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Objectives: Our study evaluated the association of the polymorphism rs724016 in the ZBTB38 gene, previously associated with height in other populations, with predictors of height, clinical outcomes, and laboratory parameters in sickle cell anemia (SCA). Methods: Cross-sectional study with individuals with SCA and aged between 3 and 20 years. Clinical, laboratory, molecular, and bone age (BA) data were evaluated. Levels of IGF-1 and IGFBP-3 were adjusted for BA, target height (TH) was calculated as the mean parental height standard deviation score (SDS), and predicted adult height (PAH) SDS was calculated using BA. Results: We evaluated 80 individuals with SCA. The homozygous genotype of the G allele of rs724016 was associated with a lower height SDS (p < 0.001) and, in a additive genetic model, was negatively associated with HbF levels (p = 0.016). Lower adjusted IGF-1 levels were associated with co-inheritance of alpha-thalassemia and with the absence of HU therapy. Elevated HbF levels were associated with a lower deficit in adjusted growth potential (TH minus PAH). Conclusion: Our analysis shows that SNP rs724016 in the ZBTB38 is associated with shorter height and lower HbF levels, an important modifier of SCA.
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PURPOSE: People living with the human immunodeficiency virus (PLWH) developed higher life expectancy along with chronic bone disease over the past years. Our purpose is to evaluate bone mineral density, bone microarchitecture and fractures in young PLWH and understand the disease's contribution to bone derangements and fracture risk. METHODS: Eighty-one HIV-infected and 54 control young (20-50 years) male and female subjects were enrolled in this study. Methods for patient evaluation included DXA-VFA (dual energy X-rays and vertebral fracture assessment), HR-pQCT (high resolution peripheral quantitative computed tomography), biochemistry and FRAX. RESULTS: Fifty participants from each group completed all exams. Median age was 40 (25-49) vs. 36.5 (22-50) for the HIV and control groups, respectively (p 0.120). Ethnicity, body mass index, serum phosphorus, 25-hydroxyvitamin D, PTH and CTX were similar between groups, although ALP and OC suggested higher bone turnover in PLWH. VFA identified morphometric vertebral fractures in 12% of PLWH. PLWH had lower values for lumbar spine areal BMD and Z score, volumetric BMD, trabecular bone fraction (BV/TV) and trabecular number measured at the distal tibia by HR-pQCT; as a consequence, trabecular separation and heterogeneity were higher (all p < 0.05). The FRAX-estimated risk for hip and major osteoporotic fractures was statistically higher in PLWH (p < 0.001). CONCLUSION: Our results confirm severe bone impairment and fractures associated with HIV in young patients. Thus, we developed a screening protocol for young PLWH to detect bone fragility, reduce skeletal disease progression and morbimortality, decrease fracture risk, and increase quality of life.
Subject(s)
HIV Infections , Osteoporotic Fractures , Spinal Fractures , Humans , Male , Female , Adult , Bone Density , HIV , Quality of Life , Osteoporotic Fractures/diagnostic imaging , Osteoporotic Fractures/epidemiology , Osteoporotic Fractures/etiology , HIV Infections/complications , Absorptiometry, Photon , RadiusABSTRACT
ABSTRACT Bisphosphonates (BPs) are medications widely used in clinical practice to treat osteoporosis and reduce fragility fractures. Its beneficial effects on bone tissue have been consolidated in the literature for the last decades. They have a high affinity for bone hydroxyapatite crystals, and most bisphosphonates remain on the bone surface for a long period of time. Benefits of long-term use of BPs: Large and important trials (Fracture Intervention Trial Long-term Extension and Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly-Pivotal Fracture Trial) with extended use of alendronate (up to 10 years) and zoledronate (up to 6 years) evidenced significant gain of bone mineral density (BMD) and vertebral fracture risk reduction. Risks of long-term use of BPs: The extended use of antiresorptive therapy has drawn attention to two extremely rare, although severe, adverse events. That is, atypical femoral fracture and medication-related osteonecrosis of the jaw are more common in patients with high cumulative doses and longer duration of therapy. BPs have demonstrated safety and effectiveness throughout the years and evidenced increased BMD and reduced fracture risks, resulting in reduced morbimortality, and improved quality of life. These benefits overweight the risks of rare adverse events.
