Local Bone Research Articles

Modic changes: From potential molecular mechanisms to future research directions (Review).

Low back pain (LBP) is a leading cause of disability worldwide. Although not all patients with Modic changes (MCs) experience LBP, MC is often closely associated with LBP and disc degeneration. In clinical practice, the focus is usually on symptoms related to MC, which are hypothesized to be associated with LBP; however, the link between MC and nerve compression remains unclear. In cases of intervertebral disc herniation, nerve compression is often the definitive cause of symptoms. Recent advances have shed light on the pathophysiology of MC, partially elucidating its underlying mechanisms. The pathogenesis of MC involves complex bone marrow‑disc interactions, resulting in bone marrow inflammation and edema. Over time, hematopoietic cells are gradually replaced by adipocytes, ultimately resulting in localized bone marrow sclerosis. This process creates a barrier between the intervertebral disc and the bone marrow, thereby enhancing the stability of the vertebral body. The latest understanding of the pathophysiology of MC suggests that chronic inflammation plays a significant role in its development and hypothesizes that the complement system may contribute to its pathological progression. However, this hypothesis requires further research to be confirmed. The present review we proposed a pathological model based on current research, encompassing the transition from Modic type 1 changes (MC1) to Modic type 2 changes (MC2). It discussed key cellular functions and their alterations in the pathogenesis of MC and outlined potential future research directions to further elucidate its mechanisms. Additionally, it reviewed the current clinical staging and pathogenesis of MC, recommended the development of an updated staging system and explored the prospects of integrating emerging artificial intelligence technologies.

Microvesicles Released by Osteoclastic Cells Exhibited Chondrogenic, Osteogenic, and Anti-Inflammatory Activities: An Evaluation of the Feasibility of Their Use for Treatment of Osteoarthritis in a Mouse Model

Extracellular vesicles (EVs), particularly exosomes (EXOs) of various skeletal and stem cells, were shown to delay osteoarthritis (OA) progression, and apoptotic bodies (ABs), another EV subtype, of osteoclasts showed osteoanabolic actions and were involved in the osteoclastic-regulation of local bone formation. Moreover, this study demonstrates that microvesicles (MVs) released by osteoclasts displayed potent pro-chondrogenic, pro-osteogenic, and anti-inflammatory activities. These activities were unique to osteoclastic MVs and were not shared by osteoclastic ABs and EXOs or MVs of other cell types. Because chronic synovial inflammation, progressive articular cartilage erosion, abnormal subchondral bone remodeling, and inability to regenerate articular cartilage are key etiologies of OA, we postulate that the foregoing activities of osteoclastic MVs could simultaneously target multiple etiologies of OA and could thereby be an effective therapy for OA. Accordingly, this study sought to assess the feasibility of an osteoclastic MV-based strategy for OA with a mouse tibial plateau injury model of OA. Briefly, tibial plateau injuries were created on the right knees of adult C57BL/6J mice, MVs were intraarticularly injected into the injured joints biweekly, and the OA progression was monitored histologically at five weeks post-injury. The MV treatment reduced the OA-induced losses of articular cartilage area and thickness, decreased irregularity in the articular cartilage surface, reduced loss of gliding/intermediate zone of articular cartilage, reduced osteophyte formation, suppressed synovial inflammation, and decreased the OARSI OA score. In summary, treatment with osteoclastic MVs delayed or reversed OA progression. Thus, this study supports the feasibility of an osteoclastic MV-based therapy for OA.

3D-Printed PCL Scaffolds Loaded with bFGF and BMSCs Enhance Tendon-Bone Healing in Rat Rotator Cuff Tears by Immunomodulation and Osteogenesis Promotion.

