Prevalence and Risk Factors of Osteonecrosis of the Jaw in Patients with Bisphosphonate Exposure in Casablanca, Morocco: An Observational Study

Objective: To study the prevalence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) and to determine the risk factors associated with the occurrence of this pathology. Method: An observational retrospective study was conducted in the Department of Oncology, Rheumatology, and Maxillofacial Surgery of Ibn Rochd University Hospital, Casablanca. The study utilized complete medical records from 2014 to 2022 and included consultations of patients receiving bisphosphonates (BPs) in July and September 2022. Statistical analysis was performed using SPSS version 16.0. Results: Our study population comprised 104 patients, of whom 91% were women and 49% were over 65 years old. Seventy-two percent of patients had a general pathology. Among them, 64 patients were treated with zoledronate, 43 with alendronate, and the remainder with risedronate, ibandronate, and pamidronate. The most common indications for treatment were bone metastasis following breast cancer (29.8%) and osteoporotic fractures (19.2%). Sixty-seven patients received intravenous (IV) treatment;only 10.5% exhibited good oral health. Fifty percent of patients underwent dental treatment, primarily tooth extractions. Osteonecrosis of the jaw (ONJ) was diagnosed in 1.9% of patients, predominantly in stages 1 and 2. Conclusion: Second and third-generation bisphosphonates are more strongly associated with the development of ONJ. Risk factors include monthly IV administration, poor oral health, comorbidities such as diabetes, medications like corticosteroids, invasive dental procedures, and not only oncological conditions but also rare indications such as bone algodystrophy. Nevertheless, our observed prevalence of 1.9% aligns with international rates ranging from 0.8% to 12%. However, most of the studies that have been carried out have been retrospective studies with insufficient numbers of patients. Further prospective epidemiological studies based on standardized protocols with rigorous and appropriate follow-up over several years are essential to determine the exact prevalence of ONJ.

Establishment and assessment of rodent models of medication-related osteonecrosis of the jaw(MRONJ)

Medication-related osteonecrosis of the jaw(MRONJ)is primarily associated with administering antiresorptive or antiangiogenic drugs.Despite significant research on MRONJ,its pathogenesis and effective treatments are still not fully understood.Animal models can be used to simulate the pathophysiological features of MRONJ,serving as standardized in vivo experimental platforms to explore the pathogenesis and therapies of MRONJ.Rodent models exhibit excellent effectiveness and high reproducibility in mimicking human MRONJ,but classical methods cannot achieve a complete replica of the pathogenesis of MRONJ.Modified rodent models have been reported with improvements for better mimicking of MRONJ onset in clinic.This review summarizes representative classical and modified rodent models of MRONJ created through various combinations of systemic drug induction and local stimulation and discusses their effectiveness and efficiency.Currently,there is a lack of a unified assessment system for MRONJ models,which hinders a standard definition of MRONJ-like lesions in rodents.Therefore,this review comprehensively summarizes assessment systems based on published peer-review articles,including new approaches in gross observation,histological assessments,radiographic assessments,and serological assessments.This review can serve as a reference for model establishment and evaluation in future preclinical studies on MRONJ.

Oral microbiota and host innate immune response in bisphosphonate-related osteonecrosis of the jaw

Bacterial biofilms have emerged as potential critical triggers in the pathogenesis of bisphosphonate（BP）-related osteonecrosis of the jaw（ONJ） or BRONJ. BRONJ lesions have shown to be heavily colonized by oral bacteria, most of these difficult to cultivate and presents many clinical challenges. The purpose of this study was to characterize the bacterial diversity in BRONJ lesions and to determine host immune response. We examined tissue specimens from three cohorts（n530）; patients with periodontal disease without a history of BP therapy（Control, n510）, patients with periodontal disease having history of BP therapy but without ONJ（BP, n55） and patients with BRONJ（BRONJ, n515）. Denaturing gradient gel electrophoresis of polymerase chain reaction（PCR）-amplified 16 S r RNA gene fragments revealed less bacterial diversity in BRONJ than BP and Control cohorts. Sequence analysis detected six phyla with predominant affiliation to Firmicutes in BRONJ（71.6%）, BP（70.3%） and Control（59.1%）. Significant differences（P,0.05） in genera were observed, between Control/BP, Control/BRONJ and BP/BRONJ cohorts. Enzyme-linked immunosorbent assay（ELISA）results indicated that the levels of myeloperoxidase were significantly lower, whereas interleukin-6 and tumor necrosis factor-alpha levels were moderately elevated in BRONJ patients as compared to Controls. PCR array showed significant changes in BRONJ patients with downregulation of host genes, such as nucleotide-binding oligomerization domain containing protein 2, and cathepsin G, the key modulators for antibacterial response and upregulation of secretory leukocyte protease inhibitor, proteinase 3 and conserved helix–loop–helix ubiquitous kinase. The results suggest that colonization of unique bacterial communities coupled with deficient innate immune response is likely to impact the pathogenesis of ONJ.

