Two-stage reconstruction using a vancomycin-impregnated cement spacer for finger osteomyelitis with bone and joint destruction.

OBJECTIVES: Septic arthritis and osteomyelitis are serious infections. Several treatment methods for the small joints and bones of the hands have been reported. We hypothesized that antibiotic-impregnated cement spacers could be useful for purulent finger osteomyelitis with bone and joint destruction. PATIENTS AND METHODS: Seven patients with finger osteomyelitis with bone and joint destruction were treated using vancomycin (VCM)-impregnated cement spacers. During the first surgery, a cement spacer was placed in the space created after debridement, maintaining finger length. Intraoperative specimens were tested for bacterial growth. Systemic antibiotic treatment was administered. A second surgery was performed 6-8 weeks after the first. After spacer removal, reconstruction surgeries were performed: arthrodesis using the Masquelet technique (n = 5), vascularized bone grafting (n = 1), and silicone implant arthroplasty (n = 1). We assessed the pathogenic bacteria, duration of antibiotic treatment, infection control, time to bone union, pain on visual analogue scale (VAS) (0 - 100), total active motion (TAM) of the affected fingers, and grip strength. RESULTS: The pathogenic bacteria were methicillin-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and unknown in 3, 3, and 1 patients, respectively. Mean duration of antibiotic treatment was 6.4 weeks. In all patients, infection resolved without recurrence. One patient underwent joint arthroplasty; otherwise, bone union was achieved in 6 patients. Mean VAS score for pain was 0.9. Mean TAM was 147° for the index and middle fingers and 50° for the thumb. Mean grip strength was 86.4% of that of the unaffected side. CONCLUSION: VCM-impregnated cement spacers could be useful for finger osteomyelitis, facilitating effective infection control and the maintenance of finger length, even in severe conditions.

Nintedanib-induced osteomyelitis of the jaw against the background of COVID-19 infection.

PURPOSE: Various medications are administered to treat Coronavirus Disease 2019 (COVID-19) infection and prevent its complications. Some medicines have complications and long-term effects, which may mimic other conditions, making precise diagnosis difficult. This report aims to bring to light one such complication, medication-related osteonecrosis of the jaw (MRONJ), secondary to a commonly prescribed medication for preventing lung fibrosis post-COVID-19 infection. METHOD: A 33-year-old male reported to our department with the typical clinical and radiological features of Mucormycosis of the upper jaw post-COVID-19 infection. However, on detailed evaluation of his history (controlled diabetic and short duration of steroid therapy) and review of the mycology staining, bacteriology, culture, and histopathological reports, we came to a negative diagnosis for Mucormycosis. The patient was, however, on treatment for the prevention of lung fibrosis with Nintedanib (tyrosine kinase inhibitor) 150 mg twice a day for one month. RESULT: In the absence of predisposing factors and negative laboratory findings for mucormycosis, we arrived at a diagnosis of MRONJ, attributable to Nintedanib therapy given to prevent lung fibrosis post-COVID-19 infection. CONCLUSION: The use of Nintedanib has recently increased due to the high incidence of lung fibrosis post-COVID-19 infection. However, Nintedanib should be considered a causative agent for osteonecrosis of the jaw in the absence of other obvious predisposing factors. Therefore, Nintedanib must be administered after a thorough consideration of risk factors.

Pharmacokinetic and pharmacodynamic considerations for optimizing antimicrobial therapy used to treat bone and joint infections: an evidence-based algorithmic approach.

