Heterotopic Ossification Formation Research Articles

Platelet-rich plasma does not influence magnetic resonance imaging findings of the gluteus muscles after total hip arthroplasty through the Hardinge approach.

Total hip arthroplasty through the Hardinge approach damages the hip abductor muscles. MRI can be used to assess adverse postoperative events. In this prospective randomized controlled trial, we evaluated MRI findings and whether platelet-rich plasma affected postoperative healing of the gluteal muscles (gluteus medius and minimus). Forty patients with hip osteoarthritis requiring treatment with total hip arthroplasty, aged between 60 and 76 years, were included. Patients were randomized into two groups: 19 patients in the platelet-rich plasma group and 21 in the placebo group. Platelet-rich plasma or placebo was injected into the gluteus medius tendon incision line during closure. Postoperative hip MRI and plain radiographs were taken 3 and 12 months after surgery. MRI showed fatty atrophy of the gluteal muscles in all 40 patients (100%), gluteal muscle tear in 11 patients (28%), and atrophy in 16 patients (40%) at both 3 and 12 months postoperatively. Fluid collections related to the operated hip joint were seen in 18 patients (45%) at 3 months and 13 patients (33%) at 12 months, heterotopic ossification formation in nine patients (23%) at 3 months, and 12 patients (31%) at 12 months. There were no significant differences in imaging findings between the two groups. MRI can be a valuable tool for evaluating postoperative healing after total hip arthroplasty. Fatty atrophy of the gluteal muscles was a common finding. Platelet-rich plasma injection into the gluteus medius tendon did not improve healing detected by MRI.

Tranexamic Acid and Heterotopic Ossification Formation Following Elbow Surgery: A Prospective Randomized Controlled Trial.

This study investigates whether the intra-operative administration of intravenous tranexamic acid (TXA), known for its hemostatic and potential anti-inflammatory properties, affects the incidence of heterotopic ossification (HO) following surgery for elbow fracture-dislocations. Design: Prospective, randomized clinical trial. Hand and Upper Extremity Surgery Unit. Patients aged 18 to 75 years with acute traumatic elbow fracture-dislocations requiring surgical management from June 1, 2016, to October 31, 2022, were eligible. Inclusion criteria included traumatic non-pathological elbow fracture-dislocations. Patients were randomized 1:1 to receive either intraoperative TXA or no additional treatment. The primary outcome was the occurrence of heterotopic ossification (HO), defined by new bone formation observed in radiographic exams during postoperative follow-ups. Secondary outcomes included the presence of clinically relevant HO, reoperation rate due to symptomatic HO, and time to HO reoperation. Compared were patients who received TXA with controls.

Regulation of macrophage-mediated osteogenesis by kaempferol liposomes in trauma-induced heterotopic ossification.

Heterotopic ossification (HO) is characterized by abnormal bone formation outside the skeleton following injury or inherited disease, leading to limb dysfunction and neurological deficits. Current treatment options for HO are largely ineffective. A network pharmacological analysis was conducted to identify the active ingredients and protein targets in Astragalus and Cinnamon Twig Five-Substance Decoction (ACTFSD) on HO. Protein-protein interaction analysis and Gene Ontology Enrichment Analysis were used to investigate the key genes associated with the target proteins. Molecular docking was employed to validate the interactions between the core components and targets of ACTFSD. Kaempferol was encapsulated in liposomes synthesized via the thin-film dispersion method. In vitro and in vivo experiments were conducted to evaluate the therapeutic effects of kaempferol liposomes. Kaempferol, an active ingredient in ACTFSD, effectively inhibits the PTGS2\ NF-κB pathway, regulates macrophage immune responses, and reduces cytokine released by macrophages induce abnormal osteogenesis in tendon stem cells (TDSCs), thereby slowing the formation of HO. Kaempferol liposomes demonstrate better therapeutic effect than kaempferol alone. This study indicates that targeting macrophages may represent an effective therapeutic strategy for HO. Furthermore, kaempferol liposomes appear to be a promising treatment for trauma-induced HO. These findings provide potential new directions for future HO treatment strategies.

