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Glucocorticoids (GC) and parathyroid hormone (PTH) are widely used therapeutic endocrine hormones where their effects on bone and joint arise from actions on multiple skeletal cell types. In osteocytes, GC and PTH exert opposing effects on perilacunar canalicular remodeling (PLR). Suppressed PLR can impair bone quality and joint homeostasis, including in GC-induced osteonecrosis. However, combined effects of GC and PTH on PLR are unknown. Given the untapped potential to target osteocytes to improve skeletal health, this study sought to test the feasibility of therapeutically mitigating PLR suppression. Focusing on subchondral bone and joint homeostasis, we hypothesize that PTH(1-34), a PLR agonist, could rescue GC-suppressed PLR. The skeletal effects of GC and PTH(1-34), alone or combined, were examined in male and female mice by micro-computed tomography, mechanical testing, histology, and gene expression analysis. For each outcome, females were more responsive to GC and PTH(1-34) than males. GC and PTH(1-34) exerted regional differences, with GC increasing trabecular bone volume but reducing cortical bone thickness, stiffness, and ultimate force. Despite PTH(1-34)'s anabolic effects on trabecular bone, it did not rescue GC's catabolic effects on cortical bone. Likewise, cartilage integrity and subchondral bone apoptosis, tartrate-resistant acid phosphatase (TRAP) activity, and osteocyte lacunocanalicular networks showed no evidence that PTH(1-34) could offset GC-dependent effects. Rather, GC and PTH(1-34) each increased cortical bone gene expression implicated in bone resorption by osteoclasts and osteocytes, including Acp5, Mmp13, Atp6v0d2, Ctsk, differences maintained when GC and PTH(1-34) were combined. Since PTH(1-34) is insufficient to rescue GC's effects on young female mouse bone, future studies are needed to determine if osteocyte PLR suppression, due to GC, aging, or other factors, can be offset by a PLR agonist.
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Densidade Óssea , Remodelação Óssea , Glucocorticoides , Osteócitos , Hormônio Paratireóideo , Animais , Osteócitos/efeitos dos fármacos , Osteócitos/metabolismo , Hormônio Paratireóideo/farmacologia , Feminino , Masculino , Camundongos , Glucocorticoides/farmacologia , Remodelação Óssea/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Microtomografia por Raio-XRESUMO
Background: Oncogenic osteomalacia is a rare paraneoplastic association of Phosphaturic mesenchymal tumor (PMT) secreting excessive levels of a PTH like substance. They usually remain undiagnosed and patients suffer for years. The rarity of this tumor and its non-specific clinical presentations poses great challenge to the treating surgeons. Its management is poorly described in literature. We report two of such rare cases without much diagnostic delay. Case report: We had 2 cases; A 53-year-old south east Asian male with 6 months of debilitating pain over multiple sites, and another 44-year-old male patient with complaints of low back ache, and pain over both lower and upper limbs for 1.5 years. Both had low serum phosphorus and elevated FGF-23 values, but all other parameters were normal. A PMT was suspected and confirmed on a Ga68- DOTATOC scan in both cases, and on complete excision, their symptoms and the altered blood parameters got normalized. Histology was consistent with PMT. Conclusion: Accurate and timely diagnosis of a PMT with non-specific features are extremely challenging, but not without solutions. Even though a tumor of rarity, with the appropriate imaging modalities like Ga68- DOTATOC scan, and estimation of FGF-23 and serum phosphorus levels, they can be diagnosed. Once identified, complete removal is often curative within a few months.
