Aflibercept combined with triamcinolone acetonide in the treatment of diabetic macular edema:optical coherence tomography and optical coherence tomography angiography

AIM:To analyze the relationship between optical coherence tomography(OCT)and OCT angiography(OCTA)imaging in patients with diabetic macular edema(DME)who are treated with a combination of aflibercept and triamcinolone acetonide(TA).METHODS:A total of 76 eyes newly diagnosed DME were included in this study.They were randomly assigned to receive either aflibercept or a combination of aflibercept and TA.Injections once a month for a total of three injections.Central macular thickness(CMT),number of hyperreflective foci(HRF),height of subretinal fluid(SRF),and area of foveal avascular zone(FAZ)were evaluated using OCT and OCTA at baseline and after each monthly treatment.RESULTS:Both groups showed improvement in best corrected visual acuity(BCVA)and reduction in macular edema after treatment,and the difference in BCVA between the two groups was statistically significant after each treatment(P<0.05).The difference in CMT between the two groups was statistically significant after the first two injections(P<0.01),but not after the third injection(P=0.875).The number of HRF(1mo:7.41±8.25 vs 10.86±7.22,P=0.027;2mo:5.33±6.13 vs 9.12±8.61,P=0.034;3mo:3.58±3.00 vs 6.37±5.97,P=0.007)and height of SRF(1mo:82.39±39.12 vs 105.77±42.26μm,P=0.011;2mo:36.84±10.02 vs 83.59±37.78μm,P<0.01;3mo:11.57±3.29 vs 45.43±12.60μm,P<0.01)in combined group were statistically significant less than aflibercept group after each injection,while the area of FAZ showed no significant change before and after treatment in both groups.CONCLUSION:The combination therapy of aflibercept and TA shows more significant effects on DME eyes with decreased HRF and SRF.However,both aflibercept and combination therapy show no significant change in the area of FAZ.

Retinal capillary plexus in Parkinson’s disease using optical coherence tomography angiography

AIM:To evaluate the alterations of the retinal microvasculature and foveal avascular zone in patients with Parkinson’s disease(PD)using optical coherence tomography angiography(OCT-A).METHODS:A retrospective study of PD patients examined in the Ophthalmology Department of the General Hospital of Athens,“Georgios Gennimatas”from March 2021 to March 2022 was conducted.Totally 44 patients with PD were included and 18 healthy controls were examined,hence a total of 124 eyes were enrolled in the study.The foveal and parafoveal superficial and deep capillary plexus vascular density(fSCP-VD,fDCP-VD,pSCP-VD,pDCP-CD)and foveal avascular zone(FAZ)were quantified with OCTA.Optical coherence tomography(OCT)was used to measure macular thickness.Our statistical analysis was conducted by using a mixed effect linear regression model.RESULTS:After adjustment for age and gender,the mean parafoveal superficial capillary plexus vascular density(pSCP-VD)and mean parafoveal deep capillary plexus vascular density(pDCP-VD)were significantly decreased in individuals with PD(P<0.001 in both)by-2.35(95%CI-3.3,-1.45)and-7.5(95%CI-10.4,-4.6)respectively.fSCP-VD and fDCP-VD didn’t approach statistical significance.The FAZ area and perimeter were significantly decreased(P<0.001 in both)by-0.1 mm^(2)(95%CI-0.13,-0.07)and-0.49 mm^(2)(95%CI-0.66,-0.32)respectively.Circularity didn’t approach statistical significance.Central retinal thickness(CRT)was significantly decreased in individuals with PD(P<0.001)by-23.1μm(95%CI-30.2,-16)and temporal retinal thickness(TRT)was decreased(P=0.025)by-11μm(95%CI-22,-1.5)while nasal retinal thickness(NRT)only approached statistical significance(P=0.066).CONCLUSION:The mean pSCP-VD,pDCP-VD,CRT and TRT are significantly decreased and FAZ is altered in individuals with PD.These findings can be potentially used as biomarkers for the diagnosis and evaluation of early PD.

