Osteoporosis

DEFINITION: A skeletal condition characterized by compromised bone strength and deterioration of bone quality, resulting from reduced bone mass; fractures are the major complication and are associated with significantly increased risks of morbidity and mortality, especially in older women

ANATOMY OR SYSTEM AFFECTED: Bones

CAUSES: Aging, disease (hyperparathyroidism, multiple myeloma), gastrointestinal disorders, anorexia nervosa, physical inactivity, vitamin D deficiency, alcohol abuse

SYMPTOMS: Increased bone fractures, severe and localized back pain, reduced height

DURATION: Chronic

TREATMENTS: Bisphosponates, parathyroid hormone, raloxifene, denosumab, calcitonin, calcium and vitamin D supplements

Causes and Symptoms

Bone is constantly being remodeled by cells: old bone is reabsorbed by the osteoclasts, and new bone is formed by the osteoblasts. Several factors control these processes of bone formation and resorption, which are about equal in adults. In children, formation exceeds resorption, and the bone mass increases. Later in life, however, bone resorption exceeds bone formation and bone mass is lost. When bone mass is reduced, the bone becomes soft and mechanically weak and more vulnerable to fractures. While some loss of bone mass is a normal part of the aging process, this does not typically lead to significantly thinner or weaker bones. However, some people develop a disease known as osteoporosis, which leads to thinner and weaker bones and increased risk of fractures.

There is no known cure for osteoporosis. Prevention is the only strategy for combating bone mineral loss and the development of osteoporosis. A balanced diet including adequate calcium and vitamin D intake as well as regular weight-bearing and muscle-strengthening exercises can prevent bone loss. Risk factors for osteoporosis include lifestyle factors such as low calcium intake, vitamin D deficiency, excess vitamin A intake, inadequate physical activity, smoking, and alcohol abuse; genetic factors such as certain endocrine, gastrointestinal, autoimmune, and hematologic disorders; and some medications.

Osteoporosis is sometimes divided into primary and secondary forms. Primary osteoporosis can be further divided into two types based on the rate of bone changes. Type I, also known as postmenopausal or high-turnover osteoporosis, is most commonly seen in people who have gone through menopause. Type II, sometimes called senile osteoporosis or low-turnover osteoporosis, is linked to calcium deficiency and is seen in older adults, usually age sixty-five or older. Secondary osteoporosis is associated with an underlying disease, such as hyperparathyroidism or multiple myeloma, or medication, and may occur in younger as well as older individuals.

A third type of osteoporosis has been found in young females who are amenorrheic (having no menstrual cycles) in association with eating disorders such as anorexia nervosa. Osteoporotic fractures can occur in people in their twenties and thirties who have been amenorrheic for several years. Because this condition was first found in athletic women, the link between eating disorders, amenorrhea, and osteoporosis was named the Female Athlete Triad.

No matter the type of osteoporosis, it is considered a clinically silent disease, as it is usually asymptomatic until a fracture occurs. The frequency of osteoporosis and related fractures is expected to increase in parallel with the increase in the older population. Females are more vulnerable to this condition, especially after menopause. As the life span for males increases, however, so will their risk of osteoporosis.

In the early postmenopausal period, the distal end of the radius and ulna (wrist) are particularly susceptible to fractures; a few years later, the patient is likely to sustain vertebral fractures. The most common presentation of such a fracture is a sudden onset of very severe, localized back pain, often occurring spontaneously. The pain can be so severe that it incapacitates the patient and may require the administration of narcotics for relief. Unlike the pain caused by a disk rupture, this pain does not radiate to the legs, although some radiation anteriorly may be present. The pain usually lasts about four weeks and is then spontaneously relieved unless nerve compression or secondary arthritic changes complicate the condition.

When multiple vertebrae have collapsed, the body height is reduced and the patient’s arms appear to be disproportionately long. Normally, both measurements—body height and arm span—are equal. In osteoporosis complicated by several vertebral fractures, body height is reduced, but the arm span is unchanged. When multiple thoracic vertebrae collapse, kyphosis (an increased spinal curvature) develops. The space between the ribs and the pelvic cavity is also reduced. When lumbar vertebrae are collapsed, the lower end of the ribs may lie over the pelvic cavity. At this stage, the patient’s lung functions may be compromised because the chest movements are limited. Pneumonia is a common, sometimes fatal complication.

Progressive and long-standing osteoporosis may be complicated by fractures of the femoral neck. Although most of these fractures are preceded by a fall, it is probable that in some cases the bones are so weakened and fragile that they fracture spontaneously and cause the patient to fall. Fractures of the femoral neck are associated with significant mortality and morbidity risks, with 12 to 20 percent of the patients dying within six months of the fracture and about half losing the ability to live independently.