Prevention and treatment of osteonecrosis of the jaw

Purpose: to update recommendations for the prevention and treatment of osteonecrosis of the jaw in patients on bisphophonate therapy. Osteonecrosis of the jaw is a rare and serious complication of bisphosphonate therapy. Also, it is one of the important and growing clinical public health issues, because biphosphonates are now more commonly used than before. Bisphophonates are primarly used in the treat-ment of cancer-related conditions such as bone metastases, hypercalcemia, lytic skeletal lesions. More recently, bisphophonate has been approved for the management of osteoporosis. The etiology and pathogenesis remain unknown, however, two important risk factors have been identified, i.e. the potency and length of bisphos- phonate use, and recent dental intervention. Recommendations: prior to the introduction of bisphosphonate therapy, all patients should undergo complete dental examination, any active oral cavity infec-tion should be treated and the potential sites of new infection removed. During bisphosphonate therapy, patients should strictly comply with oral hygiene and avoid any invasive procedure of the oral cavity.

Bisphosphonate-related osteonecrosis of the jaws: A report on 30 cases

Aim: To report a series of thirty cases of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Material and Methods: For 30 patients with BRONJ, gender, age, underlying diagnosis, type of bisphosphonate (BP), administration route and duration, location and stage of osteonecrosis, symptoms and oral health status, radiological findings of the jaws, treatment and outcome, were recorded. Results: Underlying diagnoses in the series (12 male;18 female;mean age 70.50 ± 9.62) were: 12 multiple myeloma, 7 breast cancer, 3 prostate carcinoma, 1 kidney/lung/ bladder/mediastinal cancer, 1 chronic lymphocytic leukemia, 1 osteoporosis, 1 palatal osteosarcoma + osteoporosis, 1 non-Hodgkin’s lymphoma. Forty-seven osteonecrotic lesions were detected;30 localized in the mandible,17 inthe maxilla;trigger events were tooth extraction in 31 cases (66%), periodontal disease in 4 (8.50%), incongruous dentures in 3 (6.40%), perimplantitis in 1 (2.10%), unknown in 8 (17%). Twenty-nine patients had received treatment using amino bisphosphonates (25 zoledronate, 2 pamidronate, 2 alendronate) and 1 clodronate;the administration route was intravenous in 27 patients, oral in 2 and intramuscular in 1. Mean number of doses to bone exposure for patients was 34.11 for zoledronate, 50.50 for pamidronate, 146 for alendronate, and 500 for clodronate. Among statistical data the only significant finding was that panoramic dental radiography gave no concrete support for diagnosis of ONJ lesions (p ≤ 0.04). Conclusions: Our case series reflects literature data. We emphasize the insufficient role of panoramic radiography to study osteonecrotic lesions and the role of poor oral hygiene.

Photodynamic Therapy for Medication-Related Osteonecrosis of the Jaws: A Case Report

Medication-related osteonecrosis of the jaws (MRONJ) is a relatively new disease. MARX reported first cases in 2003. MRONJ relates to oral and parenteral bisphosphonates as well as to the so-called target cancer therapies but the list of medications only grows. Although MRONJ is a relatively rare condition, it can be associated to significant morbidity with feeding limitations and intense pain. More severe cases can lead to potentially life-threatening infections. Every patient initiating bisphosphonate and/or target cancer therapy must visit a dentist before starting medication because preventive measures for MRONJ are much more effective compared to surgical management of the lesions. Surgical resolution can be especially difficult to obtain in the coexistence of certain complication factors like wider bone exposures, history of nitrogen containing bisphosphonates use (mainly zolendronate) and immunodeficiency. Recently, researchers have given attention to laser therapy associated to photosensitive agents as a possible option to management of some MRONJ lesions. Our case report demonstrates the use of photodynamic therapy in a denosumab related lesion in the mandible. It seems that denosumab related lesions are more amenable to treatment and total resolution because of the marked differences between its chemical and metabolic characteristics when compared to bisphosphonates.