Clinical Value of ABCB1 and PAI-1 Gene Polymorphisms in Predicting Glucocorticoid-induced Adverse Reactions in Nephrotic Syndrome Patients

Objective Glucocorticoid(GC)-induced adverse reactions(ARs)have been extensively studied due to their potential impact on patients’health.This study aimed to examine the potential correlation between two polymorphisms[adenosine triphosphate-binding cassette B1(ABCB1)C3435T and plasminogen activator inhibitor-1(PAI-1)4G/5G]and various GC-induced ARs in nephrotic syndrome(NS)patients.Methods In this study,513 NS patients who underwent GC treatment were enrolled.Then,the patients were divided into two groups based on ABCB1 C3435T and PAI-14G/5G genotyping,and intergroup comparisons of clinicopathological data and GC-induced ARs were performed.Univariate and multivariate logistic analyses were subsequently conducted to identify potential risk factors for GC-induced ARs,and a nomogram was subsequently established and validated via the area under the ROC curve(AUC),calibration curve and decision curve analysis(DCA).Results We identified ABCB1 C3435T as an independent risk factor for the development of steroid-associated avascular necrosis of the femoral head(SANFH)(OR:2.191,95%CI:1.258–3.813,P=0.006)but not as a risk factor for the occurrence of steroid diabetes mellitus(S-DM).On the other hand,PAI-14G/5G was identified as an independent risk factor for the development of both SANFH(OR:2.198,95%CI:1.267–3.812,P=0.005)and S-DM(OR:2.080,95%CI:1.166–3.711,P=0.013).Notably,no significant correlation was found between the two gene polymorphisms and other GC-induced ARs.In addition,two nomograms were established and validated to demonstrate strong calibration capability and clinical utility.Conclusion Assessing ABCB1 C3435T and PAI-14G/5G before steroid treatment in NS patients could be useful for identifying patients at a high risk of developing SANFH and S-DM.

Bilateral Avascular Necrosis of the Femoral Head in Renal Transplant Recipient: A Case Report

Osteoarticular complications are common after renal transplantation. The complications may result from the bone condition prior to transplantation or the iatrogenic effects of the treatments administered. These complications lead to significant morbidity and mortality, in addition to chronic pain and functional impairment. We report the clinical case of bilateral avascular necrosis (AVN) of the femoral head in a kidney transplant recipient. Clinical Case: 53-year-old male with a history of chronic hypertension. He underwent chronic hemodialysis for 12 months and was treated with Entecavir for chronic hepatitis B. The patient received a kidney transplant from a non-related living donor. Induction therapy included Thymoglobulin along with tapered corticosteroids, reaching a dose of 5 mg/day after 3 months, Mycophenolate mofetil (2 g/day), and Tacrolimus adjusted based on residual levels. There was good recovery of renal graft function. After six months, the patient reported bilateral hip pain and functional impairment of both lower limbs. Pelvic X-rays showed signs suggestive of bilateral AVN of the femoral heads. The diagnosis was confirmed by MRI. The patient underwent right hip drilling and total left hip replacement (THR). A right THR was performed a year later. Conclusion: AVN constitutes a frequent cause of morbidity and mortality after RT. The pathophysiology of osteonecrosis remains complex and multifactorial. We emphasize the importance of conducting a thorough assessment of bone health in patients both before and after RT.

Bilateral pericapsular end nerve blocks for steroid-induced avascular necrosis following COVID-19 infection requiring bilateral total hip replacement

