Interorgan communication in neurogenic heterotopic ossification: the role of brain-derived extracellular vesicles

Brain-derived extracellular vesicles participate in interorgan communication after traumatic brain injury by transporting pathogens to initiate secondary injury.Inflammasome-related proteins encapsulated in brain-derived extracellular vesicles can cross the blood‒brain barrier to reach distal tissues.These proteins initiate inflammatory dysfunction,such as neurogenic heterotopic ossification.This recurrent condition is highly debilitating to patients because of its relatively unknown pathogenesis and the lack of effective prophylactic intervention strategies.Accordingly,a rat model of neurogenic heterotopic ossification induced by combined traumatic brain injury and achillotenotomy was developed to address these two issues.Histological examination of the injured tendon revealed the coexistence of ectopic calcification and fibroblast pyroptosis.The relationships among brain-derived extracellular vesicles,fibroblast pyroptosis and ectopic calcification were further investigated in vitro and in vivo.Intravenous injection of the pyroptosis inhibitor Ac-YVAD-cmk reversed the development of neurogenic heterotopic ossification in vivo.The present work highlights the role of brain-derived extracellular vesicles in the pathogenesis of neurogenic heterotopic ossification and offers a potential strategy for preventing neurogenic heterotopic ossification after traumatic brain injury.

Endochondral ossification of hindlimbs in embryonic development of Japanese Quail(Coturnix japonica)

The endochondral ossification of hindlimb is essential to a bird’s ability to stand,walk and fly.Most hindlimb is ossified in the embryos before hatching in precocial birds.However,the molecular mechanisms of hindlimb ossification in birds is still unclear.Therefore,we tried to examine the process of hindlimb ossification and its molecular regulation by using an animal model—Japanese Quail(Coturnix japonica).We selected four critical stages(Embryo Day:E6,E8,E12 and E16) of skeletal development of embryonic quails for hindlimb skeleton staining to show the process of endochondral ossification and to examine the molecular regulation of endochondral osteogenesis by RNA-Seq analysis.The results showed that ossification became increased with embryonic development and most hindlimb was ossified before hatching.RNA-Seq analysis revealed that various signaling pathways were involved with endochondral ossification with thyroid hormone signaling and WNT signaling pathway particularly enriched.Moreover,the expression levels of 42 genes were continuously upregulated and 14 genes were continuously downregulated from E6 to E16.The present study might provide new insights into complex molecular mechanisms in regulation of endochondral ossification.

Piezo1 expression in chondrocytes controls endochondral ossification and osteoarthritis development

Piezo proteins are mechanically activated ion channels,which are required for mechanosensing functions in a variety of cell types.While we and others have previously demonstrated that the expression of Piezo1 in osteoblast lineage cells is essential for boneanabolic processes,there was only suggestive evidence indicating a role of Piezo1 and/or Piezo2 in cartilage.Here we addressed the question if and how chondrocyte expression of the mechanosensitive proteins Piezo1 or Piezo2 controls physiological endochondral ossification and pathological osteoarthritis(OA)development.Mice with chondrocyte-specific inactivation of Piezo1(Piezo1^(Col2a1Cre)),but not of Piezo2,developed a near absence of trabecular bone below the chondrogenic growth plate postnatally.Moreover,all Piezo1^(Col2a1Cre) animals displayed multiple fractures of rib bones at 7 days of age,which were located close to the growth plates.While skeletal growth was only mildly affected in these mice,OA pathologies were markedly less pronounced compared to littermate controls at 60 weeks of age.Likewise,when OA was induced by anterior cruciate ligament transection,only the chondrocyte inactivation of Piezo1,not of Piezo2,resulted in attenuated articular cartilage degeneration.Importantly,osteophyte formation and maturation were also reduced in Piezo1^(Col2a1Cre) mice.We further observed increased Piezo1 protein abundance in cartilaginous zones of human osteophytes.Finally,we identified Ptgs2 and Ccn2 as potentially relevant Piezo1 downstream genes in chondrocytes.Collectively,our data do not only demonstrate that Piezo1 is a critical regulator of physiological and pathological endochondral ossification processes,but also suggest that Piezo1 antagonists may be established as a novel approach to limit osteophyte formation in OA.

