Nonunion Research Articles

γ-Fe2O3/Polydopamine/TiO2 nano-porous array composite coating (FPTCC) to modulate antibacterial, osteogenesis, and osseointegration through photothermal-magnetic response

Delayed-union or non-union of fractures due to infection and localized low osteogenic activity is a great physical, psychological and financial burden for patients. Therefore, there is an urgent need to find an economical and effective solution. In this study, a γ-Fe2O3/polydopamine/TiO2 nano-porous arrays composite coating (FPTCC) with photothermal-magnetic responsiveness was fabricated. The characterization of FPTCC was analyzed by FT-IR, SEM, and EDS. The photothermal ability, photothermal stability and magnetic hysteresis curves were examined to evaluate photothermal-magnetic response properties of FPTCC. The results demonstrated that FPTCC has outstanding hydrophilicity, strong substrate bonding and stable remotely controlled photothermal-magnetic response properties. Furthermore, in vitro and in vivo biological experiments were performed to verify the capability of FPTCC to modulate antibacterial, osteogenesis and osseointegration under the intervention of NIR irradiation and static magnetic field. In conclusion, the FPTCC with biocompatibility, antibacterial, and osteogenic capabilities may provide a potential strategy for the prevention and treatment of delayed-union or non-union of fracture.

Double plating and iliac crest bone graft can safely fix femoral shaft nonunion

Introduction Femoral shaft nonunion can be extremely vexing and result in significant morbidity. We aimed to evaluate the outcomes of patients with nonunion of the femoral shaft fracture undergoing double plating and bone grafts from the iliac crest and femoral canal. Methods This retrospective study included 44 patients with femoral shaft nonunion between March 2020 to March 2022. Patients underwent dual plating, bone grafting from the iliac crest, and the utilization of the femoral canal. Age, sex, body mass index (BMI), the two surgical interventions interval, union time after the second surgery, hip range of motion (ROM), limb length discrepancy (LLD), infections, and deep vein thrombosis (DVT) were evaluated. Results Patients comprised 21 males (47.7%) and 23 females (52.3%), with a mean age of 42.3 ± 15.2 years. The mean BMI was 26.7 ± 3.77 kg/m2. The mean duration between the two surgical interventions for the patients was 17.07 ± 6.6 months. The patients were followed for ≥ 12 months. All patients achieved successful union and fracture healing, with an average time of 5 months. The mean hip flexion and extension were 112.84 ± 7.7˚ and 14.8 ± 5.2˚ degrees, respectively. Thirteen patients showed LLD after the first surgery, with a mean LLD of 7.15 ± 5.04 millimeters. LLDs were successfully rectified in all patients following the surgical intervention. No patients experienced postoperative infections or DVT. Conclusion According to our findings, the utilization of double-plate fixation in combination with iliac crest and femoral canal bone graft has proven to be a secure, productive, and straightforward surgical alternative for the management of femoral nonunion.

Comparison of Single-Stage and Dual-Stage Approaches for Nonunion Repair in the Absence of Evident Infections

OBJECTIVE: This study aimed to determine if routine dual-stage nonunion repair (DSR) surgery lead to better outcomes than single-stage nonunion (SSR) repair surgery in fracture nonunions without evident clinical or laboratory signs of infection. METHODS: Design: Retrospective comparison study Setting: Level One Trauma Center affiliated with an academic teaching hospital Patient selection Criteria: Skeletally mature patients diagnosed with fracture nonunion between June 2013 and January 2022 were included. Patients with previous non-operative treatment, definitive external fixation, previous or current diagnosis of FRI, or less than 12 months of follow-up were excluded. Outcome measures and comparison: Patient characteristics and details of the primary and the revision surgery were recorded. Comparison of the primary outcome measures - FRI, recalcitrant nonunion, and implant failures were performed between SSR and DSR groups RESULTS: A total of 113 patients met the eligibility criteria. Eighty-six patients (mean age 44.8 years, range – 17 – 80 years, 64 percent males) underwent SSR, while 27 patients (mean age 50.8 years, range 21-77 years, 52 percent males) underwent DSR. Seventy six percent underwent SSR and 24 percent underwent DSR. Baseline characteristics were similar between groups (open fractures, p=0.918; smoking, p=0.86; lower limb fractures, p=0.238; Diabetes, p=0.503; ESR, p=0.27; CRP, p=0.11; age, p=0.11; CCI, p=0.06) except for a higher rate of DSR in cases initially treated elsewhere (p = 0.015) and in obese patients (p=0.044). Bone grafting was more frequent in DSR using plates (p = 0.030). No significant differences were observed in subsequent infections (6.97 % vs 7.41 %, p=0.939), persistent nonunion (28.2 % vs 14.81 %, p=0.169), or implant failure (19.76 % vs 22.22 %, p=0.782) between SSR and DSR. CONCLUSION: No difference was found in infection, recalcitrant nonunion, and implant failure between single stage repair and dual stage repair for nonunions without overt signs of infection. The study challenges the routine use of DSR, questions the necessity of subjecting patients to two surgical procedures, and advocates for a more judicious approach in the absence of overt FRI in a fracture nonunion. LEVEL OF EVIDENCE: Level III

