ObjectiveTo explore the role and significance of hypoxia inducible factor lα (HIF-lα) and hypoxia microenvironment in the pathogenesis of post-traumatic heterotopic ossification by detecting the expression of HIF-lα in rat model of heterotopic ossification after Achilles tenotomy. MethodsA total of 140 male Sprague Dawley rats, aged 8-10 weeks, and weighing (210.1±10.6) g, were randomly divided into experimental group (n=70) and control group (n=70). In experimental group, the Achilles tendon was cut off and clamped to prepare post-traumatic heterotopic ossification model; in control group, only Achilles tendon was exposed. The general condition of rats was observed after operation, and at 2, 3, 4, 5, 6, 7, 8, 10, 12, and 14 days after operation, the Achilles tendon tissue was harvested from 6 rats for gross observation, histological observation, and immunohistochemical staining observation, and real-time fluorescence quantitative PCR and Western blot were used to detect the expressions of HIF-lα gene and protein at different time points in 2 groups. The X-ray films were taken and histological examination was done at 10 weeks after operation to evaluate the formation of heterotopic ossification. ResultsDuring the experiment, 1 rat died in experimental group at 3 days after operation, and the other rats survived to the end of the experiment. Gross and histological staining showed that the Achilles tendon had no obvious change, with normal tendon structure in control group at each time point. In experimental group, atrophy and necrosis of Achilles tendon stump were observed, with infiltration of inflammatory cells; and the hardness of Achilles tendon tissue gradually increased with the time; there were a large number of irregular connective tissue and cartilage cells. When compared with control group, the HIF-lα mRNA and protein expressions were significantly increased in experimental group at each time point (P < 0.05). Immunohistochemical staining showed that HIF-lα was positive in experimental group. According to the results of X-ray films and histological examination at 10 weeks after operation, heterotopic ossification was found in experimental group, but no heterotopic ossification in control group. ConclusionThe expression of HIF-lα significantly increases at early stage of post-traumatic heterotopic ossification after Achilles tenotomy, suggesting that the local hypoxia microenvironment plays an important role in the pathogenesis of heterotopic ossification.
ObjectiveTo explore the value of matrix metalloproteinase 9 (MMP-9) in predicting the occurrence of heterotopic ossification by observing the expression of MMP-9 in heterotopic ossification of the early trauma rat model. MethodsA total of 132 male Sprague Dawley rats, aged 4-5 weeks, weighing (135.0±6.5) g, were randomly divided into experimental group and control group (n=66). In experimental group, the Achilles tendon was cut off and clamped to prepare heterotopic ossification model; in control group, only Achilles tendon was exposed by making a incision. The general condition of the rats was observed after operation; at 2, 3, 4, 5, 6, 7, and 8 days after operation, the Achilles tendon tissue was harvested for gross observation, histological observation, and immunohistochemical staining observation; the serum and Achilles tendon tissue were harvested to detect the expressions of MMP-9 protein and mRNA by ELISA and RT-PCR. The X-ray films at 5 and 10 weeks and histological examination at 10 weeks after operation were used to observe heterotopic ossification. ResultsAll rats survived to the end of the experiment. The Achilles tendon had no significant change in control group at each time point, showing normal tendon structure. In experimental group, the hardness of Achilles tendon tissue gradually increased with the time; there were a large number of irregular connective tissue and cartilage cells; and immunohistochemical staining for MMP-9 was positive results. The MMP-9 protein and mRNA expression levels of experimental group were significantly higher than those of the control group at each time point (P < 0.05). MMP-9 protein and mRNA expression levels of experimental group showed an increasing tendency (P < 0.05). According to the results of X-ray films and histological observation, heterotopic ossification occurred at 10 weeks after operation in experimental group, but no heterotopic ossification was observed in control group. ConclusionIn early heterotopic ossification of rat Achilles tendon, the expression of MMP-9 increases significantly, indicating that it has reference significance in predicting heterotopic ossification.
Objective To evaluate the incidence of heterotopic ossification (HO) after single-level Bryan cervical artificial disc replacement, and to identify the relationship between HO and the effectiveness. Methods The cl inical data of 48 patients undergoing single-level Bryan cervical artificial disc replacement between October 2005 and October 2007 were reviewedretrospectively. There were 27 males and 21 females with an average age of 40.5 years (range, 33-51 years), including 8 cases of cervical myelopathy, 27 cases of nerve root cervical spondylosis, and 13 cases of mixed cervical spondylosis with an average disease duration of 10.3 months (range, 2-14 months). The involved segments included C3, 4 in 3 cases, C4, 5 in 6 cases, C5, 6 in 30 cases, and C6, 7 in 9 cases. The outcomes were evaluated using Visual Analogue Scale (VAS) score, the neck disabil ity index (NDI), and cervical range of motion (ROM). According to patients with or without HO, 48 patients were divided into 2 groups (HO group and no HO group). VAS score, NDI, and cervical ROM were compared between 2 groups at 1, 2, 3, and 4 years after operation. Results No severe complication occurred during and after operation in all patients. Forty-eight patients were followed up 48-72 months (mean, 56.6 months). VAS score and NDI were significantly improved when compared with preoperative values at all time points (P lt; 0.05); except at 3 days after operation, no significant difference was found in cervical ROM at the other time points when compared with preoperation (P gt; 0.05). Thirteen patients (27.08%) had HO at 4 years after operation, including 8 cases of grade 1, 3 cases of grade 2, and 2 cases of grade 3. There was no significant difference in VAS score, NDI, and cervical ROM between 2 groups at 1, 2, 3, and 4 years (P gt; 0.05). Conclusion The incidence of HO after single-level Bryan cervical artificial disc replacement is relatively high. However, HO has no effect on the cervical ROM and the effectiveness.
