Both alendronate and risedronate are effective for secondary causes of bone loss, such as corticosteroid use, androgen deprivation therapy/hypogonadism, and rheumatologic conditions.28 Oral bisphosphonates may cause GI irritation, however. Abdominal pain associated with alendronate use is between 1% and 7%, vs 2% to 12% for risedronate.23 Neither medication is recommended for use in patients with an estimated glomerular filtration rate <35 mL/min.23 There is no clearly established duration of therapy for men.
Zoledronic acid infusions, given intravenously (IV) once a year, are available for men who cannot tolerate oral bisphosphonates. In a multicenter double-blind, placebocontrolled trial, zoledronic acid was found to reduce the risk of vertebral fractures in men with primary or hypogonadism-associated osteoporosis by 67% (1.6% vertebral fractures in the treatment group after 24 months vs 4.9% with placebo).29 Given within 90 days of a hip fracture repair, zoledronic acid was associated with both a reduction in the rate of new fractures and an increased survival rate.30
Adverse effects of zoledronic acid include diffuse bone pain (3%-9%), fever (9%-22%) and flu-like symptoms (1%-11%). Osteonecrosis of the jaw has been reported in <1% of patients.23
Recombinant human parathyroid hormone stimulates bone growth
Teriparatide, administered subcutaneously (SC) once a day, directly stimulates bone formation. In a randomized placebo controlled trial of 437 men with a T-score of -2, teriparatide was found to increase BMD at the spine and femoral neck. Participants were randomized to receive teriparatide (20 or 40 mcg/d) or placebo. Those who received teriparatide had a doserelated increase in BMD from baseline at the spine (5.9% with 20 mcg and 9% with 40 mcg) and femoral neck (1.5% and 2.9%, respectively) compared with the placebo group.31 Teriparatide was shown to reduce vertebral fractures by 51% compared with placebo in a randomized study of 355 men with osteoporosis.32
Teriparatide is indicated for men with severe osteoporosis and those for whom bisphosphonate treatment has been unsuccessful. Its use is limited to 2 years due to a dose-dependent risk of osteosarcoma. Teriparatide is contraindicated in patients with skeletal metastasis and has been associated with transient hypercalcemia 4 to 6 hours after administration.23 Its use in combination with bisphosphonates is not recommended due to the lack of proven benefit, risk of adverse effects, and associated cost.5
Testosterone boosts bone density
Testosterone therapy is recommended for men with low levels of testosterone (<200 ng/dL), high risk for fracture, and contraindications to pharmacologic agents approved for the treatment of osteoporosis.5 Supplementation of testosterone to restore correct physiologic levels will decrease bone turnover and increase bone density.33 In a meta-analysis of 8 trials with a total of 365 participants, testosterone administered intramuscularly was found to increase lumbar BMD by 8% compared with placebo. The effect on fractures is not known.12
Did you know?1,2,4,5,9-12,16,17
• Although US women are 4 times more likely than men to suffer from osteoporosis, men incur between 30% and 40% of osteoporotic fractures.
• Men who sustain hip fractures have a mortality rate of up to 37.5%—2 to 3 times that of women with hip fractures.
• Men treated with androgen deprivation therapy face an increased risk of osteoporosis.
• About 13% of white men older than 50 years will experience at least one osteoporotic fracture in their lifetime.
• The Endocrine Society, American College of Physicians, and National Osteoporosis Foundation recommend screening all men ages 70 years or older—and younger men with risk factors for fracture and/or a history of fracture after age 50—for osteoporosis.
Monoclonal antibody reduces fracture risk
Denosumab, a monoclonal antibody that prevents osteoclast formation leading to decreased bone resorption, is administered SC every 6 months.23 In a placebo-controlled trial of 242 men with low bone mass, denosumab increased BMD at the lumbar spine (5.7%), total hip (2.4%), femoral neck (2.1%), trochanter (3.1%), and one-third radius (0.6%) compared with placebo after one year.34 In men receiving androgen deprivation therapy for nonmetastatic prostate cancer, denosumab has been shown to increase BMD and reduce the incidence of vertebral fractures.35
Adverse effects include hypocalcemia, hypophosphatemia, fatigue, and back pain.23 No data exist on the ability of denosumab to reduce fracture risk in men without androgen deprivation.
Calcium and vitamin D for men at risk
Men who are at risk for or have osteoporosis should consume 1000 mg to 1200 mg of calcium per day. Ideally, this should come through dietary sources, but calcium supplementation may be added when diet is inadequate.5 The Institute of Medicine recommends a calcium intake of 1000 mg/d for men ages 51 to 70 years and 1200 mg/d for men ages 70 and older.36