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2.
Arch Osteoporos ; 17(1): 110, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35920939

RESUMO

PURPOSE/INTRODUCTION: The objective of this study was to describe osteoporosis-related care patterns during the coronavirus disease 2019 (COVID-19) pandemic in Alberta, Canada, relative to the 3-year preceding. METHODS: A repeated cross-sectional study design encompassing 3-month periods of continuous administrative health data between March 15, 2017, and September 14, 2020, described osteoporosis-related healthcare resource utilization (HCRU) and treatment patterns. Outcomes included patients with osteoporosis-related healthcare encounters, physician visits, diagnostic and laboratory test volumes, and treatment initiations and disruptions. The percent change between outcomes was calculated, averaged across the control periods (2017-2019), relative to the COVID-19 periods (2020). RESULTS: Relative to the average control March to June period, all HCRU declined during the corresponding COVID-19 period. There was a reduction of 14% in patients with osteoporosis healthcare encounters, 13% in general practitioner visits, 9% in specialist practitioner visits, 47% in bone mineral density tests, and 13% in vitamin D tests. Treatment initiations declined 43%, 26%, and 35% for oral bisphosphonates, intravenous bisphosphonates, and denosumab, respectively. Slight increases were observed in the proportion of patients with treatment disruptions. In the subsequent June to September period, HCRU either returned to or surpassed pre-pandemic levels, when including telehealth visits accounting for 33-45% of healthcare encounters during the COVID periods. Oral bisphosphonate treatment initiations remained lower than pre-pandemic levels. CONCLUSIONS: This study demonstrates the COVID-19 pandemic and corresponding public health lockdowns further heightened the "crisis" around the known gap in osteoporosis care and altered the provision of care (e.g., use of telehealth and initiation of treatment). Osteoporosis has a known substantial care and management disparity, which has been classified as a crisis. The COVID-19 pandemic created additional burden on osteoporosis patient care with healthcare encounters, physician visits, diagnostic and laboratory tests, and treatment initiations all declining during the initial pandemic period, relative to previous years.


Assuntos
COVID-19 , Osteoporose , Alberta/epidemiologia , COVID-19/epidemiologia , COVID-19/terapia , Controle de Doenças Transmissíveis , Estudos Transversais , Difosfonatos/uso terapêutico , Humanos , Osteoporose/epidemiologia , Osteoporose/terapia , Pandemias
3.
Elife ; 112022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35942681

RESUMO

For the treatment of postmenopausal osteoporosis, several drug classes with different mechanisms of action are available. Since only a limited set of dosing regimens and drug combinations can be tested in clinical trials, it is currently unclear whether common medication strategies achieve optimal bone mineral density gains or are outperformed by alternative dosing schemes and combination therapies that have not been explored so far. Here, we develop a mathematical framework of drug interventions for postmenopausal osteoporosis that unifies fundamental mechanisms of bone remodeling and the mechanisms of action of four drug classes: bisphosphonates, parathyroid hormone analogs, sclerostin inhibitors, and receptor activator of NF-κB ligand inhibitors. Using data from several clinical trials, we calibrate and validate the model, demonstrating its predictive capacity for complex medication scenarios, including sequential and parallel drug combinations. Via simulations, we reveal that there is a large potential to improve gains in bone mineral density by exploiting synergistic interactions between different drug classes, without increasing the total amount of drug administered.


Our bones are constantly being renewed in a fine-tuned cycle of destruction and formation that helps keep them healthy and strong. However, this process can become imbalanced and lead to osteoporosis, where the bones are weakened and have a high risk of fracturing. This is particularly common post-menopause, with one in three women over the age of 50 experiencing a broken bone due to osteoporosis. There are several drug types available for treating osteoporosis, which work in different ways to strengthen bones. These drugs can be taken individually or combined, meaning that a huge number of drug combinations and treatment strategies are theoretically possible. However, it is not practical to test the effectiveness of all of these options in human trials. This could mean that patients are not getting the maximum potential benefit from the drugs available. Jörg et al. developed a mathematical model to predict how different osteoporosis drugs affect the process of bone renewal in the human body. The model could then simulate the effect of changing the order in which the therapies were taken, which showed that the sequence had a considerable impact on the efficacy of the treatment. This occurs because different drugs can interact with each other, leading to an improved outcome when they work in the right order. These results suggest that people with osteoporosis may benefit from altered treatment schemes without changing the type or amount of medication taken. The model could suggest new treatment combinations that reduce the risk of bone fracture, potentially even developing personalised plans for individual patients based on routine clinical measurements in response to different drugs.


