Aims

The involvement of long non-coding RNA (lncRNA) in bone marrow mesenchymal stem cell (MSC) osteogenic differentiation during osteoporosis (OP) development has attracted much attention. In this study, we aimed to disclose how LINC01089 functions in human mesenchymal stem cell (hMSC) osteogenic differentiation, and to study the mechanism by which LINC01089 regulates MSC osteogenesis.

Addressing bone defects is a complex medical challenge that involves dealing with various skeletal conditions, including fractures, osteoporosis (OP), bone tumours, and bone infection defects. Despite the availability of multiple conventional treatments for these skeletal conditions, numerous limitations and unresolved issues persist. As a solution, advancements in biomedical materials have recently resulted in novel therapeutic concepts. As an emerging biomaterial for bone defect treatment, graphene oxide (GO) in particular has gained substantial attention from researchers due to its potential applications and prospects. In other words, GO scaffolds have demonstrated remarkable potential for bone defect treatment. Furthermore, GO-loaded biomaterials can promote osteoblast adhesion, proliferation, and differentiation while stimulating bone matrix deposition and formation. Given their favourable biocompatibility and osteoinductive capabilities, these materials offer a novel therapeutic avenue for bone tissue regeneration and repair. This comprehensive review systematically outlines GO scaffolds’ diverse roles and potential applications in bone defect treatment.

Cite this article: Bone Joint Res 2024;13(12):725–740.

Introduction. PIEZO mechanoreceptors are increasingly recognized to play critical roles in fundamental physiological processes like proprioception, touch, or tendon biomechanics. However, their gating mechanisms and downstream signaling are still not completely understood, mainly due to the lack of effective tools to probe these processes. Here, we developed new tailor-made nanoswitches enabling wireless targeted actuation on PIEZO1 by combining molecular imprinting concepts with magnetic systems. Method. Two epitopes from functionally relevant domains of PIEZO1 were rationally selected in silico and used as templates for synthesizing molecularly imprinted nanoparticles (MINPs). Highly-responsive superparamagnetic zinc-doped iron oxide nanoparticles were incorporated into MINPs to grant them magnetic responsiveness. Endothelial cells (ECs) and adipose tissue-derived stem cells (ASCs) incubated with each type of MINP were cultured under or without the application of cyclical magnetomechanical stimulation. Downstream effects of PIEZO1 actuation on cell mechanotransduction signaling and stem cell fate were screened by analyzing gene expression profiles. Result. Nanoswitches showed sub-nanomolar affinity for their respective epitope, binding PIEZO1-expressing ECs similarly to antibodies. Expression of genes downstream of PIEZO1 activity significantly changed after magnetomechanical stimulation, demonstrating that nanoswitches can transduce this stimulus directly to PIEZO1 mechanoreceptors. Moreover, this wireless actuation system proved effective for modulating the expression of genes related to musculoskeletal differentiation pathways in ASCs, with RNA-sequencing showing pronounced shifts in extracellular matrix organization, signal transduction, or collagen biosynthesis and modification. Importantly, targeting each epitope led to different signaling effects, implying distinct roles for each domain in the sophisticated function of these channels. Conclusion. This innovative wireless actuation technology provides a promising approach for dissecting PIEZO-mediated mechanobiology and suggests potential therapeutic applications targeting PIEZO1 in regenerative medicine for mechanosensitive tissues like tendon. Acknowledgements. EU's Horizon 2020 ERC under grant No. 772817 and Horizon Europe under grant No. 101069302; FCT/MCTES for PD/BD/143039/2018, COVID/BD/153025/2022, 10.54499/2020.03410.CEECIND/CP1600/CT0013, 10.54499/2022.05526.PTDC, 10.54499/UIDB/50026/2020, 10.54499/UIDP/50026/2020, and 10.54499/LA/P/0050/2020

Introduction

Anterior shoulder instability results in labral and osseous glenoid injuries. With a large osseous defect, there is a risk of recurrent dislocation of the joint, and therefore the patient must undergo surgical correction. An MRI evaluation of the patient helps to assess the soft tissue injury. Currently, the volumetric three-dimensional (3D) reconstructed CT image is the standard for measuring glenoid bone loss and the glenoid index. However, it has the disadvantage of exposing the patient to radiation and additional expenses. This study aims to compare the values of the glenoid index using MRI and CT.

