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Annals of Internal Medicine Feb 2023The prevalence of osteoporosis is increasing in the United States. (Meta-Analysis)
Meta-Analysis Review
Effectiveness and Safety of Treatments to Prevent Fractures in People With Low Bone Mass or Primary Osteoporosis: A Living Systematic Review and Network Meta-analysis for the American College of Physicians.
BACKGROUND
The prevalence of osteoporosis is increasing in the United States.
PURPOSE
To evaluate low bone mass and osteoporosis treatments to prevent fractures.
DATA SOURCES
Ovid MEDLINE ALL, Ovid Evidence Based Medicine Reviews: Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov from 2014 through February 2022.
STUDY SELECTION
Adults receiving eligible interventions for low bone mass or osteoporosis. Randomized controlled trials (RCTs) for fracture outcomes, and RCTs and large observational studies ( ≥1000) for harms.
DATA EXTRACTION
Abstracted by 1 reviewer and verified by a second. Independent, dual assessments of risk of bias and certainty of evidence (CoE).
DATA SYNTHESIS
We included 34 RCTs (in 100 publications) and 36 observational studies. Bisphosphonates and denosumab reduced hip, clinical and radiographic vertebral, and other clinical fractures in postmenopausal females with osteoporosis (moderate to high CoE). Bisphosphonates for 36 months or more may increase the risk for atypical femoral fractures (AFFs) and osteonecrosis of the jaw (ONJ), but the absolute risks were low. Abaloparatide and teriparatide reduced clinical and radiographic vertebral fractures but increased the risk for withdrawals due to adverse events (WAEs; moderate to high CoE). Raloxifene and bazedoxifene for 36 months or more reduced radiographic vertebral but not clinical fractures (low to moderate CoE). Abaloparatide, teriparatide, and sequential romosozumab, then alendronate, may be more effective than bisphosphonates in reducing clinical fractures for 17 to 24 months in older postmenopausal females at very high fracture risk (low to moderate CoE). Bisphosphonates may reduce clinical fractures in older females with low bone mass (low CoE) and radiographic vertebral fractures in males with osteoporosis (low to moderate CoE).
LIMITATION
Few studies examined participants with low bone mass, males, or Black-identifying persons, sequential therapy, or treatment beyond 3 years.
CONCLUSION
Bisphosphonates, denosumab, abaloparatide, teriparatide, and romosozumab, followed by alendronate, reduce clinical fractures in postmenopausal females with osteoporosis. Abaloparatide and teriparatide increased WAEs; longer duration bisphosphonate use may increase AFF and ONJ risk though these events were rare.
PRIMARY FUNDING SOURCE
American College of Physicians. (PROSPERO: CRD42021236220).
Topics: Male; Adult; Female; Humans; Aged; Bone Density Conservation Agents; Teriparatide; Alendronate; Osteoporosis, Postmenopausal; Denosumab; Network Meta-Analysis; Fractures, Bone; Osteoporosis; Diphosphonates; Spinal Fractures; Physicians
PubMed: 36592455
DOI: 10.7326/M22-0684 -
Advances in Therapy Jan 2022The fully human monoclonal antibody denosumab was approved for treatment of osteoporosis in 2010 on the basis of its potent antiresorptive activity, which produces... (Review)
Review
The fully human monoclonal antibody denosumab was approved for treatment of osteoporosis in 2010 on the basis of its potent antiresorptive activity, which produces clinically meaningful increases in bone mineral density (BMD) and reduces fracture risk at key skeletal sites. At that time, questions remained regarding the long-term safety and efficacy of this receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor; and with clinical experience, new questions have arisen regarding its optimal use. Here, we examine these questions through the lens of data from the FREEDOM trial program and other studies to determine where denosumab fits in the osteoporosis treatment landscape. Clinical consensus and evidentiary support have grown for denosumab as a highly effective anti-osteoporosis therapy for patients at high risk of fracture. In the 10-year FREEDOM Extension study, denosumab treatment produced progressive incremental increases in BMD, sustained low rates of vertebral fracture, and further reduction in nonvertebral fracture risk without increased risk of infection, cancer, or immunogenicity. There was no evidence that suppression of bone turnover or mineralization was excessive, and rates of osteonecrosis of the jaw (ONJ) and atypical femoral fracture (AFF) were very low. It is now recognized, however, that transitioning to another anti-osteoporosis therapy after denosumab discontinuation is essential to mitigate a transient rebound of bone turnover causing rapid BMD loss and increased risk of multiple vertebral fractures (MVFs). Taken together, the available data show that denosumab has a favorable benefit/risk profile and is a versatile agent for preventing osteoporotic fractures in the short and long term. Video abstract: Denosumab in the Treatment of Osteoporosis-10 Years Later (MP4 62727 KB).
