As Men Live Longer, Osteoporosis Looms Larger

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Of the more than 10 million Americans age 50 and older estimated to have osteoporosis, approximately two million are men.

And an additional 16 million have low bone mass, putting them at increased risk for osteoporosis and fragility fractures. The lifetime risk for osteoporotic fracture in men is estimated to be 13-25%. As in women, the most common site of fracture is the spine, but each year about 80,000 U.S. men break a hip.

Yet a general misperception persists, even among some clinicians, that as heart disease is to women, so osteoporosis is to men -- that is, a condition primarily affecting one sex and therefore underdiagnosed and undertreated in the other.

"Women have cardiovascular events about 10 years later than men but do worse after a CV [cardiovascular] event. Men have bone events 10 years later than women but do worse after bone-related events," said Robert A. Adler, MD, of Hunter Holmes McGuire Veterans Affairs Medical Center-Richmond in Virginia. Similarly, while information about heart disease is based largely on studies in men, information on osteoporosis is based on studies in women, so the evidence and research database is much smaller for osteoporosis in men than in women.

"Most of the risk factors in men and women are similar, with the exception of menopause in women and hypogonadism in men, and both sexes experience age-related bone loss," said Eric S. Orwoll, MD, of Oregon Health & Science University in Portland.

He added that generally speaking, the cycle of bone formation and resorption is similar over the years in both sexes, but one major difference, of course, is that men do not experience menopause with its dramatic drop in estrogen at around age 50. "Over time, testosterone and estrogen also decrease in men, but the decline is much more gradual, and therefore the marked increase in osteoclastic activity and more abrupt bone loss experienced by women around age 50 starts later in men. On imaging, osteoporosis looks similar in both sexes, although men have more bone to begin with."

Despite men having a higher peak bone mass, markers of bone turnover are similar in both sexes, and both have an increase in markers with age, Orwoll added.

Causes

As men age, however, the natural decline in testosterone and the reduced conversion of testosterone to estrogen are the most common drivers of osteopenia and osteoporosis. Yet men are far less likely to be screened for bone density as they enter these vulnerable years.

Other predisposing variables in men are the same as identified in women, including family history; prior fracture; use of glucocorticosteroids or other drugs; and having rheumatoid arthritis, cancer, or endocrine, kidney, or gastrointestinal diseases. Antiandrogen drugs for prostate cancer are a sex-specific risk factor but are analogous to endocrine therapy for breast cancer in women. Adverse lifestyle variables such as excess alcohol, smoking, poor diet, and being sedentary or having to be immobile also raise susceptibility.

Furthermore, some men may be more resistant to accepting the fact they are a risk for a "ladies' disease," said Adler. "All the ads about osteoporosis are aimed at women, and men may think they are not at risk."

Again, sex-specific data are lacking, but Orwoll said that in his clinical experience, once men are definitively diagnosed with osteoporosis, they accept their condition -- despite being less aware of their risk and need for screening.

Increased Morbidity and Mortality

Older men who sustain a hip fracture have an approximately 37% chance of dying within a year, which is twice the risk of death faced by women after a hip fracture. "We don't deal with many diseases with such a high mortality rate," Adler said.

Moreover, male postoperative morbidity is greater. After a hip fracture more than 50% of men will never regain the same level of independence, and they have a greater chance than women of having to enter long-term care -- mostly due to the higher prevalence of co-morbidities in men who have a hip fracture.

One study found that men suffering hip fracture were more likely to be living with a partner than women and were more affected in terms of activities of daily living. Men were sicker, as evidenced by a higher American Society of Anesthesiologists rating of preoperative risk.

In addition to their greater mortality, men were also more likely to sustain a postoperative medical complication.

Medications

About a quarter of women with osteoporosis never fill their prescriptions for medications, said Adler, adding that the rate is likely to be at least as high in men, although no data are available.

Apart from gender-specific testosterone or estrogen therapy, both sexes are prescribed the same non-hormonal treatments, and there are many effective options.

