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Keywords = bone fracture healing

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22 pages, 1078 KiB  
Review
The Cannabinoid Pharmacology of Bone Healing: Developments in Fusion Medicine
by Gabriel Urreola, Michael Le, Alan Harris, Jose A. Castillo, Augustine M. Saiz, Hania Shahzad, Allan R. Martin, Kee D. Kim, Safdar Khan and Richard Price
Biomedicines 2025, 13(8), 1891; https://doi.org/10.3390/biomedicines13081891 - 3 Aug 2025
Viewed by 330
Abstract
Background/Objectives: Cannabinoid use is rising among patients undergoing spinal fusion, yet its influence on bone healing is poorly defined. The endocannabinoid system (ECS)—through cannabinoid receptors 1 (CB1) and 2 (CB2)—modulates skeletal metabolism. We reviewed preclinical, mechanistic and clinical evidence to clarify how individual [...] Read more.
Background/Objectives: Cannabinoid use is rising among patients undergoing spinal fusion, yet its influence on bone healing is poorly defined. The endocannabinoid system (ECS)—through cannabinoid receptors 1 (CB1) and 2 (CB2)—modulates skeletal metabolism. We reviewed preclinical, mechanistic and clinical evidence to clarify how individual cannabinoids affect fracture repair and spinal arthrodesis. Methods: PubMed, Web of Science and Scopus were searched from inception to 31 May 2025 with the terms “cannabinoid”, “CB1”, “CB2”, “spinal fusion”, “fracture”, “osteoblast” and “osteoclast”. Animal studies, in vitro experiments and clinical reports that reported bone outcomes were eligible. Results: CB2 signaling was uniformly osteogenic. CB2-knockout mice developed high-turnover osteoporosis, whereas CB2 agonists (HU-308, JWH-133, HU-433, JWH-015) restored trabecular volume, enhanced osteoblast activity and strengthened fracture callus. Cannabidiol (CBD), a non-psychoactive phytocannabinoid with CB2 bias, accelerated early posterolateral fusion in rats and reduced the RANKL/OPG ratio without compromising final union. In contrast, sustained or high-dose Δ9-tetrahydrocannabinol (THC) activation of CB1 slowed chondrocyte hypertrophy, decreased mesenchymal-stromal-cell mineralization and correlated clinically with 6–10% lower bone-mineral density and a 1.8–3.6-fold higher pseudarthrosis or revision risk. Short-course or low-dose THC appeared skeletal neutral. Responses varied with sex, age and genetic background; no prospective trials defined safe perioperative dosing thresholds. Conclusions: CB2 activation and CBD consistently favor bone repair, whereas chronic high-THC exposure poses a modifiable risk for nonunion in spine surgery. Prospective, receptor-specific trials stratified by THC/CBD ratio, patient sex and ECS genotype are needed to establish evidence-based cannabinoid use in spinal fusion. Full article
(This article belongs to the Topic Cannabis, Cannabinoids and Its Derivatives)
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11 pages, 782 KiB  
Article
Exploring the Association Between Platelet Count, the Systemic Immune Inflammation Index, and Fracture Risk in Postmenopausal Women with Osteoporosis: A Cross-Sectional Study
by Cecilia Oliveri, Anastasia Xourafa, Rita Maria Agostino, Valentina Corigliano, Antonino Botindari, Agostino Gaudio, Nunziata Morabito, Alessandro Allegra and Antonino Catalano
J. Clin. Med. 2025, 14(15), 5453; https://doi.org/10.3390/jcm14155453 - 2 Aug 2025
Viewed by 333
Abstract
Background/Objectives: Platelets play a role in bone metabolism and fracture healing. This study aimed to investigate the association between platelet indices and the derived systemic immune inflammation index (SII) with fracture risk in postmenopausal women. Methods: Platelet count, mean platelet volume, platelet distribution [...] Read more.