Heterotopic Ossification After Shoulder Arthroplasty: A Systematic Review.

Shoulder arthroplasty is increasing in incidence over time. One potential complication that is not well studied following shoulder arthroplasty is heterotopic ossification (HO), the abnormal growth of extraskeletal bone in soft tissue. HO has been described as a complication in total hip arthroplasty literature but less described in the setting of shoulder arthroplasty. The aim of this systematic review is to present available evidence regarding the incidence, risk factors, and potential management of HO after shoulder arthroplasty. A systematic search was conducted in June 2023 using Pubmed, Embase, and Ovid Medline databases to retrieve all relevant studies evaluating the occurrence of HO after shoulder arthroplasty. The search was done in duplicate, and a quality assessment of all studies was included. A total of 170 studies were retrieved, of which 6 were included, involving 1,028 patients undergoing shoulder arthroplasty with 1,038 operated shoulders. HO developed postoperatively in 28% of the included shoulders and was symptomatic in 12% with most cases occurring in shoulders that developed osteoarthritis and cuff tear arthropathy. Men appear to have an increased risk of developing HO post shoulder arthroplasty. Fewer than 2% of HO shoulders went on to have revision surgery, and no notable differences were observed in the postoperative mean elevation and external rotation angles of non-HO and HO shoulders. In addition, no reported benefit of the use of nonsteroidal anti-inflammatory drugs was found against the formation of HO after shoulder arthroplasty. HO occurs in 28% of shoulder arthroplasties in our review. Most of these were asymptomatic in the reviewed articles. Male patients and revision surgery with osteoarthritis and cuff tear arthroplasty seem to be at higher risk of developing HO post shoulder arthroplasty. Nonsteroidal anti-inflammatory drugs seem to not prevent the development of HO after shoulder arthroplasty; yet, future studies are needed to verify this claim. Level III; Systematic Review.

The Unrecognized Orthopedic Burden of COVID-19: Heterotopic Ossification of the Hip Joint.

COVID-19 has extensively affected the health-care organization with varying impact on different medical specialties. Long term ICU admission is associated with a less familiar complication: the formation of heterotopic ossifications (HO). In this case report we would like to emphasize the unrecognized burden of the coronavirus pandemic in patient care from the perspective of the orthopedic surgeon. We describe two patients with major HOs around their hip joints after COVID-19. Current literature underlines the increased prevalence of HO formation in COVID-19 patients requiring long-lasting mechanical ventilation and ICU admission including prone positioning. Preventing HO formation remains a difficult undertaking without obvious evidence supporting a golden standard treatment. We advice early passive mobilization during ICU stay, also during prone positioning, serum ALP follow-up during admission, NSAID administration if possible and a low threshold in the use of radiotherapy of joints with a limited range of motion.

Using an Intraoperative Stress Examination to Direct Treatment in Posterior Femoral Head Fracture-Dislocations.

