The matrix of bone comprises organic and inorganic components. Collagen, proteins, and lipids constitute the organic portion of the bone matrix. The inorganic matrix, which represents 65% of bone’s total weight, is largely composed of calcium and phosphate, with smaller amounts of magnesium, sodium, and potassium. Hydroxyapatite is the principal mineral component of bone and is 40% calcium by weight. Histologically, bone can be subdivided into two types: cancellous (spongy) and cortical (compact). Cancellous bone has a large surface area, and its metabolic activity is much more rapid than that of cortical bone. Viewed microscopically, bone of normal strength and density has a honeycomb appearance, whereas osteoporotic bone appears less dense, with a weaker, more spindly structure.

Bone mass is the total quantity of bone tissue in the skeleton. Greater bone mass equals more bone, which indicates a stronger skeleton. Most diagnostic studies for osteoporosis measure bone density of a part of the skeleton, another indicator for osteoporosis because high density also is representative of bone strength. Although bone mass and density differ slightly in meaning, these terms are used interchangeably in this chapter.

Bone mass undergoes predictable changes throughout the life cycle. During the first several decades of life, active growth occurs, building toward peak bone mass, the maximal bone density a person achieves. Peak bone mass is usually achieved by age 30. In women after this age, there is a plateau or very slow decline from peak bone mass until menopause. Declining ovarian function accelerates the loss of bone mass at a rate of approximately 2% to 4% per year; this loss is most rapid in the first 2 years after menopause and gradually subsides within 5 to 10 years. This decline in bone loss then slows, but bone mass continues to decrease over the years. Total loss of bone can approach 50%. For men, bone mass decreases gradually, particularly after age 50, as testosterone levels diminish, without the sharper dip associated with menopause. However, men with hypogonadism also experience an accelerated rate of bone loss. All adults after age 30 are on a lifelong course of decreasing bone mass leading to senile osteoporosis, but women have the additional burden of postmenopausal osteoporosis from estrogen deficiency.

Osteoporosis may be etiologically divided into primary and secondary types. Primary osteoporosis is further subdivided into three types: postmenopausal (type I), principally affecting cancellous bone; age-associated disease (type II), a slower loss of cancellous and cortical bone seen in both sexes, especially past the age of 70; and idiopathic osteoporosis, in which bone loss occurs in young and middle-aged men and premenopausal women. Secondary osteoporosis is the result of underlying conditions (Table 48-1).

Bone is continually replaced by a process called bone remodeling. Humans remodel their skeletons to a greater degree than most other mammals at a rate that increases with age. Each year, approximately 20% of the skeleton is remodeled. Bone remodeling can be divided into two processes: resorption and formation. During resorption, osteoclasts excavate the bone surface by dissolving the mineral component of the bone and hydrolyzing the organic matrix. Saucer-shaped cavities are produced on the surface of cancellous bone; tunnels are formed in cortical bone. Cancellous bone is subject to more remodeling activity and quicker turnover than cortical bone because its large surface area provides a greater number of remodeling sites and its metabolic rate is more rapid. Menopause actually causes increased activation of these remodeling sites, intensifying resorption and producing deeper cavities in cancellous bone.

Formation is carried out by osteoblasts, which migrate to the pits and tunnels and begin to fill them in by secreting collagen fibrils to form the bone matrix. After this protein matrix is formed, it becomes mineralized through the deposition of calcium hydroxyapatite crystals. Adequate intake of vitamin D and calcium is required for mineralization. During both the resorption and formation phases of remodeling, biochemical markers reflective of these processes are released into the bloodstream.

In the pathogenesis of osteoporosis, the most important aspect of remodeling is the rate of formation relative to resorption. During childhood and early adulthood, as bone mass builds, the rate of formation exceeds that of resorption; it then plateaus until about the age of 40. Thereafter, resorption outpaces formation, and bone density continues to decrease.

Also significant is each person’s peak bone mass, which becomes the starting point for later loss. Slow decreases in mass in someone who achieved a relatively low peak may ultimately yield the same net bone mass as a more rapid decline in someone whose peak mass was high. This highlights the importance of
proper nutrition and exercise during the years of active bone growth to attain maximal peak mass.

Osteoporotic changes are more significant at certain body sites. Because cancellous bone has greater remodeling activity than cortical bone, it is subject to a more rapid loss of density. The vertebral body, femoral neck, and distal radius are composed of cancellous bone, and they are therefore the most common sites of osteoporotic fractures. Other fracture sites are the pelvis, tibial plateau, proximal humerus, and ribs.