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OBJECTIVE: There is limited information on population-specific norms of trabecular-bone-score (TBS) and its associated factors. Here, we provide norms of TBS in Asian-Indians and its relationship with serum 25-hydroxyvitamin D [25(OH)D] and intact-parathyroid hormone (iPTH). PARTICIPANTS AND MEASUREMENTS: TBS, bone-mineral-density (BMD), and vertebral-fractures (VFs) were assessed using dual-energy X-ray absorptiometry in 923 healthy Asian-Indians (aged 20-60 years). Serum 25(OH)D, iPTH, T4/TSH,, glycosylated-haemoglobin (HbA1c) were measured and associations with TBS assessed using multivariable linear regression. Subjects with BMD Z-score ≤ -2.0 or ≥2.0 at any sites, VFs, TSH > 10.0 or <0.05 µIU/ml, blood-glucose >11.1 mmol/L or HbA1c > 8.0% were excluded for generating Asian-Indian norms. RESULTS: TBS norms were generated in 744 healthy Asian-Indians (M:F,389:385). The cut-offs generated for 'normal', 'partially-degraded', and 'degraded' TBS were >1.305, 1.204-1.305 and <1.204, respectively. Mean TBS was lower in females than males (p < .001). There was 75% congruency in TBS categories between Asian-Indian and existing norms. Specificity (97.8 vs. 77.9%, p < .001) and diagnostic-accuracy (97.8% vs. 78.4%, p < .001) of TBS to detect osteoporosis were higher with Asian-Indian norms. The sensitivity of 'partially-degraded' TBS to diagnose osteopenia was also higher with Asian-Indian norms. In multivariable regression, gender, body-mass-index (BMI), BMD-L1-L4, serum PTH, daily dietary-calorie intake and calcium intake were associated with TBS. Though 25(OH)D inversely correlated with PTH, 25(OH)D was not associated with TBS. CONCLUSION: This study provides norms for TBS in Asian-Indians with gender-specific differences. Increasing age and higher BMI were associated with lower TBS. Associations of TBS with circulating PTH and/or 25(OH)D need confirmation in further studies.
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Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are often complicated by high-turnover renal osteodystrophy (HTRO) and secondary hyperparathyroidism (SHPT), characterized by disturbances in mineral metabolism and skeletal abnormalities. Genetic variations within the vitamin D receptor (VDR) gene, known as VDR gene polymorphisms, have been implicated in modulating the susceptibility to HTRO and SHPT. This systematic review aims to evaluate the existing literature on the association between VDR gene polymorphisms and the development of these complications in ESRD and hemodialysis patients. A comprehensive literature search across multiple databases was conducted, and studies investigating VDR gene polymorphisms and HTRO or SHPT in ESRD or hemodialysis patients were included. The included studies examined various VDR gene polymorphisms, such as BsmI, ApaI, TaqI, and FokI, and their associations with clinical outcomes like parathyroid hormone (PTH) levels, bone mineral density, and the development of SHPT or HTRO. The findings suggest that certain VDR gene polymorphisms, notably the ApaI "aa" genotype, BsmI "bb" genotype, TaqI "tt" genotype, and FokI variant, may contribute to the pathogenesis of SHPT and HTRO by affecting PTH levels, bone turnover markers, and vitamin D sensitivity. However, the studies had relatively small sample sizes and were conducted in different populations, limiting generalizability. Further larger-scale studies, functional investigations, and exploration of gene-environment interactions are warranted to elucidate the underlying mechanisms and facilitate personalized treatment approaches for CKD and ESRD patients with mineral and bone disorders.
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Primary hyperparathyroidism (PHPT) is a common endocrine disease characterized by hypercalcemia due to inappropriately high parathyroid hormone secretion. While in the typical, symptomatic form of the disease diagnosis is set easily and standard management is surgical removal of the hyperfunctioning parathyroid (HP), this may not be the case in more subtle forms of PHPT, such as the asymptomatic and the normocalcemic PHPT. Localization of the HP could also be challenging, especially in small-sized adenomas, ectopic lesions or multiglandular disease. An experienced surgical team is essential to achieve curative parathyroidectomy. In this article, we used illustrative clinical vignettes to dissect the approach to the patient with PHPT, from the diagnosis establishment to the suggested investigation to identify classical and non-classical PHPT features and the methodology to locate the abnormal tissue. Accordingly, we elaborated on appropriate management, both surgical and conservative.
