Mechanical stress modulates bone formation and organization of the extracellular matrix(ECM),the interaction of which affects heterotopic ossification(HO).However,the mechanically sensitive cell populations in HO and ...Mechanical stress modulates bone formation and organization of the extracellular matrix(ECM),the interaction of which affects heterotopic ossification(HO).However,the mechanically sensitive cell populations in HO and the underlying mechanism remain elusive.Here,we show that the mechanical protein Polysyctin-1(PC1,Pkd1)regulates CTSK lineage tendon-derived mesenchymal stem cell(TDMSC)fate and ECM organization,thus affecting HO progression.First,we revealed that CTSK lineage TDMSCs are the major source of osteoblasts and fibroblasts in HO and are responsive to mechanical cues via single-cell RNA sequencing analysis and experiments with a lineage tracing mouse model.Moreover,we showed that PC1 mediates the mechanosignal transduction of CTSK lineage TDMSCs to regulate osteogenic and fibrogenic differentiation and alters the ECM architecture by facilitating TAZ nuclear translocation.Conditional gene depletion of Pkd1 or Taz in CTSK lineage cells and pharmaceutical intervention in the PC1-TAZ axis disrupt osteogenesis,fibrogenesis and ECM organization,and consequently attenuate HO progression.These findings suggest that mechanically sensitive CTSK-lineage TDMSCs contribute to heterotopic ossification through PC1-TAZ signaling axis mediated cell fate determination and ECM organization.展开更多
BACKGROUND Among all forms of heterotopic ossification,heterotopic mesenteric ossification(HMO)is rare,with fewer than 100 reported cases to date.Postoperative early small bowel obstruction caused by HMO is even rarer...BACKGROUND Among all forms of heterotopic ossification,heterotopic mesenteric ossification(HMO)is rare,with fewer than 100 reported cases to date.Postoperative early small bowel obstruction caused by HMO is even rarer,presenting extremely high surgical risks,the potential for multiple surgeries,and a poor prognosis.There have been no reported cases of conservative treatment for resolving such early postoperative obstruction.CASE SUMMARY A 57-year-old male presented with severe postoperative small bowel obstruction shortly after undergoing open radical resection for transverse colon cancer.Laparotomy revealed extensive adhesions in the proximal jejunum and mesen-tery,making it too difficult to relieve without injuring the small bowel.Addi-tionally,multiple fixed nodules were found in the mesentery during the opera-tion.Pathology confirmed the presence of heterotopic ossification.The patient was treated with methylprednisolone on postoperative day 1,which gradually relieved his symptoms.CONCLUSION Hormone therapy may have a potential role in treating small bowel obstruction caused by early HMO after operative intervention.展开更多
Heterotopic mesenteric ossification(HMO)is a rare medical condition,with<100 cases reported globally by 2024.This disorder is characterized by abnormal bone tissue formation within the mesentery,often following abd...Heterotopic mesenteric ossification(HMO)is a rare medical condition,with<100 cases reported globally by 2024.This disorder is characterized by abnormal bone tissue formation within the mesentery,often following abdominal trauma,ischemia,or infection.This editorial reviews the case presented by Zhang et al,involving a 34-year-old male who developed persistent left lower abdominal pain after sustaining blunt trauma to the abdomen.Diagnostic challenges arose due to the rarity and nonspecific presentation of HMO,which shares histopathological features with conditions such as myositis ossificans and necessitates differentiation from malignancies like sarcomas.Advanced imaging revealed calcifications suggestive of HMO,but definitive diagnosis was achieved only through surgical resection and histopathological analysis,which confirmed the presence of ectopic bone formation.Although benign,HMO can result in severe complications,such as bowel perforation or obstruction.Therefore,awareness of HMO is crucial for clinicians to ensure timely and appropriate treatment.展开更多