Assuntos
Conservadores da Densidade Óssea , Osteoporose Pós-Menopausa , Osteoporose , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Osteoporose/tratamento farmacológico , Osteoporose Pós-Menopausa/tratamento farmacológico
4.
Sci Rep ; 12(1): 11545, 2022 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-35799050

RESUMO

A drug holiday of 3 months does not promote separation of sequestra and is not correlated with treatment outcomes after surgical therapy in osteoporosis patients who receive antiresorptive agents and who have medication-related osteonecrosis of the jaw. Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse effect of antiresorptive agents alone or in combination with immune modulators or antiangiogenic medications, in the absence of radiation exposure to the head and neck region. The effectiveness of surgical treatment for MRONJ has been reported, but the timing of the operation remains controversial. The purpose of this study was to clarify whether preoperative drug holidays of antiresorptive agents promote sequestrum separation and improve treatment outcomes in patients who receive low doses of antiresorptive agents. This retrospective study included 173 patients who received low-dose antiresorptive agents and underwent surgical therapy. The effects of a drug holiday on the separation of sequestra and treatment outcomes were analyzed using logistic and Cox regression analyses. Multivariate analysis revealed that administration of an antiresorptive agent for more than 4 years, a high number of lymphocytes, and an extensive osteolytic area were significantly correlated with separation of sequestra, but drug holiday did not promote sequestrum separation. Furthermore, a drug holiday of 90, 120 or 180 days did not show any improvement in treatment outcomes. The drug holiday of the antiresorptive agents for the treatment of MRONJ is unnecessary, and surgical therapy should be performed early.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Osteoporose , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/tratamento farmacológico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/cirurgia , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/uso terapêutico , Humanos , Osteoporose/induzido quimicamente , Osteoporose/complicações , Osteoporose/tratamento farmacológico , Preparações Farmacêuticas , Estudos Retrospectivos , Resultado do Tratamento
5.
Front Cell Infect Microbiol ; 12: 910970, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35811672

RESUMO

S. aureus infection of bone is difficult to eradicate due to its ability to colonize the osteocyte-lacuno-canalicular network (OLCN), rendering it resistant to standard-of-care (SOC) antibiotics. To overcome this, we proposed two bone-targeted bisphosphonate-conjugated antibiotics (BCA): bisphosphonate-conjugated sitafloxacin (BCS) and hydroxybisphosphonate-conjugate sitafloxacin (HBCS). Initial studies demonstrated that the BCA kills S. aureus in vitro. Here we demonstrate the in vivo efficacy of BCS and HBCS versus bisphosphonate, sitafloxacin, and vancomycin in mice with implant-associated osteomyelitis. Longitudinal bioluminescent imaging (BLI) confirmed the hypothesized "target and release"-type kinetics of BCS and HBCS. Micro-CT of the infected tibiae demonstrated that HBCS significantly inhibited peri-implant osteolysis versus placebo and free sitafloxacin (p < 0.05), which was not seen with the corresponding non-antibiotic-conjugated bisphosphonate control. TRAP-stained histology confirmed that HBCS significantly reduced peri-implant osteoclast numbers versus placebo and free sitafloxacin controls (p < 0.05). To confirm S. aureus killing, we compared the morphology of S. aureus autolysis within in vitro biofilm and infected tibiae via transmission electron microscopy (TEM). Live bacteria in vitro and in vivo presented as dense cocci ~1 µm in diameter. In vitro evidence of autolysis presented remnant cell walls of dead bacteria or "ghosts" and degenerating (non-dense) bacteria. These features of autolyzed bacteria were also present among the colonizing S. aureus within OLCN of infected tibiae from placebo-, vancomycin-, and sitafloxacin-treated mice, similar to placebo. However, most of the bacteria within OLCN of infected tibiae from BCA-treated mice were less dense and contained small vacuoles and holes >100 nm. Histomorphometry of the bacteria within the OLCN demonstrated that BCA significantly increased their diameter versus placebo and free antibiotic controls (p < 0.05). As these abnormal features are consistent with antibiotic-induced vacuolization, bacterial swelling, and necrotic phenotype, we interpret these findings to be the initial evidence of BCA-induced killing of S. aureus within the OLCN of infected bone. Collectively, these results support the bone targeting strategy of BCA to overcome the biodistribution limits of SOC antibiotics and warrant future studies to confirm the novel TEM phenotypes of bacteria within OLCN of S. aureus-infected bone of animals treated with BCS and HBCS.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Osteomielite , Infecções Estafilocócicas , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Difosfonatos/farmacologia , Difosfonatos/uso terapêutico , Modelos Animais de Doenças , Fluoroquinolonas , Camundongos , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus , Distribuição Tecidual , Vancomicina/farmacologia
6.
J Hand Surg Asian Pac Vol ; 27(3): 553-559, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35808877

RESUMO

Atypical ulna fracture (AUF) is relatively rare and is known to be associated with prolonged bisphosphonate (BP) use. The developmental mechanism remains unclear. We report a patient with an AUF associated with BP and severe spinal deformity. The patient was an 85-year-old woman receiving oral alendronate for 8 years without vitamin D supplementation. During regular kitchen work, she needed left upper limb support. She presented with atraumatic pain over the ulna. Radiographs revealed a transverse fracture in the proximal ulna and ulna bowing deformity. Whole-spine standing radiographs showed severe degenerative kyphoscoliosis. The skin induration with pigmentation on her left elbow that suggested prolonged overload and during standing work, coincided exactly with fracture location. This report suggests that 'direct stress', with persistent local overload on the proximal ulna, is one of the developmental mechanisms of AUF, in addition to persistent suppression of bone remodelling by prolonged BP use and vitamin D deficiency. Level of Evidence: Level V (Therapeutic).