INTRODUCTION: Bone and joint infections (BJIs) are a major health concern causing remarkable morbidity and mortality. However, which antimicrobial treatment could be the best according to specific clinical scenarios and/or to the pharmacokinetic/pharmacodynamic (PK/PD) features remains an unmet clinical need. This multidisciplinary opinion article aims to develop evidence-based algorithms for empirical and targeted antibiotic therapy of patients affected by BJIs. AREAS COVERED: A multidisciplinary team of four experts had several rounds of assessment for developing algorithms devoted to empirical and targeted antimicrobial therapy of BJIs. A literature search was performed on PubMed-MEDLINE (until April 2023) to provide evidence for supporting therapeutic choices. Four different clinical scenarios were structured according to specific infection types (i.e. vertebral osteomyelitis, prosthetic joint infections, infected non-unions and other chronic osteomyelitis, and infectious arthritis), need or not of surgical intervention or revision, isolation or not of clinically relevant bacterial pathogens from blood and/or tissue cultures, and PK/PD features of antibiotics. EXPERT OPINION: The proposed therapeutic algorithms were based on a multifaceted approach considering the peculiar features of each antibiotic (spectrum of activity, PK/PD properties, bone penetration rate, and anti-biofilm activity), and could be hopefully helpful in improving clinical outcome of BJIs.

Diffuse Sclerosing Osteomyelitis: A Potential Risk Indicator for Peri-implantitis? A Case Series.

PURPOSE: To propose diffuse osteomyelitis as risk indicator for peri-implantitis following the loss of several dental implants in patients that present with highly sclerotic bone areas. MATERIALS AND METHODS: A total of six "nightmare cases"-three of which were treated at the Department of Periodontology of the University Hospitals of the Catholic University Leuven and three of which were referred there for a second opinion-were retrospectively analyzed using radiographs obtained via contact with referring clinicians in order to fully reconstruct the treatment pathway and dental history for each of these patients. RESULTS: All patients suffered from early implant failures and/or severe peri-implantitis with bone loss and crater formation up to the apical level, as well as the loss of all or nearly all implants. Re-examination of their preand postoperative CBCTs, in combination with several bone biopsies, confirmed the diagnosis of a diffuse sclerosing osteomyelitis in the treated area. Osteomyelitis could be linked to a longstanding history of chronic and/or therapyresistant periodontal/endodontic pathology. CONCLUSION: The current retrospective case series seems to suggest that diffuse osteomyelitis should be considered as a risk indicator for severe peri-implantitis. Int J Oral Maxillofac Implants 2023;38:503-515. doi: 10.11607/jomi.9773.

Comparison of the efficacy and safety of standard- and high-dose daptomycin: A systematic review and meta-analysis.

AIMS: Standard doses of daptomycin at 4 and 6 mg/kg were used for the treatment of skin and soft tissue for infections and bacteraemia, respectively. However, increased doses of daptomycin are recommended for complicated infections by Gram-positive organisms. METHODS: A systematic review was conducted using 4 databases. We compared treatment success between standard-dose (SD, 4-6 mg/kg) and high-dose (HD, >6 mg/kg) daptomycin in patients with all-cause bacteraemia, complicated bacteraemia, infective endocarditis, osteomyelitis and foreign body/prosthetic infection as the primary outcome. We also compared the success between SD and HD2 (≥8 mg/kg) daptomycin treatments in patients with these diseases as the secondary outcome. The incidence of creatine phosphokinase (CPK) elevation was evaluated as safety. RESULTS: In patients with complicated bacteraemia and infective endocarditis, the treatment success was significantly lower in the SD group than in the HD group (odds ratio [OR] 0.48, 95% confidence interval [CI] 0.30-0.76 and OR 0.50, 95% CI 0.30-0.82) and HD2 group (OR 0.38, 95% CI 0.21-0.69 and OR 0.30, 95% CI 0.15-0.60), respectively. A significant difference was demonstrated only in the HD2 group in patients with bacteraemia, including simple infection. SD did not decrease the success rate for the treatment of osteomyelitis and foreign body/prosthetic infection. The incidence of elevated CPK was significantly lower in SD group than in HD group. CONCLUSION: SD daptomycin was associated with significantly lower treatment success than HD in patients with complicated bacteraemia/infective endocarditis. The CPK elevation should be considered in patients treated with high daptomycin doses.

