Zoledronic acid an option for osteoporotic men

The Food and Drug Admi-nistration’s recent approval of yearly zoledronic acid infusions for the treatment of low bone mass in men with osteoporosis will give clinicians a treatment option for men other than oral weekly therapy.

The agency’s decision brings the total number of indications for the intravenous formulation of zoledronic acid to three, including the treatment of postmenopausal osteoporosis (as well as the reduction of new clinical fractures in patients who have experienced a recent low-trauma hip fracture) and the treatment of Paget’s disease of bone. It is the only osteoporosis treatment that has been approved for the reduction of fractures of the hip, vertebrae and non-vertebral bones.

The other two drugs that are approved to increase bone mass in men with osteoporosis — alendronate — “certainly represent very good therapeutic choices with . . . evidence in women for spine, hip, and nonvertebral fracture reduction,” the director of the University of Cincinnati Bone Health and Osteoporosis Center, one of the centers that participated in a randomized, double-blind dial that formed the basis for the FDA’s decision said.

Intravenous dosing would be medically indicated for men in three categories: those who can’t tolerate an oral agent of upper GI problems, those with lower GI problems that interfere with drug absorption, and those who can’t remember to take an oral agent. “And certainly it can be considered a convenience option for someone who might be a candidate for oral therapy.”

“We don’t have fracture reduction data in men, really, with any of these agents in terms of preplanned primary end point [but] there’s no real reason to feel that bisphosphonates work any different for osteoporosis in men than they do in women.”

During the 2-year trial that the FDA evaluated, 153 osteoporotic men received a 15-minute infusion of zoledronic acid once per year and 148 other osteoporotic men received weekly oral alendronate. The men who were treated with zoledronic acid increased their lumber spine bone mineral density by a mean of 6.1 percent over 2 years. This change BMD was similar to the 6.2 percent increase in the aledronate group. Each patient in the study received 1,000 mg calcium and 800-1,000 IU of vitamin D each day. The men had a mean age of 64 years (range of 25-86 years). Some of the men had significant osteoporosis secondary to hypogonadism.

Signs and symptoms of an acute phase reaction occurred in some patients in the first 3 days after the zoledronic acid infusion. The use of zoledronic acid was associated with myalgia (17.1 percent), fever (15.7 percent), fatigue (12.4 percent), arthralgia (11.1 percent), pain (10.5 percent), chills (9.8 percent), headache (9.8 percent), influenza-like illness (8.5 percent), malaise (5.2 percent) and back pain (3.3 percent). No patients developed osteonecrosis of the jaw. There was one death in each group; the two groups had similar rates of serious adverse events.

The FDA has “generally felt” that drugs with proven antifracture efficacy in postmenopausal women can be approved, based on noninferiority “bridging” studies without fracture data, for new dosing regimens or new populations such as glucocorticoid users of men. That is why studies in those circumstances have been smaller and not powered to detect fracture reduction. “The lack of the fracture data doesn’t concern me particularly in this population because of the really robust fracture reduction data that we’ve seen in postmenopausal women.”

Zoledronic acid, available as a 5-mg dose in a 100-mL ready-to-infuse solution, has been used by more than 164,000 US patients since it was approved by the FDA in 2007.