Bone Osteonecrosis Research Articles

The effects of bisphosphonates on osteonecrosis of jaw bone: a stem cell perspective.

Bisphosphonate-induced osteonecrosis of the jaw (BIONJ) is a commonly encountered side effect of Bisphosphonates (BPs). Although certain aspects of BIONJ have been studied, the effects of BPs on the proliferation, differentiation, and maintenance of dental stem cells (DSC) in way that might account for development of BIONJ have not been evaluated. In the current study, Dental Pulp Stem Cells (DPSCs), Periodontal Stem Cells (PDLSCs), and human Tooth Germ Stem Cells (hTGSCs) were characterized and then each stem cell type were treated with selected BPs: Zoledronate (ZOL), Alendronate (ALE), and Risedronate (RIS). Negative effect on osteogenesis capacity of DSCs has not been observed after differentiation experiments in vitro. BPs exerted inhibitory effect on the migratory capacities of stem cells confirmed by in vitro scratch assay analysis. Angiogenesis of endothelial cells was blocked by BPs treatment in tube formation analysis. In conclusion, inhibitory effects of BPs on migration capacity of DSCs localized in close proximity to the jaw bone might be the primary reason for the side effects of BPs in the development of BIONJ process. Therefore, further in vivo evidence is required to investigate DSC properties in BP treated animals which might elucidate the importance of DSCs in BIONJ formation.

History of concentrated or expanded mesenchymal stem cells for hip osteonecrosis: is there a target number for osteonecrosis repair?

Despite multiple possible treatments, the risk of collapse remains the main problem of osteonecrosis. Heart failure (HF). In an effort to address the reverse this issue, curative strategies with regenerative medicine are increasingly being considered. The aim of this technology is to halt or reverse progression of the disease to collapse. The pioneering report by Hernigou published in 2002 was the first pilot study suggesting that injection of bone marrow stem cells was a safe approach able to improve osteonecrosis in patients with early stages. Since then, an impressive number of studies and trials employing unselected BM-derived cells (1000 the last 2years) showed that delivery of those cells to the site of osteonecrosis during core decompression was somehow able to ameliorate the patient with osteonecrosis. In order to translate the promise of this cell therapy into better clinical benefit, many questions need to be addressed. In this review, we therefore analyzed current clinical experience of the literature and our experience of 4000 cases to address these questions and particularly the number of cells that should be injected. After almost 20years of clinical research in this field, we are still far from having drawn conclusions on the number of cells we should inject in regenerating hip osteonecrosis. Findings are difficult to interpret due to heterogeneity of causes of osteonecrosis, as well as differences in the cells count, sample quality, and stages of osteonecrosis. The authors address specific issues, as cell quality, cell numbers, volume of osteonecrosis, concentration of cells, and ex vivo expansion. Bone marrow mesenchymal stem cells are supposed to be "functionally competent," but are collected from the bon, marrow of patients with diseases and risk factors of osteonecrosis. The recipient organ (bone osteonecrosis) is a tissue where several alterations have already occurred. These questions are addressed in this review. In this review, we analyzed current clinical experience regarding cell therapy and address issues that should be a guide for future cell-based therapeutic application in osteonecrosis.