BACKGROUND Osteonecrosis or avascular necrosis(AVN)of the hip was one of the dreaded complications of coronavirus disease 2019(COVID-19),which emerged in patients who received steroid therapy.Corticosteroids have been a mainstay in the treatment protocol of COVID-19 patients.Popular corticosteroid drugs used in patients suffering from COVID-19 were intravenous(IV)or oral dexamethasone,methylprednisolone or hydrocortisone.The use of such high doses of corticost-eroids has shown very positive results and has been lifesaving in many cases.Still,long-term consequences were drug-induced diabetes,osteoporosis,Cushing syndrome,muscle wasting,peripheral fat mobilization,AVN,hirsutism,sleep disturbances and poor wound healing.A significant number of young patients were admitted for bilateral total hip replacements(THR)secondary to AVN following steroid use for COVID-19 treatment.AIM To assess the efficacy of bilateral pericapsular end nerve group(PENG)blocks in patients posted for bilateral THR post-steroid therapy after COVID-19 infection and assess the time taken to first ambulate after surgery.METHODS This prospective observational study was conducted between January 2023 and August 2023 at Care Hospitals,Hyderabad,India.Twenty young patients 30-35 years of age who underwent bilateral THR were studied after due consent over 8 months.All the patients received spinal anaesthesia for surgery and bilateral PENG blocks for postoperative analgesia.RESULTS The duration of surgery was 2.5 h on average.Seventeen out of twenty patients(85%)had a Visual Analog Score(VAS)of less than 2 and did not require any supplementation.One patient was removed from the study,as he required re-exploration.The remaining two patients had a VAS of more than 8 and received IV morphine post-operatively as a rescue analgesic drug.Fifteen out of seventeen patients(88.2%)could be mobilized 12 h after the procedure.CONCLUSION Osteonecrosis or AVN of the hip was one of the dreaded complications of COVID-19,which surfaced in patients who received steroid therapy requiring surgical intervention.Bilateral PENG block is an effective technique to provide post-operative analgesia resulting in early mobilization and enhanced recovery after surgery.

股骨头坏死临床诊疗规范

股骨头坏死（osteonecrosis of the femoral head,ONFH）又称缺血性股骨头坏死（avascular necrosis,AVN）,系骨科常见且难治性疾病。由于非创伤性ONFH病理机制尚未完全明了,因此从源头上防治此病尚不可能,但目前国内外专家对诊疗主要方面存在共识[1-3],国内发表的专家建议（2007）[4]和专家共识（2012）[5]对ONFH规范化的诊疗起了重要作用。

股骨头无菌性坏死(综述)

股骨头无菌性坏死(avascular necrosis of the femoral head,ANF)是导致股骨头无菌性、缺血性坏死,使股骨头塌陷变形并最终导致继发性骨关节炎的疾患。

成人股骨头缺血性坏死的螺旋CT诊断分析

股骨头缺血坏死（avascular necrosis of femoral head,ANFH）是临床常见的骨科疾病,病情进展常导致髓关节畸形和功能障碍,约60%的患者最终双侧受累。早期的诊断和治疗对改善患者预后有积极意义。

Osteonecrosis of the femoral head: An update in year 2012

Osteonecrosis is a phenomenon involving disruption to the vascular supply to the femoral head, resulting in articular surface collapse and eventual osteoarthritis. Although alcoholism, steroid use, and hip trauma remain the most common causes, several other etiologies for osteonecrosis have been identified. Basic science research utilizing animal models and stem cell applications continue to further elucidate the pathophysiology of osteonecrosis and promise novel treatment options in the future. Clinical studies evaluating modern joint-sparing procedures have demonstrated significant improvements in outcomes, but hip arthroplasty is still the most common procedure performed in these affected younger adults. Further advances in joint-preserving procedures are required and will be widely studied in the coming decade.

Microvascular changes after conbercept therapy in central retinal vein occlusion analyzed by optical coherence tomography angiography