Assuntos
Conservadores da Densidade Óssea , Fraturas Ósseas , Fraturas da Ulna , Idoso de 80 Anos ou mais , Alendronato/uso terapêutico , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Feminino , Humanos , Radiografia , Fraturas da Ulna/induzido quimicamente , Fraturas da Ulna/diagnóstico por imagem
7.
Br J Hosp Med (Lond) ; 83(6): 1-7, 2022 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-35787163

RESUMO

Hypercalcaemia is a common metabolic abnormality and its differential diagnosis is vast. Immobility is an uncommon cause of hypercalcaemia. Immobilisation hypercalcaemia is independent of parathyroid hormone and is associated with low levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D. In addition, it is characterised by elevated levels of markers of bone resorption and low levels of bone-specific alkaline phosphatase, highlighting an imbalance of bone remodelling favouring osteoclastic bone resorption. Although immobilisation hypercalcaemia is a diagnosis of exclusion, physicians need to be aware of this condition to avoid excessive and invasive investigations when all other causes of parathyroid hormone-independent hypercalcaemia have been excluded. Management of immobilisation hypercalcaemia revolves around early mobilisation and rehabilitation together with pharmacotherapeutic agents such as intravenous isotonic saline, calcitonin and bisphosphonates. Denosumab may be a potential alternative yet off-label treatment for immobility hypercalcaemia in patients with renal insufficiency.


Assuntos
Reabsorção Óssea , Hipercalcemia , Reabsorção Óssea/complicações , Reabsorção Óssea/tratamento farmacológico , Diagnóstico Diferencial , Difosfonatos/uso terapêutico , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/etiologia , Hipercalcemia/terapia , Hormônio Paratireóideo/uso terapêutico
8.
Comput Math Methods Med ; 2022: 2368564, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35844452

RESUMO

Background: Bisphosphonate is currently considered one of the drugs for the first-line treatment of osteoporosis because of its ability to inhibit bone resorption, but the molecular mechanism of its effect on osteocyte proliferation and bone formation of diabetic osteoporosis is still unclear. Objective: To confirm the potential effect on of bisphosphonate on osteocyte proliferation and bone formation in patients having diabetic osteoporosis (DO). Methods: Sixty DO patients admitted to our hospital from February 2019 to April 2021 were randomly selected and divided into the bisphosphonate group and the control group. The total incidence, incidence of hip fracture, efficacy, bone mineral density, osteocalcin, pain score, osteocyte proliferation, bone formation index, serum calcium, and phosphorus contents were compared between two groups. Results: The curative effect of bisphosphonic acid group was better than that of control group, and the difference was statistically significant (P < 0.05). Compared with the control group, the bone mineral density and osteocalcin in the bisphosphonic acid group were significantly improved after treatment, and the pain score in the bisphosphonic acid group was significantly lower than that in the control group (P < 0.05). After intervention treatment, the OD and PINP values in the bisphosphonate group were significantly different from those in the control group (P < 0.05). After treatment, the contents of serum calcium and phosphorus in the bisphosphonic acid group were significantly higher than those in the control group (P < 0.05). The incidence of hip fracture, spinal fracture, and other fractures in the bisphosphonic acid group was significantly lower than that in the control group (P < 0.05). Conclusion: The treatment of DO with bisphosphonate is capability of effectively improving bone cell proliferation and bone formation, further alleviating clinical symptoms and promoting the improvement of the disease.


Assuntos
Conservadores da Densidade Óssea , Diabetes Mellitus , Fraturas do Quadril , Osteoporose , Densidade Óssea , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Cálcio , Proliferação de Células , Diabetes Mellitus/tratamento farmacológico , Difosfonatos/farmacologia , Difosfonatos/uso terapêutico , Humanos , Osteocalcina/farmacologia , Osteocalcina/uso terapêutico , Osteócitos , Osteogênese , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Dor/tratamento farmacológico , Fósforo/farmacologia , Fósforo/uso terapêutico
9.
Int J Mol Sci ; 23(13)2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35805927

RESUMO

Neridronate or ((6-amino-1-hydroxy-1-phosphonohexyl) phosphonic acid) is an amino-bisphosphonate (BP) synthetized in Italy in 1986. Bisphosphonates are molecules with a P-C-P bond in their structure that allows strong and selectively binding to hydroxyapatite (HAP) as well as osteoclasts inhibition through different mechanisms of action. Neridronate was initially used to treat Paget disease of the bone, demonstrating effectiveness in reducing bone turnover markers as well as pain. The interesting molecular properties of neridronate foster its wide use in several other conditions, such as osteogenesis imperfecta, and osteoporosis. Thanks to the unique safety and efficacy profile, neridronate has been used in secondary osteoporosis due to genetic, rheumatic, and oncological diseases, including in pediatric patients. In the last decade, this drug has also been studied in chronic musculoskeletal pain conditions, such as algodystrophy, demonstrating effectiveness in improving extraskeletal outcomes. This review highlights historical and clinical insights about the use of neridronate for metabolic bone disorders and musculoskeletal pain conditions.