Characteristics and incidence of vaccine adverse events after Bacille Calmette-Guérin vaccination: A national surveillance study in Japan from 2013 to 2017.

BACKGROUND: Japan amended the recommended age for the Bacille Calmette-Guérin (BCG) vaccination to less than 6 months after 2005, but subsequently amended the recommended age to 5-8 months (latest amendment, <1 year) in April 2013 due to the increasing incidence of BCG-associated osteitis/osteomyelitis since 2005. METHODS: We collected data on BCG-associated vaccine adverse events (VAEs) in the population aged <1 year between April 2013 and March 2017. The incidence of BCG-associated VAE was analyzed using census and vaccine coverage data from the government website. We compared the incidence of VAEs in patients vaccinated at less than 6 months with those vaccinated at 6 months or older. RESULTS: Among the 581 BCG-associated VAEs recorded during the study period, 354 (61%) were male, and the average age at vaccination was 5.7 months. The incidence of VAEs per million population aged <1 year at vaccination was highest for suppurative lymphadenitis (63.7), followed by skin lesions (38.4), and BCG-associated osteitis/osteomyelitis (3.1). Disseminated BCG and anaphylaxis were rare (1.1 and 1.6%, respectively). The incidence of VAEs in the population vaccinated at <6 months of age was higher for BCG-associated osteitis/osteomyelitis (3.8) and disseminated BCG (1.3) than in the population vaccinated at ≥6 months. CONCLUSIONS: The population vaccinated at <6 months of age was more likely to develop BCG-associated osteitis/osteomyelitis than the population vaccinated at ≥6 months of age, indicating that the change in the recommended vaccination age in 2013 might have contributed to the subsequent decrease in the incidence of BCG-associated osteitis/osteomyelitis.

Nonexposed antiresorptive agent-related osteomyelitis of the jaw: a single-center cohort study.

INTRODUCTION: The nonexposed variant of antiresorptive agent-related osteonecrosis of the jaw (ARONJ) presents with nonspecific clinical findings. The diagnosis of nonexposed ARONJ poses a critical challenge, and there is little evidence regarding its treatment and outcomes. This study aimed to examine the clinical outcomes in patients with nonexposed antiresorptive agent-related osteomyelitis of the jaw (AROMJ). The terms ARONJ and AROMJ were used separately in this study. MATERIALS AND METHODS: We enrolled patients with nonexposed AROMJ (osteomyelitis of the jaw without bone exposure associated with antiresorptive agents) with partial reference to an existing position paper on ARONJ. The initiating event of osteomyelitis was limited to periodontitis. Based on the findings of bone scintigraphy, panoramic radiography, computed tomography, and histopathological examination, we also used the hierarchical diagnostic criteria (HDC) for osteomyelitis of the jaw. RESULTS: There were 58 confirmed cases of nonexposed AROMJ based on the HDC. All patients had sufficient clinical findings to be diagnosed with nonexposed AROMJ as osteomyelitis underwent extraction with bone debridement. The healing rate was 93.1% (54/58). Univariable analysis showed a strong association between the healing status and malignant disease, while multivariable analysis showed no strong association between them. CONCLUSIONS: The present study had a relatively large sample size of patients with nonexposed AROMJ. The primary disease in patients with nonexposed AROMJ may not have a strong association with the healed status of the lesion. Based on its high healing rate, extraction with bone debridement in confirmed nonexposed AROMJ may prevent progression.

Moderate to Severe Soft Tissue Diabetic Foot Infections: A Randomized, Controlled, Pilot Trial of Post-debridement Antibiotic Treatment for 10 versus 20 days.