Background/Objectives: Platelets play a role in bone metabolism and fracture healing. This study aimed to investigate the association between platelet indices and the derived systemic immune inflammation index (SII) with fracture risk in postmenopausal women. Methods: Platelet count, mean platelet volume, platelet distribution width (PDW), platelet crit, percentage of large platelets (P-LCR), platelet–lymphocyte ratio, and the SII, calculated as (NxP)/L, where N, P, and L represented neutrophils, platelets and lymphocytes counts, respectively, were evaluated. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Results: A total of 124 women (mean age 68.4 ± 9 years) were stratified into two groups based on the median platelet count; the “lower platelet count group” (n = 58) had a count of 200,000 (174,000 to 226,000), while the “higher platelet count group” (n = 66) had a count of 281,500 (256,500 to 308,500). The higher platelet count group showed a higher hip fracture risk (7.4 vs. 4.5%, p = 0.08) and lower lumbar spine BMD (0.773 vs. 0.83 gr/cm2, p = 0.03). By dividing the participants into two groups with higher SSI (950,848.6 ± 746,097.99) (n = 61) and lower SII (355,751.2 ± 88,662.6) (n = 63), the group with the higher SII showed the higher hip fracture risk (7.4 vs. 3.6%, p = 0.01). Univariate regression analysis revealed correlations between chronological age and PDW (r = 0.188, p = 0.047), and P-LCR (r = 0.208, p = 0.03), as well as associations between vitamin D status and P-LCR (r = −0.301, p = 0.034), and between SII and hip fracture risk (r = 0.12, p = 0.007). Conclusions: Platelet count and SII were associated with fracture risk in postmenopausal women undergoing osteoporosis assessment. Given their reproducibility and cost-effectiveness, these markers warrant further investigation in future prospective studies focused on bone fragility. Full article
(This article belongs to the Special Issue Diagnosis, Treatment, Prevention and Rehabilitation in Osteoporosis)
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14 pages, 1095 KiB  
Article
Bone Mineral Density and Intermuscular Fat Derived from Computed Tomography Images Using Artificial Intelligence Are Associated with Fracture Healing
by Yilin Tang, Xiaodong Wang, Ming Li and Liang Jin
Bioengineering 2025, 12(7), 785; https://doi.org/10.3390/bioengineering12070785 - 19 Jul 2025
Viewed by 530
Abstract
Objectives: To employ artificial intelligence (AI) to automatically measure bone mineral density (BMD) and intramuscular fat in computed tomography (CT) images of patients with fractures and explore the association between these parameters and fracture healing. Methods: This retrospective study included patients who underwent [...] Read more.
Objectives: To employ artificial intelligence (AI) to automatically measure bone mineral density (BMD) and intramuscular fat in computed tomography (CT) images of patients with fractures and explore the association between these parameters and fracture healing. Methods: This retrospective study included patients who underwent baseline CT scans for rib fracture diagnosis and follow-up CT scans for fracture healing assessment at our hospital between 2012 and 2023. The volumetric BMD of the entire first lumbar vertebra (L1) and the paraspinal intramuscular fat area (PIFA) at the midsection of L1 in the baseline CT were extracted using AI. The primary outcomes, including callus formation, volume increase, and poor healing, and logistic regression were used to analyze the relationships between BMD and PIFA with primary outcomes. Results: Overall, 297 fractures from 53 patients (24 males; mean age: 53.83 ± 10.86 years) were included in this study. In multivariate regression analysis, a 1 standard deviation (SD) decrease in BMD was identified as an independent prognostic factor for reduced callus formation (odds ratio [OR] = 0.70, 95% confidence interval [CI] = 0.50–0.97), diminished volume increase (OR = 0.70, 95% CI = 0.51–0.96), and elevated poor fracture healing at follow-up (OR = 2.08, 95% CI = 1.38–3.13). Similarly, a 1 SD increase in PIFA was an independent prognostic factor for reduced callus formation (OR = 0.24, 95% CI = 0.16–0.37), diminished volume increase (OR = 0.33, 95% CI = 0.23–0.49), and elevated poor fracture healing at follow-up (OR = 2.09, 95% CI = 1.50–2.93). Therefore, a model combining BMD, PIFA, and clinical characteristics significantly outperformed a model that included only clinical characteristics in predicting callus formation, volume increase, and poor fracture healing, with areas under the curve of 0.790, 0.749, and 0.701, respectively (all p < 0.001). Conclusions: BMD and PIFA can be used as early predictors of fracture healing outcomes and can help clinicians select appropriate interventions to prevent poor healing. Full article
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23 pages, 4725 KiB  
Tutorial
Fragility Fractures of the Pelvis—Current Understanding and Open Questions
by Amber Gordon, Michela Saracco, Peter V. Giannoudis and Nikolaos K. Kanakaris
J. Clin. Med. 2025, 14(14), 5122; https://doi.org/10.3390/jcm14145122 - 18 Jul 2025
Viewed by 850
Abstract
Fragility fractures of the pelvis (FFPs) are common in elderly patients, particularly those with osteoporosis. FFPs can be associated with high mortality, morbidity, and functional decline. Known risk factors include being over 80 years old and delays in surgical intervention when this is [...] Read more.
