Traditionally, osteoporosis has been considered a disease of elderly white women; however, as understanding of the pathophysiology of the disease increases, we are beginning to appreciate that women of other racial and ethnic heritages and men are also at substantial risk. This article will focus on the risk to men.

The National Osteoporosis Foundation (NOF) currently estimates that 2.3 million men have osteoporosis and another 11.8 million have low bone mass (NOF, 2002). In comparison, the NOF estimates that 7.8 million women have osteoporosis, and an additional 21.8 million have low bone mass. With life expectancy increasing for both men and women, the NOF predicts that by 2020, approximately 40 million women and 20.5 million men will have low bone mass or osteoporosis (NOF, 2002) (Figure).

At present, the lifetime risk of hip, forearm or clinically diagnosed vertebral fracture for a man aged 50 years or older is 13% (Melton et al., 1992). (In comparison, this probability is 40% for a woman of the same age.) Because of changing demographics and secular increases in fracture, the annual incidence of osteoporotic fractures will also increase (Eastell et al., 1998; Seeman, 1997). Hip fracture incidence in the United States is expected to triple by 2050; worldwide, it will quadruple (Melton, 1993; Riggs et al., 1995). At present, men sustain about 25% of all hip fractures in the United States (Ray et al., 1997); it is estimated that by 2050, approximately 200,000 hip fractures will occur annually among men in the United States and approximately 1.8 million hip fractures in men will occur worldwide (Cooper et al., 1992). Twenty percent of the current annual expenditure of $21.7 billion for treatment of osteoporotic fractures is attributable to fractures in men (Ray et al., 1997); this will increase proportionately as fracture incidence increases.

Mortality after hip fracture is disproportionately higher in men than in women. Regardless of duration of follow-up, men are at least twice as likely to die (Cooper, 1997; Eastell et al., 1998; Ray et al., 1997), and this gender disparity is not explained by differences in age, comorbid conditions, functional limitations prior to fracture or surgical complications. Excess mortality in men after other major fractures (pelvis, distal femur, proximal humerus, proximal tibia and multiple rib) has also been reported (Center et al., 1999). No excess mortality has been reported in association with prevalent vertebral fracture (Ismail et al., 1998).

In combination, these elements (the current and future prevalence of low bone mass and osteoporosis; the current and future incidence of osteoporotic fracture; and the personal, social and economic cost of fracture) emphasize the relevance of this disease burden in men and underscore the importance of both identifying men at risk and implementing definitive management strategies.

Approximately 60% to 85% of hip fractures, 40% to 45% of wrist fractures, and 70% to 90% of vertebral fractures in men are estimated to result from low bone density or osteoporosis (Melton et al., 1997). Direct measurement of bone mineral density (BMD) is necessary to accurately diagnose osteoporosis and low bone mass. Standardized, published criteria for defining at-risk groups of men do not exist at present. The threshold of 2.5 standard deviations (SD) below young adult normal BMD for diagnosis of osteoporosis in women, according to World Health Organization (WHO) criteria, is an empiric choice that was based on the lifetime risk of fracture in women relative to the distribution of BMD measured at the hip or forearm (WHO Study Group, 1994). Because data regarding the relationship between BMD and fracture risk in men are limited and because men have larger bones (and, therefore, greater areal BMD than women), there has been some uncertainty about the appropriate diagnostic criterion in men. Recent reports suggest that the appropriate threshold for diagnosis of osteoporosis in men is 2.5 SD below the young adult normal male average (Melton, 2001; Melton et al., 2001, 2000, 1998), and that BMD predicts fracture risk in men as it does in women (Melton et al., 1998). The currently accepted gold standard measure is dual energy X-ray absorptiometry (DEXA) of the hip and spine (NOF, 1998), but some evidence suggests that measurement of the wrist may have better predictive value in men (Melton et al., 1998).

