Denosumab Results in Improved BMD in High-Risk Patients with Osteoporosis

In postmenopausal women with osteoporosis, history of previous fracture, and prior treatment with bisphosphonate, denosumab (DMab) may be an appropriate treatment option. In this patient population, DMab was associated with greater improvements in bone mineral density (BMD) at all measured skeletal sites when compared with ibandronate (IBN) and risedronate (RIS), according to the findings of recent open-label trials.

Pei-Ran Ho, MD, and colleagues reported their findings at ENDO 2013: The Endocrine Society’s 95^th Annual Meeting & Expo in San Francisco on June 15, 2013.

According to the researchers, poor compliance with bisphosphonate treatment is common and often associated with poor outcomes. In two randomized, open-label studies, treatment with subcutaneous DMab every six months was associated with greater increases in BMD at 12 months versus treatment with monthly oral IBN or RIS. In this study, the authors aimed to evaluate treatment effects of these medications in a subset of patients with a high risk for fracture. They defined “high risk” as having a prior fragility fracture.

In the comparison study of DMab with IBN, 31% of 767 total subjects had a previous fracture. BMD improvements at the total hip (TH), femoral neck (FN), and lumbar spine (LS) measurements were greater after DMab treatment in patients with prior fracture (p < 0.0001) and in patients without previous fracture (p < 0.05). DMab was shown to have a greater treatment effect at the FN in patients with prior fracture (p = 0.002), but no significant treatment difference was noted at the TH or LS between the two subgroups.

A previous fracture was documented in 35% of 809 patients in the comparison study of DMab with RIS. DMab was associated with greater BMD increases at all skeletal sites measured when compared with RIS in patients with prior fracture (p < 0.0001) and in patients without prior fracture (p < 0.01). However, there was no significant difference in treatment effect between those with or without prior fracture.

It was noted that a greater proportion of patients with previous fracture reported serious adverse events. There was no specific pattern of events noted. Additionally, more of the higher risk patients treated with DMab (23.6%) reported infections than those treated with IBN (19.2%) and RIS (21.0%). According to the authors, no cases of delayed fracture healing, atypical femoral fracture, or osteonecrosis of the jaw were reported.

The authors concluded that in patients previously treated with bisphosphonate, including those with previous fracture, transitioning to DMab resulted in greater BMD improvements than transitioning to IBN or RIS. They also concluded that “DMab is a treatment option in subjects at higher risk of fracture who received prior oral bisphosphonate therapy,” although classification of high risk does not seem to influence the degree of treatment effect.

The study was sponsored by Amgen and GlaxoSmithKline. All authors disclosed financial ties to pharmaceutical companies.