Bisphosphonate associated osteomyelitis of the jaw in patients with bony exposure: prevention, a new way of thinking

Objective There is strong evidence of a link between the use of systemic bisphosphonates (BPs) and osteonecrosis of the jaw, especially in cancer patients. Among risk factors for BRONJ, tooth extraction and immune suppressive drugs seem to have significant role on bone healing. Therefore, the importance of these parameters in development of BRONJ was reviewed in this retrospective study in two maxillofacial surgery units. Material and Methods From 2007 to 2012, 46 patients on bisphosphonate who had developed oral bony lesions participated in this study. The pharmacological exposure, comorbidities, maxillofacial findings, types of treatment and outcome data were collected from clinical and radiological records. Results The most frequently used BP was alendronate (67%). Tooth extraction was reported in 61% of patients with BRONJ. Systemic corticosteroids were prescribed in 35 cases (76%) as an adjuvant for BP. Patients on corticosteroids had a lower probability of bony lesion healing (

Bisphosphonates and implants in the jaw bone

Insertion of metal implants in bone is one of the commonest of all surgical procedures. The success of these operations is dependent on the fixation of the implants, which, in turn, depends on the strength of the bone that holds them. If the quality of the bone holding the implant could be improved locally, surgical procedures would become simpler and rehabilitation would become faster. Bisphosphonates are anti-resorptive drugs that act specifically on osteoclasts, thereby maintaining bone density and strength. Once released from the surface of a coated implant, bisphosphonates reduce osteoclast activity, thereby changing the balance of bone turnover in favor of bone formation, leading to a net gain in local bone density. During the last decades, the effects of bisphosphonate treatment on the stability of implants have been tested in several clinical and animal studies, but not in human jaws. This may be because it has been suggested that there is a link between the use of bisphosphonates (especially those given intravenously) and a condition called osteonecrosis of the jaw (ONJ). The pathophysiology and treatment of ONJ is controversial. The difficulty in treating ONJ has highlighted the importance of prevention. The overall aim of the present thesis was to evaluate the effect of local and systemic use of bisphosphonates on bone tissue. Could a thin, bisphosphonate-eluting fibrinogen coating improve the fixation of metal implants in the human jaw? Would it be possible to reproduce ONJ and prevent the development of this condition in an animal model? In two clinical studies, a total number of 96 implants were inserted in 21 patients. In a randomized trial with a paired design, one implant in each pair was coated with a thin fibrinogen layer containing two bisphosphonates (pamidronate and ibandronate). The bisphosphonate-coated implants showed better stability as measured by resonancefrequency analysis. Radiographic intraoral films also showed less bone loss. Three animal models were developed. In a study comparing local and systemic effects of bisphosphonates, zoledronate-coated screws inserted in rats showed better fixation in spite of a drug treatment that is known to induce ONJ-like lesions when given systemically. In another rat model, ONJ-like lesions were reproducibly induced at sites of tooth extraction whereas there were no signs of bone cell death in uninjured sites. Finally, rat experiments showed that the development of ONJ-like lesions after tooth extraction could be prevented by early mucoperiosteal coverage. In conclusion, a thin, bisphosphonate-eluting fibrinogen coating can improve the fixation of dental implants in human bone. This may lead to new possibilities in orthopaedic surgery and dentistry. The pathophysiology of ONJ is strongly linked to bone exposure in combination with drugs that reduce resorption

Bisphosphonates and implants in the jaw bone

Insertion of metal implants in bone is one of the commonest of all surgical procedures. The success of these operations is dependent on the fixation of the implants, which, in turn, depends on the strength of the bone that holds them. If the quality of the bone holding the implant could be improved locally, surgical procedures would become simpler and rehabilitation would become faster. Bisphosphonates are anti-resorptive drugs that act specifically on osteoclasts, thereby maintaining bone density and strength. Once released from the surface of a coated implant, bisphosphonates reduce osteoclast activity, thereby changing the balance of bone turnover in favor of bone formation, leading to a net gain in local bone density. During the last decades, the effects of bisphosphonate treatment on the stability of implants have been tested in several clinical and animal studies, but not in human jaws. This may be because it has been suggested that there is a link between the use of bisphosphonates (especially those given intravenously) and a condition called osteonecrosis of the jaw (ONJ). The pathophysiology and treatment of ONJ is controversial. The difficulty in treating ONJ has highlighted the importance of prevention. The overall aim of the present thesis was to evaluate the effect of local and systemic use of bisphosphonates on bone tissue. Could a thin, bisphosphonate-eluting fibrinogen coating improve the fixation of metal implants in the human jaw? Would it be possible to reproduce ONJ and prevent the development of this condition in an animal model? In two clinical studies, a total number of 96 implants were inserted in 21 patients. In a randomized trial with a paired design, one implant in each pair was coated with a thin fibrinogen layer containing two bisphosphonates (pamidronate and ibandronate). The bisphosphonate-coated implants showed better stability as measured by resonancefrequency analysis. Radiographic intraoral films also showed less bone loss. Three animal models were developed. In a study comparing local and systemic effects of bisphosphonates, zoledronate-coated screws inserted in rats showed better fixation in spite of a drug treatment that is known to induce ONJ-like lesions when given systemically. In another rat model, ONJ-like lesions were reproducibly induced at sites of tooth extraction whereas there were no signs of bone cell death in uninjured sites. Finally, rat experiments showed that the development of ONJ-like lesions after tooth extraction could be prevented by early mucoperiosteal coverage. In conclusion, a thin, bisphosphonate-eluting fibrinogen coating can improve the fixation of dental implants in human bone. This may lead to new possibilities in orthopaedic surgery and dentistry. The pathophysiology of ONJ is strongly linked to bone exposure in combination with drugs that reduce resorption