A number of factors predisposing an individual to osteoporosis have been identified. Some of these factors cannot be changed. For example, advanced age increases the risk of developing osteoporosis. Furthermore, although both sexes are affected by osteoporosis, females tend to be more vulnerable because, in addition to the accelerated rate of bone loss that occurs after menopause, women tend to have smaller skeletons than men do and, therefore, are likely to reach the threshold at which bone fragility is increased well before men do. White people and Asian people are more susceptible to osteoporosis than people of African or Latino heritage. The reasons for these racial differences are not well understood. Finally, people with large body frames are less likely to develop osteoporosis than those with small body frames, probably because their bone reserve allows them to lose bone for a longer period before reaching the threshold at which the bone fragility is significantly increased. Genetic research has also determined that variations in the gene for the vitamin D receptor (VDR) may contribute to 7 to 10 percent of the difference in bone mass density because of its influence on calcium intake. For those with a family history of osteoporosis or hip fracture, this factor could lead to identification of an individual’s risk factor and enable early intervention.

A number of risk factors that can be reversed have also been identified. A low dietary calcium intake is associated with a reduced bone mass and an increased fracture rate. Conversely, an elevated calcium intake, particularly before puberty, is associated with an increased mass. In 1994, the US National Institutes of Health consensus statement recommended an increase in daily calcium, and in 1997 the National Academy of Sciences’ recommended dietary allowance (RDA) increased from 800 milligrams per day to 1,300 milligrams at age nine up to age eighteen. Men from age nineteen to seventy years should take in 1,000 milligrams, increasing to 1,200 milligrams at age seventy-one. Women from age nineteen to fifty should take in 1,000 milligrams, increasing to 1,200 milligrams after the age of fifty-one. Higher doses may be detrimental, as they may cause the formation of kidney stones, so the benefit must be weighed against the risk in each case. Getting the greatest percentage of the calcium from the diet is preferred, but, if it is to be taken as a supplement, no more than 500 milligrams should be taken at one time and always with meals. Calcium is not absorbed well, so having stomach acid present, as well as vitamin D and protein, enhances the absorption. Vitamin D deficiency and excess vitamin A intake are also risk factors for the development of osteoporosis.

Physical inactivity is associated with a reduced bone mass and therefore an increased predisposition to developing osteoporosis. There is also evidence that people who have a sedentary lifestyle are more susceptible to osteoporosis than those who are physically active. During the formative years, exercise is imperative to develop the highest bone density possible. Then throughout the rest of life, exercise is essential to slow the rate of bone loss, particularly weight-bearing and muscle-strengthening exercises. Several factors modulate the response of the skeleton to exercise. These include the subject’s age and sex; the intensity, frequency, and type of exercise; and the subject’s endocrinal status. The current recommendation for exercise in relationship to osteoporosis is preventive: a variety of exercise, both weight-bearing and vigorous, to be done regularly (thirty to sixty minutes per day, three to five days per week) throughout life. Variety is essential because no single exercise stresses all bones equally. The stimulus to build bone comes from the muscle that is attached to the bone pulling on the attachment site, which makes the bone remodel itself to resist the stress.

In older adults, exercise may have a secondary benefit. Often, a fracture is precipitated by a fall, and the cause of the fall may be a loss of balance or coordination. Maintaining an active lifestyle helps with balance and coordination, all of which may help in the prevention of a fall. Studies in the elderly have demonstrated that a general exercise such as walking is not enough to maintain gains in bone density in the long term. Exercise studies of one or two years’ duration show a decline begins after about one year. To combat that loss, a regular strength-training regimen, targeting the most common fracture sites, done two or three times a week for twenty minutes to stimulate specific bones, should be added to any other activities that are done.

Cigarette smoking is associated with osteoporosis; however, the underlying mechanism is not clearly understood. It is possible that cigarette smokers are more likely to lead a sedentary life and have a reduced dietary calcium intake compared to nonsmokers. Cigarette smoking may have a direct effect on bone cells, or it may have an indirect effect by modulating the release of substances that may affect the activity of these cells, such as the parathyroid hormone or calcitonin secretion. Smoking cessation is highly recommended to reduce one's risk of developing osteoporosis. Alcohol abuse is also a risk factor for the development of osteoporosis, and cirrhosis of the liver further increases an individual's risk for osteoporosis. Excessive alcohol intake should be avoided.

A number of drugs may increase the risk for osteoporosis. These include long-term anticoagulation medications, hormonal therapies, glucocorticosteroids, some immunosuppressants, lithium, thiazolidinediones (glitazones), and long-term proton pump inhibitor use. For a person at risk of osteoporosis, anytime that medications are prescribed, calcium interaction should be considered.