BACKGROUND: The optimal duration of antibiotic therapy for soft-tissue infections of the diabetic foot remains unknown. OBJECTIVE: We determine if antibiotic therapy after debridement for a short (10 days), compared with a long (20 days), duration for soft-tissue infections of the diabetic foot results in similar rates of clinical remission and adverse events (AE). SUMMARY OF BACKGROUND DATA: The optimal duration of systemic antibiotic therapy, after successful debridement, for soft tissue infections of diabetic patients is unknown. Because of the high recurrence risk, overuse is commonplace. METHODS: This was a randomized, controlled, non-inferiority pilot trial of cases of diabetic foot infection (excluding osteomyelitis) with the primary outcome of "clinical remission at 2-months follow-up". RESULTS: Among 66 enrolled episodes (17% females; median age 71 years), we randomized 35 to the 10-day arm and 31 to the 20-day arm. The median duration of the parenteral antibiotic therapy was 1 day, with the remainder given orally. In the intention-to-treat population, we achieved clinical remission in 27 (77%) patients in the 10-day arm compared to 22 (71%) in the 20-days arm ( P = 0.57). There were a similar proportion in each arm of AE (14/35 versus 11/31; P = 0.71), and remission in the per-protocol population (25/32 vs 18/27; P = 0.32). Overall, 8 soft tissue DFIs in the 10-day arm and 5 cases in the 20-day arm recurred as a new osteomyelitis [8/35 (23%) versus 5/31 (16%); P = 0.53]. Overall, the number of recurrences limited to the soft tissues was 4 (6%). By multivariate analysis, rates of remission (intention-to-treat population, hazard ratio 0.6, 95%CI 0.3-1.1; per-protocol population 0.8, 95%CI 0.4-1.5) and AE were not significantly different with a 10-day compared to 20-day course. CONCLUSIONS: In this randomized, controlled pilot trial, post-debridement antibiotic therapy for soft tissue DFI for 10 days gave similar (and non-inferior) rates of remission and AEs to 20 days. A larger confirmatory trial is under way. TRIAL REGISTRATION: ClinicalTrials NCT03615807.

Is mandibular osteomyelitis a sequela of SSRI-induced dental implant failure? A systematic review & case report.

BACKGROUND: To determine if the utilization of selective serotonin reuptake inhibitors (SSRIs) increases the risk of osteomyelitis as a sequela of dental implant failure. We also report the case of a patient on long-term SSRIs who presented with dental implant failure and subsequently developed mandibular osteomyelitis. METHODS: We performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) in PubMed, Google Scholar and Embase, for all records pertaining to SSRIs, dental implants, and mandibular osteomyelitis. RESULTS: SSRIs are associated with increased risk of dental implant failure, and our results suggest that they may be independently associated with mandibular osteomyelitis in the setting of implant failure. Though there was no evidence of mandibular osteomyelitis specifically following SSRI-related dental implant failure, there were a few case reports on osteomyelitis resulting from failed dental implant osseointegration. CONCLUSIONS: In the context of long-term SSRI utilization, our findings suggest that osteomyelitis should be considered in the differential diagnosis of patients with recent dental implant placement or failure.

Patterns of Care and Treatment Outcomes for Outpatient Daptomycin-Containing Regimens in Osteomyelitis.