Topics: Bone Density; Bone Density Conservation Agents; Denosumab; Female; Humans; Osteoporosis; Osteoporosis, Postmenopausal; Osteoporotic Fractures
PubMed: 34762286
DOI: 10.1007/s12325-021-01936-y -
The Journal of Clinical Endocrinology... Apr 2022Antiresorptive therapy significantly reduces fracture risk in patients with benign bone disease and skeletal-related events (SREs) in patients with bone metastases (BM).... (Review)
Review
CONTEXT
Antiresorptive therapy significantly reduces fracture risk in patients with benign bone disease and skeletal-related events (SREs) in patients with bone metastases (BM). Osteonecrosis of the jaw (ONJ) is a rare but severe condition manifested as necrotic bone lesion or lesions of the jaws. ONJ has been linked to the use of potent antiresorptive agents, termed medication-related ONJ (MRONJ).
OBJECTIVE
We aimed to identify the differences various aspects of MRONJ among distinct patient categories and provide recommendations on how to mitigate the risk and optimally manage MRONJ in each of them.
METHODS
A working group of the European Calcified Tissue Society (ECTS) and 2 experts performed an updated detailed review of existing literature on MRONJ incidence, characteristics, and treatment applied in bone diseases with variable severity of skeletal insult, ranging from osteoporosis to prevention of cancer treatment-induced bone loss and SREs in cancer patients with BM.
RESULTS
The risk for MRONJ is much higher in patients with advanced malignancies compared to those with benign bone diseases because of the higher doses and more frequent administration of antiresorptive agents in individuals with compromised general health, along with coadministration of other medications that predispose to MRONJ. The overall risk for MRONJ is considerably lower than the benefits in all categories of patients.
CONCLUSION
The risk for MRONJ largely depends on the underlying bone disease and the relevant antiresorptive regimen applied. Physicians and dentists should keep in mind that the benefits of antiresorptive therapy far outweigh the risk for MRONJ development.
Topics: Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Bone Neoplasms; Diphosphonates; Humans; Jaw; Syndrome
PubMed: 34922381
DOI: 10.1210/clinem/dgab888 -
Journal of Translational Medicine Sep 2023Osteoporosis is a systemic bone disease characterized by low bone mass, microarchitectural deterioration, increased bone fragility, and fracture susceptibility. It... (Review)
Review
Osteoporosis is a systemic bone disease characterized by low bone mass, microarchitectural deterioration, increased bone fragility, and fracture susceptibility. It commonly occurs in older people, especially postmenopausal women. As global ageing increases, osteoporosis has become a global burden. There are a number of medications available for the treatment of osteoporosis, categorized as anabolic and anti-resorptive. Unfortunately, there is no drugs which have dual influence on bone, while all drugs have limitations and adverse events. Some serious adverse events include jaw osteonecrosis and atypical femoral fracture. Recently, a novel medication has appeared that challenges this pattern. Romosozumab is a novel drug monoclonal antibody to sclerostin encoded by the SOST gene. It has been used in Japan since 2019 and has achieved promising results in treating osteoporosis. However, it is also accompanied by some controversy. While it promotes rapid bone growth, it may cause serious adverse events such as cardiovascular diseases. There has been scepticism about the drug since its inception. Therefore, the present review comprehensively covered romosozumab from its inception to its clinical application, from animal studies to human studies, and from safety to cost. We hope to provide a better understanding of romosozumab for its clinical application.
Topics: Animals; Female; Humans; Aged; Osteoporosis; Antibodies, Monoclonal; Aging; Bone Development
PubMed: 37759285
DOI: 10.1186/s12967-023-04563-z -
PloS One 2022Maxillofacial trauma can be limited to superficial lacerations, abrasions, and facial bone fractures. The objective of this study was to determine the etiology, pattern,...
INTRODUCTION
Maxillofacial trauma can be limited to superficial lacerations, abrasions, and facial bone fractures. The objective of this study was to determine the etiology, pattern, and predictors of soft tissue and bony injuries.
MATERIALS AND METHODS
This study was conducted in the department of maxillofacial surgery Lady Reading hospital Pakistan from Jan 2019 to June 2021. The nonprobability consecutive sampling technique was used for the selection of patients. All patients were assessed clinically and radiologically. The neurosensory examination was done for any altered sensation, anesthesia, or paresthesia. Motor nerve function was also assessed clinically. Data were analyzed using SPSS version 26. The etiology and pattern of maxillofacial trauma were stratified among age and genders using the chi-square test to see effect modifiers. Tests for regression analysis were also applied. P≤0.05 was considered significant.