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PURPOSE: This aim of this study was to assess the possible association between diurnal oscillations and biochemical markers associated with calcium homeostasis. This included the markers parathyroid hormone (PTH), total calcium, total alkaline phosphatase, phosphate, and 25-hydroxyvitamin D (25-OH-D). By examining the influence of circadian rhythms on these parameters, the study aimed to deepen the understanding of calcium metabolism dynamics and its clinical implications. PATIENTS AND METHODS: Blood samples from 24 Caucasian male volunteers aged 20 to 40 (mean age 26) with normal pulse, blood pressure, and BMI were analyzed for biochemical markers related to calcium homeostasis. Data was obtained from the Bispebjerg study of diurnal variations. Blood samples were collected every three hours over a 24-hour period. Patients were fasting from 22:00 to 09:00. The participants spent 24 h in the hospital ward, receiving regular meals and engaging in low-intensity activities. They experienced 15 h of daylight and 9 h of complete darkness during sleep. Diurnal oscillations were analyzed using cosinor analysis with statistical significance set at p < 0.05. RESULTS: Total calcium, phosphate, and PTH exhibited significant diurnal variations. Total calcium and PTH were inversely synchronized while PTH and phosphate oscillated in synchronization. The three parameters showed relatively large amplitude/reference range ratios from 25.4% to 41.5%. CONCLUSION: This study found notable fluctuations in total calcium, phosphate, and PTH levels over a 24-hour cycle, while 25-OH-D and total alkaline phosphatase remained consistent. It highlights the importance of considering sampling times for total calcium, PTH, and phosphate in clinical settings.
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GNAS variants were recently described in 1% of patients not known to have pseudohypoparathyroidism/inactivating PTH/PTHrP signalling disorder 2 in the UK Genetics of Obesity Study. We describe a new missense GNAS variant, c.791A > C, p.(Asp264Thr), in a family with obesity, hyperphagia and mild PTH resistance. A 6-year-old female (body mass index +4.3 SD score [SDS], height +1.9 SDS) presented with hyperphagia and obesity from age 3 years. She had subtle brachydactyly, macrocephaly, and mildly delayed development. The 12-year-old brother (height +2.1 SDS, body mass index +2.9 SDS) had hyperphagia, obesity, mildly delayed development, and autism. He had subtle brachydactyly, as did the affected mother. We assessed the functional effect of the mutant, measuring cAMP production in cells transfected with wild type and mutant GNAS after ligand stimulation. Cells with the mutant GNAS showed impaired cAMP generation through melanocortin receptor 4, GH releasing hormone receptor, and PTH receptor. These cases demonstrate the clinical heterogeneity of monogenic disease, suggesting a need to test for PHP1A in children with obesity even without classical signs of PHP1A.
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Fibroblast growth factor 23 (FGF23) plays a crucial role in managing renal phosphate and the synthesis of 1,25(OH)2-vitamin D3, which is essential for bone homeostasis. Developing robust in vitro systems to study FGF23-regulating mechanisms is crucial for advancing our knowledge and identifying potential therapeutic targets. The traditional in vitro 2D culture system results in relatively low expression of FGF23, complicating further exploration of its regulatory mechanisms and potential therapeutic targets. Herein, we reported a high-throughput approach to generate preosteoblastic cell spheroids with enhanced FGF23 production. For this purpose, murine preosteoblast cell line (MC3T3-E1) was cultured in our previously reported nonadherent microwells (200 µm in diameter, 148 µm in depth, and 100 µm space in between) and self-assembled into spheroids with a diameter of 92.3 ± 15.0 µm after 24 h. Compared with monolayer culture, the MC3T3-E1 spheroids showed a significant upregulation of FGF23 in both gene and protein levels after 24 h of serum-free induction. RNA sequencing and western blotting analysis further suggested that the enhanced FGF23 production in MC3T3-E1 spheroids was attributed to the activation of the parathyroid hormone (PTH)/PTH1R signaling pathway. Impressively, inhibition of PTH signaling through small molecular inhibitors or short hairpin RNA targeting PTH1R effectively reduced FGF23 production. In summary, the current study revealed the efficacy of the high-throughput formation of preosteoblast cell spheroid in stimulating FGF23 expression for mechanistic studies. Importantly, our findings highlight the potential of the current 3D spheroid system for target identification and drug discovery.