To examine the results of a treatment algorithm incorporating an examination under anesthesia (EUA) performed intraoperatively after fixation of the femoral head through a Smith-Petersen approach to determine the need for posterior wall or capsule repair. Retrospective review. Two Level 1 trauma centers. All acute, traumatic femoral head fractures from posterior hip dislocations treated at participating centers over a 5-year period from 2017 to 2022. Injuries were classified according to the Pipkin system. The primary outcome was the result of intraoperative EUA performed after femoral head fixation to determine the need for Kocher-Langenbeck exposure for posterior wall and/or capsule fixation. The secondary outcomes included rates of avascular necrosis, heterotopic bone formation, late instability, and conversion to total hip arthroplasty (THA). In total, 63 men and 22 women with a mean age of 32.5 (range 18-71) years were studied. Seventy-nine of 85 (92.9%) patients had a stable EUA after fixation of the femoral head through a Smith-Petersen approach. Six (6/85, 7.1%) underwent an additional Kocher-Langenbeck approach for posterior wall or capsule fixation. This included 1 Pipkin I, 1 Pipkin II, and 4 Pipkin IV injuries. Of the Pipkin IV injuries, 51/55 (92.7%) had stable EUA and did not require fixation of their posterior wall. This included seven patients with wall involvement >20%. Five patients were excluded because of planned fixation of their posterior wall based on preoperative imaging. Of patients with at least 6 months follow-up, 16 of 65 (26.4%) developed radiographic evidence of avascular necrosis and 21 of 65 (32.3%) evidence of heterotopic bone formation. Seven out of 65 (10.8%) were converted to THA over the study period. When comparing patients with a single exposure and those with additional KL exposure, it was found that they did not vary in their rate of avascular necrosis (27.1% vs. 0.0%, P = 0.3228), heterotopic ossification formation (30.5% vs. 50.0%, P = 0.3788), or conversion to THA (10.2% vs. 16.7%, P = 0.510). This study found residual posterior hip instability after femoral head fixation in patients with and without posterior wall fractures after posterior dislocations. The results of this study support the use of an EUA after femoral head fixation to identify residual posterior hip instability in all femoral head fractures from posterior hip dislocations, regardless of Pipkin type. Use of the Smith-Petersen exposure remains a viable surgical option and may be improved with the incorporation of an EUA after femoral head fixation. For Pipkin IV injuries with posterior wall fractures with indeterminate stability, an EUA accurately identifies residual instability. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Palovarotene (Sohonos), a synthetic retinoid for reducing new heterotopic ossification in fibrodysplasia ossificans progressiva: history, present, and future.

Retinoids are metabolic derivatives of vitamin A and play crucial roles in the regulation of various tissues and organs during prenatal and postnatal development. Active retinoids, like all-trans-retinoic acid, are synthesized in the cytoplasm and subsequently interact with nuclear retinoic acid receptors (RARα, RARβ, and RARγ) to enhance transcription of specific genes. In the absence of retinoids, RARs can still bind to response elements of target genes but repress their transcription. Chondrogenic cell differentiation and cartilage maturation in the growth plate require the absence of retinoid signaling and transcriptional repression by unliganded RARs. This led to the hypothesis that synthetic retinoid agonists may be pharmacological agents to inhibit those cellular processes and counter the excessive formation of cartilage and bone in conditions like heterotopic ossification (HO). HO can be instigated by diverse culprits including trauma, invasive surgeries, inflammatory disorders, or genetic conditions. One such genetic disease is fibrodysplasia ossificans progressiva (FOP), a rare disorder driven by activating mutations in the ACVR1 gene. Patients with FOP have severe and progressive HO formation in soft tissues, leading to extensive permanent loss of mobility and increased mortality. Synthetic retinoid agonists selective for RARα or RARγ showed efficacy against injury-induced and genetic HO in mouse models. The RARγ agonists showed the highest effectiveness, with palovarotene being selected for clinical trials in patients with FOP. Post hoc analyses of phase II and phase III clinical trials showed that palovarotene has significant disease-modifying effects for FOP, but with significant risks such as premature growth plate closure in some younger subjects. This review provides an overview of retinoid and RAR roles in skeletal development and discusses the identification of palovarotene as a potential FOP therapy, the clinical data supporting its regulatory approval in some countries, and the potential applications of this drug for other relevant disorders besides FOP.

Prophylactic Irradiation for the Prevention of Heterotopic Ossification After Foot Amputation: A Case Series.

The formation of heterotopic ossification (HO) is a common complication after transosseous partial foot amputation. Development of HO in weightbearing and/or superficial areas can lead to increased pressures, which increases the likelihood of wound formation and pain. Current treatment modalities for HO of the foot include mechanical off-loading and surgical resection; however, prophylactic measures such as nonsteroidal anti-inflammatory drugs, bisphosphonates, and other medical therapies have been attempted previously with mixed efficacy. Radiation therapy is another prophylactic method that may be used for the prevention of HO in patients after transosseous partial foot amputation. The present case series evaluated ten patients who underwent transosseous partial foot amputation for HO resection immediately followed by single low-dose radiation treatment. All of the patients received radiation between 700 and 800 cGy, with 6 MV photons directed at the area of concern within 48 hours of surgery. Postoperatively, 10% of patients had HO recurrence, 80% remained fully weightbearing, 90% went on to primarily heal their surgical incisions, and 80% had postoperative pain relief; however, 30% went on to below-the-knee amputation due to chronic pain and/or infectious or nonfunctional pathology. Radiation therapy is a relatively available and safe modality for the prevention of HO that may be used prophylactically in cases of high suspicion of or known HO formation of the foot.

