Evaluation of bone mineral density, microarchitecture, and detection of fractures on young patients living with human immunodeficiency virus: when and how to screen?

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.

Chronic psychosocial stress triggers microglial-/macrophage-induced inflammatory responses leading to neuronal dysfunction and depressive-related behavior.

Chronic environmental stress and traumatic social experiences induce maladaptive behavioral changes and is a risk factor for major depressive disorder (MDD) and various anxiety-related psychiatric disorders. Clinical studies and animal models of chronic stress have reported that symptom severity is correlated with innate immune responses and upregulation of neuroinflammatory cytokine signaling in brain areas implicated in mood regulation (mPFC; medial Prefrontal Cortex). Despite increasing evidence implicating impairments of neuroplasticity and synaptic signaling deficits into the pathophysiology of stress-related mental disorders, how microglia may modulate neuronal homeostasis in response to chronic stress has not been defined. Here, using the repeated social defeat stress (RSDS) mouse model we demonstrate that microglial-induced inflammatory responses are regulating neuronal plasticity associated with psychosocial stress. Specifically, we show that chronic stress induces a rapid activation and proliferation of microglia as well as macrophage infiltration in the mPFC, and these processes are spatially related to neuronal activation. Moreover, we report a significant association of microglial inflammatory responses with susceptibility or resilience to chronic stress. In addition, we find that exposure to chronic stress exacerbates phagocytosis of synaptic elements and deficits in neuronal plasticity. Importantly, by utilizing two different CSF1R inhibitors (the brain penetrant PLX5622 and the non-penetrant PLX73086) we highlight a crucial role for microglia (and secondarily macrophages) in catalyzing the pathological manifestations linked to psychosocial stress in the mPFC and the resulting behavioral deficits usually associated with depression.

Long-term consequences of osteoporosis therapy with bisphosphonates

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.

Long-term consequences of osteoporosis therapy with bisphosphonates.

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.

Chronic hypoparathyroidism is associated with increased cortical bone density evaluated using high-resolution peripheral quantitative computed tomography.

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.

Refinement of saliva microRNA biomarkers for sports-related concussion.

BACKGROUND: Recognizing sport-related concussion (SRC) is challenging and relies heavily on subjective symptom reports. An objective, biological marker could improve recognition and understanding of SRC. There is emerging evidence that salivary micro-ribonucleic acids (miRNAs) may serve as biomarkers of concussion; however, it remains unclear whether concussion-related miRNAs are impacted by exercise. We sought to determine whether 40 miRNAs previously implicated in concussion pathophysiology were affected by participation in a variety of contact and non-contact sports. Our goal was to refine a miRNA-based tool capable of identifying athletes with SRC without the confounding effects of exercise. METHODS: This case-control study harmonized data from concussed and non-concussed athletes recruited across 10 sites. Levels of salivary miRNAs within 455 samples from 314 individuals were measured with RNA sequencing. Within-subjects testing was used to identify and exclude miRNAs that changed with either (a) a single episode of exercise (166 samples from 83 individuals) or (b) season-long participation in contact sports (212 samples from 106 individuals). The miRNAs that were not impacted by exercise were interrogated for SRC diagnostic utility using logistic regression (172 samples from 75 concussed and 97 non-concussed individuals). RESULTS: Two miRNAs (miR-532-5p and miR-182-5p) decreased (adjusted p < 0.05) after a single episode of exercise, and 1 miRNA (miR-4510) increased only after contact sports participation. Twenty-three miRNAs changed at the end of a contact sports season. Two of these miRNAs (miR-26b-3p and miR-29c-3p) were associated (R > 0.50; adjusted p < 0.05) with the number of head impacts sustained in a single football practice. Among the 15 miRNAs not confounded by exercise or season-long contact sports participation, 11 demonstrated a significant difference (adjusted p < 0.05) between concussed and non-concussed participants, and 6 displayed moderate ability (area under curve > 0.70) to identify concussion. A single ratio (miR-27a-5p/miR-30a-3p) displayed the highest accuracy (AUC = 0.810, sensitivity = 82.4%, specificity = 73.3%) for differentiating concussed and non-concussed participants. Accuracy did not differ between participants with SRC and non-SRC (z = 0.5, p = 0.60). CONCLUSION: Salivary miRNA levels may accurately identify SRC when not confounded by exercise. Refinement of this approach in a large cohort of athletes could eventually lead to a non-invasive, sideline adjunct for SRC assessment.

Definition and management of very high fracture risk in women with postmenopausal osteoporosis: a position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Association of Bone Assessment and Metabolism (ABRASSO).

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.

Definition and management of very high fracture risk in women with postmenopausal osteoporosis: a position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Association of Bone Assessment and Metabolism (ABRASSO)

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.

Effects of physical training on physical and functional fitness, physical activity level, endothelial function, hemodynamic variables, bone metabolism, and quality of life of post-bariatric patients: study protocol for a randomized controlled trial.

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.

Chronic delta-9-tetrahydrocannabinol (THC) treatment counteracts SIV-induced modulation of proinflammatory microRNA cargo in basal ganglia-derived extracellular vesicles.