Both sexes appear to respond equally well to drug therapy, although there are no head-to-head trials comparing the responses of men and women, Adler explained. Of note, medications approved for use in treating osteoporosis in men are generally based on studies demonstrating improvement in bone density, whereas the approval for women requires proof that fractures are reduced.

But in one of the rare studies in men, an international randomized controlled trial showed that over the course of 24 months, two annual infusions of the antiresorptive zoledronic acid significantly reduced the risk of new morphometric vertebral fractures by 67% among men with osteoporosis.

This reduction was similar to that reported elsewhere in postmenopausal women with osteoporosis who received zoledronic acid (relative risk reduction 71% at 2 years), suggesting that the anti-fracture effect of zoledronic acid is independent of sex -- which is likely to be true of other osteoporosis medications.

Attitudes

Are men less likely to follow a calcium-rich, bone-friendly diet and take bone-supporting calcium and vitamin D supplements? "Again, we have no data, but that may well be the case, as all the ads on TV and in magazines about osteoporosis are aimed at women," Adler said. "The common impression is that men are less health conscious, including about osteoporosis," added Orwoll.

Absent firm data, a small interview-based study documented male osteoporosis patients' dissatisfaction with drug side effects, the high costs of the medication, and the limited data on long-term safety or efficacy in men. Adverse gastrointestinal effects with bisphosphonates led some to discontinue their use or to seek alternatives. A few patients in the study said they had pursued adjunctive therapies, such as chiropractic, massage, or physical therapy for pain relief or to restore function after an injury.

Most participants reported taking daily calcium supplements, but few described making any dietary changes to increase calcium intake from food, and none took vitamin D. Despite not linking the lack of exercise to osteoporosis, almost all interviewees reported participating in some exercise such as walking, jogging, swimming, or stretching in order to maintain range of motion and flexibility.

Screening and Treatment

Screening for osteoporosis is not routine in men, and in any case can be difficult for some to access bone mineral density dual-energy x-ray absorptiometry (DXA), since Medicare covers this for men only in limited circumstances. There is not consensus amongst (U.S.) guidelines around routine screening for osteoporosis in men.

Moreover, men are also less likely to receive treatment following a low-trauma fracture, which increases their risk of sustaining subsequent bone breakage. Even after a high-trauma fracture of the hip, treatment rates for osteoporosis remain low.

Although osteoporosis in men remains underdiagnosed, newer strategies for determining which men need bone density assessment are emerging. "Observational studies are providing insights that allow targeted testing and treatment of those men at the highest risk for fracture," Adler said. Nonetheless, the fear of treatment side effects for a disorder that is asymptomatic before fracture and other barriers is slowing the pace of advancement.

The gender gap in awareness persists: "I've been struggling for some years to get the message across that men are also at risk for osteoporosis," said Adler. "Hopefully, the fact that the mortality risk for men is twice that for women after hip fracture will ring a bell with some."

Points to Remember

• By age 70, all men should be screened with DXA to evaluate bone density, which is the amount of bone mineral divided by the area of the bone scanned. Screening is especially important for men 80 and older. Guidelines vary on this.

• Screening should also be done in younger men who have established risk factors, including delayed puberty, hypogonadism, history of fractures, and lengthy use of glucocorticoids.

• Since osteoporosis in men is more often due to non-idiopathic factors, secondary causes such as diabetes, cancer, digestive diseases, and inflammatory conditions such as rheumatoid arthritis and inflammatory bowel disease should be ruled out.

• Men with low bone mass or low-trauma bone breakage should have comprehensive lab tests for blood count, 25-hydroxy vitamin D, and testosterone levels, as well as urinary calcium excretion.

Read previous installments in this series:

Part 1: New Insights Into the Complex Biology of Osteoporosis

Part 2: The Latest on Osteoporosis Treatment and Diagnosis

Part 3: Osteoporotic Fragility Fractures

Part 4: Case Study: First-Time Mom's Severe Low Back Pain After Breastfeeding