18F]NaF PET/CT as a Marker for Fibrodysplasia Ossificans Progressiva: From Molecular Mechanisms to Clinical Applications in Bone Disorders.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic bone disorder characterized by episodic flare-ups in connective tissue, which are frequently followed by the formation of heterotopic ossification. The absence of available plasma-soluble biomarkers for flare-ups or heterotopic bone formation poses severe challenges to the monitoring of disease activity to measure or predict disease progression. Recently, 18-fluor-sodium fluoride positron emission tomography/computed tomography ([18F]NaF PET/CT) was introduced as a potential marker for ossifying FOP activity. This review discusses the pharmacokinetics of [18F]NaF in relation to the pathophysiology of FOP, and its use as a marker of local bone metabolism in a variety of bone-related disorders. In addition, the review specifically addresses the applicability of [18F]NaF PET/CT imaging in FOP as a monitoring modality.

Role of hedgehog signaling in the pathogenesis and therapy of heterotopic ossification.

Heterotopic ossification (HO) is a pathological process that generates ectopic bone in soft tissues. Hedgehog signaling (Hh signaling) is a signaling pathway that plays an important role in embryonic development and involves three ligands: sonic hedgehog (Shh), Indian hedgehog (Ihh) and desert hedgehog (Dhh). Hh signaling also has an important role in skeletal development. This paper discusses the effects of Hh signaling on the process of HO formation and describes several signaling molecules that are involved in Hh-mediated processes: parathyroid Hormone-Related Protein (PTHrP) and Fkbp10 mediate the expression of Hh during chondrogenesic differentiation. Extracellular signal-regulated kinase (ERK), GNAs and Yes-Associated Protein (YAP) interact with Hh signaling to play a role in osteogenic differentiation. Runt-Related Transcription Factor 2 (Runx2), Mohawk gene (Mkx) and bone morphogenetic protein (BMP) mediate Hh signaling during both chondrogenic and osteogenic differentiation. This paper also discusses possible therapeutic options for HO, lists several Hh inhibitors and explores whether they could serve as emerging targets for the treatment of HO.

Heterotopic ossification following total hip arthroplasty. Which is the predominant risk factor: surgical approach or post-operative prophylaxis?

To investigate the impact of surgical approach and post-operative prophylaxis on heterotopic ossification (HO) development after total hip arthroplasty (THA). A retrospective analysis of 312 patients who underwent THA between January 2009 and April 2016. Patients were categorized by surgical approach (direct lateral or posterolateral), prosthesis type, and post-operative prophylaxis (Etoricoxib 60mg daily for two weeks). Two orthopaedic surgeons independently assessed radiographs at serial intervals, and HO was graded as per Brooker classification. Bivariate analysis and regression modelling were performed to assess the associations and confounding effects of different variables, RESULTS: Bivariate analysis identified factors correlated with higher HO incidence: absence of prophylaxis, older age, longer symptom evolution, and lower pre-surgery physical activity. Regression modelling showed a correlation between the direct-lateral approach, post-operative prophylaxis, symptom evolution, and higher HO incidence. Patients with longer symptom evolution before surgery and without post-operative prophylaxis are at higher risk of developing HO. While the direct lateral approach showed higher HO rates, the difference was insignificant. A two-week prophylactic regimen of Etoricoxib 60mg daily after THA effectively reduced HO formation. Pharmacological prophylaxis should be evaluated case-by-case, considering patient characteristics and risk factors.

Involvement of the Wnt/β-catenin signalling pathway in heterotopic ossification and ossification-related diseases.