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Bisphosphonates (BPs) are medications widely used in clinical practice to treat osteoporosis and reduce fragility fractures. Its beneficial effects on bone tissue have been consolidated in the literature for the last decades. They have a high affinity for bone hydroxyapatite crystals, and most bisphosphonates remain on the bone surface for a long period of time. Benefits of long-term use of BPs: Large and important trials (Fracture Intervention Trial Long-term Extension and Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly-Pivotal Fracture Trial) with extended use of alendronate (up to 10 years) and zoledronate (up to 6 years) evidenced significant gain of bone mineral density (BMD) and vertebral fracture risk reduction. Risks of long-term use of BPs: The extended use of antiresorptive therapy has drawn attention to two extremely rare, although severe, adverse events. That is, atypical femoral fracture and medication-related osteonecrosis of the jaw are more common in patients with high cumulative doses and longer duration of therapy. BPs have demonstrated safety and effectiveness throughout the years and evidenced increased BMD and reduced fracture risks, resulting in reduced morbimortality, and improved quality of life. These benefits overweight the risks of rare adverse events.
Subject(s)
Bone Density Conservation Agents , Fractures, Bone , Osteoporosis, Postmenopausal , Osteoporosis , Humans , Female , Diphosphonates/adverse effects , Bone Density Conservation Agents/adverse effects , Quality of Life , Osteoporosis/drug therapy , Alendronate , Zoledronic Acid/therapeutic use , Osteoporosis, Postmenopausal/drug therapyABSTRACT
PURPOSE: This cross-sectional study aimed to assess bone mineral density (BMD), bone microarchitecture and fracture prevalence in women with chronic postsurgical hypoparathyroidism (hypoPT). METHODS: Twenty-seven women with postsurgical hypoPT and 44 age-matched healthy women were included. Dual-energy X-ray absorptiometry was used to evaluate areal BMD and vertebral fracture assessment. High-resolution peripheral quantitative computed tomography assessed microarchitecture and volumetric BMD at the distal radius and tibia. Biochemical parameters, including fibroblast growth factor 23, C-terminal cross-linking telopeptide of type I collagen (ICTP), and procollagen type I N-terminal propeptide (P1NP), were also measured. Previous low-impact fractures were assessed and the 10-year fracture risk was estimated using the FRAX tool for the Brazilian population. RESULTS: No participant had prevalent clinical fractures, and both groups showed low risk for major and hip based on FRAX tool, but two hypoPT patients had moderate to severe morphometric vertebral fractures. Women with hypoPT had increased aBMD in the lumbar spine, femoral neck and total hip (p < 0.05) and higher cortical vBMD in the radius (p = 0.020) and tibia (p < 0.001). Trabecular bone was not affected. Both P1NP and ICTP suggested low bone turnover rates, but no significant correlation was observed between bone density or microstructure and any of the biochemical parameters. CONCLUSIONS: The prevalence of fragility fractures was low in HypoPT women and compatible with low fracture risk estimated by the FRAX tool. Patients had a higher aBMD and cortical vBMD than those of healthy control women, but the association with decreased bone turnover remains unclear.
Subject(s)
Fractures, Bone , Hypoparathyroidism , Spinal Fractures , Humans , Female , Cross-Sectional Studies , Bone Density , Fractures, Bone/epidemiology , Absorptiometry, Photon , Spinal Fractures/diagnostic imaging , Spinal Fractures/epidemiology , Spinal Fractures/etiology , Tomography, X-Ray Computed/methods , Radius/diagnostic imaging , Hypoparathyroidism/diagnostic imaging , Hypoparathyroidism/epidemiology , Cortical BoneABSTRACT
Several drugs are available for the treatment of osteoporosis in postmenopausal women. Over the last decades, most patients requiring pharmacological intervention were offered antiresorptive drugs as first-line therapy, while anabolic agents were considered a last resource for those with therapeutic failure. However, recent randomized trials in patients with severe osteoporosis have shown that anabolic agents reduce fractures to a greater extent than antiresorptive medications. Additionally, evidence indicates that increases in bone mineral density (BMD) are maximized when patients are treated with anabolic agents first, followed by antiresorptive therapy. This evidence is key, considering that greater increases in BMD during osteoporosis treatment are associated with a more pronounced reduction in fracture risk. Thus, international guidelines have recently proposed an individualized approach to osteoporosis treatment based on fracture risk stratification, in which the stratification risk has been refined to include a category of patients at very high risk of fracture who should be managed with anabolic agents as first-line therapy. In this document, the Brazilian Society of Endocrinology and Metabolism and the Brazilian Association of Bone Assessment and Metabolism propose the definition of very high risk of osteoporotic fracture in postmenopausal women, for whom anabolic agents should be considered as first-line therapy. This document also reviews the factors associated with increased fracture risk, trials comparing anabolic versus antiresorptive agents, efficacy of anabolic agents in patients who are treatment naïve versus those previously treated with antiresorptive agents, and safety of anabolic agents.