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OBJECTIVE: Previous studies indicate a possible bidirectional stimulatory relationship between parathyroid hormone (PTH) and adrenocortical hormones, but the pattern of adrenocortical secretion in hypoparathyroidism is unknown. We aimed to characterize the adrenocortical secretion in patients with postsurgical hypoparathyroidism, and whether continuous subcutaneous PTH (1-34) infusion alters secretion patterns. DESIGN: Crossover interventional study. METHODS: We recruited ten patients with postsurgical hypoparathyroidism with very low PTH levels on stable treatment with active vitamin D and calcium. Cortisol, cortisone and aldosterone levels were measured in microdialysate from subcutaneous tissue over 24h, before and during continuous subcutaneous PTH (1-34) infusion. Cortisol was also assayed in serum, saliva and urine, and aldosterone and ACTH in serum and plasma, respectively. Ten patients with primary hyperparathyroidism and ten healthy volunteers matched for sex and age served as controls. RESULTS: Hypoparathyroid patients displayed both ultradian and circadian rhythmicity for tissue cortisol, cortisone and aldosterone. Tissue aldosterone and cortisone levels were significantly lower in hypoparathyroid patients than in healthy controls, with no difference in tissue cortisol, but a higher cortisol to cortisone ratio. Treatment with PTH (1-34) increased tissue levels of aldosterone, cortisol and cortisone and reduced the ratio of cortisol to cortisone. CONCLUSION: Adrenocortical hormone levels are reduced in postsurgical hypoparathyroidism, and partly restored by short-term continuous subcutaneous PTH (1-34) therapy.
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Polyetheretherketone (PEEK) is a high-performance polymer suitable for use in biomedical coatings. The implants based on PEEK have been extensively studied in dental and orthopedic fields. However, their inherent inert surfaces and poor osteogenic properties limit their broader clinical applications. Thus, there is a pressing need to produce a multifunctional PEEK implant to address this issue. In response, we developed sulfonated PEEK (sPEEK)-Cobalt-parathyroid hormone (PTH) materials featuring multifunctional nanostructures. This involved loading cobalt (Co) ions and PTH (1-34) protein onto the PEEK implant to tackle this challenge. The findings revealed that the controlled release of Co2+ notably enhanced the vascular formation and the expression of angiogenic-related genes, and offered antimicrobial capabilities for sPEEK-Co-PTH materials. Additionally, the sPEEK-Co-PTH group exhibited improved cell compatibility and bone regeneration capacity in terms of cell activity, alkaline phosphatase (ALP) staining, matrix mineralization and osteogenic gene expression. It surpassed solely sulfonated and other functionalized sPEEK groups, demonstrating comparable efficacy even when compared to the titanium (Ti) group. Crucially, animal experiments also corroborated the significant enhancement of osteogenesis due to the dual loading of cobalt ions and PTH (1-34). This study demonstrated the potential of bioactive Co2+ and PTH (1-34) for bone replacement, optimizing the bone integration of PEEK implants in clinical applications.
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Hyperphosphatemic Familial Tumoral Calcinosis (HFTC) is a rare disorder caused by deficient FGF23 signaling and resultant ectopic calcification. In this study, we systematically characterized and quantified macro- and micro-calcification in an HFTC cohort using computed tomography (CT) and 18F-sodium fluoride positron emission tomography/CT (18F-NaF PET/CT). Fourier-transform infrared (FTIR) spectroscopy was performed on four phenotypically different calcifications from a patient with HFTC, showing the dominant component to be hydroxyapatite. Eleven patients with HFTC were studied with CT and/or 18F-NaF PET/CT. Qualitative review was done to describe the spectrum of imaging findings on both modalities. CT-based measures of volume (e.g., total calcific burden and lesion volume) and density (Hounsfield units) were quantified and compared to PET-based measures of metabolic activity (e.g., mean standardized uptake values). Microcalcification scores (mCSs) were calculated for the vasculature of six patients using 18F-NaF PET/CT and visualized on a standardized vascular atlas. Ectopic calcifications were present in 82% of patients, predominantly near joints and the distal extremities. Considerable heterogeneity was observed in total calcific burden per patient (823.0 ± 670.1 cm3, n = 9) and lesion volume (282.5 ± 414.8 cm3, n = 27). The largest lesions were found at the hips and shoulders. 18F-NaF PET offered the ability to differentiate active vs. quiescent calcifications. Calcifications were also noted in multiple anatomic locations, including brain parenchyma (50%). Vascular calcification was seen in the distal aorta, carotid, and coronaries in 50%, 70%, 73%, and 50%, respectively. 18F-NaF-avid, but CT-negative calcification was seen in a 17-year-old patient, implicating early onset vascular calcification. This first systematic assessment of calcifications in a cohort of patients with HFTC has identified the early onset, prevalence, and extent of macro- and micro-calcification. It supports 18F-NaF PET/CT as a clinical tool for distinguishing between active and inactive calcification, informing disease progression, and quantification of ectopic and vascular disease burden.
Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare disorder in which patients develop sometimes large debilitating calcifications of soft tissues and blood vessels. It is caused by deficient fibroblast growth factor-23 that leads to high phosphate levels, which contributes to the calcifications. The calcifications and manifestations of this disorder have not been well characterized. We determined the mineral composition of the calcifications to be hydroxyapatite. Capitalizing on the fact fluoride can be integrated into hydroxyapatite, we used radiolabeled sodium fluoride positron emission tomography/computed tomography scans (18F-NaF PET/CT) to characterize and quantify the calcifications in 11 patients. 82% of the patients had calcifications, with the largest located at the hips and shoulders. Micro-calcifications were found in the blood vessels of most patients, including children. The technique also enabled us to differentiate between active versus stable calcifications. This first systematic assessment of calcifications in patients with HFTC showed the utility of 18F-NaF PET/CT as a tool to identify and quantify calcifications, as well as distinguish between active and stable calcifications. This approach will inform disease progression and may prove useful for measuring response to treatment.
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X-linked hypophosphatemia (XLH) is a genetic disease that results in excessive FGF23, chronic hypophosphatemia, and musculoskeletal abnormalities, with affected patients experiencing symptoms such as bone pain, bone deformity, fracture, and pseudofracture. Burosumab is a fully human monoclonal antibody that binds to FGF23, improving lowered serum 1,25(OH)2D and phosphate levels in patients with XLH. There are insufficient data on the use of burosumab, its safety, and the outcomes of treated patients in a real-world setting. The SUNFLOWER (Study of longitUdinal observatioN For patients with X-Linked hypOphosphatemic rickets/osteomalacia in collaboration With Asian partnERs) study is an ongoing longitudinal, observational cohort study of patients with XLH in Japan and South Korea. Enrollment occurred between April 2018 and December 2020. This interim analysis compared the background characteristics of patients who received burosumab with those who did not, and assessed improvements in biomarkers, physical and motor function, health-related quality-of-life (HRQOL) and other patient-reported outcome (PRO) measures, as well as the safety of burosumab treatment in 143 Japanese patients from 15 institutions over 6 mo. The patients had a median [interquartile range] age of 17.5 [11.0, 38.8] yr and 98 (68.5%) were female. Among patients aged <18 and ≥18 yr, 40/73 (54.8%) and 25/70 (35.7%) received burosumab, respectively. More patients aged ≥18 who received burosumab had bone pain at baseline vs those not treated with burosumab (6/25, 24.0% vs 2/45, 4.4%, p=.021). Patients treated with burosumab had improved serum phosphate and 1,25(OH)2D levels; moreover, rickets severity and HRQOL/PRO measures, such as pain, appeared to improve over 6 mo of burosumab treatment, and no new safety concerns were identified. This study identified trends in the background characteristics of patients with XLH who receive burosumab in real-world clinical practice. Furthermore, the results support the use of burosumab therapy in real-world settings.