AIM: To investigate microvascular changes in eyes with central retinal vein occlusion(CRVO) complicated by macular edema before and after intravitreal conbercept injection and evaluate correlations between these changes and best-corrected visual acuity(BCVA) and retinal thickness. METHODS: Twenty-eight eyes of 28 patients with macular edema caused by CRVO were included in this retrospective study. All patients received a single intravitreal conbercept injection to treat macular edema. BCVA and the results of optical coherence tomography angiography(OCTA) automatic measurements of the vessel density in the superficial(SCP) and deep retinal capillary plexus(DCP), the foveal avascular zone(FAZ) area, the FAZ perimeter(PERIM), the vessel density within a 300-μm wide ring surrounding the FAZ(FD-300), the acircularity index(AI), the choriocapillaris flow area, and retinal thickness were recorded before and at one month after treatment and compared with the results observed in age-and sexmatched healthy subjects. RESULTS: The vessel density in the SCP and DCP, the FD-300, and the flow area of the choriocapillaris were allsignificantly lower in CRVO eyes than in healthy eyes, while the AI and retinal thickness were significantly higher(all P<0.05). After treatment, retinal thickness was significantly decreased, and the mean BCVA had markedly improved from 20/167 to 20/65(P=0.0092). The flow area of the choriocapillaris was also significantly improved, which may result from the reduction of shadowing effect caused by the attenuation of macular edema. However, there were no significant changes in SCP and DCP vessel density after treatment. The flow area of the choriocapillaris at baseline was negatively correlated with retinal thickness.CONCLUSION: OCTA enables the non-invasive, layerspecific and quantitative assessment of microvascular changes both before and after treatment, and can therefore be used as a valuable imaging tool for the evaluation of the follow-up in CRVO patients.

Modified porous tantalum rod technique for the treatment of femoral head osteonecrosis

AIM: To study a modified porous tantalum technique for the treatment of osteonecrosis of the femoral head.METHODS: The porous tantalum rod was combined with endoscopy,curettage,autologous bone grafting and use of bone marrow aspirates from iliac crest aspiration in 49 patients(58 hips) with a mean age of 38 years.The majority of the patients had idiopathic osteonecrosis,followed by corticosteroid-induced osteonecrosis.Thirtyeight hips were of Steinberg stage Ⅱ disease and 20 hips were of stage Ⅲ disease.Patients were followed for 5 years and were evaluated clinically with the Merle D'Aubigne and Postel score and radiologically.The primary outcome of the study was survival based on the conversion to total hip arthroplasty(THA).Secondary outcomes included deterioration of the osteonecrosis to a higher disease stage at 5 years compared to the preoperative period and identification of factors that were associated with survival.The Kaplan-Meier survival analysis was performed to evaluate the survivorship ofthe prosthesis,and the Fisher exact test was performed to test associations between various parameters with survival.RESULTS: No patient developed any serious intraoperative or postoperative complication including implant loosening or migration and donor site morbidity.During the 5-year follow up,1 patient died,7 patients had disease progression and 4 hips were converted to THA.The 5-year survival based on conversion to THA was 93.1% and the respective rate based on disease progression was 87.9%.Stage Ⅱ disease was associated with statistically significant better survival rates compared to stage Ⅲ disease(P = 0.04).The comparison between idiopathic and non-idiopathic osteonecrosis and between steroid-induced and non-steroid-induced osteonecrosis did not showed any statistically significant difference in survival rates.The clinical evaluation revealed statistically significantly improved Merle d'Aubigne scores at 12 mo postoperatively compared to the preoperative period(P < 0.001).The mean preoperative Merle d'Aubigne score was 13.0(SD: 1.8).The respective score at 12 mo improved to 17.0(SD: 2.0).The 12-mo mean score was retained at 5 years.CONCLUSION: The modified porous tantalum rod technique presented here showed encouraging outcomes.The survival rates based on conversion to THA are the lowest reported in the published literature.

