• Osteoporosis affects millions of Americans. Individuals with osteoporosis are at high risk of suffering one or more fractures, which are often physically debilitating and can potentially lead to a downward spiral in physical and mental health.
  • The most common form of osteoporosis is known as “primary osteoporosis.” It is the result of the cumulative impact of bone loss and deterioration of bone structure as people age. This bone loss can be minimized and osteoporosis prevented through adequate nutrition, physical activity, and, if necessary, appropriate treatment.
  • There are a wide variety of diseases and certain medications and toxic agents that can cause or contribute to the development of osteoporosis. If recognized as a potential threat, this form of the disease—known as secondary osteoporosis—can often be prevented through proper nutrition and physical activity, along with appropriate therapy if needed.
  • A number of childhood diseases cause rickets, a condition that results from a delay in depositing calcium phosphate mineral in growing bones. This delay leads to skeletal deformities, especially bowed legs. In adults, the equivalent disease is called osteomalacia. Both diseases can generally be prevented by ensuring adequate levels of vitamin D, but they can have devastating consequences for affected individuals.
  • Patients with chronic renal disease are at risk for developing a complex bone disease known as renal osteodystrophy. While dialysis and transplantation have extended the life-expectancy of these patients, it may not prevent further progression of bone disease.
  • Paget’s disease of bone is a progressive, often crippling disorder of bone remodeling that commonly involves the spine, pelvis, legs, or skull (although any bone can be affected). If diagnosed early, its impact can be minimized.
  • A large number of genetic and developmental disorders affect the skeleton. Among the more common of these is osteogenesis imperfecta (OI). Patients with this condition have bones that break easily.
  • Some skeletal disorders tend to develop later in life. One of the most common of these acquired skeletal disorders is a malignancy of the bone. These malignancies can originate in the bone (primary tumors) or, much more commonly, result from the seeding of bone by tumors outside of the skeleton (metastatic tumors). Primary bone cancer also occurs in children. Both types of tumors can destroy bone.

The body systems that control the growth and maintenance of the skeleton, which are described in Chapter 2, can be disrupted in different ways that result in a variety of bone diseases and disorders. These include problems that can occur at or before birth, such as genetic abnormalities and developmental defects, as well as diseases such as osteoporosis and Paget’s disease of bone that damage the skeleton later in life. In addition to conditions that affect bone directly, there are many other disorders that indirectly affect bone by interfering with mineral metabolism. This chapter reviews some of the more common diseases, disorders, and conditions that both directly and indirectly affect bone.


As pointed out in Chapter 2, osteoporosis is a disease characterized by low bone mass and deterioration of bone structure that causes bone fragility and increases the risk of fracture. For practical purposes, the World Health Organization has defined osteoporosis as a bone mineral density (BMD) value more than 2.5 standard deviations below the mean for normal young White women. Osteoporosis is a common disease affecting millions of Americans. As described in Chapters 4 and 5, it can have devastating consequences. Individuals with osteoporosis are at high risk of suffering one or more fractures, injuries that can often be physically debilitating and potentially lead to a downward spiral in physical and mental health (Figure 3-1). Generalized osteoporosis is the most common form of the disease, affecting most of the skeleton. Osteoporosis can also occur in localized parts of the skeleton as a result of injury or conditions that reduce muscle forces on the bone, such as limb paralysis. There are a variety of different types of osteoporosis. The most common form of osteoporosis is known as “primary osteoporosis”—that is, osteoporosis that is not caused by some other specific disorder. Bone loss caused by specific diseases or medications (see below) is referred to as “secondary osteoporosis.” Each of these major categories of osteoporosis is discussed in more detail on the following pages.


Figure 3-1

Bone Fracture Areas in Osteoporosis. Source: NOF 2004.

Classical Case

“A classical case of osteoporosis may start in a woman about 55 years of age with a wrist fracture. Ten years later she may present with back pain, with or without minor trauma, and thoracolumbar spine x-rays may show a vertebral fracture. She might have one of several risk factors: low body weight, premature menopause, a family history of fractures, smoking, heavy alcohol consumption, inactivity, calcium or vitamin D deficiency, or corticosteroid use. The back pain may remit and relapse with subsequent vertebral fractures. Approximately 10–15 years later, at the age of 75–80 years, the patient may fall and sustain a hip fracture, resulting in hospitalization, a 20 percent excess risk of death, considerable functional impairment and possibly a loss of independence if she survives. Although this scenario is instantly recognizable, osteoporosis may present with any of a wide range of fractures and at a variety of ages; it is also increasingly recognized among men” (WHO 2003). Recognition that the first fracture was a sentinel event may have triggered a detailed assessment that could potentially have prevented additional fractures. See Chapter 8 for more information on such assessments.

Primary Osteoporosis

Primary osteoporosis is mainly a disease of the elderly, the result of the cumulative impact of bone loss and deterioration of bone structure that occurs as people age (Seeman 2003). This form of osteoporosis is sometimes referred to as age-related osteoporosis. Since postmenopausal women are at greater risk, the term “postmenopausal” osteoporosis is also used. Younger individuals (including children and young adults) rarely get primary osteoporosis, although it can occur on occasion. This rare form of the disease is sometimes referred to as “idiopathic” osteoporosis, since in many cases the exact causes of the disease are not known, or idiopathic. Since the exact mechanisms by which aging produces bone loss are not all understood (that is, it is not always clear why some postmenopausal women develop osteoporosis while others do not), age-related osteoporosis is also partially idiopathic. A brief review of “idiopathic” primary osteoporosis and a more detailed review of the more common condition of age-related osteoporosis follows.