In this article,we make a comment on the recent article by Sun et al,focusing on the advances of neutrophil extracellular traps(NETs)formation in common osteoarticular diseases.Neutrophils are the first line to elimin...In this article,we make a comment on the recent article by Sun et al,focusing on the advances of neutrophil extracellular traps(NETs)formation in common osteoarticular diseases.Neutrophils are the first line to eliminate invading pathogens including fungal and bacterial infections via releasing hydrolytic enzymes and reactive oxygen species.Besides,neutrophils will accumulate at the inflammatory site and release NETs,which are composed of histones,DNA and granular proteins.Traumatic heterotopic ossification(THO)was generally believed to develop through four stages:Inflammation,chondrogenesis,osteogenesis,and bone maturation.Thus,it can be seen that THO was related to inflammation and bone formation.Apart from immune and infectious diseases,recent studies have also shown that NETs play a significant role in the pathogenesis of THO.This article focuses on elaborating the role of NETs in the onset of THO,discussing the existing problems in the current research and outlining future directions.展开更多
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). H...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.展开更多
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 ...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.展开更多
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...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.展开更多
BACKGROUND Heterotopic ossification(HO)is a rare clinical phenomenon that refers to bone formation in nonossifying tissues.CASE SUMMARY This report presents two cases of HO beneath the upper abdominal median incision ...BACKGROUND Heterotopic ossification(HO)is a rare clinical phenomenon that refers to bone formation in nonossifying tissues.CASE SUMMARY This report presents two cases of HO beneath the upper abdominal median incision after radical gastrectomy.The first patient had postoperative pain below the incision area.There were no signs of anastomotic leakage,and the wound healed.Computed tomography(CT)findings 2 wk postoperatively were negative for HO,but the 6-wk CT showed HO beneath the incision.The patient refused reoperation,and after conservative therapy,the pain was gradually relieved after 2 wk.In the second case,postoperative recovery was uneventful,and HO was only detected on routine follow-up CT after 4 mo.An anti-adhesion membrane was applied beneath the peritoneum in both patients.Our findings suggest that HO beneath the abdominal incision might form at approximately 1 mo postoperatively.It may cause intractable pain;however,reoperation is usually not required.CONCLUSION In our cases,we suspect that HO may be related to the use of foreign materials beneath the peritoneum,which needs to be further investigated.展开更多
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 recommende...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.展开更多
BACKGROUND Neurogenic heterotopic ossification is an acquired serious complication described in patients with central nervous system disorders and defined by bone formation in non-osseous tissue.CASE SUMMARY We presen...BACKGROUND Neurogenic heterotopic ossification is an acquired serious complication described in patients with central nervous system disorders and defined by bone formation in non-osseous tissue.CASE SUMMARY We present an unusual case of a 13-yr-old boy presenting with hip pain and severe gait impairment 5 mo after the diagnosis of hemiplegia following a spontaneous intracerebral haemorrhage.Computed tomography revealed bilateral heterotopic ossification of both the paretic and the non-paretic limbs,with entrapment of the sciatic nerve.The choice of surgical or nonsurgical management of such patients depends on the timing of diagnosis,the symptoms,and the extent of maturation of the ossified lesions.Surgical resection remains the only treatment with proven,evidence-based effectiveness.The choice of surgical approach largely depends on the location of the ossified lesions.CONCLUSION We believe the plane of dissection presented is a satisfactory option for resection of a posteromedial mass and sciatic nerve release.展开更多
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 instanc...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.展开更多
