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Understanding Key Risk Factors and Therapeutic Options

Belinda R. Beck, PhD; M. Rebecca Shoemaker, MD


In Brief: Bone loss throughout life is a normal consequence of aging; however, some people are more predisposed to developing osteoporosis and sustaining associated fractures than others. But the risk of osteoporosis can be reduced by: (1) maximizing skeletal mass during the growing years, (2) consuming 1,000 to 1,500 mg of calcium per day, (3) participating in lifelong weight-bearing exercise, and (4) considering pharmacologic intervention at menopause. Pharmacologic options include calcium, vitamin D, estrogen, bisphosphonates, selective estrogen receptor modulators, and calcitonin. Any such medication should be taken in conjunction with exercise and fall precautions.

Osteoporosis is a systemic disease characterized by low bone mass and microarchitectural deterioration of bone tissue that renders bone more susceptible to fracture (1). Although first described around 1820 by the French pathologist Lobstein (2), the negative impact of osteoporosis on the health of the aging population has attracted serious attention in the clinical community only over the past few decades. The magnitude of the problem is only now being fully recognized.

Incidence and Fracture Risk

According to the diagnostic criteria for osteoporosis (table 1) formulated by a study group of the World Health Organization (WHO) in 1993, 70% of white American women over the age of 80 could be classified as osteoporotic (3). In fact, up to 30% of all postmenopausal women (an estimated 9.4 million in the United States) have osteoporosis according to WHO criteria, with another 54% (16.8 million) having osteopenia, or low bone mass.

TABLE 1. Diagnostic Criteria for Osteoporosis as Formulated by the World Health Organization (3)
Bone Status Relationship of Patient BMD to Mean Peak BMD

Normal < 1 SD below
Osteopenia > 1 SD below but < 2.5 SD below
Osteoporosis > 2.5 SD below
Severe osteoporosis and fragility fracture > 2.5 SD below

BMD = bone mineral density; SD = standard deviation

Low bone mass is not in and of itself pathologic, but the associated increased risk of fracture is critical. The annual incidence of osteoporotic fracture is almost three times that of myocardial infarction. The lifetime risk of osteoporotic fracture in 50-year-old women and men has been estimated to be 39.7% and 13.1%, respectively (4). In the United States, the annual dollar cost of hip fracture alone may be as high as $10 billion. The human costs, including loss of mobility and independence, are equally profound. Twenty-five percent of patients who fracture their hip require some degree of long-term care (5), and 50,000 deaths annually can be attributed to hip fracture.

Men are less susceptible to osteoporotic fracture than women are, primarily by virtue of achieving greater peak bone mass and larger bone size. Although fracture incidence may be lower in men than in women, mortality rate is substantially higher in men (hip fracture: 21% versus 8%) (6).

Risk Factors

Individuals who do not attain a normal peak bone mass by about age 20 are at greatest risk of developing osteoporosis in later years. The gradual loss of bone through remodeling inefficiency (see "Bone Acquisition and Loss," page 73) occurs at roughly the same rate in all people. In those with low initial bone mass, however, remodeling-related bone loss will reduce bone mass to levels that place them at increased risk of fragility fracture (figure 1: not shown).

The skeleton comprises two different types of bone: cortical and trabecular. Cortical bone is dense and compact and composes the outer shell of all bones as well as the shafts of long bones. Trabecular bone is spongelike in appearance, consisting of interconnected plates and struts of bone and thus is far less dense. Trabecular bone is found in the ends of long bones and within smaller bones such as the vertebrae.

Although trabecular bone accounts for only 20% of total skeletal mass, it is the site of 80% of bone remodeling. Thus, any factor that increases the rate of bone turnover is likely to affect trabecular bone sites to the greatest extent. To compound the problem, loss of trabecular bone may result in a substantial loss of whole-bone strength due to architectural disruption. That is, aggressive bone resorption can completely eliminate the bone struts that connect trabecular plates, which reduces bone strength much more than does losing the equivalent amount of cortical bone (figure 2: not shown).

