Abstract
Romosozumab is an antisclerostin antibody that increases bone formation and decreases bone resorption. This study aimed to identify predictors of the response to romosozumab in women with postmenopausal osteoporosis previously treated with denosumab. The study had an observational pre-post design and included 167 women with primary osteoporosis. Romosozumab 210 mg was administered subcutaneously every 4 weeks for 12 months in 87 patients who had been treated with denosumab (DMAb group) and 80 who had not (naïve group). The safety, incidence of new fractures, and changes in bone mineral density (BMD) and bone turnover markers were recorded. At 12 months, a response was defined as a ≥ 3.0% increase in BMD and a non-response as a ≥ 3.0% decrease in BMD. Non-serious adverse events occurred in six patients (3.6%) in each group. New fractures occurred in three patients (4.0%) in the DMAb group and one (1.6%) in the naïve group. At 12 months, the changes in BMD at the lumbar spine and total hip were + 12.6% and + 4.7%, respectively, in the naïve group and + 3.9% and + 0.5% in the DMAb group. Bone turnover markers increased gradually after discontinuation of denosumab. A higher P1NP at baseline was associated with a response to romosozumab and a higher TRACP-5b at 3 months and longer duration of treatment with denosumab were associated with no BMD response at the total hip (TH). Longer denosumab use (≥18 months) followed by romosozumab may be associated with reduced TH BMD response and requires validation in larger prospective studies.