Denosumab treatment in postmenopausal women with osteoporosis reply

Bone and mineral researc

EARLY FINDINGS FROM PROLIA (R) POST-MARKETING SAFETY SURVEILLANCE FOR ATYPICAL FEMORAL FRACTURE, OSTEONECROSIS OF THE JAW, SEVERE SYMPTOMATIC HYPOCALCEMIA, AND ANAPHYLAXIS

Bone and mineral researc

Findings from Denosumab (Prolia (R)) Post-marketing Safety Surveillance for Atypical Femoral Fracture, Osteonecrosis of the Jaw, Severe Symptomatic Hypocalcemia, and Anaphylaxis

Bone and mineral researc

Findings from Denosumab (Prolia (R)) Postmarketing Safety Surveillance for Serious Infections

Bone and mineral researc

Evolution of subject characteristics in FREEDOM and its extension for up to 8 years

Diabetes mellitus: pathophysiological changes and therap

Invasive Oral Procedures and Events in Postmenopausal Women With Osteoporosis Treated With Denosumab for Up to 10 Years

Context: Antiresorptive therapy has been associated with osteonecrosis of the jaw (ONJ), an infrequent but potentially serious adverse event.Objective: To assess information on invasive oral procedures and events (OPEs)-dental implants, tooth extraction, natural tooth loss, scaling/root planing, and jaw surgery-during the 7-year Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) Extension study and to present details of positively adjudicated ONJ cases.Design: Randomized, double-blind, placebo-controlled, 3-year trial (FREEDOM) followed by 7 years of open-label denosumab (FREEDOM Extension). At Extension Year 3, women were asked to record their history of invasive OPEs since the start of the Extension to Year 2.5 and oral events in the prior 6 months. The questionnaire was then administered every 6 months until the end of the Extension.Setting: Multicenter, multinational clinical trial.Patients: Postmenopausal women with osteoporosis.Interventions: Subcutaneous denosumab 60 mg or placebo every 6 months for 3 years, then 7 years of open-label denosumab.Main Outcome Measures: Self-reports of OPEs and adjudicated cases of ONJ.Results: Of respondents, 45.1 % reported at least one invasive OPE. The exposure-adjusted ONJ rate in FREEDOM Extension was 5.2 per 10,000 person-years. ONJ incidence was higher in those reporting an OPE (0.68%) than not (0.05%).Conclusions: Although invasive OPEs were common in these denosumab-treated women and were associated with an increased ONJ incidence, the overall rate of ONJ was low, and all cases with complete follow-up resolved with treatment.Bone and mineral researc

Denosumab or zoledronic acid in postmenopausal women with osteoporosis previously treated with oral bisphosphonates

Denosumab and zoledronic acid (ZOL) are parenteral treatments for patients with osteoporosis. The objective of the study was to compare the effect of transitioning from oral bisphosphonates to denosumab or ZOL on bone mineral density (BMD) and bone turnover. This was an international, multicenter, randomized, double-blind trial. Atotal of 643 postmenopausalwomenwith osteoporosis previously treated with oral bisphosphonates participated in the study. Subjects were randomized 1:1 to scdenosumab60mgevery 6 months plus iv placebo once or ZOL 5 mg iv once plus sc placebo every 6 months for 12 months. Changes in BMD and bone turnover markers were measured. BMD change from baseline at month 12 was significantly greater with denosumab compared with ZOL at the lumbar spine (primary end point; 3.2% vs 1.1%; P <.0001), total hip (1.9% vs 0.6%; P <.0001), femoral neck (1.2% vs -0.1%; P <.0001), and one-third radius (0.6% vs 0.0%; P <.05). The median decrease from baseline was greater with denosumab than ZOL for serum C-telopeptide of type 1 collagen at all time points after day 10 and for serum procollagen type 1 N-terminal propeptide at month 1 and at all time points after month 3 (all P <.05). Median percentage changes from baseline in serum intact PTH were significantly greater at months 3 and 9 with denosumab compared with ZOL (all P <.05). Adverse events were similar between groups. Three events consistent with the definition of atypical femoral fracture were observed (two denosumab and one ZOL). In postmenopausal women with osteoporosis previously treated with oral bisphosphonates, denosumab was associated with greaterBMDincreases at all measured skeletal sites and greater inhibition of bone remodeling compared with ZOL