Fragility fractures of the pelvis (FFPs) are common in elderly patients, particularly those with osteoporosis. FFPs can be associated with high mortality, morbidity, and functional decline. Known risk factors include being over 80 years old and delays in surgical intervention when this is required. While the role of surgery in FFPs remains less defined than in proximal femoral fractures in the elderly, studies indicate that surgical fixation offers improved survival and functional outcomes. Similarly, the choice of fixation method, whether posterior or anterior, and their combinations, vary between clinicians. It depends on the fracture type and patient-specific factors, such as bone quality and comorbidities, as well as the surgeon’s experience and the availability of resources. Additionally, orthobiologic adjuncts such as cement augmentation and sacroplasty can enhance the stability of an osteoporotic fracture during surgical intervention. Furthermore, medical treatments for osteoporosis, especially the use of teriparatide, have demonstrated beneficial effects in reducing fractures and promoting healing of the FFPs. Return to pre-injury activities is often limited, with independence rates remaining low at mid-term follow-up. Factors that influence clinical outcomes include fracture type, with Type III and IV fractures generally leading to poorer outcomes, and patient age, functional reserve, and comorbidities. The present tutorial aims to summarise the relevant evidence on all aspects of FFPs, inform an updated management strategy, and provide a template of the reconstruction ladder referring to the most available surgical techniques and treatment methods. Further research, based on large-scale studies, is needed to address the open questions described in this manuscript and refine surgical techniques, as well as determine optimal treatment pathways for this vulnerable patient population. Full article
(This article belongs to the Special Issue The “Orthogeriatric Fracture Syndrome”—Issues and Perspectives)
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14 pages, 1990 KiB  
Article
Radiographic Healing After Intramedullary Nailing with or Without Lateral Plate Augmentation in Atypical Subtrochanteric Femoral Fractures: A Retrospective Study
by Le Wan, Chan-Young Lee, Taek-Rim Yoon and Kyung-Soon Park
J. Clin. Med. 2025, 14(14), 4976; https://doi.org/10.3390/jcm14144976 - 14 Jul 2025
Viewed by 323
Abstract
Background: Atypical subtrochanteric femoral fractures (ASFs), frequently linked to long-term bisphosphonate use, present significant fixation challenges due to impaired bone healing. While intramedullary (IM) nailing is the standard treatment, delayed union or nonunion remains common. This study aimed to evaluate whether supplementing [...] Read more.
Background: Atypical subtrochanteric femoral fractures (ASFs), frequently linked to long-term bisphosphonate use, present significant fixation challenges due to impaired bone healing. While intramedullary (IM) nailing is the standard treatment, delayed union or nonunion remains common. This study aimed to evaluate whether supplementing IM nailing with lateral plate augmentation improves radiographic healing in patients with ASFs. Methods: This retrospective comparative study included 12 elderly female patients with ASFs treated between October 2013 and October 2023. Five patients underwent IM nailing alone (IM group), while seven received IM nailing with additional lateral plate fixation (Plate + IM group). Fracture healing was assessed using the modified Radiographic Union Score for Tibial fractures (mRUST) at 3, 6, and 12 months postoperatively. Intergroup comparisons were performed using the Mann–Whitney U test. Results: The median mRUST scores in the IM group were 4 (IQR 3.5–4), 6 (IQR 4.5–6.5), and 8 (IQR 7–9) at 3, 6, and 12 months, respectively. In the Plate + IM group, the scores were 5 (IQR 4–6), 8 (IQR 8–8), and 10 (IQR 10–11), respectively. The Plate + IM group demonstrated significantly higher mRUST scores at all assessed time points (3 months: p = 0.018; 6 months: p = 0.003; 12 months: p = 0.006). No implant failures or postoperative infections occurred in either group during the 12-month follow-up period. One patient (20%) in the IM group developed fracture nonunion, while no nonunion cases were observed in the Plate + IM group. Conclusions: Lateral plate augmentation as an adjunct to IM nailing may promote faster and more consistent radiographic healing in atypical subtrochanteric femoral fractures. This dual-fixation strategy may offer a biomechanically more robust option for patients at risk of delayed union, potentially contributing to a lower risk of nonunion, though further prospective studies are required to confirm this finding. Full article
(This article belongs to the Section Orthopedics)
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30 pages, 2419 KiB  
Systematic Review
Rehabilitation Protocols for Surgically Treated Acetabular Fractures in Older Adults: Current Practices and Outcomes
by Silviya Ivanova, Ondrej Prochazka, Peter V. Giannoudis, Theodoros Tosounidis, Moritz Tannast and Johannes D. Bastian
J. Clin. Med. 2025, 14(14), 4912; https://doi.org/10.3390/jcm14144912 - 10 Jul 2025
Viewed by 427
Abstract
Background/Objectives: Acetabular fractures in older adults pose significant challenges due to bone fragility, complex fracture patterns, and increased comorbidities. Surgical management, including isolated open reduction and internal fixation (ORIF) and ORIF combined with acute total hip arthroplasty (THA) (combined hip procedure—CHP), have [...] Read more.