BACKGROUND Cervical disc arthroplasty(CDA)is an alternative treatment to traditional interbody fusion that maintains postoperative cervical spine mobility.However,the CDA postoperative period is impacted by osteolysis...BACKGROUND Cervical disc arthroplasty(CDA)is an alternative treatment to traditional interbody fusion that maintains postoperative cervical spine mobility.However,the CDA postoperative period is impacted by osteolysis,subsidence,metallosis,or heterotopic ossification(HO).We report a case of severe HO in a seronegative spondyloarthritis patient after cervical Bryan disc arthroplasty.CASE SUMMARY A 34-year-old man received hybrid surgery for C4-C5 and C5-C6 arthroplasty with Bryan discs and C6-C7 arthrodesis with polyetheretherketone cage due to traumatic herniation of the intervertebral disc(HIVD).After four years,cervical spine radiographs revealed severe HO around the Bryan discs over the C4-C5 and C5-C6 levels.The magnetic resonance image revealed HIVD over the C3-C4 level with spinal cord compression.Seronegative spondyloarthritis was diagnosed after consultation with a rheumatologist.A second CDA for the adjacent segment disease HIVD with Baguera C disc over the C3-C4 level achieved an excellent outcome.CONCLUSION Minimizing intraoperative tissue trauma and achieving postoperative interbody stability avoid soft tissue traction to prevent HO formation after CDA.展开更多
Background: Radiation therapy prophylaxis for heterotopic ossification is well-established for the hip, either pre or post-operatively. There is limited data for this treatment in non-hip sites. We report our institut...Background: Radiation therapy prophylaxis for heterotopic ossification is well-established for the hip, either pre or post-operatively. There is limited data for this treatment in non-hip sites. We report our institution’s experience. Methods: From October 2004 to August 2015, a total of 39 non-hip sites in 38 patients were treated with prophylactic radiation therapy for heterotopic ossification at our institution. An IRB approved retrospective review was performed. There were 15 patients who received treatments to the elbow, 13 to the knee (1 bilateral for a total of 14 knees), and 10 to other sites (leg stump (2), pubic symphysis (2), femur (1), foot (1), humerus stump (1), abdominal wall (1), shoulder (1), thigh (1)). All but 1 patient were treated with a single fraction treatment with 700 or 800 cGy. One patient received 2000 cGy in 10 fractions to the abdominal wall for heterotopic ossification extending from the xiphoid process. Results: Fifteen patients underwent treatment to the elbow with a median follow-up of 5 months (0 - 99). Median age for this group was 50 years (37 - 69). Nine (60.0%) patients had evidence of heterotopic ossification prior to surgery. All (100%) of the elbow patients were free from recurrence at last follow-up. There were no acute or late toxicities noted. For treatment to the knee, there were 4 (28.6%) recurrences, all in cases where there were pre-operative heterotopic ossification. There were two other recurrences in the non-hip, elbow or knee sites: one patient who received radiation therapy to the abdominal wall and one patient who underwent treatment to the thigh. Conclusions: Prophylactic radiation therapy with 700 cGy or 800 cGy in 1 fraction either before or after surgery remains a safe and effective treatment for both hip and most non-hip sites. Fractionated treatment may be used for larger treatment fields, however experience is limited.展开更多
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.H...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.展开更多
BACKGROUND:Heterotopic ossification of skeletal muscle is a clinically serious complication.For heterotopic ossification of skeletal muscles,the cells involved in the process of heterotopic ossification remain unclear...BACKGROUND:Heterotopic ossification of skeletal muscle is a clinically serious complication.For heterotopic ossification of skeletal muscles,the cells involved in the process of heterotopic ossification remain unclear.OBJECTIVE:To investigate the involvement of myocytes,fascia cells,and endothelial cells in the process of heterotopic ossification in skeletal muscle and to observe the cell origin of heterotopic ossification in skeletal muscle induced by bone morphogenetic protein 4.METHODS:Both C2C12 cells and the myotubes formed by the C2C12 cells in the induction medium were cultured,and 500 ng/mL bone morphogenetic protein 4 was added to the medium respectively,and whether the C2C12 cells and myotubes continued to proliferate within 10 days under the treatment were