooms should be well lit.
- Have regular eye checkups.
- Consider installing grab bars in bathrooms especially near shower, tub, or toilet.
Two types of drugs are used to prevent and treat osteoporosis:
- Antiresorptive Drugs. Antiresorptives include bisphosphonates, hormone replacement therapy, selective estrogen-receptor modulators (SERMs), and calcitonin. Bisphosphonates are the standard drugs used for osteoporosis. Denosumab (Prolia) is a new type of antiresorptive. These drugs block resorption (preventing bone break down), which slows the rate of bone remodeling, but they cannot rebuild bone. Because resorption and reformation occur naturally as a continuous process, blocking resorption may eventually also reduce bone formation.
- Anabolic (Bone-Forming) Drugs. Drugs that rebuild bone are known as anabolics. The primary anabolic drug is low-dose parathyroid hormone (PTH), which is administered through injections. This drug may help restore bone and prevent fractures. PTH is still relatively new, and long-term effects are still unknown. Fluoride is another bone-building drug, but it has limitations and is not commonly used.
Both types of drugs are effective in preventing bone loss and fractures, although they may cause different types of side effects.
Bisphosphonates are the primary drugs for preventing and treating osteoporosis. They can help reduce the risk of both spinal and hip fractures, including among patients with prior bone breaks.
Studies indicate that these drugs are effective and safe for up to 5 years. Eventually, however, bone loss continues with bisphosphonates. This may be due to the fact that bone breakdown is one of two phases in a continuous process of rebuilding bone. Over time, blocking resorption interrupts this process and impairs the second half of the process -- bone formation.
Candidates. Clinical guidelines recommend that the following people should take or consider taking bisphosphonates:
- Any woman who has a T score of -2.5 or lower on a DXA scan
- Women who have a T score between -1 and -2.5 (indicates low bone density [osteopenia]) and a history of fractures
Brands. Bisphosphonates for osteoporosis prevention and treatment are available in different forms:
- Oral bisphosphonates. These pills include alendronate (Fosamax, generic), risedronate (Actonel), and ibandronate (Boniva). Alendronate and risedronate are taken once a week. Ibandronate is available as a once-monthly pill. Risedronate is also available as a once-a-month pill and in a pill that contains calcium. Alendronate is available in a formulation that has vitamin D . Risedronate and alendronate are approved for both men and women.
- Injectable bisphosphonates. Zoledronic acid (Reclast) is approved for treatment and prevention of osteoporosis in postmenopausal women. It is given as a once-yearly injection. The injectable form of ibandronate (Boniva) requires injections 4 times a year. Injectable bisphosphonates are an alternative for patients who may have difficulty swallowing pills or sitting upright after oral bisphosphonate treatment.
Side Effects. The most distressing side effects of bisphosphonates are gastrointestinal problems, particularly stomach cramps and heartburn. These symptoms are very common and occur in nearly half of all patients. Other side effects may include irritation of the esophagus (the tube that connects the mouth to the stomach) and ulcers in the esophagus or stomach. Some patients may have muscle and joint pain. To avoid stomach problems, doctors recommend:
- Take the pill on an empty stomach in the morning with 6 - 8 ounces of water (not juice or carbonated or mineral water).
- After taking the pill, remain in an upright position. Do not eat or drink for at least 30 - 60 minutes. (Check your drug’s dosing instructions for exact time.)
- If you develop chest pain, heartburn, or difficulty swallowing, stop taking the drug and see your doctor.
Other Concerns. In 2010, the FDA warned that bisphosphonates may increase the risk for atypical thigh bone (femoral) fractures if used long term (more than five years). The FDA recommends that doctors consider periodically reevaluating patients who have been on bisphosphanates for longer than five years. Patients should inform their doctors if they experience any new thigh or groin pain. (A femoral fracture is usually preceded by several months of dull, aching pain in the thigh or groin area.) Do not stop taking your medication unless your doctor tells you to do so.
Osteonecrosis (bone death) of the jaw is a rare side effect that has occurred mainly in patients who received intravenous bisphosphonates for cancer treatment (not osteoporosis). Many of these patients had major dental procedures before developing osteonecrosis. However, this bone decay condition has also been reported in some patients who have taken bisphosphonates by mouth (mainly alendronate). Symptoms may include jaw pain or swelling, gum infections, and poor healing of the gums. Talk to your doctor or dentist if you experience any jaw or gum discomfort while taking a bisphosphonate drug.
There have also been concerns raised that bisphosphonates may increase the risk for atrial fibrillation, a heart rhythm disorder common in elderly patients. The FDA is monitoring reports of atrial fibrillation among patients who use bisphosphonates but at this time does not recommend any changes to prescribing practices. To date, the FDA has not identified a link between these drugs and increased risk of atrial fibrillation.
Denosumab (Prolia) is a new drug approved for treatment of osteoporosis in postmenopausal women who are at high risk for fracture. Denosumab is the first “biological therapy” drug approved for osteoporosis. It is considered an antiresorptive drug, but it works in a different way than bisphosphonates. It is a monoclonal antibody that works by targeting RANKL, a chemical factor involved with bone resorption.