Pediatric Scaphoid Nonunions: Does Insurance Status Play a Role?

Objective: There are no studies that evaluate the effects that insurance or socioeconomic status may have on treatment and outcomes of scaphoid nonunions in children. We evaluated whether there is an association between insurance status and (1) time from injury to hand surgeon evaluation, (2) time from specialist evaluation to surgery, and (3) postoperative outcomes of scaphoid fracture nonunions in children. Methods: A chart review was performed for patients who underwent surgical treatment of scaphoid fracture nonunion from January 2015 and April 2021 at a large tertiary care pediatric hospital. Underinsured patients were defined as those with no medical insurance or Medicaid/state-funded insurance. Results: There were 21 privately insured patients and 17 patients who were underinsured. There was no difference in age, race, or fracture characteristics between the two groups. The mean time between injury and hand surgeon evaluation was 192 SD 195 days for the privately insured group compared with 155 SD 205 days for the underinsured group (P = 0.57). The mean time between specialist evaluation and surgical treatment was 35 SD 54 days for the privately insured group and 31 SD 31 days for the underinsured group (P = 0.82). Union was achieved in 80% of patients with private insurance compared with 88% of underinsured patients after primary surgery (P = 0.67). There was no difference detected in the proportion of patients who had residual pain (15% vs 19%), range of motion deficits (38% vs 40%), strength deficit (6% vs 7%), and return to activity (94% vs 93%) between privately insured and underinsured patients, respectively (P = 1.00). Conclusions: There was no difference in time from injury to specialist evaluation, time from evaluation to surgery, or postoperative outcomes based on insurance status for pediatric patients with scaphoid fracture nonunions. Although insurance status was not associated with access to care for pediatric scaphoid fracture nonunions at our institution, this information may not be generalizable to other populations, including patients who sustain primary scaphoid fractures and who have not yet developed nonunions. Level of Evidence: Level III—retrospective cohort study.

Polytrauma impairs fracture healing accompanied by increased persistence of innate inflammatory stimuli and reduced adaptive response.

The field of bone regeneration has primarily focused on investigating fracture healing and nonunion in isolated musculoskeletal injuries. Compared to isolated fractures, which frequently heal well, fractures in patients with multiple bodily injuries (polytrauma) may exhibit impaired healing. While some papers have reported the overall cytokine response to polytrauma conditions, significant gaps in our understanding remain in how fractures heal differently in polytrauma patients. We aimed to characterize fracture healing and the temporal local and systemic immune responses to polytrauma in a murine model of polytrauma composed of a femur fracture combined with isolated chest trauma. We collected serum, bone marrow from the uninjured limb, femur fracture tissue, and lung tissue over 3 weeks to study the local and systemic immune responses and cytokine expression after injury. Immune cell distribution was assessed by flow cytometry. Fracture healing was characterized using microcomputed tomography (microCT), histological staining, immunohistochemistry, mechanical testing, and small angle X-ray scattering. We detected more innate immune cells in the polytrauma group, both locally at the fracture site and systemically, compared to other groups. The percentage of B and T cells was dramatically reduced in the polytrauma group 6 h after injury and remained low throughout the study duration. Fracture healing in the polytrauma group was impaired, evidenced by the formation of a poorly mineralized and dysregulated fracture callus. Our data confirm the early, dysregulated inflammatory state in polytrauma that correlates with disorganized and impaired fracture healing.