The October 2024 Wrist & Hand Roundup360 looks at: Circumferential casting versus plaster splinting in preventing redisplacement of distal radial fractures; Comparable outcomes for operative versus nonoperative treatment of scapholunate ligament injuries in distal radius fractures; Perceived pain during the reduction of Colles fracture without anaesthesia; Diagnostic delays and physician training are key to reducing scaphoid fracture nonunion; Necrotizing fasciitis originating in the hand: a systematic review and meta-analysis; Study design influences outcomes in distal radial fracture research; Long-term results of index finger pollicization for congenital thumb anomalies: a systematic review; Enhancing nerve injury diagnosis: the evolving role of imaging and electrodiagnostic tools.

Aims. In order to release the contracture band completely without damaging normal tissues (such as the sciatic nerve) in the surgical treatment of gluteal muscle contracture (GMC), we tried to display the relationship between normal tissue and contracture bands by magnetic resonance neurography (MRN) images, and to predesign a minimally invasive surgery based on the MRN images in advance. Methods. A total of 30 patients (60 hips) were included in this study. MRN scans of the pelvis were performed before surgery. The contracture band shape and external rotation angle (ERA) of the proximal femur were also analyzed. Then, the minimally invasive GMC releasing surgery was performed based on the images and measurements, and during the operation, incision lengths, surgery duration, intraoperative bleeding, and complications were recorded; the time of the first postoperative off-bed activity was also recorded. Furthermore, the patients’ clinical functions were evaluated by means of Hip Outcome Score (HOS) and Ye et al’s objective assessments, respectively. Results. The contracture bands exhibited three typical types of shape – feather-like, striped, and mixed shapes – in MR images. Guided by MRN images, we designed minimally invasive approaches directed to each hip. These approaches resulted in a shortened incision length in each hip (0.3 cm (SD 0.1)), shorter surgery duration (25.3 minutes (SD 5.8)), less intraoperative bleeding (8.0 ml (SD 3.6)), and shorter time between the end of the operation and the patient’s first off-bed activity (17.2 hours (SD 2.0)) in each patient. Meanwhile, no serious postoperative complications occurred in all patients. The mean HOS-Sports subscale of patients increased from 71.0 (SD 5.3) to 94.83 (SD 4.24) at six months postoperatively (p < 0.001). The follow-up outcomes from all patients were “good” and “excellent”, based on objective assessments. Conclusion. Preoperative MRN analysis can be used to facilitate the determination of the relationship between contracture band and normal tissues. The minimally invasive surgical design via MRN can avoid nerve damage and improve the release effect. Cite this article: Bone Jt Open 2024;5(9):776–784

Pelvic osteotomies for hip dysplasia results can be variable and depend on the amount of preexisting arthritis. Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) is a technique designed to measure early arthritis, and could be used to select hips that would benefit from a joint-preserving reconstructive procedure. Our objective was to investigate the role of preoperative dGEMRIC in predicting the success of PAO in patients 40 and above. We hypothesized that patients who failed had lower preoperative dGEMRIC index compared to those who did not.

Following IRB approval, patients 40 or older who underwent PAO between 1990–2013 and had preoperative dGEMRIC scan and minimum follow-up of 4 years were identified. Patients with prior hip surgeries or any pathologies were removed leading to a total of 70 patients (Age: 44.2 ± 2.9 years old, BMI: 25.7 ± 4.5 Kg/m²). We only included the first hip undergoing PAO for those with bilateral PAO. Out of 70, 19 had failure defined by the need for total hip replacement or WOMAC pain score of 10 and above within 10 years after index PAO surgery. Articular cartilage was segmented on the 3D pre-operative dGEMRIC scan. The average thickness and dGEMRIC index across the whole articular surface were analyzed.

Failed hips had a lower dGEMRIC index by 115 ± 20 ms (P<0.001). All but one failed hips had a dGMERIC index of 400 or less (range: 313 – 479 ms), while all survived hips had a dGMERIC index of greater than 400 (range: 403 – 691 ms). Similar trends were observed when comparing the dGEMRIC index within the 6 subgroups (P<0.01). There were no differences in cartilage thickness (combined femoral head and acetabular cartilage) between the failed and survived hips (p>0.2).