Assuntos
Dor Musculoesquelética , Osteoporose , Densidade Óssea , Criança , Difosfonatos/uso terapêutico , Humanos , Dor Musculoesquelética/tratamento farmacológico , Osteoporose/tratamento farmacológico
10.
Arch Osteoporos ; 17(1): 97, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35854163

RESUMO

Trends in bone mineral density monitoring, and drug treatment for osteoporosis, in Australia were examined. Rates of DEXA scanning have increased in response to changes to government policy affecting reimbursement. The drug denosumab is being utilised at an increasing rate, while bisphosphonate use has declined. Osteoporosis prevalence remained stable over the same timeframe, while rate of hip fractures declined, suggesting that introduction of osteoporosis screening was associated with a reduction in adverse osteoporosis outcomes, but may also have been associated with overutilisation. INTRODUCTION: Radiology interventions to diagnose and medications to manage osteoporosis in Australia are reimbursed under the Medicare benefits schedule (MBS) and Pharmaceutical Benefits Scheme (PBS). Monitoring of these databases enables changes in utilisation of these practices to be monitored over time. METHODS: This study examined rates of utilisation for bone mineral density (BMD) measurement and osteoporosis pharmacotherapy subsidised under the MBS. Rates of osteoporosis and hip fracture were estimated using data reported by the Australian Bureau of Statistics (ABS) and Australian Institute for Health and Welfare (AIHW). RESULTS: Rates of BMD measurement increased since the technology was first reimbursed, with changes to policy regarding reimbursement for screening for individuals over 70 leading to an increase in BMD measurement after 2007. Prescribing rates also increased over time, initially with the introduction of oral bisphosphonates and subsequently for denosumab, which has subsequently become the most commonly prescribed agent for osteoporosis management in Australia, while bisphosphonate use has declined. Osteoporosis prevalence in Australia has remained relatively static at 3-4% of the population since 2001 to 2017, while rates of minimal trauma hip fracture hospitalisations have declined from 195 per 100,000 to 174 per 100,000 in the same timeframe. CONCLUSION: Available data indicates that osteoporosis screening rates changed over time from 2001 to 2018 and that changes to government policy had a significant effect on the rates at which screening was performed. Over the same timeframe, there was a sustained reduction in hip fracture hospitalisation rates, with no change to reported osteoporosis prevalence. This suggests that policy changes permitting unlimited access to BMD measurement were associated with a reduction in osteoporotic fractures, but may also have been associated with overutilisation. Prospective studies to assess the efficacy of specific policies to ensure screening is performed in accordance with best-practice guidelines may be desirable.


Assuntos
Conservadores da Densidade Óssea , Fraturas do Quadril , Osteoporose , Fraturas por Osteoporose , Idoso , Austrália/epidemiologia , Densidade Óssea , Denosumab/uso terapêutico , Difosfonatos/uso terapêutico , Fraturas do Quadril/complicações , Humanos , Programas Nacionais de Saúde , Osteoporose/diagnóstico por imagem , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/complicações , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/epidemiologia , Estudos Prospectivos
11.
Cells ; 11(14)2022 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-35883606

RESUMO

Immunotherapy is an attractive therapeutic strategy for the treatment of osteosarcoma (OS). The unique features of γδ T cells have made them popular for cancer immunotherapy. Here, we expanded γδ T cells using human peripheral blood mononuclear cells (PBMCs) and investigated their therapeutic potential against OS cells. PBMCs from healthy donors were cultured for 10 days with CON medium (unstimulated control); EX media, CON with recombinant human interleukin-2 (rhIL-2) and zoledronate; and EX28 media, CON with rhIL-2, zoledronate, and CD3/CD28 activator. The expanded γδ T cells were isolated by magnetic cell separation or fluorescence-activated cell sorting, cultured with two OS cell lines (KHOS/NP and MG-63) at various cell ratios with or without doxorubicin or ifosfamide, and analyzed for cytotoxicity and cytokine secretion. The number of CD3+γδTCR+Vγ9+ triple-positive γδ T cells and concentrations of IFN-γ and TNF-α were highest in the rhIL-2 (100 IU) and zoledronate (1 µM) supplemented culture conditions. The CD3/CD28 agonist did not show any additional effects on γδ T cell expansion. The expanded γδ T cells exhibited potent in vitro cytotoxicity against OS in a ratio- and time-dependent manner. The γδ T cells may enhance the effect of chemotherapeutic agents against OS and may be a new treatment strategy, including chemo-immunotherapy, for OS.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Receptores de Antígenos de Linfócitos T gama-delta , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/terapia , Antígenos CD28/metabolismo , Difosfonatos/metabolismo , Difosfonatos/farmacologia , Humanos , Imidazóis/metabolismo , Imidazóis/farmacologia , Leucócitos Mononucleares/metabolismo , Osteossarcoma/metabolismo , Osteossarcoma/terapia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/uso terapêutico , Linfócitos T/metabolismo , Linfócitos T/transplante , Ácido Zoledrônico/farmacologia
12.
Anticancer Res ; 42(8): 4139-4143, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35896231

RESUMO

BACKGROUND/AIM: Post-menopausal breast cancer (BC) patients who receive adjuvant aromatase inhibitor (AI) therapy may be at increased risk of bone loss, osteoporosis, and bone fracture. We aimed to evaluate the efficacy and safety of oral bisphosphonate minodronate in preventing bone loss complications. PATIENTS AND METHODS: Patients receiving AI and 80% of those with suboptimal bone mineral density (BMD) were prescribed monthly oral minodronate 50 mg every 4 weeks for 72 weeks. BMD, bone metabolism markers, incidence of bone fractures, medication compliance, and other adverse events (AE) were examined every 24 weeks following administration. RESULTS: Fifty postmenopausal BC patients with a median age of 64.0 years were enrolled. The mean value of lumbar spine BMD was higher than that of the value before the minodronate administration at each observation point. Before and after the treatment, the median serum values of Tartrate-resistant Acid Phosphatase 5b (TRACP-5b) (mU/dl) and serum type I collagen cross-linked N-telopeptide (NTX) (nmolBCE/l) were decreased from 535.7 and 18.5 to 230.1 and 11.9, respectively. No adverse grade 2 or higher event was observed throughout this study. CONCLUSION: The combined administration of minodronate and AIs was safe and effective in preventing bone loss complications in postmenopausal BC patients.