Osteonecrosis of the jaw in a patient taking once-yearly infusion of zoledronic acid for osteopenia

Osteonecrosis of the jaw (ONJ) is an adverse effect of nitrogen-containing bisphosphonates. Advancing age, intravenous administration of zoledronic acid (ZOL), history of dento-alveolar surgery, and concomitant systemic diseases such as diabetes are known as risk factors for developing ONJ. However, despite numerous studies, the exact pathophysiology remains unclear and management strategies are largely anecdotal. Once-yearly intravenously administered 5 mg ZOL was approved by the US Food and Drug Administration in 2007 for the treatment of osteoporosis and its efficacy with 3 year-regimen had been recently proven in preventing new clinical fracture. Although occurrences of ONJ have been reported to be rare with this drug administration, available data is very limited and long-term outcomes are lacking. We present a case of ONJ identified in an osteopenic patient with an intermittent but long standing sore mouth related to exposed mandibular bone. Once-yearly infusion of zoledronic acid used in the treatment of osteopenia may contribute to the spontaneous development of ONJ, especially in those presenting with multiple comorbidity factors. This report suggests the importance of health care professionals keeping abreast of new developments in this area and providing appropriate information to their patients.

Jaw Osteonecrosis in Patients Receiving Oral Bisphosphonates Therapy

We describe the cases of three patients, under the care of the rheumatology service, who presented with osteonecrosis of the jaw whist on oral bisphosphonate therapy. The first case is of a 74-year-old woman with a 12 year history of sero-negative inflammatory arthritis, having been on oral steroids for 11 years, Methotrexate for the preceding 6 years, and oral bisphosphonates for 9 years. Clinical and radiographic examination revealed extensive jaw necrosis. The second patient was a 72-year-old woman with temporal arteritis, on long term oral steroids, and oral bisphosphonates presenting with jaw osteonecrosis. The third case is of an 81-year-old lady with a diagnosis of Polymyalgia Rheumatica on reducing dose of prednisolone along with calcium and vitamin D3 and oral bisphosphonate therapy as part of steroid induced prophylaxis guidelines. On reviewing the literature regarding bisphosphonate-associated osteonecrosis of the jaw, there is indeed recognition of this occurring with oral bisphosphonates. However, this is far less common than with intravenous preparations. Reports to the UK MHRA regarding adverse reactions have shown 53 cases of osteonecrosis of the jaw associated with oral bisphosphonates, but this is thought to represent under-reporting. We suggest consideration of patient counselling and consent, and preventive dental work prior to initiation of oral bisphosphonate therapy.

Kinematics ofmandibular advancement devices(MADs):Why do some MADs move the lower jaw backward duringmouth opening?

Mandibular advancement devices(MADs)are widely used treatments for obstructive sleep apnea.MADs function by advancing the lower jaw to open the upper airway.To increase patient comfort,most patients allow the mouth to be opened.However,not all systems maintain the lower jaw in a forward position during mouth opening,which results in the production of a retrusion that favors the collapse of the upper airway.Furthermore,the kinematic behavior of the mechanism formed by the mandible-device assembly depends on jaw morphology.This means that,during mouth opening,some devices cause lower jaw protrusion in some patients,but cause its retraction in others.In this study,we report the behavior of well-known devices currently on themarket.To do so,we developed a kinematic model of the lower jawdevice assembly.Thismodelwas validated for all devices analyzed using a high-resolution camera system.Our results show that some of the devices analyzed here did not produce the correct behavior during patient mouth opening.

Surgical Treatment of Osteonecrosis of the Femoral Head Using Minimally Invasive Surgical Drilling and Cancellous Grafting at Brazzaville University Hospital

