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BACKGROUND: We assessed the long-term (24 months) efficacy and safety of monthly calcifediol (0.266 mg) in the correction and maintenance of total 25(OH)D levels in postmenopausal women with basal values <30 ng/mL. METHODS: We initially enrolled 45 consecutive patients during the period September 2019-September 2020. After an initial visit, patients were instructed to return at 3, 6, 9, 12 and 24 months for measuring serum total 25(OH)D, ionised calcium, creatinine and isoenzyme of alkaline phosphatase (bALP). Here, we report only the per-protocol analysis, because the COVID-19 pandemic precluded adherence to the scheduled visits for some patients. RESULTS: The patients' mean age was 62.4 ± 9.0 years. Mean basal 25(OH)D levels were 20.5 ± 5.3 ng/mL. There was a continuous increase of mean 25(OH)D values (p for trend < 0.001). However, mean values at month 24 (36.7 ± 15.9) were not significantly different in respect to values at month 12 (41.2 ± 11.18). At 24 months, only 1 out 19 patients had a value <20 ng/mL. There was a significant decrease with time of mean values of bALP (p < 0.0216), with no significant changes between 12 and 24 months. No significant changes were observed as far as ionised calcium or creatinine were concerned. CONCLUSIONS: The long-term administration of calcifediol maintains stable and sustained 25(OH)D concentrations, with no safety concerns.
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Calcifediol , Posmenopausia , Deficiencia de Vitamina D , Humanos , Femenino , Persona de Mediana Edad , Posmenopausia/sangre , Anciano , Calcifediol/sangre , Calcifediol/administración & dosificación , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/tratamiento farmacológico , Calcio/sangre , Calcio/administración & dosificación , COVID-19 , Vitamina D/sangre , Vitamina D/análogos & derivados , Vitamina D/administración & dosificación , Creatinina/sangre , Fosfatasa Alcalina/sangre , SARS-CoV-2 , Resultado del TratamientoRESUMEN
A 47-year-old postmenopausal woman with osteoporosis was treated with denosumab, which was discontinued due to side effects. She was therefore transitioned to a yearly intravenous infusion of zoledronic acid. An increase in bone turnover markers together with bone loss at the lumbar spine was observed before the second infusion, suggesting an overshooting of bone resorption due to denosumab discontinuation. On physical examination, the patient was restless and reported having lost about 10 kg since the last visit. A solitary left inferior thyroid nodule was noted on neck palpation. Circulating thyroid hormone levels were elevated, with suppressed thyroid-stimulating hormone. A thyroid scan showed increased uptake in the left inferior nodule with suppression of the remainder of the thyroid gland. A diagnosis of hyperthyroidism due to toxic adenoma was made. The patient was treated with radioactive iodine ablation, with consequent complete normalization of thyroid function. She continued yearly treatment with zoledronic acid. She remained clinically well with no further fractures. Bone turnover markers were appropriately suppressed and bone mineral density increased in the spine and hip. This case illustrates how the overshooting phenomenon following denosumab discontinuation may be compounded by the development of secondary conditions, which can result in suboptimal response to antiresorptive osteoporosis medications.