Heterotopic ossification (HO) is a pathological condition characterized by the formation of bone within soft tissues. The development of HO is a result of abnormal activation of the bone formation programs, where multiple signalling pathways, including Wnt/β-catenin, BMP and hedgehog signalling, are involved. The Wnt/β-catenin signalling pathway, a conserved pathway essential for various fundamental activities, has been found to play a significant role in pathological bone formation processes. It regulates angiogenesis, chondrocyte hypertrophy and osteoblast differentiation during the development of HO. More importantly, the crosstalk between Wnt signalling and other factors including BMP, Hedgehog signalling, YAP may contribute in a HO-favourable manner. Moreover, several miRNAs may also be involved in HO formation via the regulation of Wnt signalling. This review aims to summarize the role of Wnt/β-catenin signalling in the pathogenesis of HO, its interactions with related molecules, and potential preventive and therapeutic measures targeting Wnt/β-catenin signalling.

The Use of Tranexamic Acid for Primary Prophylaxis of Heterotopic Ossification Following Total Hip Arthroplasty

BackgroundHeterotopic ossification (HO) is a relatively common complication after total hip arthroplasty (THA) and can range from a radiographic observation only to severely disabling and requiring revision surgery. Prophylaxis is recommended for high-risk patients, though the ideal method and targeted population are open to debate. Tranexamic acid (TXA) is a medication increasingly being used to reduce blood loss associated with orthopaedic surgeries, including THA. MethodsA retrospective review of 357 patients undergoing THA from November 2020 through December 2023 was conducted. The patients were grouped based on whether they received intravenous TXA perioperatively or not, and their propensity score matched 2:1 TXA to no TXA on age, body mass index, sex, Charlson Comorbidity Index, and perioperative celecoxib use. Univariate and multivariate analyses were performed. ResultsAfter propensity score matching, the only significant differences between groups were American Society of Anesthesiologists (ASA) scores and preoperative celecoxib use between groups, as the TXA group had fewer patients who had an ASA of 3 or more (38.9 versus 58.5%, P < 0.001) and more patients who had taken celecoxib preoperatively (16.3 versus 5.9%, P = 0.010). Perioperatively, patients were more likely to undergo THA using the anterior approach (74.5 versus 57.6%, P = 0.002) and were more likely to receive postoperative celecoxib prescriptions (44.8 versus 31.4%, P = 0.021), but there was no difference in other nonsteroidal anti-inflammatory drug (NSAID) usage postoperatively. Postoperatively, patients who received TXA had a lower rate of HO on the last postoperative x-ray (20.1 versus 33.9%, P = 0.007). Multivariable logistic regression, to assess predictors of HO, found that patients who had TXA were 42% less likely to have visible HO (OR [odds ratio] = 0.58, P = 0.047), while holding surgical approach, American Society of Anesthesiologists score, preoperative and postoperative celecoxib use, and postoperative other nonsteroidal anti-inflammatory drug use constant. ConclusionsThe use of TXA in patients undergoing primary THA results in a decreased likelihood ofHO formation on postoperative x-rays.

Staged Management for Distal Femur Fractures: Impacts on Reoperation, Stiffness, and Overall Outcomes.

To evaluate the outcomes of staged management with external fixation (ex-fix) prior to definitive fixation of distal femur fractures. Design: Retrospective cohort. Single Level I Trauma Center. Adults treated operatively between 2004 and 2019 for distal femur fractures (OTA/AO 33A/33C) were identified using Current Procedural Terminology codes. Excluded cases were those with screw only fixation, acute distal femur replacement, 33B fracture pattern, no radiographs available, or did not have 6-months of follow-up. Postoperative complication rates including surgical site infection [SSI], reoperation to promote bone healing, final knee arc of motion <90 degrees, heterotopic ossification formation, and reoperation for stiffness were compared between patients treated with ex-fix prior to definitive fixation and those not requiring ex-fix. A total of 407 patients were included with a mean follow-up of 27 months (median [IQR] of 12 [7,33] months), (range 6-192 months). Most patients were male (52%) with an average age of 48 [Range: 18-92] years. Ex-fix was utilized in 150 (37%) cases and 257 (63%) cases underwent primary definitive fixation. There was no difference in SSI rates (p=0.12), final knee arc of motion <90 degrees (p=0.51), and reoperation for stiffness (p=0.41) between the ex-fix and no ex-fix groups. The 150 patients requiring ex-fix spent an average of 4.2 days (SD 3.3) in the ex-fix before definitive fixation. These patients were further analyzed by comparing the duration of time spent in ex-fix, <4 days (n=82) and ≥4 days (n=68). Despite longer time spent in ex-fix prior to definitive fixation, there was again no significant difference in any of the complication and reoperation rates when comparing the two groups, including final knee arc of motion <90 degrees (p=0.63), reoperation for stiffness (p=1.00), and SSI (p=0.79). Ex-fix of distal femur fractures as a means of temporary stabilization prior to definitive ORIF does not increase the risk of complications such as SSI, final knee arc of motion <90 degrees, or reoperations for bone healing or stiffness when compared to single stage ORIF of distal femur fractures. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