Malignant Transformation of Ossifying Fibroma into Parosteal Osteosarcoma with High-grade Component: Presentation of an Unusual Case and Review of the Literature

Background: Parosteal Osteosarcoma of the Jaw (POSJ) is a rare entity that is associated with a high survival rate. Several case reports and case series of POSJ have been published in the literature, but few authors have described development of this tumor by possible transformation from a fibro-osseous neoplasm. Objective: We present a rare occurrence of parosteal osteosarcoma with involvement of the posterior maxilla, orbit floor, and infra-temporal fossa in a 20-year-old man. Furthermore, we performed a literature review regarding clinical, radiological, and histological features; treatment strategies; and etiology/pathophysiology. Methods: A PubMed search yielded a total of 74 articles and the articles were sorted according to their corresponding key area of focus. Results: This was a case of POSJ with high-grade component in the maxillofacial region of a 20-year old male. Co-expression of MDM2 and CDK4 was confirmed. At 2.5-year follow-up, the patient had died. The literature review revealed 18 articles including 20 cases of POSJ. Four cases represent the possible development of this tumor by transformation from a fibro-osseous neoplasm: Two cases of fibrous dysplasia, one case of cemento-ossifying fibroma, and the case of Ossifying Fibroma (OF) in the present study. Conclusion: In conclusion, we found an unusual case of POSJ of the midface in a patient with a previous diagnosis of OF in the same region. To our knowledge, there have been no previous reports of development of POSJ in OF. Furthermore, this is the first described case of high-grade surface osteosarcoma in the craniofacial region

Bisphosphonate Associated Osteonecrosis of the Jaw: An Update on Pathophysiology, Risk Factors, and Treatment

Osteonecrosis of the jaw in patients treated with bisphosphonates is a relatively rare but well known complication at maxillofacial units around the world. It has been speculated that the medication, especially long-term i.v. bisphosphonate treatment, could cause sterile necrosis of the jaws. The aim of this narrative review of the literature was to elaborate on the pathological mechanisms behind the condition and also to gather an update on incidence, risk factors, and treatment of bisphosphonate associated osteonecrosis of the jaw. In total, ninety-one articles were reviewed. All were published in internationally recognized journals with referee systems. We can conclude that necrotic lesions in the jaw seem to be following upon exposure of bone, for example, after tooth extractions, while other interventions like implant placement do not increase the risk of osteonecrosis. Since exposure to the bacterial environment in the oral cavity seems essential for the development of necrotic lesions, we believe that the condition is in fact chronic osteomyelitis and should be treated accordingly

Surgical Management of Granular Cell Tumor of the Orbit : Case Report and Literature Review

Introduction: Granular Cell Tumors (GCTs) of the orbit are rare-entity soft-tissue tumors, and few reports have been published in the literature. The treatment of the choice is total excision. Early diagnosis prior to surgery is valuable for the distinction of malignant from benign tumor. Case presentation: We report a case of a 55-year-old woman with a solitary slow-growing mass in the right orbit with the involvement of the rectus inferior muscle, and present a review of the recent literature. The lesion had a diameter of 1 cm and was noticed 2 years before the examination. Excisional biopsy confirmed the diagnosis of GCT. The tumor was resected through a retroseptal transconjunctival approach. The final histological examination revealed findings characteristic of GCT, including positive reaction for protein S-100, SOX10, and calcitonin and negative reaction for desmin, myogenin, Smooth Muscle Antigen (SMA), Melan-A, and HMB-45. There were no signs of malignancy in this sample. Disturbance of motility was not noted by the patient after surgery. Conclusion: GCT should be included in the differential diagnosis of intraorbital lesions, particularly those that involve the orbit muscles. A biopsy is recommended before surgical resection, to exclude malignancy and prevent radical resection