High formability Mg-Zn-Gd wire facilitates ACL reconstruction via its swift degradation to accelerate intra-tunnel endochondral ossification

After reconstructing the anterior cruciate ligament(ACL),unsatisfactory bone tendon interface healing may often induce tunnel enlargement at the early healing stage.With good biological features and high formability,Magnesium-Zinc-Gadolinium(ZG21)wires are developed to bunch the tendon graft for matching the bone tunnel during transplantation.Microstructure,tensile strength,degradation,and cytotoxicity of ZG21 wire are evaluated.The rabbit model is used for assessing the biological effects of ZG21 wire by Micro-CT,histology,and mechanical test.The SEM/EDS,immunochemistry,and in vitro assessments are performed to investigate the underlying mechanism.Material tests demonstrate the high formability of ZG21 wire as surgical suture.Micro-CT shows ZG21 wire degradation accelerates tunnel bone formation,and histologically with earlier and more fibrocartilage regeneration at the healing interface.The mechanical test shows higher ultimate load in the ZG21 group.The SEM/EDS presents ZG21 wire degradation triggered calcium phosphate(Ca-P)deposition.IHC results demonstrate upregulation of Wnt3a,BMP2,and VEGF at the early phase and TGFβ3 and Type II collagen at the late phase of healing.In vitro tests also confirmed the Ca-P in the metal extract could elevate the expression of Wnt3a,βcatenin,ocn and opn to stimulate osteogenesis.Ex vivo tests of clinical samples indicated suturing with ZG21 wire did not weaken the ultimate loading of human tendon tissue.In conclusion,the ZG21 wire is feasible for tendon graft bunching.Its degradation products accelerated intra-tunnel endochondral ossification at the early healing stage and therefore enhanced bone-tendon interface healing in ACL reconstruction.

DAPK2 promotes autophagy to accelerate the progression of ossification of the posterior longitudinal ligament through the mTORC1 complex

Background:Ossification of the posterior longitudinal ligament(OPLL)is a prevalent condition in orthopedics.While death-associated protein kinase 2(DAPK2)is known to play roles in cellular apoptosis and autophagy,its specific contributions to the advancement of OPLL are not well understood.Methods:Ligament fibroblasts were harvested from patients diagnosed with OPLL.Techniques such as real-time reverse transcriptasepolymerase chain reaction(RT-qPCR)and Western blot analysis were employed to assess DAPK2 levels in both ligament tissues and cultured fibroblasts.The extent of osteogenic differentiation in these cells was evaluated using an alizarin red S(ARS)staining.Additionally,the expression of ossification markers and autophagy markers was quantified.The autophagic activity was further analyzed through LC3 immunofluorescence and transmission electron microscopy(TEM).An in vivo heterotopic bone formation assay was conducted in mice to assess the role of DAPK2 in ossification.Results:Elevated DAPK2 expression was confirmed in both OPLL patient tissues and derived fibroblasts,in contrast to non-OPLL controls.Silencing of DAPK2 significantly curtailed osteogenic differentiation and autophagy in these fibroblasts,evidenced by decreased levels of LC3,and Beclin1,and reduced autophagosome formation.Additionally,DAPK2 was found to inhibit the mechanistic target of the rapamycin complex 1(mTORC1)complex’s activity.In vivo studies demonstrated that DAPK2 facilitates ossification,and this effect could be counteracted by the mTORC1 inhibitor rapamycin.Conclusion:DAPK2 enhances autophagy and osteogenic processes in OPLL through modulation of the mTORC1 pathway.

Heterotopic mesenteric ossification caused by trauma:A case report

BACKGROUND Heterotopic mesenteric ossification(HMO)is a clinically rare condition characterized by the formation of bone tissue in the mesentery.The worldwide reporting of such cases is limited to just over 70 instances in the medical literature.The etiology of HMO remains unclear,but the disease is possibly induced by mechanical trauma,ischemia,or intra-left lower quadrant abdominal infection,leading to the differentiation of mesenchymal stem cells into osteoblasts.Here,we present a rare case of HMO that occurred in a 34-year-old male,who presented with left lower quadrant abdominal pain.CASE SUMMARY We report the case of a 34-year-old male patient who presented with left lower abdominal pain following trauma to the left lower abdomen.He subsequently underwent surgical treatment,and the postoperative pathological diagnosis was HMO.CONCLUSION We believe that although there is limited literature and research on HMO,when patients with a history of trauma or surgery to the left lower abdomen present with corresponding imaging findings,clinicians should be vigilant in distinguishing this condition and promptly selecting appropriate diagnostic and therapeutic interventions.