Assuntos
Conservadores da Densidade Óssea , Doenças Ósseas Metabólicas , Neoplasias da Mama , Fraturas Ósseas , Inibidores da Aromatase/efeitos adversos , Densidade Óssea , Conservadores da Densidade Óssea/efeitos adversos , Neoplasias da Mama/complicações , Difosfonatos/efeitos adversos , Feminino , Fraturas Ósseas/etiologia , Humanos , Imidazóis , Pessoa de Meia-Idade , Pós-Menopausa
13.
Eur Rev Med Pharmacol Sci ; 26(13): 4659-4665, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35856356

RESUMO

OBJECTIVE: The Italian Association for Medical Oncology (AIOM) recommends preventive treatment of skeletal-related events in order to improve survival and the quality of life of patients with advanced malignancies. The aim of the study was to evaluate whether routine clinical practice is in agreement with recommendations about the use of denosumab. PATIENTS AND METHODS: A survey was carried out in Italy in the oncological setting. RESULTS: The answers to the survey showed that a large proportion of patients with metastases from solid tumors receive treatment; almost all oncologists administered denosumab every 4 weeks but for a shorter period of time than recommended. CONCLUSIONS: This survey showed that Italian oncologists favor the use of bone-targeted therapy to prevent skeletal-related events in patients affected by metastatic breast, prostate or lung cancer, in agreement with current recommendations.


Assuntos
Conservadores da Densidade Óssea , Neoplasias Ósseas , Neoplasias Pulmonares , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Denosumab/uso terapêutico , Difosfonatos/uso terapêutico , Humanos , Neoplasias Pulmonares/patologia , Masculino , Qualidade de Vida
14.
BMC Oral Health ; 22(1): 291, 2022 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-35843929

RESUMO

OBJECTIVE: Implantology represents the gold standard for oral rehabilitation, unfortunately, often, despite there are no local contraindications to this type of rehabilitation, there are uncertainties regarding the general health of our patients. Many patients nowadays take bisphosphonate drugs, often without first seeking advice from an oral surgeon or a dentist. The purpose of this review is precisely to highlight any contraindications to this type of treatment reported in the literature, in patients who take or have taken bisphosphonate drugs. METHODS: For this study the scientific information sources were consulted using as search terms "("bisphosphonate AND "dental implant")", obtaining 312 results, these were subsequently skimmed according to the inclusion and exclusion criteria, and further evaluated their relevance to the study and the presence of requested outcomes. RESULTS: Only 9 manuscripts (RCTs, Multicentric studies and Clinical Trials) were included in this review, as they respected the parameters of this review, they were analyzed and it was possible to draw important results from them. Surely from this study it is understood that the use of bisphosphonate drugs does not represent an absolute contraindication to implant therapy, it is evident how adequate pharmacological prophylaxis, and an adequate protocol reduce the risks regarding implant failures. Furthermore, the values of marginal bone loss over time seem, even if not statistically significant, to be better in implant rehabilitation with bisphosphonate drugs association. Only a few molecules like risedronate, or corticosteroids, or some conditions like smoking or diabetes have shown a high risk of surgical failure. CONCLUSION: Although this study considered different studies for a total of 378 patients and at least 1687 different dental implants, showing better results in some cases for dental implant therapy in cases of bisphosphonate intake, further clinical, randomized and multicentric studies are needed, with longer follow-ups, to fully clarify this situation which often negatively affects the quality of life of our patients and places clinicians in the face of doubts.


Assuntos
Implantes Dentários , Difosfonatos , Implantação Dentária Endóssea/métodos , Implantes Dentários/efeitos adversos , Falha de Restauração Dentária , Difosfonatos/efeitos adversos , Humanos , Qualidade de Vida
15.
Cochrane Database Syst Rev ; 7: CD012432, 2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35866376

