Denosumab and infections

Introduction: Medication-related osteonecrosis of the jaw (MRONJ) is an oral complication in cancer patients being treated with either antiresorptives, mainly denosumab and bisphosphonates, or antiangiogenic drugs. Osimertinib is a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) for the treatment of patients with EGFR T790M advanced non-small-cell lung cancer (NSCLC). TKI-induced osteonecrosis of the jaw has been reported in recent years, but these cases almost occur in combination with bisphosphonates, and the data on MRONJ associated to osimertinib is scarce...

Medication-related osteonecrosis of the jaw (MRONJ) is a complication of certain pharmacological treatments such as bisphosphonates, denosumab, and angiogenesis inhibitors. There are currently no guidelines on its management, particularly in advanced stages. The human amniotic membrane (hAM) has low immunogenicity and exerts anti-inflammatory, antifibrotic, antimicrobial, antiviral, and analgesic effects. It is a source of stem cells and growth factors promoting tissue regeneration. hAM acts as an anatomical barrier with suitable mechanical properties (permeability, stability, elasticity, flexibility, and resorbability) to prevent the proliferation of fibrous tissue and promote early neovascularization at the surgical site...

Denosumab is a newly approved treatment for osteoporosis in China. However, the clinical safety and advantages of denosumab have not been much established. The current study evaluates the real-world safety of denosumab versus zoledronic acid in treating cancer-free adults aged 50 years or older with osteoporosis to provide clinical settings guidelines. PURPOSE: A head-to-head comparison of the safety profiles between denosumab (60 mg subcutaneously every 6 months) and zoledronic acid (5 mg, intravenously yearly) was performed in cancer-free adults aged 50 years or older with osteoporosis...

Immobilization is an uncommon etiology of hypercalcemia. It is usually seen in conditions associated with limited movements such as spinal cord injuries, vascular events, or following prolonged hospitalization. Hereby, we present a case of a young patient who had prolonged hospitalization following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). During her prolonged and complicated hospital stay, she developed severe hypercalcemia secondary to immobilization, which was resistant to treatment with hydration, calcitonin, and denosumab...

OBJECTIVE: The purpose of this review is to discuss the existing literature regarding patients who have experienced seizures after administration of a bone density conservation agent (BDCA). DATA SOURCES: A comprehensive literature review was performed between September and October 2021 using the following keywords: osteoporosis/drug therapy, seizures/chemically induced, hypercalcemia, hypocalcemia, osteoporosis, seizure risk, osteoclast medication, seizures, bisphosphonates, risedronate, zoledronic acid, pamidronate, denosumab, Prolia, Xgeva, calcitonin, BDCAs...

Chronic kidney disease (CKD) is associated with bone and mineral disturbances in the form of renal osteodystrophy. The American College of Rheumatology Guidelines for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis 2017 recommend against treatment with denosumab in adult patients who have received an organ transplant and who are continuing treatment with glucocorticoids due to lack of adequate safety data on infections in adults treated with multiple immunosuppressive agents. Therefore, this study was conducted to compare the safety of denosumab in patients with CKD, especially in a group of patients who received immunosuppressive medications, and to assess the rate of infections in such group in comparison to patients with normal renal function...

CONTEXT: Recent meta-analyses of randomized controlled trials have raised concerns that denosumab might increase the risk of infection. However, data of denosumab on the risk of community-acquired pneumonia are sparse. OBJECTIVE: This work aimed to examine the risk of community-acquired pneumonia in individuals receiving denosumab compared to those receiving alendronate. METHODS: We conducted a propensity score-matched cohort study with a UK primary care database (IQVIA Medical Research Database)...

Antiresorptive agents such as bisphosphonates (BP) and denosumab are commonly prescribed for the management of primary bone malignancy, bone metastasis, osteoporosis, Paget disease, or other bone disorders. Medication-related osteonecrosis of the Jaws (MRONJ) is a rare but significant complication of antiresorptive medications. Duration, dose, and antiresorptive potency as well as concomitant diseases, additional medications, and local factors affect MRONJ incidence and severity. MRONJ pathophysiology is still poorly understood...

Invasive dental treatment such as tooth extraction following treatment with strong anti-bone resorptive agents, including bisphosphonates and denosumab, reportedly promotes osteonecrosis of the jaw (ONJ) at the extraction site, but strategies to prevent ONJ remain unclear. Here we show that in mice, administration of either active vitamin D analogues, antibiotics or anti-inflammatory agents can prevent ONJ development induced by tooth extraction during treatment with the bisphosphonate zoledronate. Specifically, tooth extraction during treatment with zoledronate induced osteonecrosis in mice, but administration of either 1,25(OH)2 D3 or ED71, both active vitamin D analogues, significantly antagonized osteonecrosis development, even under continuous zoledronate treatment...