A Rabbit Model of Hormone-induced Early Avascular Necrosis of the Femoral Head

Objective To establish an experimental model of early stage avascular necrosis of the femoral head （ANFH） caused by corticosteroid in adult rabbits and to observe the pathological changes with various imaging techniques. Methods ANFH was induced by a combination of hypersensitivity vasculitis caused by injection of horse serum and subsequent administration of a high dose of corticosteroid. The pathological changes were detected with digital radiography （DR）, computed tomography （CT）, magnetic resonance imaging （MRI）, ink artery infusion angiography, hematoxylin-eosin staining, and immunohistochemistry. Results The imageological and pathological changes corresponded to the clinical characteristics of early stage ANFH. DR showed bilaterally increased bone density, an unclear epiphyseal line, and blurred texture of cancellous bone. CT showed spot-like low-density imaging of cancellous bone, thinner cortical bone, osteoporosis, and an unclear epiphyseal line. MR! showed bone marrow edema and spot-like high signals in T2-weighted imaging in cancellous bone. Ink artery infusion angiography showed fewer obstructed blood vessels in the femoral head. HE staining of pathological sections showed fewer trabeculae and thin bone, an increased proportion of empty osteocyte lacunae, decreased hematopoiesis, thrombosis, and fat cell hypertrophy. Immunohistochemistry showed attenuated expression of vascular endothelial growth factor in osteoblasts and chondrocytes, and on the inner membrane of blood vessels. Conclusion Experimental rabbit model of early stage ANFH caused by corticosteroid can be successfully established and provide the foundation for developing effective methods to treat early stage ANFH.

Vascular endothelial growth factor for the treatment of femoral head osteonecrosis: An experimental study in canines

AIM To evaluate the treatment of osteonecrosis of the femoral head(ONFH) with the use of vascular endothelial growth factor(VEGF).METHODS In 30 mature beagles(6 groups of 5 beagles) ONFH was induced cryosurgically and one of the following solutions was administered locally in the femoral head(FH) in each group: Single injection of 500 μg VEGF(t-VEGFμ group); single injection of 500 ng VEGF(t-VEGFn group); continuous delivery of 500 μg VEGF through osmotic micropump(t-VEGFpump-μ group); continuous delivery of 500 ng VEGF through osmotic micropump(t-VEGFpump-n group); single injection of 0.9% sodium chloride(t-NS group), while one group that served as control group did not receive any local solution(No-t group). FHs were retrieved 12 wk postoperatively, underwent decalcification and hematoxylin/eosin and toluidine blue staining. In two canines per group, one half of FH was processed without decalcification and stained with modified Masson Trichrome. Histological sections were observed by light microscopy and measured with a semi-automatized bone histomorphometry system and Bone Volume/Total Volume(BV/TV), Marrow Volume/Total Volume(MaV/TV), and Trabecular Thickness(TbT h) were assessed. Standard and robust tests(Welch, Brown Forsythe) of analysis of variance along with multiple comparisons, were carried out among the categories.RESULTS The untreated(No-t) group had signs of osteonecrosis, whereas the VEGF groups revealed reversal of the osteonecrosis. Statistical analysis of the decalcified specimens revealed a significantly better BV/TV ratio and a higher Tb Th between the VEGF treatment groups(except the t-VEGFn group) and the No-t group or the control t-NS group. Single dose 500 μg VEGF group had significantly better BV/TV ratio and higher Tb Th when compared to the No-t group(50.45 ± 6.18 vs 29.50 ± 12.27, P = 0.002 and 151.44 ± 19.07 vs 107.77 ± 35.15, P = 0.161 respectively) and the control t-NS group(50.45 ± 6.18 vs 30.9 ± 6.67, P = 0.004 and 151.44 ± 19.07 vs 107.14 ± 35.71, P = 0.151 respectively). Similar differences were found for the prolonged VEGF delivery/pump groups of 500 μg and 500 ng. Analysis of the totality of specimens(decalcified/non-decalcified) enhanced the aforementioned differences and additionally revealed significant differences in the comparison of the TbT h.CONCLUSION In an experimental model of ONFH in canines it was found that local treatment with VEGF leads to bone tissue remodeling and new bone formation.

Experimental Study of Vascular Endothelial Growth Factor Gene Therapy for Avascular Necrosis of the Femoral Head

To explore a new method for the therapy of the avascular necrosis of the femoral head, the recombinant plasmid pCD-hVEGF 165 was mixed with collagen and was implanted in the necrotic femoral head The expression of vascular endothelial growth factor (VEGF) was detected by RNA dot hybridization and immunohistochemical method The repair of the femoral head was observed by histological method The results showed that the expression of VEGF was detectable in the femoral head treated with VEGF gene Angiogenesis in these femoral heads was more abundant than the control Bone repairing was augmented in the femoral head treated with VEGF gene The results suggest that angiogenesis in bone tissue could be augmented by gene transfection of VEGF and bone repairing would be accelerated accordingly