BACKGROUND: Early invasion of the central nervous system (CNS) by human immunodeficiency virus (HIV) (Gray et al. in Brain Pathol 6:1-15, 1996; An et al. in Ann Neurol 40:611-6172, 1996), results in neuroinflammation, potentially through extracellular vesicles (EVs) and their micro RNAs (miRNA) cargoes (Sharma et al. in FASEB J 32:5174-5185, 2018; Hu et al. in Cell Death Dis 3:e381, 2012). Although the basal ganglia (BG) is a major target and reservoir of HIV in the CNS (Chaganti et al. in Aids 33:1843-1852, 2019; Mintzopoulos et al. in Magn Reson Med 81:2896-2904, 2019), whether BG produces EVs and the effect of HIV and/or the phytocannabinoid-delta-9-tetrahydrocannabinol (THC) on BG-EVs and HIV neuropathogenesis remain unknown. METHODS: We used the simian immunodeficiency virus (SIV) model of HIV and THC treatment in rhesus macaques (Molina et al. in AIDS Res Hum Retroviruses 27:585-592, 2011) to demonstrate for the first time that BG contains EVs (BG-EVs), and that BG-EVs cargo and function are modulated by SIV and THC. We also used primary astrocytes from the brains of wild type (WT) and CX3CR1+/GFP mice to investigate the significance of BG-EVs in CNS cells. RESULTS: Significant changes in BG-EV-associated miRNA specific to SIV infection and THC treatment were observed. BG-EVs from SIV-infected rhesus macaques (SIV EVs) contained 11 significantly downregulated miRNAs. Remarkably, intervention with THC led to significant upregulation of 37 miRNAs in BG-EVs (SIV-THC EVs). Most of these miRNAs are predicted to regulate pathways related to inflammation/immune regulation, TLR signaling, Neurotrophin TRK receptor signaling, and cell death/response. BG-EVs activated WT and CX3CR1+/GFP astrocytes and altered the expression of CD40, TNFα, MMP-2, and MMP-2 gene products in primary mouse astrocytes in an EV and CX3CR1 dependent manners. CONCLUSIONS: Our findings reveal a role for BG-EVs as a vehicle with potential to disseminate HIV- and THC-induced changes within the CNS.

Beyond Myelination: Possible Roles of the Immune Proteasome in Oligodendroglial Homeostasis and Dysfunction.

Oligodendroglia play a critical role in CNS homeostasis by myelinating neuronal axons in their mature stages. Dysfunction in this lineage occurs when early stage OPCs are not able to differentiate to replace dying Mature Myelinating Oligodendrocytes. Many hypotheses exist as to why de- and hypo-myelinating disorders and diseases occur. In this review, we present data to show that oligodendroglia can adopt components of the immune proteasome under inflammatory conditions. The works reviewed further reflect that these immune-component expressing oligodendroglia can in fact function as antigen presenting cells, phagocytosing foreign entities and presenting them via MHC II to activate CD4+ T cells. Additionally, we hypothesize, based on the limited literature, that the adoption of immune components by oligodendroglia may contribute to their stalled differentiation in the context of these disorders and diseases. The present review will underline: (1) Mechanisms of neuroinflammation in diseases associated with Immune Oligodendroglia; (2) the first associations between the immune proteasome and oligodendroglia and the subtle distinctions between these works; (3) the suggested functionality of these cells as it is described by current literature; and (4) the hypothesized consequences on metabolism. In doing so we aim to shed light on this fairly under-explored cell type in hopes that study of their functionality may lead to further mechanistic understanding of hypo- and de-myelinating neuroinflammatory disorders and diseases.

X-linked hypophosphatemic rickets: Description of seven new variants in patients followed up in reference hospitals in Rio de Janeiro.

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.

Lower bone density and microarchitecture alterations in HIV-infected Brazilian men aged 50 years and older are associated with estradiol levels.

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.

Chronic stress disrupts the homeostasis and progeny progression of oligodendroglial lineage cells, associating immune oligodendrocytes with prefrontal cortex hypomyelination.

Major depressive disorder (MDD) is a chronic debilitating illness affecting yearly 300 million people worldwide. Oligodendrocyte-lineage cells have emerged as important neuromodulators in synaptic plasticity and crucial components of MDD pathophysiology. Using the repeated social defeat (RSDS) mouse model, we demonstrate that chronic psychosocial stress induces long-lasting losses and transient proliferation of oligodendrocyte-precursor cells (OPCs), aberrant differentiation into oligodendrocytes, and severe hypomyelination in the prefrontal cortex. Exposure to chronic stress results in OPC morphological impairments, excessive oxidative stress, and oligodendroglial apoptosis, implicating integrative-stress responses in depression. Analysis of single-nucleus transcriptomic data from MDD patients revealed oligodendroglial-lineage dysregulation and the presence of immune-oligodendrocytes (Im-OL), a novel population of cells with immune properties and myelination deficits. Im-OL were also identified in mice after RSDS, where oligodendrocyte-lineage cells expressed immune-related markers. Our findings demonstrate cellular and molecular changes in the oligodendroglial lineage in response to chronic stress and associate hypomyelination with Im-OL emergence during depression.

Assessment of trabecular and cortical parameters using high-resolution peripheral quantitative computed tomography, histomorphometry and microCT of iliac crest bone core in hemodialysis patients.

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.

Use of aromatase inhibitors in patients with breast cancer is associated with deterioration of bone microarchitecture and density

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.

Use of aromatase inhibitors in patients with breast cancer is associated with deterioration of bone microarchitecture and density.

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.

Microarchitectural parameters and bone mineral density in patients with tumour-induced osteomalacia by HR-pQCT and DXA.

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.

Prevention and treatment of oral adverse effects of antiresorptive medications for osteoporosis - A position paper of the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Stomatology and Oral Pathology (Sobep), and Brazilian Association for Bone Evaluation and Osteometabolism (Abrasso).

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.