OBJECTIVE: Post-traumatic critical-sized bone defects pose a reconstructive challenge for reconstructive surgeons. The vascularized fibula graft is a well-described treatment for osseous defects of the femur and tibia. This study aimed to assess long-term patient-reported quality of life, the success-, and complication rates in lower extremity reconstruction with vascularized fibula grafts.
METHODS: A retrospective cohort of 29 patients who underwent fibula graft reconstruction for critical-sized bone defects after post-traumatic tibial and femoral bone loss between 1990 and 2021 was included. To assess the health-related quality of life and return to work and satisfaction, a cross-sectional survey was performed using the short-form-36, lower extremity functional scale, and a self-made questionnaire including the DN4, satisfaction, and subjective ankle function.
RESULTS: The median bone defect size was 8 cm (IQR 9-7 cm). The mental component scores were comparable to the Dutch population norm, whereas the impaired physical function scores were associated with pain (r 0.849, p < 0.001). Neuropathic symptoms were reported in 7 out of 19 patients, and 11 out of 19 patients returned to normal daily activity. All respondents reported positive or neutral scores on overall satisfaction with the recovery. Bone healing was uneventful in 19 out of 29 patients. Union was achieved in 25 out of 29 patients. Persistent nonunion was observed in 4 patients, leading to amputation in 2 patients.
CONCLUSIONS: Vascularized fibula graft use led to high union rates and limb salvage in patients with post-traumatic segmental bone loss of the tibia and femur. Patient satisfaction with the overall recovery was positive; however, functional outcomes remained impaired.

The Latarjet procedure, including coracoid transfer, is indicated for anterior glenohumeral instability and significant bone loss. However, even in experienced hands, the Latarjet procedure is associated with potential complications including neurovascular injury, graft resorption leading to painful or broken hardware and secondary subscapularis damage, prominent hardware, and graft non-union. An adjustable suture button technique may minimize hardware complications, and show low rates of non-union and resorption. (Perhaps, overly rigid fixation of the coracoid using screws contributes to the resorption.) Coracoid transfer may be avoided using various graft sources including iliac crest bone grafting. Despite loss of the \"sling effect\" provided by coracoid and conjoined tendon transfer, the procedure shows good outcomes with low recurrent instability for indicated patients. While technically complex, bone graft and suspensory fixation may be performed arthroscopically. Time will tell if this technique may supersede the Latarjet.

Postmenopausal osteoporosis (PMO) is a common disease associated with aging, and estrogen deficiency is considered to be the main cause of PMO. Recently, however, osteoimmunology has been revealed to be closely related to PMO. On the one hand, estrogen deficiency directly affects the activity of bone cells (osteoblasts, osteoclasts, osteocytes). On the other hand, estrogen deficiency-mediated osteoimmunity also plays a crucial role in bone loss in PMO. In this review, we systematically describe the progress of the mechanisms of bone loss in PMO, estrogen deficiency-mediated osteoimmunity, the differences between PMO patients and postmenopausal populations without osteoporosis, and estrogen deficiency-mediated immune cells (T cells, B cells, macrophages, neutrophils, dendritic cells, and mast cells) activity. The comprehensive summary of this paper provides a clear knowledge context for future research on the mechanism of PMO bone loss.

BACKGROUND: Mechanical unloading-induced bone loss threatens prolonged spaceflight and human health. Recent studies have confirmed that osteoporosis is associated with a significant reduction in bone microvessels, but the relationship between them and the underlying mechanism under mechanical unloading are still unclear.
METHODS: We established a 2D clinostat and hindlimb-unloaded (HLU) mouse model to simulate unloading in vitro and in vivo. Micro-CT scanning was performed to assess changes in the bone microstructure and mass of the tibia. The levels of CD31, Endomucin (EMCN) and histone deacetylase 6 (HDAC6) in tibial microvessels were detected by immunofluorescence (IF) staining. In addition, we established a coculture system of microvascular endothelial cells (MVECs) and osteoblasts, and qRT‒PCR or western blotting was used to detect RNA and protein expression; cell proliferation was detected by CCK‒8 and EdU assays. ChIP was used to detect whether HDAC6 binds to the miRNA promoter region.
RESULTS: Bone mass and bone microvessels were simultaneously significantly reduced in HLU mice. Furthermore, MVECs effectively promoted the proliferation and differentiation of osteoblasts under coculture conditions in vitro. Mechanistically, we found that the HDAC6 content was significantly reduced in the bone microvessels of HLU mice and that HDAC6 inhibited the expression of miR-375-3p by reducing histone acetylation in the miR-375 promoter region in MVECs. miR-375-3p was upregulated under unloading and it could inhibit MVEC proliferation by directly targeting low-density lipoprotein-related receptor 5 (LRP5) expression. In addition, silencing HDAC6 promoted the miR-375-3p/LRP5 pathway to suppress MVEC proliferation under mechanical unloading, and regulation of HDAC6/miR-375-3p axis in MVECs could affect osteoblast proliferation under coculture conditions.
CONCLUSIONS: Our study revealed that disuse-induced bone loss may be closely related to a reduction in the number of bone microvessels and that the modulation of MVEC function could improve bone loss induced by unloading. Mechanistically, the HDAC6/miR-375-3p/LRP5 pathway in MVECs might be a promising strategy for the clinical treatment of unloading-induced bone loss.