Background/Objectives: Acetabular fractures in older adults pose significant challenges due to bone fragility, complex fracture patterns, and increased comorbidities. Surgical management, including isolated open reduction and internal fixation (ORIF) and ORIF combined with acute total hip arthroplasty (THA) (combined hip procedure—CHP), have advanced considerably. Nevertheless, optimal postoperative rehabilitation and particularly weight-bearing (WB) recommendations remain controversial and inconsistent. This review aims to assess rehabilitation protocols, focusing on WB strategies following the surgical treatment of acetabular fractures in older adults. It also examines differences in WB restrictions by surgical technique (ORIF vs. CHP) and their impact on recovery, complications, reoperations, and mortality. Methods: A systematic review of PubMed, Embase, and the Cochrane Library (2006–2024) included studies involving patients aged ≥65 years treated surgically for displaced acetabular fractures. Data included WB protocols (full, partial, toe-touch), length of stay (LOS), healing, functional outcomes (mobility, Harris and Oxford Hip Scores), complications, reoperations, delayed THA, compliance, readmission, and mortality. Due to heterogeneity, findings were narratively synthesized. Risk of bias was assessed using ROBINS-I and RoB2. Results: Twenty studies involving 929 patients (530 isolated ORIF, 399 CHP) were analyzed. The overall mean follow-up was 3.5 years (range: 1–5.25 years). Postoperative WB protocols were reported in 19 studies (95%). Immediate full WB was permitted in 0% of isolated ORIF studies (0/13), with partial WB recommended by 62% (8/13) for durations typically between 6 and 12 weeks. On the other hand, immediate full WB was allowed in 53% (9/17) of CHP studies. Functional outcomes were moderate following isolated ORIF (mean HHS: 63–82 points), with delayed THA conversion rates ranging from 16.5% to 45%. CHP demonstrated superior functional outcomes (mean HHS: 70–92 points), earlier independent ambulation, and higher patient satisfaction (74–90%), yet increased orthopedic complications, including dislocations (8–11%) and implant loosening (up to 18%). LOS varied from 12 to 21 days (mean 16 days) for isolated ORIF and from 8 to 25 days (mean 17 days) for CHP. Readmission within 30 days was not explicitly reported in any study. Mortality at 1 year varied significantly (ORIF: 0–25%; CHP: 0–14%), increasing markedly at long-term follow-up (up to 42% ORIF, up to 70% CHP at five years). Compliance with WB restrictions was monitored in only two studies (11%). Conclusions: Postoperative rehabilitation after acetabular fracture surgery in older adults remains inconsistent and lacks standardization. Combining ORIF with acute THA may enable earlier weight-bearing and improved short-term function but carries risks such as dislocation and implant loosening. In contrast, isolated ORIF avoids these implant-related complications but often requires prolonged weight-bearing restrictions. Robust evidence is still missing. Future trials are essential to establish standardized protocols that balance mechanical protection and functional recovery. Full article
(This article belongs to the Special Issue The “Orthogeriatric Fracture Syndrome”—Issues and Perspectives)
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15 pages, 959 KiB  
Article
Rewriting the Treatment Paradigm: Ilizarov Method Achieves High Success in Septic Non-Unions Without Local Antibiotics or Biologic Adjuncts
by Filippo Vandenbulcke, Andrea Dorotei, Emiliano Malagoli and Alexander Kirienko
Biomedicines 2025, 13(7), 1665; https://doi.org/10.3390/biomedicines13071665 - 8 Jul 2025
Viewed by 315
Abstract
Background/Objectives: The aim of this study is to describe the characteristics of a cohort of patients who underwent surgery for septic non-union of the lower extremities. Methods: We analyzed clinical data from 74 patients affected by septic non-union of long bones [...] Read more.
Background/Objectives: The aim of this study is to describe the characteristics of a cohort of patients who underwent surgery for septic non-union of the lower extremities. Methods: We analyzed clinical data from 74 patients affected by septic non-union of long bones in the lower extremities, treated with the Ilizarov method between January 2006 and December 2021. The primary objective of our study was to describe the time from surgery to bone union. Results: Patients had undergone a median of three previous surgical interventions, had an average bone defect of 5.4 cm, with 43.4% of patients having a Non-Union Scoring System (NUSS) > 75 points, and 46.5% of patients having been considered candidates for limb amputation in other centers. Bone union was achieved in 73 patients (98.65%), while infection resolution was achieved in 68 patients (91.89%). In 63 patients (85.13%), healing was obtained with one surgical procedure only. Only 11 re-interventions were necessary after frame removal (14.86%): 10 were due to re-fractures (13.51%) and 1 to an infection recurrence, which resulted in an amputation (1.35%). At a time of 6.01 ± 3.9 years follow-up, the Association for the Study and Application of the Methods of Ilizarov (ASAMI) scoring system indicated excellent or good outcomes in 97.3% for the bone subscale and in 89.2% for the functional subscale. The Patient Global Impression of Change (PGIC) showed that 96.8% of patients were “very much improved” or “much improved”. Patients who have suffered a more recent trauma or fewer previous surgeries achieved a better outcome. Conclusions: Despite some limitations, this study shows that treatment of septic non-unions using the Ilizarov method is both highly effective in bone and infection healing and results in a satisfactory functional outcome. The results observed in our cohort suggest that the Ilizarov method could be critically re-evaluated as a primary treatment option for these challenging cases. The clinical relevance of these findings lies in their potential to significantly alter the current treatment paradigm, by questioning the need for biologic adjuncts and local antibiotics, thereby reducing healthcare costs. Full article
(This article belongs to the Special Issue New Insights into Bone and Cartilage Biology)
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36 pages, 1647 KiB  
Review
Three-Dimensionally Printed Scaffolds and Drug Delivery Systems in Treatment of Osteoporosis
by Cosmin Iulian Codrea and Victor Fruth
Biomimetics 2025, 10(7), 429; https://doi.org/10.3390/biomimetics10070429 - 1 Jul 2025
Viewed by 740
Abstract
The increasing incidence of osteoporotic fractures determines ongoing research on new methods and strategies for improving the difficult healing process of this type of fracture. Osteoporotic patients suffer from the intense side effects of accustomed drug treatment and its systemic distribution in the [...] Read more.