Introduction: Osteonecrosis of the femoral head (ONTF) is a debilitating condition. Several treatments have been proposed with controversial results. The aim of our study was to evaluate treatment by surgical drilling coupled with in situ cancellous grafting. Materials and methods: Our study was a case-control study conducted at Brazzaville University Hospital from 1st January 2018 to 31 December 2023. It compared two groups of patients with ONTF: non-operated (13 patients, 20 hips) and operated (22 patients, 35 hips). We used the visual digital scale (VDS) for pain assessment, the Merle D’Aubigne-Postel (MDP) scoring system for clinical and functional assessment, and the evolution of necrosis. Results: The group of non-operated patients had a mean age of 35.69 ± 3.4 years, no improvement in pain with an EVN above seven at the last recoil and a mean global MDP score falling from 12.7 before offloading to 10.13 at one year. The group of patients operated on had a mean age of 37.86 ± 7.02 years, a significant reduction in pain (p = 0.00004) and a significantly increased MDP score (p = 0.0034). A comparison of the two groups of patients showed significant stabilization of the necrotic lesions in the operated patients (p = 0.00067), with better satisfaction in the same group. Conclusion: Surgical drilling combined with grafting in the treatment of early-stage ONTF has improved progress in our series. The technique is reproducible and less invasive. It has made it possible to delay unfavorable progression and, consequently, hip replacement surgery.

Imaging approach for jaw and maxillofacial bone tumors with updates from the 2022 World Health Organization classification

Jaw and maxillofacial bone lesions encompass a wide variety of both neoplastic and non-neoplastic pathologies.These lesions can arise from various tissues,including bone,cartilage,and soft tissue,each presenting distinct challenges in diagnosis and treatment.While some pathologies exhibit characteristic imaging features that aid in diagnosis,many others are nonspecific.This overlap often necessitates a multimodal imaging approach,combining techniques such as radiographs,computed tomography,and magnetic resonance imaging to achieve a diagnosis or narrow the diagnostic considerations.This article provides a comprehensive review of the imaging approach to jaw and maxillofacial bone tumors,including updates on the 2022 World Health Organization classification of these tumors.The relevant anatomy of the jaw and dental structures that is important for accurate imaging interpretation is discussed.

Characterization of tumors of jaw:Additive value of contrast enhancement and dual-energy computed tomography

BACKGROUND Currently,the differentiation of jaw tumors is mainly based on the lesion’s morphology rather than the enhancement characteristics,which are important in the differentiation of neoplasms across the body.There is a paucity of literature on the enhancement characteristics of jaw tumors.This is mainly because,even though computed tomography(CT)is used to evaluate these lesions,they are often imaged without intravenous contrast.This study hypothesised that the enhancement characteristics of the solid component of jaw tumors can aid in the differentiation of these lesions in addition to their morphology by dual-energy CT,therefore improving the ability to differentiate between various pathologies.AIM To evaluate the role of contrast enhancement and dual-energy quantitative parameters in CT in the differentiation of jaw tumors.METHODS Fifty-seven patients with jaw tumors underwent contrast-enhanced dual-energy CT.Morphological analysis of the tumor,including the enhancing solid component,was done,followed by quantitative analysis of iodine concentration(IC),water concentration(WC),HU,and normalized IC.The study population was divided into four subgroups based on histopathological analysis-central giant cell granuloma(CGCG),ameloblastoma,odontogenic keratocyst(OKC),and other jaw tumors.A one-way ANOVA test for parametric variables and the Kruskal-Wallis test for nonparametric variables were used.If significant differences were found,a series of independent t-tests or Mann-Whitney U tests were used.RESULTS Ameloblastoma was the most common pathology(n=20),followed by CGCG(n=11)and OKC.CGCG showed a higher mean concentration of all quantitative parameters than ameloblastomas(P<0.05).An IC threshold of 31.35×100μg/cm^(3) had the maximum sensitivity(81.8%)and specificity(65%).Between ameloblastomas and OKC,the former showed a higher mean concentration of all quantitative parameters(P<0.001),however when comparing unilocular ameloblastomas with OKCs,the latter showed significantly higher WC.Also,ameloblastoma had a higher IC and lower WC compared to“other jaw tumors”group.CONCLUSION Enhancement characteristics of solid components combined with dual-energy parameters offer a more precise way to differentiate between jaw tumors.