A bisphosphonatecoating improves the fixation of metal implants in human bone. A randomized trial of dental implants

Abstract Many surgical procedures use metal implants in bone. The clinical results depend on the strength of the bone holding these implants. Our objective was to show that a drug released from the implant surface can improve parameters reflecting the quality or amount of this bone. Sixteen patients received paired dental titanium implants in the maxilla, in a randomized, double-blinded fashion. One implant in each pair was coated with a thin fibrinogen layer containing 2 bisphosphonates. The other implant was untreated. Fixation was evaluated by measurement of resonance frequency (implant stability quotient; ISQ) serving as a proxy for stiffness of the implant-bone construct. Increase in ISQ at 6 months of follow-up was the primary variable. None of the patients had any complications. The resonance frequency increased 6.9 ISQ units more for the coated implants (p = 0.0001; Cohen's d = 1.3). The average difference in increase in ISQ, and the effect size, suggested a clinically relevant improvement. X-ray showed less bone resorption at the margin of the implant both at 2 months (p = 0.012) and at 6 months (p = 0.012). In conclusion, a thin, bisphosphonate-eluting fibrinogen coating might improve the fixation of metal implants in human bone. This might lead to new possibilities for orthopedic surgery in osteoporotic bone and for dental implants. Highlights Dental implants coated with bisphosphonates showed higher resonance frequency. Resonance frequency reflects stiffness of the bone-implant construct. Randomized double-blinded trial with internal controls. First clinical study to show improved implant fixation in bone by coating with a drug

Ibandronate Reduces the Surface Bone Resorption of Mandibular Bone Grafts : A Randomized Trial With Internal Controls

ABSTRACT Autologous bone grafts are considered the gold standard for reconstruction of the edentulous alveolar ridges. However, this procedure is associated with unpredictable bone loss caused by physiological bone resorption. Bisphosphonates are antiresorptive drugs that act specifically on osteoclasts, thereby maintaining bone density, volume, and strength. It was hypothesized that the resorption of bone grafts treated with an ibandronate solution would be less advanced than bone grafts treated with saline. Ten patients who underwent bilateral sagittal split osteotomy were included in a randomized double-blind trial with internal controls. Each patient received a bone graft treated with a solution of ibandronate on one side and a graft treated with saline (controls) contralaterally. Radiographs for the measurement of bone volume were obtained at 2â\u80\u89weeks and at 6 months after surgery. The primary endpoint was the difference in the change of bone volume between the control and the ibandronate bone grafts 6 months after surgery. All of the bone grafts healed without complications. One patient was excluded because of reoperation. In eight of the nine patients, the ibandronate bone grafts showed an increase in bone volume compared with baseline, with an average gain of 126â\u80\u89mm3 (40% more than baseline) with a range of +27 to +218â\u80\u89mm3. Only one ibandronate-treated graft had a decrease in bone volume (8%). In the controls, an average bone volume loss of â\u88\u92146â\u80\u89mm3 (58% of baseline) with a range of â\u88\u9229 to â\u88\u92301â\u80\u89mm3 was seen. In the maxillofacial field, the reconstructions of atrophic alveolar ridges, especially in the esthetical zones, are challenging. These results show that bone grafts locally treated with ibandronate solution increases the remaining bone volume. This might lead to new possibilities for the maxillofacial surgeons in the preservation of bone graft volumes and for dental implant installations. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.Funding agencies: Department of Oral and Maxillofacial Surgery and the Department of Radiology at Linköping University, Linköping, Sweden, and the Swedish Research Council.</p

Primary Chronic Osteomyelitis of the Jaws in Children : An Update on Pathophysiology, Radiological Findings, Treatment Strategies, and Prospective Analysis of Two Cases

Objective. Primary chronic osteomyelitis (PCO) of the jaws in children is associated with pain, trismus, and swelling. In children, temporomandibular joint involvement is rare and few studies have been published due to the relatively low incidence. This paper presents two cases of mandibular PCO in children with the involvement of the collum mandibulae. In addition, a review of the literature regarding demographic data, histological, radiological, and laboratory findings, and treatment strategies of PCO was also performed. Material and Methods. Prospective analyses of two PCO cases. A PubMed search was used and the articles were sorted according to their corresponding key area of focus. Results. Review of the literature revealed twenty-four cases of PCO with two cases of mandibular condyle involvement. The mean age was 18 years; the male to female ratio was 1 : 3. Most of the patients were treated with anti-inflammatory drugs in combination with decortication. Clinical recurrence was seen in 7 cases. Conclusion. A combination of anti-inflammatory drugs and surgical intervention appears to be the first choice of treatment. However, surgical removal of necrotic tissue adjacent to collum mandibulae has its limitations in children. Further investigations are of utmost importance in order to increase our knowledge and understanding of this disease