observed under a microscope.Myogenic cells(L6,derived from rats)and fibroblast-derived cells(derived from human)were co-cultured.After treatment with 500 ng/mL bone morphogenetic protein 4 and 10 ng/mL transforming growth factor-β,osteogenic and chondrogenic differentiation potential within 21 days were observed using Safranine O staining and Alcian blue staining.Using transgenic animal FVB/N-TgN(TIE2-LacZ)182Sato mice,15μL of adeno-associated virus-bone morphogenetic protein 4(5×1010 PFU/mL)were implanted in the thigh muscle space of genetic mice for 10 and 14 days.X-gal staining was used to observe the formation of new blood vessel endothelium in the differentiated bone.RESULTS AND CONCLUSION:(1)Bone morphogenetic protein 4 caused myotube breakdown and increased C2C12 cell proliferation.Compared with other groups,the pure fibroblast-derived cell group had a higher area of positive alcian blue and safarin O staining(P<0.05)and a lower area of alkaline phosphatase staining(P<0.05),while the pure L6 group had a bigger area of alkaline phosphatase staining(P<0.05)but a smaller area of positive alcian blue and safarin O staining(P<0.05).(2)Transplantation of adeno-associated virus-bone morphogenetic protein 4-adsorbed gelatin sponge into FVB/N-TgN(TIE2-LacZ)182Sato mice resulted in heterotopic ossification.(3)X-gal staining results demonstrated that there was no obvious staining in chondrocytes and differentiated bones and Tie2+endothelial cells did not participate in the formation of the alienated bone.(4)These findings verify that fibroblasts are the primary source of osteoblasts during the adeno-associated virus-bone morphogenetic protein 4-induced ectopic endochondral ossification in skeletal muscle,but myogenic cells are the main source of osteoblasts.Tie2+endothelial cells might not be the cell source for cartilage and bone.展开更多
Heterotopic ossification (HO) is the abnormal, non-neoplastic presence of lamellar bone in soft tissue. The ectopic formation of lamellar bone in non-osseus tissues secondary to traumatic injuries of the spinal cord o...Heterotopic ossification (HO) is the abnormal, non-neoplastic presence of lamellar bone in soft tissue. The ectopic formation of lamellar bone in non-osseus tissues secondary to traumatic injuries of the spinal cord or the brain is defined as Neurogenic HO. The pathophysiology of HO is not clear. But several theories like overactive humoral mechanisms after fracture healing, imbalance of pro-osteoinductive and anti-osteoinductive mediators located on the soft tissues and gene mutations in such as bone morphogenetic proteins-4 (BMP-4) are proposed. Casualty factors leading to increased risk of HO include older age, blast mechanism of injury, location of injury and traumatic brain injury. The aim of this paper is to demonstrate a case of HO located in the brain without history of trauma or any other risk factors.展开更多
Metal debris from metal-on-metal (MoM) total hip arthroplasties (THA) has been suspected to cause periprosthetic heterotopic ossifications (HO). We determined the influence of disseminated cobalt, chromium and molybde...Metal debris from metal-on-metal (MoM) total hip arthroplasties (THA) has been suspected to cause periprosthetic heterotopic ossifications (HO). We determined the influence of disseminated cobalt, chromium and molybdenum on the development of HO. Native blood samples from patients with 86 high-carbon and 16 low-carbon Co28Cr6Mo articulations were analysed by high-resolution inductively coupled plasma mass-spectrometry (HR ICP-MS). The results revealed that high-carbon metal-on-metal articulations showed lower metal blood levels (Co 1.03 to 1.60 μg/l, Cr 0.77 to 0.88 μg/l, Mo 0.45 to 0.56 μg/l) whereas low-carbon articulations achieved higher metal blood levels (Co 2.59 to 6.85 μg/l, Cr 1.25 to 3.55 μg/l, Mo 0.45 to 0.64 μg/l), but no correlation between metal ion blood level or carbon content and the development of HO could be found in these MoM articulations. Hence, metal debris from MoM articulation does not stimulate heterotopic bone formation despite other well-known local reactions.展开更多
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 ...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.展开更多
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 ...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.展开更多