Idiopathic Primary Osteoporosis

There are several different forms of idiopathic osteoporosis that can affect both children and adolescents, although these conditions are quite rare (Norman 2003). Juvenile osteoporosis affects previously healthy children between the ages of 8 and 14. Over a period of several years, bone growth is impaired. The condition may be relatively mild, causing only one or two collapsed bones in the spine (vertebrae), or it may be severe, affecting virtually the entire spine. The disease almost always goes into remission (spontaneously) around the time of puberty with a resumption of normal bone growth at that time. Patients with mild or moderate forms of the disease may be left with a curvature of the spine (kyphosis) and short stature, but those with a more severe form of the disease may be incapacitated for life.

Primary osteoporosis is quite rare in young adults. In this age-group, the disease is usually caused by some other condition or factor, such as anorexia nervosa or glucocorticoid use (Khosla et al. 1994). When idiopathic forms of primary osteoporosis do occur in young adults, they appear in men as often as they do in women (this is in contrast to age-related primary osteoporosis, which occurs more often in women). The characteristics of the disease can vary broadly and may involve more than one disorder. Some young adults with idiopathic primary osteoporosis may have a primary defect in the regulation of bone cell function, resulting in depressed bone formation, increased bone resorption, or both (see Chapter 2). Others with a mild form of the disease may simply have failed to achieve an adequate amount of skeletal mass during growth. In some patients, the disease runs a mild course, even without treatment, and the clinical manifestations are limited to asymptomatic spinal compression fractures. More typically, however, multiple spine fractures occur over a 5–10 year period leading to a height loss of up to 6 inches.

Age-Related Osteoporosis

Age-related osteoporosis is by far the most common form of the disease (Figure 3-2). There are many different causes of the ailment, but the bone loss that leads to the disease typically begins relatively early in life, at a time when corrective action (such as changes in diet and physical activity) could potentially slow down its course. While it occurs in both sexes, the disease is two to three times more common in women (see Chapter 4). This is partly due to the fact that women have two phases of age-related bone loss—a rapid phase that begins at menopause and lasts 4–8 years, followed by a slower continuous phase that lasts throughout the rest of life (Riggs et al. 2002). By contrast, men go through only the slow, continuous phase. As a result, women typically lose more bone than do men. The rapid phase of bone loss alone in women results in losses of 5–10 percent of cortical bone (which makes up the hard outer shell of the skeleton) and 20–30 percent of trabecular bone (which fills the ends of the limb bones and the vertebral bodies in the spine, the sites of most osteoporotic fractures). The slow phase of bone loss results in losses of 20–25 percent of cortical and trabecular bone in both men and women, but over a longer period of time (Riggs et al. 2002).


Figure 3-2

Progressive Spinal Deformity in Osteoporosis. Note: Compression fractures of thoracic vertebrae lead to loss of height and progressive thoracic kyphosis (dowager’s hump). Lower ribs eventually rest on ileac crests, and downward pressure on viscera (more…)

Although other factors such as genetics and nutrition contribute, both the rapid phase of bone loss in postmenopausal women and the slow phase of bone loss in aging women and men appear to be largely the result of estrogen deficiency. (This is demonstrated by the fact that correction of estrogen deficiency can prevent these changes.) For women, the rapid phase of bone loss is initiated by a dramatic decline in estrogen production by the ovaries at menopause. The loss of estrogen action on estrogen receptors in bone results in large increases in bone resorption (see Chapter 2), combined with reduced bone formation. The end result is thinning of the cortical outer shell of bone and damage to the trabecular bone structure (see Figure 2-5, Chapter 2). There may be some countervailing forces on this process, as the outside diameter of the bone can increase with age, thus helping to maintain bone strength (Ahlborg et al. 2003).

By contrast, the slower phase of bone loss is thought to be caused by a combination of factors including age-related impairment of bone formation, decreased calcium and vitamin D intake, decreased physical activity, and the loss of estrogen’s positive effects on calcium balance in the intestine and kidney as well as its effects on bone (Riggs et al. 2002). This leads to further impairment of absorption of calcium by the intestine and reduced ability of the kidney to conserve calcium. If the amount of calcium absorbed from the diet is insufficient to make up for the obligatory calcium losses in the stool and urine, serum calcium begins to fall. Parathyroid hormone levels will then increase, removing calcium from bone to make up for the loss, as illustrated in Figure 3-3. The net result of this process is an increase in bone resorption. It is important to realize that these mineral losses need not be great to result in osteoporosis. A negative balance of only 50–100 mg of calcium per day (far less than the 300 mg of calcium in a single glass of milk) over a long period of time is sufficient to produce the disease.

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Figure 3-3

Schematic Representation of Model for Bone Loss in Postmenopausal Women and Aging Men. Source: Riggs et al. 1998.

For aging men, sex steroid deficiency also appears to be a major factor in age-related osteoporosis. Although testosterone is the major sex steroid in men, some of it is converted by the aromatase enzyme into estrogen.

In men, however, the deficiency is mainly due to an increase in sex hormone binding globulin, a substance that holds both testosterone and estrogen in a form that is not available for use by the body. Between 30–50 percent of elderly men are deficient in biologically active sex steroids (Khosla et al. 1998). In fact, except for the lack of the early postmenopausal phase, the process of bone loss in older men is similar to that for older women.

As with women, the loss of sex steroid activity in men has an effect on calcium absorption and conservation, leading to progressive secondary increases in parathyroid hormone levels. As in older women, the resulting imbalance between bone resorption and formation results in slow bone loss that continues over life. Since testosterone may stimulate bone formation more than estrogen does, however, decreased bone formation plays a relatively greater role in the bone loss experienced by elderly men.