BACKGROUND: Use of daptomycin at doses ≥ 6 mg/kg for treatment of osteomyelitis is increasing in clinical practice; unfortunately, limited data are available to guide optimal dosing and duration. The objective of this study was to assess daptomycin dosing and duration regimens for osteomyelitis treatment. METHODS: This was a retrospective, multi-site, cohort study conducted in an integrated healthcare delivery system. Nonpregnant patients ≥ 18 years of age with osteomyelitis diagnosed between November 1, 2003 and June 30, 2011, ≥ 2 weeks outpatient daptomycin therapy, and ≥ 1 month of follow-up were included. Daptomycin doses < 6 mg/kg and ≥ 6 mg/kg at durations of < 6 weeks and ≥ 6 weeks were examined with univariate and multivariate analyses to assess treatment success and all-cause mortality. RESULTS: A total of 247 patients were included, with 39 (15.8%), 37 (15.0%), 107 (43.3%), and 64 (25.9%) receiving < 6 mg/kg and ≥ 6 weeks, < 6 mg/kg and < 6 weeks, ≥ 6 mg/kg and ≥ 6 weeks, and ≥ 6 mg/kg and < 6 weeks of daptomycin therapy, respectively. Patients had a mean age of 58 years and had received prior vancomycin therapy (65.6%). Patients receiving < 6 weeks of therapy were less likely to experience treatment success compared with ≥ 6 weeks (41.5% vs 25.3%, adjusted odds ratio = 0.55; 95% confidence interval = 0.31-0.98) independent of duration. There were no differences across groups in mortality after adjustment. CONCLUSION: In a diverse clinical population, daptomycin for treatment of osteomyelitis of 6 weeks or longer duration was associated with success independent of dose. This finding supports longer treatment with daptomycin as a first-line agent in antimicrobial stewardship initiatives.

Skeletal-related side effects of acute lymphoblastic leukemia treatment in children / Az akut lymphoblastos leukaemiával kezelt gyermekek csontrendszerét érinto mellékhatások.

Összefoglaló. Bevezetés: A gyermekkori akut lymphoblastos leukaemia kezelése napjainkban 80% feletti túlélést tesz lehetové, de fontos cél a kezelés okozta mellékhatások kivédése és a gyermekek hosszú távú életminoségének javítása is. Célkituzés: A kemoterápia csontrendszerre kifejtett mellékhatásainak vizsgálata és a prognosztikai tényezok feltárása, a rizikófaktorok összegyujtése. Módszerek: Retrospektív vizsgálatunkba a Semmelweis Egyetem II. Gyermekgyógyászati Klinikáján 2007 és 2016 között kezelt 215, akut lymphoblastos leukaemiás gyermek közül a csontelváltozást észlelt betegeket vontuk be a következo, csontrendszert érinto megbetegedésekkel: 38 gyermeknél csökkent csontásványianyag-tartalom, 5 fonél osteonecrosis, 3 fonél osteomyelitis és 2 fo esetében patológiás fractura volt detektálható. Különbözo követési idopontokban gyujtöttünk oszteodenzitometriai adatokat, D-vitamin-, foszfát-, alkalikusfoszfatáz- és lipidszinteket is. Eredmények: Az oszteodenzitometriai értékek már a diagnóziskor csökkent értéket mutatnak, az intenzív vénás kemoterápia hatására pedig további csökkenés figyelheto meg (a lumbális gerinc Z-score-értéke a kezelés kezdetén: -1,5 ± 1,02, az intenzív vénás kezelés végén -1,8 ± 0,5). A Z-score-értékek a fenntartó terápia végére javuló tendenciát mutattak (-1,6 ± 0,5; p<0,05), majd az utánkövetés során ismételt javulás (-1,2 ± 0,4 [p<0,01] és -0,9 ± 0,4) figyelheto meg. A D-vitamin-szintek esetében az intenzív vénás kemoterápiát követoen fokozatos javulást láthattunk (20 ± 3,1 ng/ml vs. többéves utánkövetéskor 31 ± 2,6 ng/ml; p<0,001). A foszfát- és alkalikusfoszfatáz-szintek nem változtak számottevo mértékben a vizsgált idotartam során. A koleszterinszintek a terápia során folyamatos növekedést mutattak (a kemoterápia kezdetén 3,28 ± 0,3 mM/l vs. a fenntartó kezelés végén 4,62 ± 0,2 mM/l; p<0,0001). A HDL-koleszterin esetében szintén hasonló tendenciát figyelhettünk meg (a diagnóziskor 0,53 ± 0,09 mM/l vs. a fenntartó kezelés végén 1,48 ± 0,14 mM/l). Következtetés: Kiemelendo, hogy a gyógyult gyermekek utánkövetése, az oszteodenzitometriai mérések és a laborparaméterek ellenorzése rendkívül fontos, mivel csontelváltozásokkal a leukaemiás betegek esetén számolni kell. Orv Hetil. 2020; 161(49): 2086-2093. INTRODUCTION: Current treatment of pediatric acute lymphoblastic leukemia allows survival above 80%, but it is also very important to prevent treatment-related side effects and to improve long-term quality of life. OBJECTIVE: Our aim was to assess the side effects of chemotherapy on the skeletal system and to identify prognostic and risk factors. METHODS: Between 2007 and 2016, 215 children were treated with acute lymphoblastic leukemia at the 2nd Department of Paediatrics, Semmelweis University. In our retrospective study, we analyzed data of these children with skeletal-related side-effects (38 children with reduced bone mineral density, 5 with osteonecrosis, 3 with osteomyelitis and 2 with pathologic fracture). RESULTS: Osteodensitometric data, vitamin D, phosphate, alkaline phosphatase and lipid levels were collected at different follow-up times. Osteodensitometric values were already reduced at the time of diagnosis (lumbar spine Z-score: -1.5 ± 1.02) and intensive venous chemotherapy caused further decrease (-1.8 ± 0.5). Z-score showed an improving tendency at the end of the maintenance therapy (-1.6 ± 0.5; p<0.05), followed by further improvement later (-1.2 ± 0.4 [p<0.01] and -0.9 ± 0.4). Vitamin D levels showed improvement after intensive venous chemotherapy (20 ± 3.1 ng/ml vs. 31 ± 2.6 ng/ml at multi-year follow-up; p<001). Phosphate and alkaline phosphatase levels did not change considerably during the period considered. Cholesterol levels increased continuously during treatment (at the time of diagnosis 3.28 ± 0.3 mM/l vs. at the end of the maintenance therapy 4.62 ± 0.2 mM/l; p<0.0001). A similar trend was observed with HDL cholesterol levels (0.53 ± 0.09 mM/l vs. 1.48 ± 0.14 mM/l). CONCLUSION: In summary, we can conclude that follow-up of these children, osteodensitometric measurements and monitoring of laboratory parameters are extremely important, as bone abnormalities can occur in leukemia patients. Orv Hetil. 2020; 161(49): 2086-2093.