Functional Outcome of Extensor Mechanism Salvage in Patella Fracture Non-union Using Krackow Sutures: A Case Report

Functional Outcome of Extensor Mechanism Salvage in Patella Fracture Non-union Using Krackow Sutures: A Case Report

Morphometric Study of Nutrient Foramen of Human Adult Humerus and Its Clinical & Medico-legal Implications

BACKGROUND: Nutrient arteries, along with other arteries supplying the humerus, are crucial not only for the healing of serious injuries such as humeral shaft fractures but also for microsurgical vascularized bone transplantation. Therefore, understanding the precise location and morphometry of nutrient foramen in bones like the humerus is essential to prevent common complications, such as non-union of fractures. This study aims to examine the location and topography of nutrient foramen in the humerus and to establish their clinical & medico-legal significance.MATERIAL METHODS: The study was conducted on 400 dried adult humerus bones of both sexes from Western Uttar Pradesh, sourced from the Department of Anatomy & Department of Forensic Medicine & Toxicology at Mahatma Vidur Autonomous State Medical College, Bijnor. Measurements and observations were carried out using an osteometric board.RESULT: Nutrient foramen was absent in 30 humerus (7.50%), single in 76.50%, and double in 16% of cases. Most humerus had medium-sized foramina (1-2 mm) on both the left and right sides, accounting for 78.80%. The majority of foramina were found on the anteromedial surface (85.02%), with fewer on the posterior surface. Additionally, most foramina were located in the middle third of the humeral diaphysis.CONCLUSION: Surgeons and orthopedists must possess precise knowledge of the number, size, shape, direction, and location of the nutrient foramen to accurately assess the humerus's vascular supply and avoid injury during surgical procedures. Morphometric data is also essential in identifying unknown remains, evaluating the severity and timing of trauma, and determining potential surgical complications in cases of medical malpractice.

The effect of the Hippocampus erectus decoction on improving osteoporosis in zebrafish

The seahorse is a traditional Chinese herbal medicine that has been utilized for the treatment of conditions such as osteoporosis, nonunion fractures, knee osteoarthritis, and herniated lumbar disks.Zebrafish is an excellent animal model to study the effects of herbal preparations on osteogenesis and bone metabolism, and bone biology is highly similar to that of mammals, so it has been used to develop multiple glucocorticoid-induced osteoporosis (GIOP) models. Our study aimed to explore whether the decoction of Hippocampus erectus (DHe) administered in zebrafish larvae promotes bone health under physiological and osteoporotic conditions. In zebrafish larvae, 25 µM prednisolone solution was successfully used to induce the zebrafish osteoporosis model, which can significantly inhibit the mineralization area and degree of bone mineralization, reduce the activity of alkaline phosphatase, and increase tartrate-resistant acid phosphatase activity. The results showed that 0.3 g/L DHe had a significant improvement effect on osteoporosis in zebrafish by enhancing the mineralization degree and phosphatase activity of zebrafish, while also promoting the expression of genes associated with bone development. It can be considered a good candidate to develop new drugs against osteoporosis.

Effect of Ketorolac Administration on the Rate of Nonunion of Operatively Treated Pediatric Long-Bone Fractures

