Supplements Fracture Prevention in Osteoporosis
Importance of Early Diagnosis and Treatment of Osteoporosis to Prevent Fractures
Osteoporosis affects about 10 million individuals in the United States, a number that is expected to increase substantially in coming decades as the elderly population burgeons. The chief debilitating consequence of osteoporosis, fracture, will affect about half the women and a third of the men in their lifetime, posing a daunting challenge to managed healthcare systems in terms of delivering optimal care and restraining cost. By encouraging optimal postfracture follow-up care and identifying those members at higher risk for fracture and in need of prompt treatment, managed care organizations can enhance the cost-effective management of osteoporosis, dampening downstream costs. This manuscript reviews the pathophysiology of osteoporosis, examines issues related to the diagnosis of osteoporosis, especially the role of bone mineral density measurement, and focuses on the impact of various treatment options in reducing fracture risk. Early assessment and treatment emerge as medically prudent steps in reducing the risk for osteoporosis-related fracture.
(Am J Manag Care. 2006;12:S181-S190)
A major and growing public health concern, osteoporosis substantially increases the risk for fracture, and, in turn, early disability and mortality. The National Osteoporosis Foundation estimates that, in the United States, 10 million individuals, 80% of whom are women, already have osteoporosis, with an additional 34 million individuals at risk because of low bone mass.1 The prevalence of low bone density increases dramatically with age, affecting 37% of women between the ages of 50 and 59 years, 50% between the ages of 60 and 69 years, 75% between 70 and 79 years, and 87% of women over age 80.2 In 2001, 27% of women and 5% of men receiving Medicare had been diagnosed with osteoporosis.3
Osteoporosis is responsible for more than 1.5 million fractures annually–700 000 vertebral and 850 000 nonvertebral, including 300 000 hip fractures.4 In their lifetime, 30% to 50% of women and 15% to 30% of men will incur an osteoporosis-related fracture.5 For healthcare systems, osteoporosis-related fractures will become an increasingly important driver of healthcare costs over the coming decades. Currently, the annual estimated direct cost for the treatment of osteoporotic fracture ($10 billion-$18 billion) is at least comparable with Medicare expenditures for coronary heart disease ($10.6 billion).1,6,7 By 2020, healthcare spending for osteoporosis-related fractures is anticipated to at least double, ranging from $31 billion to $62 billion.8
Although all osteoporosis-related fractures are debilitating, vertebral and hip fractures exert especially profound effects, increasing mortality risks and diminishing quality of life.9 Individuals with a hip or vertebral fracture experience a 20% excess risk for mortality 5 years after the fracture, with most of the excess mortality occurring within the first 6 months.4 Moreover, the consequences of an osteoporosis-related fracture can be devastating to the individual's quality of life. For example, 1 year after a hip fracture, 40% of patients are unable to walk independently and 80% are restricted in some activity of daily living, including driving and shopping.4 Disconcertingly, 27% of post-hip fracture patients enter a nursing home facility for the first time.
The chief goal of osteoporosis management is to prevent fractures. An understanding of the pathophysiology of osteoporosis provides a foundation that appreciates the role of different therapeutic options in the management of this disorder.
Structurally, bone can be divided into 2 types: cortical bone, the compact and durable outer layer, and trabecular bone, a more delicate interconnected interior latticework. Because trabecular bone displays a greater surface area and is more metabolically active than cortical bone, it is more susceptible to bone loss.10
Osteoporosis is a skeletal disorder characterized by bone loss, low bone mass, and structural degradation of bone tissue, especially trabecular bone, yielding attenuated bone strength that, in turn, increases the risk of fracture.6 Bone strength reflects not only changes in bone density, but also in bone quality–which encompasses bone architecture, the presence or absence of microfractures, mineralization, and bone turnover.6
Bone is not inert; instead, it teems with metabolic activity throughout life. After the cessation of linear growth, bone remodeling or turnover–a repeated 120-day cycle of bone resorption including or involving 10 days by cells called osteoclasts followed by 3 months of formation of new bone by cells called osteoblasts–continues through adulthood, maintaining skeletal homeostasis, providing bone elasticity, repairing stress microfractures and producing a steady source of extracellular calcium.11
In osteoporosis, bone resorption exceeds bone formation, thus leading to bone loss and increasing skeletal fragility.11 The bone turnover process results in the release of several key biochemical markers found in either the serum or the urine that reflect either bone formation or resorption (Table 1).