Subject(s)
Anabolic Agents , Bone Density Conservation Agents , Osteoporosis, Postmenopausal , Osteoporosis , Osteoporotic Fractures , Humans , Female , Osteoporosis, Postmenopausal/complications , Osteoporosis, Postmenopausal/drug therapy , Anabolic Agents/therapeutic use , Brazil , Osteoporosis/drug therapy , Osteoporotic Fractures/etiology , Osteoporotic Fractures/prevention & control , Osteoporotic Fractures/drug therapy , Bone DensityABSTRACT
ABSTRACT Several drugs are available for the treatment of osteoporosis in postmenopausal women. Over the last decades, most patients requiring pharmacological intervention were offered antiresorptive drugs as first-line therapy, while anabolic agents were considered a last resource for those with therapeutic failure. However, recent randomized trials in patients with severe osteoporosis have shown that anabolic agents reduce fractures to a greater extent than antiresorptive medications. Additionally, evidence indicates that increases in bone mineral density (BMD) are maximized when patients are treated with anabolic agents first, followed by antiresorptive therapy. This evidence is key, considering that greater increases in BMD during osteoporosis treatment are associated with a more pronounced reduction in fracture risk. Thus, international guidelines have recently proposed an individualized approach to osteoporosis treatment based on fracture risk stratification, in which the stratification risk has been refined to include a category of patients at very high risk of fracture who should be managed with anabolic agents as first-line therapy. In this document, the Brazilian Society of Endocrinology and Metabolism and the Brazilian Association of Bone Assessment and Metabolism propose the definition of very high risk of osteoporotic fracture in postmenopausal women, for whom anabolic agents should be considered as first-line therapy. This document also reviews the factors associated with increased fracture risk, trials comparing anabolic versus antiresorptive agents, efficacy of anabolic agents in patients who are treatment naïve versus those previously treated with antiresorptive agents, and safety of anabolic agents.
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BACKGROUND: Evidence of the benefits induced from resistance exercise on health markers of post-bariatric patients is limited. The study will investigate the effects of a resistance training (RT) program on muscle mass and strength, bone metabolism biomarkers, bone mineral density (BMD), bone microarchitecture, and endothelial function of patients subjected to Roux-en-Y gastric bypass. METHODS/DESIGN: This randomized controlled trial will include 60 post-bariatric patients, physically inactive, aging 18 to 50 years, with a post-surgery period ≥ 12 months. They will be randomly assigned into two groups: (i) the non-exercised control group, which will receive the standard clinical follow-up, or (ii) the intervention group which will consist of RT (60 min/session; 3 times/week, for 6 months). The primary outcomes will include muscle mass and strength, bone metabolism biomarkers, BMD, and bone microarchitecture. The secondary outcomes will be anthropometry, hemodynamic measurements, cardiovascular risk factors, health-related quality of life (QoL), and endothelial function. Outcomes will be assessed by blood biomarkers of bone formation and reabsorption, dual X-ray absorptiometry, repetition maximum and handgrip strength tests, high-resolution peripheral quantitative computed tomography, 36-Item Short-Form Health Survey, venous occlusion plethysmography, and nailfold videocapillaroscopy. DISCUSSION: It is expected that there are greater benefits from the RT program, possibly improving muscle mass and strength, bone metabolism, density and microarchitecture, QoL, and cardiovascular risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT04193397. Registered on 7 December 2019.
