Osteoporosis Risk Factors
FDA Reviewing Long-Term Use of Bisphosphonates
The Food and Drug Administration (FDA) is currently reviewing whether long-term (more than 3 - 5 years) use of bisphosphonate drugs provides any benefits for fracture prevention. Possible concerns for long-term use of bisphosphonates are increased risks for thigh bone (femoral fractures), esophageal cancer, and osteonecrosis (bone death) of the jaw.
Screening for Osteoporosis
United States Preventive Services Task Force (USPSTF) Recommendations
New recommendations from the USPSTF include:
Osteoporosis is a progressive skeletal disease in which bones become thin, weak, brittle, and prone to fracture. Osteoporosis literally means “porous bones.” Thinning bones are caused by loss of bone density. Calcium and other minerals contribute to the bone mineral density that helps strengthen and protect bones.
The skeleton consists of groups of bones which protect and move the body.
Bones are made of living tissue that is constantly being broken down (resorbed) and formed again. 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 formation, your bones lose density and you are at increased risk for osteoporosis.
Until a healthy adult is around age 40, the process of formation and resorption 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. Eventually, 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 is usually 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.
The Role of Sex Hormones in Bone Breakdown
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 ovaries produce most of the estrogen in the body, but estrogen 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 stop 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.
Studies suggest that falling levels of testosterone and estrogen can contribute to bone loss in elderly men. Both hormones are important for bone strength 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:
Causes of Secondary Osteoporosis
Secondary osteoporosis results from medications or other medical conditions.
Medications. Medications that can cause osteoporosis include:
Medical Conditions. Osteoporosis can be secondary to other medical conditions, including alcoholism, diabetes, thyroid imbalances, chronic liver or kidney disease, Crohn's disease, celiac disease, scurvy, rheumatoid arthritis, leukemia, cirrhosis, gastrointestinal diseases, vitamin D deficiency, lymphoma, hyperparathyroidism, anorexia nervosa, premature menopause, and rare genetic disorders such as the Marfan and Ehlers-Danlos syndromes.
The main risk factors for osteoporosis are:
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. Osteoporosis is most common among postmenopausal women, and screening for low bone density is recommended for all women over the age of 65.
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. Low body weight (less than 127 pounds or a BMI less than 21) is a risk factor for osteoporosis.
People whose parents had a fracture due to osteoporosis are themselves at increased risk for osteoporosis.
Women. Estrogen deficiency is a primary risk factor for osteoporosis in women. Estrogen deficiency is associated with:
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 both preventing and speeding up bone loss in men and women. Calcium and vitamin D deficiencies are risk factors 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.
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.
Smoking. Smoking can affect calcium absorption and estrogen levels.
Alcohol. Excessive consumption of alcoholic beverages can increase the risk for bone loss.
Lack of Sunlight. Vitamin D is made in the skin using energy from the ultraviolet rays in sunlight. Vitamin D is necessary for the absorption of calcium in the stomach and gastrointestinal tract and is the essential companion to calcium in maintaining strong bones.
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:
Exercise and good nutrition during the first three decades of life (when peak bone mass is reached) are excellent safeguards against osteoporosis (and other health problems).
Low bone density increases the risk for fracture. Bone fractures are the most serious complication of osteoporosis. Spinal vertebral 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. In addition to causing disability, hip fractures can increase the risk of early death. Complications of hip fractures include hospital-acquired infections and blood clots in the lungs.
Osteoporosis is usually quite advanced before symptoms appear. Unfortunately, a fracture of the wrist or hip is often the first sign of osteoporosis. These fractures can occur even after relatively minor trauma, such as bending over, lifting, jumping, or falling from a standing position.
Compression fractures can occur in the vertebrae of the spine as a result of weakened bone. 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.
Candidates for Bone Density Testing
Because osteoporosis can occur with few symptoms, testing is important. Bone density testing is recommended for:
In addition to age, the main risk factors for osteoporosis are:
Other risk factors that may indicate a need for bone mineral density testing include:
Tests Used for Measuring Bone Density
Central DXA. Bone densitometry is a test for measuring bone density. The standard technique for determining bone density is 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.