Lifestyle and genetic factors that increase the rate or degree of remodeling will hasten the generalized loss of bone over time. Examples include sex, race, heredity, age, diet, circulating hormones, exercise, medications, alcohol and tobacco consumption, and diseases such as gastrointestinal disorders, diabetes, hyperparathyroidism, and hyperthyroidism.

Sex. As previously mentioned, men are somewhat protected from the development of osteoporosis and risk of fracture by virtue of attaining greater peak bone mass and larger bones in their youth than women do. In addition, women ultimately lose more bone mineral with age than do men (7). (The profound influence of menopause is discussed in the "Circulating hormones" subsection below.) Also, the gradual age-related increase in cross-sectional area of both axial and appendicular bones that accompanies the age-related loss in bone density appears to be greater in men than in women (8). This geometric adaptation somewhat attenuates losses in bone strength that accompany increasing porosity by improving the bone's mechanical competence.

Men also appear to maintain the structural integrity of trabecular bone to a greater extent than in women, which, as previously mentioned, has a substantial effect on the strength of a bone. A final factor contributing to the reduced risk of fracture in aging males is a reduced tendency to fall. This characteristic is likely to be related to greater muscle strength and balance competency throughout life (9).

Race and ethnicity. African-Americans have greater bone mineral density (BMD) than do non-Hispanic Caucasians (10). Interestingly, Hispanics have bone mass similar to Caucasians but fracture rates closer to those of African-Americans (11), which suggests that ethnicity (eg, cultural factors) as well as race (genetic constitution) may influence bone health.

Heredity. Patients with a family history of osteoporosis have a greater chance of developing the condition. It is likely that this is related to genetic elements responsible for determining the mass of all connective tissue, but it may also be associated with similarity of environmental influences on the bones of individuals living under the same conditions.

Age. Given that bone loss accumulates over time, it is intuitive that the older a person gets, the greater the risk of osteoporosis.

Diet. The skeleton functions as an internal buffer for calcium and phosphorus, serving both as a reserve to offset systemic shortages and as a storage site (12). The effect of deficient intake of these nutrients is illustrated in figure 3 (not shown).

Low calcium intake is related to an increased risk of osteoporosis and fracture (13). It is noteworthy that the average dietary intake of calcium in men is much higher than in women at all ages after 10 years (14), a statistic that may additionally contribute to the sex disparity in the incidence of osteoporosis.

Certain vitamins (C, D, and K) and other minerals (copper, manganese, and zinc) also serve vital roles in the production of bone matrix.

Circulating hormones. The hormone with the most apparent influence on bone mass in women is estrogen. Behaviors that create estrogen deficiency premenopausally, such as chronic energy deficit incurred by overexercising and/or eating disorders such as anorexia or bulimia nervosa that induce amenorrhea, have extreme negative consequences for bone. (See the "Female athlete triad" subsection below.) Because estrogen inhibits the action of osteoclasts, any reduction in circulating levels will increase osteoclast activation and bone resorption.

Menopause stems from the dramatic drop in circulating estrogen that normally occurs in women in their early 50s. The crucial contribution of estrogen to bone health becomes very apparent at this time as rates of bone loss accelerate in the early postmenopausal years. A decrease in BMD of 1% per year in an untreated postmenopausal woman may translate to a loss of 40% to 50% of peak bone mass in a 90-year-old woman (15). With such losses in BMD, it is possible that even women who enter menopause with normal bone mass may, without intervention, lose enough bone to develop osteoporosis postmenopausally.

Exercise. It has been argued that the reduction in bone mass with age is attributable to the tendency to become more sedentary with advancing years, and an element of truth exists in this assertion. It is certainly known that chronic extreme reductions in bone loading—such as occur during immobilization, spinal cord injury, and space flight—result in substantial bone loss (16-18). A reduction in the intensity of habitual activities is naturally a less extreme form of skeletal unloading but may contribute to an increased rate of bone loss because of reduced mechanical stimulation of osteoblasts.

Female athlete triad. At the opposite extreme of skeletal unloading, chronic intense overexercising has been associated with reduced bone mass in premenopausal women. Chronic overexercising is often accompanied by disordered eating, amenorrhea, and osteoporosis, which collectively have been called the female athlete triad.