Rotator cuff tears are the most common conditions in sports medicine and attract increasing attention. Scar tissue healing at the tendon-bone interface results in a high rate of retears, making it a major challenge to enhance the healing of the rotator cuff tendon-bone interface. Biomaterials currently employed for tendon-bone healing in rotator cuff tears still exhibit limited efficacy. As a promising technology, 3D printing enables the customization of scaffold shapes and properties. Bone marrow mesenchymal stem cells (BMSCs) have multidifferentiation potential and valuable immunomodulatory effects. The basic fibroblast growth factor (bFGF), known for its role in proliferation, has been reported to promote osteogenesis. These properties make them applicable in tissue engineering. In this study, we developed a 3D-printed polycaprolactone (PCL) scaffold loaded with bFGF and BMSCs (PCLMF) to restore the tendon-bone interface and regulate the local inflammatory microenvironment. The PCLMF scaffolds significantly improved the biomechanical strength, histological score, and local bone mineral density at regenerated entheses at 2 weeks postsurgery and achieved optimal performance at 8 weeks. Furthermore, PCLMF scaffolds facilitated BMSC osteogenic differentiation and suppressed adipogenic differentiation both in vivo and in vitro. In addition, RNA-seq showed that PCLMF scaffolds could regulate macrophage polarization and inflammation through the MAPK pathway. The implanted scaffold demonstrated excellent biocompatibility and biosafety. Therefore, this study proposes a promising and practical strategy for enhancing tendon-bone healing in rotator cuff tears.

Nanocapsuled Neutrophil Extracellular Trap Scavenger Combating Chronic Infectious Bone Destruction Diseases.

Chronic infectious bone destruction diseases, such as periodontitis, pose a significant global health challenge. Repairing the bone loss caused by these chronic infections remains challenging. In addition to pathogen removal, regulating host immunity is imperative. The retention of neutrophil extracellular traps (NETs) in chronic infectious niches is found to be a barrier to inflammation resolution. However, whether ruining the existing NETs within the local infectious bone lesions can contribute to inflammation resolve and bone repair remains understudied. Herein, a nanocapsuled delivery system that scavenges NETs dual-responsively to near-infrared light as a switch and to NETs themselves as a microenvironment sensor is designed. Besides, the photothermal and photodynamic effects endow the nanocapsules with antibacterial properties. Together with the ability to clear NETs, these features facilitate the restoration of the normal host response. The immunocorrective properties and inherent pro-osteogenic effects finally promote local bone repair. Together, the NET scavenging nanocapsules address the challenge of impaired bone repair in chronic infections due to biased host response caused by excessive NETs. This study provides new concepts and strategies for repairing bone destruction attributable to chronic infections via correcting biased host responses in chronic infectious diseases.

Time-lapse HR-pQCT reliably assesses and monitors local bone turnover in patients with chronic kidney disease.

Bone turnover assessment and monitoring are essential for chronic kidney disease (CKD)-associated bone care. Patients with CKD suffer from significantly elevated fracture risk due to abnormally high or low bone turnover, which requires diametrically opposite treatments informed by patient-specific bone turnover data. However, a reliable, accessible, non-invasive bone turnover assessment and monitoring tool remains an unmet clinical need. Combining time-lapse (TL) analysis with high-resolution peripheral quantitative computed tomography (HR-pQCT) scans obtained over time allows for in vivo temporospatial bone remodeling assessment. This study aimed to evaluate the feasibility of applying TL HR-pQCT to assess and monitor local bone formation and resorption in patients with CKD. A customized TL HR-pQCT pipeline was developed on a second-generation HR-pQCT platform and optimized using ex vivo cadaveric phantom and in vivo scan-rescan HR-pQCT images. The annualized least significant change in bone formation and resorption were evaluated using in vivo longitudinal reproducibility images. Finally, the feasibility of the TL HR-pQCT pipeline in assessing and monitoring bone turnover was evaluated in patients with end stage kidney disease (ESKD; n = 9). We found that a 2-month time-lapse period was sufficient for the TL HR-pQCT pipeline to reliably assess and monitor local bone turnover in a cohort of patients with ESKD. We also demonstrated the importance of characterizing TL HR-pQCT precision metrics using longitudinal baseline/follow-up rather than short-term scan-rescan datasets. The TL HR-pQCT pipeline assessed a range of bone formation metrics consistent with the gold standard histomorphometric bone formation reported in the literature for patients with CKD and ESKD. Our findings highlight that TL HR-pQCT holds promise as a "virtual bone biopsy" that reliably assesses and monitors local bone turnover for CKD bone care. Subsequent work will focus on validating this TL HR-pQCT pipeline against the gold standard bone biopsy with quantitative histomorphometry.