Both cross-sectional and longitudinal studies have shown that, in men, BMD declines with age at an average rate of less than 1% per year at the hip, spine and other sites (Burger et al., 1994; Davis et al., 1991; Jones et al., 1994; Melton et al., 1998). Because men do not experience a period of rapid bone loss such as that seen in women during the several years immediately following menopause and because the rate of loss may be slower in men (Burger et al., 1994), age-related osteoporosis is less common in men than in women. As a consequence, 70% to 80% of osteoporosis in men is estimated to be secondary to other conditions or medications (Compston, 2001; Eastell et al., 1998; Orwoll and Klein, 1995). (Risk factors for osteoporosis in men are listed in Table 1.) Although these risk factors alone cannot suffice to diagnose osteoporosis, they help guide identification of men at risk and are useful in counseling patients about lifestyle modification.

Men who are older than 65 years of age, who present with a history of low-trauma fracture, who have any of the medical conditions or use the medications shown in Table 1, and who have radiographic evidence of bone loss or vertebral compression should have BMD testing (Eastell et al., 1998; Orwoll and Klein, 1995). Additional laboratory testing may be used to rule out secondary causes, including serum calcium, serum creatinine, alkaline phosphatase, serum phosphorus, liver functions, serum testosterone, serum thyroid stimulating hormone, serum 25-hydroxyvitamin D, complete blood count and serum protein electrophoresis (Eastell et al., 1998; Orwoll and Klein, 1995). In rare instances, bone biopsy may be indicated (Eastell et al., 1998; Orwoll and Klein, 1995). Steps in the evaluation of fracture risk in men are shown in Table 2.

Modifiable risk factors, including smoking, inadequate calcium and/or vitamin D, excessive alcohol intake, and inadequate exercise, should be addressed. Current guidelines recommend 1200 mg/day of calcium; 400 international units (IU) of vitamin D are recommended until age 70 and 600 IU thereafter (Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, 1997). Because most fractures occur as a result of falls, attention should also be paid to minimizing risk factors for falling.

Analogous to the 1998 NOF recommendations for women, definitive pharmacologic treatment should be offered to men whose T-scores are ≤-2.0 or to men who have risk factors and whose T-scores are ≤-1.5. At present, therapeutic options for men are limited. Testosterone replacement has been shown to increase BMD in hypogonadal men (Katznelson, 1998; Katznelson et al., 1996; Snyder et al., 1999). Current guidelines for prevention and treatment of glucocorticoid-induced osteoporosis recommend use of bisphosphonates (alendronate [Fosamax] 10 mg daily or risedronate [Actonel] 5 mg daily) (American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis, 2001). At present, only alendronate is indicated for treatment of idiopathic osteoporosis in men, and it may be given either as 10 mg/day or 70 mg/week.

In summary, men are at risk of osteoporosis and fragility fracture. The consequences of hip fracture in men are worse than in women, and the incidence of this and other fractures is anticipated to increase markedly over the next several decades. As a consequence, the disease burden of osteoporosis will continue to increase in the absence of definitive intervention. Approximately 20% to 30% of osteoporosis in men is believed to be idiopathic; the remaining 70% to 80% is secondary to other conditions or medications. Assessment of risk factors can aid in identification of men at risk, but definitive diagnosis depends on the measurement of BMD. Bone mineral density testing should be offered to men with these risk factors, to men who present with a low-trauma fracture, and to men with other evidence of reduced bone mass or vertebral compression. Counseling about modification of lifestyle to reduce risk factors such as smoking, nutrition, exercise and fall prevention should be given to all men at risk. Pharmacologic therapy should be considered for men with low BMD (T-score ≤-1.5) and risk factors and for men with osteoporosis (T-score ≤-2.0).

Dr. Wehren has practiced obstetrics and gynecology for almost 20 years. She is currently working toward a Ph.D. in epidemiology at University of Maryland School of Medicine, and her research focus is osteoporosis and hip fracture outcomes in men and women.

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Osteoporosis Increases Mortality Risk in Men