Denosumab slows down the bone-breakdown process. However, because it also slows down the bone build-up and remodeling process, it is unclear what its longterm effects may be. Possible concerns are that denosumab may slow the healing time for broken bones or cause unusual fractures. For now, denosumab is recommended for women who cannot tolerate or who have not been helped by other osteoporosis treatments.
Denosumab is given as an injection in a doctor’s office twice a year (once every six months). Common side effects include back pain, pain in the arms and legs, high cholesterol levels, muscle pain, and bladder infection. Denosumab can lower calcium levels and should not be taken by women who have low blood calcium levels (hypocalcemia) until this condition is corrected.
Because denosumab is a biologic drug, it can affect or weaken the immune system and may increase the risk for serious infections. Other potential adverse effects include inflammation of the skin (dermatitis, rash, eczema) and inflammation of the inner lining of the heart (endocarditis). Denosumab may increase the risk of jaw bone problems such as osteonecrosis.
Raloxifene (Evista) belongs to a class of drugs called selective estrogen-receptor modulators (SERMs). These drugs are similar, but not identical, to estrogen. Raloxifene provides the bone benefits of estrogen without increasing the risks for estrogen-related breast and uterine cancers.
While there are many SERM drugs, raloxifene is the only one approved for both treatment and prevention of osteoporosis in postmenopausal women. Studies indicate that raloxifene can stop the thinning of bone and help build better quality and stronger bone. Raloxifene is recommended for postmenopausal women with low bone mass or younger postmenopausal women with osteoporosis. It can help prevent bone loss and reduce the risk of vertebral (spine) fractures. It is less clear how effective it is for preventing other types of fractures.
A thrombus is a blood clot that forms in a vessel and remains there. An embolism is a clot that travels from the site where it formed to another location in the body. Thrombi or emboli can lodge in a blood vessel and block the flow of blood in that location, depriving tissues of normal blood flow and oxygen. This can result in damage, destruction (infarction), or even death of the tissues (necrosis) in that area.
Side Effects. Raloxifene increases the risk for blood clots in the veins. Because of this side effect, raloxifene also increases the risk for stroke (but not other types of heart disease). These side effects, though rare, are very serious. Women should not take this drug if they have a history of blood clots, or if they have certain risk factors for stroke and heart disease. More common mild side effects include hot flashes and leg cramps.
Teriparatide (Forteo), an injectable drug made from selected amino acids found in parathyroid hormone, may help reduce the risks for spinal and non-spinal fractures. Although high persistent levels of parathyroid hormone (PTH) can cause osteoporosis, daily injections of low doses of this hormone actually stimulate bone production and increase bone mineral density. Teriparatide is usually recommended for patients with osteoporosis who are at high risk of fracture.
Side effects of PTH are generally mild and include nausea, dizziness, and leg cramps. No significant complications have been reported to date.
Early animal studies reported bone tumors in mice that were given parathyroid long-term. Such effects have not been observed in humans to date. However, people with Paget disease, (a disorder in which bone thickens but also weakens), should not take parathyroid hormone, because they are at higher than normal risk for bone tumors.
Produced by the thyroid gland, natural calcitonin regulates calcium levels by inhibiting the osteoclastic activity, the breakdown of bone. The drug version is derived from salmon and is available as a nasal spray (Miacalcin) and an injected form (Calcimar). Calcitonin is not used to prevent osteoporosis. It treats osteoporosis. It may be effective for spinal protection (but not hip) in both men and women. Calcitonin may be an alternative for patients who cannot take a bisphosphonate or SERM. It also appears to help relieve bone pain associated with established osteoporosis and fracture.
Side Effects. Side effects include headache, dizziness, anorexia, diarrhea, skin rashes, and edema (swelling). The most common adverse effect experienced with the injection is nausea, with or without vomiting. This occurs less often with the nasal spray. The nasal spray may cause nosebleeds, sinusitis, and inflammation of the membranes in the nose. Also, many people who take calcitonin develop resistance or allergic reactions after long-term use.
Hormone Replacement Therapy
Hormone replacement therapy (HRT) was formerly used to prevent osteoporosis, but is rarely used for this purpose today. Studies have shown that estrogen increases the risk for breast cancer, blood clots, strokes, and heart attacks. For this reason, women need to balance the benefits that HRT has on bone-loss protection, with the risks it carries for other serious health conditions. The FDA recommends that women first try other medications for prevention of osteoporosis.
[For more information on HRT, see In-Depth Report #40: Menopause.]
New SERMs. Bazedoxifene (Viviant) and lasofoxifene (Fablyn) are two new selective estrogen receptor modulators (SERMs) that are currently being considered for approval by the FDA. The FDA is weighing the potential benefits of these drugs against their risks, which include stroke. If approved, the FDA may limit these drugs to certain groups of women, such as those at significantly high risk for fractures.
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Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.
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