B. Lawrence Riggs, M.D.

Mayo Clinic and Foundation

Dr. Riggs reviewed the challenges and opportunities in the field of bone health. He began by describing the complex and dynamic functions of bone, which include promoting locomotion, protecting internal organs, remodeling in response to mechanical strain, remodeling to repair microdamage, remodeling to support calcium homeostasis, and producing hematologic and immune cells in the bone marrow.

The key to healthy bones is maintaining optimal levels of “bone mass.” Bone mass varies over time in individuals, depending upon how much new bone is being formed and how much is being lost (also known as resorption). Bone turnover is a measure of the net rate of formation and resorption in an individual. Both men and women tend to have higher rates of formation than resorption during their childhood years (particularly around puberty). During adulthood, rates of resorption generally equal formation, leading to relatively stable levels of bone mass. After menopause, women experience periods of net bone loss, as demonstrated in Figure 1 below. Men also lose bone after age 50, although on average only half as much as women. One reason for this is that estrogen is as important to bone health for men as it is for women, but, unlike post-menopausal women, elderly men tend not to suffer a rapid decline in estrogen levels. That said, there is evidence that elderly men may face a period of rapid bone loss once they fall below a threshold level of estrogen. Roughly half of men over the age of 75 have fallen below this threshold level.

Figure 1

Bone Turnover at the Tissue Level: Patterns in Women. Source: Lawrence Riggs, Mayo Clinic.

Bone mass is determined by a variety of endogenous factors such as genetics, age, and sex, as well as exogenous factors including nutritional status (e.g., levels of calcium, protein, and Vitamin D), activity levels, environmental risk factors (e.g., smoking, alcohol consumption), presence of certain diseases, and use of certain drugs (e.g., corticosteroids).

The primary bone disease affecting Americans is age-related osteoporosis. Individuals with this disease are more prone to fractures. Fracture risk is increased by the following: low bone density, previous fractures, microstructural damage, high bone turnover, and trauma (e.g., due to a fall). Fortunately, osteoporosis is a preventable and treatable public health problem. Enormous advances have been made in understanding its pathophysiology. Effective drug therapy can help to prevent and treat the disease. The challenge is to implement education and awareness programs oriented toward the public and health care professionals. If these efforts are made, there is a very real opportunity to bring osteoporosis under control within the near future.

Unfortunately, the prospects for preventing other related bone disorders are less bright. These diseases include Paget’s Disease, which affects approximately 3% of Americans over the age of 40. This localized bone disease (caused by excessive bone resorption from abnormal osteoclasts (OC) with replacement by abnormal bone) can be painful and deforming. While genetics plays a role in the disease, there is also strong evidence that the measles virus contributes as well. Fortunately, drugs known as bisphosphonates offer the potential for excellent control of (or perhaps even a “cure” for) the disease in many patients.

A rarer but more debilitating genetic bone disease is Osteogenesis Imperfecta or OI. At least six genotypes of the disease have been found, which is characterized by increased bone fragility, ranging from mild to severe. Severe fragility can result in multiple fractures, deformity, and even death before or shortly after birth. Bisphosphonate therapy has recently been shown to reduce fractures in severe cases (even among small children). Gene therapy may offer some hope for the future.

L. Joseph Melton, III, M.D.

Mayo Clinic and Foundation

Dr. Melton reviewed the burden caused by the most common of bone diseases, osteoporosis. He began by noting that most people have relatively stable bone mass in mid-life, but lose bone as they get older (particularly women during and after menopause).

Projecting data from the National Health and Nutrition Examination Survey (NHANES), it is estimated that more than 10 million Americans over the age of 50 have osteoporosis, including 7.8 million women and 2.3 million men. Another 33.6 million over the age of 50 have low bone mass and thus are at risk for osteoporosis. Looking to the future, the aging of the population will drive rapid increases in these figures, as demonstrated in Table 1.

Table 1

Projected Prevalence of Osteoporosis and/or Low Bone Mass of the Hip in U.S. Women and Men ≥ 50 Years Old.