Adolescent with osteomyelitis after intramuscular administration of a vaccine: A case report.

OBJECTIVE: To emphasize adverse outcomes associated with applying adult immunization protocols to the pediatric population. CASE SUMMARY: A 15-year-old female with no past medical history developed severe pain in her left arm and decreased range of motion 11 days after receiving an intramuscular injection of the human papillomavirus vaccine. Over the following month, she was treated with a short course of steroids for frozen shoulder and gabapentin for Parsonage-Turner syndrome. During the third visit to a specialist for severe pain and loss of left arm mobility, she was sent to the emergency department for further workup. An x-ray and magnetic resonance imaging of the left arm were suspicious for osteomyelitis. The diagnosis was confirmed by incision and drainage of the abscess and a bone biopsy. A 6-week course of antibiotic therapy was initiated after the biopsy results. The injury was attributed to overpenetration by the needle during the intramuscular injection she had received in the previous month. PRACTICE IMPLICATIONS: As the number of states allowing pharmacists to vaccinate patients of all ages grows, pharmacists must be prepared to safely provide vaccinations to patients of varying sizes. Assessing body habitus while balancing the constant responsibilities of a community pharmacy will be a challenge. Introduction of a guidance document with specific needle lengths based on weight, age, and sex can address potential errors before they occur.

BCG-induced discitis and osteomyelitis in a patient with a history of bladder cancer.

This article describes the diagnosis and treatment of a patient with lumbar discitis and osteomyelitis caused by Bacillus Calmette-Guérin instillation therapy for treatment of superficial bladder cancer. Treatment of this rare condition consists of antituberculosis microbial therapy and one or more IV antibiotics to cover multidrug-resistant bacteria in the bone.