A combination of chronic exercise and restricted calorie intake can produce a substantial negative energy balance, which disrupts circulating hormones enough to deprive the ovaries and skeleton of the essential influence of estrogen. In spite of the normally positive influence of weight-bearing exercise on bone, this withdrawal of estrogen accelerates bone resorption and bone loss.

It should be noted, however, that gymnasts demonstrate an exception to this effect: They typically have very dense bones in spite of often being amenorrheic. The difference in bone density between gymnasts and other highly trained female athletes is the large discrepancy in magnitude of forces placed on the skeleton during different activities—much higher forces are generated in gymnastics.

Medications. Several medications, including corticosteroids, anticonvulsants, cyclosporin, and heparin are known to decrease bone density. Individuals on prolonged corticosteroid therapy are known to lose enough bone mass (19) to triple their fracture risk (20). Glucocorticoids exert a direct effect on bone by decreasing osteoblast replication and differentiation, inhibiting type 1 collagen gene expression, decreasing synthesis of bone matrix elements, and increasing bone resorption. Indirect effects of glucocorticoids on bone may include suppression of gonadal hormone secretion, impairment of intestinal calcium absorption, decreased renal tubular reabsorption, and secondary hyperparathyroidism (21).

Tobacco and alcohol. It is difficult to make confident assertions about the effect of alcohol and tobacco use on bone mass, given that it is normally impossible to isolate the effects of these substances from other lifestyle factors. In general, however, both excessive alcohol and tobacco intake are likely to be detrimental to bone health, with the evidence being strongest against tobacco (22).

Tobacco use is associated with an increased risk of fracture, especially later in life. Bone mass reduction may be mediated by decreased production and increased degradation of circulating estrogen.

The influence of alcohol on bone density is even less well characterized. Alcohol abuse may be associated with increased risk of fracture; however, this relationship appears to be stronger in men than women and is not consistent across all studies. If there is an increased risk with alcohol consumption, it may be related to reduced bone formation.

Other diseases. Diabetes, hyperparathyroidism, and hyperthyroidism impair bone health. Hyperglycemia, which may occur in diabetics, can lead to excessive loss of phosphate through the urine. (Inorganic phosphate is an essential element of bone matrix.) Both hyperparathyroidism and hyperthyroidism create conditions of high bone turnover due to excessive secretion of the respective hormones. Increased bone resorption and bone formation lead to generalized bone loss.

Abnormalities of the hepatogastrointestinal tract that impair the absorption of calcium, phosphate, and vitamin D from the gut can also cause bone disease. Examples of such gastrointestinal disorders include inflammatory bowel disease, gastrectomy, celiac disease, Crohn's disease, jejunoileal bypass, and pancreatic insufficiency. Cushing's disease and depression, associated with elevated levels of endogenous cortisol, may cause bone loss in the manner of corticosteroid therapy, but likely to a lesser extent.

Accurate Diagnosis

Diagnosis of osteoporosis begins with a careful history and physical evaluation aimed at documenting the severity of the disease and identifying secondary causes.

Osteoporosis itself is not evident on physical examination unless it is in an advanced stage. Its diagnosis is based on radiologic studies or a history of atraumatic fracture. Thus, what is usually seen clinically is the consequence of osteoporosis: fracture.

The most obvious sign of a patient who has advanced osteoporosis is the exaggerated kyphotic curvature often referred to as a dowager's hump. This posture is indicative of fracture of the anterior aspect of thoracic vertebral bodies, resulting in an exaggerated thoracic curvature. Kyphosis does not always occur in women who have vertebral fractures, and, in fact, some women are not aware of fractures until evidence is seen on radiologic exams. Similarly, other clinically important sites, such as the proximal femur and distal radius, exhibit no indication of osteoporosis on exam until a fracture occurs.

Bone mass is highly correlated to its mineral content. Thus, bone mineral content (BMC), relatively simple to measure radiologically, is most frequently used to estimate bone mass. The standard technique for measuring BMC is dual-energy x-ray absorptiometry (DEXA). Size differences between bones of different people are partially accounted for by dividing the BMC (g) by the area of the bone measured (cm2) to obtain a value of BMD in g/cm2. DEXA administers a very low dose of radiation while producing a BMD measure of acceptable precision (normally 2021% to 99%).