The big problem with osteoporosis is the risk of a fracture, which grows exponentially as individuals age and bone mass weakens (see Figure 2 below). Dr. Melton believes that virtually all fractures in the elderly are due at least in part to low bone density. In fact, the lifetime risk of a hip, spine, or forearm fracture is nearly 40% among 50-year-old Caucasian women and more than 13% among Caucasian men. Given improving life expectancy and the increasing incidence of hip fractures, data from Sweden suggest that these risks may rise dramatically in the years ahead (see Table 2).

Figure 2

Age-Related Fractures. Source: Cooper C; Melton LJ. Epidemiology of osteoporosis. TEM 1992; 3:224–229, with permission from Elsevier.

Table 2

Lifetime Risk of Hip Fracture at Age 50 Years.

Not surprisingly, individuals who suffer fractures frequently lose the ability to perform everyday functions. Dr. Melton shared data showing that roughly one in 10 individuals who suffer a hip fracture becomes functionally dependent as a result of the fracture, while nearly twice that many end up in a nursing home. In fact, 140,000 nursing home admissions each year are the direct result of a hip fracture. More than 4% of spine fracture victims become functionally dependent, while 1.9% end up in a nursing home. A study of women in Rancho Bernardo, California, found that those women suffering hip fractures are more than 11 times more likely to need help cooking meals, 4.6 times more likely to need help shopping, 2.8 times more likely to need help with heavy housework, and 1.6 times more likely to need help putting on their socks than are their peers who have not suffered a hip fracture. (See Table 3 for additional data on the disabling nature of spine and wrist fractures.)

Table 3

Risk of Functional Impairment with Minimal Trauma Fractures Among Women in Rancho Bernardo, CA.

And while disability and loss of functional status may be the most common impact from fractures, a small but significant portion of women and men die as a direct result of a fracture. In fact, hip fractures alone result in a 12% to 20% decline in expected survival. Survival rates for men are much worse than for women, especially among very old men.

Dr. Melton concluded his comments by noting that osteoporosis is as prevalent as the most common chronic diseases. The risk of disabling and life-threatening fractures that are related to osteoporosis is high. Looking ahead, the incidence of fractures will increase dramatically with the aging of the population. As a result, greater investments in preventive strategies are urgently needed.

Anna Tosteson, Sc.D.

Center for the Evaluative Clinical Sciences at Dartmouth Medical School

Dr. Tosteson reviewed estimates of the economic burden imposed by bone disease. Summarizing the results of several cost-of-illness studies, she noted that the direct costs of osteoporosis in 2001 are between $11.6 and $17.1 billion. Data from one study suggest that the vast majority (76%) of these costs are estimated to be the result of white women who have the disease, with another 18% the result of white men. Only 6% of the costs are attributable to nonwhite men and women with osteoporosis. Hip fractures account for 63% of the costs, with other fractures accounting for 37%. Just under two-thirds (63%) of these costs are due to hospital services, with another 28% the result of nursing home care. The government pays for the lion’s share of the health care costs of osteoporosis in women over the age of 45, with Medicare paying nearly half (48%) and Medicaid covering nearly a quarter (24%) of the expenses.

Osteoporosis not only imposes direct costs on society, but indirect costs as well, including the costs of morbidity and premature mortality. Moreover, as older Americans remain in the workforce, osteoporosis results in loss of productivity.

While cost-of-illness studies have helped to establish osteoporosis as a public health priority and have identified the high direct costs of the disease, they have not adequately addressed prevention, considered the economic consequences of the disease over a lifetime, or adequately measured indirect costs. To get at some of these issues, Dr. Tosteson shared the results of several cost-effectiveness studies that were designed to assess the relative value of alternative interventions. The rationale behind these types of studies is to ensure that expenditures provide benefits that are worth the additional costs. This type of analysis is especially important in an era of limited financial resources. Most cost-effectiveness studies have focused on postmenopausal women, considering single-age cohorts. These studies have helped to determine the appropriate age of intervention and the expected amount of time before the benefits of treatment are to be realized. This latter calculation can have a significant impact on the perceived benefits for different stakeholders. For example, a private insurer that covers post-menopausal women until they reach the age of 65 (and become eligible for Medicare) will typically have a 10-year time horizon. For these insurers, widespread bone density testing and medication may not be cost-effective, since relatively few fractures are likely to occur during the 10 years of coverage. On the other hand, targeted programs aimed at high-risk individuals are likely to be cost-effective for these insurers. A government insurer such as Medicare, however, may view widespread screening and interventions among postmenopausal women as highly cost-effective, as these early interventions may prevent fractures (and the associated costs of hospitalization and nursing home care) in later years.