Clinical Manifestations, Management, and Outcomes of Osteitis/Osteomyelitis Caused by Mycobacterium bovis Bacillus Calmette-Guérin in Children: Comparison by Site(s) of Affected Bones.

OBJECTIVE: To evaluate the clinical manifestations, management, and outcomes of Mycobacterium bovis Bacillus Calmette-Guérin (BCG) osteitis/osteomyelitis. STUDY DESIGN: We reviewed 71 cases of BCG osteitis/osteomyelitis registered in Taiwan's vaccine injury compensation program (VICP) in 1998-2014. Demographic, clinical, laboratory, treatment, and outcome data were compared according to site(s) of infection. RESULTS: Involvement of a long bone of the lower extremity was present in 36.6% of the children, followed by foot bone (23.9%), rib or sternum (15.5%), upper extremity long bone (9.9%), hand bone (7%), multiple bones (4.2%), and vertebrae (2.8%). Children with lower extremity long bone involvement had a longer interval from receipt of BCG vaccine to presentation (median, 16.0 months; P = .02), and those with foot bone infection had higher rates of swelling (94.1%; P = .02) and local tenderness (76.5%; P = .004). Surgical intervention was performed in 70 children, with no significant difference in the number of procedures by site (median, 1.0 procedure per patient). Among the 70 children who received antimicrobial therapy, those with vertebral and multifocal infections had a longer duration of treatment (P < .001) and/or second-line antituberculosis medications (P = .002). Three children with vertebral and multifocal infections had major sequelae with kyphosis or leg length discrepancy. Outcomes were good for children with involvement of the ribs, sternum, and peripheral bones without multifocal involvement. The average time for functional recovery was 6.2 ± 3.9 months. CONCLUSION: Children with BCG osteitis/osteomyelitis in different bones had distinct presentations and outcomes. Pediatricians should consider BCG bone infection in young vaccinated children with insidious onset of signs and symptoms, and consider affected site(s) in the management plan.

Surgically treated osteonecrosis and osteomyelitis of the jaw and oral cavity in patients highly adherent to alendronate treatment: a nationwide user-only cohort study including over 60,000 alendronate users.

Osteonecrosis of the jaw (ONJ) is rare (2.53/10,000 person-years) among alendronate users, but long-term and compliant use are associated with an increased risk of surgically treated ONJ. Risk of surgically treated ONJ is higher in patients with rheumatoid diseases and use of proton pump inhibitors. INTRODUCTION: ONJ is a rare event in users of oral bisphosphonates. Our aims were to evaluate if the risk of surgically treated ONJ increases with longer or more compliant treatment with alendronate for osteoporosis and to identify risk factors for surgically treated ONJ. METHODS: Open nationwide register-based cohort study containing one nested case-control study. Patients were treatment-naïve incident users of alendronate 1996-2007 in Denmark, both genders, aged 50-94 at the time of beginning treatment (N = 61,990). Participants were followed to 31 December 2013. RESULTS: Over a mean of 6.8 years, 107 patients received surgery for ONJ or related conditions corresponding to an incidence rate of 2.53 (95% confidence interval (CI) 2.08 to 3.05) per 10,000 patient years. Recent use was associated with an adjusted odds ratio (OR) 4.13 (95% CI 1.94 to 8.79) compared to past use. Similarly, adherent users (medication possession ratio (MPR) >50%) were at two to threefold increased risk of ONJ compared to low adherence (MPR <50%), and long-term (>5 years) use was related with higher risk (adjusted OR 2.31 (95% CI (1.14 to 4.67)) than shorter-term use. History of rheumatoid disorders and use of proton pump inhibitors were independently associated with surgically treated ONJ. CONCLUSIONS: Our data suggest that recent, long-term, and compliant uses of alendronate are associated with an increased risk of surgically treated ONJ. Nevertheless, the rates remain low, even in long-term adherent users. ONJ risk appears higher in patients with conditions likely to indirectly affect the oral mucosa.