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...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.展开更多
基金National Natural Science Foundation of China(Grant Nos.82261160397,82272560)Central South University Research Programme of Advanced Interdisciplinary Studies(2023QYJC011)+4 种基金National Natural Science Foundation of China(Grant Nos.82472521,81922017)Hunan Provincial Science and Technology Department(2023JJ30896)Key Research and Development Program of Hunan Province(2022SK2023)Science and Technology Innovation Program of Hunan Province(2023RC1027)Major Basic Research Projects in Hunan Province(No.2024JC0004)。
文摘Mechanical stress modulates bone formation and organization of the extracellular matrix(ECM),the interaction of which affects heterotopic ossification(HO).However,the mechanically sensitive cell populations in HO and the underlying mechanism remain elusive.Here,we show that the mechanical protein Polysyctin-1(PC1,Pkd1)regulates CTSK lineage tendon-derived mesenchymal stem cell(TDMSC)fate and ECM organization,thus affecting HO progression.First,we revealed that CTSK lineage TDMSCs are the major source of osteoblasts and fibroblasts in HO and are responsive to mechanical cues via single-cell RNA sequencing analysis and experiments with a lineage tracing mouse model.Moreover,we showed that PC1 mediates the mechanosignal transduction of CTSK lineage TDMSCs to regulate osteogenic and fibrogenic differentiation and alters the ECM architecture by facilitating TAZ nuclear translocation.Conditional gene depletion of Pkd1 or Taz in CTSK lineage cells and pharmaceutical intervention in the PC1-TAZ axis disrupt osteogenesis,fibrogenesis and ECM organization,and consequently attenuate HO progression.These findings suggest that mechanically sensitive CTSK-lineage TDMSCs contribute to heterotopic ossification through PC1-TAZ signaling axis mediated cell fate determination and ECM organization.
基金Supported by Major Basic Research Project of Shanxi Provincial Natural Science Foundation,No.202203021221185 and No.202103021224379.
文摘BACKGROUND Among all forms of heterotopic ossification,heterotopic mesenteric ossification(HMO)is rare,with fewer than 100 reported cases to date.Postoperative early small bowel obstruction caused by HMO is even rarer,presenting extremely high surgical risks,the potential for multiple surgeries,and a poor prognosis.There have been no reported cases of conservative treatment for resolving such early postoperative obstruction.CASE SUMMARY A 57-year-old male presented with severe postoperative small bowel obstruction shortly after undergoing open radical resection for transverse colon cancer.Laparotomy revealed extensive adhesions in the proximal jejunum and mesen-tery,making it too difficult to relieve without injuring the small bowel.Addi-tionally,multiple fixed nodules were found in the mesentery during the opera-tion.Pathology confirmed the presence of heterotopic ossification.The patient was treated with methylprednisolone on postoperative day 1,which gradually relieved his symptoms.CONCLUSION Hormone therapy may have a potential role in treating small bowel obstruction caused by early HMO after operative intervention.
基金Supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,No.NRF-RS-2023-00237287 and No.NRF-2021S1A5A8062526Local Government-University Cooperation-Based Regional Innovation Projects,No.2021RIS-003.
文摘Heterotopic mesenteric ossification(HMO)is a rare medical condition,with<100 cases reported globally by 2024.This disorder is characterized by abnormal bone tissue formation within the mesentery,often following abdominal trauma,ischemia,or infection.This editorial reviews the case presented by Zhang et al,involving a 34-year-old male who developed persistent left lower abdominal pain after sustaining blunt trauma to the abdomen.Diagnostic challenges arose due to the rarity and nonspecific presentation of HMO,which shares histopathological features with conditions such as myositis ossificans and necessitates differentiation from malignancies like sarcomas.Advanced imaging revealed calcifications suggestive of HMO,but definitive diagnosis was achieved only through surgical resection and histopathological analysis,which confirmed the presence of ectopic bone formation.Although benign,HMO can result in severe complications,such as bowel perforation or obstruction.Therefore,awareness of HMO is crucial for clinicians to ensure timely and appropriate treatment.