DEVELOPMENT OF IN-SITU TEMPERATURE PREDICTION MODELS FROM CADAVERIC HUMAN FEMUR FOR BONE DRILLING

Thermal osteonecrosis of bone in drilling procedure is caused by improper parameters which can lead to poor bone-implant integration and loss of fixation. In this study, Taguchi technique for parameter optimization and multiple regression models for temperature prediction were employed. The main aim of the study was to determine the optimal parameters of bone drilling to control the temperature rise below the thermal osteonecrosis threshold (47[Formula: see text]C) in respect of the bone density variations at different drilling directions. A 32 full factorial design with nine sets of parameters was used in the study. Drilling operations were performed along the longitudinal, radial and circumferential directions at the proximal-diaphysis, mid-diaphysis and distal-diaphysis regions of the 10 adult cadaveric femurs with different feed rates (40, 60 and 80[Formula: see text]mm/min) and spindle speeds (500, 1000 and 1500[Formula: see text]rpm) using 3.2[Formula: see text]mm diameter surgical drill bit. The in-situ drilling temperatures were measured with T-type thermocouple. The optimum drilling parameters for each drilling direction were determined from signal to noise ratios and the effect of each parameter was determined using analysis of variance. By using computed tomography scan data of patients, the proposed method is able to predict the temperature rise at the bone-drilling sites, optimal parameters and possibility for the occurrence of thermal osteonecrosis. This important tool could assist in reducing localized temperature induced from surgical drilling by up to 32% and 18[Formula: see text]C and as such significantly reduce associated osteonecrosis and improve patient outcome and quality of life.

Third tarsal bone osteonecrosis associated with chronic recurrent cellulitis in an adult horse

SummaryA 17‐year‐old Irish Draught cross gelding with a history of chronic recurrent right hindlimb cellulitis was evaluated due to acute onset of severe lameness affecting this limb. Scintigraphic examination identified marked radiopharmaceutical uptake within the central and third tarsal bones and the lameness improved following tibial and peroneal nerve blocks. Distal intertarsal joint collapse was observed but the radiographic changes were considered insufficient to explain the lameness severity. Magnetic resonance imaging revealed marked bone pathology affecting both the central and third tarsal bones. A subcutaneous abscess developed on the dorsolateral aspect of the limb, but clear evidence of joint infection was not established. Computed tomography showed lytic lesions affecting mainly the third tarsal bone, so the animal was treated surgically for suspected osteomyelitis involving this bone by implantation of gentamicin impregnated polymethylmethacrylate. Shortly following surgery the horse developed gastric rupture and was euthanased. Osteonecrosis of the third tarsal bone was identified, but sepsis was not demonstrated to be the cause. It is hypothesised that osteonecrosis developed as a sequel to chronic osteomyelitis which may have responded to previous antimicrobial treatment. The report also highlights the importance of gastric disorders as a differential for discomfort in animals undergoing treatment for orthopaedic disease.

Three different radiological indicators for diagnosis of adult acetabular dysplasia: study protocol for a diagnostic trial and preliminary results

Background and objectives: Acetabular dysplasia is often characterized by acetabular bone hyperplasia and osteonecrosis of the femoral head. These pathological changes can alter the position of the center of the femoral head, causing abnormal values on anteroposterior radiographs of the adult pelvis involving the Wiberg anterior center-edge (CE) angle, acetabular angle (Sharp angle), and acetabular head index, eventually resulting in the inaccurate diagnosis of acetabular dysplasia. Herein, we introduce and verify three X-ray indicators, offshoring index (OFI), moving up index (MUI) and teardrop baseline offshoring index (TBOI). All data will be expressed as relative ratios, as we expect to make an accurate diagnosis by avoiding the generation of errors resulting from measurement angles. Design: A single-center, diagnostic trial. Methods: Two hundred adult patients (100 female and 100 male) will be scheduled to undergo pelvic X-ray examinations at the Third Hospital of Hebei Medical University in China. The affected and healthy sides will be measured and analyzed using commercial software. Outcome measures and preliminary results: The primary outcome measure is the sensitivity of OFI of the femoral head for diagnosing adult acetabular dysplasia. Secondary outcome measures include the specificity, positive and negative predictive values, and positive and negative likelihood ratios of OFI, and sensitivity specificity, positive and negative predictive values, and positive and negative likelihood ratios of MUI and TBOI of the femoral head for diagnosing adult acetabular dysplasia as well as the rate of correct diagnosis; correlation of OFI, MUI and TBOI to CE angle, Sharp angle and acetabular head index; and risk factors for hip dysfunction as analyzed by logistic regression analysis. In our pre-tests, pelvic X-ray data from 241 male patients showed that the OFI, MUI and TBOI were 86.8 ± 0.6%, 75.8 ± 2.0% and 76.2 ± 0.5%, which closely correlated with CE angle, Sharp angle, and acetabular head index (AHI). Discussion: This study is designed to verify that three new X-ray indicators, OFI, MUI and TBOI, as diagnostic indicators for adult acetabular dysplasia, can increase diagnostic accuracy and effectively avoid diagnostic errors in comparison with the CE angle, Sharp angle, and AHI. Ethics and dissemination: The study was approved by the Ethics Committee of the Third Hospital of Hebei Medical University in China (approval No. KE2016-011-1). The study will be performed in accordance with the relevant laws and regulations of the Declaration of Helsinki. All the participatns will be fully informed of the study protocol and experimental process, and provide written informed consent with the premise of fully understanding the treatment plan. The results of this study will be disseminated in peer-reviewed journals or presented at scientific meetings. Trial registrations: This trial was registered in the Chinese Clinical Trial Registry with registration number: ChiCTR1800016375 (protocol version: 1.0).