[Salmonella osteomyelitis - a rare differential diagnosis of bone tumors]. / Salmonellenosteomyelitis ­ eine seltene Differenzialdiagnose eines Knochentumors.

This case describes a rare salmonella infection suspected to be an osseous lymphoma. A 27-year-old female presented herself with painful swelling of her knee, with prednisolone-treated Crohn's disease as her only pre-existing condition. Salmonella species group C were detected in the osseous material derived from an extraction. The disease was treated with intravenous ceftriaxone, oral cotrimoxazole as well as multiple debridements. The working diagnosis should thus always be questioned and bone pain in patients who are immunosuppressed should be further investigated.

Delayed diagnosis of central skull-base osteomyelitis with abscess: case report and learning points.

Central skull-base osteomyelitis (CSBO) is a rare life-threatening infection, usually resulting from medial spread of necrotising otitis externa. Here, we describe a case with no identifiable source of infection, causing a delay in diagnosis. An 80-year-old man with Crohn's disease treated with mesalazine presented with collapse and tonic-clonic seizure. Computed tomography and magnetic resonance imaging showed a nasopharyngeal mass that was initially thought to be a neoplasm. Awaiting formal biopsy, he represented with collapse and repeat imaging showed features of abscess formation. Review of previous scans revealed skull-base erosion and the diagnosis was revised to skull-base osteomyelitis. This is the first reported case of CSBO associated with mesalazine use, an aminosalicylate used in Crohn's disease. It is only the second reported case with abscess formation. We discuss the learning points in making a timely diagnosis and examine the potential association of factors such as mesalazine use and abscess formation in this case.

A retrospective study of osteomyelitis and osteonecrosis of the jaws and its etiologic implication of bisphosphonate in Asians.

OBJECTIVE: The objective of this study were to find the annual case trend of inflammatory jawbone diseases and to investigate the impact of medication-related osteonecrosis of the jaws (MRONJ). MATERIAL AND METHODS: A retrospective study of 372 patients diagnosed with inflammatory jawbone condition except for alveolar osteitis from 2007 to 2015 was initiated. History taking and investigation of etiologic factors MRONJ, osteoradionecrosis (ORN), odontogenic infection, foreign body, and trauma were investigated. A separate analysis showed the number of MRONJ cases in two age groups (under 70 years; 70 years and over) and serum C-terminal peptide (s-CTX) values that were found. RESULTS: The results showed that the number of MRONJ cases was significantly larger in the older age group (p < 0.05). Regarding gender and sites of lesions, MRONJ was significantly frequent in the female and the mandible (p < 0.05). The R 2 values for the regression analysis for MRONJ (R 2 = 0.9234) and odontogenic etiology (R 2 = 0.0427) signified linear increase in the number of MRONJ cases, whereas bone lesions due to traditional odontogenic etiology stayed stationary. CONCLUSION: The number of MRONJ has escalated, and most of the patients are elderly people. The current trend of inflammatory conditions of the jaw may have changed since the advent of MRONJ. CLINICAL RELEVANCE: Long-term bisphosphonate therapy became a major risk factor for the osteomyelitis and osteonecrosis of the jaws. Thorough medical history, taking would be essential and communication with prescribing physicians should be emphasized during the dental treatment planning.

Bisphosphonate related osteonecrosis of calvarial bone.

BACKGROUND: A case of bisphosphonate related osteonecrosis of calvarial bone has not been reported. METHODS: The 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. RESULTS: Surgical debridement was performed and final pathology was consistent with osteonecrosis and osteomyelitis. CONCLUSIONS: This case illustrates that bisphosphonates can induce osteonecrosis of calvarial bone.