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Family Practice Apr 2024Medication-related ear canal osteonecrosis (MRECO) is a growing concern linked to prolonged anti-resorptive medication use. Despite primary care providers being key...
INTRODUCTION
Medication-related ear canal osteonecrosis (MRECO) is a growing concern linked to prolonged anti-resorptive medication use. Despite primary care providers being key prescribers of these medications, there is limited information about MRECO in primary care literature. This article presents a case of bisphosphonate-induced osteonecrosis of the external auditory canal (EAC), emphasizing the vital role of primary care providers in identifying this rare yet significant side effect of anti-resorptive medication.
MAIN SYMPTOMS AND CLINICAL FINDINGS
A 65-year-old female, on long-term alendronic acid for osteoporosis, presented to primary care with a 2-year history of left-sided ear blockage and itchiness. Despite prolonged topical treatment for ear wax, symptoms persisted, leading to an Otolaryngology referral. Microsuction revealed exposed bone in the left EAC.
DIAGNOSES, INTERVENTIONS, AND OUTCOMES
A computed tomography scan confirmed bony erosion of the left EAC, and in the absence of other osteonecrosis risk factors, bisphosphonate-induced osteonecrosis was diagnosed. Management involved bisphosphonate discontinuation, regular aural toilet, and topical treatment, achieving complete ear canal epithelialisation within 6 months.
CONCLUSION
MRECO, a rare complication of anti-resorptive therapy, is anticipated to rise with increasing antiresorptive medication use in the ageing population. Unexplained ear symptoms in those with a history of current or prior anti-resorptive therapy should raise clinical concern, prompting evaluation for exposed bone in the EAC. Raising awareness of MRECO among primary care providers is crucial for early diagnosis and timely management.
Topics: Female; Humans; Aged; Bisphosphonate-Associated Osteonecrosis of the Jaw; Diphosphonates; Bone Density Conservation Agents; Alendronate; Primary Health Care
PubMed: 38413046
DOI: 10.1093/fampra/cmae012 -
Orthopedic Research and Reviews 2024While osteoporosis increases the risk of fragility fractures, bisphosphonate has been proven to increase bone strength and reduce the risk of vertebral and non-vertebral...
BACKGROUND
While osteoporosis increases the risk of fragility fractures, bisphosphonate has been proven to increase bone strength and reduce the risk of vertebral and non-vertebral fractures. In addition to its efficacy, substituting the brand with generic medication is a strategy to optimize healthcare expenditures. This study aimed to evaluate the efficacy of generic alendronate treatment and assess potential adverse events in patients with osteoporosis.
MATERIALS AND METHODS
A retrospective review was conducted on 120 patients who met the indications for osteoporosis treatment, received weekly generic alendronate (70 mg) for >1 year, and underwent evaluation through standard axial dual-energy X-ray absorptiometry (DXA). The outcomes of this study were the percent change in bone mineral density (BMD) at the lumbar spine, femoral neck, and total hip after one year of treatment. The major adverse events occurring during medication that led to the discontinuation of drug administration were documented.
RESULTS
Most patients were female (96.7%) with an average age of 69.0 ± 9.3 years. The percent change in BMD increased at all sites after one year of generic alendronate treatment (lumbar spine: 5.6 ± 13.7, -value <0.001; femoral neck: 2.3 ± 8.3, -value = 0.023; total hip: 2.1 ± 6.2, -value = 0.003), with over 85% of patients experiencing increased or stable BMD. Three patients discontinued the medication due to adverse effects: two had dyspepsia, and one had persistent myalgia.
CONCLUSION
Generic alendronate may be considered an effective antiresorptive agent for osteoporosis treatment with a low incidence of adverse effects.
PubMed: 38410814
DOI: 10.2147/ORR.S445202 -
Biomolecules Feb 2024Bone is a site of distant metastases, which are a common cause of morbidity and mortality with a high socio-economic impact, for many malignant tumours. In order to...