RESUMO

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse reaction experienced by some individuals to certain medicines commonly used in the treatment of cancer and osteoporosis (e.g. bisphosphonates, denosumab, and antiangiogenic agents), and involves the progressive destruction of bone in the mandible or maxilla. Depending on the drug, its dosage, and the duration of exposure, this adverse drug reaction may occur rarely (e.g. following the oral administration of bisphosphonate or denosumab treatments for osteoporosis, or antiangiogenic agent-targeted cancer treatment), or commonly (e.g. following intravenous bisphosphonate for cancer treatment). MRONJ is associated with significant morbidity, adversely affects quality of life (QoL), and is challenging to treat. This is an update of our review first published in 2017. OBJECTIVES: To assess the effects of interventions versus no treatment, placebo, or an active control for the prophylaxis of MRONJ in people exposed to antiresorptive or antiangiogenic drugs. To assess the effects of non-surgical or surgical interventions (either singly or in combination) versus no treatment, placebo, or an active control for the treatment of people with manifest MRONJ. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched four bibliographic databases up to 16 June 2021 and used additional search methods to identify published, unpublished, and ongoing studies.  SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing one modality of intervention with another for the prevention or treatment of MRONJ. For 'prophylaxis of MRONJ', the primary outcome of interest was the incidence of MRONJ; secondary outcomes were QoL, time-to-event, and rate of complications and side effects of the intervention. For 'treatment of established MRONJ', the primary outcome of interest was healing of MRONJ; secondary outcomes were QoL, recurrence, and rate of complications and side effects of the intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results, extracted the data, and assessed the risk of bias in the included studies. For dichotomous outcomes, we reported the risk ratio (RR) (or rate ratio) and 95% confidence intervals (CIs). MAIN RESULTS: We included 13 RCTs (1668 participants) in this updated review, of which eight were new additions. The studies were clinically diverse and examined very different interventions, so meta-analyses could not be performed. We have low or very low certainty about available evidence on interventions for the prophylaxis or treatment of MRONJ. Prophylaxis of MRONJ Five RCTs examined different interventions to prevent the occurrence of MRONJ. One RCT compared standard care with regular dental examinations at three-month intervals and preventive treatments (including antibiotics before dental extractions and the use of techniques for wound closure that avoid exposure and contamination of bone) in men with metastatic prostate cancer treated with zoledronic acid. The intervention seemed to lower the risk of MRONJ (RR 0.10, 95% CI 0.02 to 0.39, 253 participants). Secondary outcomes were not evaluated. Dentoalveolar surgery is considered a common predisposing event for developing MRONJ and five RCTs tested various preventive measures to reduce the risk of postoperative MRONJ. The studies evaluated plasma rich in growth factors inserted into the postextraction alveolus in addition to standardised medical and surgical care versus standardised medical and surgical care alone (RR 0.08, 95% CI 0.00 to 1.51, 176 participants); delicate surgery and closure by primary intention versus non-traumatic tooth avulsion and closure by secondary intention (no case of postoperative MRONJ in either group); primary closure of the extraction socket with a mucoperiosteal flap versus application of platelet-rich fibrin without primary wound closure (no case of postoperative MRONJ in either group); and subperiosteal wound closure versus epiperiosteal wound closure (RR 0.09, 95% CI 0.00 to 1.56, 132 participants).  Treatment of MRONJ Eight RCTs examined different interventions for the treatment of established MRONJ; that is, the effect on MRONJ cure rates.  One RCT analysed hyperbaric oxygen (HBO) treatment used in addition to standard care (antiseptic rinses, antibiotics, and surgery) compared with standard care alone (at last follow-up: RR 1.56, 95% CI 0.77 to 3.18, 46 participants).  Healing rates from MRONJ were not significantly different between autofluorescence-guided bone surgery and conventional bone surgery (RR 1.08, 95% CI 0.85 to 1.37, 30 participants). Another RCT that compared autofluorescence- with tetracycline fluorescence-guided sequestrectomy for the surgical treatment of MRONJ found no significant difference (at one-year follow-up: RR 1.05, 95% CI 0.86 to 1.30, 34 participants).  Three RCTs investigated the effect of growth factors and autologous platelet concentrates on healing rates of MRONJ: platelet-rich fibrin after bone surgery versus surgery alone (RR 1.05, 95% CI 0.90 to 1.22, 47 participants), bone morphogenetic protein-2 together with platelet-rich fibrin versus platelet-rich fibrin alone (RR 1.10, 95% CI 0.94 to 1.29, 55 participants), and concentrated growth factor and primary wound closure versus primary wound closure only (RR 1.38, 95% CI 0.81 to 2.34, 28 participants).   Two RCTs focused on pharmacological treatment with teriparatide: teriparatide 20 µg daily versus placebo in addition to standard care (RR 0.96, 95% CI 0.31 to 2.95, 33 participants) and teriparatide 56.5 µg weekly versus teriparatide 20 µg daily in addition to standard care (RR 1.60, 95% CI 0.25 to 1.44, 12 participants). AUTHORS CONCLUSIONS: Prophylaxis of medication-related osteonecrosis of the jaw One open-label RCT provided some evidence that dental examinations at three-month intervals and preventive treatments may be more effective than standard care for reducing the incidence of medication-related osteonecrosis of the jaw (MRONJ) in individuals taking intravenous bisphosphonates for advanced cancer. We assessed the certainty of the evidence to be very low. There is insufficient evidence to either claim or refute a benefit of the interventions tested for prophylaxis of MRONJ in patients with antiresorptive therapy undergoing dentoalveolar surgery. Although some interventions suggested a potential large effect, the studies were underpowered to show statistical significance, and replication of the results in larger studies is pending. Treatment of medication-related osteonecrosis of the jaw The available evidence is insufficient to either claim or refute a benefit, in addition to standard care, of any of the interventions studied for the treatment of MRONJ.