A number of diseases and disorders are associated with osteoporosis, including genetic factors such as cystic fibrosis, hemochromatosis, and porphyria. Endocrine disorders associated with osteoporosis include hyperparathyroidism, anorexia nervosa, diabetes mellitus, Cushing syndrome, and excess thyroid hormone. Gastrointestinal disorders such as celiac disease, Crohn's disease, cirrhosis, and malabsorption can increase the risk of osteoporosis. Rheumatoid arthritis and hematologic disorders such as multiple myeloma, thalassemia, and leukemia also put individuals at risk of developing osteoporosis.

Treatment and Therapy

Several tests are available to confirm the diagnosis of osteoporosis, quantify its degree, and identify underlying diseases that might cause or aggravate the osteoporosis.

X-rays used to be the only way to evaluate patients with osteoporosis. Although they are helpful in assessing bone involvement from other diseases, they are not useful for the detection of early osteoporosis because the characteristic appearances are seen only when at least 40 percent of the bone mass has been lost. In the 1990s, a new analysis technique was developed using a simple X-ray of the hand and then computer analysis. It is able to reveal as little as 1 percent bone loss.

The most accurate technique available to measure bone density uses a technique called dual X-ray absorptiometry (DXA). DXA is based on the principle that if a beam of radiation is directed at a bone, the amount of radiation trapped by the bone is proportional to the amount of mineral and calcium inside. By knowing the amount of radiation aimed at the bone and the amount reaching a detector crystal across the bone, the amount of mineral can be calculated. To differentiate the radiation trapped by the surrounding muscles and fat from the radiation trapped by the bone itself, radiation with two different peaks (which are absorbed to a different extent by bone and soft tissue) is used. The exposure to radiation is minimal, one-fiftieth the radiation as in a chest X-ray. The same densitometry machine can do whole-body or single-site readings, making it even more useful for diagnosis.

Osteoporosis therapy includes several options. Several drugs have been used or investigated for use. Bisphosphonates are usually the first-line choice when pharmacological therapy is indicated. Bisphosphonates include alendronate, ibandronate, risedronate, and zoledronic acid. Parathyroid hormone (teriparatide) delivered subcutaneously may also be a first-line treatment choice among patients with the highest risk for fracture. Teriparatide works by increasing the action of osteoblasts and causes bones to become denser and more resistant to fractures. Other medications such as estrogen receptor modulators (raloxifene, lasofoxifene, tibolone) are recommended for postmenopausal people with osteoporosis.

Calcitonin, a hormone produced by the thyroid gland, specifically inhibits the osteoclasts, which are the bone resorbing cells. As a result, there is a relative increase in the rate of bone formation, and the bone mass increases. After the initial increase, however, the bone mass tends to stabilize, and the continued administration of calcitonin beyond this point may be associated with a decline in bone mass. Therefore, the risks of calcitonin may outweigh the benefits.

Calcium supplements are useful if the patient’s dietary calcium intake is less than recommended. Similarly, if the daily vitamin D intake is below the recommended level of 600 to 800 international units in the elderly population, supplementation is recommended. Vitamin D supplements may also be necessary in patients who are taking a medication that interferes with vitamin D metabolism. Excessive vitamin D and calcium intake, however, may lead to the development of kidney stones.

Several nonpharmacological treatments may also improve quality of life and functional status in persons with osteoporosis. Progressive quadriceps strength and proprioception training and balance training are associated with a decrease in falls in postmenopausal people with osteoporosis. Pilates and weight-bearing exercises may also improve function in persons with osteoporosis, and tai chi may improve balance and lessen the risk of falls. Smoking cessation and reducing alcohol intake are also recommended.

Perspective and Prospects

The early diagnosis of osteoporosis and the ability to quantify its degree have represented major strides in the diagnosis, management, and prevention of this disease. It is now recommended that all people approaching menopause be checked to determine a baseline bone density reading and to help with prevention and possible treatment options. Indeed, physicians can now identify patients with early osteoporosis and assess their response to treatment accurately. Additionally, modifiable risk factors increasing the likelihood of developing osteoporosis have been identified; these include a low dietary calcium and vitamin D intake, cigarette smoking, excessive alcohol use, anorexia nervosa or bulimia nervosa, and a sedentary lifestyle. Education of the public, therefore, has an important part to play in the prevention and management of osteoporosis.

Working with young people may be the best way to combat osteoporosis. For many people, making the right choices early in life may have great influence in preventing this debilitating disease later in life. For the older adult, attempts are being made to develop risk profiles that can be used to estimate the individual patient’s fracture risk. This in turn will allow physicians to identify those in the population who are particularly likely to benefit from specific therapy. Moreover, the increased understanding of bone formation, bone resorption, and bone metabolism has led to a considerable amount of research work on the development of effective treatment programs. Drugs that can build strong bones, or ones that can prevent further bone loss, will need to be continually studied, and everything that can be done to reduce side effects from these or other drugs that affect calcium stores in the bones must be a top priority of research dollars spent.

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