Search Results (85)

Background: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) represents a severe complication associated with bisphosphonate therapy commonly used in patients with osteoporosis and malignancies. Methods: This retrospective study evaluates the risk factors and clinical outcomes of BRONJ patients treated at the Oral and Maxillofacial Surgery Clinic in Iaşi, Romania, with the goal of optimizing preventive and therapeutic strategies. Data from 72 BRONJ patients treated between January 2013 and December 2023 were analyzed. Results: The majority (83.3%) of patients had underlying malignancies, predominantly breast and prostate cancers. The mandible was most affected, with tooth extraction identified as the primary triggering event. Systemic comorbidities, notably arterial hypertension, diabetes mellitus, and concurrent chemotherapy, were significantly associated with increased BRONJ severity. Surgical intervention was frequently required, with sequestrectomy being the predominant procedure, reflecting advanced disease at the time of diagnosis. Conclusions: The findings underline the critical importance of early identification, preventive dental management, and a collaborative multidisciplinary approach to improve patient prognosis. Full article

Background: In 2020, the definition of Bisphosphonate-Related Osteonecrosis of the Jaws (BRONJ) was revised. The current definition is Medication-Related Osteonecrosis of the Jaws (MRONJ), to underline the fact that not only bisphosphonates are implicated in the onset of the disease. This study aims to investigate the efficacy of marginal resection using a piezoelectric device in patients with BRONJ. Methods: A retrospective study was conducted on subjects treated at the Dental Clinic University Hospital of Padua (Italy) from January 2017 to April 2024. Only patients diagnosed with BRONJ stages 1 and 2, who underwent marginal resection of the maxillae using a piezoelectric instrument were included. Patients who had received radiotherapy to the head and neck region, those with MRONJ, and those with primary tumors of the maxillary bones were excluded. Marginal resection was considered an effective treatment when complete epithelialization of the surgical site was achieved, with no signs or symptoms of disease, and the condition remained stable one-year post-operation. Results: In total, 21 patients (17 females and 4 males) were selected. A single resection was performed for each patient, resulting in a total of 21 surgeries: 14 in the mandible and 7 in the maxilla. At one-year post-surgery, 20 patients showed no signs or symptoms of the disease. One patient experienced two recurrences, both of which were subsequently treated. Conclusions: marginal resection using a piezoelectric device is an effective procedure for the treatment of BRONJ, although it remains a relatively invasive and destructive therapeutic approach. Full article

Background: Oral bisphosphonates (BPs) are the standard therapy for osteoporosis and skeletal metastases, and exhibit anti-tumor properties in preclinical models. Observational studies assessing their impact on colorectal cancer (CRC) risk have yielded inconsistent results. We aimed to systematically review and meta-analyze the association between oral bisphosphonate use and CRC risk, applying a unified exposure definition. Methods: A systematic search was conducted in PubMed, Embase, and Scopus (January 1966–April 2025) to identify cohort, nested case–control, or population-based case–control studies reporting adjusted estimates of relative risk, odds ratios (ORs), or hazard ratios (HRs) for CRC among oral bisphosphonate users. Two reviewers independently screened studies, extracted data, and assessed quality using the Newcastle–Ottawa Scale. Random-effects meta-analyses pooled risk estimates for “any use” of bisphosphonates, with subgroup analyses by duration of use (<1, 1–3, >3 years). We assessed publication bias through Egger’s test and the trim-and-fill method. Results: A total of eight studies published between 2010 and 2020, including 29,169 CRC cases, fulfilled the inclusion criteria. Any bisphosphonate use was not significantly associated with CRC risk (pooled OR 0.97; 95% C.I., 0.90–1.03). However, 1–3 years of use conferred a protective effect (OR 0.86; 95% C.I., 0.73–0.99), as did >3 years (OR 0.91; 95% C.I., 0.85–0.97). Heterogeneity was moderate, and no significant publication bias was detected. Conclusions: While overall oral bisphosphonate exposure is not significantly linked to CRC risk, prolonged use (≥1 year) appears to reduce risk. Prospective studies and randomized trials are needed to confirm these chemo-preventive effects and guide clinical recommendations. Full article

