Osteoporosis Rx Approval Opens Options to Men

The Food and Drug Administration's recent approval of yearly zoledronic acid infusions for treating low bone mass in men with osteoporosis will give providers a treatment option for men other than oral weekly therapy, according to Dr. Nelson Watts.

The agency's decision brings the total number of indications for the intravenous formulation of zoledronic acid (Reclast) 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 other nonvertebral bones.

The other drugs approved to increase bone mass in men with osteoporosis—alendronate (Fosamax) and risedronate (Actonel)—”represent very good therapeutic choices with … evidence in women for spine, hip, and nonvertebral fracture reduction,” said Dr. Watts, director of the University of Cincinnati Bone Health and Osteoporosis Center, which was one of the centers that participated in a randomized, double-blind trial that formed the basis for the FDA's decision. Dr. Watts is a paid consultant to Novartis Pharmaceutical Corp., which manufactures Reclast and is on the company's speakers bureau.

Intravenous dosing would be medically indicated for men in three categories: those who can't tolerate an oral agent because 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.

“We don't have fracture reduction data in men with any of these agents in terms of a preplanned primary end point [but] there's no real reason to feel that bisphosphonates work any differently for osteoporosis in men than they do in women,” Dr. Watts said in an interview.

During the 2-year Novartis-sponsored trial, 153 osteoporotic men received a 15-minute infusion of zoledronic acid once per year, and 148 other osteoporotic men received weekly oral alendronate. Those who were treated with zoledronic acid increased their lumbar spine bone mineral density by a mean of 6.1% over 2 years. This change in BMD was similar to the 6.2% increase in the alendronate 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 had significant osteoporosis secondary to hypogonadism.

In the trial, signs and symptoms of an acute phase reaction occurred in some patients in the first 3 days following the zoledronic acid infusion. Treatment with zoledronic acid was associated with myalgia (17.1%) fever (15.7%), fatigue (12.4%), arthralgia (11.1%), pain (10.5%), chills (9.8%), headache (9.8%), influenza-like illness (8.5%), malaise (5.2%), and back pain (3.3%). 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, on the basis of noninferiority “bridging” studies without fracture data, for new dosing regimens or for new populations such as glucocorticoid users or men, Dr. Watts noted. That is why studies in those circumstances have been smaller and not powered to detect a reduction in fractures.

“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,” he said.

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

“Intravenous Reclast compares in price with the cost of a year's therapy with a brand name oral preparation. Medicare has generally covered this for postmenopausal women, and in some states it's already covering it for men,” Dr. Watts said.

IV dosing is indicated for men with upper or lower GI problems and for those who forget to take pills. DR. WATTS

The Food and Drug Administration's recent approval of yearly zoledronic acid infusions for treating low bone mass in men with osteoporosis will give providers a treatment option for men other than oral weekly therapy, according to Dr. Nelson Watts.

The agency's decision brings the total number of indications for the intravenous formulation of zoledronic acid (Reclast) 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 other nonvertebral bones.

The other drugs approved to increase bone mass in men with osteoporosis—alendronate (Fosamax) and risedronate (Actonel)—”represent very good therapeutic choices with … evidence in women for spine, hip, and nonvertebral fracture reduction,” said Dr. Watts, director of the University of Cincinnati Bone Health and Osteoporosis Center, which was one of the centers that participated in a randomized, double-blind trial that formed the basis for the FDA's decision. Dr. Watts is a paid consultant to Novartis Pharmaceutical Corp., which manufactures Reclast and is on the company's speakers bureau.

Intravenous dosing would be medically indicated for men in three categories: those who can't tolerate an oral agent because 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.

“We don't have fracture reduction data in men with any of these agents in terms of a preplanned primary end point [but] there's no real reason to feel that bisphosphonates work any differently for osteoporosis in men than they do in women,” Dr. Watts said in an interview.

