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Bone remodeling plays an important role in the bone healing process; for example, following fracture. The relative ratio of the receptor activator of nuclear factor kappa B ligand (RANKL)/ osteoprotegerin (OPG) controls osteoclast differentiation, thereby playing a pivotal role in the regulation of bone remodeling. Propofol, a widely used anesthetic agent in orthopedic procedures, is considered to possess potential antioxidant properties owing to its structural similarity to α-tocopherol. Antioxidants are known to enhance bone healing. Accordingly, in the present study, we aimed to investigate osteoblastic differentiation and RANKL/OPG expression following propofol administration, in order to assess the potentially beneficial effects of this drug on the bone remodeling process, using calvarial primary osteoblasts from newborn mice. Calvarial pre-osteoblast cells were cultured in media containing clinically relevant concentrations of propofol, and cytotoxicity, effects on cell proliferation, osteogenic activity, and osteoclastogenesis were examined. The present findings indicated that propofol did not exert cytotoxic effects or alter cell proliferation in primary calvarial osteoblasts. Further, propofol did not affect osteoblast differentiation. The RANKL/OPG ratio was found to be decreased following propofol administration, and osteoclastogenesis was significantly reduced, indicating that propofol attenuated the osteoclastogenesis-supporting activity of osteoblasts. The results demonstrate that propofol, at clinically relevant concentrations, exerts beneficial effects on bone remodeling by attenuating osteoclastogenesis via suppression of the RANKL/OPG expression axis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Purpose: This prospective, double-blind, placebo-controlled study was designed to determine the efficacy of nitrous oxide (N(2)O) in alleviating the pain that followed sequential injection of propofol and rocuronium., Methods: A total of 205 adult patients (age, 18-68 years) received one of the following combinations: NaCl and 100 % O(2) (group C); 0.5 mg/kg lidocaine and 100 % O(2) (group L); NaCl and a mixture of 67 % N(2)O/O(2) (group N); or 0.5 mg/kg lidocaine and a mixture of 67 % N(2)O/O(2) (group LN). Vein occlusion was released after 1 min, and 5 ml propofol was injected over 10 s. Pain was evaluated on a visually enlarged, laminated, numeric rating (0-10) scale. The remainder of the induction dose of propofol (with a 3-ml bolus of normal saline and 0.6 mg/kg rocuronium) was then injected. The response to the rocuronium injection was assessed with a four-point scale (0-3)., Results: The incidence and severity of pain from the propofol injection in groups L, N, and LN were significantly lower than those in group C (P < 0.001). Frequency and intensity of the withdrawal response were significantly less in groups N and LN than in groups C and L (no response, P < 0.001; severe response, P < 0.001)., Conclusions: Pretreatment with inhaled N(2)O can reduce the pain associated with propofol and rocuronium injection. Moreover, N(2)O (with or without lidocaine) is more effective than lidocaine alone in reducing rocuronium-related withdrawal reactions associated with sequential injection of propofol and rocuronium.