DAMPs, PAMPs, NLRs, RIGs, CLRs and TLRs - Understanding the Alphabet Soup in the Context of Bone Biology.

The purpose of this review is to summarize the current understanding of cell-autonomous innate immune pathways that contribute to bone homeostasis and disease. Germ-line encoded pattern recognition receptors (PRRs) are the first line of defense against danger and infections. In the bone microenvironment, PRRs and downstream signaling pathways, that mount immune defense, interface intimately with the core cellular processes in bone cells to alter bone formation and resorption. The role of PRR engagement on bone remodeling has been best described as a result of activated macrophages secreting effector molecules that reshape the characteristics of bone-resident cells. However, it is being increasingly recognized that local bone resident-cells like osteoclasts and osteoblasts possess an arsenal of PRRs. The engagement of these PRRs by stimuli in the bone niche can drive cell-autonomous (aka cell-intrinsic) responses that, in turn, impact bone-remodeling dramatically, irrespective of immune cell effectors. Indeed, this vital role for cell-autonomous innate immune responses is evident in how reduced PRR activity within osteoclast progenitors correlates with their reduced differentiation and abnormal bone remodeling. Further, cell-intrinsic PRR activity has now been shown to influence the behavior of osteoblasts, osteocytes and other local immune/non-immune cell populations. However, distinct PRR families have varying impact on bone homeostasis and inflammation, emphasizing the importance of investigating these different nodes of innate immune signaling in bone cells to better identify how they synergistically and/or antagonistically regulate bone remodeling in the course of an immune response. Innate immune sensing within bone resident cells is a critical determinant for bone remodeling in health and disease.

Polymer-based antimicrobial strategies for periodontitis.

Periodontitis is a chronic inflammatory condition driven by plaque-associated microorganisms, where uncontrolled bacterial invasion and proliferation impair host immune responses, leading to localized periodontal tissue inflammation and bone destruction. Conventional periodontal therapies face challenges, including incomplete microbial clearance and the rise of antibiotic resistance, limiting their precision and effectiveness in managing periodontitis. Recently, nanotherapies based on polymeric materials have introduced advanced approaches to periodontal antimicrobial therapy through diverse antimicrobial mechanisms. This review explored specific mechanisms, emphasizing the design of polymer-based agents that employ individual or synergistic antimicrobial actions, and evaluated the innovations and limitations of current strategies while forecasting future trends in antimicrobial development for periodontitis.

Drug-Loaded Microspheres on NIR-Responsive PLA/MXene Scaffolds: Controlled Release and Bone Tissue Regeneration.

The resection of bone tumors results in large bone defects with some residual tumor cells, and the treatment of this type of bone defect area often faces a dilemma, namely, the trade-off between bone repair and antitumor after the resection of bone tumors. In order to promote local bone repair, and at the same time inhibit tumor recurrence by continuous and controlled drug administration, we developed a multifunctional NIR-responsive scaffold, whose main components are polylactic acid and MXene, and loaded with PLGA/DOX microspheres, and we hope that the scaffold can take into account both antitumor and bone repair in the bidirectional modulation effect of NIR. The results showed that the scaffold with 1% MXene content had relatively good performance in photothermal therapy (PT) and other aspects, and it could be smoothly increased to 50 °C within 2 min under NIR illumination, and the drug release of microspheres was increased by 10% after illumination compared with that at body temperature. In vivo experiments in animals showed that this scaffold effectively limited the in situ recurrence of tumor cells and lung metastasis and was able to promote osteogenic differentiation under NIR irradiation. Therefore, this scaffold can not only control the release of antitumor drugs but also enhance the antitumor effect through the bidirectional modulation effect of PT and at the same time promote bone formation, which provides a good application solution for the integrated treatment of the bone defect area after bone tumor surgery.