Assuntos
Osteonecrose , Osteoporose , Antibacterianos/uso terapêutico , Denosumab/efeitos adversos , Difosfonatos/efeitos adversos , Humanos , Masculino , Osteoporose/tratamento farmacológico , Teriparatida
16.
Front Cell Infect Microbiol ; 12: 886411, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35811676

RESUMO

One of the most prominent characteristics of bisphosphonate-related osteonecrosis of the jaw(BRONJ) is its site-specificity. Osteonecrosis tends to occur specifically in maxillofacial bones, in spite of a systemic administration of the medicine. Previous studies suggested rich blood supply and fast bone turnover might be reasons for BRONJ. Yet, a sound scientific basis explaining its occurrence is still lacking. The present study aimed to explore the role of Porphyromonas gingivalis (P. gingivalis), an important oral pathogen, on the site-specificity of bisphosphonate-induced osteonecrosis and to elucidate its underlying mechanism. Mice were intraperitoneally injected with zoledronic acid (ZA) or saline for 3 weeks. In the third week, the right mandibular first molars were extracted and circular bone defects with a diameter of 1 mm were created in right femurs. After the operation, drug administration was continued, and P. gingivalis suspension was applied to the oral cavities and femur defects. The mice were killed after four or eight weeks postoperatively. The right mandibles and femurs were harvested for micro-CT and histological analyses. A poor healing of bone defects of both jaws and femurs was noted in mice injected with both ZA and P. gingivalis. Micro-CT analysis showed a decreased bone volume, and histological staining showed an increased number of empty osteocyte lacunae, a decreased collagen regeneration, an increased inflammatory infiltration and a decreased number of osteoclasts. In addition, the left femurs were collected for isolation of osteoclast precursors (OCPs). The osteoclastogenesis potential of OCPs was analyzed in vitro. OCPs extracted from mice of ZA-treated groups were shown to have a lower osteoclast differentiation potential and the expression level of related genes and proteins was declined. In conclusion, we established a mouse model of bisphosphonate-related osteonecrosis of both the jaw and femur. P. gingivalis could inhibit the healing of femur defects under the administration of ZA. These findings suggest that P. gingivalis in the oral cavity might be one of the steering compounds for BRONJ to occur.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/tratamento farmacológico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Difosfonatos/efeitos adversos , Fêmur/patologia , Imidazóis/farmacologia , Camundongos , Porphyromonas gingivalis , Ácido Zoledrônico/uso terapêutico
17.
São Paulo; s.n; 20220601. 109 p.
Tese em Português | LILACS, BBO - Odontologia | ID: biblio-1370762

RESUMO

O carcinoma secretório em glândula salivar é uma neoplasia recentemente descrita que tem os mesmos aspectos morfológicos, imuno-histoquímicos e genéticos do carcinoma secretório de origem mamária. O carcinoma secretório tem características celulares reminiscentes de uma célula secretora lactacional, isto é, um citoplasma vacuolado repleto de gotas lipídicas e um material secretado, por vezes de forma apócrina, que pode lembrar o leite. Mais recentemente, algum nível de diferenciação lactacional foi sugerida no carcinoma secretório de origem salivar. O objetivo do estudo foi verificar se existe uma diferenciação do tipo lactacional em carcinomas secretórios de origem salivar, comparando a outros tipos de carcinomas salivares mais comuns. Foram realizadas reações imuno-histoquímicas para as seguintes proteínas: receptores hormonais (receptor de prolactina e receptor do hormônio do crescimento), proteínas associadas ao produto de secreção da glândula mamária lactacional (mucina-1 (MUC-1), MUC4, globulina de gordura 1 do leite humano, lactoferrina) e proteínas associadas à via Akt-mTOR (PTEN, p-Akt, p-mTOR, p4EBP1, eIF4E, pS6). A maioria dos casos de carcinoma secretório foi negativa para receptor de prolactina e de hormônio do crescimento. Lactoferrina foi positiva em todos os grupos tumorais, porém somente em carcinoma secretório observou-se um padrão de marcação intensa, difuso tanto em célula como em secreção. Todos os casos de carcinoma secretório foram positivos para globulina de gordura do tipo 1, porém o mesmo padrão de marcação foi observado em outros tumores. A maioria dos casos de carcinoma secretório foram positivos para MUC1 e MUC4. Nenhum caso de carcinoma secretório foi positivo para Akt, mas PTEN foi difusamente expresso em 57,1% dos casos. mTOR foi expresso em mais da metade dos casos de carcinoma secretório e dos outros tumores salivares. Entre as proteínas à jusante de mTOR, somente eIF4E demonstrou alta expressão no grupo de estudo. A expressão de marcadores lactacionais não é exclusiva do carcinoma secretório, porém a expressão de lactoferrina é distinta neste grupo de tumores quando comparado aos demais tumores salivares estudados.


