Can sphingosine-1-phosphate control bisphosphonate-mediated bone formation?

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The jawbone necrosis caused by bisphosphonate (BP) is a globally recognized adverse effect of BP treatment. In 2008, the Japanese Society of Oral and Maxillofacial Surgeons defined guidelines for prevention, diagnosis, and medical treatment of this adverse effect, and obtained consensus for these guidelines in Japan. However, many aspects related to the morbidity of this condition have not been clarified, and there are no instructions for medical treatment. A recent study showed that sphingosine-1-phosphate (S1P) participates in bone remodeling regulation. Although we have shown experimentally that RANKL/OPG imbalance was produced by adding risk factors to BP, the aim of this study was to verify whether S1P further influences BP-mediated bone remodeling.