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Conservadores de la Densidad Ósea , Enfermedades Óseas Metabólicas , Osteoporosis Posmenopáusica , Osteoporosis , Neoplasias de la Tiroides , Femenino , Humanos , Persona de Mediana Edad , Denosumab/uso terapéutico , Ácido Zoledrónico/uso terapéutico , Radioisótopos de Yodo/uso terapéutico , Neoplasias de la Tiroides/tratamiento farmacológico , Conservadores de la Densidad Ósea/uso terapéutico , Osteoporosis/tratamiento farmacológico , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Densidad Ósea , Osteoporosis Posmenopáusica/tratamiento farmacológicoRESUMEN
AIM: This guideline (GL) is aimed at providing a clinical practice reference for the management of sporadic primary hyperparathyroidism (PHPT) in adults. PHPT management in pregnancy was not considered. METHODS: This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology (AME) and Società Italiana dell'Osteoporosi, del Metabolismo Minerale e delle Malattie dello Scheletro (SIOMMMS) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence. Those classified as "critical" were considered for the clinical practice recommendations. RESULTS: The present GL provides recommendations about the roles of pharmacological and surgical treatment for the clinical management of sporadic PHPT. Parathyroidectomy is recommended in comparison to surveillance or pharmacologic treatment in any adult (outside of pregnancy) or elderly subject diagnosed with sporadic PHPT who is symptomatic or meets any of the following criteria: ⢠Serum calcium levels >1 mg/dL above the upper limit of normal range. ⢠Urinary calcium levels >4 mg/kg/day. ⢠Osteoporosis disclosed by DXA examination and/or any fragility fracture. ⢠Renal function impairment (eGFR <60 mL/min). ⢠Clinic or silent nephrolithiasis. ⢠Age ≤50 years. Monitoring and treatment of any comorbidity or complication of PHPT at bone, kidney, or cardiovascular level are suggested for patients who do not meet the criteria for surgery or are not operated on for any reason. Sixteen indications for good clinical practice are provided in addition to the recommendations. CONCLUSION: The present GL is directed to endocrinologists and surgeons - working in hospitals, territorial services or private practice - and to general practitioners and patients. The recommendations should also consider the patient's preferences and the available resources and expertise.
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Hiperparatiroidismo Primario , Humanos , Hiperparatiroidismo Primario/terapia , Hiperparatiroidismo Primario/diagnóstico , Hiperparatiroidismo Primario/epidemiología , Italia/epidemiología , Paratiroidectomía/normas , Femenino , AdultoAsunto(s)
Osteomalacia , Síndromes Paraneoplásicos , Humanos , Calcio , Huesos/patología , Osteomalacia/patología , Calcio de la DietaRESUMEN
We isolated five Bacillaceae from a degraded wetland environment and sequenced their genomes using Illumina NextSeq. Here, we report draft genome sequences of Bacillus velezensus-SC119, Priestia megaterium strain SC120, Bacillus zhangzhouensis strain SC123, Bacillus pumilis strain SC124, and Bacillus idriensis strain SC127. The genomes range between 3,657,353 and 5,772,725 bp with % GC between 37.62% and 46.38%.
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PURPOSE: Hypercalcemic primary hyperparathyroidism (PHPT) is a common endocrine disorder that has been very well characterized. In contrast, many aspects of normocalcemic primary hyperparathyroidism (NPHPT) such as natural history, organ damage, and management are still matter of debate. In addition, both the pathophysiology and molecular basis of NPHPT are unclear. We investigated whether PHPT and NPHPT patient cohorts share the same pattern of genetic variation in genes known to be involved in calcium and/or bone metabolism. RESEARCH DESIGN AND METHODS: Genotyping for 9 single nucleotide polymorphisms (SNPs) was performed by Real-Time PCR (TaqMan assays) on 27 NPHPT and 31 PHPT patients evaluated in a tertiary referral Center. The data of both groups were compared with 54 in house-controls and 503 subjects from the 1000 Genomes Project. All groups were compared for allele/haplotype frequencies, on a single locus, two loci and multi-locus basis. RESULTS: The NPHPT group differed significantly at SNPs in OPG and ESR1. Also, the NPHPT cohort was peculiar for pairwise associations of genotypes and for the overrepresentation of unusual multilocus genotypes. CONCLUSIONS: Our NPHPT patient set harbored a definitely larger quota of genetic diversity than the other samples. Specific genotypes may help in defining subgroups of NPHPT patients which deserve ad hoc clinical and follow-up studies.