文摘In this article,we make a comment on the recent article by Sun et al,focusing on the advances of neutrophil extracellular traps(NETs)formation in common osteoarticular diseases.Neutrophils are the first line to eliminate invading pathogens including fungal and bacterial infections via releasing hydrolytic enzymes and reactive oxygen species.Besides,neutrophils will accumulate at the inflammatory site and release NETs,which are composed of histones,DNA and granular proteins.Traumatic heterotopic ossification(THO)was generally believed to develop through four stages:Inflammation,chondrogenesis,osteogenesis,and bone maturation.Thus,it can be seen that THO was related to inflammation and bone formation.Apart from immune and infectious diseases,recent studies have also shown that NETs play a significant role in the pathogenesis of THO.This article focuses on elaborating the role of NETs in the onset of THO,discussing the existing problems in the current research and outlining future directions.
文摘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.
基金The European Union(European Social Fund-ESF)Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework(NSRF)-Research Funding Program:Heracleitus Ⅱ
文摘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.
文摘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.
基金Supported by the Clinical and Practical New Technology Development Fund of Qilu Hospital of Shandong University.
文摘BACKGROUND Heterotopic ossification(HO)is a rare clinical phenomenon that refers to bone formation in nonossifying tissues.CASE SUMMARY This report presents two cases of HO beneath the upper abdominal median incision after radical gastrectomy.The first patient had postoperative pain below the incision area.There were no signs of anastomotic leakage,and the wound healed.Computed tomography(CT)findings 2 wk postoperatively were negative for HO,but the 6-wk CT showed HO beneath the incision.The patient refused reoperation,and after conservative therapy,the pain was gradually relieved after 2 wk.In the second case,postoperative recovery was uneventful,and HO was only detected on routine follow-up CT after 4 mo.An anti-adhesion membrane was applied beneath the peritoneum in both patients.Our findings suggest that HO beneath the abdominal incision might form at approximately 1 mo postoperatively.It may cause intractable pain;however,reoperation is usually not required.CONCLUSION In our cases,we suspect that HO may be related to the use of foreign materials beneath the peritoneum,which needs to be further investigated.
文摘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.
文摘BACKGROUND Neurogenic heterotopic ossification is an acquired serious complication described in patients with central nervous system disorders and defined by bone formation in non-osseous tissue.CASE SUMMARY We present an unusual case of a 13-yr-old boy presenting with hip pain and severe gait impairment 5 mo after the diagnosis of hemiplegia following a spontaneous intracerebral haemorrhage.Computed tomography revealed bilateral heterotopic ossification of both the paretic and the non-paretic limbs,with entrapment of the sciatic nerve.The choice of surgical or nonsurgical management of such patients depends on the timing of diagnosis,the symptoms,and the extent of maturation of the ossified lesions.Surgical resection remains the only treatment with proven,evidence-based effectiveness.The choice of surgical approach largely depends on the location of the ossified lesions.CONCLUSION We believe the plane of dissection presented is a satisfactory option for resection of a posteromedial mass and sciatic nerve release.
基金Supported by Natural Science Foundation of Fujian Province,China No.2021J01545Natural Science Foundation of Zhangzhou City,Fujian Province,China No.ZZ2021J25.
文摘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.