Background: Nonunion is a rare yet serious complication in pediatric fracture healing that can lead to patient morbidity and economic burden. The administration of nonsteroidal anti-inflammatory drugs (NSAIDs) has been associated with an increased risk of fracture nonunion in adults, but data are lacking in the pediatric population. This study examines the relationship between postoperative ketorolac administration and nonunion in operatively managed pediatric long-bone fractures. Methods: A retrospective cohort study was conducted with use of TriNetX, a research network that encompasses data from the United States, Canada, and Western Europe. A total of 462,260 patients from 52 health-care organizations met the inclusion criteria. Patients <18 years old with operatively managed upper or lower-extremity long-bone fractures were included. The exposure of interest was ketorolac administration within 30 days postoperatively between 2003 and 2023. Nonunion was identified and verified with use of the pertinent medical codes. Absolute risks and hazard ratios (HRs) were calculated for both study groups. Significance was set at p < 0.05. Results: After propensity score matching, 48,778 patients were identified per group. The incidence of nonunion was 2.19% in the ketorolac group and 0.93% in the non-ketorolac group (HR, 2.71; 95% confidence interval [CI]: 2.46, 3.21; p < 0.0001). Subgroup analyses demonstrated a higher risk of nonunion in patients with lower-extremity fractures (HR, 3.45; 95% CI: 3.14, 3.75; p < 0.0001) than in those with upper-extremity fractures (HR, 2.11; 95% CI: 1.84, 2.32; p < 0.0001). Among the fracture location subgroups, the greatest HR for nonunion was observed in patients with femoral fractures, followed sequentially by those with tibial and/or fibular fractures, humeral fractures, and radial and/or ulnar fractures. Conclusions: To our knowledge, this is the largest study to date to explore postoperative ketorolac use and nonunion in the setting of operatively managed pediatric long-bone fractures. Nonunion in children was rare, occurring in <1% of all included patients. Ketorolac administration was associated with a 2 to 3-fold increase in nonunion risks, with pronounced implications for patients with lower-extremity fractures, particularly those with femoral fractures. Clinicians should weigh the therapeutic advantages of non-opiate analgesia with ketorolac against the risk of nonunion in order to optimize postoperative pain management and recovery. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Treatment of Bone Defects and Nonunion via Novel Delivery Mechanisms, Growth Factors, and Stem Cells: A Review.

Bone nonunion following a fracture represents a significant global healthcare challenge, with an overall incidence ranging between 2 and 10% of all fractures. The management of nonunion is not only financially prohibitive but often necessitates invasive surgical interventions. This comprehensive manuscript aims to provide an extensive review of the published literature involving growth factors, stem cells, and novel delivery mechanisms for the treatment of fracture nonunion. Key growth factors involved in bone healing have been extensively studied, including bone morphogenic protein (BMP), vascular endothelial growth factor (VEGF), and platelet-derived growth factor. This review includes both preclinical and clinical studies that evaluated the role of growth factors in acute and chronic nonunion. Overall, these studies revealed promising bridging and fracture union rates but also elucidated complications such as heterotopic ossification and inferior mechanical properties associated with chronic nonunion. Stem cells, particularly mesenchymal stem cells (MSCs), are an extensively studied topic in the treatment of nonunion. A literature search identified articles that demonstrated improved healing responses, osteogenic capacity, and vascularization of fractures due to the presence of MSCs. Furthermore, this review addresses novel mechanisms and materials being researched to deliver these growth factors and stem cells to nonunion sites, including natural/synthetic polymers and bioceramics. The specific mechanisms explored in this review include BMP-induced osteoblast differentiation, VEGF-mediated angiogenesis, and the role of MSCs in multilineage differentiation and paracrine signaling. While these therapeutic modalities exhibit substantial preclinical promise in treating fracture nonunion, there remains a need for further research, particularly in chronic nonunion and large animal models. This paper seeks to identify such translational hurdles which must be addressed in order to progress the aforementioned treatments from the lab to the clinical setting.

Outcomes of external versus internal fixation for traumatic lower limb fractures in low- and middle-income countries.

Lower limb fractures are common in low- and middle-income countries (LMICs) and represent a significant burden to the existing orthopaedic surgical infrastructure. In high income country (HIC) settings, internal fixation is the standard of care due to its superior outcomes. In LMICs, external fixation is often the surgical treatment of choice due to limited supplies, cost considerations, and its perceived lower complication rate. The aim of this systematic review protocol is identifying differences in rates of infection, nonunion, and malunion of extra-articular femoral and tibial shaft fractures in LMICs treated with either internal or external fixation. This systematic review protocol describes a broad search of multiple databases to identify eligible papers. Studies must be published after 2000, include at least five patients, patients must be aged > 16 years or treated as skeletally mature, and the paper must describe a fracture of interest and at least one of our primary outcomes of interest. We did not place restrictions on language or journal. All abstracts and full texts will be screened and extracted by two independent reviewers. Risk of bias and quality of evidence will be analyzed using standardized appraisal tools. A random-effects meta-analysis followed by a subgroup analysis will be performed, given the anticipated heterogeneity among studies, if sufficient data are available. The lack of easily accessible LMIC outcome data, combined with international clinical guidelines that are often developed by HIC surgeons for use in HIC environments, makes the clinical decision-making process infinitely more difficult for surgeons in LMICs. This protocol will guide research on surgical management, outcomes, and complications of lower limb shaft fractures in LMICs, and can help guide policy development for better surgical intervention delivery and improve global surgical care.

