“What do you mean I should be tested for osteoporosis? Isn’t that a woman’s disease?!” your patient asks incredulously. But he really gets upset when you send him to the women’s health center to get a bone scan.
This scenario could play out often in coming years if physicians heed a recommendation of a new Endocrine Society clinical guideline: All men age 70 and over should have a bone mineral density (BMD) test to check for osteoporosis.
Make no bones about it, osteoporosis is a serious problem for older men.
“Based on low bone density, there are about 10 million Americans with osteoporosis, and about 20 percent of those are men,” said Nelson Watts, M.D., who chaired the guideline committee. Watts is director of Mercy Health Osteoporosis and Bone Health Services in Cincinnati. “Of the two million fractures each year due to osteoporosis, about 600,000 are in men.”
Perhaps because their bone loss lacks the accelerator of menopause and their larger stature endows them with greater strength than women, men’s bones typically become brittle a decade later than women’s. The medical problems that increase with aging may also explain why mortality after a hip fracture is two to three times higher in men than in women.
The aging population, with more men living long enough to develop weakness in their bones, highlights the need for “Osteoporosis in Men: An Endocrine Society Clinical Practice Guideline,” which was published in the June issue of The Journal of Clinical Endocrinology & Metabolism.
In addition to those over 70, the guideline says that men age 50–69 should be tested if they have other risk factors, the most important of these being a history of fracture after age 50. Additional reasons for testing men in this age range include diseases and conditions such as delayed puberty, hypogonadism, hyperparathyroidism, hyperthyroidism, chronic obstructive pulmonary disease, long-term use of synthetic hormones, and life choices such as alcohol abuse or smoking.
The preferred test is dual-energy x-ray absorptiometry (DXA) of the spine and hip, although in cases of men who have hyperparathyroidism or are receiving androgendeprivation therapy (ADT) for prostate cancer, the guideline suggests measuring the forearm DXA. In both instances, the evidence indicates that the forearm is a better indicator of the patient’s osteoporosis risk.
The guideline recommends that men being evaluated for osteoporosis receive a complete physical examination, including history. Laboratory tests should include serum calcium, phosphate, creatinine, alkaline phosphatase, liver function, 25-hydroxyvitamin D (25[OH]D), total testosterone, complete blood count, and 24-hour urinary calcium.
These lab results, the history, and physical examination may indicate the need for further testing, such as thyroid function tests, to home in on speciﬁc causes.
Who Needs Treatment
The question of which male patients should be treated with drugs is controversial among doctors and other experts. Because osteoporosis is widely seen as a woman’s disease, women have been the focus of most of the studies, and there have been many large clinical trials using women to test the efﬁcacy of various drugs in reducing fractures. In contrast, the studies in men have generally been small, with change in BMD as the primary end point, so “the experts have to shift the evidence for nuggets” in their approach to treating men, Watts said.
Complicating the treatment decision is that there is no single controlling indicator, such as a T-score. “In selecting men or women for treatment, the emphasis has moved from just looking at a T-score to including other clinical risk factors such as age, prior fracture history, family history of osteoporosis, glucocorticoid use, cigarette smoking, low body weight, and the FRAX tool or other fracture risk–assessment tools that allow us to objectively put those things together and make better treatment decisions,” Watts said.
For example, a BMD T-score of –2.5 or less indicates a need for treatment but leaves out many men who might beneﬁt from treatment because most men who suffer fractures have a T-score above this level. The guideline states that “FRAX, Garvan, or other fracture risk calculators can improve the assessment of fracture risk,” but even these algorithms do not incorporate some of the known risk factors.
Given these caveats, the guideline recommends pharmacological treatment “for men age 50 or older who have had spine or hip fractures, those with T-scores of –2.5 or below, and men at high risk of fracture based on low bone mineral density and/or clinical risk factors.”
The guideline recommends that therapeutic drugs should be chosen only from the list currently approved by U.S. and European regulatory agents for general use—alendronate, risedronate, zoledronic acid, and teriparatide. Denosumab is the only drug speciﬁcally indicated for use in men receiving ADT for nonmetastatic prostate cancer.