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Hipercalcemia , Hiperparatiroidismo Primario , Humanos , Hiperparatiroidismo Primario/genética , Hipercalcemia/genética , Calcio , Fenotipo , Genotipo , Hormona ParatiroideaRESUMEN
BACKGROUND: We sought to investigate the mutual interplay between bone, glucose and lipid metabolism in a wide cohort of community-based subjects. METHODS: We studied 1240 blood donors (F/M ratio 1/3.2, mean age 41.9 ± 11.7 SD). Serum ionized (Ca++), magnesium (Mg++), 25-hydroxy-vitamin D [25(OH)D], PTH-1-84, 1,25-dihydroxyvitamin D [1,25(OH)2D], total cholesterol (C), HDL-C, triglycerides and glucose were measured and LDL-C levels were calculated in all subjects. RESULTS: 25(OH)D negatively correlated with BMI (R = -0.11), PTH (R = -0.16) (p < 0.0001), total C (R = -0.06, p < 0.05) and triglycerides (R = -0.13, p < 0.0001) and positively with 1,25(OH)2D (R = 0.12) and creatinine (R = 0.17) (p < 0.0001). Serum PTH positively correlated with total C (R = 0.08, p < 0.01), LDL-C (R = 0.1, p < 0.001), triglycerides (R = 0.09, p < 0.01) and glucose (R = 0.15, p < 0.0001) and negatively with HDL-C (R = -0.09, p < 0.01). The odds of showing abnormal serum triglycerides and HDL-C increased as 25(OH)D decreased (p < 0.0001 and p < 0.03) and PTH increased (p < 0.03 and p = 0.05), while the odds of showing abnormal LDL-C levels increased in association with elevated PTH (p < 0.01). CONCLUSION: Vitamin D, PTH, glucose and lipid metabolism are mutually influenced. Hypovitaminosis D predisposes toward worsening lipid profiles through the actions of PTH, while serum PTH levels per se associate with higher glucose and LDL-C levels.
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Glucosa , Deficiencia de Vitamina D , Humanos , Adulto , Persona de Mediana Edad , LDL-Colesterol , Metabolismo de los Lípidos , Hormona Paratiroidea , Vitamina D , Vitaminas , TriglicéridosRESUMEN
INTRODUCTION: Tumor-induced osteomalacia (TIO) is an uncommon paraneoplastic syndrome due to the overproduction of fibroblast growth factor 23 (FGF23). It is predominantly caused by mesenchymal tumors and cured upon their complete removal. Non-surgical treatment is an alternative option but limited to specific clinical conditions. METHODS: We report a challenging case of TIO caused by a tumor involving the occipital bone. We also performed a literature review of TIO caused by tumors localized at this site, focusing on clinical findings, treatment, and outcomes. RESULTS: The patient, a 62-year-old male, presented with a long-lasting history of progressive weakness. Biochemical evaluation revealed severe hypophosphatemia due to low renal tubular reabsorption of phosphate with raised intact FGF23 values. A 68 Ga-DOTATATE PET/TC imaging showed a suspicious lesion located in the left occipital bone that MRI and selective venous catheterization confirmed to be the cause of TIO. Stereotactic gamma knife radiosurgery was carried out, but unfortunately, the patient died of acute respiratory failure. To date, only seven additional cases of TIO have been associated to tumors located in the occipital bone. Furthermore, the tumor involved the left side of the occipital bone in all these patients. CONCLUSION: The occipital region is a difficult area to access so a multidisciplinary approach for their treatment is required. If anatomical differences could be the basis for the predilection of the left side of the occipital bone, it remains to be clarified.