Automatic segmentation of foveal avascular zone based on adaptive watershed algorithm in retinal optical coherence tomography angiography images

The size and shape of the foveal avascular zone(FAZ)have a strong positive correlation with several vision-threatening ret inovascular diseases.The identification,segmentation and analysis of FAZ are of great significance to clinical diagnosis and treatment.We presented an adaptive watershed algorithm to automatically extract F AZ from retinal optical coherence tomography angiography(OCTA)images.For the traditional watershed algorithm,"over-segmentation"is the most common problem.FAZ is often incorrectly divided into multiple regions by redundant"dams".This paper analyzed the relationship between the"dams"length and the maximum inscribed circle radius of FAZ,and proposed an adaptive watershed algorithm to solve the problem of"over-segmentation".Here,132 healthy retinal images and 50 diabetic retinopathy(DR)images were used to verify the accuracy and stability of the algorithm.Three ophthal-mologists were invited to make quan titative and qualitative evaluations on the segmentation results of this algorithm.The quantitative evaluation results show that the correlation coffi-cients between the automatic and manual segmentation results are 0.945(in healthy subjects)and 0.927(in DR patients),respectively.For qualitative evaluation,the percentages of"perfect segmentation"(score of 3)and"good segmentation"(score of 2)are 99.4%(in healthy subjects)and 98.7%(in DR patients),respectively.This work promotes the application of watershed algorithm in FAZ segmentation,making it a useful tool for analyzing and diagnosing eye diseases.

Microstructures and properties of cancellous bone of avascular necrosis of femoral heads

The aim of this study is to investigate microscopic structure and characterize cancellous bone of avascular necrosis of the femoral head （ANFH）. The rabbit model of the ANFH is established. The histopathologic features are studied successfully. The differences between the steroidinjection group （S.G.） and the controlled group （C.G.） are examined, including the weight of rabbits, the hematological examination and the three-dimensional stnactures. It is found that the plasma levels of cholesterol （CHO）, high-density lipoprotein （HDL） and low-density lipoprotein （LDL） in S.G. are lower than those in C.G. when the triglyceride （TG） increased in the S.G.; but the bone mineral content （BMC） and the structural model index （SMI） of the organ and tissue decreased significantly in S.G. Three-dimensional structures of the femoral head are obtained using micro-computed tomography （CT） scanning and the mechanical model is established to analyze the influences of these structural changes on the mechanical properties of the cancellous bone.

The process of retinal vascularization in retinopathy of prematurity after ranibizumab treatment in China

AIM: To explore the process of retinal vascularization and risk factors for retinopathy of prematurity(ROP) treated with intravitreal ranibizumab(IVR) as monotherapy.METHODS: Infants with type 1 ROP who received IVR as primary treatment from August 2014 to October 2016 at Peking University People’s Hospital’s Ophthalmology Department were included in the study. All eyes received 0.25 mg ranibizumab at initial treatment. Retinal vascularization was evaluated clinically. Potential risk factors were also recorded and examined.RESULTS: Retinal vascularization was completed in 126 eyes(62.7%), and retinal vascularization terminated in zone II and zone III with 16 eyes(7.9%) and 44 eyes(21.9%), respectively, after more than 1-year follow-up. In multivariate regression analysis, lower birth weight(BW), severity of ROP and repeated injections were found to be risk factors for peripheral avascular area(P<0.05). CONCLUSION: In our retrospective study, 29.8% of the ROP eyes treated with ranibizumab have peripheral avascular area at the last follow-up. Lighter BW and the severity of ROP are risk factors. Furthermore, repeated injections also increase the risk of retinal peripheral avascular area remaining in ROP patients.