Dr. Tosteson concluded by noting that bone diseases result in large economic costs to society, costs which are increasing. Fortunately, opportunities for cost-effective prevention and treatment are also increasing; these approaches must be identified and implemented. Successful implementation requires consideration of the impact of alternative strategies on the health of the entire population.

The panel included presentations by two individuals whose stories demonstrate the personal burden suffered by those who live with osteoporosis and other bone diseases on a daily basis.

Linda Johnson

Linda Johnson, who suffers from osteoporosis, has become a national spokesperson on the disease. Her story is a classic example of the terrible consequences that occur when the medical profession fails to recognize the possibility of osteoporosis in a younger woman.

She began suffering bone fractures while still in her thirties. One of her most vivid memories from this time is when her young sons and daughters would remind each other “not to touch mommy because she will break.” Even as pain levels increased and her quality of life suffered, her doctor blamed her problems on clumsiness. After she turned 40, her internist attributed her problems to being a natural consequence of “getting old.” Finally, after breaking her ankle at the age of 43, an orthopedist diagnosed osteoporosis. At this point she had lost bone mass and was shorter than earlier in life, probably due to spine fractures. The doctor told her there was no treatment available for osteoporosis. He advised her to take calcium supplements and to exercise, although he provided no guidance on what types of exercises would be helpful and safe. While she had a long list of “don’ts” with respect to her life, she did find that exercise made her feel better. Yet she remained paralyzed with fear, particularly after her physician gave her the following advice: “above all else, don’t fall.”

Today at age 55, Ms. Johnson has finally turned the corner on the disease. Thanks to medical treatment, calcium supplements, and exercise, her bone mass has improved. She is no longer considered to have osteoporosis, but rather is classified as osteopenic (i.e., she has low bone mass). She has even regained some height.

As she reflects on her experience, Ms. Johnson is concerned about the millions of other individuals who have osteoporosis or who are at risk of getting it. She reminded the audience that osteoporosis is not necessarily your “grandmother’s disease.” It can affect younger individuals, and therefore it is critical for the public and medical professionals to learn more about the disease. Failure to follow this strategy may mean that the disease of osteoporosis “breaks the bank” with respect to health care costs. As Ms. Johnson noted, “people with osteoporosis do not just die; they slowly break apart.”

Jean Mandeville

Jean Mandeville offers the perspective of a parent who has two children with bone disease, a daughter (now 25 years old) with osteoporosis and a son (now 28 years old) with severe OI. Her son suffered nearly a dozen bone fractures at birth. Her instructions from the physicians upon taking him home were to “be careful.” When her son was two months old, she heard the horrible sound of his arm breaking as she turned him over in his crib. To date, he has suffered 140 fractures, some caused by acts as simple as sneezing or being startled. Fractures, however, are not the only health problems he faces. Like many OI sufferers, he also must endure problems such as scoliosis, broken teeth, hernias, kidney stones, and hearing loss. He presently requires full-time oxygen. Only three feet tall, he has never slept through the night.

Yet like many OI patients, Ms. Mandeville’s son is highly intelligent and engaging, a true joy to be around. He spoke in complete sentences by the age of one and was reading at the age of two. He showed an interest in politics by age five, querying his mother on whom she was going to vote for in the presidential election, and why. His tremendous intellectual abilities and engaging personality are as much or more a part of him as are his disabilities. Like many OI sufferers, his personality and story make him an excellent spokesperson for the disease. But like all OI sufferers, he would like help as well. With limited treatment options and no possibility for prevention, OI remains a terrible disease that needs to be further researched. To that end, Ms. Mandeville called for the following: better tools to assess the strength of bones in OI patients and to evaluate the relative merits of various therapies for OI; creation of a national center for OI that could serve as a clearinghouse for information on the disease; and increased spending on OI research to reduce the burden of the disease.