Subject(s)
Gastric Bypass , Quality of Life , Biomarkers , Gastric Bypass/adverse effects , Hand Strength , Hemodynamics , Humans , Physical Fitness/physiology , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: X-linked hypophosphatemic rickets (XLHR) is a rare genetic disease, often delayed in diagnosis due to the low degree of suspicion and limited access to sophisticated diagnostic tools that confirm the diagnosis, such as genetic testing. METHODS: Through a cross-sectional and observational study, 26 patients with a previously presumptive diagnosis of X-linked hypophosphatemic rickets (based on clinical history, laboratory findings, and physical examination), were followed for approximately 12 months. During 12 months of follow-up, only 16 patients underwent genetic testing and enrolled in the study. Previous data were analyzed, such as clinical history (e.g., gender, current age, age of clinical diagnosis, age of admission to hospital, family history, and previous orthopedic surgery), physical exam, imaging tests (e.g., radiological changes) and laboratory tests (e.g., tubular maximum reabsorption rate of phosphate to glomerular filtration rate, alkaline phosphatase, and phosphate levels) at the time of the patient's admission to IEDE and UFRJ, to corroborate and substantiate our research. These data were extracted from the medical records of the patients. RESULTS: Among the 16 patients analyzed by molecular biology techniques, the new generation sequencing (NGS), using DNA samples from oral swabs, we obtained seven variants never previously described, which were verified by Sanger sequencing. Among the seven variants never previously described, the most common coding impact was the nonsense mutation. We found two frameshift, one intronic splicing variant, three nonsense, and one deletion splice junction loss. Among patients with new mutations who presented data in the medical record, 100% showed a reduction in TmP/GFR (average of 1.98 mg/dl), the most sensitive laboratory parameter at the time of diagnosis, as well as serum phosphorus (100% had hypophosphatemia on arrival at the referral hospitals--average of 2.4 mg/dl and median 2.3 mg/dl). We also performed NGS on three mothers of the patients with identified mutations. Among these mothers, only one tested negative for the mutation and no family history was reported as well. This mother had serum phosphate of 3.5 mg/dl (normal range: 2.5-4.5 mg/dl) at the time of genetic test collection. The others had a positive test, low serum phosphorus at the time of the molecular test, in addition to a positive family history. CONCLUSION: This study describes seven new variants in the PHEX gene and aims to increase the knowledge of the scientific community about the types of mutations involving this gene, increasing information on the genetic basis of this condition, enabling future considerations about genotype-phenotype correlation, in addition to diagnosis accurate and early.
Subject(s)
Familial Hypophosphatemic Rickets , Brazil , Cross-Sectional Studies , Familial Hypophosphatemic Rickets/genetics , Hospitals , Humans , PHEX Phosphate Regulating Neutral Endopeptidase/genetics , Phosphates , PhosphorusABSTRACT
OBJECTIVE: Combination antiretroviral treatment (cART) allows for longer survival for people living with HIV and hence long-term complications of both disease and treatment are common. Our purpose was to evaluate bone alterations in men living with HIV (MLWH) and receiving cART and to identify associated factors that can be corrected or mitigated. PATIENTS AND DESIGN: Thirty MLWH and 36 healthy controls (≥50 years) were studied for areal bone mineral density (aBMD) and body composition (dual-energy X-ray absorptiometry), volumetric bone mineral density (vBMD) and bone microstructure (high-resolution peripheral quantitative computed tomography [HR-pQCT]), serum calcium, phosphate, parathyroid hormone, 25(OH)D, testosterone (T), estradiol (E2 ), glucose, creatinine, and albumin levels. RESULTS: The proportion of patients classified as osteoporosis (according to the lowest aBMD T-score) was higher among MLWH as compared to controls (17.9% vs. 5.9%, p = .011). The MLWH showed significant alterations in cortical and trabecular bone on HR-pQCT, which were not associated with the duration of HIV infection or cART. These differences in vBMD and bone microstructure seen in HR-pQCT persisted in the nonosteoporotic MLWH as compared to nonosteoporotic control subjects. Body mass index (BMI) and fat mass were lower in MLWH and positively associated with total vBMD, cortical bone area, and thickness. E2 and E2 /T ratios were lower in MLWH than in controls and significantly correlated with several cortical and trabecular bone parameters. Multivariate regression analysis entering simultaneously age, BMI, and E2 defined that E2 is an independent influence on bone parameters evaluated by HR-pQCT. CONCLUSION: MLWH have alterations in bone volumetric density and microstructure when compared with controls, irrespective of aBMD, which are associated with lower E2 and BMI.
