Review
Medicine, General & Internal
Alejandro Lorenzo-Pouso, Jose Bagan, Leticia Bagan, Pilar Gandara-Vila, Cintia M. Chamorro-Petronacci, Pablo Castelo-Baz, Andres Blanco-Carrion, Maria Angeles Blanco-Fernandez, Oscar Alvarez-Calderon, Javier Carballo, Mario Perez-Sayans
Summary: This manuscript critically reviewed the medication-related osteonecrosis of the jaw (MRONJ), updating key terminology, concepts, and current trends in prevention and diagnosis, while examining therapeutic options available. By perusing relevant literature, the review updated the understanding of MRONJ, highlighting gaps in knowledge and emphasizing the need for further research.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Immunology
Weidong Zhang, Ling Gao, Wenhao Ren, Shaoming Li, Jingjing Zheng, Shasha Li, Chunmiao Jiang, Shuying Yang, Keqian Zhi
Summary: Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse drug effect, with hypotheses involving reduced bone remodeling, infection, inflammation, and bisphosphonates-induced immune dysfunction. Treatment with bisphosphonates disrupts mucosal and osteo immune homeostasis, impairing the body's ability to resist infection and repair from injury, contributing to the development of MRONJ.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Toxicology
Bhumrapee Srivichit, Chanisa Thonusin, Nipon Chattipakorn, Siriporn C. Chattipakorn
Summary: Bisphosphonates are commonly used in the treatment of bone and joint diseases, but long-term use can lead to osteonecrosis. Osteonecrosis is characterized by cell death and impaired cell functions, with medication-related osteonecrosis of the jaw being the most concerning condition. In addition to surgical treatment, non-surgical interventions have been explored to mitigate bisphosphonate-induced osteonecrosis.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Medicine, General & Internal
Gabor Kammerhofer, Daniel Vegh, Dorottya Banyai, Adam Vegh, Arpad Joob-Fancsaly, Peter Hermann, Zoltan Geczi, Tamas Hegedus, Kata Sara Somogyi, Bulcsu Bencze, Zita Biczo, Donat Huba Juhasz, Peter Zaborszky, Marta Ujpal, Mihaly Tamas Vaszilko, Zsolt Nemeth
Summary: This study aimed to evaluate the association between hyperglycemia and medication-related osteonecrosis of the jaw (MRONJ). The results showed a significant association between hyperglycemia and MRONJ, suggesting that hyperglycemia may lead to vascular anomaly and immune dysfunction, resulting in necrosis after tooth extraction.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Dentistry, Oral Surgery & Medicine
Puhan He, Kevin Francois, Nima Missaghian, Anh D. Le, Thomas R. Flynn, Rabie M. Shanti
Summary: This study aims to compare the types of bacteria isolated in osteomyelitis, osteoradionecrosis, and MRONJ cases. The results show that non-resident bacteria are more frequently isolated in osteomyelitis patients, while opportunistic organisms are more commonly found in patients diagnosed with osteoradionecrosis. There is no difference in the frequency of resident bacteria between different disease types.
JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY
(2022)
Article
Cell Biology
Wen Pan, Jianyu Gu, Shihan Xu, Chunmei Zhang, Jinsong Wang, Songlin Wang, Junji Xu
Summary: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious complication in patients with osteoporosis or metastatic bone cancer. The study found that dietary nitrate, abundant in green vegetables, can protect against BRONJ-like lesions in mice. Nitrate intake increased plasma nitric oxide levels, reducing monocyte necrosis and inflammatory cytokine production. The findings suggest that dietary nitrate can inhibit monocyte necroptosis in BRONJ and promote bone remodeling after injury.
CELL PROLIFERATION
(2023)
Review
Chemistry, Multidisciplinary
Krzysztof Wrobel, Maciej Sikora, Maciej Checinski, Maria Jas, Dariusz Chlubek
Summary: MRONJ is a condition that is becoming more common in dental and maxillofacial practice, requiring comprehensive, accessible, and up-to-date data. Besides bisphosphonates, angiogenesis inhibitors and anti-RANKL monoclonal antibodies can also increase the risk of the disease. Thorough physical examination, periodic correction of dental prostheses, and adequate preparation for oral procedures can prevent or minimize the risk of MRONJ.
APPLIED SCIENCES-BASEL
(2021)
Review
Oncology
Ioannis Gkouveris, Akrivoula Soundia, Panagiotis Gouveris, Dionysia Zouki, Danny Hadaya, Sotirios Tetradis
Summary: Medication-related Osteonecrosis of the Jaw (MRONJ) is a significant complication of antiresorptive medications used in the management of bone diseases. Studies have shown that these medications may affect immune system components, particularly macrophages, and their involvement in the pathogenesis of MRONJ. Understanding the role of macrophages in MRONJ pathophysiology could lead to new insights for disease prevention and control.