Patients with a high dGMERIC index (indicating high GAG content) may have a higher chance of successful outcomes following PAO. Current efforts are underway to develop a multi-modal predictive model to evaluate risk of failure after PAO.

Dislocation after total hip replacement (THR) is a devastating complication. Risk factors include patient and surgical factors. Mitigation of this complication has proven partially effective. This study investigated a new innovating technique to decrease this problem using rare earth magnets. Computer simulations with design and magnetic finite element analysis software were used to analyze and quantitate the forces around hip implants with embedded magnets into the components during hip range of motion. N52 Neodymium-Iron-Boron rare earth magnets were sized to fit within the existing acetabular shells and the taper of a hip system. Additionally, magnets placed within the existing screw holes were studied. A 50mm titanium acetabular shell and a 36mm ceramic liner utilizing a taper sleeve adapter were modeled which allowed for the use of a 12mm × 5mm magnet placed in the center hole, an 18mm × 15mm magnet within the femoral head, and 10mm × 5mm magnets in the screw holes. Biomechanical testing was also performed using in-vitro bone and implant models to determine retention forces through a range of hip motion. The novel system incorporating magnets generated retentive forces between the acetabular cup and femoral head of between 10 to 20 N through a range of hip motion. Retentive forces were stronger at the extreme position hip range of motion when additional magnets were placed in the acetabular screw holes. Greater retentive forces can be obtained with specially designed femoral head bores and acetabular shells specifically designed to incorporate larger magnets. Mechanical testing validated the loads obtained and demonstrated the feasibility of the magnet system to provide joint stability and prevent dislocations. Rare earth magnets provide exceptional attractive strength and can be used to impart stability and prevent dislocation in THR without the complications and limitations of conventional methods

Background. FORECAST is a prospective longitudinal cohort study exploring mechanism-based prognostic factors for pain persistence in sciatica. Here, we share an update on this largest deeply-phenotyped primary care sciatica cohort. Methods/results. Our cohort includes 180 people with sciatica (score >4 on Stynes’ Sum Score), aged 18–85, within 3 months of symptom onset. Psychosocial factors, self-reported sensory profiling, clinical examination, quantitative sensory testing (QST), biological samples (blood and skin samples), and Magnetic Resonance Neurography of lumbar nerve roots were collected at baseline. Pain persistence was determined at three and twelve months with the Sciatica Bothersomeness Index (SBI) and a numeric pain rating scale (NRS) as primary outcomes. Recruitment nears completion, with 160 participants enrolled to date. 127 and 96 participants have completed 3 and 12 months follow-up respectively. Overall, 56% of our cohort are female, with a mean age (SD) of 54.14yrs (16.57). Ethnicity data approximates local populations. SBI at baseline was (median [IQR]) 13[10-17], and interim longitudinal data shows stepwise improvement at 3 and 12 months. Baseline ‘average’ pain intensity was 5.56 (2.15) for leg pain, and 4.14(2.82) for low back pain (LBP). Overall, pain scores decreased at 3 and 12 months, with greater reductions in leg pain than LBP at 12 months. However, around 55–80% and 40–65% of people reported persistent pain at 3 and 12 months respectively. Conclusion. Leg pain severity was moderate and higher than LBP at baseline. All primary outcome measures demonstrate improvement over time, however 40–65% of patients report persistent pain at 12 months. Conflicts of interest. LR: Paid facilitation of post-graduate courses internationally. SK, MT, FP, KM, WS, CP, CR, SC: No conflicts of interest. GC: Editor in Chief of Health Psychology Review. Director of board of directors, MentalCHealth Care setting NoordWestVlaanderen. JF: Copyright holder of ODI (Oswestry Disability Index). Served on a data monitoring committee for a clinical trial of 2 different surgical approaches to cervical disc herniation (FORVAD). Member of HTA Prioritisation Committee B: Inside hospital Care from 2015-February 2019. Member of HTA Interventional Procedures Panel from 2010–2015. Trustee and board member of 3 spine related charities – Back to Back; British Scoliosis Research Foundation and BackCare. Expert instructed by both claimant and defendant solicitors in negligence and person injury cases. GB: Paid consultancy (RNA-seq) with Ivy Farm and Coding.bio. ABS: Paid post-graduate lecturing internationally. Co-chair NeupSig sciatica working group (unpaid). Sources of funding. This project is funded by UKRI and Versus Arthritis as part of the UKRI Strategic Priorities Fund (SPF) Advanced Pain Discovery Platform (APDP), a co-funded initiative by UKRI (MRC, BBSRC, ESRC), Versus Arthritis, the Medical Research Foundation and Eli Lilly and Company Ltd (Grant MR/W027003/1). Additional funding has been received from the back to back charity to expand longitudinal components of the study. LR has received support with PhD fees from the CSP charitable trust. ABS is supported by a Wellcome Trust Clinical Career Development Fellowship. (222101/Z/20/Z). WS is partly funded through the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and King's College London. FP is funded by a Dorothy Hodgkin Career Development Fellowship in Chemistry in association with Somerville College. GB is supported by the Wellcome Trust (223149/Z/21/Z) and Diabetes UK (19/0005984). GC and KRM are partly funded by UKRI and Versus Arthritis as part of the Advanced Pain Discovery Platform (APDP) PAINSTORM (MR/W002388/1). The UKRI and Versus Arhthritis (APDP) are the major funders of FORECAST. All other funders provided either some people support, or funded projects with legacy data that we reuse