Subject(s)
Bone Diseases, Metabolic , HIV Infections , Absorptiometry, Photon/methods , Aged , Bone Density , Brazil , Estradiol , HIV Infections/drug therapy , Humans , Male , Middle Aged , RadiusABSTRACT
Patients with end-stage renal disease develop changes in bone quality and quantity, which can be assessed using different methods. This study aimed to compare and to correlate bone parameters obtained in vivo using high-resolution peripheral quantitative computed tomography (HR-pQCT) with those obtained by bone biopsy using histomorphometry and microcomputed tomography (microCT) analysis of the iliac crest core, and to evaluate if HR-pQCT is helpful in aiding with categorization of those with high turnover. Twenty hemodialysis patients, 13 females (7 postmenopausal), underwent bone biopsy from 2018 to 2020. The mean age was 48.5 ± 10.6 years, and the mean hemodialysis vintage was 15 years. Histomorphometry identified mineralization defects, low turnover, and high turnover in 65%, 45%, and 35% of the patients, respectively. The highest values of trabecular bone volume (BV/TV) were obtained by histomorphometry, while the highest values of cortical thickness (Ct.Th) were obtained by HR-pQCT at the distal tibia. Moderate correlations were found between BV/TV values obtained by microCT of the bone core and HR-pQCT at the distal radius (r = 0.531, p = 0.016) and at the distal tibia (r = 0.536, p = 0.015). BV/TV values obtained from the bone core by histomorphometry and microCT were also significantly correlated (r = 0.475, p = 0.04). Regarding Ct.Th, there was a strong correlation between the radius and tibia HR-pQCT (r = 0.800, p < 0.001), between bone core microCT and the distal radius HR-pQCT (r = 0.610, p < 0.01), as between histomorphometry and microCT (r = 0.899, p < 0.01). In groups classified by bone turnover, patients with high turnover presented lower BV/TV, Tb.N, Tb.Th, and Ct.Th than those with low turnover in peripheral sites using HR-pQCT. By this method, it was possible to identify low turnover from tibia BV/TV > 12,4% plus Tb.Sp ≤ 0.667 mm (AUC 0.810, 95% CI 0.575 to 0.948) and high turnover from total bone mineral density (BMD) ≤ 154.2 mg HA/cm3 (AUC 0.860, 95% CI 0.633 to 0.982, p < 0.001) and cortical BMD ≤ 691.6 mg HA/cm3 (AUC 0.840, 95% CI 0.609 to 0.963, p < 0.001). In conclusion, HR-pQCT had significant correlation with iliac crest bone in BV/TV and Ct.Th, which are known to provide bone strength. This method is quick and non-invasive and may be helpful in categorizing those with high versus low turnover in hemodialysis patients.
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ABSTRACT Objective: To evaluate changes in bone density and architecture in postmenopausal women with breast cancer (BC) and use of aromatase inhibitor (AI). Subjects and methods: Thirty-four postmenopausal women with BC, without bone metastasis, renal function impairment and who were not receiving bone-active drugs were selected from a population of 523 outpatients treated for BC. According to the presence of hormonal receptors, HER2 and Ki67, seventeen had positive hormonal receptors and received anastrozole (AI group), and seventeen were triple-negative receptors (non-AI group), previously treated with chemotherapy. Areal bone mineral density (aBMD) and vertebral fracture assessment (VFA) analyses were performed by DXA; vBMD and bone microarchitecture were evaluated by HR-pQCT. Fracture risk was estimated using the FRAX tool. Results: No patient referred previous low-impact fracture, and VFA detected one moderate vertebral fracture in a non-AI patient. AI patients showed lower aBMD and BMD T-scores at the hip and 33% radius and a higher proportion of osteoporosis diagnosis on DXA (47%) vs non-AI (17.6%). AI group had significantly lower values for vBMD at the entire, cortical and trabecular bone compartments, cortical and trabecular thickness and BV/TV. They also had a higher risk for major fractures and for hip fractures estimated by FRAX. Several HR-pQCT parameters evaluated at distal radius and distal tibia were significantly associated with fracture risk. Conclusion: AI is associated with alterations in bone density and microarchitecture of both the cortical and trabecular compartments. These findings explain the overall increase in fracture risk in this specific population.