An underlying diagnosis of osteonecrosis of bone is associated with worse outcomes than osteoarthritis after total hip arthroplasty

BackgroundWell-designed studies of complications and readmission rates in patients undergoing total hip arthroplasty (THA) with osteonecrosis are lacking. Our objective was to examine if a diagnosis of osteonecrosis was associated with complications, mortality and readmission rates after THA.MethodsWe analyzed prospectively collected data from an integrated healthcare system’s Total Joint Replacement Registry of adults with osteonecrosis vs. osteoarthritis (OA) undergoing unilateral primary THA during 2001–2012, in an observational cohort study. We examined mortality (90-day), revision (ever), deep (1 year) and superficial (30-day) surgical site infection (SSI), venous thromboembolism (VTE, 90-day), and unplanned readmission (90-day). Age, gender, race, body mass index, American Society of Anesthesiologists class, and diabetes were evaluated as confounders. We used logistic or Cox regression to calculate odds or hazard ratios (OR, HR) with 95% confidence intervals (CI).ResultsOf the 47,523 primary THA cases, 45,252 (95.2%) had OA, and 2,271 (4.8%) had osteonecrosis. Compared to the OA, patients with osteonecrosis were younger (median age 55 vs. 67 years), and were less likely to be female (42.5% vs. 58.3%) or White (59.8% vs. 77.4%). Compared to the OA, the osteonecrosis cohort had higher crude incidence of 90-day mortality (0.7% vs. 0.3%), SSI (1.2% vs. 0.8%), unplanned readmission (9.6% vs. 5.2%) and revision (3.1% vs. 2.4%). After multivariable-adjustment, patients with osteonecrosis had a higher odds/hazard of mortality (OR: 2.48; 95% CI:1.31–4.72), SSI (OR: 1.67, 95%CI:1.11–2.51), unplanned 90-day readmissions (OR: 2.20; 95% CI:1.67–2.91) and a trend towards higher revision rate 1-year post-THA (HR: 1.32; 95% CI: 0.94–1.84), than OA patients.ConclusionsCompared to OA, a diagnosis of osteonecrosis was associated with worse outcomes post-THA. A detailed preoperative discussion including the risk of complications is needed for informed consent from patients with osteonecrosis.

MTX-LPDに広範囲の顎骨壊死が生じ顎骨切除を要した1例

MTX-LPDに広範囲の顎骨壊死が生じ顎骨切除を要した1例

Autofluorescence image of post-radiation maxillary bone osteonecrosis in a 64-year-old patient – Case Report

1. Ziółkowska E, Biedka M, Windborska W. Odczyn popromienny u chorych na raka regionu głowy i szyi: mechanizmy i konsekwencje. Otolaryngol. 2011; 4: 147–153. Google Scholar

Bisphosphonate related osteonecrosis of calvarial bone

BackgroundA case of bisphosphonate related osteonecrosis of calvarial bone has not been reported. MethodsThe clinical, imaging, and histopathological findings of the patient are presented. A 72-year-old female treated with bisphosphonates for osteoporosis presented with an open wound of her scalp. CT, MRI and bone scan suggested lytic and sclerotic changes with inflammation. ResultsSurgical debridement was performed and final pathology was consistent with osteonecrosis and osteomyelitis. ConclusionsThis case illustrates that bisphosphonates can induce osteonecrosis of calvarial bone.