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Hipofosfatemia , Neoplasias de Tejido Conjuntivo , Osteomalacia , Síndromes Paraneoplásicos , Masculino , Humanos , Persona de Mediana Edad , Neoplasias de Tejido Conjuntivo/etiología , Neoplasias de Tejido Conjuntivo/complicaciones , Síndromes Paraneoplásicos/complicaciones , Síndromes Paraneoplásicos/cirugía , Osteomalacia/etiología , Osteomalacia/patología , Hipofosfatemia/etiología , Hipofosfatemia/patología , Hipofosfatemia/cirugíaRESUMEN
CONTEXT: Suppression of bone turnover, greater trabecular volume, and normal-high normal all-site bone mineral density (BMD) are hallmarks of postsurgical hypoparathyroidism (HypoPT). Impairment in the trabecular microarchitecture with possible higher risk of vertebral fractures (VF) in women with postmenopausal HypoPT has also been described. Currently, no data on bone marrow adipose tissue (BMAT) are available in HypoPT. OBJECTIVE: To assess BMAT by magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H-MRS) in postmenopausal women with chronic postsurgical HypoPT. METHODS: This cross-sectional pilot study, conducted at an ambulatory referral center, included 29 postmenopausal women (mean age 66 ± 8.4 years) with postsurgical HypoPT and 31 healthy postmenopausal women (mean age 63 ± 8.5). Lumbar spine MRI was performed and BMAT was measured by applying PRESS sequences on the L3 body. Lumbar spine, femoral neck, and total hip BMD were measured by dual x-ray absorptiometry (DXA); site-matched spine trabecular bone score (TBS) was calculated by TBS iNsight (Medimaps, Switzerland); VF assessment was performed with lateral thoracic and lumbar spine DXA. RESULTS: Fat content (FC) and saturation level (SL%) were higher (P <.0001 and P <.001), while water content (W) was lower in HypoPT compared to controls (P <.0001). FC significantly correlated with years since menopause and body weight (P <.05) in HypoPT, while TBS negatively correlated with FC and SL% (P <.05) and positively with residual lipids (RL) and W (P <.05). CONCLUSION: We demonstrate for the first time that BMAT is increased in postmenopausal women with postsurgical hypoparathyroidism and negatively associated with trabecular microarchitecture.
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Hipoparatiroidismo , Fracturas de la Columna Vertebral , Humanos , Femenino , Persona de Mediana Edad , Anciano , Médula Ósea/diagnóstico por imagen , Posmenopausia , Estudios Transversales , Proyectos Piloto , Densidad Ósea , Absorciometría de Fotón/métodos , Hipoparatiroidismo/diagnóstico por imagen , Hipoparatiroidismo/etiología , Hipoparatiroidismo/patología , Tejido Adiposo/diagnóstico por imagen , Vértebras Lumbares , Fracturas de la Columna Vertebral/patología , Hueso Esponjoso/diagnóstico por imagen , Hueso Esponjoso/patologíaRESUMEN
Tumor-induced osteomalacia (TIO) is an ultrarare paraneoplastic syndrome due to overproduction of fibroblast growth factor 23 (FGF23), with profound effects on patient morbidity. TIO is an underdiagnosed disease, whose awareness should be increased among physicians for timely and proper management of patients. Symptoms reported by patients with TIO are usually nonspecific, thus rendering the diagnosis elusive, with an initial misdiagnosis rate of more than 95%. Biochemical features of TIO are represented by hypophosphatemia, increased or inappropriately normal levels of FGF23, and low to low normal circulating 1,25-dihydroxyvitamin D (1,25(OH)2D). Phosphaturic mesenchymal tumors are the pathological entities underlying TIO in most affected patients. There is now evidence that FN1-FGFR1 and FN1-FGF1 fusion genes are present in about half of tumors causing this paraneoplastic syndrome. Tumors causing TIO are small and grow slowly. They can occur in all parts of the body from head to toe with similar prevalence in soft tissue and bone. There are a number of functional and anatomical imaging techniques used for tumor localization; 68Ga DOTA-based technologies have better sensitivity. Surgery is the treatment of choice; several medical treatments are now available in case of inability to locate the tumor or in case of incomplete excision.