Subject(s)
Humans , Female , Osteoporosis , Breast Neoplasms/drug therapy , Radius , Tibia , Absorptiometry, Photon , Bone Density , Aromatase Inhibitors/adverse effectsABSTRACT
OBJECTIVE: To evaluate changes in bone density and architecture in postmenopausal women with breast cancer (BC) and use of aromatase inhibitor (AI). METHODS: Thirty-four postmenopausal women with BC, without bone metastasis, renal function impairment and who were not receiving bone-active drugs were selected from a population of 523 outpatients treated for BC. According to the presence of hormonal receptors, HER2 and Ki67, seventeen had positive hormonal receptors and received anastrozole (AI group), and seventeen were triple-negative receptors (non-AI group), previously treated with chemotherapy. Areal bone mineral density (aBMD) and vertebral fracture assessment (VFA) analyses were performed by DXA; vBMD and bone microarchitecture were evaluated by HR-pQCT. Fracture risk was estimated using the FRAX tool. RESULTS: No patient referred previous low-impact fracture, and VFA detected one moderate vertebral fracture in a non-AI patient. AI patients showed lower aBMD and BMD T-scores at the hip and 33% radius and a higher proportion of osteoporosis diagnosis on DXA (47%) vs non-AI (17.6%). AI group had significantly lower values for vBMD at the entire, cortical and trabecular bone compartments, cortical and trabecular thickness and BV/TV. They also had a higher risk for major fractures and for hip fractures estimated by FRAX. Several HR-pQCT parameters evaluated at distal radius and distal tibia were significantly associated with fracture risk. CONCLUSION: AI is associated with alterations in bone density and microarchitecture of both the cortical and trabecular compartments. These findings explain the overall increase in fracture risk in this specific population.
Subject(s)
Breast Neoplasms , Osteoporosis , Absorptiometry, Photon , Aromatase Inhibitors/adverse effects , Bone Density , Breast Neoplasms/drug therapy , Female , Humans , Radius , TibiaABSTRACT
Antiresorptive therapy is the main form of prevention of osteoporotic or fragility fractures. Medication-related osteonecrosis of the jaw (MRONJ) is a relatively rare but severe adverse reaction to antiresorptive and antiangiogenic drugs. Physicians and dentists caring for patients taking these drugs and requiring invasive procedures face a difficult decision because of the potential risk of MRONJ. The aim of this study was to discuss the risk factors for the development of MRONJ and prevention of this complication in patients with osteoporosis taking antiresorptive drugs and requiring invasive dental treatment. For this goal, a task force with representatives from three professional associations was appointed to review the pertinent literature and discuss systemic and local risk factors, prevention of MRONJ in patients with osteoporosis, and management of established MRONJ. Although scarce evidence links the use of antiresorptive agents in the context of osteoporosis to the development of MRONJ, these agents are considered a risk factor for this complication. Despite the rare reports of MRONJ in patients with osteoporosis, the severity of symptoms and impact of MRONJ in the patients' quality of life make it imperative for health care professionals to consider this complication when planning invasive dental procedures.