Systemic Lipid Metabolism Dysregulation as a Possible Driving Force of Fracture Non-Unions?

Non-unions are fractures that do not heal properly, resulting in a false joint formation at the fracture site. This condition leads to major health issues and imposes a burden on national healthcare systems. The etiology of non-unions is still not fully understood; therefore, we aimed to identify potential systemic factors that may contribute to their formation. We conducted a cross-sectional concomitant proteomic and metabolomic pilot study of blood plasma in patients with non-unions (N = 11) and compared them with patients with bone fracture in the normal active healing phase (N = 12). We found five significantly upregulated proteins in the non-union group: immunoglobulin heavy variable 3-74, immunoglobulin lambda variable 2-18, low-density lipoprotein receptor-related protein 4, zinc-alpha-2-glycoprotein, and serum amyloid A-1 protein; and we found one downregulated protein: cystatin-C. The metabolomic study found differences in alanine, aspartate and glutamate metabolism pathways between two groups. The combined results of proteomic and metabolomic analyses suggest that the dysregulation of lipid metabolism may contribute to non-union formation.

Prepatellar bursa mucosa: An unreported postoperative complication of patellar fracture.

Patellar fracture is a common injury caused by overstrain of the extensor mechanism or a direct trauma to the knee. The most common complications after patellar fracture are nonunion, infection, post-traumatic arthritis, joint fibrosis, symptomatic hardware, and extensor mechanism failure. These are attributed to the post-fracture flexion and extension movements, the primary damage to the articular cartilage, and the thin soft tissue coverage over the knee. To our knowledge, prepatellar bursa mucosa is an unreported postoperative complication of patellar fracture. We describe a case of a 58-year-old woman with a left patellar fracture from a fall. Complete healing was achieved after in 2 months postoperatively using the improved Kirschner wire tension band and a cable grip system; however, at 7 months postoperatively, a prepatellar skin mass appeared. The patient reported prepatellar discomfort with no pain and influence of movement of the knee and daily life. One year postoperatively, we surgically removed the implants and mass. The pathological result showed bursa mucosa. The literature review shows that pain, secondary knee dysfunction, fracture nonunion, and malunion are postoperative complications of patellar fractures. However, prepatellar bursa mucosa have not been previously reported as a postoperative complication. This case highlights the need for appropriate placement of the intraoperative implant in adults with patellar fractures.

What is the incidence and non-union rate of radiation-associated fractures? – A systematic review of the literature

BackgroundRadiation-associated fractures (RAFs) are a challenging complication in oncologic patients, yet their incidence remains unknown and optimal management lacks consensus. AimThis review aimed to evaluate the incidence of RAFs in the trunk, pelvis, and extremities as well as non-union rates of surgical and non-surgical treatment. Materials and methodsA systematic review of PubMed and Embase databases was conducted. The study was registered on PROSPERO (ID: CRD42024513017). Studies were included if they reported RAFs in oncologic populations, had a sample size of at least five patients, and provided extractable data on RAF incidence or number. The STROBE checklist was utilized for evaluation of study quality. For eligible studies, quantitative analyses were conducted to determine weighted incidence of RAF and fracture non-union. ResultsThirty-five studies comprising 9,980 patients treated with radiation therapy were included. The weighted incidence of RAFs was calculated to be 6.5% across 8,061 patients. The weighted incidence of femoral RAF was 5.2%, while pelvic RAF incidence was 17.1%. Non-union rates after initial treatment varied from 4% to 100%, with an overall weighted incidence of 48%. Treatments included intramedullary nailing, fixation with screws/plate, prosthetic replacement, conservative treatment, and amputation, with varying success rates. ConclusionThis review highlights RAFs as a significant complication of radiation therapy, with a weighted incidence of 6.5% and a non-union rate of 48%. Advanced radiation techniques have reduced RAF occurrences, but non-union remains a challenge, necessitating tailored treatment strategies. Further research is needed to optimize RAF management and improve patient outcomes.

