Nancy A. Melville

October 09, 2013

BALTIMORE – Improvements in bone-mineral density (BMD) resulting from a combination of osteoporosis agents, the antiresorptive denosumab (Prolia, Amgen) with the anabolic agent teriparatide (Forteo, Lilly), are sustained over 2 years of treatment, according to a new study presented here at the American Society for Bone and Mineral Research (ASBMR) 2013 Annual Meeting.

One-year results of the combination of these 2 therapies were reported at the ASBMR meeting a year ago and showed that the combo led to greater improvements in BMD than were seen with either agent alone; those findings were later published in the Lancet .

"The 2-year administration of teriparatide and denosumab increases BMD in a clinically meaningful way and more than has been reported with any currently approved agent," said lead author Benjamin Z. Leder, MD, an endocrinologist with Massachusetts General Hospital, in Boston.

Moderator Angela M. Cheung, MD, PhD, professor of medicine at the University of Toronto, Ontario, said the new data suggest a potentially intriguing therapeutic approach for osteoporosis. "The findings are of high interest to the osteoporosis world because the study shows that a combination of teriparatide and denosumab can increase spine and hip BMD better than either agent alone," she observed.

"For denosumab, fracture risk reduction is proportional to gain in BMD, and although we do not have fracture data, the hope is that higher gains in BMD will translate to better efficacy for fracture reduction," she added.

Combo May Be Important Therapeutic Option

Dr. Leder explained that current osteoporosis medications increase BMD modestly and reduce but do not eliminate fracture risk. Attempts to improve treatment efficacy by combining anabolic agents such as teriparatide with bisphosphonates have been unsuccessful.

Teriparatide is a human recombinant parathyroid hormone analog approved in the US 10 years ago for the treatment of osteoporosis in men and postmenopausal women; more recently, it was cleared for the treatment of glucocorticoid-induced osteoporosis in men and women.

Denosumab, a receptor activator of nuclear factor-κ (RANK) ligand inhibitor given subcutaneously every 6 months, is approved by the Food and Drug Administration for the treatment of bone loss in men and postmenopausal women with osteoporosis who are at high risk for fracture, as well as in men with prostate cancer and women with breast cancer who are at high risk for fracture because of their treatment.

In the study, Dr. Leder and his colleagues randomized 100 postmenopausal women at high risk for fracture (aged 51–91 years) who had not used oral bisphosphonates in the past 6 months or ever taken parenteral bisphosphonates or teriparatide to receive either teriparatide (20 µg sc daily) or denosumab (60 mg sc every 6 months) or to receive both therapies for 24 months.

Among the 83 women who completed all study visits, greater improvements were seen in postero-anterior (PA) spine BMD assessed by dual-energy X-ray absorptiometry (DEXA) in the combination group (12.7%) at 24 months than in either the groups taking teriparatide (9.5%; P < .001) or denosumab (8.3%; P < .001) alone.

The combination-treatment group also showed increases in femoral-neck BMD of 6.4%, compared with 2.8% in the teriparatide group (P = .002) and 4.1% in the denosumab group (P = .028).

Total hip BMD increased by 6.1% in the combination group, compared with 2.0% in the teriparatide group (P < .001) and 3.2% in the denosumab group (P < .001).

Whereas changes in the spine and femoral neck were similar between the denosumab-alone and teriparatide-alone groups, denosumab was associated with a significantly greater increase in total hip BMD than teriparatide (P = .005).

Osteoblast-activity suppression was significantly greater in the denosumab group than the combination group in year 1; however, the differences were attenuated in the second year.

"Combined teriparatide and denosumab may prove to be an important treatment option in patients who are at especially high fracture risk," said Dr. Leder.

More Data Needed to Determine Best Approach

Nevertheless, he said that additional studies are needed to determine the optimal approach to combination therapy, "specifically, whether 24 months of combined therapy would be superior to 12 months of combined therapy followed by 12 months of antiresorptive therapy alone."

And in a separate poster, he and colleagues described the effects of the combination therapy on cortical bone parameters.

The total bone density and cortical thickness of the tibia were increased more with the combination compared with either drug alone. The research also showed that the coadministration of denosumab was effective in countering teriparatide-induced changes in cortical density and porosity.

Dr. Leder has reported relationships with Amgen, Lilly, and Merck. Dr. Cheung has reported relationships with Amgen, Lilly, and Merck.

American Society for Bone and Mineral Research 2013 Annual Meeting. Abstracts 1019 and SA0372, presented October 5, 2013.

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