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This review delves into relatively less discussed role of alkaline phosphatase (ALP) as an accessible alternative to intact parathyroid hormone (iPTH) in the context of bone health assessment, particularly focussing on its potential boon for underprivileged individuals with chronic kidney disease (CKD) in South Asia. The financial constraints faced by this demographic often hinder regular monitoring of iPTH levels. ALP emerges as a promising surrogate, offering a cost-effective and practical solution for bone health evaluation in resource-constrained settings.
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Fosfatase Alcalina , Hormônio Paratireóideo , Humanos , Fosfatase Alcalina/sangue , Hormônio Paratireóideo/sangue , Insuficiência Renal Crônica/sangue , Biomarcadores/sangue , Densidade ÓsseaRESUMO
Although clinical guidelines recommend measuring total plasma 25-hydroxyvitamin D (25[OH]D) to assess vitamin D (VitD) status, this index does not account for 3-fold inter-individual variation in VitD binding protein (VDBP) level. We present 3 individuals with total plasma 25(OH)D levels of 10.8 to 12.3â ng/mL (27-30.7â nmol/L). Because Endocrine Society guidelines define VitD deficiency as 25(OH)D ≤ 20â ng/mL (50â nmol/L), all 3 would be judged to be VitD deficient. VitD3 supplementation increased 25(OH)D to the range of 31.7 to 33.8â ng/mL (79.1-84.4â nmol/L). Patient #1 exhibited secondary hyperparathyroidism; VitD3 supplementation decreased parathyroid hormone (PTH) by 34% without a clinically significant change in PTH levels in the other 2 individuals. Thus, 25(OH)D level did not distinguish between the 1 patient who had secondary hyperparathyroidism and the 2 who did not. We therefore inquired whether VitD metabolite ratios (which are VDBP-independent) might distinguish among these 3 individuals. Of all the assessed ratios, the 1,25(OH)2D/24,25(OH)2D ratio was the most informative, which had a value of 102 pg/ng in the individual with secondary hyperparathyroidism but lower values (41 and 20 pg/ng) in the other 2 individuals. These cases illustrate the value of the 1,25(OH)2D/24,25(OH)2D ratio to provide clinically relevant information about VitD status.
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Brown tumors, an exceptional bone complication of severe primary (PHP) or renal (secondary) hyperparathyroidism (RHP), are caused by long-standing, elevated parathormone (PTH)-induced osteoclast activation causing multinucleated giant cell conglomerates with hemosiderin deposits in addition to the local production of cytokines and growth factors. We aim to present an adult case series including two females displaying this complication as part of a multidisciplinary complex panel in high PTH-related ailments. The approach was different since they had distinct medical backgrounds and posed a wide area of challenges amid real-life settings, namely, a 38-year-old lady with PHP and long-term uncontrolled hypercalcemia (with a history of pregnancy-associated PHP, the removal of a cystic jaw tumor, as well as a family and personal positive diagnosis of polycystic kidney disease, probably a PHP-jaw tumor syndrome), as well as, a 26-year-old woman with congenital single kidney and chronic renal disease-associated RHP who was poorly controlled under dialysis and developed severe anemia and episodes of metabolic acidosis (including one presentation that required emergency hemodialysis and was complicated with convulsive seizures, followed by resuscitated respiratory arrest). Both subjects displayed a severe picture of PHP/RHP with PTH levels of >1000 pg/mL and >2000 pg/mL and elevated serum bone turnover markers. Additionally, they had multiple brown tumors at the level of the ribs and pelvis (asymptomatically) and the spine, skull, and pelvis (complicated with a spontaneous cervical fracture). As an endocrine approach, the control of the underlying parathyroid disease was provided via surgery in PHP (for the postparathyroidectomy hungry bone syndrome) via medical intervention (with vitamin D analogs) in RHP. Additionally, in this case, since the diagnosis was not clear, a multidisciplinary decision to perform a biopsy was taken (which proved inconclusive), and the resection of the skull tumor to confirm the histological traits. This series highlights the importance of addressing the entire multidisciplinary panel of co-morbidities for a better outcome in patients with PHP/RHP-related brown tumors. However, in the instance of real-life medicine, poor compliance and reduced adherence to recommendations might impair the overall health status. Thus, sometimes, a direct approach at the level of cystic lesion is taken into consideration; this stands for a narrow frame of decision, and it is a matter of personalized decision. As seen here, brown tumors represent the hidden face of PHP/RHP, primarily the complex and severe forms, and awareness is essential even in the modern era.