Computed tomography is the gold standard for measuring volumetric BMD, but its high radiation dosage and higher cost renders it less favorable than DEXA for clinical purposes.

A relatively new addition to the bone assessment arsenal is ultrasonography. While the bone parameter measured by ultrasound remains to be identified with certainty, many aspects of ultrasonography suggest that this method of bone assessment will be clinically useful. Positive attributes include the use of sound waves rather than radiation, an acceptable ability to predict fracture risk, device portability, and close correlation of broadband ultrasound attenuation (a value indicative of bone integrity) with DEXA-derived measures of bone density. Ultrasound is approved by the US Food and Drug Administration (FDA) as a screening tool to determine which patients will most benefit from DEXA.

It is essential to identify secondary causes of osteoporosis to establish a course of treatment. Information about diet (primarily calcium consumption but also total caloric intake of female athlete triad candidates), exercise habits (specifically, weight-bearing activities), hormone profile (note menstrual status), chronic drug therapies (eg, corticosteroids), and gastrointestinal disorders must be gleaned so that contributing factors can be targeted.

Exercise as Prevention and Therapy

The most effective method of osteoporosis management is probably prevention. During the growing years before peak bone mass is attained, the ability of bone to respond to osteogenic stimuli is greatest. The principal techniques for maximizing bone mass at this time are the consumption of adequate calcium, casual exposure to the sun for the purposes of generating vitamin D, and participation in plenty of vigorous weight-bearing activities.

Building and maintaining bone mass. Cross-sectional studies suggest that continuous weight-bearing exercise throughout life reduces the rate of bone loss. Intervention trials have also almost unanimously demonstrated that exercise can maintain or enhance bone mass in people of all ages. For example, supplemental weight-bearing exercise increased BMD in prepubertal boys compared with controls (23). Similarly, premenopausal women and young adult men have responded to both resistance and endurance exercise programs with site-specific increases in BMD (24-29).

When there is evidence of the female athlete triad, some have suggested that daily administration of oral contraceptives will stabilize levels of circulating hormones, thereby preventing the excessive bone loss related to estrogen withdrawal. Further controlled investigation is necessary to confirm this effect. A more satisfactory approach is to attain ongoing daily energy balance by increasing caloric consumption and decreasing caloric expenditure by reducing training intensity. Often both can be achieved with neither weight-gain nor performance decrement.

Whether exercise intervention can entirely prevent loss of bone subsequent to menopause remains contentious and likely depends on initial bone mass and the type of exercise performed. While many have demonstrated that both resistance and weight-bearing endurance training increase or maintain bone mass in this population (30-37), others report no such effect (38-40). The combination of hormone replacement therapy with exercise may be the most effective method of preventing postmenopausal bone loss (41,42), although some dispute this (43).

Exercise-related increases in bone mass are often quite modest (on the order of 1% to 3%). However, the mere prevention of bone loss without any gain is advantageous from a clinical standpoint, given that maintenance of bone mass reduces fracture risk.

Walking does not appear to load the skeleton enough to be osteogenic (44), unless combined with resistance exercise (45). Non-weight-bearing activities such as swimming (46) and cycling are relatively ineffective at enhancing or maintaining bone mass.

Some basic principles should be kept in mind when prescribing exercise for preventing or treating osteoporosis. First and foremost is the principle of overload. That is, the loads placed on bones during exercise must be greater than, and preferably different from, those experienced during normal daily activities. Given the principle of overload, the fact that exercise intervention elicits the greatest response from the bones of individuals with very low initial skeletal mass is not surprising (47,48). Intensity and duration of activities should be increased as ability improves.

Second, the effects of exercise are site-specific, that is, only bones that are loaded will benefit from the activity (49). For example, running will not affect the mass of upper-body bones. Third, impact activities, or activities that place relatively large loads on bone and do so quickly, such as running and jumping, are most osteogenic. Fourth, to maintain the positive effects of exercise on bone, the program must continue throughout life.

It is not possible to recommend an exercise protocol appropriate for all. Younger, otherwise healthy people can engage in higher-load activities such as running, jumping rope, stair climbing, and aerobics along with upper-body resistance exercises. Older patients with severely compromised skeletons should aim to increase their level of weight-bearing activity with lower-intensity activities (eg, walking) and complement the workout with resistance exercises for the upper and lower body.