Central DXA measures the bone mineral density at the hip, upper thigh bone (femoral neck), and spine.
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 can result from 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:
Results of T-scores indicate:
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 refers to bone mineral density that is lower than normal, but not low enough to be classified as osteoporosis. Osteopenia is considered a precursor to osteoporosis.
Doctors don’t yet know the best testing schedule for women whose first test does not reveal osteoporosis. A recent study suggests that such women may be able to wait a much longer time between screening tests than is current practice. Woman with a normal result may be able to wait for 15 years, those with mild osteopenia (bone thinning) for 5 years, and those with more advanced osteopenia for 1 year.
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 supporting 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 best sources are from calcium-rich and vitamin D-fortified foods.
The National Osteoporosis Foundation (NOF) recommends:
Dietary Sources. Good dietary sources of calcium include:
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:
However, many Americans do not get enough vitamin D solely from diet or exposure to sunlight.
Supplements. Doctors are currently reconsidering the use of calcium and vitamin D supplements. A 2012 recommendation from the U.S. Preventive Services Task Force (USPSTF) advised that healthy postmenopausal women may not require these supplements. According to the USPSTF, there is not enough evidence to prove that taking daily low-dose amounts of vitamin D supplements, with or without calcium, can prevent fractures or other health problems such as cancer. Other experts, however, recommend moderately high doses of vitamin D (800-100 IU daily) along with a sufficient intake of dietary calcium.
In addition to possible lack of benefit, calcium and vitamin D supplements are associated with certain risks, like kidney stones. Some studies suggest that calcium supplements may also increase the risk for heart attack. However, supplements may be appropriate for certain people including those who do not get enough vitamin D through sunlight exposure and those who do not consume enough calcium in their diet. Talk with your doctor about whether or not you should take supplements.
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.
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, talk to your doctor.
Specific exercises may be better than others:
Exercise plays an important role in preserving bone density in the aging person. Studies show that exercises requiring muscles to pull on bones cause the bones to retain and possibly gain calcium and strength.
Other Lifestyle Factors
Other lifestyle changes that can help prevent osteoporosis include:
Preventing Falls and Fractures
An important component in reducing the risk for fractures is preventing falls. Risk factors for falling include:
Recommendations for preventing falls or fractures from falls include:
Two types of drugs are used to prevent and treat osteoporosis:
Both types of drugs are effective in preventing bone loss and fractures, although they may cause different types of side effects. The United States Preventive Services Task Force (USPSTF) recommends that these drugs should be prescribed only to patients who have been diagnosed with osteoporosis.
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:
Brands. Bisphosphonates for osteoporosis prevention and treatment are available in different forms:
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:
Other Concerns. The FDA is currently reviewing whether long-term (more than 3 - 5 years) use of bisphosphonate drugs provides any benefits for fracture prevention. Possible concerns for long-term use of bisphosphonates are increased risks for thigh bone (femoral fractures), esophageal cancer, and osteonecrosis (bone death) of the jaw. The FDA recommends that doctors periodically reevaluate patients who have been on bisphosphonates for more than 5 years. Patients should inform their doctors if they experience any new thigh or groin pain, swallowing difficulties, or jaw or gum discomfort. Do not stop taking your medication unless your doctor tells you to do so.
For the injectable drug zoledronic acid (Reclast), kidney failure is a rare but serious side effect. Zoledronic acid should not be used by patients with risk factors for kidney failure.
Denosumab (Prolia) is a newer 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. Raloxifene is taken as a pill once a day.
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 cardiovascular 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, generic) and an injected form (Calcimar, Miacalcin, generic). 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 United States Preventive Services Task Force (USPSTF) recommends against the use of HRT for prevention of osteoporosis. [For more information on HRT, see In-Depth Report #40: Menopause.]
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