Bone is a site of distant metastases, which are a common cause of morbidity and mortality with a high socio-economic impact, for many malignant tumours. In order to engineer pharmacological therapies that are suitable for this debilitating disease, this experimental work presents injectable lipid nanoemulsions, which are endowed with a long history of safe clinical usage in parenteral nutrition, their loading with vincristine and their grafting with alendronate, with a dual purpose: merging the anticancer activity of bisphosphonates and vincristine, and enhancing bone-targeted delivery. In cell studies, alendronate synergised with the anti-migration activity of vincristine, which is important as migration plays a key role in the metastatisation process. In preliminary animal studies, carried out thanks to IVIS technology, alendronate conjugation enhanced the bone targeting of fluorescently labelled nanoemulsions. These encouraging results will drive further studies on suitable animal models of the disease.
Topics: Animals; Alendronate; Vincristine; Diphosphonates; Bone and Bones; Models, Animal
PubMed: 38397475
DOI: 10.3390/biom14020238 -
Bone May 2024Antiresorptive treatment is currently used in millions of patients with osteoporosis and cancer worldwide. Early studies of denosumab suggested a small signal in ovarian...
BACKGROUND
Antiresorptive treatment is currently used in millions of patients with osteoporosis and cancer worldwide. Early studies of denosumab suggested a small signal in ovarian cancer incidence and emerging data suggest that denosumab stimulates germ cell proliferation in the gonads. This study aims to determine the association between the use of denosumab and the risk of reproductive cancers compared with the use of alendronate.
RESEARCH DESIGN AND METHODS
Using a cohort study design, we used the Danish nationwide registries to identify a population of subjects ≥50 years of age during 2010-2017 who started denosumab after being on alendronate treatment for at least six months. The cohort was matched 1:2 with patients who had been treated with alendronate alone for at least six months. The risk of reproductive cancers and the risk difference between groups were estimated using the Longitudinal Targeted Maximum Likelihood Estimation (L-TMLE) method.
RESULTS
We identified 6054 Danish individuals who underwent treatment with denosumab. These individuals were matched with 12,108 receiving alendronate. The absolute risk of reproductive cancer was 1.05 % (95 % CI 0.75-1.34) after three years for denosumab users and was not different 0.03 % (-0.34-0.39) than for alendronate users. In supplemental analyses, there was no increased risk of non-reproductive cancers associated with the use of denosumab (risk difference of 0.54 % (-0.41-1.19). Analysis comparing denosumab users with the general population gave similar results.
CONCLUSION
There was no difference in the risk of cancer following treatment with denosumab compared to treatment with alendronate assessed after a short follow-up of 3 years.
Topics: Humans; Female; Alendronate; Denosumab; Bone Density Conservation Agents; Cohort Studies; Neoplasms; Osteoporosis, Postmenopausal
PubMed: 38395247
DOI: 10.1016/j.bone.2024.117053 -
Cureus Jan 2024Cobblestone esophagus is a rare finding that has been previously described in cases of eosinophilic esophagitis (EoE), , Barrett's esophagus, or severe reflux...
Cobblestone esophagus is a rare finding that has been previously described in cases of eosinophilic esophagitis (EoE), , Barrett's esophagus, or severe reflux esophagitis from distal gastrointestinal obstruction. We describe a case of asymptomatic cobblestone esophagus secondary to bisphosphonate use. A 67-year-old female was seen in the clinic for evaluation of microcytic anemia that was incidentally picked up on routine chronic disease follow-up. She had no gastrointestinal symptoms. She has been taking oral alendronate 70mg once a week for osteoporosis since a year ago. Barium meal was performed as the patient initially opted for non-invasive testing, which incidentally showed a diffuse "cobblestone" appearance. Subsequent oesophago-gastro-duodenoscopy (OGD) showed diffuse white nodular lesions along the esophagus with a cobblestone appearance but no ulcer or mass. Segmental esophageal biopsies were negative for fungal stain and did not show any pathology. In the absence of infection, eosinophilic esophagitis, and dysplasia, her "cobblestone" esophagus was attributed to bisphosphonate use by diagnosis of exclusion. Alendronate acid was held off, and serial barium meals over the next year showed significant interval improvement. Bisphosphonates, such as alendronate acid, are commonly associated with drug-induced esophagitis. With the cessation of the offending medication, there was indeed a significant improvement in our patient's serial barium meal. It is important to review the medication list when encountering patients who present with cobblestone esophagus, as some of these patients with drug-induced esophagitis may be asymptomatic clinically.
