Men Are Under-Screened and Under-Treated for Osteoporosis

Osteoporosis is a disease commonly encountered in orthopaedic practice, yet little progress has been made in preventive therapies for patients who are at high risk for fracture. Although osteoporotic fractures are typically thought of as affecting older women, 40 percent of fragility fractures worldwide occur in men. Men tend to fracture 5 to 10 years later than women, and the consequences of fracture among men are severe. Perioperative mortality among men following hip fracture is twice that of women (10 percent versus 5 percent), and 38 percent of men will die in the year following hip fracture compared with 28 percent of women. Peak incidence of hip fractures in men occurs between 80 to 84 years of age, so advanced age and comorbidities in men with fragility hip fractures may contribute to these differences.

Characteristics and diagnosis
There are several ways in which osteoporosis differs between men and women. Men have bigger and wider bones and tend to reach a peak bone mineral density (BMD) that is 8 to 10 percent higher than women. The increased bone size and density confer a biomechanical strength advantage. Men also lose bone in a different pattern with aging than women do; men experience a thinning of bone trabeculae, whereas women experience trabecular loss and disruption. Bone widens with age, thinning along the endosteal surface with compensatory periosteal bone apposition. Androgens support this periosteal apposition, resulting not only in wider bones but often thicker cortices in men compared with similarly aged women. Men do not experience menopause but rather a slow decline in androgen levels, unless other factors lead to hypogonadism. Secondary causes of osteoporosis are common in men and contribute to almost half of all cases. Although hypogonadism, steroids, and excess alcohol consumption are common causes, a variety of medications, endocrine disorders, gastrointestinal disorders, autoimmune diseases, and genetic conditions can also contribute to osteoporosis in men.

Although routine osteoporosis screening for men aged 70 years or older is recommended by the International Society for Clinical Densitometry (ISCD) and many other organizations, the U.S. Preventive Services Task Force does not endorse routine screening in men, citing insufficient evidence in this population. Many insurers will not cover routine screening for men without risk factors such as diabetes, hyperparathyroidism, autoimmune disease, or prior fracture. The ISCD recommends the use of the same female T-score reference database for men as for women because the fracture risk is nearly identical in men and women for a given BMD. Trabecular bone score (TBS) can be obtained during dual-energy X-ray absorptiometry (DXA) and can help assess bone quality, even though TBS itself is not used to diagnose osteoporosis. The Fracture Risk Assessment Tool (FRAX) combines risk factors with DXA measurements to calculate 10-year risk of hip fracture or any major osteoporotic fracture. The World Health Organization recognizes a T-score of -2.5, FRAX scores of 3 percent (hip fracture) and 20 percent (major osteoporotic fracture), or fragility fractures of the hip or spine as ways of diagnosing osteoporosis.

Treatment
Treatment for osteoporosis in men entails lifestyle changes. All men with osteoporosis should be counseled to stop smoking, limit alcohol intake, and engage in both resistance training and impact exercises if possible. Balance exercises are recommended at least twice weekly for adults aged 65 years or older, given the evidence for fall prevention. Secondary causes of osteoporosis in men should be treated, and calcium intake (diet and supplements) of 1,200 mg per day should be encouraged. Vitamin D levels should also be maintained in the normal range (>30 ng/ml).

There are fewer approved osteoporosis therapies for men than for women, but several effective antiresorptive and anabolic agents are available. Antiresorptive agents include bisphosphonates and denosumab. These agents decrease the activity of osteoclasts, slowing bone loss. Oral agents alendronate and risedronate are given weekly or monthly and have shown increases of 6 to 8 percent in spine BMD and 2 to 3 percent in femoral neck bone density in trials treating men with osteoporosis for 2 years. Both alendronate and risedronate also demonstrated a reduction in vertebral fractures, and risedronate also reduced nonvertebral fracture rates. A trial looking at two annual doses of zoledronic acid in almost 1,200 men demonstrated a 67 percent reduction in vertebral fractures at 2 years as well as increased BMD. A meta-analysis of 22 bisphosphonate treatment trials in men showed a significant decrease in fracture risk for men treated with bisphosphonates versus placebo in both the spine (relative risk [RR] = 0.368) and nonvertebral sites (RR = 0.604). Bisphosphonates are cleared through the kidneys and should be used with caution in patients with chronic kidney disease but are not recommended in patients with creatinine clearance rate less than 35 mL/minute.

Denosumab inhibits receptor activator of nuclear factor-kappa beta ligand (RANKL) signaling and decreases rates of bone resorption. Denosumab is a monoclonal antibody and can be used in patients with impaired renal function; however, the FDA recently issued a boxed warning for severe hypocalcemia in patients with advanced chronic kidney disease (e.g., dialysis patients). Denosumab injections given subcutaneously at 6-month intervals continued to show bone-mass gains over time at both vertebral and nonvertebral sites with several years of use, and men demonstrated a 62 percent reduction in vertebral fractures at 3 years. Discontinuation of denosumab treatment comes with a caution to change to another antiresorptive treatment due to a rebound effect with rapid bone loss and increased risk of vertebral fractures after discontinuation.

Anabolic agents teriparatide and abaloparatide both work through the parathyroid hormone receptor PTH1R to stimulate bone formation by increasing osteoblast activity and bone building. In men, teriparatide showed a rapid increase in bone density at the spine (5.9 percent) and femoral neck (1.5 percent) after just 11 months of use, and abaloparatide showed an 8.5 percent increase at the spine at 1 year. Both medications are given as daily subcutaneous injections for 18 to 24 months.

Although testosterone is not an FDA-approved treatment for osteoporosis, it does improve BMD in men with hypogonadism and may be used as treatment for symptomatic men with persistent hypogonadism, especially men with known pituitary or testicular disease. For men with hypogonadism who are at high fracture risk, an approved osteoporosis agent is recommended to reduce fracture risk.

Typically considered a disease of older women, osteoporosis commonly affects men, and the consequences can be severe. Despite the low cost and high availability of DXA and treatment medications, men are significantly under-screened and under-treated for osteoporosis. When encountering men aged 50 years or older with fractures, physicians should consider osteoporosis and referral to an osteoporosis specialist.

Susan V. Bukata, MD, FAAOS, FAOA, is professor and chair of orthopaedics at University of California, San Diego (UCSD). Her practice covers oncology, metabolic diseases, and rare bone diseases. She is the current president of the Orthopaedic Research Society.

Gina Woods, MD, is a clinical professor of medicine in the Division of Endocrinology and Metabolism at UCSD. She serves as director of the Osteoporosis Clinic at UCSD Health and the medical director for the UCSD School of Bone Densitometry.

References

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2. Vilaca T, Eastell R, Schini M: Osteoporosis in men. Lancet Diabetes Endocrinol 2022;10(4):273-83.
3. Rinonapoli G, Ruggiero C, Meccariello L, Bisaccia M, Ceccarini P, Caraffa A: Osteoporosis in men: a review of an underestimated bone condition. Int J Mol Sci 2021;22(4):2105.