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Hipofosfatemia , Osteomalacia , Síndromes Paraneoplásicos , Neoplasias de los Tejidos Blandos , Humanos , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/cirugía , Osteomalacia/etiologíaRESUMEN
Neuromuscular impairment is described among the non-classical complications of primary hyperparathyroidism (PHPT). However, the extent of this complications and related mechanisms have not been fully addressed. The study aimed at assessing muscle strength and its main determinants in postmenopausal women with PHPT. We studied 48 postmenopausal women with PHPT (mean age 60.8 ± 5.6 SD years; BMI 25.6 ± 5.5 kg/m2) and 38 healthy postmenopausal women (mean age 58.6 ± 5.9; BMI 25.2 ± 3.5). In all subjects, the maximum voluntary contraction (MVC, Newton, N) was measured by Hand held Dynamometer (Kayser Italia srl, Livorno, Italy) and the lumbar spine, total hip, femoral neck, and non dominant distal one-third radius areal BMD (aBMD) by dual X-ray absorptiometry (DXA) (Hologic, Waltham, MA). Serum ionized calcium (Ca++), parathyroid hormone (PTH), phosphorus (P), and 25-hydroxyvitaminD [25(OH)D] levels were measured in both groups. A subgroup of 30 PHPT women agreed to participate to the follow-up sub-study and were re-assessed 24 months after parathyroidectomy (n = 15) or after baseline evaluation (n = 15). Patients with PHPT had significant lower MVC values compared to healthy women (p < 0.001). As expected, serum Ca++ and PTH levels were higher and P lower in PHPT compared to controls. We observed a significant association between MVC and total hip and one-third radius aBMD (R = 0.320 and 0.370, p < 0.05) and negative association with Ca++ (R = -0.340, p < 0.05) in the PHPT group; MVC was positively associated with one-third radius aBMD (R = 0.360, p < 0.05) and negatively with age, BMI and myostatin (R = -0.390, -0.340 and -0.450, p < 0.05) in the group of healthy women. The linear model using BMI, Ca++, P, 25(OH)D, PTH, myostatin, and aBMD as covariates showed that one-third radius aBMD was positively associated with MVC in PHPT patients (p < 0.02) and in healthy subjects (p < 0.001). Additionally, serum PTH and myostatin were negatively associated with MVC in healthy subjects (p < 0.03 and p < 0.01). The linear model showed that surgery was associated with an increase in MVC (p < 0.05) in PHPT patients after 24 months, all other variables being equal and by controlling for baseline values of MVC. Handgrip strength is significantly impaired in postmenopausal women with PHPT. Some common mechanisms influencing muscle function exist in PHPT and in healthy subjects; they are associated with the reduced aBMD at cortical sites. Hypercalcemia seems to be one of the main determinants of impairment in muscle strength in PHPT, while no role is played by myostatin.
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Densidad Ósea , Hiperparatiroidismo Primario , Humanos , Femenino , Persona de Mediana Edad , Anciano , Densidad Ósea/fisiología , Miostatina , Hiperparatiroidismo Primario/complicaciones , Posmenopausia , Fuerza de la Mano , Absorciometría de Fotón , Hormona Paratiroidea , Vértebras LumbaresRESUMEN
In this narrative review, we present data gathered over four decades (1980-2020) on the epidemiology, pathophysiology and genetics of primary hyperparathyroidism (PHPT). PHPT is typically a disease of postmenopausal women, but its prevalence and incidence vary globally and depend on a number of factors, the most important being the availability to measure serum calcium and parathyroid hormone levels for screening. In the Western world, the change in presentation to asymptomatic PHPT is likely to occur, over time also, in Eastern regions. The selection of the population to be screened will, of course, affect the epidemiological data (ie, general practice as opposed to tertiary center). Parathyroid hormone has a pivotal role in regulating calcium homeostasis; small changes in extracellular Ca++ concentrations are detected by parathyroid cells, which express calcium-sensing