The increasing incidence of osteoporotic fractures determines ongoing research on new methods and strategies for improving the difficult healing process of this type of fracture. Osteoporotic patients suffer from the intense side effects of accustomed drug treatment and its systemic distribution in the body. To overcome these drawbacks, besides searching for new drugs, 3D-printed scaffolds and drug delivery systems have started to be increasingly seen as the main strategy employed against osteoporosis. Three-dimensionally printed scaffolds can be tailored in intricate designs and make use of nanoscale topographical and biochemical cues able to enhance bone tissue regeneration. Research regarding drug delivery systems is exploring bold new ways of targeting bone tissue, making use of designs involving nanoparticles and intricate encapsulation and support methods. The local administration of treatment with the help of a scaffold-based drug delivery system looks like the best option through its use of the advantages of both structures. Biomimetic systems are considered the future norm in the field, while stimuli-responsiveness opens the door for the next level of efficiency, patient compliance, and a drastic reduction in side effects. The successful approval of these products still requires numerous challenges throughout the development and regulatory processes, but the interest and effort in this direction are high. This review explored various strategies for managing osteoporosis, emphasizing the use of scaffolds for targeted drug delivery to bone tissue. Instead of covering the whole subject, we focused on the most important aspects, with the intention to provide an up-to-date and useful introduction to the management of osteoporosis. Full article
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28 pages, 2337 KiB  
Review
Narrative Review on the Management of Neck of Femur Fractures in People Living with HIV: Challenges, Complications, and Long-Term Outcomes
by Yashar Mashayekhi, Chibuchi Amadi-Livingstone, Abdulmalik Timamy, Mohammed Eish, Ahmed Attia, Maria Panourgia, Dushyant Mital, Oliver Pearce and Mohamed H. Ahmed
Microorganisms 2025, 13(7), 1530; https://doi.org/10.3390/microorganisms13071530 - 30 Jun 2025
Viewed by 586
Abstract
Neck of femur (NOF) fractures are a critical orthopaedic emergency with a high morbidity and mortality prevalence, particularly in people living with Human Immunodeficiency Virus (PLWHIV). A combination of HIV infection, combined antiretroviral therapy (cART), and compromised bone health further increases the risk [...] Read more.
Neck of femur (NOF) fractures are a critical orthopaedic emergency with a high morbidity and mortality prevalence, particularly in people living with Human Immunodeficiency Virus (PLWHIV). A combination of HIV infection, combined antiretroviral therapy (cART), and compromised bone health further increases the risk of fragility fractures. Additionally, HIV-related immune dysfunction, cART-induced osteoporosis, and perioperative infection risks further pose challenges in ongoing surgical management. Despite the rising global prevalence of PLWHIV, no specific guidelines exist for the perioperative and post-operative care of PLWHIV undergoing NOF fracture surgery. This narrative review synthesises the current literature on the surgical management of NOF fractures in PLWHIV, focusing on pre-operative considerations, intraoperative strategies, post-operative complications, and long-term outcomes. It also explores infection control, fracture healing dynamics, and ART’s impact on surgical outcomes while identifying key research gaps. A systematic database search (PubMed, Embase, Cochrane Library) identified relevant studies published up to February 2025. Inclusion criteria encompassed studies on incidence, risk factors, ART impact, and NOF fracture outcomes in PLWHIV. Data were analysed to summarise findings and highlight knowledge gaps. Pre-operative care: Optimisation involves assessing immune status (namely, CD4 counts and HIV-1 viral loads), bone health, and cART to minimise surgical risk. Immunodeficiency increases surgical site and periprosthetic infection risks, necessitating potential enhanced antibiotic prophylaxis and close monitoring of potential start/switch/stopping of such therapies. Surgical management of neck of femur (NOF) fractures in PLWHIV should be individualised based on fracture type (intracapsular or extracapsular), age, immune status, bone quality, and functional status. Extracapsular fractures are generally managed with internal fixation using dynamic hip screws or intramedullary nails. For intracapsular fractures, internal fixation may be appropriate for younger patients with good bone quality, though there is an increased risk of non-union in this group. Hemiarthroplasty is typically favoured in older or frailer individuals, offering reduced surgical stress and