Application of Personalized 3D-Printed Rehabilitation Orthotics in Postoperative Recovery of Jaw Fractures

Objective:To analyze the effectiveness of personalized 3D-printed rehabilitation orthotics in the postoperative recovery of jaw fractures.Methods:Relevant data were collected from 42 patients with jaw fractures treated at our hospital between October 2017 and May 2020.Patients were randomly divided into a traditional group(n=17)and a modified group(n=25).The traditional group received standard rehabilitation methods,while the modified group used personalized 3D-printed rehabilitation orthotics combined with improved rehabilitation methods.The temporomandibular disability index(TDI),quality of life scores,postoperative recovery excellence rate,and mouth opening were compared between the two groups at different follow-up times(before rehabilitation,and at 1 week,3 months,and 6 months post-surgery).Results:At 1 week,3 months,and 6 months post-surgery,the TDI in both the traditional and modified groups was significantly lower than before rehabilitation,with statistically significant differences(P<0.05).At 3 and 6 months post-surgery,the TDI in the modified group was lower than in the traditional group,with statistically significant differences(P<0.05).At 3 and 6 months post-surgery,pain,appearance,activity,recreation,work,chewing,swallowing,speech,shoulder function,and total quality of life scores in both groups were higher than before rehabilitation,with the modified group showing significantly higher scores in pain,appearance,chewing,swallowing,and total quality of life(P<0.05).Compared to before rehabilitation,mouth opening significantly improved in both groups at 3 and 6 months post-surgery,with the modified group showing significantly greater improvement(P<0.05).Conclusion:Personalized 3D-printed rehabilitation orthotics are highly effective in the postoperative recovery of jaw fractures.They can improve patients’quality of life after surgery,enhance the excellent rate of postoperative recovery,and increase mouth opening.

Osteonecrosis of the jaw in a patient with acute myeloid leukemia,who received azacitidine

The first case of osteonecrosis of the jaw(ONJ)related to azacitidine therapy was reported.A 64-year-old male with acute myeloid leukemia,who received 5-azacitidine,presented with pain and purulence of the right second premolar.An unsuccessful endodontic therapy resulted in dental extraction 6 months later.The post-extraction non-healing socket was managed with antibiotics and multiple surgical debridements without response.ONJ stage 2 was diagnosed 12 months after the initial symptoms of pain and purulence and was managed conservatively.Currently the patient is still receiving 5-azacitidine therapy,while ONJ remains asymptomatic.This case highlights the presence of alveolar bone disease prior to the appearance of ONJ.Osteonecrosis in chemotherapy,although rare,may increase as long-term survival of cancer patients,who receive those medications increases.Health care professionals need to be alert,while collaboration with an experienced oral/dental oncologist would be beneficial to the patient.

超声刀Focus刀头及Ligasure Small Jaw~刀头用于开放性甲状腺手术的对照研究

背景与目的：近年来，随着技术发展，越来越多的基于能量传递的止血工具广泛问世并应用于开放性外科手术中。超声刀Focus刀头（Harmonic Focus，HF）及Ligasure Small Jaw刀头（LSJ）都是专为开放性甲状腺手术量身定做的。本文拟对北京协和医学院中国医学科学院肿瘤医院HF及LSJ完成的开放性甲状腺手术患者的临床资料进行病例对照分析，以期比较HF及LSJ在开放性甲状腺手术中的应用效果。探讨HF及LSJ用于开放性甲状腺手术的有效性及安全性。方法：选取本院过去1年内甲状腺癌初治患者，由同一外科医师主刀使用HF或LSJ完成甲状腺全切除＋中央区清扫术，纳入HF组100例，LSJ组104例。通过比较两组手术时间及术后第1天引流量，比较两者在甲状腺手术中应用的有效性。通过比较两组术后并发症来评估安全性。结果：有效性：HF组平均手术时间为（95．8±18．0）min，LSJ组平均手术时间为（97．8±19．1）min，差异无统计学意义（P=-0．363）；术后首日引流量HF组为（35．2±20．3）mL，LSJ组为（36．3±23．8）mL，差异无统计学意义（P=0．977）。安全性：HF组出现暂时性声带麻痹者1例（1．0％），LSJ组术后伤口出现术区血肿者1例（1．0％）；暂时I生甲状旁腺功能低下者HF组18例（18．O％），LSJ组16例（15．4％）；HF组术后首日甲状旁腺素平均下降（12．3±12．8）pg／mL，LSJ组平均下降（13．9±13．4）μg／mL；血清离子钙HF组平均下降（0．20±0．13）mg／dL，LSJ组平均下降（0．20±0．16）mg／dL，差异均无统计学意义（P均〉0．05）。结论：HF及LSJ在开放性甲状腺手术中均安全、有效，手术并发症相当。