RESULTS
A total of 253 patients meeting inclusion criteria were included in this study. The majority of these patients were males, 223 (88.1%), while only 30 (11.9%) were females. The mean age for the group was 25.4 ± 12.6 years. RTAs were the most common causes of trauma (63.6%) followed by assault (15.0%), falls (11.5%), FAIs (5.9%), and sports (0.4%). The most vulnerable skeletal part was the mandible (22.9%) followed by Zygoma (7.1%), significantly predicted by RTAs. Soft tissue laceration analysis showed a high frequency of multiple lacerations (38%) significantly predicted by FAIs. The frequency of trigeminal nerve injury was 5.5% (14 patients) and that of the facial nerve was 1.6% (4 patients). The strongest association of nerve injury was with firearm injury (47%), followed by road traffic accidents and sports injuries.
CONCLUSION
Road traffic accident was the most common etiological factor and mandible fracture was commonly predicted by RTA. Trigeminal nerve injuries were common, frequency of nerve injuries was highly associated with mandible fracture and was predicted by FAI.
Topics: Adolescent; Adult; Causality; Child; Female; Firearms; Humans; Lacerations; Male; Mandibular Fractures; Maxillofacial Injuries; Trigeminal Nerve Injuries; Wounds, Gunshot; Young Adult
PubMed: 36174089
DOI: 10.1371/journal.pone.0275515 -
Journal of Bone Oncology Apr 2022Skeletal-related events (SREs) are complications of bone metastases and carry a significant patient and economic burden. Denosumab is a receptor activator of nuclear... (Review)
Review
Skeletal-related events (SREs) are complications of bone metastases and carry a significant patient and economic burden. Denosumab is a receptor activator of nuclear factor-κB ligand (RANKL) inhibitor approved for SRE prevention in patients with multiple myeloma and patients with bone metastases from solid tumors. In phase 3 trials, denosumab showed superiority to the bisphosphonate zoledronate in reducing the risk of first on-study SRE by 17% (median time to first on-study SRE delayed by 8.2 months) and the risk of first and subsequent on-study SREs by 18% across multiple solid tumor types, including some patients with multiple myeloma. Denosumab also improved pain outcomes and reduced the need for strong opioids. Additionally, a phase 3 trial showed denosumab was noninferior to zoledronate in delaying time to first SRE in patients with newly diagnosed multiple myeloma. Denosumab has a convenient 120 mg every 4 weeks recommended dosing schedule with subcutaneous administration. Rare but serious toxicities associated with denosumab include osteonecrosis of the jaw, hypocalcemia, and atypical femoral fracture events, with multiple vertebral fractures reported following treatment discontinuation. After a decade of real-world clinical experience with denosumab, we are still learning about the optimal use and dosing for denosumab. Despite the emergence of novel and effective antitumor therapies, there remains a strong rationale for the clinical utility of antiresorptive therapy for SRE prevention. Ongoing studies aim to optimize clinical management of patients using denosumab for SRE prevention while maintaining safety and efficacy.
PubMed: 35242510
DOI: 10.1016/j.jbo.2022.100416 -
Dental and Medical Problems 2021Extractions of third molars constitute about 90% of the scheduled surgical procedures performed by oral surgeons. Wisdom tooth surgery is associated with complications,...
BACKGROUND
Extractions of third molars constitute about 90% of the scheduled surgical procedures performed by oral surgeons. Wisdom tooth surgery is associated with complications, such as the lingual and inferior alveolar nerve damage, bleeding, tooth/jaw fractures, tooth displacement into the adjacent anatomical spaces, trismus, infections, and other.
OBJECTIVES
The aim of the study was to analyze complications after wisdom tooth extraction in patients treated at the Department of Oral Surgery of Jagiellonian University Medical College in Kraków, Poland, in the years 2016-2018.
MATERIAL AND METHODS
A retrospective analysis of the medical records of 339 patients treated in the outpatient setting was performed. The inclusion criterion comprised a single extraction of a third molar. The exclusion criteria were multiple extractions, comorbidities and pregnancy. No antibiotic prophylaxis was used. The incidence of post-extraction complications, such as oroantral communication, postoperative hematoma, acute inflammation of the surrounding tissues, trismus, and transient paresthesia in relation to patient gender and age, the developmental stage and location of the removed tooth as well as the type of surgery were studied.
