The results of the present study suggest that denosumab is associated with greater bone mineral density (BMD) increase at all measured skeletal sites and greater inhibition of bone remodeling compared with zoledronic acid in postmenopausal women with osteoporosis previously treated with oral bisphosphonates.

Osteoporosis is a chronic, progressive condition that generally requires long-term management. Oral bisphosphonates are a commonly prescribed treatment for osteoporosis, but inconvenient dosing regimens and side effects can lead to low adherence. Suboptimal adherence to osteoporosis medication can reduce antifracture efficacy and increase health care use and costs. Although more extended dosing intervals can improve adherence, efficacy remains an influential determinant of patient preference for and adherence with osteoporosis medications. Once-yearly IV bisphosphonate therapy with zoledronic acid (ZOL) has been shown to reduce the risk of hip, vertebral, and nonvertebral fractures. Although patients in one clinical trial expressed a preference for once-yearly ZOL over a weekly bisphosphonate regimen, switching from oral bisphosphonates to ZOL did not further increase BMD. Denosumab is a fully human monoclonal antibody against RANKL administered SC every 6 months. In a 3-year, placebo-controlled, pivotal osteoporosis trial, denosumab significantly reduced burn turnover markers (BTMs), increased BMD, and reduced the risk of hip, vertebral, and nonvertebral fractures. Three studies have shown that individuals who received prior bisphosphonate therapy and transitioned to denosumab had greater BMD gains at all measured skeletal sites compared with continuing alendronate or initiating ibandronate or risedronate.

Rationale behind research:

Although parenteral bisphosphonates, such as ZOL have become a treatment option for osteoporosis, there is no evidence that cycling through bisphosphonate agents offers therapeutic benefits to patients with osteoporosis, whether assessed by BMD or BTMs.

Objective:

To compare the effect of transitioning from oral bisphosphonates to denosumab or ZOL on bone mineral density (BMD) and bone turnover.

Study outcomes

• Primary Outcomes: Mean percentage change from baseline in lumber spine BMD at month 12
• Secondary Outcomes: Mean percentage change from baseline in total hip BMD at month 12. The mean percentage change from baseline in the femoral neck and one third radius BMD at month 12 in overall population and the median percentage changes from baseline in serum BTMs, iPTH, and albumin-adjusted calcium in subjects participating in BTM sub study were also noted. Safety end points included AEs.

Time Points: Month 12



Outcomes:

Baseline: Baseline demographics and clinical characteristics were similar between the two treatment groups.

Bone Mineral Density:

- BMD at lumbar spine increased by 3.2% from baseline in the denosumab group compared with 1.1% in the ZOL group

- BMD at total hip increased by 1.9% from baseline in the denosumab group compared with 0.6% in the ZOL group

- Femoral neck BMD increased by 1.2% from baseline in the denosumab group compared with 0.1% in ZOL group

- BMD at one-third radius increased by 0.6% from baseline in the denosumab group compared with ZOL group

In postmenopausal women with osteoporosis previously treated with oral bisphosphonates, denosumab was associated with greater BMD increases at all measured skeletal sites and greater inhibition of bone remodeling compared with ZOL.