Current concepts on osteonecrosis of the femoral head

It is estimated that 20000 to 30000 new patients are diagnosed with osteonecrosis annually accounting for approximately 10% of the 250000 total hip arthroplasties done annually in the United States. Thelack of level 1 evidence in the literature makes it difficult to identify optimal treatment protocols to manage patients with pre-collapse avascular necrosis of the femoral head, and early intervention prior to collapse is critical to successful outcomes in joint preserving procedures. There have been a variety of traumatic and atraumatic factors that have been identified as risk factors for osteonecrosis, but the etiology and pathogenesis still remains unclear. Current osteonecrosis diagnosis is dependent upon plain anteroposterior and frog-leg lateral radiographs of the hip, followed by magnetic resonance imaging(MRI). Generally, the first radiographic changes seen by radiograph will be cystic and sclerotic changes in the femoral head. Although the diagnosis may be made by radiograph, plain radiographs are generally insufficient for early diagnosis, therefore MRI is considered the most accurate benchmark. Treatment options include pharmacologic agents such as bisphosphonates and statins, biophysical treatments, as well as joint-preserving and joint-replacing surgeries. the surgical treatment of osteonecrosis of the femoral head can be divided into two major branches: femoral head sparing procedures(FHSP) and femoral head replacement procedures(FHRP). In general, FHSP are indicated at pre-collapse stages with minimal symptoms whereas FHRP are preferred at post-collapse symptomatic stages. It is difficult to know whether any treatment modality changes the natural history of core decompression since the true natural history of core decompression has not been delineated.

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.

Association of Toll-like receptor 4 Signaling Pathway with Steroid-induced Femoral Head Osteonecrosis in Rats

Osteonecrosis of the femoral head is frequently observed in patients treated with excessive corticosteroids. However, the pathogenesis of corticosteroid-induced osteonecrosis remains unclear. The purpose of this study was to investigate the role of Toil-like receptor 4 （TLR4） signaling pathway in steroid-induced femoral head osteonecrosis in rats. Male Sprague-Dawley rats were injected intramus- cularly with 20 mg/kg methylprednisolone （MP） for 8 weeks, twice per week. The animals were sacri- ficed at 2, 4 and 8 weeks after the last MP injection, respectively, and then allocated to the 2-, 4- and 8-week model groups （n=24 each）. Rats in the control group （n=12） were not given any treatment. Histopathological analysis was performed and the concentration of tartrate-resistant acid phosphatase （TRAP） in plasma was determined. The activation of osteoclasts in the femoral head was assessed by TRAP staining. The expression of TLR4, MyD88, TRAF6 and NF-Id3 p65 that are involved in TLR4 signaling, and MCP-1 production were detected by using real-time PCR （RT-PCR） and Western blotting. The results showed that the osteonecrosis in the femoral head was clearly observed and the concentra- tion of TRAP in the plasma was increased in the model rats. The femoral head tissues in MP-treated rats were positive for TRAP and the intensity of TRAP staining was greater in MP-treated rats than in con- trol rats. As compared with the control group, the mRNA expression of TLR4 signaling-related factors was enhanced significantly at 4 and 8 weeks, and the protein levels of these factors increased signifi- cantly with time. It was concluded that MP could induce the femoral head osteonecrosis in rats, which was associated with osteoclast activation via the TLR4 signaling pathway. These findings suggest that TLR4 signaling pathway plays a pivotal role in the pathogenesis of steroid-induced osteonecrosis.

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.

Role of Electromagnetic Stimulation in the Treatment of Osteonecrosis of the Femoral Head in Early Stages

Osteonecrosis of the femoral head is a disorder that leads to collapse and osteoarthritis in young patients. This study examines the effectiveness of pulsed electromagnetic fields [PEMF] in the treatment of osteonecrosis of the head in precollapse bone stages. A retrospective evaluation was done of 51 patients including 70 hips with symptomatic osteonecrosis of the hip treated with pulsed electromagnetic fields. Criteria for inclusion in the study group were evidence of osteonecrosis and absence of collapse of the femoral head. The average follow-up was 26 months (range, 18 - 90). Etiologies included idiopathic (40 cases), steroid use (26) and alcohol (4). To demonstrate the existence of osteonecrosis and its evolution, magnetic resonance imaging [MRI] and plain radiography techniques were used. Results: Procedures were radiological success in 80% of cases, and no progression to collapse in 88.57% of hips. Eight of the 70 hips had radiographic progression to collapse. This study suggests that selected PEMF reduce the incidence of progression of osteonecrosis of femoral head in early stage.