Doctors say this is good news because Prolia differs radically from Fosamax and its cousins, offering a good alternative for patients who can't take bisphosphonates. "This was somewhat of a breakthrough in that it's a completely different mechanism and a completely different chemical compound," says Dr. Aurelia Nattiv, who directs the UCLA Osteoporosis Center.
Here's a closer look at how Prolia compares to current osteoporosis drugs and who might benefit most from taking it.
An estimated 10 million Americans have osteoporosis, the bone-weakening disease that is diagnosed via tests for bone mineral density. One out of every two women age 50 and older — and one in four men in that age group — will have an osteoporosis-related fracture in their lifetime, according to the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Bone tissue is not static — living cells and structural minerals are broken down and replaced in a cycle of normal turnover. With age, this balance in turnover shifts to favor bone loss over bone renewal.
Most osteoporosis drugs — including the bisphosphonates, hormone therapy and hormone modulators such as Evista, calcitonins such as Fortical and Miacalcin, and now Prolia — work by slowing normal bone loss. One drug, Forteo, acts on the bone-building side.
Prolia is a little bit different from the other osteoporosis drugs in that it's a complicated biological molecule — an antibody — that was specifically designed to bind to, and inactivate, a protein in the body involved in bone metabolism. That protein, RANKL, stimulates the breakdown of bone tissue during normal bone turnover. By inhibiting RANKL, Prolia suppresses bone breakdown and prevents bone loss.
Prolia's effectiveness looks quite comparable to bisphosphonate drugs, says Dr. Sundeep Khosla, an osteoporosis expert at the Mayo Clinic in Rochester, Minn., who has no financial ties to the drug's makers (or to other drug companies that make osteoporosis medications). "There haven't been head-to-head trials, but if you look at the fracture risk reductions of the drug compared to the bisphosphonates, it's probably at least as potent. It's probably about as good as you're going to get."
In a three-year clinical trial of 7,868 postmenopausal women with osteoporosis, Prolia was found to prevent the rate of the most common type of osteoporotic fractures (vertebral fractures) by 68%. Of women taking Prolia, 2.3% suffered these fractures, a collapse of a bone in the spine, compared with 7.2% in the control group.
The researchers, who reported their findings last year in the New England Journal of Medicine, also found that hip fractures were reduced by 40% and other types of fractures, such as ones in the wrist, leg or shoulder, by 20%.
The hip-fracture reduction is especially noteworthy, Nattiv says. "Every single FDA-approved drug prevents vertebral fractures," Nattiv says, and to approximately the same degree — about 50%. "Not all of them protect against hip fractures. That really is a very important outcome from the studies."
Hip fractures can be devastating. Not only do they have a major effect on a person's ability to do normal daily activities, research has found that some 40% of seniors who break their hips have to move into a nursing home — often for good.
Worse, 25% of people die within five years of breaking a hip.
Because Prolia has a different chemical makeup and action in the body, it may be most helpful to osteoporosis patients who cannot take bisphosphonates, Khosla says. Some people have allergic reactions, and other can't tolerate their side effects, such as flu-like symptoms and aching bones and muscles. People with low-functioning kidneys cannot take bisphosphonates either.
But, Khosla adds, Prolia is likely to cause the same rare but serious side effects that plague the bisphosphonates, such as osteonecrosis of the jaw and atypical fractures. That's because these things are probably not specific to individual drugs, "rather a side effect of just having marked suppression of bone turnover."
A few cases of jaw osteonecrosis — death of bone tissue — have already been reported on Prolia. No cases of atypical fractures have emerged yet, but Khosla believes it's only a matter of time.
Side effects specific to Prolia include skin infections, some serious enough to require hospitalization, and other infections, such as in the ears, urinary tract and the heart. Back pain and pain in the muscles and bones have been reported, as have elevated cholesterol levels.
Prolia, given by injection every six months, will cost $1,650 per year. That's competitive to the once-yearly injection of the bisphosphonate Reclast, commonly listed at $1,300 per year before factoring in insurance, and not that much more than an annual supply of brand-name bisphosphonate pills at just under $1,000 per year. The generic form of Fosamax's alendronate pills, to be taken either daily or weekly, probably is the cheapest option — in the $100-to-$200 range per year.