Article
Dentistry, Oral Surgery & Medicine
Vy Ngoc Thuy Tran, Risa Chaisuparat
Summary: The study investigated the morphology and quantity of osteoclasts in MRONJ, showing enhanced activity and increased number. Presence of osteoblasts, inflammation, and bacteria correlated with changes in osteoclasts. TRAP-positive numbers and intensity did not significantly differ between MRONJ and other groups.
JOURNAL OF ORAL PATHOLOGY & MEDICINE
(2021)
Article
Dentistry, Oral Surgery & Medicine
Isabel Pennings, Alison Moskowitz, Gunjan Shah, Cherry Estilo, Joseph M. Huryn, SaeHee K. Yom
Summary: We report a case of osteonecrosis of the jaw (ONJ) associated with pembrolizumab, a rare yet potentially emerging complication. The temporal relationship and treatment regimen suggest an association between pembrolizumab/GVD therapy and ONJ development, with the possibility of thrombocytosis and anatomical factors playing a role. As the use of pembrolizumab is expected to increase, documenting such cases is important for informing dental treatment in cancer patients undergoing pembrolizumab therapy.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY
(2023)
Article
Medicine, General & Internal
Yesel Kim, Jeong-Kui Ku
Summary: This study successfully established a MRONJ rat model on the calvaria, which mimicked the characteristics of MRONJ and can be used for developing treatments for MRONJ.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Oncology
Hironobu Hata, Kenji Imamachi, Michihiro Ueda, Masashi Matsuzaka, Hiroaki Hiraga, Toshihisa Osanai, Toru Harabayashi, Katsuya Fujimoto, Satoshi Oizumi, Masato Takahashi, Kazuhito Yoshikawa, Jun Sato, Yutaka Yamazaki, Yoshimasa Kitagawa
Summary: The study aimed to clarify the incidence of MRONJ and the corresponding survival rate of patients treated with zoledronic acid for different types of cancer. The results showed that patients with shorter survival times did not develop MRONJ, and dentists need to be aware of prognosis-related factors to predict MRONJ risk for effective dental management planning.
SUPPORTIVE CARE IN CANCER
(2022)
Article
Dentistry, Oral Surgery & Medicine
Anubhuti Sood, Vivek Nayyar, Ajoy Roychoudhury, Ashu Seith Bhalla, Deepika Mishra
Summary: The COVID-19 pandemic has led to the emergence of new variants of SARS-CoV-2 and the development of several post-COVID conditions. This report describes a new post-COVID condition observed in patients who have recently recovered from COVID-19 and have received high dose steroid treatment - spontaneous de novo development of steroid induced avascular necrosis in the jaws. This condition is distinct from previously reported medication-related osteonecrosis of the jaws and further research is needed to understand its features.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY
(2023)
Article
Endocrinology & Metabolism
Ioannis Gkouveris, Danny Hadaya, Naseim Elzakra, Akrivoula Soundia, Olga Bezouglaia, Sarah M. Dry, Flavia Pirih, Tara Aghaloo, Sotirios Tetradis
Summary: Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication of antiresorptive or antiangiogenic medications. This research identified the overexpression of high mobility group box 1 (HMGB1) during osteocytic death in the early phase of MRONJ, and demonstrated the role of the HMGB1-RAGE pathway in promoting bone necrosis. The HMGB1-RAGE pathway may serve as a promising therapeutic target for MRONJ.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Ilaria Roato, Rodolfo Mauceri, Vincenzo Notaro, Tullio Genova, Vittorio Fusco, Federico Mussano
Summary: The pathogenesis of medication-related osteonecrosis of the jaw (MRONJ) involves various factors, and antiresorptive drugs (ARDs), such as bisphosphonates (BPs) and denosumab (Dmab), play a significant role in its development. The time exposure, cumulative dose, and administration intensity of these drugs are crucial in the treatment of patients, particularly cancer patients who have the highest incidence of MRONJ. BPs and Dmab have different mechanisms of action on bone and immune subsets, which ultimately contribute to the onset of MRONJ. However, there is a lack of data on the effects of Dmab, highlighting the need for further studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Obstetrics & Gynecology
I. R. Reid
Summary: Optimizing bone health involves not smoking, limiting alcohol intake, maintaining a healthy body weight, consuming adequate protein and calcium, and using vitamin D supplements for those with poor sunlight exposure. Calcium supplements are not recommended due to potential side effects and lack of proven value.
Review
Nutrition & Dietetics
Sarah M. Bristow, Mark J. Bolland, Greg D. Gamble, William Leung, Ian R. Reid
Summary: The review found no significant association between calcium intake and change in bone mineral density in older adults, especially among women over 60 years old. The positive findings in studies with high rates of hormone treatment or osteoporosis therapy use were likely due to confounding effects from co-administration of calcium supplements with these medications.