文摘BACKGROUND Cervical disc arthroplasty(CDA)is an alternative treatment to traditional interbody fusion that maintains postoperative cervical spine mobility.However,the CDA postoperative period is impacted by osteolysis,subsidence,metallosis,or heterotopic ossification(HO).We report a case of severe HO in a seronegative spondyloarthritis patient after cervical Bryan disc arthroplasty.CASE SUMMARY A 34-year-old man received hybrid surgery for C4-C5 and C5-C6 arthroplasty with Bryan discs and C6-C7 arthrodesis with polyetheretherketone cage due to traumatic herniation of the intervertebral disc(HIVD).After four years,cervical spine radiographs revealed severe HO around the Bryan discs over the C4-C5 and C5-C6 levels.The magnetic resonance image revealed HIVD over the C3-C4 level with spinal cord compression.Seronegative spondyloarthritis was diagnosed after consultation with a rheumatologist.A second CDA for the adjacent segment disease HIVD with Baguera C disc over the C3-C4 level achieved an excellent outcome.CONCLUSION Minimizing intraoperative tissue trauma and achieving postoperative interbody stability avoid soft tissue traction to prevent HO formation after CDA.
文摘Background: Radiation therapy prophylaxis for heterotopic ossification is well-established for the hip, either pre or post-operatively. There is limited data for this treatment in non-hip sites. We report our institution’s experience. Methods: From October 2004 to August 2015, a total of 39 non-hip sites in 38 patients were treated with prophylactic radiation therapy for heterotopic ossification at our institution. An IRB approved retrospective review was performed. There were 15 patients who received treatments to the elbow, 13 to the knee (1 bilateral for a total of 14 knees), and 10 to other sites (leg stump (2), pubic symphysis (2), femur (1), foot (1), humerus stump (1), abdominal wall (1), shoulder (1), thigh (1)). All but 1 patient were treated with a single fraction treatment with 700 or 800 cGy. One patient received 2000 cGy in 10 fractions to the abdominal wall for heterotopic ossification extending from the xiphoid process. Results: Fifteen patients underwent treatment to the elbow with a median follow-up of 5 months (0 - 99). Median age for this group was 50 years (37 - 69). Nine (60.0%) patients had evidence of heterotopic ossification prior to surgery. All (100%) of the elbow patients were free from recurrence at last follow-up. There were no acute or late toxicities noted. For treatment to the knee, there were 4 (28.6%) recurrences, all in cases where there were pre-operative heterotopic ossification. There were two other recurrences in the non-hip, elbow or knee sites: one patient who received radiation therapy to the abdominal wall and one patient who underwent treatment to the thigh. Conclusions: Prophylactic radiation therapy with 700 cGy or 800 cGy in 1 fraction either before or after surgery remains a safe and effective treatment for both hip and most non-hip sites. Fractionated treatment may be used for larger treatment fields, however experience is limited.
基金Supported by Scientific research project of Hunan Education Department,No.21B0075Science project of Hunan Provincial Health Commission,No.B2015-82。
文摘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.
文摘BACKGROUND:Heterotopic ossification of skeletal muscle is a clinically serious complication.For heterotopic ossification of skeletal muscles,the cells involved in the process of heterotopic ossification remain unclear.OBJECTIVE:To investigate the involvement of myocytes,fascia cells,and endothelial cells in the process of heterotopic ossification in skeletal muscle and to observe the cell origin of heterotopic ossification in skeletal muscle induced by bone morphogenetic protein 4.METHODS:Both C2C12 cells and the myotubes formed by the C2C12 cells in the induction medium were cultured,and 500 ng/mL bone morphogenetic protein 4 was added to the medium respectively,and whether the C2C12 cells and myotubes continued to proliferate within 10 days under the treatment were observed under a microscope.Myogenic cells(L6,derived from rats)and fibroblast-derived cells(derived from human)were co-cultured.After treatment with 500 ng/mL bone morphogenetic protein 4 and 10 ng/mL transforming growth factor-β,osteogenic and chondrogenic differentiation potential within 21 days were observed using Safranine O staining and Alcian blue staining.Using transgenic animal FVB/N-TgN(TIE2-LacZ)182Sato mice,15μL of adeno-associated virus-bone morphogenetic protein 4(5×1010 PFU/mL)were implanted in the thigh muscle space of genetic mice for 10 and 14 days.X-gal staining was used to observe the formation of new blood vessel endothelium in the differentiated bone.RESULTS AND CONCLUSION:(1)Bone morphogenetic protein 4 caused myotube breakdown and increased C2C12 cell proliferation.Compared with other groups,the pure fibroblast-derived cell group had a higher area of positive alcian blue and safarin O staining(P<0.05)and a lower area of alkaline phosphatase staining(P<0.05),while the pure L6 group had a bigger area of alkaline phosphatase staining(P<0.05)but a smaller area of positive alcian blue and safarin O staining(P<0.05).(2)Transplantation of adeno-associated virus-bone morphogenetic protein 4-adsorbed gelatin sponge into FVB/N-TgN(TIE2-LacZ)182Sato mice resulted in heterotopic ossification.(3)X-gal staining results demonstrated that there was no obvious staining in chondrocytes and differentiated bones and Tie2+endothelial cells did not participate in the formation of the alienated bone.(4)These findings verify that fibroblasts are the primary source of osteoblasts during the adeno-associated virus-bone morphogenetic protein 4-induced ectopic endochondral ossification in skeletal muscle,but myogenic cells are the main source of osteoblasts.Tie2+endothelial cells might not be the cell source for cartilage and bone.