Effects of Ab501 (certolizumab mice equivalent) in arthritis induced bone loss.

Introduction - Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease, which causes local and systemic bone damage. The main goal of this work was to analyze, how treatment intervention with Ab501 (certolizumab mice equivalent) prevents the disturbances on bone structure and mechanics induced by arthritis. Methods - Thirty DBA/1 collagen-induced arthritis (CIA) mice were randomly housed in experimental groups, as follows: arthritic untreated (N=9), preventive intervention (N=10) and treatment intervention (N=11). A non-induced group (N=5) was used as a control. Mice were monitored during 70 days after disease induction for the inflammatory score, ankle perimeter and body weight. After 70 days of disease progression mice were sacrificed and bone samples were collected for histology, micro-computed tomography (µCT) and 3-point bending analysis. In addition, blood samples were also collected for bone turnover markers quantification. Results - Results showed that Ab501 administration was able to control and abrogate disease development both in preventive and early therapeutic intervention. µCT results revealed that Ab501 was able to preserve trabecular bone structure when delivered before arthritis induction. Conclusion - Ab501 preventive administration was able to control inflammation and prevent the degradative effects of arthritis on trabecular bone structure in a CIA DBA/1 mice model.

Safety assessment of microwave ablation in sheep vertebral bodies

Background Spine is the most common location for bone metastases. Microwave ablation (MWA) is a technique for minimally invasive tumor treatment. The aim of the current study was to determine whether MWA is a safe option for treatment in vertebral bodies and to gain data on the amount of cortical insulation in the spine. Method MWA was applied with different settings for power and time in both in- and ex-vivo sheep vertebral bodies. Safety was evaluated by temperature measurements at critical surrounding structures (e.g. spinal cord, nerve root). Furthermore, the distribution of heat through the bone at 5 mm from the ablation needle was measured and compared to the temperature at the posterior wall. Results An effect of cortical insulation in the spine was found, for ablations with 20–30 and 50 W (p < 0.01). Ablations with wattage levels of 40–50 W almost instantly led to temperatures over 60 °C at the posterior wall. The temperature remained below 60 °C for 4 min in ex-vivo ablations with 20 and 30 W. However, in the in-vivo experiment paralysis was frequently seen (10/12 sheep) in lower wattages (20–30 W) as well and the experiment was therefore terminated. Conclusion MWA is an effective approach for local bone destruction in the spine. However, given the high risk of complications, caution is advised for treatment in vertebral bodies without better local distribution accuracy. Since cortical insulation appears insufficient to protect the spinal canal from excess heat, MWA involves a risk of paralysis.

MINERAL COMPONENT OF ORAL FLUID AS AN INDICATOR OF REPARATIVE OSTEOGENESIS AFTER TOOTH EXTRACTION

Tooth extraction is known to results in the formation of a bone defect and the gradual atrophy of the alveolar process, which can negatively impact the outcomes of dental rehabilitation. Adequate alveolar bone volume and the complete morphology of the alveolar process are essential for achieving aesthetic and functional reconstruction. The aim of this study was to determine the effect of cryopreserved placenta and quercetin on the levels of total and ionized calcium in oral fluid during the process of reparative osteogenesis following tooth extraction. Results. The study found that the content of total calcium in the oral fluid of patients showed a statistically significant increase on the 20th day after the tooth extraction procedure: by 5.2%, 3.7%, and 4.8% in the 1st, 2nd, and 3rd clinical groups, respectively. The dynamics of ionized calcium were even more pronounced. On day 20 after tooth extraction, the levels of ionized calcium increased significantly in all three clinical groups: by 23.0%, 9.6%, and 33.3%, respectively. In the second clinical group, the ionized calcium content was lower by 16.7% compared to the control group, and by 12.1% compared to the group where cryopreserved placenta was used alongside the standard treatment protocol, with these differences being statistically significant. Ninety days after tooth extraction, the levels of ionized calcium showed a statistically significant decrease: by 13.2%, 6.3%, and 13.5%, respectively, in the 1st, 2nd, and 3rd clinical groups. The least change in total and ionized calcium levels in the oral fluid was observed in patients treated with the standard protocol supplemented with cryopreserved placenta and quercetin. This may be attributed to local bone tissue resorption in the lower jaw, resulting in the release of this mineral from the bones.

