Osteolytic bone disorders are characterized by an overall reduction in bone mineral density which enhances bone ductility and vulnerability to fractures. This disorder is primarily associated with superabundant osteoclast formation and bone resorption activity. Nicorandil (NIC) is a vasodilatory anti-anginal drug with ATP-dependent potassium (KATP) channel openings. However, NIC is adopted to manage adverse cardiovascular and coronary events. Recent research has demonstrated that NIC also possesses anti-inflammatory peculiarity through the regulation of p38 MAPK and NF-κB signaling pathways. Both MAPK and NF-κB signaling pathways play pivotal roles in RANKL-induced osteoclast formation and bone resorption function. Herein, we hypothesized that NIC may exert potential biological effects against osteoclasts, and revealed that NIC dose-dependently suppressed bone marrow macrophage (BMM) precursors to differentiate into TRAP + multinucleated osteoclasts in vitro. Furthermore, osteoclast resorption assays demonstrated anti-resorptive effects exhibited by NIC. NIC had no impact on osteoblast differentiation or mineralization function. Based on Biochemical analyses, NIC relieved RANKL-induced ERK, NF-κB and p38 MAPK signaling without noticeable effects on JNK MAPK activation. However, the attenuation of NF-κB and p38 MAPK activation was sufficient to hamper the downstream induction of c-Fos and NFATc1 expression. Meanwhile, NIC administration markedly protected mice from ovariectomy (OVX)-induced bone loss through in vivo inhibition of osteoclast formation and bone resorption activity. Collectively, this work demonstrated the potential of NIC in the management of osteolytic bone disorders mediated by osteoclasts.

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Background The indirect reduction is one kind of micro-invasive technology. The most important mechanism of indirect reduction is traction.The purpose of this study was to independently develop a traction reduction device on lower limb fracture and explore the clinical effect of micro-invasive treatment on tibial fracture adopting this device. Methods A retrospective study was conducted on 21patients with tibial fracture adopted this device to assist fracture reduction during operation from August 2019 to June 2022. The cases included 10 tibial plateau fractures, 6 tibial shaft fractures and 5 distal tibia (pilon )fractures. 3 tibial shaft fracture cases were adopted intramedullary needle internal fixations, the others cases were adopted plate internal fixations.Demographic data, fracture type, perioperative data, and radiological evaluation were collected. Clinical outcomes were graded using Rasmussen function score and American orthopedic foot and ankle society (AOFAS) score. Results The cases were followed up from 12 to 33 months.All cases had no complications such as blood vessel and nerve injuries,infection and internal fixation fail. All cases got bony healing. The mean Rasmussen anatomy score before operation of tibial plateau cases was (6.60 ± 3.13), the score immediately after operation was (17.20 ± 1.03), and there was statistical significance difference between two groups(P༜0.05). The mean Rasmussen function score of tibial plateau fracture cases at the last follow-up was(28.20 ± 1.55).The mean length difference between both lower limbs of tibia shaft fracture cases immediately after operation was (2.17 ± 2.04) mm, and the mean varus-valgus angulation of tibia shaft fracture immediately after operation was (1.67 ± 0.82)°, the mean fracture anteroposterior angulation of tibia shaft fracture immediately after operation was (2.00 ± 1.10)°. The Burwell-Charnley radiological assessment immediately after operation of distal tibia cases was as follow, 5 cases got anatomical reduction and 1 got good reduction. The mean AOFAS score of ankle and foot function at the last follow-up was( 93.60 ± 5.73). Conclusions The traction reduction device on lower limb fracture is safe effective to application, convenient to use, and has definite reduction effect. It can be applied in supine, lateral and prone positions, and be applied to micro-invasive treatment on complex tibia fracture.