Background/Objectives: Medication-related osteonecrosis of the jaw (MRONJ) is a challenging condition often associated with bisphosphonate use, leading to impaired bone healing and difficult clinical management. Given the lack of predictable therapeutic options, this study investigated the effects of systemic ozone therapy on MRONJ healing. This study aimed to analyze the effects of systemic ozone therapy on oral hard and soft tissue healing in senescent rats with medication-related osteonecrosis of the jaw (MRONJ) induced by antiresorptive therapy. Methods: Twenty-eight senescent Wistar rats, aged eighteen months and weighing ~350 g, were used for this study. The animals were divided into four groups. The negative control (SAL) group received saline applications, while the control-treated (SAL+OZ) group received saline applications and ozone therapy (0.7 mg/kg). The MRONJ (ZOL) group received Zoledronate, an intravenous antiresorptive drug (100 μg/kg), and the MRONJ-treated (ZOL+OZ) group received zoledronate application and was treated with systemic ozone therapy (0.7 mg/kg). All rats underwent molar extraction in the third week of the experiment and were euthanized in the seventh week of the experiment. The mandibles were resected, reduced, and prepared for microtomographic analysis, histopathological/histometric analysis, and immunohistochemistry. Results: The ZOL group presented characteristics of vitreous, non-vital, and dense bone, poor vascularization, and high values of inflammation markers compatible with MRONJ. In contrast, the ZOL+OZ group exhibited improvement in alveolar bone and soft tissue healing, a decrease in nonvital bone area, and modulation of local inflammation. Conclusions: It can be concluded that Ozone therapy improved oral hard and soft tissue healing of MRONJ in senescent female rats subjected to antiresorptive drugs and might be considered for future clinical applications. Full article

Medication-related osteonecrosis of the jaw (MRONJ) is a multifactorial condition defined as an adverse drug reaction that results in progressive jawbone destruction and necrosis in individuals treated with certain medications, occurring without a history of prior radiotherapy. These drugs are mainly bisphosphonates, denosumab, and other bone-modifying agents, anti-angiogenic agents such as anti-endothelial growth factor, tyrosine kinase inhibitors, and proteins classified as mammalian targets of rapamycin. The diagnosis of MRONJ is based on clinical (exposed jawbone, fistula with pus, hyperplasia of the mucosa overlying the necrotic bone tissue) and radiological evaluation. We report four cases of clinical and radiological evidence of osteonecrosis of the jaw that are unrelated to the use of antiresorptive or anti-angiogenic agents. In two instances, histological and microbiological evidence was also found (high concentration of Actinomyces, the microbe most commonly found in oral sites affected by MRONJ). These atypical cases are reported to highlight the possibility that other, previously undocumented, drugs may also contribute to the development of ONJ Full article

This review systematically examines the oral complications associated with conventional and novel anti-cancer therapies. It highlights that while molecularly targeted agents including monoclonal antibodies targeting the vascular endothelial growth factor and its receptor, the epidermal growth factor receptor, tyrosine kinase inhibitors, and immune checkpoint inhibitors tend to exhibit a lower overall toxicity profile compared to traditional cytotoxic chemotherapeutics, they are nonetheless linked to significant oral adverse events. These complications encompass inflammatory mucosal reactions known as mucositis, salivary gland dysfunction leading to a sensation of dryness in the mouth, taste alterations referred to as dysgeusia, and, critically, medication-related osteonecrosis of the jaw. In particular, bone-modifying agents such as bisphosphonates and denosumab disrupt bone remodeling and the formation of new blood vessels, thereby increasing the susceptibility to osteonecrosis of the jaw, especially following invasive dental procedures. The review delineates the multifactorial pathogenesis underlying these toxicities, which involves direct cell toxicity, impaired wound healing, and secondary infections. Furthermore, it emphasizes the importance of pre-treatment dental evaluation and preventive strategies including patient education, prophylactic dental care, and the integration of adjunctive therapies such as laser therapy and autologous platelet concentrates to mitigate these adverse effects. The analysis advocates for interdisciplinary collaboration between oncologists and dental professionals to optimize management protocols, enhance treatment adherence, and ultimately improve the quality of life for oncology patients undergoing anti-cancer therapy. Full article