Minimally invasive balloon-assisted sinus floor elevation vs. conventional transcrestal procedure in terms of new bone formation in a split-mouth Goettingen minipig model

PurposeCurrently, maxillary sinus floor (SF) elevation is based on off-the-shelf allogeneic, xenogeneic or synthetic bone augmentation materials (BAM) that are implanted via an open lateral sinus wall approach (OSFE). However, this invasive method is associated with postoperative complications caused by an inadequate blood supply of the alveolar ridge. Balloon-assisted procedures are minimal invasive alternatives with lower complication rates. The aim was to evaluate local new bone (NB) formation in the SF following the application of a particulate BAM (Easy graft) via two different SF elevation techniques in a split mouth mini-pig sinus augmentation model.Material and methodsSeven adult Goettingen minipigs were used for evaluation of a biphasic ceramic (PLGA/ß-TCP) BAM in the elevated SF region. Treatments were randomized to the contralateral sinus sites and included two procedures: OSFE (control group) versus minimally invasive SF elevation by a balloon-lift-control system (BLC) (treatment group). The animals were euthanized after 28 and 56 days for analysis of new bone (NB) formation.ResultsThe biphasic synthetic BAM implanted via BLC increased more NB formation (5.2 ± 1.9 mm and 4.9 ± 1.6 mm vs. 2.6 ± 0.5 mm) and osseointegration of the particles (18.0 ± 6.0% and 25.1 ± 18.2% vs. 10.1 ± 8.0%, p < 0.05) compared to the control.ConclusionsImplantation of a biphasic synthetic BAM enhanced NB formation in the mini-pig maxillary sinus at both time points and in both groups, although BLC resulted in a slightly better total NB formation compared to the control.Graphical abstract

Early resistance rehabilitation improves functional regeneration following segmental bone defect injury

Many studies have explored different loading and rehabilitation strategies, yet rehabilitation intensity and its impact on the local strain environment and bone healing have largely not been investigated. This study combined implantable strain sensors and subject-specific finite element models in a 2 mm rodent segmental bone defect model. After injury animals were underwent high or low intensity rehabilitation. High intensity rehabilitation increased local strains within the regenerative niche by an average of 44% compared to the low intensity rehabilitation. Finite element modeling demonstrated that resistance rehabilitation significantly increased compressive strain by a factor of 2.0 at week 2 and 4.45 after 4 weeks of rehabilitation. Animals that underwent resistance running had the greatest bone volume and improved functional recovery with regenerated femurs that matched intact failure torque and torsional stiffness values. These results demonstrate the potential for early resistance rehabilitation to improve bone healing.

The Use of the Facial Sinus Wall as Bone Shell Onlay Graft for Maxillary Posterior Ridge Reconstruction: A Retrospective Case Series.