Stage IV grade C localized periodontitis (pre-puberal localized aggressive periodontitis/LPP), an extremely rare form of periodontal disease, occurs in otherwise healthy individuals (no signs of dental plaque/calculus) due a hyper-aggressive auto-immune response to high periodontopathic bacteria levels. Methods: A 4-year-old Caucasian girl with unusually high mobility of the deciduous lower left canine and localized gingival inflammation was misrecognized by multiple clinicians (initially diagnosed with hypophosphatasia, genetic and metabolic disorders, all turning negative), over a period of 4-6 months, despite initial radiographs showing clear pathognomonic signs. The LPP diagnostic was made by the last clinician, but by then the tooth was lost. Similar inflammation signs appeared around the lower deciduous right canine. X-ray examination showed similar bone and periodontal loss as previously seen, while periodontopathic bacteria tested highly positive. The patient received both mechanical cleaning and ten days of systemic antibiotic treatment (Augmentin and Metronidazole). Results: Two months later, inflammation signs disappeared, with periodontal regeneration radiologically present, and only small periodontopathic bacteria precursor concentrations. Conclusions: Despite initial periodontal loss, an adequate treatment can keep under control an LPP disease. Moreover, bone and periodontal regeneration appears if periodontopathic bacteria scores are kept lower, showing the importance of fast adequate diagnostic and treatment.

UNASSIGNED: Titanium dental implants, traditionally used for tooth replacement, face certain biological and aesthetic limitations. Recently, zirconia has become a notable alternative, valued for its aesthetics and biocompatibility. This study evaluated the efficacy of two-piece zirconia dental implants, particularly their impact on inflammatory cytokines and their survival rate over one year.
UNASSIGNED: This study was a single-center, prospective trial and included adults aged 18 and above. 2021-2022, nine two-piece tissue-level zirconia implants were placed in eight patients. Following a three-month osseointegration phase, crowns were cemented. Over a year, we assessed Plaque and Gingival indices, Pocket Depth, and tissue color and texture. Peri-apical radiographs measured bone levels, and IL-1β in peri-implant crevicular fluid (PICF) was quantified using ELISA.
UNASSIGNED: Eight subjects (ages 31-63) participated. One implant failed after six months, resulting in a one-year survival rate of 88.8%. Plaque and Gingival indices rose, but peri-implant soft tissue remained stable in color and texture. At 12 months, average bone loss was minimal and insignificant compared to the baseline. IL-1β levels were similar to those at contralateral teeth, with no correlation between IL-1β, Pocket Depth, and Bleeding on Probing.
UNASSIGNED: Two-piece zirconia implants emerged as a viable tooth replacement option, with an 88.8% one-year survival rate. They maintained stable soft tissue and bone levels, indicating their potential as effective dental restoratives.