Aims

Adenosine, lidocaine, and Mg²⁺ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery.

Aims

The aim of this study was to compare outcomes after growth-friendly treatment for early-onset scoliosis (EOS) between patients with skeletal dysplasias versus those with other syndromes.

Introduction. Autologous Matrix Induced Chondrogenesis (AMIC) for surgical treatment of osteochondral lesions of the talus (OCLT) has shown excellent clinical and radiological results at short term follow up two years after surgery. However, no mid-term follow up data is available. Aim. 1. To evaluate the clinical outcome after AMIC-aided reconstruction of osteochondral lesions of the talus at a minimum follow up time of five years. 2. To evaluate the morphology and quality of the regenerated cartilage by magnetic resonance imaging (MRI) at on at a minimum follow up time of five years. Methods. Seventeen patients prospectively underwent surgery receiving a AMIC-aided repair of OCLT consisting of debridement, autologous grafting, and sealing of the defect with a collagen scaffold (Chondro-Gide, Geistlich Surgery, Wolhusen, Switzerland). Clinical and radiological assessment was performed before and after a minimum of 60 months after surgery (average 78 months, range, 60–120). Clinical examination included the American Orthopaedic Foot & Ankle Society (AOFAS) ankle score and the Visual Analogue Scale (VAS). Radiological imaging consisted of MRI. The Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score was applied. Results. The AOFAS ankle score improved significantly from a mean of 60 points preoperatively (range, 17–79) to 91 points (range, 70–100) postoperatively (p< 0.01). The preoperative pain score averaged a VAS of 5 (range, 2–8), improving to an average of 1.1 (range 0–8) (p< 0.01). The MOCART score for cartilage repair tissue on postoperative MRI averaged 71 points (range, 50–90). Conclusion. The AMIC-procedure is safe for the treatment of OCLT with overall good clinical and magnetic resonance imaging results at five years follow up

Aims

Periacetabular osteotomy (PAO) is the preferred treatment for symptomatic acetabular dysplasia in adolescents and young adults. There remains a lack of consensus regarding whether intra-articular procedures such as labral repair or improvement of femoral offset should be performed at the time of PAO or addressed subsequent to PAO if symptoms warrant. The purpose was to determine the rate of subsequent hip arthroscopy (HA) in a contemporary cohort of patients, who underwent PAO in isolation without any intra-articular procedures.