Lifting weights that are readily available in the home environment (eg, large cans of food, heavy books) may substitute for expensive gym equipment and thus enhance compliance. Those unfamiliar with correct lifting techniques, however, should first consult an exercise specialist.

Too much or inappropriate exercise can be harmful. Excessive loading of an insufficient skeleton can result in fatigue damage and stress fracture. Also, certain exercises that involve deep forward flexion—such as sit-ups, toe touching, and rowing—should be avoided by patients already diagnosed as having vertebral osteoporosis.

Preventing falls. It is crucial to note that exercise can indirectly benefit the skeleton in the absence of gains in bone mass. Improving muscle strength reduces the risk of falling. Similarly, activities that improve balance and proprioception will reduce falls and fracture risk. Specific exercises can be prescribed with these goals in mind. Strengthening the quadriceps and gluteal muscles (leg and hip extension) will enhance the ability to rise safely from the seated position, and standing on one foot for periods of time will improve balance. Naturally, all new exercises should be initiated under supervision and with adequate support devices to prevent temporarily increasing the risk of falls.

Though walking, in and of itself, is unlikely to noticeably increase BMD, the associated health and balance benefits will reduce the risk of falls and consequently the incidence of fracture. Walking up and down hills and stairs will load the skeleton to a greater degree than will walking on level ground.


Calcium. Although calcium consumption alone is not considered adequate protection against osteoporosis, it plays an important role in the prevention and management of postmenopausal osteoporosis. In 1994, a National Institutes of Health consensus panel proposed optimal calcium intake levels for women of all ages (table 2). The guidelines reflect the need for augmented calcium intake during times of increased bone metabolism, such as growing phases, pregnancy, and postmenopausal years.

TABLE 2. Optimal Calcium Intake Levels for Women of Various Ages
Hormone Status Age in Years Recommended Daily Calcium Intake (mg)

Premenopausal 11-24 1,400
Premenopausal 25-50 1,000
Premenopausal, pregnant or lactating 25-50 1,400
Postmenopausal, taking estrogen < 65 1,000
Postmenopausal, not taking estrogen < 65 1,500
Postmenopausal > 65 1,500

Based on the results of more than 20 randomized trials of calcium versus placebo supplementation, calcium treatment has a small, but significantly beneficial effect on BMD. There is a trend toward increased efficacy in women in later menopause with lower bone density than in perimenopausal women with relatively preserved bone density (15,50). Supplemental calcium has been shown to decrease not only bone loss in postmenopausal women, but also the risk of a vertebral fracture, up to 45%, in women who had already suffered a vertebral fracture (51,52). Further, a large trial of 3,000 postmenopausal women randomized to receive placebo or calcium and vitamin D found that by year 3 of the study, the probability of nonvertebral fracture and hip fracture had been reduced by 24% and 29%, respectively (53).

Calcium is an essential adjunct to other treatment interventions. For example, the positive effects of exercise on BMD may occur only when mean calcium intake surpasses 1,000 mg/day (54).

While calcium can be obtained from a number of foods, the best sources are dairy products. (An 8-ounce glass of milk contains approximately 300 mg of calcium.) If dietary calcium does not meet the daily requirement, calcium supplements are readily available in the form of calcium carbonate, calcium citrate, and calcium phosphate. Calcium carbonate is cheapest and dissolves well but should be taken with meals to be properly absorbed. Calcium citrate and calcium phosphate are more easily absorbed than the carbonate salt and do not need to be taken with meals. Calcium citrate is most recommended for people with kidney stones but is the most expensive. Recently, manufacturers have begun to fortify some foods with calcium, such as orange juice, cereals, and bread. Foods so fortified are normally well labeled. No more than 500 to 600 mg of calcium should be taken at one time. Iron or fiber supplements should not be taken simultaneously with calcium because they reduce absorption.

Vitamin D. Calcium absorption from the intestine depends on adequate vitamin D availability. The skin synthesizes vitamin D following sunlight exposure; however, the ability to do so decreases with age. Thus, dietary products, such as vitamin D-fortified milk or supplements, become an important source.