Catheter-Assisted Interlaminar Approach for Cervical Epidural Steroid Injection in Patient with Cervical Stenosis Caused by Ossification of Posterior Longitudinal Ligament: A Case Report

We present the case of a 64-year-old man with cervical ossification of the posterior longitudinal ligament (OPLL) experiencing chronic neck pain and radiculopathy for 6 months. A catheter-assisted interlaminar Cervical Epidural Steroid Injection (CESI) was performed under fluoroscopic guidance, targeting the affected C2-C6 levels. Significant improvement was observed after this procedure, with decreased pain scores (visual analogue scale (VAS) 8 to 2) and improved mobility. This technique not only enhances the effectiveness of CESI but also reduces the likelihood of complications such as stroke or epidural hematoma and thus provides an alternative treatment option for patients with multiple stenotic levels who are unsuitable for surgery or are unresponsive to conservative therapy such as medication or physical therapy.

Transcriptomic and proteomic studies of condylar ossification of the temporomandibular joint in porcine embryos

Background:The ossification mechanism of the temporomandibular joint(TMJ)condyle remains unclear in human embryo.The size and structure of TMJ,shape of articular disc and the characteristics of omnivorous chewing in the pig are similar to those of humans.The pig is an ideal animal for studying the mechanism of ossification of the TMJ condyle during the embryonic period.Method:In a previous study by our group,it was found that there was no condylar ossification on embryonic day(E)45,but the ossification of condyle occurred between E75 and E90.In this study,a total of 12 miniature pig embryos on E45 and E85 were used.Six embryos were used for tissue sections(3 in each group).The remaining six embryos were used for transcriptomic and proteomic studies to find differential genes and proteins.The differentially expressed genes in transcriptome and proteomic analysis were verified by QPCR.Results:In total,1592 differential genes comprising 1086 up-regulated genes and 506 down-regulated genes were screened for fold changes of≥2 to≤0.5 between E45 and E85.In the total of 4613 proteins detected by proteomic analysis,there were 419 differential proteins including 313 up-regulated proteins and 106 down-regulated proteins screened for fold changes of≥2 to≤0.5 between E45 and E85.A total of 36 differential genes differing in both transcriptome and proteome analysis were found.QPCR analysis showed that 14 of 15 selected genes were consistent with transcriptome analysis.Conclusion:Condylar transcriptome and proteomic analysis during the development of TMJ in miniature pigs revealed the regulatory genes/proteins of condylar ossification.

Post-traumatic heterotopic ossification in front of the ankle joint for 23 years:A case report and review of literature

BACKGROUND Heterotopic ossification(HO)refers to the formation of new bone in non-skeletal tissues such as muscles,tendons or other soft tissues.Severe muscle and soft tissue injury often lead to the formation of HO.However,anterior HO of the ankle is rarely reported.CASE SUMMARY We report a patient with massive HO in front of the ankle joint for 23 years.In 1998,the patient was injured by a falling object on the right lower extremity,which gradually formed a massive heterotopic bone change in the right calf and dorsum of the foot.The patient did not develop gradual ankle function limitations until nearly 36 mo ago,and underwent resection of HO.Even after 23 years and resection of HO,the ankle joint was still able to move.CONCLUSION It is recommended that the orthopedist should be aware of HO and distinguish it from bone tumor.

Post-laparotomy heterotopic ossification of the xiphoid process: A case report

BACKGROUND Heterotopic ossification(HO)represents all types of extraskeletal ossification in the body.It occurs in various areas,including the skin,subcutaneous tissue,muscle,and joints.Surgical excision is recommended for symptomatic HO.Postoperative radiotherapy,oral nonsteroidal anti-inflammatory drugs,and topical sealants,such as bone wax,have been recommended as preventive measures.As HO is rare in occurrence,these recommendations are based on personal experiences,and there is a lack of information on individualized treatments depending on its location.CASE SUMMARY A 62-year-old male was admitted for symptomatic HO along a laparotomy scar.Surgical excision was performed for an 11 cm-sized ossification originating from the xiphoid process,and bone wax was applied to the excisional margin.However,the surgical wound failed to heal.After several weeks of saline-soaked gauze dressing,delayed wound closure was performed.The patient was finally discharged eight weeks after the excision.Because HO can occur in various areas of the body,a treatment strategy that may be effective for some may not be for others.Bone wax has been used as a topical sealant over excisional margins in the shoulder,elbow,and temporomandibular joints.However,in our case,its application on an abdominal surgical wound delayed its primary healing intention.The valuable lesson was that,when choosing a treatment method for HO based on available research data,its location must be considered.CONCLUSION Complete excision should be the priority treatment option for symptomatic HO along the laparotomy scar.Bone wax application is not recommended.Core Tip:Heterotopic ossification(HO)represents all types of extraskeletal ossification,and occurs in various areas,including the skin,muscle,and joints.There are some suggested treatment and preventive approaches for symptomatic HO,which include surgical excision and preventive measures such as postoperative radiotherapy,oral nonsteroidal anti-inflam-matory drugs,and topical sealants(bone wax).However,these recommendations are based on personal experiences limited to HO in certain locations.It is important to individualize our treatment approaches depending on its location.For symptomatic HO along the laparotomy scar,complete surgical excision should be the priority treatment option,and bone wax application is not recommended.