Aims. The purpose of this study was to evaluate the mid-term outcomes of autologous matrix-induced chondrogenesis (AMIC) for the treatment of larger cartilage lesions and deformity correction in hips suffering from symptomatic femoroacetabular impingement (FAI). Methods. This single-centre study focused on a cohort of 24 patients with cam- or pincer-type FAI, full-thickness femoral or acetabular chondral lesions, or osteochondral lesions ≥ 2 cm. 2. , who underwent surgical hip dislocation for FAI correction in combination with AMIC between March 2009 and February 2016. Baseline data were retrospectively obtained from patient files. Mid-term outcomes were prospectively collected at a follow-up in 2020: cartilage repair tissue quality was evaluated by MRI using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. Patient-reported outcome measures (PROMs) included the Oxford Hip Score (OHS) and Core Outcome Measure Index (COMI). Clinical examination included range of motion, impingement tests, and pain. Results. A total of 12 hips from 11 patients were included (ten males, one female, mean age 26.8 years (SD 5.0), mean follow-up 6.2 years (SD 5.2 months)). The mean postoperative MOCART score was 66.3 (SD 16.3). None of the patients required conversion to total hip arthroplasty. Two patients had anterior impingement. External hip rotation was moderately limited in four patients. There was a correlation between MOCART and follow-up time (r. s. = -0.61; p = 0.035), but not with initial cartilage damage, age, BMI, or imaging time delay before surgery. PROMs improved significantly: OHS from 37.4 to 42.7 (p = 0.014) and COMI from 4.1 to 1.6 (p = 0.025). There was no correlation between MOCART and PROMs. Conclusion. Based on the reported mid-term results, we consider AMIC as an encouraging treatment option for large cartilage lesions of the hip. Nonetheless, the clinical evidence of AMIC in FAI patients remains to be determined, ideally in the context of randomized controlled trials. Cite this article: Bone Joint J 2024;106-B(5 Supple B):32–39

Introduction. The practice of limb lengthening using intramedullary nails has surged in popularity in recent years. Our study explores the relationship between femur lengthening and overall height gain in adults undergoing cosmetic limb lengthening with telescoping magnetic intramedullary lengthening nails (MILNs). Materials & Methods. Demographic information, pre- and postoperative radiographic data, and secondary outcomes, such as mechanical angles and sagittal alignment, were analyzed for 42 adult femurs MILNs (PRECICE 2, NuVasive, Inc.). Height was assessed with a digital stadiometer. Limb lengthening was defined as the amount of nail distraction seen on a calibrated weight bearing X-ray at consolidation. mLDFA, mMPTA, MAD, AMA, and femoral sagittal bow were evaluated as secondary outcomes. Results. Mean starting height was 163.5 cm (SD 10.4, range 137–179) Post -lengthening mean height increased to 171.1 cm (SD 10.1, range 146.7–185.3). Average height gain was 7.5 cm (SD 1.3 cm, range 5.1–9.5). Average femoral lengthening was 7.3 cm (SD 1.14, range 4.1–10.1). There were no statistically significant difference between height gain and femur lengthening. Secondary outcomes showed reductions in femoral sagittal bow and AMA. Conclusions. We conclude that measuring femur lengthening is a reliable and accurate method of measuring gained height in deformity-free patients undergoing limb lengthening. We further reason that straightening of both femoral and spinal sagittal bow counteracts potential lengthening loss over the anatomical axis, versus mechanical axis lengthening

Introduction. Frame HI is the #Days for device removal/cm. IM Nail HI is less relevant (31–45 D/cm). Albizzia HI was 33 D/cm (1991–2003). Patients felt fine approximately 1M after end of lengthening (EoL), resuming normal life and sports. This sometimes resulted in implants fractures (e.g. skying before bone fusion). Ideally, the full fusion should occur at the EoL. We decided to shorten the HI to reach this target, optimising all parameters. Materials & Methods. The evolution of care has been monitored over a 32-year clinical experience with a fully weight-bearing nails (Albizzia then G-nail). Monitoring was with X-rays, DEXA, blood bone activity, and in London with special 5G CBCT Scans. We implemented several changes in the Care of patients and measured them according to the ‘Five Principles’ (stability, function, ‘Roads-vascular supply’, ‘Materials-calories’ and ‘Workers-BFC’, with actions on food intake, activity levels and on muscle and bone vascular growths. Results. Preop: training (vascularity, muscle force). Op & Postop: spine morphine, IM sawing preserving BFC, controlled hypo-pressure, low hydration, 50 cm leg elevation, walking, resistance bike, full motion (drainage, muscle reactivation), discharge 3–4h postop (including bilateral). Postop daily intense gym training. POD07-21: Distraction increased to fight non-linear hyper-ossification (44–50 mm gain at POD30) +/- aided by NSAIDs. HI decreased to 12–20D/cm, sometimes 8D/cm with some ‘soft fusion’ during lengthening, hardening within 1W after EoL. Conclusions. The surgeon is not a passive X-rays observer, but has an active role in changing the healing speed and decreasing HI for patient safety. Electro/Magnetic nails (torque 1 Nm) may be clocked by bone fusion, which does not occur with the G-Nail (19 Nm). An holistic vision for patients and treatments at several levels is essential to accelerate bone healing, and to return fast to full normal life, after a short ‘lengthening parenthesis’

