A Novel Surgical Technique for the Management of Large-Volume Neurogenic Heterotopic Ossification Following a Spinal Cord Injury: The Sashimi Technique.

This case series investigates the efficacy of the "sashimi technique," a novel surgical approach utilizing a curved chisel for the resection of heterotopic ossification (HO). The main focus is on reducing resection margins and preventing excessive bone removal while maintaining optimal functional outcomes and preventing recurrence. Two cases illustrate successful outcomes in patients with spinal cord injuries and severe HO of the hip, emphasizing the precision of using the curved chisel-based technique in improving patient mobility while still achieving a desired resection margin. The study highlights the effectiveness of using a curved chisel in protecting neurovascular structures and maintaining resection precision. Additionally, the integration of postoperative radiotherapy and pharmacological treatment is emphasized as a strategy to prevent recurrence. The goal of this procedure is to improve functional outcomes and patient quality of life.

Bilateral Well Leg Compartment Syndrome Localized in the Anterior and Lateral Compartments following Urologic Surgery in Lithotomy Position.

Well leg compartment syndrome (WLCS) is a rare but severe complication after the surgery in lithotomy position. We present a case of bilateral WLCS that occurred after the prolonged urologic surgery in lithotomy position. A 50-year-old man complained of severe bilateral lower leg pain and swelling sixteen hours after the surgery. Physical examination, elevated serum creatine kinase value, contrasting computed tomography, and elevated compartment pressure strongly suggested the development of bilateral WLCS localized in the anterior and lateral compartments. Emergent single-incision fasciotomy was performed four hours after diagnosis. The patient was treated successfully without any neuromuscular dysfunction. An early and accurate diagnosis is important to avoid the delay of treatment and development of neuromuscular dysfunction.

Tumor necrosis factor receptor-associated factor 6 is required to inhibit foreign body giant cell formation and activate osteoclasts under inflammatory and infectious conditions.

Osteoclasts and foreign body giant cells (FBGCs) are derived from common progenitors and share properties such as multi-nucleation capacity induced by cell-cell fusion; however, mechanisms underlying lineage determination between these cells remain unclear. Here we show that, under inflammatory conditions, osteoclasts are stimulated in a manner similar to M1 macrophages, while formation of FBGCs, which exhibit M2-like phenotypes, is inhibited in a manner similar to that seen in M1/M2 macrophage polarization. FBGC/osteoclast polarization was inhibited by conditional knockout of tumor necrosis factor receptor associated factor 6 (Traf6) in adults in vivo and in vitro. Traf6-null mice were previously reported to die soon after birth, but we found that Traf6 deletion in adults did not cause lethality but rather inhibited osteoclast activation and prevented FBGC inhibition under inflammatory conditions. Accordingly, basal osteoclastogenesis was significantly inhibited by Traf6 deletion in vivo and in vitro and accompanied by increased bone mass. Lipopolysaccharide-induced osteoclast formation and osteolysis were significantly inhibited in Traf6 conditional knockout mice. Our results suggest that Traf6 plays a crucial role in regulating M1 osteoclast and M2 FBGC polarization and is a potential therapeutic target in blocking FBGC inhibition, antagonizing osteolysis in inflammatory conditions, and increasing bone mass without adverse effects in adults.

A serum metabolomics-based profile in low bone mineral density postmenopausal women.

Osteoporosis is characterized as a metabolic disorder of bone tissue, and various metabolic markers are now available to support its diagnosis and evaluate treatment effects. Substances produced as end products of metabolomic activities are the correlated factors to the biological or metabolic status, and thus, metabolites are considered highly sensitive markers of particular pathological states, including osteoporosis. Here we undertook comprehensive serum metabolomics analysis in postmenopausal women with or without low bone mineral density (low BMD vs controls) for the first time using capillary electrophoresis/mass spectrometry. Among the metabolites tested, 57 were detected in sera. Levels of hydroxyproline, Gly-Gly and cystine, differed significantly between groups, with Gly-Gly and cystine significantly lower in the low BMD group and hydroxyproline, a reported marker of osteoporosis, significantly higher. Levels of TRACP5b, a bone resorption marker, were significantly higher in the low BMD group, supporting the study's validity. Taken together, our findings represent novel metabolomic profiling in low BMD in postmenopausal women.

Bcl6 promotes osteoblastogenesis through Stat1 inhibition.