Background and Objectives: Osteomyelitis is a progressive bone infection requiring a combination of antimicrobial and anti-inflammatory therapies. While antibiotics remain the cornerstone of treatment, the role of NSAIDs and steroidal anti-inflammatory drugs (SAIDs) in modulating inflammation and improving clinical outcomes warrants further investigation. This systematic review evaluates the effectiveness and safety of combined antibiotic and NSAID/SAID therapy in osteomyelitis, aligning treatment strategies with disease stage and pathogenesis. Materials and Methods: A systematic search was conducted in Web of Science, Scopus, and PubMed from July 2024 to November 2024, following PRISMA and CARE guidelines. The studies were selected based on detailed pharmacological data, treatment outcomes, and follow-up analysis. The risk of bias was assessed using the Critical Appraisal Skills Programmed (CASP) tool. Statistical reliability between coders was evaluated using Cohen’s kappa coefficient (κ = 0.636–0.909) and intra-class correlation coefficient (ICC = 1.0). Results: Four case studies, representing acute, chronic, recurrent, and SAPHO syndrome-associated osteomyelitis, demonstrated variable responses to combined therapy. Antibiotics alone were effective in acute cases, while NSAIDs/SAIDs significantly contributed to inflammatory control in chronic and immune-mediated osteomyelitis. Glucocorticoids (e.g., prednisolone, methylprednisolone) showed efficacy in reducing systemic inflammation, with no major adverse effects reported. The transition from intravenous to oral antibiotic therapy was observed in all cases, ensuring sustained infection control. Conclusions: This review highlights the critical role of NSAIDs/SAIDs in complementing antibiotic therapy, particularly in chronic and refractory osteomyelitis. Stage-specific pharmacological interventions improve treatment outcomes, and future research should explore bisphosphonates and immunomodulatory agents to refine therapeutic approaches. These findings reinforce the need for personalized osteomyelitis management based on pathogenesis, microbiology, and disease progression. Full article

Background: This study aimed to evaluate the efficacy of pentoxifylline and tocopherol therapy in patients with medication-related osteonecrosis of the jaw (MRONJ). Methods: During this study, 43 patients participated, including 21 women and 22 men with a mean age of 66.8 years, who showed 63 areas of osteitis altogether. The diagnosis was made based on X-ray imaging and histopathological findings. All the subjects received pharmacological treatment with pentoxifylline 400 mg and tocopherol 400 IU. The study scheme consisted of initial observation and two follow-up examinations every 5–6 months. MRONJ severity, peripheral blood parameters, and CRP levels were evaluated. The obtained results were statistically analyzed. Results: Complete remission occurred in 46% of the subjects, with a higher rate among those taking bisphosphonates intravenously compared to oral administration. The efficacy of pentoxifylline and tocopherol treatment was not influenced by gender or lesion location. Moreover, the worst response to treatment was observed in the group with the highest disease stage, as determined in the initial study. Conclusions: Pentoxifylline and tocopherol therapy in MRONJ was effective in patients taking oral and intravenous bisphosphonates, in patients with osteoporosis, and undergoing oncological treatment. This treatment approach allows surgery to be avoided or significantly reduced. The good response to pharmacotherapy observed in patients with early stages of MRONJ shows an urgent need to monitor the patients treated with bisphosphonates carefully to diagnose MRONJ at the initial phase. Full article