Superficial foveal avascular zone area changes before and after idiopathic epiretinal membrane surgery

To investigate the foveal morphological changes and foveal avascular zone（FAZ）area before and after epiretinal membrane（ERM）surgery.Twenty-two eyes with treatmentnaive ERM were included in this retrospective study.The central foveal thickness（CFT）and FAZ area were measured via swept-source optical coherence tomography（SS-OCT）and OCT angiography pre-and postoperatively.The unaffected fellow eyes were used as controls.The preoperative superficial FAZ area was significantly smaller in patients（0.08±0.04 mm^2）than in controls（0.33±0.09 mm^2;P〈0.001）.The postoperative superficial FAZ（0.12±0.06 mm^2）area was significantly greater than the preoperative area（P〈0.001）.The preoperative superficial FAZ area was strongly negatively correlated with CFT（P〈0.001,rho=-0.763）.ERM induced significant foveal morphological changes and reduction of the superficial FAZ area.Foveal thickness was restored and FAZ area increased postoperatively.However,the process is rather slow and the recovery is incomplete.

BASIC FIBROBLAST GROWTH FACTOR GENE TRANSFECTION TO ENHANCE THE REPAIR OF AVASCULAR NECROSIS OFTHE FEMORAL HEAD

Objective To explore a new method for the therapy of avascular necrosis of the femoral head. Method The recombinant plasmid pCD-rbFGF was mixed with collagen and was implanted in the necrotic femoral head. Expression of basic fibroblast growth factor (bFGF) was examined by RT-PCR and immunohistochemical method. Re-pair of the femoral head was observed by histological and histomorphometric analysis. Result Expression of bFGF was detected in the femoral head transfected with bFGF gene, indicating significant increase of angiogenesis 2 weeks after gene transfection and increased new bone formation 8 weeks after gene transfection on histom-orphometric analysis (P< 0.01). Conclusion Transfection of bFGF gene enhances bone tissue angiogenesis. Repair in osteonecrosis would be accelerated accordingly.

Prevention of Femoral Head Deformity after Ischemic Necrosis Using Ibandronate Acid and Growth Factor in Immature Pigs

Background: Femoral head deformity is the most severe sequela of ischemic necrosis in skeletally immature patients. Development of severe deformity shortens useful survival time of the joint due to the appearance of early degenerative changes. Preservation of the trabecular architecture through inhibition of osteoclastic bone resorption may minimize the development of the deformity in an animal model of ischemic necrosis of the femoral head. Aims: To determine if a highly potent antiabsorptive agent, ibandronate, would inhibit bone resorption during necrotic femoral head repair to avoid subsequent flattening and deformity, to determine if the use of platelet-rich plasma stimulates bone repair and neovascularization of the damaged femoral head, and to evaluate if the combination of both therapies can preserve the femoral head while stimulating new bone formation in an animal model of ischemic necrosis. Methods: Ischemic necrosis of the femoral head was induced by surgical ligature of the circumflex vessels in 10 Landrace pigs. The animals were divided into four different groups and were administered ibandronate acid, platelet-rich plasma, or both. The contralateral, untreated femoral heads with surgical ligature of the circumflex vessels served as the control group. All animals were killed three months after surgery and the femoral head was evaluated both radiographically and histologically. The femur length was measured on radiographs and compared among the groups.Results: Final femoral length was significantly longer in the group treated with a combination of both therapies (platelet-rich plasma-ibandronate acid) compared to the others groups, with a significant difference between groups. The histological findings showed increased osteoblastic activity and thickened trabiculae, a higher rate of neovascularization, and focal hyperplasia greater bone resorption and neovascularization. Only slight changes (femoral length) were observed in the animals that received platelet-rich plasma in situ favoring revascularization that was, however, only seen in the first months of administration. Conclusions: Radiographic and histological studies showed that a combination of both therapies (platelet-rich plasma and ibandronate acid) preserved the trabecular architecture and prevented femoral head deformity in the early phase of ischemic necrosis repair in immature pigs, coinciding with reports by other authors. Clinical Relevance: These findings support the concept that a combination of antiresorptive and anabolic agents can significantly improve bone healing and decrease femoral head deformity following ischemic necrosis in the fragmentation stage. Further studies would be necessary to determine the optimal dose and longterm effectiveness for the use in pediatric patients.