Adequate daily intake of vitamin D for persons through the age of 50 is 200 IU (5 micrograms). For adults age 51 to 70, the recommendation is 400 IU/day (10 micrograms/day), and those older than 71 should consume 600 IU/day (15 micrograms/day). The recommended intake for pregnant and lactating women of all ages is 200 IU/day. In the absence of sunlight, the recommended intake of vitamin D for all ages should be increased by 200 IU/day. Although one large study (55) showed that vitamin D treatment alone, compared with placebo, resulted in decreased femoral bone loss, there has been no evidence that vitamin D alone reduces the risk of fracture (56).

In almost all pharmacologic osteoporosis intervention studies, participants are routinely given calcium and vitamin D in addition to the study medication or placebo, which is the case for the clinical trials discussed below.

Estrogen replacement. Estrogen replacement therapy (ERT) is a powerful agent in preserving BMD at menopause, when endogenous estrogen levels substantially decline. ERT has its greatest protective effect if initiated at the time of or soon after menopause, before any postmenopausal bone loss has occurred. If women start ERT in early menopause, they not only can prevent the expected decline in BMD, but they can actually increase their BMD by 2% to 8% at the lumbar spine and hip (57). However, for women who choose not to start early, ERT later in menopause can still be beneficial, with a potential 5% to 10% increase in BMD at the lumbar spine and hip (58).

Most data for ERT and fractures are from observational studies. These studies have concluded that ERT users have a 25% to 50% decreased risk of hip fracture compared with nonusers, with greater protection the earlier it is started and the longer it is continued (59-61). The protective effects of ERT are lost if it is discontinued. Approximately 10 years after stopping ERT, BMD and fracture risk are the same as for women of similar age who never took estrogen (62).

Bisphosphonates. The bisphosphonate group includes alendronate sodium, etidronate disodium, pamidronate disodium, and risedronate sodium. These analogues of inorganic pyrophosphate, an endogenous inhibitor of bone resorption, also decrease bone resorption. Of these agents, alendronate shows greatest efficacy in increasing BMD and preventing fractures and is the only FDA-approved bisphosphonate for osteoporosis. It is used for prevention (5-mg dose) as well as for treatment of established osteoporosis (10-mg dose).

A primary prevention study (63) of postmenopausal women without osteoporosis at baseline showed that 5 mg of alendronate daily for 2 years resulted in a 3% to 4% BMD increase at the spine and hip, compared with a 4% to 5% increase for ERT, while the placebo group showed a steady decline in BMD. Most of the increase in BMD occurred in the first year of treatment. In a treatment study (64), postmenopausal women with low bone mass at baseline treated with 10 mg of alendronate daily gained 4.9% BMD at the lumbar spine (figure 4: not shown) and 3.0% at the hip; both increases were significantly greater than in placebo-taking controls. Some evidence suggests that some of the gains in BMD can be maintained even after the discontinuation of alendronate (65), an effect that, as mentioned, has not been shown for ERT.

Randomized controlled trials also support alendronate's role in fracture reduction. The Fracture Intervention Trial (66) showed that 3 years of alendronate treatment (plus vitamin D and calcium) in women who had a prior osteoporotic fracture resulted in a relative risk reduction in hip fractures (51%), clinically evident spine fractures (55%), and wrist fractures (48%) compared with a control group. This risk reduction of approximately 50% of nonspinal fractures has been supported in other large randomized trials of alendronate versus placebo (64). The addition of alendronate affords almost double the reduction in hip fractures provided by calcium and vitamin D alone (51% vs 29%) (53,66).

Alendronate is also a powerful tool in preventing the bone loss that occurs with corticosteroid treatment. In a large, randomized trial of just 48 weeks' duration, alendronate treatment resulted in a 2.4% increase in lumbar spine bone density, compared with a 0.4% loss of bone density in the placebo group of corticosteroid-treated subjects (67).