Background: Teriparatide (TPT) acts against severe primary (postmenopausal) osteoporosis (MOP), and it requires continuation with another anti-resorptive drug to conserve or enhance the effects on fracture risk reduction. Objective: To analyse the sequential pharmacotherapy in MOP who were treated upon a 24-month daily 20 µg TPT protocol (24-mo-TPT) followed by another 12 months of anti-resorptive drugs (12-mo-AR) amid real-life settings. Hypotheses: 1. TPT candidates had a more severe fracture risk profile versus those who did not fulfil the TPT criteria according to the national protocol of TPT initiation; 2. Patients treated with TPT improved their DXA profile after 24 mo; 3. After 1 year of therapy since the last TPT injection, the improved bone profile and fracture risk at the end of the TPT protocol were conserved; 4. The mineral metabolism assays and fracture risk status were similar at TPT initiation between those who finished the 24 mo protocol and those who prematurely stopped it. Methods: This was a longitudinal, retrospective, multicentre study in MOP. The entire cohort (group A) included the TPT group (B) versus the non-TPT group (non-B). Group B included subjects who finished 24-mo-TPT (group P) and early droppers (ED), and then both continued 12-mo-AR. Results: Group B (40.5%) from cohort A (N = 79) vs. non-B had lower T-scores, increased age and years since menopause. A similar profile of demographic features, BTM, and prevalent fractures (73%, respectively, 57%) was found in group P (72%) vs. ED (21.8%). Group P: osteocalcin was statistically significantly higher at 12 mo (+308.39%), respectively, at 24 mo (+171.65%) vs. baseline (p < 0.001 for each), while at 12-mo-AR became similar to baseline (p = 0.615). The cumulative probability of transient hypercalcemia-free follow-up of protocol had the highest value of 0.97 at 6 mo. An incidental fracture (1/32) was confirmed under 24-mo-TPT. BMD had a mean percent increase at the lumbar spine of +8.21% (p < 0.001), of +12.22% (p < 0.001), respectively, of +11.39% (p < 0.001). The pharmacologic sequence for 12-mo-AR included bisphosphonates (24.24% were oral BP) or denosumab (13%). BTM showed a suppression at 12-mo-AR (p < 0.05), while all BMD/T-scores were stationary. No incidental fracture was registered during 12-mo-AR. Conclusions: All research hypotheses were confirmed. This study in high-risk MOP highlighted an effective sequential pharmacotherapy in reducing the fracture risk as pinpointed by BMD/T-score measurements and analysing the incidental fractures profile. Full article

Background: Advancements in pharmacology have led to the introduction of novel antiresorptive and antiangiogenic drugs, which are associated with the side effect of medication-related osteonecrosis of the jaw (MRONJ). The aim of this study was to evaluate the impact of different blood levels of vitamin D on the course of treatment, as well as the role of vitamin D supplementation during the treatment of primary diseases involving bisphosphonates or denosumab. Methods: The clinical trial involved 64 patients diagnosed with medication-related osteonecrosis of the jaw (MRONJ) treated at the Department of Oral Surgery. Participants underwent baseline panoramic radiographs and Cone Beam Computed Tomography (CBCT) scans, with MRONJ severity categorized according to the AAOMS classification. This study included two groups: 37 patients (n = 37) in the experimental group received high-dose vitamin D supplementation (10,000 IU/day for 4 weeks, followed by a maintenance dose of 5000 IU/day), while 27 patients (n = 27) in the control group received no supplementation. Vitamin D levels were measured at baseline, 3 months, and 6 months, and the relationship between vitamin D supplementation and clinical outcomes, including MRONJ risk and healing, was evaluated. All participants received an antibiotic regimen pre- and post-surgery. Pain intensity was assessed at multiple time points using the Visual Analog Scale (VAS). Results: This study showed significant increases in serum vitamin D levels in the experimental group at 3 and 6 months (p < 0.05). In the prophylactic context, Vitamin D supplementation prior to or during tooth extraction reduced the risk of developing severe MJRON (OR = 68.57; p < 0.001). In the therapeutic context among patients with established MJRON, vitamin D supplementation did not significantly predict postoperative complications (p = 0.079) or complete healing (OR = 2.34; p = 0.051). However, overall healing rates were somewhat higher in the supplemented group, though they did not reach statistical significance. Antibiotic protection uses also reduced the need for further treatment (OR = 6.20; p < 0.001). Conclusions: Prophylactic high-dose vitamin D supplementation may help prevent severe MRONJ in at-risk patients undergoing tooth extraction. Once MRONJ is established, however, vitamin D alone may not significantly alter immediate postoperative outcomes, although further research is needed to clarify its potential adjunctive benefits. Full article