Bone mass is tightly controlled by a balance between osteoclast and osteoblast activities. Although these cell types mature via different pathways, some factors reportedly regulate differentiation of both. Here, in a search for factors governing osteoblastogenesis but also expressed in osteoclasts to control both cell types by one molecule, we identified B cell lymphoma 6 (Bcl6) as one of those factors and show that it promotes osteoblast differentiation. Bcl6 was previously shown to negatively regulate osteoclastogenesis. We report that lack of Bcl6 results in significant inhibition of osteoblastogensis in vivo and in vitro and in defects in secondary ossification center formation in vivo. Signal transducer and activator of transcription 1 (Stat1) reportedly attenuates osteoblast differentiation by inhibiting nuclear translocation of runt-related transcription factor 2 (Runx2), which is essential for osteoblast differentiation. We found that lack of Bcl6 resulted in significant elevation of Stat1 mRNA and protein expression in osteoblasts and showed that Stat1 is a direct target of Bcl6 using a chromatin immune-precipitation assay. Mice lacking both Bcl6 and Stat1 (DKO) exhibited significant rescue of bone mass and osteoblastic parameters as well as partial rescue of secondary ossification center formation compared with Bcl6-deficient mice in vivo. Altered osteoblastogenesis in Bcl6-deficient cells was also restored in DKO in vitro. Thus, Bcl6 plays crucial roles in regulating both osteoblast activation and osteoclast inhibition.

Experimental assessment of a novel intramedullary nail for callus distraction by the segmental bone transport method.

BACKGROUND: Segmental bone transport (SBT) is a revolutionary method for treating extensive bone defects, and it is in wide clinical use. Although external fixation is generally used to perform SBT, it is associated with problems such as complications due to pin placement and limitations of the amount and rate of lengthening. As a way to overcome these problems we developed a novel intramedullary (IM) nail for SBT that minimizes damage to the surrounding tissue and improves the amount and rate of bone lengthening. The purpose of this study was to perform SBT in the femur of beagle dogs using the novel IM nail that we devised, and to evaluate the morphology and quality of the regenerated bone and circulation status in the surrounding tissue. We also considered the possibilities and limitations of the IM in regard to clinical application. METHODS: This experiment was conducted on six beagle dogs. The novel IM nail we devised was inserted into the marrow cavity of the femur, and a 30-mm bone defect was created. After a 7-day postoperative waiting period, a bone segment was transported by 1.0 mm per day in two 0.5-mm increments. Because the nail broke in two dogs, they received only partial elongation by 15 mm over a 15-day period, with a 15-mm defect remaining, whereas full elongation by 30 mm in 30 days was performed in the other four dogs. The elongation was followed by a 30-day bone hardening period. RESULTS: The macroscopic and histological results demonstrated that high-quality, new bone had replaced the 30-mm bone defect created in the femur of all six dogs. The density and number of blood vessels that had penetrated the elongated segment of bone from the surrounding muscles was greater than in the corresponding segment of the contralateral femur, which served as a control. The results imply that the traction stimulus induced vigorous angiogenesis in the surrounding tissue. CONCLUSION: We concluded that this method has tremendous potential for clinical application, and will overcome the limitations of conventional external fixators.

Aldehyde-stress resulting from Aldh2 mutation promotes osteoporosis due to impaired osteoblastogenesis.

Osteoporosis is a complex disease with various causes, such as estrogen loss, genetics, and aging. Here we show that a dominant-negative form of aldehyde dehydrogenase 2 (ALDH2) protein, ALDH2*2, which is produced by a single nucleotide polymorphism (rs671), promotes osteoporosis due to impaired osteoblastogenesis. Aldh2 plays a role in alcohol-detoxification by acetaldehyde-detoxification; however, transgenic mice expressing Aldh2*2 (Aldh2*2 Tg) exhibited severe osteoporosis with increased levels of blood acetaldehyde without alcohol consumption, indicating that Aldh2 regulates physiological bone homeostasis. Wild-type osteoblast differentiation was severely inhibited by exogenous acetaldehyde, and osteoblastic markers such as osteocalcin, runx2, and osterix expression, or phosphorylation of Smad1,5,8 induced by bone morphogenetic protein 2 (BMP2) was strongly altered by acetaldehyde. Acetaldehyde treatment also inhibits proliferation and induces apoptosis in osteoblasts. The Aldh2*2 transgene or acetaldehyde treatment induced accumulation of the lipid-oxidant 4-hydroxy-2-nonenal (4HNE) and expression of peroxisome proliferator-activated receptor gamma (PPARγ), a transcription factor that promotes adipogenesis and inhibits osteoblastogenesis. Antioxidant treatment inhibited acetaldehyde-induced proliferation-loss, apoptosis, and PPARγ expression and restored osteoblastogenesis inhibited by acetaldehyde. Treatment with a PPARγ inhibitor also restored acetaldehyde-mediated osteoblastogenesis inhibition. These results provide new insight into regulation of osteoporosis in a subset of individuals with ALDH2*2 and in alcoholic patients and suggest a novel strategy to promote bone formation in such osteopenic diseases.