Assuntos
Técnicas de Cultura de Células , Difosfonatos , Glucocorticoides
18.
BMJ Open ; 12(6): e056600, 2022 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-35701060

RESUMO

INTRODUCTION: Patients receiving radiotherapy are at risk of developing radiotherapy-related insufficiency fractures, which are associated with increased morbidity and pose a significant burden to patients' quality of life and to the health system. Therefore, effective preventive techniques are urgently required. The RadBone randomised controlled trial (RCT) aims to determine the feasibility and acceptability of a musculoskeletal health package (MHP) intervention in women undergoing pelvic radiotherapy for gynaecological malignancies and to preliminary explore clinical effectiveness of the intervention. METHODS AND ANALYSIS: The RadBone RCT will evaluate the addition to standard care of an MHP consisting of a physical assessment of the musculoskeletal health, a 3-month prehabilitation personalised exercise package, as well as an evaluation of the fracture risk and if required the prescription of appropriate bone treatment including calcium, vitamin D and-for high-risk individuals-bisphosphonates. Forty participants will be randomised in each group (MHP or observation) and will be followed for 18 months. The primary outcome of this RCT will be feasibility, including the eligibility, screening and recruitment rate, intervention fidelity and attrition rates; acceptability and health economics. Clinical effectiveness and bone turnover markers will be evaluated as secondary outcomes. ETHICS AND DISSEMINATION: This study has been approved by the Greater Manchester East Research Ethics Committee (Reference: 20/NW/0410, November 2020). The results will be published in peer-reviewed journals, will be presented in national and international conferences and will be communicated to relevant stakeholders. Moreover, a plain English report will be shared with the study participants, patients' organisations and media. TRIAL REGISTRATION NUMBER: NCT04555317.


Assuntos
Neoplasias dos Genitais Femininos , Difosfonatos , Estudos de Viabilidade , Feminino , Neoplasias dos Genitais Femininos/radioterapia , Humanos , Estudos Prospectivos , Projetos de Pesquisa
19.
BMC Infect Dis ; 22(1): 544, 2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35701730

RESUMO

PURPOSE: The recent coronavirus disease (COVID-19) pandemic mainly affects the respiratory system; however, several oral and maxillofacial post-COVID-19 complications have also been observed. This series reports the growing number of osteonecrosis cases associated with post-COVID-19 patients. MATERIALS AND METHODS: This is a retrospective, multi-center case series that reports cases with maxillary osteonecrosis after various periods of SARS-CoV-2 infection in the period between January and August 2021 based on the PROCESS guidelines. RESULTS: Twelve cases were reported with post-COVID-19 manifestation of spontaneous osteonecrosis of the maxillary jaw. Five patients were hospitalized during COVID-19 management and all of the twelve cases had at least one systematic Co-morbidity, and undertake corticosteroids prescription based on the COVID-19 disease treatment protocol. The mean onset of osteonecrosis symptoms appearance was 5.5 ± 2.43 weeks calculated from the day of the negative PCR test. The management was successfully done through surgical debridement and pre and post-operative antibiotics. No anti-fungal medications were prescribed as the fungal culture and the histopathological report were negative. CONCLUSION: Post-COVID-related osteonecrosis of the jaw (PC-RONJ) could be now considered as one of the potential post-COVID-19 oral and maxillofacial complications that occurs unprovokedly and mainly in the maxilla.


Assuntos
COVID-19 , Osteonecrose , COVID-19/complicações , Difosfonatos/uso terapêutico , Humanos , Morbidade , Osteonecrose/tratamento farmacológico , Osteonecrose/epidemiologia , Osteonecrose/etiologia , Estudos Retrospectivos , SARS-CoV-2
20.
PLoS One ; 17(6): e0269335, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35657923

RESUMO

BACKGROUND: Bone metastases in breast cancer patients are a common concern for medical doctors and dentists. Bone-modifying agents, which are necessary to prevent skeletal-related events (SREs), are associated with osteonecrosis of the jaw as an adverse side effect. Hypersensitivity to alcohol is an unfavorable response caused by deficiency of aldehyde dehydrogenase-2 (ALDH2) activity. Inactive ALDH2 is associated with osteoporosis, but its influence on bone metastases is unclear. The aim of our study was to evaluate the effects of alcohol sensitivity on bone metastases and SREs in primary operable breast cancer patients. METHODS: We retrospectively analyzed patients who were administered docetaxel, an anti-tumor agent, for histologically diagnosed breast cancer between April 2004 and September 2015. Alcohol sensitivity was assessed based on medical records of hypersensitivity to alcohol. The primary endpoint was time to bone metastases and the secondary endpoint was time to first SRE from the initial docetaxel administration. Data were stratified by alcohol sensitivity and tumor stages, and differences were estimated by the Kaplan-Meier method. Prognostic risk factors were analyzed by the multivariate Cox proportional hazards model. RESULTS: The median follow-up period of patients with high sensitivity to alcohol (n = 45) was 54 months and that for those with low sensitivity (n = 287) was 64 months. Stratification by alcohol sensitivity revealed that tumor stage exhibited significant correlations with the cumulative incidence of bone metastases in low-sensitivity patients; however, no differences were found in high-sensitivity patients. In multivariate analysis, alcohol sensitivity was a significant prognostic risk factor for bone metastases (HR 2.721, 95% CI 1.268-5.841, P = 0.010). CONCLUSION: Alcohol sensitivity may be a prognostic risk factor for bone metastases. More detailed genetic investigations and metabolic analyses are needed.


Assuntos
Neoplasias Ósseas , Neoplasias da Mama , Aldeído-Desidrogenase Mitocondrial , Neoplasias Ósseas/secundário , Osso e Ossos/patologia , Neoplasias da Mama/patologia , Difosfonatos/uso terapêutico , Docetaxel/uso terapêutico , Feminino , Humanos , Estudos Retrospectivos
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