The role of vascular endothelial growth factor in ossification

Osteogenesis and angiogenesis are two closely correlated processes during bone growth, development, remodelling and repair. Vascular endothelial growth factor （VEGF） is an essential mediator during the process of angiogenesis. Based on an extensive literature search, which was carried out using the PubMed database and the keywords of osteogenesis, VEGF, endochondral ossification and intramembranous ossification, this manuscript reviews the role of VEGF in ossification, with emphasis on its effect in endochondral and intramembranous ossification. Osteogenesis and angiogenesis are closely correlated processes. VEGF acts as an essential mediator durin~ these processes. It not only functions in bone an^io^enesis but also in various aspects of bone develooment.

Neuromuscular electrical stimulation and testosterone did not influence heterotopic ossification size after spinal cord injury: A case series

Neuromuscular electrical stimulation(NMES) and testosterone replacement therapy(TRT) are effective rehabilitation strategies to attenuate muscle atrophy and evoke hypertrophy in persons with spinal cord injury(SCI). However both interventions might increase heterotopic ossification(HO) size in SCI patients. We present the results of two men with chronic traumatic motor complete SCI who also had pre-existing HO and participated in a study investigating the effects of TRT or TRT plus NMES resistance training(RT) on body composition. The 49-year-old male, Subject A, has unilateral HO in his right thigh. The 31-year-old male, Subject B, has bilateral HO in both thighs. Both participants wore transdermal testosterone patches(4-6 mg/d) daily for 16 wk. Subject A also underwent progressive NMES-RT twice weekly for 16 wk. Magnetic resonance imaging scans were acquired prior to and post intervention. Cross-sectional areas(CSA) of thewhole thigh and knee extensor skeletal muscles, femoral bone, and HO were measured. In Subject A(NMES-RT + TRT), the whole thigh skeletal muscle CSA increased by 10%, the knee extensor CSA increased by 17%, and the HO + femoral bone CSA did not change. In Subject B(TRT), the whole thigh skeletal muscle CSA increased by 13% in the right thigh and 6% in the left thigh. The knee extensor CSA increased by 7% in the right thigh and did not change in the left thigh. The femoral bone and HO CSAs in both thighs did not change. Both the TRT and NMES-RT + TRT protocols evoked muscle hypertrophy without stimulating the growth of preexisting HO.

Chondrogenesis mediates progression of ankylosing spondylitis through heterotopic ossification

Ankylosing spondylitis(AS)is chronic inflammatory arthritis with a progressive fusion of axial joints.Anti-inflammatory treatments such as anti-TNF-αantibody therapy suppress inflammation but do not effectively halt the progression of spine fusion in AS patients.Here we report that the autoimmune inflammation of AS generates a microenvironment that promotes chondrogenesis in spine ligaments as the process of spine fusion.Chondrocyte differentiation was observed in the ligaments of patients with earlystage AS,and cartilage formation was followed by calcification.Moreover,a large number of giant osteoclasts were found in the inflammatory environment of ligaments and on bony surfaces of calcified cartilage.Resorption activity by these giant osteoclasts generated marrow with high levels of active TGF-β,which induced new bone formation in the ligaments.Notably,no Osterix+osteoprogenitors were found in osteoclast resorption areas,indicating uncoupled bone resorption and formation.Even at the late and maturation stages,the uncoupled osteoclast resorption in bony interspinous ligament activates TGF-βto induce the progression of ossification in AS patients.Osteoclast resorption of calcified cartilage-initiated ossification in the progression of AS is a similar pathologic process of acquired heterotopic ossification(HO).Our finding of cartilage formation in the ligaments of AS patients revealed that the pathogenesis of spinal fusion is a process of HO and explained why anti-inflammatory treatments do not slow ankylosing once there is new bone formation in spinal soft tissues.Thus,inhibition of HO formation,such as osteoclast activity,cartilage formation,or TGF-βactivity could be a potential therapy for AS.