Outcomes of sliding hip screw fixation in stable versus unstable intertrochanteric hip fractures

Purpose: Unstable intertrochanteric (IT) fractures are common orthopedic injuries in the elderly people with high morbidity. The treatment of unstable IT fractures with sliding hip screw (SHS) is still controversial. The purpose of our study is to assess the outcomes of conventional SHS in unstable IT fractures in comparison to stable ones. Methods: A total of 35 stable and 23 unstable IT fracture cases were treated with SHS between January 2017 and December 2018. Patients were evaluated for infection, revision rate, screw cut-out, development of post-traumatic arthritis or heterotopic ossification, and mortality. Results: The mean age of the patients at the time of surgery was 69.8 and 73.9 years for stable and unstable IT fractures, respectively, with 38 males (25 stable vs. 13 unstable) and 20 females (10 in each group). The mean follow-up was 42.2 and 49.4 weeks in stable and unstable IT fractures, respectively. We found a significant association between the occurrence of screw cut-out in unstable fractures compared to stable ones (17.4% vs. 0%, respectively, p = 0.01). There was an obvious trend for nonunion and higher revision rates in unstable IT fractures (17.4% vs. 2.9%, p = 0.056). Logistic regression analysis did not reveal any statistically significant confounder that might affect the rates of fracture union or revision rates. Post-traumatic arthritis and heterotopic ossification occurred in one case of unstable IT fracture. There were no reported cases of infection. Conclusion: There are higher risks of screw cut-out, nonunion, and the need for revision when the SHS is used to treat unstable IT fractures.

Application of distal radius coronal bone structure matching in the treatment of distal radius fractures

To investigate the clinical effect of coronal bone structure matching(CBSM)in the treatment of distal radius fracture. A total of 39 cases of distal radius fracture between Jannary 2018 and Jannary 2022 were included in this study. Among them there were 22 males and 17 females with an average age of (48.9±16.3) years old, ranged from 22 to 65 years old. All patients were treated with open reduction and internal fixation with plates. Based on the measurement of CBSM value on the X-ray film the next day after surgery. All patients were divided into matched group and mismatched group according to the coronal bone structure matching in the normal range or not. There were 27 patients in the matched group, including 15 males and 12 females, the age ranged from 22 to 64 years old with an average of (48.0±16.2) years old. AO classification of fracture was C1 in 6 cases and C2 in 21 cases;the operation time ranged from 1 to 6 days after injury;9 cases were complicated with ulnar styloid process fracture. There were 12 patients in the mismatched group, including 7 males and 5 females;the age ranged from 22 to 65 years old with an average of (48.8±15.8) years old. AO classification of fracture was C1 in 4 cases and C2 in 8 cases;the time from injury to operation ranged from 1 to 5 days;4 cases were complicated with ulnar styloid process fracture. The X-ray films were used to evaluate fracture healing, humeral height, ulnar angle and palm tilt angle at 3 months after operation. The range of wrist motion(pronation, supination, palmar inclination and dorsiflexion), function outcomes(Gartland-Werley score) and pain levels (visual analogue scale, VAS) were compared between the two groups at the last follow-up. The average follow-up time of 39 patients were(9.5±4.3)months, ranged from 6 to 14 months. All patients healed in one stage without postoperative infection, fracture nonunion and fracture displacement occurred. Compared with match group at the last follow-up, the VAS in the mismatch group was increased[(2.5±1.3)points vs (1.6±1.0)points], the wrist pronation were decreased[(70.5±12.6)° vs (80.5±9.4)°], with statistically significant difference(P<0.05). There was no significant difference in the range of motion(supination, palmar inclination, dorsiflexion)and excellent good rate between the two groups at last follow-up after operation (P>0.05). Wrist dysfunction, limited pronation, and wrist pain may occur when the postoperative matching degree of the distal radius fracture is not within the normal range.

