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Male Osteoporosis and Hormones

– Is low testosterone tied to diminished bone health in men?


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Expert Critique

FROM THE ASCO Reading Room
Afreen Shariff, MD
Afreen Shariff, MD Assistant Professor of Medicine Duke University Hospital, Division of Endocrinology, Diabetes and Metabolism
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Declines in estrogen correlate with bone loss in women, and a similar relationship may exist in men as testosterone levels drop with age.

The science is far from settled, but researchers are starting to understand the problem and what to do about it. The goal is to reduce the risk of fracture, which often is associated with worse outcomes for men than women.

"Osteoporosis secondary to other medical conditions is more common [in men than in women]," said Nancy Lane, MD, director of the UC Davis Center for Healthy Aging. "Therefore, when men do develop osteoporosis, it is important to check for other medical conditions, such as hypogonadism or alcohol-related bone disease."

How Common Is It?

The Osteoporotic Fractures in Men Study (MrOS), of which Lane was a chief investigator, set out to study male osteoporosis in the late 1990s, enrolling more than 11,000 men from the U.S., Sweden, and Hong Kong. MrOS found a baseline prevalence in men of 2% to 7%, depending on the measurement used: 2% using a female-specific World Health Organization osteoporosis score and 7% using a male-specific National Osteoporosis Foundation score.

A recent review by Terra Arnason, MD, PhD, of the University of Saskatchewan in Canada, and colleagues, found a prevalence of about 2% in men ages 60 to 70; 4% in those ages 71 to 80; just over 10% in those ages 81 to 90; and jumping to 23% in men over 90.

According to the National Institutes of Health, osteoporosis in men is primarily age-related, but frequently is secondary to other causes, including exposure to glucocorticoid medications, smoking, alcohol, gastrointestinal disease -- and hypogonadism or age-related testosterone decline.

Just how much of male osteoporosis is attributable to waning testosterone levels?

"It's difficult to answer how often testosterone compares to other causes of osteoporosis in men because there has been limited investigation of testosterone deficiency as a cause," said Abraham Morgentaler, MD, director of Men's Health Boston, affiliated with Harvard and Beth Israel Deaconess Medical Center. "However, there is strongly suggestive evidence that testosterone deficiency is a major driver of reduced bone mass."

The mechanisms by which age-related testosterone decline affects bone health aren't clear, but there are several possibilities, according to Arnason's review. Androgen receptors have been found on all types of bone cells, so testosterone levels could play a direct role in bone formation. Also, testosterone is converted to estrogen via aromatase; with less testosterone to convert, some men also may make less estrogen, and estrogen plays a key role in healthy bone metabolism. That's why women are affected by osteoporosis to a greater extent as they age: the estrogen drop-off brought on by menopause is a detriment to bone health.

Fear of Fracture

Although the prevalence of osteoporosis among men is lower than that among women, the consequences of male osteoporosis are significant.

The morbidity and mortality associated with male hip fractures are worse than that among women, and men with known fragility fractures are less likely to receive treatment for bone disease compared with women, according to Arnason's review. She and colleagues noted that testosterone's role in muscle strength and physical performance could be linked directly to fracture risk, as increased muscle weakness could predispose men to a higher rate of falls, potentially leading to fracture.

Since osteoporosis is regarded as a women's disease, there's little early warning in men, and the condition usually is brought to a doctor's attention when the patient has a fracture.

That's raised questions as to whether there's a need for screening and earlier diagnosis.

Screening in Men

The United States Preventive Services Task Force (USPSTF) doesn't recommend screening for osteoporosis in men, citing insufficient evidence to assess the risks and benefits. However, the Endocrine Society recommends that all men age 70 and up, as well as those ages 50-69 with risk factors, including prior fracture, smoking, and hypogonadism, have their bone mineral density checked with dual-energy x-ray absorptiometry (DXA) scans.

Lane said it's generally a good idea to assess men's bone health at age 70, about 5-10 years after that of women. Doctors could check height loss and fracture history at least, which can be followed with bone density testing: "A low bone mass finding in men should then be followed by a work-up for secondary causes of osteoporosis," she said.

Given that hypogonadism is one of those secondary causes, Morgentaler follows the Endocrine Society guidelines and keeps a close eye on the bone health of men already diagnosed with this condition. "I believe men with testosterone deficiency should routinely undergo bone density testing," he said.

How and When to Treat

Almost all current medications used to treat osteoporosis or osteopenia in women have demonstrated similar efficacy in men, Lane noted. That includes bisphosphonates like alendronate (Fosamax), risedronate (Actonel), and zoledronic acid (Reclast), as well as the recombinant parathyroid hormone therapy teriparatide (Forteo) and the monoclonal antibody denosumab (Prolia).

In addition to adequate calcium and vitamin D intake, further drug treatment depends on the severity of the disease. For a man with osteoporosis without fractures, an anti-resorptive agent such as a bisphosphonate or denosumab is appropriate, Lane said. If he has osteoporosis and a history of fractures, "it might be best to start with an anabolic agent, like a parathyroid compound, and then after 1.5 to 2 years of treatment switch to an anti-resorptive agent," she added.

Although the use of testosterone to treat what may be normal age-related hormonal changes has been controversial, especially given questions about the risk of heart attack with testosterone therapy, some experts say testosterone replacement may help protect bone health.

The Endocrine Society guidelines recommend testosterone therapy "in lieu of a 'bone drug'" for men at "borderline" high risk for fracture who have serum testosterone levels consistently below 200 ng/dl along with symptoms of androgen deficiency, or "organic" hypogonadism.

"In my practice, we routinely offer testosterone therapy to men with osteopenia who are testosterone-deficient," Morgentaler said.

"For men with osteoporosis, we generally will refer to a specialist in bone metabolism since there may be multiple contributing causes, but will also recommend testosterone therapy if they are deficient."