The April 2024 Spine Roundup. 360. looks at: Lengthening behaviour of magnetically controlled growing rods in early-onset scoliosis: a multicentre study; LDL, cholesterol, and statins usage cause pseudarthrosis following lumbar interbody fusion; Decision-making in the treatment of degenerative lumbar spondylolisthesis of L4/L5; Does the interfacing angle between pedicle screws and support rods affect clinical outcomes after posterior thoracolumbar fusion?; Returning to the grind: how workload influences recovery post-lumbar spine surgery; Securing the spine: a leap forward with s2 alar-iliac screws in adult spinal deformity surgery

The April 2024 Foot & Ankle Roundup³⁶⁰ looks at: Safety of arthroscopy combined with radial extracorporeal shockwave therapy for osteochondritis of the talus; Bipolar allograft transplantation of the ankle; Identifying risk factors for osteonecrosis after talar fracture; Balancing act: immediate versus delayed weightbearing in ankle fracture recovery; Levelling the field: proximal supination osteotomy’s efficacy in severe and super-severe hallux valgus; Restoring balance: how adjusting the tibiotalar joint line influences movement after ankle surgery.

Aims

Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA).

Aims. As an alternative to external fixators, intramedullary lengthening nails (ILNs) can be employed for distraction osteogenesis. While previous studies have demonstrated that typical complications of external devices, such as soft-tissue tethering, and pin site infection can be avoided with ILNs, there is a lack of studies that exclusively investigated tibial distraction osteogenesis with motorized ILNs inserted via an antegrade approach. Methods. A total of 58 patients (median age 17 years (interquartile range (IQR) 15 to 21)) treated by unilateral tibial distraction osteogenesis for a median leg length discrepancy of 41 mm (IQR 34 to 53), and nine patients with disproportionate short stature treated by bilateral simultaneous tibial distraction osteogenesis, with magnetically controlled motorized ILNs inserted via an antegrade approach, were retrospectively analyzed. The median follow-up was 37 months (IQR 30 to 51). Outcome measurements were accuracy, precision, reliability, bone healing, complications, and patient-reported outcome assessed by the Limb Deformity-Scoliosis Research Society Score (LD-SRS-30). Results. A median tibial distraction of 44 mm (IQR 31 to 49) was achieved with a mean distraction index of 0.5 mm/day (standard deviation 0.13) and median consolidation index of 41.2 days/cm (IQR 34 to 51). Accuracy, precision, and reliability were 91%, 92%, and 97%, respectively. New temporary range of motion limitations occurred in 51% of segments (34/67). Distraction-related equinus deformity treated by Achilles tendon lengthening was the most common major complication recorded in 16% of segments (11/67). In 95% of patients (55/58) the distraction goal was achieved with 42% unplanned additional interventions per segment (28/67). The median postoperative LD-SRS-30 score was 4.0 (IQR 3.6 to 4.3). Conclusion. Tibial distraction osteogenesis using motorized ILNs inserted via an antegrade approach appears to be a reliable and precise procedure. Temporary joint stiffness of the knee or ankle should be expected in up to every second patient. A high rate and wide range of complications of variable severity should be anticipated. Cite this article: Bone Joint J 2024;106-B(3):293–302