The effect of 8 or 5 years of denosumab treatment in postmenopausal women with osteoporosis: results from the FREEDOM Extension study

Abstract

SummaryThe FREEDOM study and its Extension provide long-term information about the effects of denosumab for the treatment of postmenopausal osteoporosis. Treatment for up to 8 years was associated with persistent reduction of bone turnover, continued increases in bone mineral density, low fracture incidence, and a favorable benefit/risk profile.IntroductionThis study aims to report the results through year 5 of the FREEDOM Extension study, representing up to 8 years of continued denosumab treatment in postmenopausal women with osteoporosis.MethodsWomen who completed the 3-year FREEDOM study were eligible to enter the 7-year open-label FREEDOM Extension in which all participants are scheduled to receive denosumab, since placebo assignment was discontinued for ethical reasons. A total of 4550 women enrolled in the Extension (2343 long-term; 2207 cross-over). In this analysis, women in the long-term and cross-over groups received denosumab for up to 8 and 5 years, respectively.ResultsThroughout the Extension, sustained reduction of bone turnover markers (BTMs) was observed in both groups. In the long-term group, mean bone mineral density (BMD) continued to increase significantly at each time point measured, for cumulative 8-year gains of 18.4 and 8.3 % at the lumbar spine and total hip, respectively. In the cross-over group, mean BMD increased significantly from the Extension baseline for 5-year cumulative gains of 13.1 and 6.2 % at the lumbar spine and total hip, respectively. The yearly incidence of new vertebral and nonvertebral fractures remained low in both groups. The incidence of adverse and serious adverse events did not increase over time. Through Extension year 5, eight events of osteonecrosis of the jaw and two events of atypical femoral fracture were confirmed.ConclusionsDenosumab treatment for up to 8 years was associated with persistent reductions of BTMs, continued BMD gains, low fracture incidence, and a consistent safety profile.Electronic supplementary materialThe online version of this article (doi:10.1007/s00198-015-3234-7) contains supplementary material, which is available to authorized users.

Efficacy and Safety of Denosumab for the Treatment of Osteoporosis in Patients with Chronic Kidney Disease

“…Treatment with denosumab has been associated with significant reductions in fracture risk across a wide range of patient groups [15,17]. Furthermore, long-term clinical trial follow-up data from the FREEDOM study demonstrates that denosumab treatment for up to 8 years is associated with a persistent reduction of bone turnover, continued increases in BMD without therapeutic plateau, and low fracture incidence [18]. It is unknown whether treatment for osteoporosis with denosumab is safe or effective in patients with CKD.…”

Comparative effects of denosumab or bisphosphonate treatment on bone mineral density and calcium metabolism in postmenopausal women

“…Analysis of ongoing long-term studies suggests that denosumab has a continuous beneficial effect on bone density compared to certain types of bisphosphonate, like zoledronic acid, in which bone density gain reaches a plateau 17,18 . In the open-label extension of the pivotal FREEDOM trial, denosumab treatment for up to 8 years induced continued increases in BMD by DXA at the lumbar spine and total hip with the final changes from baseline being 18.4% at the lumbar spine and 8.3% at the total hip 17 .…”

A revision in the definition of osteoporosis

“…One can reasonably infer that most of the internal bone problems on osteoporotic patients are not easy to detect using the currently available diagnostic methods, such as bone densitometry or biochemical markers, available to clinicians at present. Most cases of osteoporotic patients' frailty syndrome-which is possibly caused by internal bone problems-have to be treated with antiresorptive or osteoanabolic agents; known to effectively reduce the risk of osteoporotic fractures based on long-term prospective studies [10][11][12][13][14][15][16][17][18] . The weakness of implementating a more personalized pharmaceutical treatment on osteoporotic patients with internal bone problems is obvious.…”