The fragility of porous bone predisposes not only to fractures from trauma but also to nonviolent fractures. Nonviolent fractures, caused by minimal trauma that would not result in fracture in a young adult, are responsible for 90% of hip and wrist fractures in the elderly. Overall, the spine is the most common site for osteoporotic fractures. Secondary to vertebral compression, spinal fractures may occur in the absence of recognizable trauma, triggered perhaps by a cough or sneeze. In fact, 50% of people with vertebral fractures from osteoporosis have no recollection of back pain, and only one third of persons with vertebral fractures are clinically diagnosed. Fractured vertebrae assume a wedge shape, narrowing anteriorly, causing kyphosis, height and waistline loss, and abdominal protrusion.

Osteoporosis affects an estimated 25 million Americans, 80% of whom are women. Approximately 1.5 million osteoporotic fractures occur each year (Galsworthy & Wilson, 1996; Kessenich, 1996b). Fifty percent of women and 20% of men over age 65 will experience an osteoporotic fracture during their lifetime. Only one woman in nine between the ages of 60 and 70 has normal BMD, nearly one third have osteoporosis, and the remainder have osteopenia, which is subnormal BMD not severe enough to be classified as frank osteoporosis (Ross, 1996). Men over age 50 have a higher risk of suffering an osteoporotic fracture than of developing prostate cancer (“Men are at risk,” 1996). In America, the cost of acute and long-term care for patients with osteoporotic fractures is estimated to be $10 to $18 billion per year (Kessenich, 1996a).

The most common osteoporotic fracture is the vertebral crush fracture; approximately 500,000 of these occur per year in the United States. Mostly affecting women over age 55, vertebral fractures may result in chronic back, rib, or abdominal pain, kyphosis, and poor body image (Galsworthy & Wilson, 1996). For 60% to 87% of those with symptomatic vertebral fractures, activities such as carrying, lifting, walking, shopping, and house cleaning are difficult (Ross, 1996). Although less debilitating in the long term, Colles’ fractures of the distal radius, occurring at a rate of 200,000 per year, may hinder the patient’s ability to function in the workplace, because those affected are often young enough still to be employed (Lindsay, 1992).

Most significant in terms of complications, death, and cost is osteoporotic hip fracture. Each year in the United States, more than 7 million days of restricted activity, 3.4 million hospital bed days, and 60,000 nursing home admissions are attributable to hip fractures. Nineteen percent of patients with hip fractures require long-term nursing home care (Ross, 1996). Hip fractures, which occur at a rate of approximately 250,000 per year, claim the lives of 25% of those affected within the first year after the fracture. This death rate is attributable to peri- and postoperative complications, including pneumonia, deep vein thrombosis, and pulmonary embolism. Of those who survive, only 20% have a complete return of function (Lindsay, 1992). The vast majority suffer permanent disability, with compromised ability to perform activities of daily living.

A few studies have demonstrated an association between osteoporosis and an increased death rate from stroke in elderly women, although it is not clear why this is so. Every decrease of one standard deviation of BMD was associated with a 70% increase of risk of death from stroke (Browner et al, 1993).

Definitive diagnostic criteria are:

Suggestive diagnostic criteria are:

Historical findings related to osteoporosis differ based on whether the patient is presenting before or after an osteoporotic fracture. Those evaluated before the fracture stage are likely to be asymptomatic; the history, therefore, is directed at risk factor evaluation. Those who have had osteoporotic fractures are more likely to have related complaints, although they, too, may be asymptomatic. Table 48-2 lists pertinent historical data for the assessment of osteoporosis.

The physical exam should include measurement of height and careful inspection of the posture and spinal curves. Kyphosis and loss of space between the inferior portion of the anterior rib cage and the iliac crests are indicators of collapse of the vertebral bodies. A protuberant abdomen may also be noted. Mild to moderate scoliosis may appear, particularly if there have been fractures of vertebrae between T2 and T11. A complete musculoskeletal exam should be performed, including palpation of the spine, paravertebral muscles, and other involved areas for tenderness or deformity, range of motion, and assessment of gait. Assessments of muscle mass, strength, and balance help identify deficits that may be correctable. The examiner should also look for physical manifestations of diseases that could cause secondary osteoporosis (see Table 48-1).

The most reliable diagnostic tool for osteoporosis is DEXA, a measure of BMD. BMD is the strongest indicator of future fracture risk; in fact, low BMD is more strongly predictive of future fracture than elevated cholesterol levels and high blood pressure are for myocardial infarction and stroke, respectively. DEXA provides a high-resolution, very reproducible image of the lumbar spine, intertrochanteric regions of the hip, and the wrist. Radiation exposure from DEXA is less than 3 mrem, one-tenth that of a routine chest x-ray. DEXA is less costly than quantitative computed tomography, which exposes the patient to 100 to more than 1000 mrem. Other positive attributes of BMD measurement are ease and noninvasiveness, reproducibility for reliable follow-up measurements, a strong correlation between bone density and bone strength, and evidence of treatment response through BMD readings. Changes in bone density significant enough to show on DEXA (variations of at least 2% to 4%), however, may not be evident for at least a year. This limits the utility of DEXA in terms of assessing immediate or short-term response to treatment.