THE FIRST 200 CERAMIC-ON-CERAMIC HIP RESURFACING IMPLANTS AT MINIMUM TWO-YEAR FOLLOW-UP

Hip resurfacing arthroplasty (HRA) is a bone conserving alternative to total hip arthroplasty. We present the early 2-year clinical and radiographic follow-up of a novel ceramic-on-ceramic (CoC) HRA in an international multi-centric cohort.Patients undergoing HRA between September 2018 and January 2021 were prospectively included. Patient-reported outcome measures (PROMS) in the form of the Forgotten Joint Score (FJS), HOOS Jr, WOMAC, Oxford Hip Score (OHS) and UCLA Activity Score were collected preoperatively and at 1- and 2-years post-operation. Serial radiographs were assessed for migration, component alignment, evidence of osteolysis/loosening and heterotopic ossification formation.200 patients were identified to have reached 2-year follow-up. Of these, 185 completed PROMS follow-up at 2 years. There was significant improvement in HOOS (p&lt; 0.001) and OHS (p&lt; 0.001) and FJS (p&lt; 0.001) between the pre-operative and 2-year outcomes. Patients reported improved pain (p&lt;0.001), function (p&lt;0.001) and reduced stiffness (p&lt;0.001) as measured by the WOMAC score. Patients had improved activity scores on the UCLA Active Score (P&lt;0.001) with 53% reporting return to impact activity at 2 years. There was no osteolysis and the mean acetabular cup inclination angle was 41deg and the femoral component shaft angle was 137deg. No fractures were reported over but there was one sciatic nerve palsy with partial recovery. Two patients were revised; one at 3 months for pain due to a misdiagnosed back problem and another at 33 months for loosening of the acetabular component with delamination of the titanium ingrowth surface.CoC resurfacing at 2-years post-operation demonstrate promising results with satisfactory PROMS.

Estrogen Deficiency Exacerbates Traumatic Heterotopic Ossification in Mice.

Traumatic heterotopic ossification (HO) is a devastating sequela of orthopedic surgeries and traumatic injuries; however, few studies have explored the effects of the estrogen-deficient state on HO formation. In the present study, we investigated the impact of estrogen deficiency on ectopic cartilage and bone formation in tendon after Achilles tenotomy in an ovariectomized mouse model. A total of 45 female C57BL/6 mice were randomly divided into three groups: sham-operated (control), estrogen depletion by ovariectomy (OVX) and OVX with 17β-estradiol supplementation (OVX + E2), with 15 animals in each group. Three weeks after OVX, all mice were subjected to an Achilles tenotomy using a posterior midpoint approach to induce HO. At 1, 3 and 9 weeks after tenotomy, the left hind limbs were harvested for histology, immunohistochemistry and immunofluorescence evaluations. The volume of ectopic bone was assessed by micro-CT. Mice in the OVX group formed more ectopic cartilage 3 weeks after tenotomy, as well as ectopic bone 9 weeks after tenotomy, compared to the control group. Estrogen deficiency resulted in more severe inflammatory infiltration at the injury sites 1 week after tenotomy, involving the recruitment of more macrophages and mast cells, as well as increasing the expressions of pro-inflammatory mediators, including IL-1β, IL-6, and TNF-α. Moreover, the local TGF-β/SMAD signaling pathway was dysregulated after OVX, which manifested as upregulated expressions of TGF-β and pSMAD2/3. E2 supplementation protected against OVX-induced HO deterioration, inhibited inflammatory infiltration, and downregulated the TGF-β/SMAD signaling pathway. Estrogen deficiency exacerbated HO formation in the Achilles tenotomy model. These findings might be attributable to the disturbance of the inflammatory response and the activation of TGF-β/SMAD signaling at the injury sites during the early stages of HO development.