To evaluate the performance and clinical outcome of vertical and horizontal bone augmentation (VHBA) in posterior maxillary regions combining lateral window sinus floor elevation (LWSFE) with a horizontal bone shell technique applying the maxillary facial sinus wall as a bone plate. In 18 patients, LWSFE was combined with a horizontal bone shield augmentation procedure utilizing the maxillary facial sinus bone wall as a lateral bone plate. Both the sinus cavity and the lateral bone box created were grafted with a mixture of autogenous bone/venous blood and bovine bone mineral. The primary aim was to assess the performance of combined techniques enabling subsequent implant placement. Using radiographic measurements (preoperative, after VHBA, at implant placement, and at follow-up), bone gain/reduction of augmented horizontal ridge width (HRW) and vertical bone height (VBH) were evaluated. Additionally, clinical outcome assessing implant survival/success rate, marginal bone loss (MBL), and implant health (mucositis/peri-implantitis) was evaluated. For the combined VHBA techniques, HRW and VBH increased significantly (p < 0.001) from preoperative 3.5 ± 1.4 mm/3.6 ± 2.1 mm to 9.7 ± 1.9 mm/18.0 ± 1.6 mm post-augmentation. However, HRW and VBH dimensions decreased up to 8.9 ± 1.8 mm/17.1 ± 1.4 mm at implant placement and 8.6 ± 1.7 mm/16.7 ± 1.3 mm at follow-up evaluation (3.8 ± 1.8 years; p < 0.001, respectively). Augmented bone reduction was significantly higher (-7.7%) between the augmentation procedure and implant placement than in the post-implant-placement period (-2.5%). All implants survived (100%) representing peri-implant MBL of -0.9 ± 0.7 mm, pocket depth of 3.4 + 1.8 mm, and prevalences of 5%/0% for peri-implant mucositis/peri-implantitis. The combination of horizontal bone augmentation using local bone shield transfer from the maxillary facial sinus wall with LWSFE enables sufficient reconstruction of maxillary posterior ridge.

Bone Erosions and Systemic Bone Loss on HR-pQCT in Men With Tophaceous Gout.

Gout, a prevalent inflammatory arthropathy, predominantly affects males and arises from persistent hyperuricemia, resulting in monosodium urate crystal deposition. Hyperuricemia is associated with comorbidities, exacerbating patient morbidity. Conflicting literature exists regarding uric acid's impact on bone mineral density (BMD), with potential proinflammatory effects in gout patients. Localized bone destruction (erosions) is a hallmark of gout, necessitating early detection due to its predictive role in musculoskeletal disability. This cross-sectional study included 26 tophaceous gout patients. Clinical and densitometric parameters were assessed, and high-resolution peripheral quantitative computed tomography (HR-pQCT) was used for bone microarchitecture evaluation, as well as bone erosions in metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. A healthy control group of 52 age and BMI-matched individuals was included. Despite normal areal bone mineral density (BMD), tophaceous gout patients exhibited impaired HR-pQCT parameters, including lower cortical volumetric BMD (Ct.vBMD) and higher cortical porosity at the distal radius. Similar trends were observed at the tibia. Bone erosions were prevalent (96%), with distribution across MCP and PIP joints. Patients with ≥ 4 erosions displayed increased tophi prevalence and longer uricosuric use. Erosions correlated with compromised microarchitecture, emphasizing their association with disease activity. Despite normal BMD, tophaceous gout patients manifest systemic bone loss, with bone microarchitectural deterioration and localized bone erosions, underscoring the need for detailed clinical approaches to prevent musculoskeletal disabilities, including fragility fractures, in this population.

Iliac crest vertical block grafts -placing outside or inside the bone contour: A cohort study.