Hyperactive osteoclasts and hypoactive osteoblasts usually result in osteolytic conditions such as estrogen-deficiency bone loss. Few natural compounds that both attenuating bone resorption and enhancing bone formation could exert effects on this imbalance. 5-Deoxycajanin (5-D), an isoflavonoid extracted from Cajan leaf with estrogen-like properties, were found to have beneficial pharmacological effects on rebalancing the activities of osteoclasts and osteoblasts. This study revealed that 5-D at the same concentration could inhibit osteoclastogenesis of BMMs and promoted osteoblast differentiation of BMSCs. 5-D not only attenuated the fluorescent formation of RANKL-induced F-actin belts and NFATc1, but also activated ALP and RUNX2 expressions. As to downstream factor expressions, 5-D could block osteoclast-specific genes and proteins including NFATc1 and CTSK, while increased osteogenic genes and proteins including OPG and OCN, as confirmed by Real-time PCR and Western Blotting. Additionally, the network pharmacology and molecular docking identified the involvement of 5-D in the MIF and MAPK signaling pathways and the stable binding between 5-D and MAPK2K1. Further Western blot studies showed that 5-D decreased the phosphorylation of p38 and ERK in osteoclasts, but promoted these phosphorylations in osteoblasts. In a female C57BL/6J mouse model of estrogen deficiency-induced bone loss, 5-D demonstrated efficacy in enhancing BMD through attenuating osteoclast activities and promoting osteogenesis. These results underscore the potential application of 5-D on treating osteolysis resulting from hyperactive osteoclasts and hypoactive osteoblasts, shedding light on modulating osteoclast-osteoblast homeostasis.

Staphylococcus aureus (S. aureus)-induced bone loss is a significant challenge in the treatment of osteomyelitis. Our previous study was the first to confirm that granulocyte colony-stimulating factor (G-CSF) mediates S. aureus-induced bone loss. However, the underlying mechanism remains unknown. The objective of this study was to elucidate this. We found G-CSF mediated BMSC senescence and increased IL-1β concentration of serum and bone marrow in mice after S. aureus infection. Furthermore, we demonstrated that G-CSF promoted the expression of IL1b in murine bone marrow-derived neutrophils. Notably, we identified that IL-1β mediated BMSC (bone marrow mesenchymal stromal cell) senescence in mice after S. aureus infection. Importantly, IL-1β neutralizing antibody effectively alleviated BMSC senescence and bone loss caused by S. aureus infection in mice. In terms of molecular mechanism, we found IL-1β induced BMSC senescence by JNK/P53 and JNK/BCL2 pathways. Collectively, G-CSF promotes IL-1β production which induces BMSC senescence via JNK/P53 and JNK/BCL2 pathways, leading to S. aureus-induced bone loss. This study identified novel targets for preventing and treating S. aureus-induced bone loss in osteomyelitis.

Bone transplant with osteopromotive elements - such as herbal extracts - that promote the creation of new boneis of interest to dentists. Hence, we compared the bone loss around dental implants while placing platelet rich fibrin (PRF) scaffold alone and PRF scaffold with simvastatin (SIM) and PRF scaffold with Moringaoleifera (MO). There were thirty six patients total. A total of 36 implants, or twelve implants in all three categories, were the estimated sample size. Category 1: PRF scaffolds alone. Category 2: PRF scaffolds with SIM. Category 3: PRF scaffolds with MO. Alteration in the bones were measured with CBCT. It was observed that there was decreased loss of crestal bone in PRF+ SIM and PRF+MO as compared to PRF alone. The use of herbal osteopromotive agents like simvastitin and Moringaoleifera along with PRF scaffolds can be effective in reducing bone loss around dental implants.

The aim of the present review is to discuss the roles of vitamin K (phylloquinone or menaquinones) and vitamin K-dependent proteins, and the combined action of the vitamins K and D, for the maintenance of bone health. The most relevant vitamin K-dependent proteins in this respect are osteocalcin and matrix Gla-protein (MGP). When carboxylated, these proteins appear to have the ability to chelate and import calcium from the blood to the bone, thereby reducing the risk of osteoporosis. Carboxylated osteocalcin appears to contribute directly to bone quality and strength. An adequate vitamin K status is required for the carboxylation of MGP and osteocalcin. In addition, vitamin K acts on bone metabolism by other mechanisms, such as menaquinone 4 acting as a ligand for the nuclear steroid and xenobiotic receptor (SXR). In this narrative review, we examine the evidence for increased bone mineralization through the dietary adequacy of vitamin K. Summarizing the evidence for a synergistic effect of vitamin K and vitamin D3, we find that an adequate supply of vitamin K, on top of an optimal vitamin D status, seems to add to the benefit of maintaining bone health. More research related to synergism and the possible mechanisms of vitamins D3 and K interaction in bone health is needed.