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Osteoporosis and Fractures
Missing the Bridge?
Commentary
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Angela M. Cheung, MD, PhD; Allan S. Detsky, MD, PhD
JAMA. March 27, 2008;299(12):1468-1470.
Department of Medicine, Mount Sinai Hospital and University Health Network, Toronto, Ontario, Canada; and Departments of Health Policy Management and Evaluation and Medicine, University of Toronto, Toronto.
On August 1, 2007, a bridge on interstate 35W collapsed during rush-hour traffic near Minneapolis, Minnesota, with tragic consequences. Engineers commissioned by the National Transportation Safety Board are still investigating the cause of this structural failure, and the final report is expected by fall 2008. The bridge buckled because its load exceeded the strength of its structure. Was the bridge collapse caused by an external force such as extra weight on the bridge, or was it due to structural deficiencies such as corrosion and deterioration of the truss gusset plates joining the beams? Although current evidence suggests that the collapse was due to a design flaw (the gusset plates were too thin) coupled with the 300 tons of extra construction equipment and gravel, the collapse could have been caused by one of many elements. These general principles and possible explanations for structural failure apply not only to the collapse of bridges, but also to the fracture of bones.
What Are Bones and Bone Strength?
Bones are designed to support and protect vital organs while being light and allowing for mobility. Humans are born with approximately 300 bones that fuse to become 206 bones by age 25 years. Some bones, such as the skull and ribs, support and protect the brain, heart, and lungs. Other bones provide attachment sites for muscles and allow humans to perform motor activities. However, bone is a complex organ with multiple functions. It makes blood cells, stores minerals, and plays a key role in calcium homeostasis and possibly energy metabolism.1
Fragility fractures-fractures sustained with minimal trauma such as falling from standing height-are the hallmark of osteoporosis. They occur when the load on a bone exceeds its strength. Fractures are more common than heart disease or cancer in women, affecting 1 in 2 women and 1 in 6 men older than 50 years in North America.2 Vertebral fractures are the most common osteoporotic fracture in postmenopausal women; two-thirds of these fractures are not clinically recognized.3 Postmenopausal women who have sustained multiple vertebral fractures can develop restrictive lung disease, early satiety, chronic pain, and low self-esteem. Even asymptomatic vertebral fractures are associated with decreased quality of life, increased hospitalization, and mortality.4-5 Women and men who sustain a hip fracture have pain, decreased mobility, fear of falling, and loss of independence.6 Hip fractures contribute to significant excess mortality; more than half of patients who have a hip fracture die within 5 years.7
Prior to 1993, osteoporosis was defined by the presence of a fragility fracture. With the invention of dual-energy x-ray absorptiometry machines to measure bone mineral density (BMD), the World Health Organization (WHO) established a new definition of osteoporosis in 1993 based on BMD T scores (the number of standard deviations from the mean peak BMD in young sex-matched adults).8 The goal of this change in definition was to identify and treat at-risk individuals before they developed a fragility fracture. In 2001, the National Institutes of Health amended this BMD-based definition of osteoporosis to recognize that bone strength is a combination of both BMD and "bone quality."9 However, bone quality is a vague entity that is difficult to measure clinically. As a result, clinicians still rely on BMD for fracture risk assessment and treatment decisions. In addition, pharmaceutical companies use BMD as a surrogate outcome in the development of drugs to reduce fracture risk.
However, BMD is only 1 determinant of bone strength. Applying principles from engineering, bone strength depends on a combination of its structural and material properties, both of which are modulated by bone turnover.10 Structural properties depend on the size and shape of the bone, the microarchitecture of the bone (such as cortical thickness and porosity, and trabecular thickness, number, and separation), and the amount of accumulated damage (microcracks). Material properties depend on the degree of mineralization, the crystal size of the minerals, the amount and type of collagen cross-links, other proteins, and fat. The measure of BMD by dual-energy x-ray absorptiometry is the amount of bone mineral mass within a user-defined area but is confounded by bone size, which is a strong determinant of bone strength. Bone mineral density is higher if the bone is bigger, even if the degree of mineralization of the bone is the same. Bone mineral density assumes a homogenous distribution of mineral and density and does not reflect the anisotropy (variability) of bone microarchitecture. Thus, many factors that contribute to bone strength are not captured by BMD.
How Does the Body Protect Bones From Trauma?
Bone strength, in turn, is only one determinant of fracture risk. The ability to avoid injury to the bones is another. A major function of bones is to help humans stay upright and move. Maintaining an upright stance and avoiding falls are important protectors of bones. The ability to avoid falls is a complex activity involving the coordination of bones, muscles, tendons, nerves, and the brain. When an unexpected encounter occurs, such as missing a step, stepping on a slippery surface, or receiving a glancing blow from someone walking in the opposite direction, good coordination, quick reflexes, strong muscles, and excellent balance are required to avoid a fall. In addition, all individuals experience minor injuries to the muscles, tendons, and bones on one side of the body or the other, and the rest of the structures have to compensate to stay upright and maintain mobility. When a fall occurs, the direction and the force of the impact on bone, the degree of padding around the impact site, the muscular coordination to absorb the impact of the fall, and the strength of the bone itself determine whether a fracture occurs.