文摘Heterotopic ossification (HO) is the abnormal, non-neoplastic presence of lamellar bone in soft tissue. The ectopic formation of lamellar bone in non-osseus tissues secondary to traumatic injuries of the spinal cord or the brain is defined as Neurogenic HO. The pathophysiology of HO is not clear. But several theories like overactive humoral mechanisms after fracture healing, imbalance of pro-osteoinductive and anti-osteoinductive mediators located on the soft tissues and gene mutations in such as bone morphogenetic proteins-4 (BMP-4) are proposed. Casualty factors leading to increased risk of HO include older age, blast mechanism of injury, location of injury and traumatic brain injury. The aim of this paper is to demonstrate a case of HO located in the brain without history of trauma or any other risk factors.
文摘Metal debris from metal-on-metal (MoM) total hip arthroplasties (THA) has been suspected to cause periprosthetic heterotopic ossifications (HO). We determined the influence of disseminated cobalt, chromium and molybdenum on the development of HO. Native blood samples from patients with 86 high-carbon and 16 low-carbon Co28Cr6Mo articulations were analysed by high-resolution inductively coupled plasma mass-spectrometry (HR ICP-MS). The results revealed that high-carbon metal-on-metal articulations showed lower metal blood levels (Co 1.03 to 1.60 μg/l, Cr 0.77 to 0.88 μg/l, Mo 0.45 to 0.56 μg/l) whereas low-carbon articulations achieved higher metal blood levels (Co 2.59 to 6.85 μg/l, Cr 1.25 to 3.55 μg/l, Mo 0.45 to 0.64 μg/l), but no correlation between metal ion blood level or carbon content and the development of HO could be found in these MoM articulations. Hence, metal debris from MoM articulation does not stimulate heterotopic bone formation despite other well-known local reactions.
文摘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.
基金supported by the Canadian Institutes of Health Research (grant number 115068)。
文摘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.
基金B.L.:Supported by funding from NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH1R01AR071379American College of Surgeons Clowes Award.D.M.S.:Supported by Plastic Surgery Foundation Resident Research Award+6 种基金M.S.:Supported by Plastic Surgery Foundation National Endowment AwardC.H.:Supported by Howard Hughes Medical Institute Medical Research FellowshipJ.L.:Supported by Vascular Surgery T32 5-T32-HL-076123–14A.W.J.:Supported by the NIH/NIAMS(R01 AR070773,K08 AR068316,S10OD016374)the Orthopedic Research and Education Foundation with funding provided by the Maryland Stem Cell Research Foundation,and the Musculoskeletal Transplant FoundationP.B.Y.:Supported by funding from NIH/NIAMS R01 AR057374 and NHLBI R01 HL131910Y.M.:Supported by funding from NIH/NIDCR R01 DE020843 and DE027662
文摘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.
