The healthy skeleton requires a perfect coordination of the formation and degradation of bone. Metabolic bone disease like osteoporosis is resulted from the imbalance of bone formation and/or bone resorption. Osteoporosis also reflects lower level of bone matrix, which is contributed by up-regulated osteoclast-mediated bone resorption. It is reported that monocytes/macrophage progenitor cells or either hematopoietic stem cells (HSCs) gave rise to multinucleated osteoclasts. Thus, inhibition of osteoclastic bone resorption generally seems to be a predominant therapy for treating osteoporosis. Recently, more and more natural compounds have been discovered, which have the ability of inhibiting osteoclast differentiation and fusion. Alliin (S-allyl-l-cysteine sulfoxides, SACSO) is the major component of aged garlic extract (AGE), bearing broad-spectrum natural antioxidant properties. However, its effects on bone health have not yet been explored. Hence, we designed the current study to explore its effects and role in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast fusion and differentiation. It was revealed that alliin had an inhibitory effect in osteoclasteogenesis with a dose-dependent manner via blocking the c-Fos-NFATc1 signaling pathway. In addition, alliin decreased the generation of reactive oxygen species (ROS) and down-regulated the expression of NADPH oxidase 1 (Nox1). The overall results revealed that alliin could be a potential therapeutic agent in the treatment of osteoporosis.

Skeletal homeostasis is closely effectuated by the regulation of bone formation and bone resorption. Osteoclasts are multinuclear giant cells responsible for bone resorption. Overactivated osteoclasts and excessive bone resorption result in various lytic bone diseases, such as osteoporosis, osteoarthritis, periprosthetic infection, and inflammatory aseptic loosening of orthopedic implants. In consideration of the severe side effects caused by the currently available drugs, exploitation of novel drugs has gradually attracted attention. Because of its antiinflammatory, antioxidant, and antitumor capacities, diallyl disulfide (DADS), a major oil‐soluble organosulfur ingredient compound derived from garlic, has been widely researched. However, the effects of DADS on osteoclasts and lytic bone diseases are still unknown. In this study, we investigated the effects of DADS on receptor activator of NF‐κB ligand (RANKL)‐ and LPS‐mediated osteoclastogenesis, LPS‐stimulated proinflammatory cytokines related to osteoclasts, and LPS‐induced inflammatory osteolysis. The results showed that DADS significantly inhibited RANKL‐mediated osteoclast formation, fusion, and bone resorption in a dose‐dependent manner via inhibiting the NF‐κB and signal transducer and activator of transcription 3 signaling and restraining the interaction of NF‐κB p65 with nuclear factor of activated T cells cytoplasmic 1. Furthermore, DADS also markedly suppressed LPS‐induced osteoclastogenesis and reduced the production of proinflammatory cytokines with LPS stimulation to indirectly mediate osteoclast formation. Consistent with the in vitro results, DADS prevented the LPS‐induced severe bone loss by blocking the osteoclastogenesis. All of the results indicate that DADS may be a potential and exploitable drug used for preventing and impeding osteolytic lesions.—Yang, J., Tang, R., Yi, J., Chen, Y., Li, X., Yu, T., Fei, J. Diallyl disulfide alleviates inflammatory osteolysis by suppressing osteoclastogenesis via NF‐κB–NFATc1 signal pathway. FASEB J. 33, 7261–7273 (2019). www.fasebj.org

Bone infection is a common and serious complication in the orthopedics field, which often leads to excessive bone destruction and non‐union. Osteoclast is the only type of cells which have the function of bone resorption. Its over activation is closely related to excessive bone loss. Staphylococcus aureus (S. aureus) is a major pathogen causing bone infection, which can produce a large number of strong pathogenic substances staphylococcal protein A (SPA). However, few studies were reported about the effects of SPA on osteoclastogenesis. In our study, we observed that S. aureus activated osteoclasts and promoted bone loss in bone infection specimens. Then, we investigated the effects of SPA on RANKL‐induced osteoclastogenesis in vitro, the results revealed that SPA promoted osteoclastic differentiation and fusion, and enhanced osteoclastic bone resorption. In addition, we also showed that SPA upregulated the expression of NFATc1 and c‐FOS through the activation of MAPK signaling to promote osteoclastogenesis. Our findings might help us better understand the pathogenic role of S. aureus in bone infection and develop new therapeutic strategies for infectious bone diseases.

There are still controversies between surgical treatment and conservative treatment for multiple rib fractures (MRFs). No consensus has been reached concerning the indications and timing of surgery. In this meta-analysis, we aimed to determine the optimal treatment for MRFs. Six databases (PubMed, Medline, Embase, Cochrane, Cnki, Wanfang Database) were retrieved for all eligible randomized controlled trials (RCTs) published before January 2020. MRFs were treated either with operative reduction and internal fixation or conservative treatment. The pertinent data were retrieved. The quality of RCTs was evaluated by the modified Jadad rating scale and meta-analysis was performed using RevMan 5.3 software. Seven RCTs involving 538 MRFs patients (260 were treated surgically vs. 278 conservatively) were included in this meta-analysis. Compared with conservative treatment, surgical treatment resulted in shorter length of hospital stay (WMD -8.48; 95% CI -11.34 to -5.63; P < 0.001), length of ICU stay (WMD -5.72; 95% CI -7.31 to -4.13; P < 0.001) and duration of mechanical ventilation (WMD -4.93; 95% CI -8.79 to -1.07; P = 0.01), with a lower risk of complications including pneumonia (RR 0.40; 95% CI 0.30 to 0.53; P < 0.001) and chest wall deformity (RR 0.07; 95% CI 0.03 to 0.14; P < 0.001). The sensitivity analysis carried out by excluding one study with significant heterogeneity showed that the rate of tracheostomy was lower in the surgical group than in the conservative group (RR 0.44; 95% CI 0.28 to 0.71; P = 0.0008). For patients with MRFs, surgical treatment resulted in faster recovery, a lower risk of complications and better prognosis than conservative treatment.

Impaired callus remodeling significantly contributes to the delayed healing of osteoporotic fractures; however, the underlying mechanisms remain unclear. Sensory neuronal signaling plays a crucial role in bone repair. In this study, we aimed to investigate the pathological mechanisms hindering bone remodeling in osteoporotic fractures, particularly focusing on the role of sensory neuronal signaling. We demonstrate that in ovariectomized (OVX) mice, the loss of CGRP⁺TrkA⁺ sensory neuronal signaling during callus remodeling correlates with increased Cx3cr1⁺iOCs expression within the bone callus. Conditional knockout of Cx3cr1⁺iOCs restored CGRP⁺TrkA⁺ sensory neuronal, enabling normal callus remodeling progression. Mechanistically, we further demonstrate that Cx3cr1⁺iOCs secrete Sema3A in the osteoporotic fracture repair microenvironment, inhibiting CGRP⁺TrkA⁺ sensory neurons’ axonal regeneration and suppressing nerve–bone signaling exchange, thus hindering bone remodeling. Lastly, in human samples, we observed an association between the loss of CGRP⁺TrkA⁺ sensory neuronal signaling and increased expression of Cx3cr1⁺iOCs. In conclusion, enhancing CGRP⁺TrkA⁺ sensory nerve signaling by inhibiting Cx3cr1⁺iOCs activity presents a potential strategy for treating delayed healing in osteoporotic fractures.