lower operative time. Total hip arthroplasty (THA) is considered for active patients or those with pre-existing hip joint disease but carries a higher infection risk in immunocompromised individuals. Multidisciplinary evaluation is critical in guiding the most suitable surgical approach for PLWHIV. Importantly, post-operative care carries the risk of higher infection rates, requiring prolonged antibiotic use and wound surveillance. Antiretroviral therapy (ART) contributes to bone demineralisation and chronic inflammation, increasing delayed union healing and non-union risk. HIV-related frailty, neurocognitive impairment, and socioeconomic barriers hinder rehabilitation, affecting recovery. The management of NOF fractures in PLWHIV requires a multidisciplinary, patient-centred approach ideally comprising a team of Orthopaedic surgeon, HIV Physician, Orthogeriatric care, Physiotherapy, Occupational Health, Dietitian, Pharmacist, Psychologist, and related Social Care. Optimising cART, tailoring surgical strategies, and enforcing strict infection control can improve outcomes. Further high-quality studies and randomised controlled trials (RCTs) are essential to develop evidence-based guidelines. Full article
(This article belongs to the Section Virology)
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14 pages, 1830 KiB  
Article
Intramedullary Nails vs. Locking Plates for Displaced Proximal Humerus Fractures in Patients over 60: A Comparative Clinical Study
by Marco Simone Vaccalluzzo, Marco Sapienza, Sergio Valenti, Benedetta Di Tomasi, Ludovico Lucenti, Vito Pavone and Gianluca Testa
J. Clin. Med. 2025, 14(13), 4563; https://doi.org/10.3390/jcm14134563 - 27 Jun 2025
Viewed by 378
Abstract
Background: Displaced proximal humerus fractures (PHFs) in adults represent a common orthopedic challenge, especially in elderly patients with compromised bone quality. Intramedullary nails (IM) and locking plates (LP) are the most widely used fixation techniques, though the literature remains inconclusive regarding their comparative [...] Read more.
Background: Displaced proximal humerus fractures (PHFs) in adults represent a common orthopedic challenge, especially in elderly patients with compromised bone quality. Intramedullary nails (IM) and locking plates (LP) are the most widely used fixation techniques, though the literature remains inconclusive regarding their comparative efficacy. Methods: This retrospective cohort study included 187 patients (mean age: 65.4 years) treated surgically for Neer ≥ 2-part proximal humerus fractures at a single tertiary referral center between 2018 and 2023. Patients underwent either IM nailing or LP fixation. Baseline characteristics included age, sex, smoking status, ASA score, trauma mechanism, and bone quality (assessed by the Deltoid Tuberosity Index). Functional outcomes (DASH and Constant–Murley scores), range of motion (ROM), radiographic healing, and complications were evaluated at 1, 3, 6, and 12 months postoperatively. Results were stratified by fracture type (two-, three-, and four-part fractures) and treatment group. Results: At 12 months, no statistically significant differences were found between groups in terms of DASH (p = 0.484) or Constant–Murley scores (p = 0.057). ROM recovery was comparable across all time points. Stratified analysis showed similar outcomes across fracture types. Age, smoking, and bone quality did not significantly influence clinical results. The overall complication rate was 11.8%, with no significant difference between groups. Avascular necrosis and hardware-related issues occurred predominantly in four-part fractures. Conclusions: Both intramedullary nailing and locking plate fixation provided comparable short-term outcomes for displaced PHFs. Functional recovery appeared more dependent on fracture complexity than on the choice of implant. Surgical technique should therefore be selected based on fracture morphology, patient characteristics, and surgeon experience. Full article
(This article belongs to the Special Issue Diagnosis, Treatment, Prevention and Rehabilitation in Osteoporosis)
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8 pages, 607 KiB  
Proceeding Paper
Advancements in Nanotechnology for Orthopedic Applications: A Comprehensive Overview of Nanomaterials in Bone Tissue Engineering and Implant Innovation
by Newton Neogi, Kristi Priya Choudhury, Sabbir Hossain and Ibrahim Hossain
Med. Sci. Forum 2025, 32(1), 4; https://doi.org/10.3390/msf2025032004 - 26 Jun 2025
Viewed by 496
Abstract
Orthopedic implant technology has historically seen difficulties in attaining long-term stability and biological integration, leading to complications such as implant loosening, wear debris production, and heightened infection risk. Nanotechnology provides a revolutionary method for addressing these constraints through the introduction of materials characterized [...] Read more.