Recent data suggest that falls are a stronger predictor of fractures than BMD.11 Falls increase in frequency with advancing age and account for at least 95% of hip fractures in the elderly.12 More than a third of community-dwelling elderly people will fall each year and approximately 10% will sustain a significant injury.13 The reasons for falls are multifactorial: oversedation with drugs, orthostatic hypotension, impaired gait or balance, poor eyesight and hearing, neurological problems, arthritis, sarcopenia (age-related loss of muscle mass), and environmental hazards such as slippery floors or uneven ground. Elderly individuals tend to fall sideways or backward in a manner that applies a load in a direction very different from the usual load-bearing axis of the involved bone. Because of the anisotropy of bone microarchitecture, a bone is more susceptible to fracture when the impact is in such a direction. Thus, the load of a person's own weight can lead to a femoral neck fracture in a sideways fall.
How Can Bone Fractures Be Predicted?
Experts in osteoporosis are highly cognizant of the limitations of using BMD for the prediction of fracture risk. For example, epidemiological studies have shown that for a given BMD T score (eg, T score of -2.5), a 50-year-old woman has a much lower fracture risk than an 80-year-old woman.14 Also, an individual with a history of fragility fracture after the age of 45 years has a higher risk of a bone fracture than an individual without such a history, all other factors such as age and T score being equal.15 In response to these limitations, WHO and other organizations recently have recommended using an individual's 10-year fracture risk to guide therapy decisions,16-18 a concept similar to the Framingham cardiovascular risk assessment. The risk calculation algorithm FRAX has been derived from large prospective cohort studies conducted around the world and takes into account clinical risk factors for fractures.19
Although this long-awaited WHO instrument is a substantial improvement over using BMD as the sole criterion for initiating therapy, it still has limitations. Few large prospective cohort studies that have identified risk factors for osteoporosis and fractures examined muscle strength, sarcopenia, gait, balance, history of falls, and other risk factors for falls in methodologically rigorous ways. As a result, these important factors are not included in the WHO model. In addition, the model is only applicable to treatment-naive patients and cannot be used for patients who are already undergoing therapy.
How Can Bone Fractures Be Prevented?
Bisphosphonates, in addition to calcium and vitamin D, are the current mainstay of osteoporosis therapies and have been shown to increase BMD and decrease fractures and mortality.20-21 However, in 2 well-designed randomized controlled trials in which elderly individuals were enrolled on the basis of being at increased risk of hip fracture because of factors other than low BMD, treatment with bisphosphonates did not decrease the risk of hip fractures, the primary outcome in these studies.22-23 These 2 large negative drug trials should serve as a cautionary note that current drug therapies may not address non-BMD related determinants of fracture risk. Thus, bisphosphonates may not be the most effective therapy for at least some individuals at increased risk of fractures. For these persons, interventions directed at other determinants of fracture risk, such as tai chi exercises to improve balance and muscle strength, may have a greater benefit.
In the effort to prevent fractures, does attention focus too heavily on BMD to the exclusion of other vital factors? Just as hypercholesterolemia is but one of many risk factors for coronary artery disease, low BMD is one of a number of risk factors for osteoporotic fractures. Reasons that some osteoporotic patients sustain fractures and others do not must be examined. To advance the field of osteoporosis and fractures to the next level, the current paradigm must be broadened to include the study of how muscle, nerves, and bone work together as a unit for coordination, mobility, balance, and strength. Other properties that determine bone strength besides BMD and bone size must be investigated. Assessing the risk of falls using orthostatic blood pressure measurements and validated tools, such as the timed up-and-go, functional reach, and physiological profile assessment tests, should be a routine component of assessing fracture risk.24 Exercise training and multifactorial intervention to maintain muscle strength, gait, balance, and function should be used more often in the clinical setting, and more research is needed in this area. Drug development efforts should be broadened to include drugs that can halt or slow the development of sarcopenia.
Engineering and kinesiology colleagues should be included in understanding the role of muscle function, balance, and sarcopenia in determining fracture risk. In the clinical arena, fracture prevention needs to move beyond the realm of endocrinologists and rheumatologists to include neurologists, physiatrists, physiotherapists, engineers, and muscle activation therapists. The system is only as strong as its weakest link; at times the weakest link is BMD, but often other factors require attention to avert a fracture. Like investigators for I-35W seeking to prevent the collapse of another bridge, the focus should not be solely on the density of the steel; all links in the chain that determine the integrity of the structure as a whole must be examined.
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