BACKGROUND: There is no standard treatment for giant cell tumors of the sacrum. We compared the outcomes and complications in patients with sacral giant cell tumors who underwent intralesional nerve-sparing surgery with or without (neo-) adjuvant therapies versus those who underwent non-surgical treatment (denosumab therapy and/or embolization). METHODS: We retrospectively investigated 15 cases of sacral giant cell tumors treated at two institutions between 2005 and 2020...

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...

SUMMARY: Immobilization-induced hypercalcemia is an uncommon cause of elevated calcium which is usually diagnosed following extensive systemic workup and exclusion of more common etiologies. Previously reported cases have largely described this phenomenon in adolescents and young adults a few weeks to months after the initial onset of immobilization. Metabolic workup tends to demonstrate hypercalcemia, hypercalciuria, and eventual osteoporosis. While the exact mechanism remains largely unclear, a dysregulation between bone resorption and formation is central to the pathogenesis of this disease...

Introduction: We aimed to compare annual changes in the bone mineral density (BMD) at the lumbar spine (LS) and the femoral neck (FN) in males with HIV-associated osteoporosis treated with either zoledronate (ZOL) or denosumab (Dmab). Methods: In this open label, 12-month, prospective, multicenter, cohort study, 23 male people living with HIV (PLWH) under antiretroviral therapy (ART) with low BMD were administered either a single iv infusion of ZOL 5 mg ( n  = 10) or Dmab 60 mg sc injections biannually ( n  = 13)...

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...

This study was performed to evaluate whether the use of drugs in the treatment of osteoporosis in women is associated with COVID-19 outcomes. The results showed that the risk of hospitalization, intensive care unit admission, and mortality was not altered in individuals taking anti-osteoporosis drugs, suggesting no safety issues during a COVID-19 infection. INTRODUCTION: Whether patients with COVID-19 receiving anti-osteoporosis drugs have lower risk of worse outcomes has not been reported yet...

Denosumab is associated with the development of medication-related osteonecrosis of the jaw (MRONJ), an uncommon but severe oral side effect with a higher prevalence in metastatic cancer patients than in patients with metabolic bone fragility. Although several oral triggers can initiate MRONJ, invasive oral treatments and tooth extraction still remain the most common precipitating event. In general, tooth extraction and oral surgery should be avoided in patients at increased risk of MRONJ, while extraction of non-restorable teeth should be performed based on specific risk reduction protocols to eliminate dental/periodontal infections, still protecting from MRONJ onset...

SUMMARY: Hypercalcaemia is a very common endocrine condition, yet severe hypercalcaemia as a result of fungal infection is rarely described. There are have only been two reported cases in the literature of hypercalcaemia associated with Cryptococcus infection. Although the mechanism of hypercalcaemia in these infections is not clear, it has been suggested that it could be driven by the extra-renal production of 1-alpha-hydroxylase by macrophages in granulomas. We describe the case of a 55-year-old woman with a 1,25-OH D-mediated refractory hypercalcaemia in the context of a Cryptococcus neoformans infection...

Introduction: Medication-related osteonecrosis of the jaw (MRONJ) corresponds to an adverse effect of the use of drugs such as bisphosphonates and denosumab. This condition is often associated with pain, infection, purulent secretion, paraesthesia, tooth mobility and halitosis, decreasing the patient's quality of life. The management of MRONJ tends to be conservative, through the guidance of oral hygiene, antibiotic therapy and mouthwashes. However, the use of antimicrobial photodynamic therapy (aPDT) has shown promise in the treatment of these injuries...

OBJECTIVES: To assess the influence of antiresorptive/antiangiogenic therapy on the spreading of peri-implant infections in the pharyngeal region. MATERIAL AND METHODS: This analysis was based on tissue biopsies obtained from a total of twenty-five albino rats having either received (1) amino-bisphosphonate (Zoledronate) (Zo) (n=4), (2) RANKL inhibitor (Denosumab) (De) (n=4), (3) antiangiogenic medication (Bevacizumab) (Be) (n=4), (4) Zo+Be (n=3), (5) De+Be (n=5), or (6) no medication (Co) (n=5)...

In 32-kidney transplanted patients (KTxps), the safety and the effects on BMD and mineral metabolism (MM) of one-year treatment with denosumab (DB) were studied. Femoral and vertebral BMD and T-score, FRAX score and vertebral fractures (sVF) before (T0) and after 12 months (T12) of treatment were measured. MM, renal parameters, hypocalcemic episodes (HpCa), urinary tract infections (UTI), major graft and KTxps outcomes were monitored. The cohort was composed mainly of females, n = 21. We had 29 KTxps on steroid therapy and 22 KTxps on vitamin D supplementation...