Orthopedic implant technology has historically seen difficulties in attaining long-term stability and biological integration, leading to complications such as implant loosening, wear debris production, and heightened infection risk. Nanotechnology provides a revolutionary method for addressing these constraints through the introduction of materials characterized by exceptional biocompatibility, durability, and integration potential. Nanomaterials (NMs), characterized by distinctive surface topographies and elevated surface area-to-volume ratios, facilitate improved osseointegration and provide regulated medication release, thereby creating a localized therapeutic milieu surrounding the implant site. To overcome the long-standing constraints of conventional implants, such as poor osseointegration, low mechanical fixation, immunological rejection, and implant-related infections, nanotechnology is causing a revolution in the field of orthopedic research. NMs are ideally suited for orthopedic applications due to their exceptional features, including increased tribology, wear resistance, prolonged drug administration, and excellent tissue regeneration. Because of their nanoscale size, they can imitate the hierarchical structure of real bone, which in turn encourages the proliferation of cells, lowers the risk of infection, and helps with the mending of bone fractures. This article will investigate the wide-ranging possibilities of nanostructured ceramics, polymers, metals, and carbon materials in bone tissue engineering, diagnostics, and the treatment of implant-related infections, bone malignancies, and bone healing. In addition, this paper will provide a basic overview of the most recent discoveries in nanotechnology driving the future of translational orthopedic research. It will also highlight safety evaluations and regulatory requirements for orthopedic devices. Full article
(This article belongs to the Proceedings of The 1st International Online Conference on Clinical Reports)
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11 pages, 2021 KiB  
Case Report
Microsurgical Reconstruction of Extensive Lower Limb Defects: Latissimus Dorsi Free Flap for Circumferential Soft Tissue Loss Following High-Energy Trauma
by Edoardo Filigheddu, Federico Ziani, Giovanni Arrica, Sofia De Riso, Anna Manconi, Corrado Rubino and Emilio Trignano
J. Clin. Med. 2025, 14(13), 4424; https://doi.org/10.3390/jcm14134424 - 21 Jun 2025
Viewed by 562
Abstract
Background/Objectives: High-energy trauma to the lower limb often results in extensive soft tissue loss with exposure of critical structures, posing a serious threat to limb viability. Early and effective coverage is crucial to prevent infection, promote bone healing, and preserve function. This report [...] Read more.
Background/Objectives: High-energy trauma to the lower limb often results in extensive soft tissue loss with exposure of critical structures, posing a serious threat to limb viability. Early and effective coverage is crucial to prevent infection, promote bone healing, and preserve function. This report presents the use of a latissimus dorsi free flap for circumferential soft tissue reconstruction following a severe crush injury. Methods: We describe the case of a young female patient who sustained a high-energy crush trauma with a comminuted, displaced fracture of the middle and distal third of the tibia and complete circumferential soft tissue loss. Due to the extent and location of the defect, a latissimus dorsi free flap was selected for reconstruction. The surgical technique, microsurgical anastomosis, postoperative care, and rehabilitation protocol are detailed. Results: The latissimus dorsi flap provided reliable coverage of the entire defect, protected the underlying bone and hardware, and promoted wound healing. No major complications were observed. Functional recovery was satisfactory, with progressive weight-bearing and joint mobility achieved during follow-up. Conclusions: In complex lower limb injuries with extensive soft tissue damage, free flap transfer remains a key strategy for limb salvage. The latissimus dorsi flap, due to its size, reliability, and versatility, represents a valuable option for circumferential coverage and restoration of limb function following high-energy trauma. Full article
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14 pages, 2539 KiB  
Article
Sinusoidal Extremely Low-Frequency Electromagnetic Stimulation (ELF-EMS) Promotes Angiogenesis In Vitro
by Lena Perez Font, Amanda Moya-Gomez, Hannelore Kemps, Ivo Lambrichts, Jean-Michel Rigo, Bert Brône and Annelies Bronckaers
Biomedicines 2025, 13(6), 1490; https://doi.org/10.3390/biomedicines13061490 - 17 Jun 2025
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Abstract
Background/Objectives: Angiogenesis is the multistep process of the formation of new blood vessels. It is beneficial in scenarios that require tissue repair and regeneration, such as wound healing, bone fracture repair, and recovery from ischemic injuries like stroke, where new blood vessel [...] Read more.
Background/Objectives: Angiogenesis is the multistep process of the formation of new blood vessels. It is beneficial in scenarios that require tissue repair and regeneration, such as wound healing, bone fracture repair, and recovery from ischemic injuries like stroke, where new blood vessel formation restores oxygen and nutrient supply to damaged areas. Extremely low-frequency electromagnetic stimulation (ELF-EMS), which involves electromagnetic fields in the frequency range of 0–300 Hz, have been shown to reduce ischemic stroke volume by improving cerebral blood flow and recovery effects that are dependent on eNOS. Based on previous results, we herein explore the effects of ELF-EMS treatment (13.5 mT/10 and 60 Hz) on the activation of angiogenic processes in vitro in homeostatic conditions. Methods: Using human microvascular endothelial cells (HMEC-1), we studied cell proliferation, migration, and tube formation in vitro, as well as nitric oxide production and the effect of calcium and nitric oxide (NO) on these processes. Moreover, blood vessel formation was studied using a chicken chorioallantoic membrane (CAM) assay. Results: Our results showed that ELF-EMS increases proliferation, tube formation, and both the migration and transmigration of these cells, the latter of which was mediated via NO. In turn, calcium inhibition decreased ELF-EMF-induced NO production. Furthermore, ELF-EMS significantly increased blood vessel formation in the CAM assay. Conclusions: Our results indicated that ELF-EMS exposure (13.5 mT/10 and 60 Hz) significantly induces angiogenesis in vitro and in ovo, underscoring its potential application in the treatment of conditions characterized by insufficient blood supply. Full article
(This article belongs to the Section Cell Biology and Pathology)
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17 pages, 6100 KiB  
Article
Effects of Modified Messenger RNA of Adiponectin Delivered by Lipid Nanoparticles on Adipogenesis and Bone Metabolism In Vitro and In Vivo
by Ying Xie, Qian Ma, Jinghao Wang, Zoe Xiaofang Zhu, Rady E. El-Araby, Maxwell Tu, Zhongyu Li, Xiaoyang Xu, Qisheng Tu and Jake Chen
Cells 2025, 14(12), 891; https://doi.org/10.3390/cells14120891 - 13 Jun 2025
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Abstract
Adiponectin (APN) is a secreted adipokine that plays a key role in modulating energy and bone metabolism, as well as regulating inflammatory responses. The overexpression of APN has been proposed as a potential therapeutic strategy for treating obesity and related disorders. Lipid nanoparticles [...] Read more.