The drug selection can be individualized based on considerations such as fracture history, T-score, co-morbid conditions, and parts of the body at highest risk. Generic alendronate is generally the ﬁrst choice because of its low cost and extensive track record. But men with upper or lower gastrointestinal problems may be better off with non-oral therapies, such as zoledronic acid and teriparatide. Some drugs appear to target certain areas. For example, men with a recent hip fracture may beneﬁt from zoledronic acid.
Although some osteoporosis medications have received negative coverage in the lay press, in general they are well tolerated, safe with long-term use, and effective at reducing fracture risk, Watts said.
The Role of Testosterone
Another controversial area in bone health concerns the role of testosterone. “Because testosterone and estradiol levels decline as men age, it has been suggested that this decline may be responsible, at least in part, for the decrease in BMD that occurs in aging men,” the guideline notes. “Skeletal health may be compromised when serum testosterone levels fall below 200–250 ng/ dL.” For example, one study found that baseline testosterone levels below 200 ng/dL tripled the odds of having osteoporosis at the hip and rapid hip bone loss compared with levels above 200 ng/dL.
Managing hypogonadism and low BMD with a single agent is a possibility, and the guideline, therefore, recommends that some patients try testosterone therapy alone before going on a bone drug. Because the beneﬁts and risks of testosterone therapy are not well established, the committee recommends using a “conservative level” of 200 mg/mL as the cut-off for intervention pending the availability of more data. For men with a borderline high risk for fracture, low testosterone, and symptoms of androgen deﬁciency or a known cause of androgen deﬁciency such as a pituitary disorder, the guideline suggests trying testosterone therapy three to six months to see if it alleviates the symptoms.
Testosterone therapy can also be tried in patients who have a high risk of fracture and low testosterone levels but contraindications for osteoporosis drugs. For patients already receiving testosterone therapy who are at high risk of fracture, the guideline suggests adding an agent with proven antifracture efﬁcacy, such as bisphosphonate or teriparatide.
Monitor BMD with Scans
Once a patient is on a drug, the guideline suggests monitoring BMD by DXA at the spine and hip every year or two to assess the response to treatment. If the patient’s BMD appears to reach a plateau, this frequency can be reduced. Physicians should also consider measuring a bone turnover marker three to six months after the start of treatment using a bone resorption marker for antiresorbtive therapy and a bone formation marker for anabolic therapy.
“There is uncertainty over what constitutes an adequate BMD response to treatment. Stable or increasing BMD appears to indicate a good response,” the guideline states. The drugs increase BMD modestly. For example, one study found that two years of alendronate increased BMD of the spine by 7 percent and the femoral neck by 2.5 percent. That response at least reverses the trend of loss.
As with all Endocrine Society clinical guidelines, the committee included members with a wide range of expertise and experience. Their work included a meta-analysis of the literature and systematic discussions via email, telephone, and in-person meetings. The guideline was reviewed by Endocrine Society committees and members, and representatives of organizations such as the American Society for Bone and Mineral Research and the European Society of Endocrinology. The committee rated the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to give the reader an idea of the strength of a recommendation or suggestion.
Watts said that one source of resistance to implementation of the guideline could be men themselves, who may need to be convinced that this is not just a woman’s disease.
But an even bigger obstacle could be insurance coverage, especially when it comes to the recommendation for 70-year-old men to get their BMD tested. Medicare generally covers BMD screening for women, but it covers an initial DXA in men only if the patient has vertebral fractures, radiographic osteopenia, hyperparathyroidism, or is on long-term glucocorticoids. A route to coverage might be a spine radiograph, and if that test shows osteopenia or a vertebral fracture, a subsequent DXA would be covered by Medicare.
As more men live long enough for their bones to deteriorate—from 30 to 40 percent of fractures due to osteoporosis occur in men already—the importance of having older men tested routinely could become more apparent. “Osteoporosis in men is a signiﬁcant public health problem,” Watts concluded. “It carries with it a potentially devastating, life-changing toll in patients who have fractures. We now have a pretty good sense of men who are at sufﬁciently high risk to warrant bone density testing, and we have a number of therapeutic agents that are available to reduce fracture risk.”
The only thing left is for physicians to teach their male patients that osteoporosis is an equal opportunity disease.