Twice-yearly subcutaneous injections of Denosumab ( 60 mg; Prolia ) increased bone mineral density ( BMD ) in the lumbar spine, total hip, distal 1/3 radius and total body compared to placebo at 24 months.
The ongoing, multi-center, phase 2 dose-ranging trial includes results from 337 healthy postmenopausal women with low BMD who completed two years of study.
Researchers reported Denosumab 60mg increased BMD of the lumbar spine by 7.4 percent in women administered the therapy twice yearly and 6.2 percent for Fosamax ( Alendronate ) 70mg weekly.
Across all doses and dosing intervals, Denosumab increased the BMD of the lumbar spine by 4.3 to 9.0 percent over baseline.
" The two-year results showed the continued effect of Denosumab in increasing bone mineral density in postmenopausal patients with low bone mass," said Michael Lewiecki, at the University of New Mexico School of Medicine, Albuquerque. " These data suggest Denosumab, when administered twice a year, may offer a promising alternative for the prevention and treatment of osteoporosis."
Denosumab is designed to target RANK Ligand, a protein that acts as the primary signal to promote bone removal. In many bone loss conditions, RANK Ligand overwhelms the body's natural defense against bone destruction.
Preclinical models have demonstrated that inhibiting RANK Ligand leads to significant improvements in cortical and trabecular bone density, volume and strength.
Denosumab is being studied for its potential in a broad range of bone loss conditions including osteoporosis, treatment-induced bone loss, bone metastases, multiple myeloma and rheumatoid arthritis.
Researchers also reported twice-yearly injections of Denosumab ( 60 mg ) increased total hip BMD by 5.1 percent after 24 months.
Fosamax 70 mg weekly produced a 3.4 percent increase during the same time period.
Denosumab, at all doses and dosing intervals studied, increased total hip BMD from 2.8 to 5.1 percent. Across all doses and dosing intervals, distal 1/3 radius BMD increased from 0.6 to 2.5 percent, and total body BMD increased from 0.9 to 4.5 percent.
Occurrence of adverse events was similar among the Denosumab, placebo, and Fosamax groups and showed no new pattern of events in the second year of treatment. No neutralizing antibodies to Denosumab were observed throughout the two years.
Bone loss represents a significant clinical and economic burden.
Osteoporosis is a major public health threat for an estimated 44 million Americans, or 55 percent of the people 50 years of age and older.
In the U.S.,10 million individuals are estimated to already have the disease and almost 34 million more are estimated to have low bone mass, placing them at increased risk for osteoporosis.
Of the 10 million Americans estimated to have osteoporosis, eight million are women and two million are men. In addition, one in two women and one in four men over age 50 will have an osteoporosis-related fracture in their remaining lifetime.
In Europe, recent estimates have stated that approximately 3.8 million people have experienced bone fractures related to osteoporosis.
Source: Amgen, 2005