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An 18-month-old male presented with gross motor delay and poor growth (weight z-score -2.21, length z-score -4.26). Radiographs showed metaphyseal irregularities suggesting metaphyseal dysplasia and sagittal craniosynostosis. Biochemical evaluation supported hypophosphatemic rickets [serum phosphorus 2.3 mg/dL (reference range (RR) 4.3-6.8), alkaline phosphatase 754 unit/L (RR 156-369)] due to renal phosphate wasting (TmP/GFR 4.3 mg/dL, normal for age 4.3-6.8), with C-terminal fibroblast growth factor 23 (FGF23) 125 RU/mL (>90 during hypophosphatemia suggests FGF23-mediated hypophosphatemia). Treatment was initiated with calcitriol and phosphate. Genetic analysis showed a pathogenic variant of FGF23: c.527G > A (p.Arg176Gln) indicative of autosomal dominant hypophosphatemic rickets (ADHR). Consistent with reports linking iron deficiency with the ADHR phenotype, low ferritin was detected. Following normalization of ferritin level (41 ng/mL) with oral ferrous sulfate replacement, biochemical improvement was demonstrated (FGF23 69 RU/mL, phosphorus 5.0 mg/dL and alkaline phosphatase 228 unit/L). Calcitriol and phosphate were discontinued. Three years later, the patient demonstrated improved developmental milestones, linear growth (length Z-score -2.01), radiographic normalization of metaphyses, and stabilization of craniosynostosis. While the most common cause of hypophosphatemic rickets is X-linked hypophosphatemia, other etiologies should be considered as treatment differs. In ADHR, normalization of iron leads to biochemical and clinical improvement.
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Fator de Crescimento de Fibroblastos 23 , Humanos , Masculino , Lactente , Fatores de Crescimento de Fibroblastos/sangue , Fatores de Crescimento de Fibroblastos/genética , Raquitismo Hipofosfatêmico/genética , Estatura , Raquitismo Hipofosfatêmico Familiar/genética , Raquitismo Hipofosfatêmico Familiar/tratamento farmacológico , Raquitismo Hipofosfatêmico Familiar/diagnóstico por imagemRESUMO
Cadmium (Cd) is recognized as a significant hazard to human health, with exposure linked to a variety of adverse outcomes including various cancers, cardiovascular diseases, chronic kidney disease, and osteoporosis. Residing in areas contaminated with Cd is undoubtedly a risk factor for developing the aforementioned conditions. However, the risk of developing Cd-related disorders is not uniform among individuals. Deficiencies in iron, zinc, and calcium, along with iron deficiency anemia, decreased lung function often seen in chronic obstructive pulmonary disease (COPD), and low circulating levels of parathyroid hormone (PTH), may enhance Cd intestinal absorption. Conversely, chronic liver disorders can lead to the progressive loss of hepatocytes and the release of free Cd into the circulation, resulting in elevated Cd blood levels. Moreover, studies comparing Cd blood levels between different regions within a country or between two groups of individuals, for example, those with and without osteoporosis, should consider all variables that may impact Cd levels. These include age, sex, alcohol consumption, blood levels of iron, calcium, and zinc, the presence of anemia, COPD, PTH levels, and the presence of liver or kidney disease. In this review, we delve into all factors that could influence Cd blood levels, providing a comprehensive analysis.