Diagnosis and endoscopic treatment of esophago-bronchial fistula due to gastric heterotopy

Heterotopic gastric mucosa patches are congenital gastrointestinal abnormalities and have been reported to occur anywhere along the gastrointestinal tract from mouth to anus.Complications of heterotopic gastric mucosa include dysphagia,upper gastrointestinal bleeding,upper esophageal ring stricture,adenocarcinoma and fistula formation.In this case report we describe the diagnosis and treatment of the first case of esophago-bronchial fistula due to heterotopic gastric mucosa in mid esophagus.A 40-year old former professional soccer player was referred to our department for treatment of an esophago-bronchial fistula.Microscopic examination of the biopsies taken from the esophageal fistula revealed the presence of gastric heterotopic mucosa.We decided to do a non-surgical therapeutic endoscopic procedure.A sclerotherapy catheter was inserted through which 1 mL of ready to use synthetic surgical glue was applied in the fistula and it closed the fistula opening with excellent results.

Dystrophic calcification and heterotopic ossification in fibrocartilaginous tissues of the spine in diffuse idiopathic skeletal hyperostosis(DISH)

Diffuse idiopathic skeletal hyperostosis(DISH) is a prevalent noninflammatory spondyloarthropathy characterized by ectopic mineral formation along the anterolateral aspect of the vertebral column, yet little is known about its underlying pathogenesis. Our objective was to evaluate the histopathological features and composition of ectopic mineral within spinal tissues affected by DISH in humans. Thoracic spine segments from six embalmed cadaveric donors(one female and five males;median age 82 years)meeting the radiographic diagnostic criteria for DISH were evaluated using radiological, histological, and physical analyses. Overall,the histological features of ectopic mineralization at individual motion segments were heterogeneous, including regions of heterotopic ossification and dystrophic calcification. Heterotopic ossifications were characterized by woven and lamellar bone,multifocal areas of metaplastic cartilage, and bony bridges along the anterior aspect of the intervertebral disc space. Dystrophic calcifications were characterized by an amorphous appearance, a high content of calcium and phosphorus, an X-ray diffraction pattern matching that of hydroxyapatite, and radiodensities exceeding that of cortical bone. Dystrophic calcifications were found within the anterior longitudinal ligament and annulus fibrosus in motion segments both meeting and not meeting the radiographic criteria for DISH. In summary, our findings indicate that in DISH, ectopic mineral forms along the anterior aspect of the spine by both heterotopic ossification and dystrophic calcification of fibrocartilaginous tissues. Although both types of ectopic mineralization are captured by current radiographic criteria for DISH, dystrophic calcification may reflect a distinct disease process or an early stage in the pathogenesis of DISH.

A Case of Acute Cauda Equina Syndrome for Combined Lumbar Ossification of the Posterior Longitudinal and Yellow Ligament

Acute cauda equina syndrome is known as a symptom of lumbar disc herniation, but to date, there have been no reports of cases caused by lumbar vertebral ligament ossification. We encountered a 61-year-old female patient with acute cauda equina syndrome associated with lumbar vertebral OPLL and OLF. The symptoms were improved by emergency laminectomy. One year after the surgery, the disturbances of gait and urination have been resolved.

Mesenchymal VEGFA induces aberrant differentiation in heterotopic ossification

Heterotopic ossification(HO)is a debilitating condition characterized by the pathologic formation of ectopic bone.HO occurs commonly following orthopedic surgeries,burns,and neurologic injuries.While surgical excision may provide palliation,the procedure is often burdened with significant intra-operative blood loss due to a more robust contribution of blood supply to the pathologic bone than to native bone.Based on these clinical observations,we set out to examine the role of vascular signaling in HO.Vascular endothelial growth factor A(VEGFA)has previously been shown to be a crucial pro-angiogenic and pro-osteogenic cue during normal bone development and homeostasis.Our findings,using a validated mouse model of HO,demonstrate that HO lesions are highly vascular,and that VEGFA is critical to ectopic bone formation,despite lacking a contribution of endothelial cells within the developing anlagen.