Adiponectin (APN) is a secreted adipokine that plays a key role in modulating energy and bone metabolism, as well as regulating inflammatory responses. The overexpression of APN has been proposed as a potential therapeutic strategy for treating obesity and related disorders. Lipid nanoparticles (LNPs) are promising vectors for transporting messenger ribonucleic acid (mRNA) molecules. This study tested whether delivering a stabilized version of adiponectin mRNA (APN mRNA) using lipid nanoparticles could reduce fat formation and promote bone repair in vitro and in vivo. We demonstrated that transfection with APN-LNP upregulated the mRNA and protein expression of APN, while inhibiting adipogenesis in 3T3-L1 adipocytes. APN-LNP enhanced osteogenic gene expression in MC3T3-E1 cells in a dose-dependent manner. It also reduced matrix metalloproteinase 9 expression in receptor activator of nuclear factor-kappaB ligand (RANKL)-stimulated RAW264.7 cells, suggesting an anti-resorptive effect. In vivo, a femoral fracture model was established to explore the application of APN-LNP in promoting bone healing in diet-induced obese mice. Micro-computed tomography and histology analysis indicated that intravenous injection with APN-LNP promoted bone healing. Fasting blood glucose and body weight were decreased in the APN-LNP group. Moreover, APN-LNP increased bone sialoprotein and runt-related transcription factor 2 expression in contralateral femurs, as well as interleukin-10 expression in white adipose tissues. Thus, our study provides promising preclinical data on the potential use of APN-LNP for treating bone disorders in obesity. Full article
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20 pages, 1668 KiB  
Systematic Review
Conservative Treatment with Teriparatide Versus Vertebroplasty for Acute Osteoporotic Vertebral Compression Fractures: A Meta-Analysis
by Subum Lee, Junseok W. Hur, Younggyu Oh, Sungjae An, Yeongu Chung, Danbi Park and Jin Hoon Park
J. Clin. Med. 2025, 14(11), 3967; https://doi.org/10.3390/jcm14113967 - 4 Jun 2025
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Abstract
Background/Objectives: The debate continues, despite numerous studies, on whether vertebroplasty (VP) or conservative treatment is more suitable for osteoporotic vertebral compression fractures (OVCFs). Meanwhile, teriparatide (TP) has shown promise in accelerating bone healing in OVCFs. This analysis aims to clarify the potential benefits [...] Read more.
Background/Objectives: The debate continues, despite numerous studies, on whether vertebroplasty (VP) or conservative treatment is more suitable for osteoporotic vertebral compression fractures (OVCFs). Meanwhile, teriparatide (TP) has shown promise in accelerating bone healing in OVCFs. This analysis aims to clarify the potential benefits of conservative treatment using TP over VP from several clinical studies on acute OVCFs. Methods: A literature search was performed, using the MEDLINE, Embase, Cochrane Review, Web of Science, and Google Scholar databases, for studies published up until September 2023. Five studies [one randomized controlled study (RCT) and four non-RCTs] were included in a qualitative and quantitative synthesis. Data were extracted and analyzed using a random-effects model to obtain the effect size. Results: Five studies with a total of 326 (TP = 147, VP = 179) patients were included. Within the first week of treatment, the VP group showed a significantly greater decrease in their visual analog scale (VAS) scores. There was no significant difference in VAS score reduction between the two groups from one to three months. However, after 6 months, the TP group exhibited significant superiority in VAS scores and bone mineral density (BMD). Furthermore, TP was associated with a reduced number of new-onset OVCFs, with a statistically significant estimated odds ratio of 0.15 (95% CI, 0.04–0.51, p < 0.01). Conclusions: Conservative treatment using TP for acute OVCF has been found to reduce subsequent fractures, provide equivalent or superior pain control, and increase BMD compared to VP. Nonetheless, the meta-analysis results are weak, due to the low level of evidence. Full article
(This article belongs to the Special Issue Recent Advances in the Management of Fractures)
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