RESULTS
Perioperative complications occurred in 51 (15.0%) cases, and comprised the acute inflammation of the surrounding tissues in 31 patients, trismus after the removal of 13 lower third molars, oroantral communication after the extraction of 5 upper wisdom teeth, and hematoma as well as a transient sensory alteration of the lingual nerve in 1 case each. Complications were more common in patients who had a surgical extraction of a wisdom tooth with root separation and in cases of lower third molar extractions. No statistically significant correlation was found between the patients' age or gender, the developmental stage of the extracted tooth and the number of observed complications.
CONCLUSIONS
Lower third molars and the necessity of surgical extraction with root separation are risk factors for postoperative complications in patients who require wisdom tooth removal. Complications after the removal of third molars are most often inflammatory.
Topics: Humans; Molar, Third; Poland; Retrospective Studies; Tooth Extraction; Tooth, Impacted
PubMed: 33789003
DOI: 10.17219/dmp/127028 -
Diagnostics (Basel, Switzerland) Dec 2022The increasing use of computed tomography (CT) and cone beam computed tomography (CBCT) in oral and maxillofacial imaging has driven the development of deep learning and... (Review)
Review
The increasing use of computed tomography (CT) and cone beam computed tomography (CBCT) in oral and maxillofacial imaging has driven the development of deep learning and radiomics applications to assist clinicians in early diagnosis, accurate prognosis prediction, and efficient treatment planning of maxillofacial diseases. This narrative review aimed to provide an up-to-date overview of the current applications of deep learning and radiomics on CT and CBCT for the diagnosis and management of maxillofacial diseases. Based on current evidence, a wide range of deep learning models on CT/CBCT images have been developed for automatic diagnosis, segmentation, and classification of jaw cysts and tumors, cervical lymph node metastasis, salivary gland diseases, temporomandibular (TMJ) disorders, maxillary sinus pathologies, mandibular fractures, and dentomaxillofacial deformities, while CT-/CBCT-derived radiomics applications mainly focused on occult lymph node metastasis in patients with oral cancer, malignant salivary gland tumors, and TMJ osteoarthritis. Most of these models showed high performance, and some of them even outperformed human experts. The models with performance on par with human experts have the potential to serve as clinically practicable tools to achieve the earliest possible diagnosis and treatment, leading to a more precise and personalized approach for the management of maxillofacial diseases. Challenges and issues, including the lack of the generalizability and explainability of deep learning models and the uncertainty in the reproducibility and stability of radiomic features, should be overcome to gain the trust of patients, providers, and healthcare organizers for daily clinical use of these models.
PubMed: 36611402
DOI: 10.3390/diagnostics13010110 -
Bone Dec 2021Medication-related osteonecrosis of the jaw (MRONJ) is a potentially severe adverse event affecting patients with cancer and patients with osteoporosis who have been... (Review)
Review
Medication-related osteonecrosis of the jaw (MRONJ) is a potentially severe adverse event affecting patients with cancer and patients with osteoporosis who have been treated with powerful antiresorptives (pARs) or angiogenesis inhibitors (AgIs). pARs, including nitrogen-containing bisphosphonates (N-BPs; e.g., zoledronic acid, alendronate) and anti-RANKL antibodies (e.g., denosumab), are used to manage bone metastases in patients with cancer or to prevent fragility fractures in patients with osteoporosis. Though significant advances have been made in understanding MRONJ, its pathophysiology is still not fully elucidated. Multiple species have been used in preclinical MRONJ research, including the rat, mouse, rice rat, rabbit, dog, sheep, and pig. Animal research has contributed immensely to advancing the MRONJ field, particularly, but not limited to, in developing models and investigating risk factors that were first observed in humans. MRONJ models have been developed using clinically relevant doses of systemic risk factors, like N-BPs, anti-RANKL antibodies, or AgIs. Specific local oral risk factors first noted in humans, including tooth extraction and inflammatory dental disease (e.g., periodontitis, periapical infection, etc.), were then added. Research in rodents, particularly the rat, and, to some extent, the mouse, across multiple laboratories, has contributed to establishing multiple relevant and complementary preclinical models. Models in larger species produced accurate clinical and histopathologic outcomes suggesting a potential role for confirming specific crucial findings from rodent research. We view the current state of animal models for MRONJ as good. The rodent models are now reliable enough to produce large numbers of MRONJ cases that could be applied in experiments testing treatment modalities. The course of MRONJ, including stage 0 MRONJ, is characterized well enough that basic studies of the molecular or enzyme-level findings in different MRONJ stages are possible. This review provides a current overview of the existing models of MRONJ, their more significant features and findings, and important instances of their application in preclinical research.
Topics: Animals; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Bone Neoplasms; Denosumab; Diphosphonates; Disease Models, Animal; Dogs; Humans; Mice; Rabbits; Rats; Sheep; Swine
PubMed: 34520898
DOI: 10.1016/j.bone.2021.116184