Medication-Related Osteonecrosis of the Jaw Around Dental Implants: Implant Surgery-Triggered or Implant Presence-Triggered Osteonecrosis?

Dentoalveolar surgery including tooth extractions and dental implants placement is considered the major risk factor for developing medication-related osteonecrosis of the jaw (MRONJ).In this study, a patient series of MRONJ around dental implants were carefully analyzed to describe the findings and to assess the possible risk factors. Fifteen patients with peri-implant bone osteonecrosis were selected out of a group of 250 patients (6%). Patients were divided into 2 groups according to the temporal relationship. Group 1 (G1)-necrosis immediately after implant placement (from 2 to 10 months) and defined as "implant surgery-triggered" MRONJ. Group 2-necrosis distant (from 1 to 15 years) from implant placement and defined as "implant presence-triggered" MRONJ. Epidemiological and pharmacological variables were recorded as well as specific data about osteonecrosis and dental implants. G1 included 6 patients: 5 (83.4%) treated with oral bisphosphonates (BPs) for osteoporosis and 1 (16.6%) with intravenous BPs for breast cancer. Mean duration of BP therapy (BPT) was 83.7 months. G2 included 9 patients: 8 patients (88.89%) treated with intravenous BPs for malignant disease and 1 (11.11%) with oral BPs for osteoporosis. Data confirms that not only surgical insertion of dental implants is a potential risk factor for the development of osteonecrosis but also the presence itself of the implant into the bone can be associated with this disease. Therefore, it is necessary to inform of the increased risk for MRONJ also the patients who have already osteointegrated implants and are going to start the BPT.The risk is lower for patients receiving oral BPs but it exists and seems to be higher if the implant is located in the posterior areas, if the duration of BPT is more than 3 years and if the patient is under corticosteroid therapy.

Human Immunodeficiency Virus and Total Joint Arthroplasty: The Risk for Infection Is Reduced

BackgroundHighly active antiretroviral therapy (HAART) has changed the face of human immunodeficiency virus (HIV) and allowed patients to live for many decades. HIV and HAART are known risk factors for osteonecrosis of bone, osteopenia, and osteoporosis. Therefore, the demand for total joint arthroplasty (TJA) in HIV-infected patients is on the rise. We attempted to determine whether modern treatments for HIV have impacted the rate of periprosthetic joint infection (PJI). MethodsConducting a systematic review, 25 studies with a total of 722 TJAs were identified. We extracted data on rates of PJI after primary TJA in HIV-infected patients with and without hemophilia and data on administration of HAART at the time of arthroplasty. ResultsThree hundred eighty-one TJAs were performed in 293 patients with HIV infection without hemophilia. The follow-up ranged between 1.5 months and 11 years. Nine patients developed PJI. In patients with both HIV and hemophilia, 341 primary TJAs were performed. Forty-five received treatment for PJI. Follow-up ranged between 1 year and 26 years. Rates of PJI were 2.28% and 10.98% for HIV-only patients and patients with HIV and hemophilia, respectively. This difference was statistically significant (P < .0001) with a 5.28 odds ratio for hemophilia. HAART was associated with fewer infections overall (odds ratio, 0.12). ConclusionThe rates of PJI after TJA in HIV-only patients are lower than those in patients with both HIV and hemophilia. Treatment of patients with HAART and optimization of underlying comorbidities appears to lower the rate of PJI in this patient population.