PubMed: 38374855
DOI: 10.7759/cureus.52602 -
ACS Nano Feb 2024Abdominal aortic aneurysm (AAA) remains a fatal disease in the elderly. Currently, no drugs can be clinically used for AAA therapy. Considering the pivotal role of...
Abdominal aortic aneurysm (AAA) remains a fatal disease in the elderly. Currently, no drugs can be clinically used for AAA therapy. Considering the pivotal role of neutrophils in the pathogenesis of AAA, herein we propose the targeted therapy of AAA by site-specifically regulating neutrophilic inflammation. Based on a luminol-conjugated α-cyclodextrin material (LaCD), intrinsically anti-inflammatory nanoparticles (NPs) were engineered by simple nanoprecipitation, which were examined as a nanotherapy (defined as LaCD NP). After efficient accumulation in the aneurysmal aorta and localization in pathologically relevant inflammatory cells in rats with CaCl-induced AAA, LaCD NP significantly alleviated AAA progression, as implicated by the decreased aortic expansion, suppressed elastin degradation, inhibited calcification, and improved structural integrity of the abdominal aorta. By functionalizing LaCD NP with alendronate, a calcification-targeting moiety, the aneurysmal targeting capability of LaCD NP was considerably enhanced, thereby affording significantly potentiated therapeutic outcomes in AAA rats. Mechanistically, LaCD NP can effectively inhibit neutrophil-mediated inflammatory responses in the aneurysmal aorta. Particularly, LaCD NP potently attenuated the formation of neutrophil extracellular traps (NETs), thereby suppressing NETs-mediated pro-inflammatory events and NETosis-associated negative effects responsible for AAA progression. Consequently, we demonstrated the effectiveness and underlying mechanisms of anti-NETosis nanotherapies for the targeted treatment of AAA. Our findings provide promising insights into discovering precision therapies for AAA and other inflammatory vascular diseases.
Topics: Humans; Rats; Animals; Aged; Mice; Aortic Aneurysm, Abdominal; Aorta, Abdominal; Neutrophils; Nanoparticles; Inflammation; Disease Models, Animal; Mice, Inbred C57BL
PubMed: 38369729
DOI: 10.1021/acsnano.4c00120 -
Chemistry & Biodiversity Apr 2024Kariavattom Campus Postmenopausal osteoporosis (PMO) is an old age disorder associated with estrogen deficiency, which reduces bone mass and makes bones more prone to...
Kariavattom Campus Postmenopausal osteoporosis (PMO) is an old age disorder associated with estrogen deficiency, which reduces bone mass and makes bones more prone to fracture. The present study was proposed to evaluate the invivo osteogenic efficiency of Pterospermum rubiginosum methanolic bark extract (PRME) in the PMO model. Molecular docking studies on transcription factor NFATC1 showed excellent interactions with phytochemical ligands with the lowest binding energies. Female Sprague Dawley (SD) rats (n=24) were divided into four groups, (n=6 each) sham control (Group I) and osteoporotic control (Group II) groups treated with saline, PRME (50 mg/kg/day) and alendronate (10 mg/kg/day) treated with Group III and Group IV (n=6) respectively. The serum tartrate-resistant acid phosphatase 5b and cathepsin-K also exhibited a significant rise after PRME treatment 12.33±2.30 mU/ml and 427.68±46.97 pg/ml, respectively. DEXA results exhibited a remarkable increase in total bone mineral content and density values in PRME-treated animals (0.175±0.002 g/cm) and (7.95±0.23 g) when compared to osteoporotic control (0.163±0.004 g/cm) and (6.83±0.34 g). Long-term toxicity study revealed that PRME is non-toxic, up to 100 mg/kg bodyweight for 6 months. Our findings suggest PRME protects osteoporotic SD rats from PMO damage resulting from estrogen deficiency by regulating bone remodelling markers and upregulating BMD indices.
Topics: Female; Humans; Rats; Animals; Osteoporosis, Postmenopausal; Molecular Docking Simulation; Rats, Sprague-Dawley; Bone Remodeling; Estrogens; Biomarkers
PubMed: 38369572
DOI: 10.1002/cbdv.202400172 -
International Journal of Biological... Mar 2024Injectable hydrogel-based materials have emerged as promising alendronate (ALN) delivery systems for the treatment of osteoporosis. However, their intrinsic permeability...