Novel Method of Tackling Fracture Non-Union

Novel Method of Tackling Fracture Non-Union

Biomimetic non-collagenous proteins-calcium phosphate complex with superior osteogenesis via regulating macrophage IL-27 secretion

Traumatic defects or non-union fractures presents a substantial challenge in the fields of tissue engineering and regenerative medicine. Although synthetic calcium phosphate-based biomaterials (CaPs) such as dibasic calcium phosphate anhydrate (DCPA) are commonly employed for bone repair, their inadequate cellular immune responses significantly impede sustained degradation and optimal osteogenesis. In this study, drawing inspiration from the key structure of an acidic non-collagenous protein-CaP complex (ANCPs-CaP) essential for natural bone formation, we prepared biomimetic mineralized dibasic calcium phosphate (MDCPA). This preparation utilized plant-derived non-collagenous protein Zein as the organic template and acidic artificial saliva as the mineralization medium. Physicochemical property analysis revealed that MDCPA is a complex of Zein and DCPA, which mimics the composite of the natural ANCP-CaP. Moreover, MDCPA exhibited enhanced biodegradability and osteogenic potential. Mechanistic insight revealed that MDCPA can be phagocytized and degraded by macrophages via the FCγRIII receptor, leading to the release of interleukin 27 (IL-27), which promotes osteogenic differentiation by osteoimmunomodulation. The critical role of IL-27 in osteogenesis is further confirmed using IL-27 gene knockout mice. Additionally, MDCPA demonstrates effective healing of critical-sized defects in rat cranial bones within only 4 w, providing a promising basis and valuable insights for critical-sized bone defects regeneration.

Mining and analysis of adverse event signals for alendronate based on the real-world data of FDA adverse event reporting system database

ABSTRACT Objective Our study aims to assess alendronate-related adverse events (AEs) from the US FDA adverse event reporting system database. Methods The AE data associated with alendronate between the first quarter of 2004 and the first quarter of 2024 were selected. Various signal quantification methods, including the ROR, PRR, BCPNN, and EBGM, were applied for analysis. Results In 34,943 reports where alendronate was the primary suspected drug for the AE, 24 affected system organ classes and 1046 significant preferred terms were identified in this study. Several significant AEs beyond drug instructions with strong signals were determined, including low turnover osteopathy, fracture delayed union, fracture nonunion, loss of anatomical alignment after fracture reduction, fracture malunion, periprosthetic fracture, carotid bruit, oral fibroma, traumatic occlusion, and phlebolith. The median time to onset of alendronate-related AEs was 306 days (interquartile range [IQR] 12–1,461 days), and the majority of cases occurred 2 years later (18.80%) and within 30 days (14.49%). Conclusions The current study detected multiple potential new AE signals for alendronate, and more clinical researches are required to further validate our results and clarify their associations.

Predicting Proximal Humerus Fracture Mechanical Complications: Are Computed Tomography Hounsfield Units the Answer?

The purpose was to determine whether computed tomography (CT) Hounsfield units (HU) as a proxy for bone quality can predict postoperative complications following surgical treatment of proximal humerus fractures. Sixty-six patients with 2-, 3-, or 4-part proximal humerus fractures who underwent surgical fixation at single institution and had complete radiographic data available were included. Radiographic measurements included the deltoid tuberosity index (DTI) on preoperative anterior-posterior shoulder radiographs, and the HU value from the surgical proximal humerus was determined by measuring the humeral head at the midaxial/coronal/sagittal CT image using a circle-type region of interest (≥35 mm2). Postoperative complications recorded were implant failure, development of osteonecrosis, nonunion, and acute periprosthetic fracture. Patients with and without complications were statistically compared, and binary logistic regression was performed to determine whether preoperative proximal humerus CT HU were predictive of complications. Eight patients (12.1%) developed 11 overall complications, with three patients experiencing multiple complications each. Complications included osteonecrosis (4), implant failure (5), nonunion (1), and acute periprosthetic fracture (1). No difference was observed in demographics or Neer or AO/OTA classification between those with and without complications. Patients with complications had markedly lower DTI and overall HU as well as HU in the coronal and sagittal planes. Regression analysis for average DTI demonstrated a higher DTI and had a 10 times decreased risk of complication (P = 0.040, odds ratio = -10.5, 95% confidence interval, 0.000 to 0.616). Regression analysis for average total HU also found a higher HU associated with a decreased risk of complications (P = 0.034, odds ratio = -0.020, 95% confidence interval, 0.980 to 0.962). Logistic regression analysis, including age, age-adjusted Charlson Comorbidity Index, mean DTI, and mean total HU, only found mean total HU to be notable within the model. CT HU may identify patients with poorer bone quality and thus help predict postoperative complications. Diagnostic Level III.