Matrine reduces traumatic heterotopic ossification in mice by inhibiting M2 macrophage polarization through the MAPK pathway

In this study, the role of matrine, a component derived from traditional Chinese medicine, in modulating macrophage polarization and its effects on traumatic heterotopic ossification (HO) in mice was investigated. Traumatic HO is a pathological condition characterized by abnormal bone formation in nonskeletal tissues, often following severe trauma or surgery. The mechanisms underlying HO involve an enhanced inflammatory response and abnormal bone formation, with macrophages playing a crucial role. Our study demonstrated that matrine effectively inhibits the polarization of bone marrow-derived macrophages (BMDMs) toward the M2 phenotype, a subtype associated with anti-inflammatory processes and implicated in the progression of HO. Using in vitro assays, we showed that matrine suppresses key M2 markers and inhibits the MAPK signaling pathway in BMDMs. Furthermore, in vivo experiments revealed that matrine treatment significantly reduced HO formation in the Achilles tendons of mice and downregulated the expression of markers associated with M2 macrophages and the MAPK pathway. Our findings suggest that the ability of matrine to modulate macrophage polarization and inhibit the MAPK pathway has therapeutic potential for treating traumatic HO, providing a novel approach to managing this complex condition.

Disturbed glycolipid metabolism activates CXCL13-CXCR5 axis in senescent TSCs to promote heterotopic ossification

Heterotopic ossification (HO) occurs as a common complication after injury, while its risk factor and mechanism remain unclear, which restricts the development of pharmacological treatment. Clinical research suggests that diabetes mellitus (DM) patients are prone to developing HO in the tendon, but solid evidence and mechanical research are still needed. Here, we combined the clinical samples and the DM mice model to identify that disordered glycolipid metabolism aggravates the senescence of tendon-derived stem cells (TSCs) and promotes osteogenic differentiation. Then, combining the RNA-seq results of the aging tendon, we detected the abnormally activated autocrine CXCL13-CXCR5 axis in TSCs cultured in a high fat, high glucose (HFHG) environment and also in the aged tendon. Genetic inhibition of CXCL13 successfully alleviated HO formation in DM mice, providing a potential therapeutic target for suppressing HO formation in DM patients after trauma or surgery.

Revisiting the taxonomy of abnormal calcium deposits in burn survivors: Semantics of heterotopic ossification versus calcinosis cutis

Abnormal calcium deposition is among the many sequelae that may arise following major burn injury. This may take the form of heterotopic ossification (HO) or calcinosis cutis (CC) within scarred skin. These two processes are distinct, but clinicians sometimes use the term “heterotopic ossification” as a catch-all term to reference any abnormal calcium deposition in a burn survivor. While HO is well-described, less attention has been devoted to CC. We present a case of CC to highlight the distinct presentations of CC vs. HO in hopes of promoting the use of semantically correct terms within the burn care community.

Elucidating the Mechanism of Radiation Therapy on Mesenchymal Cell Fate in Preventing Heterotopic Ossification.

Radiation therapy is a clinically proven, localized preventive measure for heterotopic ossification (HO). Despite its efficacy, there is a lack of standardization of radiation prescription dosing and fractionation, and the mechanism of the impact of radiation in HO prevention remains unknown. Here, using an established mouse model of traumatic HO induced by burn and tenotomy, we demonstrate that 7Gy in one fraction delivered to the injury site within 72 hours postoperatively significantly decreases HO formation and improves hindlimb range of motion. In-depth single-cell transcriptomic analyses, in combination with immunofluorescent staining, demonstrate decreased cellular numbers as well as aberrant endochondral differentiation and downregulation of associated upstream signaling pathways in irradiated mesenchymal progenitor cells. Our study provides the framework for future mechanistic and clinically relevant studies exploring radiation efficacy in preventing HO formation.