Injectable hydrogel-based materials have emerged as promising alendronate (ALN) delivery systems for the treatment of osteoporosis. However, their intrinsic permeability limits the sustained delivery of small-molecule drugs. In response to this challenge, we present the multifunctional hybrids composed of mesoporous silica particles decorated with hydroxyapatite and loaded with alendronate (MSP-NH-HAp-ALN), which are immobilized in collagen/chitosan/hyaluronic acid-based hydrogel. We have mainly focused on the biological in vitro/ex vivo evaluation of developed composites. It was found that the extracts released from tested systems do not exhibit hemolytic properties and are safe for blood elements and the human liver cell model. The resulting materials create an environment conducive to differentiating human bone marrow mesenchymal stem cells and reduce the viability of osteoclast precursors (RAW 264.7). Importantly, even the system with the lowest concentration of ALN caused a substantial cytotoxic effect on RAW 264.7 cells; their viability decreased to 20 % and 10 % of control on 3 and 7 day of culture. Additionally, prolonged ALN release (up to 20 days) with minimized burst release was observed, while material features (wettability, swellability, degradation, mechanical properties) depended on MSP-NH-HAp-ALN content. The obtained data indicate that developed composites establish a high-potential formulation for safe and effective osteoporosis therapy.
Topics: Humans; Alendronate; Hyaluronic Acid; Chitosan; Hydrogels; Collagen; Osteoporosis
PubMed: 38365151
DOI: 10.1016/j.ijbiomac.2024.130142 -
Anatomy & Cell Biology Mar 2024Alendronate sodium (ALS) is a nitrogen-containing bisphosphonate used for the treatment of different bone disorders. However, its adverse effect on oral soft tissue has...
Alendronate sodium (ALS) is a nitrogen-containing bisphosphonate used for the treatment of different bone disorders. However, its adverse effect on oral soft tissue has been detected. Rutin (RUT) is natural flavonoid with antioxidant and anti-inflammatory properties. This work aimed to investigate the possible effect of ALS on the tongue of adult male albino rats and to evaluate the possible protective role of RUT. Forty adult male albino rats were equally divided into four groups: group I (control), group II (RUT): Received RUT 50 mg/kg, group III (ALS): Received ALS 1 mg/kg, group IV (ALS+RUT): Received ALS and RUT with the same doses as pervious groups. The drugs were given once daily for 5 weeks. Tongue specimens were taken and processed for light and scanning electron microscopic inspection. ALS treated group revealed structural changes in the tongue in the form of decrease in the height of the filiform papillae with blunt ends, marked atrophy in some papillae with areas of focal loss, loss of some epithelial cells, pyknotic nuclei and cytoplasmic vacuoles in some epithelial cells. The lamina propria showed inflammatory cellular infiltration with congested blood vessels. Statistically, there were highly significant decrease in the number of proliferating cell nuclear antigen immunopositive cells, area percentage of Bcl-2 immunoexpression and highly significant increase in the collagen content compared to control group. Administration of RUT with ALS minimizes these changes. RUT protected the rat tongue against the histological and immunohistochemical changes induced by ALS through its antioxidant and anti-inflammatory properties.
PubMed: 38360060
DOI: 10.5115/acb.23.230 -
JA Clinical Reports Feb 2024Bisphosphonates may cause serious adverse events, including osteonecrosis of the jaw. This article describes a case of successful application of radiofrequency...
BACKGROUND
Bisphosphonates may cause serious adverse events, including osteonecrosis of the jaw. This article describes a case of successful application of radiofrequency thermocoagulation for pain caused by osteonecrosis of the jaw.
CASE PRESENTATION
An 86-year-old woman who had received alendronate sodium hydrate for osteoporosis was diagnosed with osteonecrosis of the right mandible after dental treatment. Despite repeated conservative and debridement treatments, the patient could not eat due to intractable pain; accordingly, her condition was debilitated. The patient was referred to our pain management clinic for radiofrequency thermocoagulation of the right mandibular nerve. Immediately after the procedure, her pain drastically improved and she could eat; moreover, the pain has not recurred for 3 years.
CONCLUSION
Our findings demonstrate that minimally invasive radiofrequency thermocoagulation may have long-term effects in patients with chronic pain caused by osteonecrosis of the jaw that is refractory to conservative treatment.
PubMed: 38349573
DOI: 10.1186/s40981-024-00696-2