Heterotopic ossification after the use of recombinant human bone morphogenetic protein-7

AIM To present the incidence of heterotopic ossification after the use of recombinant human bone morphogenetic protein-7(rhB MP-7) for the treatment of nonunions.METHODS Bone morphogenetic proteins(BMPs) promote bone formation by auto-induction. Recombinant human BMP-7 in combination with bone grafts was used in 84 patients for the treatment of long bone nonunions. All patients were evaluated radiographicaly for the development of heterotopic ossification during the standard assessment for the nonunion healing. In all patients(80.9%) with radiographic signs of heterotopic ossification, a CT scan was performed. Nonunion site palpation and ROM evaluation of the adjacent jointswere also carried out. Factors related to the patient(age, gender), the nonunion(location, size, chronicity, number of previous procedures, infection, surrounding tissues condition) and the surgical procedure(graft and fixation type, amount of rhB MP-7) were correlated with the development of heterotopic ossification and statistical analysis with Pearsons χ~2 test was performed.RESULTS Eighty point nine percent of the nonunions treated with rh BMP-7, healed with no need for further procedures. Heterotopic bone formation occurred in 15 of 84 patients(17.8%) and it was apparent in the routine radiologi-cal evaluation of the nonunion site, in a mean time of 5.5 mo after the rh BMP-7 application(range 3-12). The heterotopic ossification was located at the femur in 8 cases, at the tibia in 6, and at the humerus in οne patient. In 4 patients a palpable mass was present and only in one patient, with a para-articular knee nonunion treated with rhB MP-7, the size of heterotopic ossification affected the knee range of motion. All the patients with heterotopic ossification were male. Statistical analysis proved that patient's gender was the only important factor for the development of heterotopic ossification(P = 0.007). CONCLUSION Heterotopic ossification after the use of rh BMP-7 in nonunions was common but it did not compromise the final clinical outcome in most cases, and affected only male patients.

Conditional disruption of the osterix gene in chondrocytes during early postnatal growth impairs secondary ossification in the mouse tibial epiphysis

In our previous studies, we have found that the prepubertal increase in thyroid hormone levels induces osterix(Osx) signaling in hypertrophic chondrocytes to transdifferentiate them into osteoblasts. To test if Osx expressed in chondrocytes directly contributes to transdifferentiation and secondary ossification, we generated Osx^flox/flox;Col2-Cre-ERT2 mice and knocked out Osx with a single injection of tamoxifen at postnatal day(P) 3 prior to evaluation of the epiphyseal bone phenotype by μCT, histology, and immunohistochemistry(IHC) at P21. Vehicle(oil)-treated Osx^flox/flox;Col2-Cre-ERT2 and tamoxifen-treated, Cre-negative Osx^flox/flox mice were used as controls.μCT analysis of tibial epiphyses revealed that trabecular bone mass was reduced by 23% in the Osx conditional knockout(c KO) compared with control mice. Trabecular number and thickness were reduced by 28% and 8%,respectively, while trabecular separation was increased by 24% in the c KO mice. Trichrome staining of longitudinal sections of tibial epiphyses showed that bone area and bone area adjusted for total area were decreased by 22% and 18%, respectively. IHC studies revealed the presence of abundant Osx-expressing prehypertrophic chondrocytes in the epiphyses of control mice at P10, but not in the cKO mice. Furthermore, expression levels of MMP13, COL10, ALP, and BSP were considerably reduced in the epiphyses of cKO mice. We also found that Osx overexpression in ATDC5 chondrocytes increased expression of Col10, Mmp13, Alp, and Bsp. Our data indicate that Osx expressed in chondrocytes plays a significant role in secondary ossification by regulating expression of genes involved in chondrocyte hypertrophy and osteoblast transdifferentiation.

Pulsed Lavage in Cementless Total Hip Arthroplasty Reduces the Incidence ofBrooker Grade 3 and 4 Heterotopic Ossifications

Heterotopic ossification (HO) may cause pain, and can lead to loss of hip motion after total hip arthroplasty (THA). There is evidence that pulsed lavage may lower the incidence of HO formation. We assessed the effect of pulsed lavage on the incidence of HO in 87 male patients after THA. All patients received an uncemented THA through a posterolateral approach. 39 patients were treated with pulsed lavage (index group) and 48 males were treated without pulsed lavage (historical control group, matched on aetiology, gender, surgical approach and type of prosthesis). Both groups followed the same postoperative treatment regimen. HO severity was scored in both groups according to the Brooker classification by three blinded orthopaedic surgeons one year postoperatively. Good inter-observer agreement (Kappa 0.7) for scoring HO was found. The incidence of HO (51%) in the index group did not differ significantly (p = 0.53) from the control group (58%). However, the incidence of clinically relevant HO (Brooker grades 3 and 4) was significantly lower (p = 0.04) in the index group (3%) as compared to the control group (17%). These results suggest a beneficial effect of pulsed lavage on the incidence of severe heterotopic ossification after cementless THA in male patients.