Objective To review the research progress of heterotopic ossification (HO) pathogenesis.Methods Recent articles about HO including the risk factors and pathogenesis were reviewed and comprehensively analyzed. Results The pathogenesis of HO is not completely understood, but the extracellular factors, signaling pathways, and transcription factors in the pathogenesis of HO are understood deeply, such as bone morphogenic protein, Smad signaling, and core binding factor α1/runt-related transcription factor 2, which are probably involved in HO. Furthermore, some related microRNAs are also probably involved in HO. Conclusion The pathogenesis of HO should be further investigated so as to lay a foundation for preventing and treating HO.
Objective To review the progress of the research on therelationship between the central nervous system injury and the heterotopic ossification. Methods The recent articles on the central nervous system injury and the heterotopic ossification were extensively reviewed, and the related clinical signs, symptoms, pathogenesis diagnosis, risk factors, prophylaxis, and treatment of the neurogenic heterotopic ossification were investigated. Results The possible mechanism for the neurogenic heterotopic ossification might involve the roles of thebone morphogenetic protein and the basic fibroblast growth factor, which were suggested as mediators in differentiation of the progenitor cells. Sonographic, serum creatine phosphokinase, and C-reactive protein were recommended as the useful screening tools for heterotopic ossification. Colchicine and rofecoxib could be used for the prophylaxis or treatment of heterotopic ossification. Conclusion The research on the neurogenic heterotopic ossification has achieved a great development but further studies in this field are still required.
ObjectiveTo explore the influence factors of anterior bone loss (ABL) after cervical disc arthroplasty (CDA) and effects of ABL on the clinical and radiographic outcomes.MethodsOne hundred and fifty-five patients who underwent single-level Prestige-LP CDA between January 2008 and December 2017 and met the inclusive criteria were enrolled in the study. Perioperative data of patients were collected. The Japanese Orthopaedic Association (JOA) score, Neck Disability Index (NDI), and the visual analogue scale (VAS) score were used for clinical outcomes evaluation. Radiographic parameters including cervical lordosis, C2-7 range of motion (ROM), disc angle, segmental ROM, and the lengths of the upper and lower endplates were assessed on the X-ray films. Device-related complications, including ABL, subsidence, radiographic adjacent segment pathology, and heterotopic ossification, were recorded. Univariate analysis was used to analyze the related factors, and logistic regression analysis was used to screen the influence factors. Patients were grouped according to whether ABL occurred after operation, and the differences in clinical and imaging evaluation parameters were compared.ResultsThere were 94 cases (60.6%) in the ABL group and 61 cases (39.4%) in the non-ABL group. Univariate analysis showed the significant differences in age, body mass index (BMI), and intraoperative blood loss between the two groups (P<0.05). However, there was no significant difference in gender, bone mineral density (T value), preoperative blood calcium level, preoperative blood phosphorus level, preoperative alkaline phosphatase level, operative segment, operative time, and follow-up time between the two groups (P>0.05). Multivariate analysis showed that the age and BMI were influence factors for ABL after CDA (P<0.05). The JOA score, NDI, and VAS score significantly improved in both groups at 3 months after operation (P<0.05), and the scores were further improved at last follow-up (P<0.05). There was no significant difference in JOA score, NDI, and VAS score between the two groups before and after operation (P>0.05). The preoperative cervical lordosis was significantly smaller in the ABL group than in the non-ABL group (t=−2.402, P=0.018). At last follow-up, the segmental ROM was significantly greater in the ABL group than in the non-ABL group (P<0.05), and the lengths of the upper and lower endplates were less in the ABL group than in the non-ABL group (P<0.05). No significant difference in the other radiographic parameters between the two groups were found (P>0.05). Prosthesis subsidence occurred in 5 cases (3.2%), including 3 cases in the ABL group and 2 cases in the non-ABL group; the difference between the two groups was not significant (P=1.000). Heterotopic ossification occurred in 67 cases (43.2%), including 32 cases in the ABL group and 35 cases in the non-ABL group; the difference between the two groups was significant (χ2=8.208, P=0.004). High-grade heterotopic ossification was detected in 26 cases (13 cases in the ABL group and 13 cases in the non-ABL group). Twenty-nine cases (18.7%) had radiographic adjacent segment pathology, including 15 cases in the ABL group and 14 cases in non-ABL group; the difference between the two groups was not significant (χ2=1.190, P=0.276).ConclusionThe incidence of ABL after CDA was relatively high, which mainly occurred within 3 months after operation, and no longer progressing with stable radiographic features after the first 12 months. Age and BMI were independent influence factors for ABL. ABL does not affect the clinical outcomes but may preserve more ROM of prostheses.