receptors (CaSRs). Clonally dysregulated overgrowth of one or more parathyroid glands together with reduced expression of CaSRs is the most important pathophysiologic basis of PHPT. The spectrum of skeletal disease reflects different degrees of dysregulated bone remodeling. Intestinal calcium hyperabsorption together with increased bone resorption lead to increased filtered load of calcium that, in addition to other metabolic factors, predispose to the appearance of calcium-containing kidney stones. A genetic basis of PHPT can be identified in about 10% of all cases. These may occur as a part of multiple endocrine neoplasia syndromes (MEN1-MEN4), or the hyperparathyroidism jaw-tumor syndrome, or it may be caused by nonsyndromic isolated endocrinopathy, such as familial isolated PHPT and neonatal severe hyperparathyroidism. DNA testing may have value in: confirming the clinical diagnosis in a proband; eg, by distinguishing PHPT from familial hypocalciuric hypercalcemia (FHH). Mutation-specific carrier testing can be performed on a proband's relatives and identify where the proband is a mutation carrier, ruling out phenocopies that may confound the diagnosis; and potentially prevention via prenatal/preimplantation diagnosis. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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Hipercalcemia , Hiperparatiroidismo Primario , Recién Nacido , Femenino , Humanos , Hiperparatiroidismo Primario/complicaciones , Hiperparatiroidismo Primario/epidemiología , Hiperparatiroidismo Primario/genética , Calcio , Hipercalcemia/genética , Receptores Sensibles al Calcio/genética , Hormona ParatiroideaRESUMEN
Extracellular vesicles (EVs) are mediators of a range of pathological conditions. However, their role in bone loss disease has not been well understood. In this study we characterized plasma EVs of 54 osteoporotic (OP) postmenopausal women compared to 48 osteopenic (OPN) and 44 healthy controls (CN), and we investigated their effects on osteoclasts and osteoblasts. We found no differences between the three groups in terms of anthropometric measurements and biochemical evaluation of serum calcium, phosphate, creatinine, PTH, 25-hydroxy vitamin D and bone biomarkers, except for an increase of CTX level in OP group. FACS analysis revealed that OP patients presented a significantly increased number of EVs and RANKL+ EVs compared with both CN and OPN subjects. Total EVs are negatively associated with the lumbar spine T-score and femoral neck T-score. Only in the OPN patients we observed a positive association between the total number of EVs and RANKL+ EVs with the serum RANKL. In vitro studies revealed that OP EVs supported osteoclastogenesis of healthy donor peripheral blood mononuclear cells at the same level observed following RANKL and M-CSF treatment, reduced the ability of mesenchymal stem cells to differentiate into osteoblasts, while inducing an increase of OSTERIX and RANKL expression in mature osteoblasts. The analysis of miRNome revealed that miR-1246 and miR-1224-5p were the most upregulated and downregulated in OP EVs; the modulated EV-miRNAs in OP and OPN compared to CN are related to osteoclast differentiation, interleukin-13 production and regulation of canonical WNT pathway. A proteomic comparison between OPN and CN EVs evidenced a decrease in fibrinogen, vitronectin, and clusterin and an increase in coagulation factors and apolipoprotein, which was also upregulated in OP EVs. Interestingly, an increase in RANKL+ EVs and exosomal miR-1246 was also observed in samples from patients affected by Gorham-Stout disease, suggesting that EVs could be good candidate as bone loss disease biomarkers. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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Vesículas Extracelulares , MicroARNs , Humanos , Femenino , Leucocitos Mononucleares/metabolismo , Proteómica , Vesículas Extracelulares/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Biomarcadores/metabolismoRESUMEN
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.
