Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy

Abstract

Patients treated with bisphosphonates for osteoporosis may discontinue or require a switch to other therapies. Denosumab binds to RANKL and is a potent inhibitor of bone resorption that has been shown to increase bone mineral density (BMD) and decrease fracture risk in postmenopausal women with osteoporosis. This was a multicenter, international, randomized, double-blind, double-dummy study in 504 postmenopausal women ! 55 years of age with a BMD T-score of À2.0 or less and À4.0 or more who had been receiving alendronate therapy for at least 6 months. Subjects received open-label branded alendronate 70 mg once weekly for 1 month and then were randomly assigned to either continued weekly alendronate therapy or subcutaneous denosumab 60 mg every 6 months and were followed for 12 months. Changes in BMD and biochemical markers of bone turnover were evaluated. In subjects transitioning to denosumab, total hip BMD increased by 1.90% at month 12 compared with a 1.05% increase in subjects continuing on alendronate ( p < .0001). Significantly greater BMD gains with denosumab compared with alendronate also were achieved at 12 months at the lumbar spine, femoral neck, and 1/3 radius (all p < .0125). Median serum CTX levels remained near baseline in the alendronate group and were significantly decreased versus alendronate ( p < .0001) at all time points with denosumab. Adverse events and serious adverse events were balanced between groups. No clinical hypocalcemic adverse events were reported. Transition to denosumab produced greater increases in BMD at all measured skeletal sites and a greater reduction in bone turnover than did continued alendronate with a similar safety profile in both groups. ß

Efficacy of Denosumab for Control of Bone Mineral Density and Microarchitecture in Postmenopausal Women with Osteoporosis: A One-Year Experience

“…Despite all these limitations of our study, we found a clear positive effect of denosumab treatment. these results are in accordance with the already published data on denosumab efficacy in increasing BMD in comparison to placebo and bisphosphonates (3,10,13,15). in regards to the adverse events, denosumab was well tolerated by all patients with no serious adverse events, which is in full correlation with its SmPc and previously reported data (6,17,19).…”

Treatment Sequence Matters: Anabolic and Antiresorptive Therapy for Osteoporosis

“…(11)(12)(13)(14)(15)(16)(17) Effects of most osteoporosis medications differ, however, in patients who have already been pretreated with other potent osteoporosis medications. (18)(19)(20)(21)(22)(23) This is certainly true of TPTD and PTH. (24)(25)(26)(27)(28)(29)(30) BMD responses to initial TPTD/PTH followed by potent antiresorptive therapy are substantial in both spine and hip sites as a result of the effects of both components of the treatment sequence.…”

Bisphosphonates Induced Atypical Femoral Fracture in Metastatic Breast Cancer: Misleading Benign Problem in a Malignant Condition

“…If this remodeling process is interrupted by anti-resorptive drugs, microfractures will grow, fuse, and cause stress fractures [6]. The risk of AFFs is reported to increase with the increased duration of Bisphosphonate treatment, from 1.8 cases per 10 5 users per year of exposure in the first 2 years, to 113 cases per 10 5 users per year at 8 years of Bisphosphonate use [7]. Our patient developed her fracture after 6 years of Bisphosphonate use.…”