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Cádmio , Humanos , Cádmio/sangue , Disponibilidade BiológicaRESUMO
Background/Objectives: The general condition of implantology patients is crucial when considering the long- and short-term survival of dental implants. The aim of the research was to evaluate the correlation between the new corticalization index (CI) and patients' condition, and its impact on marginal bone loss (MBL) leading to implant failure, using only radiographic (RTG) images on a pixel level. Method: Bone near the dental implant neck was examined, and texture features were analyzed. Statistical analysis includes analysis of simple regression where the correlation coefficient (CC) and R2 were calculated. Detected relationships were assumed to be statistically significant when p < 0.05. Statgraphics Centurion version 18.1.12 (Stat Point Technologies, Warrenton, VA, USA) was used to conduct the statistical analyses. Results: The research revealed a correlation between MBL after 3 months and BMI, PTH, TSH, Ca2+ level in blood serum, phosphates in blood serum, and vitamin D. A correlation was also observed between CI and PTH, Ca2+ level in blood serum, vitamin D, LDL, HDL, and triglycerides on the day of surgery. After 3 months of the observation period, CI was correlated with PTH, TSH, Ca2+ level in blood serum, and triglycerides. Conclusion: The results of the research confirm that the general condition of patients corresponds with CI and MBL. A patient's general condition has an impact on bone metabolism around dental implants. Implant insertion should be considered if the general condition of the patient is not stable. However, CI has not yet been fully investigated. Further studies are necessary to check and categorize the impact of corticalization on marginal bone loss near dental implants.
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Surgeons request intraoperative parathyroid hormone (PTH) monitoring during parathyroidectomy procedures to confirm identification of abnormal gland tissue. Generally, a 50% decrease in the baseline PTH level indicates the abnormal tissue has been removed. A delay in collecting and processing PTH blood samples can complicate intraoperative decision making and prolong the procedure. The purpose of this quality improvement project was to develop tools to facilitate the specimen management process (eg, requesting, transporting, analyzing) for PTH blood samples and decrease the average total time required for transit and assay. We implemented a two-pronged initiative that involved improving the laboratory requisition form and creating a parathyroid tote box to contain all the needed information and supplies. The average total time for transit and assay decreased from 31.36 minutes before implementation to 22.06 minutes after implementation. Perioperative nurses expressed satisfaction with the changes and continue to use the revised process.
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Hormônio Paratireóideo , Humanos , Hormônio Paratireóideo/sangue , Paratireoidectomia/métodos , Paratireoidectomia/normas , Manejo de Espécimes/métodos , Manejo de Espécimes/normas , Melhoria de QualidadeRESUMO
BACKGROUND: Low serum parathyroid hormone (PTH) is an accepted marker for adynamic bone disease which is characterized by increased morbidity and mortality in maintenance hemodialysis (MHD) patients. In light of the known cross-sectional associations between PTH and malnutrition-inflammation syndrome, we aimed to examine the longitudinal associations between PTH with changes in nutritional and inflammatory parameters and clinical outcomes in MHD patients with low PTH. METHODS: This historical prospective and longitudinal study analyzed a clinical database at a single hemodialysis center, containing the medical records of 459 MHD patients (mean age of 71.4 ± 12.9 years old, 171 women), treated between the years 2007-2020. Bone turnover, nutritional and inflammatory marker levels were recorded at 0, 6, 12, 18, 24, 30, and 36 months followed by a median of 24 additional months of clinical observations. According to previous use of vitamin D analogs and/or calcium-sensing receptor agonists, the study participants were divided into treatment-related and disease-related groups. A linear mixed effects model was adjusted for baseline demographics and clinical parameters. RESULTS: Of 459 MHD patients, 81 (17.6%) had PTH lower than 150pg/mL. Among them, 30 patients had treatment-related and 51 had disease-related low PTH. At baseline, MHD patients with treatment-related low PTH had a higher rate of diabetes compared to the disease-related group. In a linear mixed effects model, increased PTH over time was associated with decreased levels of alkaline phosphatase and C-reactive protein and with increased hemoglobin and albumin, but not the geriatric nutritional risk index at 3-year follow-up. The survival rate did not differ between the groups, with the risk of hospitalizations due to fractures being higher (HR: 4.04 with 95% CI: 1.51-10.8) in the disease-related group. Statistical significance of this association was abolished after adding C-reactive protein or alkaline phosphatase to the multivariate models. CONCLUSIONS: Low serum PTH in MHD patients behaves differently depending on its cause, with a higher risk of fractures in the disease-related group. This association is dependent on inflammation. Our results should be verified in larger epidemiological studies.