Objectives: This work investigated the effect of bacterial nanocellulose (BNC) alone or with chemisorbed chlorhexidine or povidone-iodine on post-tooth extraction repair in rats undergoing bisphosphonate therapy. Methods: Forty Wistar rats were treated with zoledronic acid, subjected to tooth extractions and allocated into groups according to the material inserted in the post-extraction socket: (1) BNC (n = 10); (2) BNC/Iodine (n = 10); (3) BNC/Chlorhex (n = 10); (4) Control (n = 10). Maxillae were dissected and macro- and microscopically analyzed. Results: Oral lesion frequency on macroscopic examination did not differ between the groups, whereas it was larger in the BNC/Iodine group compared to the BNC/Chlorhex and Control. BNC/Chlorhex had significantly more connective tissue than did BNC but did not differ from the BNC/Iodine and Control. Epithelium, vital bone, non-vital bone, tooth fragment and inflammatory infiltrate did not significantly differ between the groups. BNC/Iodine showed greater CD31 immunostaining compared to BNC and the Control. Myeloperoxidase staining did not differ between the groups, and scanning electron microscopy analysis showed similar characteristics in all groups. Conclusions: BNC with chemisorbed povidone-iodine is associated with increased vascularization in post-extraction wounds of rats undergoing bisphosphonate therapy, whereas BNC with chemisorbed chlorhexidine improves connective tissue formation. BNC works as an effective carrier for the antiseptics tested. Full article

The COVID-19 pandemic has significantly impacted healthcare systems worldwide, including dental care. This study aimed to investigate the effects of the pandemic on the management of medication-related osteonecrosis of the jaw (MRONJ). Abnormal blood glucose levels may contribute to the development of MRONJ and act as an important risk factor. This retrospective study included 217 patients with MRONJ. The patients were divided into two groups: the pre-COVID-19 group (16 March 2018 to 16 March 2020; 75 patients; 46 females and 29 males; average age, 74.5 years) and the post-COVID-19 group (1 June 2022 to 1 June 2024; 142 patients; 91 females and 51 males; average age, 69.6 years). Data pertaining to demographic characteristics, length of hospital stay, glucose levels, location of lesions, and underlying diseases were collected. The average length of hospital stays was 4 and 5 days in the pre- and post-COVID-19 groups, respectively. The average fasting glucose levels were 5.5 and 5.9 mmol/L in the pre- and post-COVID-19 groups, respectively. Localization patterns shifted, with a higher incidence in the maxilla in the post-COVID-19 group. These findings suggest a significant increase in MRONJ cases and changes in clinical outcomes due to the pandemic. The increase in the number of patients treated after the pandemic highlights the importance of ongoing vigilance and adaptation in preventing MRONJ, with a particular focus on risk factors. Full article