EUROPEAN JOURNAL OF CLINICAL NUTRITION
(2022)
Article
Endocrinology & Metabolism
Dennis M. Black, Ian R. Reid, Nicola Napoli, Susan K. Ewing, Masataka Shiraki, Toshitaka Nakamura, Yasuhiro Takeuchi, Anne L. Schafer, Tiffany Y. Kim, Jane A. Cauley
Summary: The study indicates that women who experience an acute-phase reaction (APR) when starting Zoledronic acid (ZOL) will have a larger reduction in vertebral fracture risk with ZOL.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Article
Endocrinology & Metabolism
Andrew Grey, Mark J. Bolland, Anne Horne, Borislav Mihov, Greg Gamble, Ian R. Reid
Summary: The study found that a single 5 mg dose of zoledronate and 1 or 2.5 mg doses every 5 years can prevent bone loss at the hip and spine in older postmenopausal women for 8 to 10 years.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Article
Endocrinology & Metabolism
Paul D. Miller, Jonathan D. Adachi, Ben-Hur Albergaria, Angela M. Cheung, Arkadi A. Chines, Evelien Gielen, Bente L. Langdahl, Akimitsu Miyauchi, Mary Oates, Ian R. Reid, Norma Ruiz Santiago, Mark Vanderkelen, Zhenxun Wang, Zhigang Yu
Summary: This post hoc analysis examined the efficacy and safety of romosozumab in postmenopausal women with osteoporosis and mild-to-moderate chronic kidney disease (CKD). The findings showed that romosozumab effectively increased bone mineral density and reduced the risk of vertebral fractures, with a similar safety profile across different levels of kidney function.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Editorial Material
Endocrinology & Metabolism
Ian R. Reid
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Endocrinology & Metabolism
John D. Sluyter, Yoshihiko Raita, Kohei Hasegawa, Ian R. Reid, Robert Scragg, Carlos A. Camargo
Summary: Using machine learning models to predict vitamin D deficiency showed higher accuracy in predicting 25(OH)D <25 nmol/L compared to traditional models, suggesting a potential role for machine learning models in participant selection for vitamin D supplement trials.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Pharmacology & Pharmacy
Ian R. Reid, Jingyuan Wen, Anna Mellar, Mengyang Liu, Amani Jabr, Anne M. Horne
Summary: The aim of this study was to assess the safety and efficacy of two oral zoledronate preparations in postmenopausal women. The results showed that oral zoledronate had a smaller and less sustained anti-resorptive effect compared to intravenous zoledronate. However, oral zoledronate could be a viable option with dosing intervals of weeks to months.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Review
Endocrinology & Metabolism
Ian R. Reid
Summary: Fractures are common in older individuals, with a higher prevalence in older White women. However, most of the fractures occur in individuals who do not meet the bone density criteria for osteoporosis, indicating that the current definition is not suitable for treatment decisions. Treatment choices are based on calculated risk, fracture history, and bone density, and can involve medications that inhibit bone resorption or promote bone formation. Bisphosphonates are commonly used due to their effectiveness, safety, and affordability. Other options include denosumab, teriparatide, and romosozumab, each with its own unique characteristics and administration regimen.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
Ian R. Reid, Sonja Bastin, Anne M. Horne, Borislav Mihov, Gregory D. Gamble, Mark J. Bolland
Summary: Vertebral fractures are associated with height loss, reduced quality of life, and increased mortality. The impact of different components of the definition of vertebral fracture on trial outcomes was assessed using data from a six-year trial of zoledronate. Age, medication, and incident vertebral fractures were found to be factors affecting height change.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Editorial Material
Pharmacology & Pharmacy
I. R. Reid
EXPERT OPINION ON DRUG SAFETY
(2022)
Editorial Material
Endocrinology & Metabolism
Ian R. Reid
OSTEOPOROSIS INTERNATIONAL
(2023)
Article
Endocrinology & Metabolism
Rachel Murdoch, Anna Mellar, Anne M. Horne, Emma Billington, Pui Ling Chan, Gregory D. Gamble, Ian R. Reid
Summary: This study found that the use of dexamethasone can significantly reduce the acute phase response (APR) following zoledronate infusion, which is characterized by fever, musculoskeletal pain, headache, and nausea. Dexamethasone is highly effective in reducing the incidence of APR.
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Editorial Material
Endocrinology & Metabolism
Ian R. Reid
LANCET DIABETES & ENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
Ian R. Reid, Anne M. Horne, Borislav Mihov, Sonja Bastin, Gregory D. Gamble
Summary: Bisphosphonates are commonly used for osteoporosis prevention and treatment, while NSAIDs are widely used by older adults at high fracture risk. A study reanalyzed data from a clinical trial of zoledronate and found that NSAID use did not affect the bone density or fracture risk reduction effects of zoledronate. The study concluded that NSAIDs do not interfere with the efficacy of potent bisphosphonates in terms of bone density or fracture.
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)