Subject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw , Bone Density Conservation Agents , Oral Medicine , Osteoporosis , Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology , Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control , Bone Density Conservation Agents/adverse effects , Brazil , Diphosphonates , Humans , Osteoporosis/chemically induced , Osteoporosis/drug therapy , Osteoporosis/prevention & control , Pathology, Oral , Quality of LifeABSTRACT
INTRODUCTION: Tumour-induced osteomalacia (TIO) is a rare paraneoplastic condition characterised by decreased tubular phosphate reabsorption. The purpose of this study is to evaluate bone mineral density (BMD) and microarchitecture in six TIO patients, compared with 18 healthy controls. METHODS: Volumetric BMD and microarchitecture were evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT), and areal BMD by dual-energy X-ray absorptiometry (DXA). Differences between groups were significant for p < .05. RESULTS: All TIO subjects were healthy until the development of diffuse bone pain and multiple skeletal fractures and deformities. At baseline, sPi and TmPi/GFR were low and patients were on vitamin D and phosphate replacement at the study. Compared with controls, TIO patients had lower aBMD at lumbar spine and hip, and lower vBMD at trabecular, cortical and entire bone, at distal radius (R) and distal tibia (T): trabecular vBMD (R = 118.3 × 177.1; T = 72.3 × 161.3 gHA/cm3 ); cortical vBMD (R = 782.3 × 866.5; T = 789.1 × 900.9 gHA/cm3 ); total region vBMD (R = 234.5 × 317; T = 167.1 × 295.8 gHA/cm3 ). Bone microarchitecture was very heterogeneous among patients and significantly different from controls: lower cortical thickness (R = 0.59 × 0.80; T = 0.90 × 1.31 mm), bone volume-to-total volume ratio (R = 0.09 × 0.14; T = 0.06 × 0.13) and Tb.N (R = 1.46 × 2.10; T = 0.93 × 1.96 mm-1 ) and also higher Tb.Sp (R = 0.70 × 0.41; T = 1.28 × 0.45 mm) and Tb.1/N.SD (R = 0.42 × 0.18; T = 0.87 × 0.20 mm). CONCLUSION: In this original study of TIO patients, DXA and HR-pQCT evaluation identified lower areal and volumetric BMD and severely impaired microarchitecture at cortical and trabecular bones, which probably contribute to bone fragility and fractures.
Subject(s)
Bone Density , Radius , Absorptiometry, Photon , Humans , Osteomalacia , Paraneoplastic Syndromes , Tomography, X-Ray ComputedABSTRACT
OBJECTIVE: Alkaline phosphatase (ALP) is the main laboratory marker of hypophosphatasia (HPP), a rare disease unknown to most physicians. The prevalence of HPP has been widely discussed in the literature due to the diverse phenotypes of HPP. The purpose of this study was to search for patients with hypophosphatasemia based on previous biochemistry tests and reevaluate them to confirm the diagnosis of HPP. METHODS: A total of 289,247 biochemical tests for ALP in adults were performed from 2015 to 2019 in two tertiary hospitals in Rio de Janeiro were reviewed (Clementino Fraga Filho University Hospital - HUCFF - and Bonsucesso Federal Hospital - BFH). RESULTS: A total of 1,049 patients were identified with ALP levels below 40 U/L, and 410 patients had hypophosphatasemia confirmed by at least two exams. After the active search of medical reports and/or interviews based on structured questionnaires, 398 subjects were excluded due to secondary causes of reduced ALP. The remaining 12 patients were invited to attend the medical consultation at HUCFF, accompanied by at least one first-degree relative. None of the patients or their relatives had a history or clinical manifestations consistent with HPP. Serum ALP was within reference values in all relatives, but persistently low in further laboratory evaluation in all the 12 patients, in whom secondary causes were ruled out. Thus, we cannot exclude the possibility that they might carry the mutations associated with HPP. CONCLUSION: Further image evaluations and genetic testing would be appropriate to confirm this asymptomatic adult form of HPP.