ObjectiveTo evaluate the mid-term effectiveness of arthrolysis and hinged external fixation for the treatment of stiff elbow caused by heterotrophic ossification.MethodsBetween January 2014 and December 2017, 11 patients with stiff elbow caused by heterotrophic ossification were admitted. There were 9 males and 2 females with an average age of 32 years (range, 14-48 years), and left side in 6 cases and right side in 5 cases. The cause of stiff elbow included humerus fracture in 5 cases, ulna fracture in 2 cases, fracture of capitulum radii in 1 case, dislocation of capitulum radii in 1 case, terrible triad of the elbow in 1 case, and soft tissue injury in 1 case. The disease duration ranged from 7 to 18 months (mean, 11 months). Preoperative active range of motion of elbow was (19.6±17.5)° and Mayo score was 34.1±9.7. All patients received the treatment of arthrolysis and debridement of heterotrophic ossification lesion combining hinged external fixator, and active and passive rehabilitation with the help of hinged external fixator. The hinged external fixators were removed after 2 months.ResultsAll patients were followed up 13-36 months (mean, 19.1 months). All incisions healed by first intention, and no complication of infection or nerve lesion occurred postoperatively. At last follow-up, the results of X-ray films showed that no heterotrophic ossification recurred. The active range of motion of elbow was (116.4±16.6)° and Mayo score was 93.2±7.8, showing significant differences when compared with preoperative ones (t=17.508, P=0.000; t=16.618, P=0.000).ConclusionThe application of arthrolysis and debridement of heterotrophic ossification lesion combining hinged external fixator can improve the elbow’s range of motion significantly and obtain a good mid-term effectiveness.
Objective To review the basic research and cl inical progress of elbow heterotopic ossification after injury. Methods The recent l iterature concerning heterotopic ossification of the elbow was reviewed. Results Heterotopic ossification was caused by variety of stimul i and conditions. The current methods of prevention and treatment were to improve surgical techniques, to reduce trauma and bleeding, to rinse the area with bone fragments with plenty of salt water, and to use non-steroidal anti-inflammatory drugs. Conclusion Once heterotopic ossification occurred, surgical treatment is unique treatment method, so emphasis is to prevent heterotopic ossification.
ObjectiveTo compare the efficacy of selective cyclooxygenase 2 (COX2) inhibitor and non-selective COX2 inhibitor drugs in prevention of heterotopic ossification in rats model so as to provide reference for clinical drugs selection of heterotopic ossification prevention. MethodsFifty male Sprague Dawley rats, 6 to 8 weeks old, weight (190.0±8.5) g, were selected; the right Achilles tendon was cut off to induce ectopic bone formation. The rats were randomly divided into 5 groups (n=10):on the 1st day after modeling, celecoxib was given in groups A[2 mg/(kg·d)] and B[10 mg/(kg·d)], indomethacin in groups C[(2 mg/(kg·d) and D[10 mg/(kg·d)], and 2 mL of saline in group E for 10 weeks. The general condition of rats was observed after operation. At 5 and 10 weeks after operation, X-ray films of the right lower limb were taken to observe new bone formation. At 10 weeks after operation, the right Achilles tendon tissue was harvested for histological observation. Based on X-ray and histological results, heterotopic ossification was assessed. Immunohistochemical staining was used to evaluate COX2 and bone morphogenetic protein 2 (BMP-2) expression levels in local Achilles tendon. ResultsDuring the experiment, 5 rats died (2 in group B, 1 in group C, and 2 in group D), the other rats survived to the end of the experiment. General observation of Achilles tendon tissue showed that the tendon tissue volume of group B was the smallest, with soft texture and no cartilage-like tissue; the tendon tissue volume of group E was the biggest, with hard texture and cartilage-like tissue. The incidence of heterotopic ossification was 80.0% (8/10), 25.0% (2/8), 88.9% (8/9), 50.0% (4/8), and 100% (10/10) in groups A-E respectively at 10 weeks after operation; significant differences were found between groups B, D and group E (P=0.002,P=0.023) and between groups B and C (P=0.015), but no significant difference was found among the other groups (P>0.05). COX2 expression level in groups B and D was significantly lower than that in group E (P<0.05), but no significant difference was found among the other groups (P>0.05); BMP-2 expression level in group B was significantly lower than that in groups A, C, and E (P<0.05), but no significant difference was found among the other groups (P>0.05). ConclusionCelecoxib at a dose of 10 mg/(kg·d) can effectively reduce the incidence of heterotopic ossification in rats.