Histopathological features of bisphosphonates related osteonecrosis of the jaw in rats with and without vitamin d supplementation

ObjectiveAim of this study was to investigate the effect of vitamin-D3 on the osteonecrosis of bone that was induced after tooth extraction was conducted on rats that were given zoledronic acid (Z.A). Material and methodsAnimals were divided into four groups. Two of the experimental groups were divided into two subgroups, third study group was not divided into subgroups, and control group was divided into three subgroups. Z.A was administered twice per week over the course of 7 weeks, dexamethasone was administered twice a week during the 5th-6th-7th weeks to all groups. Dental extraction was performed by drilling around the tooth at 7th week. In study-group-1; vitamin-D was administered twice per week during the 5th-6th-7th weeks. In study-group 2; vitamin-D was administered twice per week during the 8th-9th-10th weeks. In study-group-3; vitamin-D was administered twice per week during the 15th-16th-17th weeks. The animals were sacrificed at 10th-15th-17th weeks, and histologic samples were taken. ResultsPostoperative-15-group had a lower osteoblast number, which was statistically significant as compared to preoperative-15 and control-15-group. Control-10-group showed significantly lower osteoclast number in comparison to preoperative-10 and postoperative-10-group. Osteoclast number was significantly higher in the osteonecrosis-17-group as compared to control-17-group. Preoperative-10-group showed significantly higher inflammation in comparison to control-10-group. Postoperative-15-group had a lower histologic osteonecrosis, which was statistically significant as compared to the control-15-group. Macroscopic osteonecrosis was significantly higher in the control-17-group in comparison to the osteonecrosis-17-group. ConclusionsWe concluded that there are some proofs for the treatment of BRONJ with systemic using of vitamin-D.

Anti-resorptive Drugs and their Impact on Maxillofacial Bone among Cancer Patients.

This article aims to give an overview on etiology, diagnosis and treatment options of osteonecrosis of the jaw bone among cancer patients receiving anti-resorptive drugs (ARDs). The physiologic bone function of continuous resorption and buildup is modified by the use of ARDs. Although ARDs proved to reduce pain and to improve the quality of life in patients with metastasizing bone disease, side effects such as medication related osteonecrosis of jaw bone (MRONJ) have been frequently reported since ARDs were firstly introduced. The new generation of ARDs such as Denosumab is associated with the same incidence of MRONJ among cancer patients. The etiology of MRONJ is not entirely understood and many hypotheses have been proposed. ARDs can modify the hard tissues directly by accumulation in the bone, or indirectly by suppression of the osteoclasts, inhibition of angiogenesis and vascularity. Some ARDs such as Bisphosphonates have reportedly the capacity to interfere directly and indirectly with the bone physiology. MRONJ can be a debilitating disease with non healing freely exposed bone in the oral cavity in patients, who already suffer from a primary cancerous disease. Knowledge of MRONJ as a potential side effect of ARDs is crucial for health professionals treating patients with bone modulating drugs.

Investigating the Effect of Vitamin D3 (1,25(Oh)2d3) (Calcitriol) on the Osteonecrosis of Bone Occured After Tooth Extraction on the Rats Have Given Zoledronic Acid (Zometa)

Investigating the Effect of Vitamin D3 (1,25(Oh)2d3) (Calcitriol) on the Osteonecrosis of Bone Occured After Tooth Extraction on the Rats Have Given Zoledronic Acid (Zometa)

Bisphosphonate Induced Mandible Bone Osteonecrosis in A Patient with Prostate Cancer

Bisphosphonate Induced Mandible Bone Osteonecrosis in A Patient with Prostate Cancer

Bisphosphonate osteo-necrosis of the jaws [BONJ], from defective function of oral epithelial intercellular junctions?

Bone osteonecrosis of the jaws (BONJ) is prevalent when diseases are treated with high bisphosphonate doses. The mouth is unique in that it has epithelial covered bony protuberances jutting into an infective environment. Should epithelium over these bony prominences be disrupted, abraded or ulcerated by trauma, extraction or therapy, not only will the mucosa not heal, but in vulnerable cases, where less-vital bone is present, there is development of BONJ. BONJ development is explained by BP’s depleting available calcium ions from healthy functioning of epithelial gap junctions and disrupting the balance between osteogenesis and osteoclasis.