Subject(s)
Alkaline Phosphatase , Hypophosphatasia , Adult , Alkaline Phosphatase/blood , Brazil , Humans , Hypophosphatasia/diagnosisABSTRACT
INTRODUCTION: To evaluate the efficacy and clinical safety of bariatric arterial embolization (BAE) in adults with body mass index (BMI) between 30 and 39.9 kg/m2 and metabolic syndrome (MS). MATERIALS AND METHODS: Between March and August 2018, ten female participants between 21 and 48-years-old, median BMI of 36.37 ± 2.58 kg/m2 and MS were enrolled in this prospective trial. We embolized the fundal branches from the left gastric and other artery sources, which resulted in embolization of at least two arteries in 9 out 10 participants. Six months after bariatric embolization, efficacy was assessed by changes in total body weight (TBW), ghrelin and Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) levels and by changes in quality of life (QOL) and in binge eating scale (BES) scores. Safety was assessed by the identification of any related complications, including gastric ulcers, screened by gastrointestinal endoscopy, performed before and one week and one month after BAE. RESULTS: Six months after embolization, TBW decreased by 6.8% (6.22 kg ± 3.6;p = .01), serum ghrelin dropped from 25.39 pg/ml ± 10.63 to 17.1 ± 8.07 (p = 0.01), and HOMA-IR decreased from 7.29 ± 5.66 to 3.73 ± 1.99 (p = 0.01). The QOL scores improved from 59.64 ± 5.59 to 69.02 ± 11.97 (p < 0.05) and in the BES from 21.50 ± 8.89 to 9.60 ± 4.40 (p = 0.01). Endoscopy revealed symptomatic gastric ulcers in two participants, which had healed without sequelae. In one participant, ultrasound revealed an asymptomatic focal arterial thrombus at the left distal radial artery puncture site. CONCLUSION: BAE is effective in reducing weight, insulin resistance and ghrelin levels and improving BES and QOL scores in patients with class I and II obesity and MS, with no major complications.
Subject(s)
Body Mass Index , Embolization, Therapeutic/methods , Metabolic Syndrome/therapy , Obesity/therapy , Weight Loss/physiology , Adolescent , Adult , Endoscopy, Gastrointestinal , Female , Humans , Male , Metabolic Syndrome/complications , Metabolic Syndrome/diagnosis , Middle Aged , Obesity/complications , Obesity/physiopathology , Pilot Projects , Prospective Studies , Quality of Life , Young AdultABSTRACT
Hypovitaminosis D is a common condition with a negative impact on health. This statement, prepared by experts from the Brazilian Society of Endocrinology and Metabolism and the Brazilian Society of Clinical Pathology/Laboratory Medicine, includes methodological aspects and limitations of the measurement of 25-hydroxyvitamin D [25(OH)D] for identification of vitamin D status, and identifies individuals at increased risk for deficiency of this vitamin in whom 25(OH)D measurement is recommended. For the general population, 25(OH)D levels between 20 and 60 ng/mL are considered normal, while individuals with levels below 20 ng/mL are considered to be vitamin D deficient. This statement identifies potential benefits of maintaining 25(OH)D levels > 30 ng/mL in specific conditions, including patients aged > 65 years or pregnant, those with recurrent falls, fragility fractures, osteoporosis, secondary hyperparathyroidism, chronic kidney disease, or cancer, and individuals using drugs with the potential to affect the vitamin D metabolism. This statement also calls attention to the risk of vitamin D intoxication, a life-threatening condition that occurs at 25(OH)D levels above 100 ng/mL.
Subject(s)
Pathology, Clinical , Aged , Brazil , Humans , Reference Values , Vitamin D/analogs & derivatives , Vitamin D DeficiencyABSTRACT
ABSTRACT Hypovitaminosis D is a common condition with a negative impact on health. This statement, prepared by experts from the Brazilian Society of Endocrinology and Metabolism and the Brazilian Society of Clinical Pathology/Laboratory Medicine, includes methodological aspects and limitations of the measurement of 25-hydroxyvitamin D [25(OH)D] for identification of vitamin D status, and identifies individuals at increased risk for deficiency of this vitamin in whom 25(OH)D measurement is recommended. For the general population, 25(OH)D levels between 20 and 60 ng/mL are considered normal, while individuals with levels below 20 ng/mL are considered to be vitamin D deficient. This statement identifies potential benefits of maintaining 25(OH)D levels > 30 ng/mL in specific conditions, including patients aged > 65 years or pregnant, those with recurrent falls, fragility fractures, osteoporosis, secondary hyperparathyroidism, chronic kidney disease, or cancer, and individuals using drugs with the potential to affect the vitamin D metabolism. This statement also calls attention to the risk of vitamin D intoxication, a life-threatening condition that occurs at 25(OH)D levels above 100 ng/mL