Challenging defect configurations and dimensions arise from severe, localized vertical alveolar ridge defects caused by trauma or prior surgery. This study aims to analyze three-dimensional bone gain, assess marginal bone stability in such defect configurations, and evaluate the impact of grafting outside the bone contour on the overall outcome, with a focus on iliac crest block grafts as a valid treatment option. The prospective cohort study evaluated patients who required vertical block grafting due to localized bone defects in the maxilla or mandible and who had received iliac grafts. Three-dimensional bone gain was analyzed using cone beam computed tomography (CBCT) after 3 months of bone healing for each treated site and implant position. A comparison between bone grafts inside and outside the bone contour was conducted. Marginal bone stability was measured using intraoral radiographs during routine annual follow-up visits. Seventy patients with 89 treated sites were evaluated. After 3 months of graft healing, the mean vertical bone gain was 11.03 ± 3.54 mm, the mean horizontal bone gain was 7.18 ± 2.00 mm, and the mean graft length was 28.19 ± 11.01 mm. A total of 217 implants were placed in the augmented regions. On implant level, a mean vertical bone gain of 10.44 ± 3.44 mm and a mean horizontal bone gain of 6.54 ± 1.86 mm were measured. Over a 43-month observation period, mesial and distal marginal bone loss averaged 0.44 ± 0.92 mm and 0.49 ± 1.05 mm, respectively. Eight implants were diagnosed with periimplantitis, resulting in the loss of four implants, while no early implant losses were reported. Within the limitations of this study, vertical bone grafts with iliac crest block grafts were found to be a dependable treatment option for dental implant placement, and placing block grafts outside the bone contour did not lead to inferior outcomes.

Polyphenols and Functionalized Hydrogels for Osteoporotic Bone Regeneration.

Osteoporosis induces severe oxidative stress and disrupts bone metabolism, complicating the treatment of bone defects. Current therapies often have side effects and require lengthy bone regeneration periods. Hydrogels, known for their flexible mechanical properties and degradability, are promising carriers for drugs and bioactive factors in bone tissue engineering. However, they lack the ability to regulate the local pathological environment of osteoporosis and expedite bone repair. Polyphenols, with antioxidative, anti-inflammatory, and bone metabolism-regulating properties, have emerged as a solution. Combining hydrogels and polyphenols, polyphenol-based hydrogels can regulate local bone metabolism and oxidative stress while providing mechanical support and tissue adhesion, promoting osteoporotic bone regeneration. This review first provides a brief overview of the types of polyphenols and the mechanisms of polyphenols in facilitating adhesion, antioxidant, anti-inflammatory, and bone metabolism modulation in modulating the pathological environment of osteoporosis. Next, this review examines recent advances in hydrogels for the treatment of osteoporotic bone defects, including their use in angiogenesis, oxidative stress modulation, drug delivery, and stem cell therapy. Finally, it highlights the latest research on polyphenol hydrogels in osteoporotic bone defect regeneration. Overall, this review aims to facilitate the clinical application of polyphenol hydrogels for the treatment of osteoporotic bone defects.

Rosuvastatin/calcium carbonate co-precipitated nanoparticles: A novel synergistic approach enhancing local bone regeneration in osteoporotic rat model

This study aimed at preparing sustained release rosuvastatin (Ru) calcium carbonate (CC) co-precipitate nano-formulation for local intra-osseous application in osteoporotic rats. Nano-formulations were prepared by the co-precipitation method using different concentrations of polyvinyl alcohol (PVA) (0.2, 0.4, 0.6 %) as a stabilizer and equimolar ratios of calcium chloride and calcium carbonate (0.1, 0.3 or 0.5 M). Pre-formulation examination including; FTIR and X-ray diffraction confirmed the formation of CC nanoparticles in a crystalline structure that was preserved before and after loading with Ru. The optimized formula showing; PS of 105.71 ± 5.10 nm, PDI of 0.25 ± 0.02, ZP of −44.70 ± 0.09 mV, % EE of 60.16 ± 1.58 and a quasi-spherical nanoparticle with nano-deposition of Ru crystals adsorbed on them as seen under TEM and SEM, was then integrated in 20 % Pluronic gel. The Ru-gel exhibited good rheological behavior with a short gelation time of 20 sec and a sustained release pattern of 30 % for the optimized Ru/CC gel versus ≈ 90 % for the Ru/CC dispersion after 6 h. In-vivo, ovariectomy-induced osteoporotic rats were used to cause a bone defect in the tibial metaphysis. The drill-hole defects were then filled with the formulations under test and examined 30 days postoperatively. Through SEM-EDX scanning, histological assessments, and evaluation of bone metabolic markers, Ru/CC treatment significantly enhanced bone healing, improved bone microarchitecture, increased trabecular bone area, enhanced osteogenic gene expression, and reduced osteoclast activity. Experiments proved that Ru/CC successfully enhances osteogenesis and reduces osteoclastogenesis, proposing it as a promising therapeutic approach for enhancing bone regeneration in osteoporosis.

