The Safety of Clodronate, Neridronate and Sequential Therapy in the Management of Bone Marrow Oedema: A Retrospective Observational Study

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Introduction: Bisphosphonates (BPs) are commonly used to treat osteoporosis as well as Bone Marrow Edema (BME). Potential adverse effects include hypocalcemia, flu-like symptoms, musculoskeletal pain, gastrointestinal issues, and, rarely, osteonecrosis of the jaw. This study evaluated the safety of intramuscular formulations of neridronate, clodronate, and their sequential combination in patients with BME. Methods: A retrospective observational study was performed on 128 outpatients referred for BME between May 2020 and June 2025. Primary outcome was reduction in clinical symptoms; secondary outcomes included Adverse Drug Reactions (ADRs) and Drug–Drug Interactions (DDIs). results: In this study we enrolled 128 patients (69 females and 59 males) with a median age of 66 years (IQR: 54.5-75). The median number of sessions needed for recovery differed depending on the drug group: Neridronate took 4 sessions (IQR: 3–4), Clodronate took 12 sessions (IQR: 5–23), and the combination of Clodronate and Neridronate took 14 sessions (IQR: 9–23). No significant interactions were observed between drug type and sex, age, or the presence of other diseases. Results: Median age was 66 years (IQR: 54.5–75), with 69 females and 59 males. Median sessions to recovery were 4 (neridronate), 12 (clodronate), and 14 (combination). Negative binomial regression showed that significantly more sessions were required for clodronate and combination therapy compared with neridronate. No severe ADRs occurred, despite polytherapy and potential DDIs. Male patients showed a non-statistically significant trend to a lower number of sessions and potentially inappropriate prescription. The number of medications was the only factor directly related to DDIs (p < 0.05). Discussion: The lower number of median sessions for clodronate was likely due to a small sample size. The low number of side effects is probably related to intramuscular administration. Factors like age and sex can be relevant in the onset of DDIs in other clinical contexts, but our population displayed a relatively low median age. Conclusion: Bisphosphonates were safe and effective for BME in our cohort, with a low risk of clinically relevant DDIs. However, larger studies are needed to confirm these results.

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