Although bone markers reflect bone turnover rates, they are not diagnostic of osteoporosis. However, they may play a role in assessing patients before and during pharmacologic therapy. Thus far, they have not been incorporated into routine clinical practice.10
Risk Factors for Osteoporosis and Osteoporosis-related Fracture
Myriad factors have been linked to the development of osteoporosis (Table 2).1
Once a fracture occurs, the risk for a subsequent fracture increases 2- to 5-fold.12,13 Both vertebral and nonvertebral fractures increase the risk of a subsequent fracture. Generally, prior fracture, low bone mineral density (BMD), advancing age, female sex, and slender body frame are established risk factors for osteoporosis-related fractures.14 In addition, the absolute risk for fracture differs notably among ethnic groups. Asian-American women, although manifesting BMD measurements similar to that of white women, have only 32% the adjusted relative risk for fracture.15 Although the reasons for these ethnic variations are not fully understood, several mechanisms have been proposed, including differences in body mass index (higher in blacks), bone architecture, genetic variations (BMD is highly heritable as a polygenetic trait), and environmental and behavioral influences.15
The clinical evaluation of the skeletal system includes a medical history, physical examination, laboratory testing, and, if appropriate, BMD testing.
Physical Examination and History. The presence of 1 or more risk factors–older age, previous fracture, low body weight, smoker, menopause, low BMD, family history of osteoporosis, hypogonadism in males, exposure to glucocorticoids–increase the risk of osteoporosis.8 The use of glucocorticoids is the most common cause of secondary osteoporosis, especially long-term use of glucocorticoids for disorders such as rheumatoid arthritis and long-term obstructive pulmonary disease.8 In fact, the risk for excessive bone loss is dramatically increased for any patient receiving orally administered glucocorticoids at a dose equivalent to prednisone 5 mg/day or more for at least 2 months.6
Further, the physical examination provides an ideal opportunity to detect manifestations of osteoporosis or vertebral fracture. For instance, height loss can be measured clinically over time. A loss of 4 cm or more would be suggestive of vertebral compression fractures. Moreover, thoracic kyphosis, or "dowager's hump," can indicate the presence of anterior wedge fractures in the thoracic spine.8
Biochemical Testing. Several biochemical assessments can be used to exclude secondary causes of osteoporosis (Table 3).
For instance, urinary markers indicative of bone resorption can detect changes in the bone remodeling process triggered by hyperparathyroidism, hyperthyroidism, and Cushing's syndrome.11 Generally, routine laboratory studies are normal in patients with osteoporosis. However, to rule out the possibility of secondary osteoporosis, certain tests should be obtained, including a blood chemistry profile, complete blood count and serum 25-OHD, and thyroid-stimulating hormone levels. Nonroutine or specialized tests may be obtained based on information gleaned from history, examination, or the routine tests already noted.15
Bone Strength and Density. Currently, there is no accurate measure of overall bone strength.6 BMD, a frequently used proxy measurement, accounts for about 70% of bone strength. Operationally, the World Health Organization defines osteoporosis as a T-score–the number of standard deviations above or below the mean BMD for young white adult women–of -2.5 (Figure 1). Zscore assessments, in contrast, compare patients' BMD with age, sex, and racematched controls.
Ordinary radiographs do not display sufficient sensitivity to diagnose osteoporosis until total BMD has declined by 50%.15 Consequently, dual-energy x-ray absorptiometry (DXA) has become the most widely used technique for assessing BMD. Because of its precision, central DXA testing has emerged as the diagnostic measure of choice. Peripheral DXA scans of the distal forearm and the middle phalanx have become available and are less expensive than central DXA testing, but the value of these measurements in predicting fracture remains unclear. Central DXA measurements of the spine and hip have the best predictive value for fracture and follow-up monitoring. Quantitative ultrasound has shown promise as a diagnostic tool in osteoporosis but not for follow-up monitoring. Early clinical findings indicate that quantitative ultrasound of the heel can predict hip fracture and nonvertebral fracture almost as well as a DXA at the femoral neck.6
Candidates for BMD Testing. There is a consensus that BMD measurements should be considered in patients who have an increased risk for osteoporosis and in all women aged 65 and older.1,6 The value of universal screening, particularly in perimenopausal women, has not been established.6 During the perimenopausal period, a large number of women would need to be evaluated and treated to prevent a single fracture. For example, in white women between the ages of 50 and 59 years, an estimated 750 BMD tests would be needed to prevent just 1 hip or vertebral fracture over a 5-year period of treatment.6 The National Institutes of Health Consensus Panel suggests an individualized approach to treatment in perimenopausal women until solid evidence of the cost-effectiveness of routine BMD screening emerges.
Medicare reimburses BMD testing every 2 years, with exceptions, which reimburse yearly, for the following patient groups16:
- Estrogen-deficient women at clinical risk for osteoporosis
- Individuals with vertebral abnormalities or osteopenia as demonstrated by x-ray film to be indicative of osteoporosis, low bone mass, or vertebral fracture
- Individuals receiving long-term glucocorticoid (steroid) therapy (yearly)
- Individuals with primary hyperparathyroidism (yearly)
- Individuals being monitored to assess the response to or efficacy of a US Food and Drug Administration (FDA)-approved osteoporosis drug therapy
BMD and Fracture Risk: An Imperfect Relationship