First deciphering of large pterosaur footprints and their trackmaker in the Junggar Basin, China

Pterosaur footprints are important trace fossils for understanding the ecological habits of pterosaurs, and they are extremely rare worldwide. Within the Lower Cretaceous of the Junggar Basin of Xinjiang, hundreds of large pterosaur footprints have been unearthed. These imprints underwent a meticulous examination encompassing their dimensions, length-to-width ratio, proportions of digital and metatarsal parts, and divarication between digits of the manus imprints. A new ichnospecies, Pteraichnus junggarensis isp. nov., has been proposed based on these detailed analyses. By comparing these footprints with the anatomical characteristics of local larger pterosaur pedal bone fossils, it is suggested that the large-sized P. junggarensis footprints were produced by Dsungaripterus weii. The successful correlation between pterosaur fossils and their footprints within the Wuerho Pterosaur Fauna marks a momentous stride in deducing trackmakers based on their footprints. Moreover, estimates of pterosaur pes length and hip height were, for the first time, derived from a comprehensive scrutiny of 54 non-pterodactyloid and pterodactyloid specimens. A salient discovery was the markedly reduced ratio of hip height to pes length in non-pterodactyloid pterosaurs in comparison to their pterodactyloid counterparts. By employing fitted linear equations grounded on footprint dimensions, it is posited that the hip height for Noripterus complicidens ranges from 0.10 to 0.20 m, while for D. weii, it ranges from 0.28 to 0.46 m. Additionally, based on the ratio of stride length to hip height in the trackways, it is inferred that the trackmakers exhibited a typical walking gait, with speeds of 0.33 and 0.25 m/s, respectively.

Curative-intent surgery for solitary bone metastasis from extremity and trunk wall sarcoma: What are the outcomes and complications?

IntroductionApproximately 40–50 % of sarcoma patients will develop lung metastasis, but only 10 % will develop bone metastasis. The survival benefit of surgery for solitary bone metastasis remains unclear. MethodsFrom 1987 to 2019, 47 patients who underwent curative-intent treatment for localized bone or soft tissue sarcoma in the extremities or trunk wall developed solitary bone metastases as the first distant recurrence. Of them, 51 % (24/47) received curative-intent metastasectomy. We compared the clinicopathologic characteristics of the metastasectomy versus non-metastasectomy patients and evaluated the prognostic impact of solitary bone metastasectomy. The primary outcome measure was disease-specific survival (DSS) after developing solitary bone metastasis. ResultsThe post-metastasis DSS was worse with larger primary tumour size (HR 1.09; 95 % CI 1.02–1.16; p = 0.01) and bone metastasis in the pelvis or spine versus other bones (HR 3.79, 95 % CI 1.46–9.87; p = 0.01), and better with curative-intent surgery for the solitary bone metastasis (HR 0.14; 95 % CI 0.06–0.34; p < 0.001). The median DSS was 43 (95 % CI, 24–69) months for the metastasectomy group vs. 13 (95 % CI, 7–19) months for the non-metastasectomy group (p < 0.001). The metastasectomy group had fewer patients with metastasis in the spine or pelvis and longer metastasis-free interval. In the multivariate analysis, curative-intent surgery for solitary bone metastasis was associated with better survival (HR 0.21; 95 % CI 0.08–0.53; p = 0.001). ConclusionsCurative-intent surgery for solitary bone metastasis from sarcoma is associated with a better prognosis and is a reasonable treatment strategy whenever feasible.