Selective estrogen receptor modulators (SERMs). The class of medications known as SERMs includes estrogen analogues, such as tamoxifen and raloxifene, that have estrogen agonist activity in bone but antagonist activity at the breast and uterus. Raloxifene appears to be the most powerful SERM in this regard and currently is the only FDA-approved SERM. In a 24-month trial of postmenopausal women (68), a group treated with raloxifene had a 2.4% increase in BMD of the lumbar spine and hip compared with the placebo-treated group. Another study (69) reported that postmenopausal women who had a prior osteoporotic fracture and received raloxifene therapy had a relative vertebral fracture risk of of 0.62 after 3 years compared with those receiving placebo. For women without a prior fracture, the relative risk was even lower at 0.48. Tamoxifen engenders an average increase in bone density of only 1% to 2% per year in most studies (70) and no reported decrease in fracture rates.

Calcitonin. Intranasal calcitonin is a weaker agent for protecting against and treating osteoporosis than those previously discussed. Women with osteoporosis given intranasal calcitonin for 2 years gained only 2% spinal BMD (71). A trend toward a lower risk of fractures in the treated group was suggested, but the study lacked the power to prove this association. In a large study (72) of 1,255 postmenopausal women who had established osteoporosis, calcitonin treatment provided a statistically significant 36% reduction in the relative risk of new vertebral fractures.

Other therapies and future directions. All of the above pharmacologic interventions act by decreasing bone resorption, providing at most a 10% increase in BMD at any given site. Once large amounts of bone have been lost, most bone cannot be restored because no anabolic treatments are available to build bone.

Anabolic steroids have been proposed as agents to increase bone formation, but, in fact, they act more by decreasing resorption, and the side effects of virilization limit their clinical use. There have been no studies of anabolic steroid effects on fracture risk as an end-point.

Fluoride, although it increases BMD, also increases the rate of stress fractures (73). Intermittent treatment with parathyroid hormone (PTH) shows promise as an anabolic agent for bone (74). In rat models, ovariectomized (and thus estrogen depleted) rats treated with PTH had increased bone mass and strength of both the vertebral bodies and femoral neck (75). Studies in humans are in progress and show promise.

Assessing and Reducing Risk

Natural loss of bone throughout life is a consequence of the fundamentally inefficient process of bone remodeling. Even though genes and behavior predispose some people to osteoporosis, the problem is widespread, particularly among women. Regular weight-bearing exercise, adequate calcium consumption, and appropriate medication at menopause, however, can reduce the risk. The choice of pharmacologic treatment or combination of treatments is a clinical decision made by the patient and the treating physician. All medication, though, should be coupled with exercise and fall precautions to achieve the ultimate goal of preventing osteoporotic fractures.


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Bone Acquisition and Loss

In adults, the amount of bone in the skeleton at any time represents that formed during growth minus what has been subsequently lost. Peak bone mass is generally reached during the third decade; in reality, however, only a small increment is gained by most after age 20. After attaining peak bone mass, men and women experience similar rates of loss throughout their lives, with the exception of the 5 to 8 years immediately following menopause, when women lose bone more rapidly.

The reason for progressive bone loss stems from a process fundamental to bone metabolism. Normal bone tissue exists in a state of constant turnover, called remodeling. The process of remodeling involves the resorption of small portions of bone at many sites in the skeleton by bone cells called osteoclasts, followed by activation of a second set of bone cells—osteoblasts—which replace the resorbed portions by way of bone formation. It is thought that this process of remodeling allows bone to: (1) adapt its shape to best suit changes in its mechanical environment, (2) minimize the accumulation of fatigue damage, and (3) release calcium into the system for use in other areas.

Although remodeling serves these important functions, inherent inefficiency creates an annual loss of 0.3% to 0.5% of bone from the skeleton as a whole. That is, formation does not entirely match resorption, resulting in a net loss of bone each remodeling cycle and an ongoing loss throughout life.

Dr Beck is a lecturer in Anatomical Sciences at the Griffith University School of Physiotherapy & Exercise Science in Queensland, Australia. Dr Shoemaker is a fellow at Stanford University School of Medicine in Stanford, California. Address correspondence to Belinda R. Beck, PhD, Griffith University School of Physiotherapy & Exercise Science, Private Mail Bag 50, Gold Coast Mail Centre, Queensland 9726, Australia; e-mail to [email protected].