Background and Objectives: Osteoporosis is becoming more prevalent with the rise in the aging population, leading to the increased use of bisphosphonates for treatment. While these medications are effective in preventing osteoporotic fractures, long-term use has been associated with atypical insufficiency fractures, primarily in the femur. However, atypical fractures in other weight-bearing bones, such as the tibia, have rarely been reported. This study aims to present a case of an atypical insufficiency fracture of the tibia in an elderly female who has been on long-term bisphosphonate therapy and to review treatment outcomes within the context of the current literature. Patient concerns: A 76-year-old female presented with pain in the proximal right tibia, developing two months prior without trauma. She had been receiving long-term bisphosphonate therapy for osteoporosis, initially taking sodium risedronate orally for 4 years, followed by intravenous ibandronate for 10 years. Physical examination revealed localized tenderness, and radiographs showed cortical thickening and a horizontal fracture line in the proximal right tibia. MRI confirmed these findings, along with surrounding edema. The laboratory results were mostly normal, but the bone formation marker osteocalcin was significantly reduced. The patient had a history of insufficiency fractures in the ipsilateral tibia and contralateral femur, previously treated conservatively with teriparatide. A similar conservative approach was attempted but failed, leading to surgical intervention with intramedullary nailing and supplementary plating. At the 8-month follow-up, the patient showed successful fracture union and resolution of symptoms. Conclusion: Long-term use of bisphosphonates, though effective for osteoporosis, can lead to atypical insufficiency fractures, primarily in the femur but also occasionally in the tibia. Clinicians should consider this possibility when patients present with pain in weight-bearing bones without a history of trauma. Prompt diagnosis through thorough history-taking, physical examination, and appropriate imaging is essential to ensure timely management. Full article

Background: Osteoporosis and vertebral fractures (VFs) are frequently observed in males living with HIV (MLWH). While bisphosphonates seem effective on bone mineral density (BMD) in MLWH, data on VFs are lacking. In this real-life longitudinal study performed on 118 MLWH (median age 53) who were followed-up for a median of 7 years, we aimed to evaluate the long-term efficacy of oral bisphosphonates on VFs in MLWH. Methods: The inclusion criteria were age >18, stable HIV infection, bisphosphonate-naïve, blood samples from the same laboratory, and three densitometries and morphometries performed with the same densitometer. Results: At baseline, VFs were detected in 29/118 patients (24.6%). Patients with VFs were older (p. 0.042), had longer HIV infection duration (p. 0.046) and antiretroviral exposure (p. 0.025), and demonstrated higher luteinizing hormone levels (LH, p. 0.044). Of the 29 patients with VFs at inclusion, 11 developed new VFs, of which 8 were under oral bisphosphonates (p. 0.018). Among the 89 without basal VFs, 11 developed VFs, of which 2 were under oral bisphosphonates. Patients with a worsened bone condition (regarding BMD and/or new VFs, n. 32) had more frequently high LH levels (>9.4 mIU/mL, p. 0.046) and higher HCV co-infection compared to patients with a stable bone condition (p. 0.045). It should be noted that 38.6% of patients discontinued oral bisphosphonates due to medical indication or personal choice, and 14.0% never started them. Conclusions: In conclusion, we found that oral bisphosphonates were not completely effective in preventing VFs, especially in patients with VFs at baseline; this is probably due to the multifactorial pathogenesis of fragility fractures in this population. A poor adherence to treatment and attention to gonadal function are also important issues in this population. Full article

Generalized arterial calcification of infancy (GACI) is a rare disease characterized by arterial calcification. GACI is caused by a mutation in the ENPP1 or ABCC6 genes. GACI causes severe hypertension and heart failure, and approximately 50% of patients die within the first 6 months. In particular, preterm infants with GACI often die due to immature cardiac function. Bisphosphonates are effective in treating GACI; however, no standardized treatment regimen is available. We experienced a case of a preterm infant with GACI born at 30 weeks gestation. Ultrasonography showed high-intensity lesions in the arteries, and computed tomography revealed calcification of the arteries throughout the body, leading to the diagnosis of GACI. We administered intravenous pamidronate, and her cardiac contraction improved. The initial scheduled interval between drug administrations was 2 months. However, the cardiac contraction worsened 1 month after the pamidronate administration. Therefore, we decreased the dosing interval and administered a second course of pamidronate, which improved her cardiac function. We then switched to oral etidronate. To improve the morbidity and mortality rates of preterm infants with GACI, it is important to obtain an early diagnosis of GACI by investigating high-intensity lesions in the arteries and performing early administration of an appropriate type of bisphosphonate. Full article