A combination of two drugs including teriparatide, a bone-building (anabolic) drug, and denosumab, a targeted therapy to stop bone loss, raised bone mineral density (BMD) better than any available treatment for postmenopausal women with osteoporosis.
Osteoporosis is characterized by fragile bones that are more likely to fracture as the bones lose density, a measure of the amount of bone calcium and minerals. Osteoporosis occurs when patients fail to form enough new bone, when excessive bone resorption occurs, or both. It is an age-related disorder, with about half of all women over the age of 50 having a fracture of the hip, wrist, or vertebra (bone of the spine) during their lifetime, according to the National Institutes of Health. Early signs include joint pains, difficulty standing, and difficulty sitting up straight. With diminishing bone density or bone mass, an increased incidence of fractures of the wrist, hip, or bones in the spine is seen. It is critical to take enough dietary calcium and vitamin D, to prevent the risk of brittle bones or bone fractures.
Most often, treatments for osteoporosis include drugs like denosumab, which prevent reabsorption of the bone by blocking the action of cells called osteoclasts that break down bone during the normal process of bone remodeling.
The drug teriparatide works by increasing the activity of cells called osteoblasts, which aid in the development of new bone.
It is not hard to understand how a two-pronged approach that prevents bone dissolution as well as enhances bone formation, is more effective than focusing all the efforts on one aspect alone. Until now, scientists could not successfully combine the two.
In the clinical trial research published in The Lancet, investigators led by Dr Benjamin Z Leder, of the Department of Medicine, at Massachusetts General Hospital in Boston randomly assigned 94 postmenopausal women with osteoporosis to receive either teriparatide (20 micrograms daily), denosumab (60 mg every 6 months), or both medications for 1 year. The investigators used low-dose x-rays and bone biomarkers to monitor changes in lumbar spine, hip bone, and femoral neck at the start of the study and at 3 months, 6 months, and 1 year.
The results indicate that the combo therapy improved BMD at the spine, hip, and femoral neck significantly better than either drug by itself.
The findings suggest that the posterior-anterior lumbar spine BMD increased more in the combination group than in the teriparatide or denosumab groups. In addition, "femoral-neck BMD also increased more in the combination group than in the teriparatide and denosumab groups, as did total-hip BMD."
"One year improvements in femoral neck (4.2%) and hip (4.9%) BMD in the combined group were greater than previously reported for any approved treatment," according to the researchers. The combine therapy slowed the reduction of bone synthesis in women.
"Combination treatment might, therefore, be useful to treat patients at high risk of fracture," the investigators conclude.
However, skeptics are still not so sure, since they could not find evidence of any difference in certain bone formation markers between the denosumab-alone and combination-therapy groups at 12 months.
In an accompanying editorial comment, bone experts Dr. Richard Eastell of the Northern General Hospital, Sheffield (UK) and Dr. Jennifer S Walsh of Mellanby Centre for Bone Research, University of Sheffield, Sheffield, UK, observed that the safety data of this combination therapy are needed as we do not know what happens when teriparatide is stopped after the recommended use for a maximum of 24 months. Cost-effectiveness data are also required.
