Amgen’s Prolia (Denosumab) has been approved for the treatment of osteoporosis in males at high risk of fracture by the Food and Drug Administration (FDA), USA. Denosumab reduced tumor-cell numbers in men with giant-cell tumor of the bone, Amgen informed.

Prolia increases bone mass in male patients with osteoporosis who are at high risk for fracture. Prolia is the first RANK ligand inhibitor to be approved by the FDA. RANK ligand is a protein that acts as the primary signal for bone removal. RANK ligand commonly overwhelms the body’s natural defenses against bone destruction – Prolia inhibits the action of this protein.

Denosumab is administered subcutaneously by injection every six months. The injection is given by a health care professional.

Sean E. Harper, M.D., executive vice president of Research and Development at Amgen, said:

“While osteoporosis and osteoporosis-related fractures are more commonly associated with postmenopausal women, osteoporosis in men is a significant issue that is increasing in prevalence as life expectancies rise. Fractures can be a life-changing event, so we are pleased that we can offer a new treatment option for the growing number of men with osteoporosis at high risk for fracture.”

Two million American males live with osteoporosis, according to the National Osteoporosis Foundation. A further 12 million are estimated to be at risk. Osteoporotic fractures, as well as osteoporosis itself are both under-treated and under-diagnosed.

The FDA approved the new indication after examining data from the ADAMO trial. ADAMO stands for A multicenter, randomized, double-blind, placebo-controlled study to compare the efficacy and safety of DenosumAb 60 mg every six months versus placebo in Males with Osteoporosis. The human trial included 242 male patients with BMD (low bone mineral density). The ones on Prolia had considerably greater gains at the lumbar spine compared to the patients on placebo, regardless of baseline testosterone levels, BMD status, estimated fracture risk or age.

In a communiqué, Amgen wrote:

“Additional results showed that patients in the study who received treatment with Prolia experienced BMD increases at all other skeletal sites assessed compared to placebo, including at the total hip (2.4 percent vs. 0.3 percent) and at the femoral neck (2.1 percent vs. 0.0 percent). Safety findings were consistent with what have been observed in other studies of Prolia in postmenopausal women with osteoporosis. The most common adverse reactions reported (per patient incidence > 5 percent) were back pain, arthralgia and nasopharyngitis. “

Denosumab was approved by the FDA for treating postmenopausal females who are at risk of osteoporosis under the brand name Prolia, in June 2010. In November 2010 it was approved under the brand name Xgeva. In May 2010, the European Commission approved denosumab for the same indication.

Denosumab adverse effects – infections of the respiratory and urinary tracts, joint pain, constipation, cataracts and rashes. Less commonly, a higher risk of developing some cancers and severe infections. One trial reported cases of eczema and skin infections that required hospitalization.

According to the company Sanford Bernstein, global sales of denosumab should reach $5 billion annually by 2015.

Osteoporosis refers to the thinning of the bones and a loss of bone mass, caused by a depletion of bone protein and calcium. People with osteoporosis are much more likely to have fractures, which heal either very slowly or poorly.

Older people, especially postmenopausal women, have a much higher risk of developing osteoporosis compared to younger patients. Patients on steroids or steroidal medications also have a greater risk of losing bone mass.

USA – osteoporosis is a serious public health threat for about 44 million men and women in the USA, according to the National Osteoporosis Foundation – this accounts for over half of all Americans over the age of 55. The Foundation reports that over 10 million Americans of both sexes currently live with the bone disease, while 34 million probably have low bone mass.

UK – approximately 3 million people in the UK have osteoporosis. Osteoporosis is estimated to cause over 230,000 fractures annually, according to the NHS (National Health Service).

As people live longer and adopt more sedentary lifestyles, osteoporosis rates are expected to continue rising for many years to come.

If a person with osteoporosis does not receive treatment, the condition will continue progressing, probably with no symptoms of pain, until a bone breaks. Most commonly, a bone in the spine, a hip bone, or the wrist fractures. Patients with a hip fracture often need major surgery. Hip fractures typically lead to walking problems, and even death if the condition is left untreated. A fracture of the spine or vertebrae may lead to a loss in height, deformity, or excruciating back pain.

Male osteoporosis has been out of the public spotlight until recently. As men have much longer lifespans today than before, it is now recognized as a major public health issue. During the 2010-2020 decade the number of men with osteoporosis is estimated to rise by 17%. About one-quarter of all men over the age of 50 will have an osteoporosis-related fracture during his remaining years of life.

Written by Christian Nordqvist