Avascular necrosis of bone in childhood cancer patients: a possible role of genetic susceptibility.

With the increasing number of paediatric cancer patients and with their prolonged survival, the evidence of a number of serious complications induced by anticancer therapy is rising. Osteonecrosis (ON) of bone is one of these treatment-related effects with amultifactorial pathogenesis. In the past few years, several polymorphisms of candidate genes with possible role in development of this disorder were studied.We summarized potential risk factors leading to increased susceptibility to osteonecrosis of bone development in cancer patients during childhood and to present current knowledge in the field of genetic aspects of this condition (Ref. 86).

Is Attention Deficit Hyperactivity Disorder a Risk for Kohler's Disease? Osteonecrosis of Navicular Bone of Foot

Abstract We present a pediatric case report of foot pain due to Kohler's disease. We discussed the etiology and treatment of Kohler’s Disease of a 5-year-old boy who had Attention Deficit Hyperactivity Disorder in this case report. Our goal is elucidate the etiology of these cases and their relationship with behavioral disorders. Key Words: Osteonecrosis of Navicula; Kohler Disease; Attention Deficit Hyperactivity Disorder (ADHD), Trauma

Could Denosumab Support Bone Integrity in Sickle Cell Disease

Sickle cell anaemia is a congenital disease characterized by painful vaso-occlusive crises. It is associated with vitamin D deficiency, osteoporosis and recurrent attacks of micro-infarctions lead to bone osteonecrosis. The most common sites of osteonecrosis in sickle cell disease are the femoral and humeral heads which could lead to severe pain and extensive physical disability. Denosumab is a new human monoclonal antibody product; it is a receptor activator of nuclear factor kappa B ligand RANKL. That decreases osteoclastic bone restoration. It is Food and Drug Administration FDA approved for osteoporosis for women with high risk of fracture; and it is also being used for the treatment and prevention of bone loss in patients undergoing hormone ablation therapy for breast and prostate cancer. Denosumab is not restricted for sickle cell disease patients within its approved indications. It has less nephrotoxicity effect than the bisphosphonates which is a big advantage for sickle cell patients. It also used as an adjuvant agent to reduce metastatic bone pain in solid tumors. The extension of Denosumab use for sickle cell patients’ osteoporosis and osteonecrosis deserve a randomized multi central trail aiming to improve bone integrity and possible reduction of the devastating pain in sickle cell disease patients.

Osteonecrosis of the Temporal Bone Secondary to Bisphosphonates: A Potentially Life‐Threatening Complication

Objectives: (1) Describe how osteonecrosis of the temporal bone can present as a potentially life-threatening side effect of bisphosphonates. (2) Recognize that bisphosphonates are commonly prescribed and as such many of our patients could potentially experience these complications. (3) Apply this knowledge to achieve a timely diagnosis and to ensure patients are counseled regarding the risk of temporal bone osteonecrosis. Methods: Case study of 2 patients presenting to our clinic in Lanarkshire, Scotland, from 2012-2013: Patient A: A 53-year- old female with cholesteatoma was also receiving intravenous bisphosphonate therapy for osteoporosis. Patient B: A 57-year- old female on bisphosphonates presented with a left-sided facial palsy. Results: Patient A: During mastoidectomy the whole of the tegmen was noted to be brittle. A large piece of tegmen was found detached from the surrounding bone but was not affected by cholesteatoma. The tegmen defect was repaired and the patient is being followed up. Patient B had examination findings in keeping with otitis externa. A computed tomography scan demonstrated bone erosion involving the descending facial nerve. Comorbidities have prevented surgical management and despite discontinuing the bisphosphonate. The facial palsy has not resolved. Conclusions: Bisphosphonates can cause osteonecrosis of the temporal bone, including lower doses used to treat osteoporosis, especially in presence of localized infections. The otolaryngologist should be aware that complications such as tegmen erosion and facial palsy may occur. Patients with known infectious ear conditions considering treatment with bisphosphonates for osteoporosis should be counseled regarding the risk of osteonecrosis of the temporal bone.