In the FREEDOM study, the median eroded surface was reduced by more than 80%%, and osteoclasts were absent from more than 50%% of biopsies in the denosumab group.
The FREEDOM study also included prespecified subgroup analyses of patients at higher risk of fracture, including those with a baseline femoral neck BMD T-score −2.5 or less.
46, 47 In the Freedom study, a multicenter, prospective, centrally randomized, Phase III open-label study, colistimethate sodium dry-powder formulation inhaled via the Turbospin® device (PH&T SpA, Milan, Italy) was compared with classic tobramycin nebulizer solution.
In the Freedom study, which compared colistin dry powder with tobramycin inhalation solution, adverse events such as cough, throat irritation, and abnormal taste were significantly more prevalent in the colistin dry-powder treatment group.
51 On the other hand, in the FREEDOM study (which was analyzed in the above meta-analysis), there was no clear relationship between overall infections and exposure to denosumab.
Univariate sensitivity analyses were performed using efficacy data from the denosumab FREEDOM study for a subpopulation of patients with T-scores of –2.5 or less at the femoral neck, and by extrapolating the treatment duration to 10 years.
The primary data from the phase 3 FREEDOM study of the effects of denosumab in women with postmenopausal osteoporosis were used to compute country-specific probabilities, using the FRAX tool (version 3.2).
As in other withdrawal studies [ 34], including the Future Revascularization Evaluation in patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM) study of pregabalin in fibromyalgia [ 35], the present study focused on a subset of patients who responded to treatment.
Because of the large number of patients included in the FREEDOM study and the wide scatter in age (60 90 years), subgroup analyses were prospectively planned before study unblinding to evaluate the effect of denosumab on new vertebral and nonvertebral fractures across various subgroups.
Iliac crest bone biopsies were collected at 24 and/or 36 months from osteoporotic postmenopausal women in the FREEDOM study (45 women receiving placebo and 47 denosumab) and at 12 months from postmenopausal women who had previously been treated with alendronate in the STAND study (21 continuing alendronate and 15 changed to denosumab at trial entry).
