Significant advances have been made in the treatment of osteoporosis over the last 20 years or so. But because people on bone density-building drugs still sustain fractures, the search for better therapies for Osteoporosis continues.

It now appears that combining two different osteoporosis medications may help those at the highest risk for fracture. The combination increases bone mineral density (BMD) more than either drug given alone, according to investigators at Massachusetts General Hospital.

After one year, women in the combination group had a greater increase in BMD at the lumbar spine, femoral neck, and hip, compared to those in the groups that received denosumab or teriparatide alone.

“The attempts at combining therapies in the past have been pretty unsuccessful,” Alexander Uihlein, an author on the study told TheDoctor. The idea of combining drugs is not new — people have tried combining bisphosphonate drugs like alendronate (Fosamax), which block bone resorption, and anabolic or bone-building therapies such as teriparatide (Forteo). But those drug combinations conferred no additional benefit, compared to either drug given alone, in terms of increasing BMD.

Still, the results of animal studies combining teriparatide with denosumab (Prolia), which blocks resorption in a different way than do the bisphosphonates, suggested a possible benefit, so the researchers enrolled 100 postmenopausal women at high risk for fracture and randomly assigned them to receive either teriparatide alone, denosumab alone, or both.

After one year, women in the combination group had a greater increase in BMD at the lumbar spine, femoral neck, and hip, compared to those in the groups that received denosumab or teriparatide alone.

“We were pleasantly surprised at the increases in bone density that we saw at one year, especially at the hip and femoral neck, sites at which teriparatide in particular is not very effective at increasing bone density,” said Uihlein.

The next step is ideally to do a trial that is large enough to show a difference in effectiveness of fracture prevention. The current study was also too small to assess the side effects of the teriparatide-denosumab combination. “We saw very few side effects; however, the number of study participants was too small to assess the safety of the [combination] treatment. But there is no reason to believe that it is an unsafe combination.”

For postmenopausal women who have severe osteoporosis or who have had a fracture despite being on medication for osteoporosis, this combination therapy may be something for their physicians to consider, Uihlein says.

This combination may also be something to consider for those who have very low bone density at the hip, since teriparatide alone is not as effective at increasing BMD at the hip as it is at the spine, but the combination is quite effective at increasing BMD at both the spine and the hip.

Uihlien cautions that this combination therapy would be very expensive, and should probably be considered, at this point at least, for women who are at the very highest risk for fracture. "That was really why the study was done: to try and find a new treatment option for those who have failed other treatment options, mostly single drug therapies," he says.

The study is published online in The Lancet.