During the 2-year Novartis-sponsored trial, 153 osteoporotic men received a 15-minute infusion of zoledronic acid once per year, and 148 other osteoporotic men received weekly oral alendronate. Those who were treated with zoledronic acid increased their lumbar spine bone mineral density by a mean of 6.1% over 2 years. This change in BMD was similar to the 6.2% increase in the alendronate 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 had significant osteoporosis secondary to hypogonadism.

In the trial, signs and symptoms of an acute phase reaction occurred in some patients in the first 3 days following the zoledronic acid infusion. Treatment with zoledronic acid was associated with myalgia (17.1%) fever (15.7%), fatigue (12.4%), arthralgia (11.1%), pain (10.5%), chills (9.8%), headache (9.8%), influenza-like illness (8.5%), malaise (5.2%), and back pain (3.3%). 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, on the basis of noninferiority “bridging” studies without fracture data, for new dosing regimens or for new populations such as glucocorticoid users or men, Dr. Watts noted. That is why studies in those circumstances have been smaller and not powered to detect a reduction in fractures.

“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,” he said.

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

“Intravenous Reclast compares in price with the cost of a year's therapy with a brand name oral preparation. Medicare has generally covered this for postmenopausal women, and in some states it's already covering it for men,” Dr. Watts said.

IV dosing is indicated for men with upper or lower GI problems and for those who forget to take pills. DR. WATTS

The Food and Drug Administration's recent approval of yearly zoledronic acid infusions for treating low bone mass in men with osteoporosis will give providers a treatment option for men other than oral weekly therapy, according to Dr. Nelson Watts.

The agency's decision brings the total number of indications for the intravenous formulation of zoledronic acid (Reclast) 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 other nonvertebral bones.

The other drugs approved to increase bone mass in men with osteoporosis—alendronate (Fosamax) and risedronate (Actonel)—”represent very good therapeutic choices with … evidence in women for spine, hip, and nonvertebral fracture reduction,” said Dr. Watts, director of the University of Cincinnati Bone Health and Osteoporosis Center, which was one of the centers that participated in a randomized, double-blind trial that formed the basis for the FDA's decision. Dr. Watts is a paid consultant to Novartis Pharmaceutical Corp., which manufactures Reclast and is on the company's speakers bureau.

Intravenous dosing would be medically indicated for men in three categories: those who can't tolerate an oral agent because 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.

“We don't have fracture reduction data in men with any of these agents in terms of a preplanned primary end point [but] there's no real reason to feel that bisphosphonates work any differently for osteoporosis in men than they do in women,” Dr. Watts said in an interview.

During the 2-year Novartis-sponsored trial, 153 osteoporotic men received a 15-minute infusion of zoledronic acid once per year, and 148 other osteoporotic men received weekly oral alendronate. Those who were treated with zoledronic acid increased their lumbar spine bone mineral density by a mean of 6.1% over 2 years. This change in BMD was similar to the 6.2% increase in the alendronate 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 had significant osteoporosis secondary to hypogonadism.

In the trial, signs and symptoms of an acute phase reaction occurred in some patients in the first 3 days following the zoledronic acid infusion. Treatment with zoledronic acid was associated with myalgia (17.1%) fever (15.7%), fatigue (12.4%), arthralgia (11.1%), pain (10.5%), chills (9.8%), headache (9.8%), influenza-like illness (8.5%), malaise (5.2%), and back pain (3.3%). 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, on the basis of noninferiority “bridging” studies without fracture data, for new dosing regimens or for new populations such as glucocorticoid users or men, Dr. Watts noted. That is why studies in those circumstances have been smaller and not powered to detect a reduction in fractures.

“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,” he said.

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

“Intravenous Reclast compares in price with the cost of a year's therapy with a brand name oral preparation. Medicare has generally covered this for postmenopausal women, and in some states it's already covering it for men,” Dr. Watts said.

IV dosing is indicated for men with upper or lower GI problems and for those who forget to take pills. DR. WATTS