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Osteonecrosis de los Maxilares Asociada a Difosfonatos , Conservadores de la Densidad Ósea , Neoplasias Óseas , Osteonecrosis de los Maxilares Asociada a Difosfonatos/epidemiología , Osteonecrosis de los Maxilares Asociada a Difosfonatos/etiología , Osteonecrosis de los Maxilares Asociada a Difosfonatos/prevención & control , Conservadores de la Densidad Ósea/efectos adversos , Neoplasias Óseas/secundario , Difosfonatos/efectos adversos , Humanos , Maxilares , SíndromeRESUMEN
CONTEXT: Numerous studies have demonstrated detrimental skeletal consequences following bariatric surgery. METHODS: A working group of the European Calcified Tissue Society (ECTS) performed an updated review of existing literature on changes of bone turnover markers (BTMs), bone mineral density (BMD), and fracture risk following bariatric surgery and provided advice on management based on expert opinion. LITERATURE REVIEW: Based on observational studies, bariatric surgery is associated with a 21-44% higher risk of all fractures. Fracture risk is time-dependent and increases approximately 3 years after bariatric surgery. The bariatric procedures that have a malabsorptive component (including Roux-en-Y Gastric bypass (RYGB) and biliopancreatic diversion (BPD)) have clearly been associated with the highest risk of fracture. The extent of high-turnover bone loss suggests a severe skeletal insult. This is associated with diminished bone strength and compromised microarchitecture. RYGB was the most performed bariatric procedure worldwide until very recently, when sleeve gastrectomy (SG) became more prominent. There is growing evidence that RYGB is associated with greater reduction in BMD, greater increase in BTMs, and higher risk of fractures compared with SG but RCTs on optimal management are still lacking. EXPERT OPINION: In all patients, it is mandatory to treat vitamin D deficiency, to achieve adequate daily calcium and protein intake and to promote physical activity before and following bariatric surgery. In post-menopausal women and men older than 50 years, osteoporosis treatment would be reasonable in the presence of any of the following criteria: i) history of recent fragility fracture after 40 years of age, ii) BMD T-score ≤ -2 at hip or spine, iii) FRAX score with femoral neck BMD exceeding 20% for the 10-year major osteoporotic fracture probability or exceeding 3% for hip fracture. Zoledronate as first choice should be preferred due to intolerance of oral formulations and malabsorption. Zoledronate should be used with caution due to hypocemia risk. It is recommended to ensure adequate 25-OH vitamin D level and calcium supplementation before administering zoledronate. CONCLUSIONS: The bariatric procedures that have a malabsorptive component have been associated with the highest turnover bone loss and risk of fracture. There is a knowledge gap on osteoporosis treatment in patients undergoing bariatric surgery. More research is necessary to direct and support guidelines.
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Cirugía Bariátrica , Densidad Ósea , Remodelación Ósea , Derivación Gástrica , Obesidad Mórbida , Fracturas Osteoporóticas , Cirugía Bariátrica/efectos adversos , Femenino , Gastrectomía/efectos adversos , Derivación Gástrica/efectos adversos , Humanos , Masculino , Obesidad Mórbida/cirugía , Estudios Observacionales como Asunto , Fracturas Osteoporóticas/etiología , Ácido Zoledrónico/uso terapéuticoRESUMEN
The main function of fibroblast growth factor 23 (FGF23) is the regulation of phosphate metabolism through its action on the sodium-dependent phosphate cotransporters in the proximal renal tubules. Additionally, FGF23 interacts with vitamin D and parathyroid hormone in a complex metabolic pathway whose detailed mechanisms are still not clear in human physiology and disease. More recently, research has also focused on the understanding of mechanisms of FGF23 action on organs and system other than the kidneys and bone, as well as on its interaction with other metabolic pathways. Collectively, the new evidence are successfully used for the clinical evaluation and management of FGF23-related disorders, for which new therapies with many potential applications are now available.
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Factores de Crecimiento de Fibroblastos , Fosfatos , Humanos , Huesos/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Hormona Paratiroidea/metabolismo , Fosfatos/metabolismo , Proteínas Cotransportadoras de Sodio-Fosfato , Vitamina DRESUMEN
Osteosarcoma (OS) is a skeletal tumor affecting mainly children and adolescents. The presence of distance metastasis is frequent and it is localized preferentially to the lung, representing the main reason for death among patients. The therapeutic approaches are based on surgery and chemotherapeutics. However, the drug resistance and the side effects associated with the chemotherapy require the identification of new therapeutic approaches. The understanding of the complex biological scenario of the osteosarcoma will open the way for the identification of new targets for its treatment. Recently, a great interest of scientific community is for extracellular vesicles (EVs), that are released in the tumor microenvironment and are important regulators of tumor proliferation and the metastatic process. At the same time, circulating extracellular vesicles can be exploited as diagnostic and prognostic biomarkers, and they can be loaded with drugs as a new therapeutic approach for osteosarcoma patients. Thus, the characterization of OS-related EVs could represent a way to convert these vesicles from antagonists for human health into therapeutic and/or diagnostic agents.