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 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.

Official Position of the Brazilian Association of Bone Assessment and Metabolism (ABRASSO) on the evaluation of body composition by densitometry-part II (clinical aspects): interpretation, reporting, and special situations.

OBJECTIVE: To present an updated and evidence-based guideline for the use of dual-energy x-ray absorptiometry (DXA) to assess body composition in clinical practice. MATERIALS AND METHODS: This Official Position was developed by the Scientific Committee of the Brazilian Association of Bone Assessment and Metabolism (Associação Brasileira de Avaliação Óssea e Osteometabolismo, ABRASSO) and experts in the field who were invited to contribute to the preparation of this document. The authors searched current databases for relevant publications in the area of body composition assessment. In this second part of the Official Position, the authors discuss the interpretation and reporting of body composition parameters assessed by DXA and the use of DXA for body composition evaluation in special situations, including evaluation of children, persons with HIV, and animals. CONCLUSION: This document offers recommendations for the use of DXA in body composition evaluation, including indications, interpretation, and applications, to serve as a guiding tool in clinical practice and research for health care professionals in Brazil.

Official position of the Brazilian Association of Bone Assessment and Metabolism (ABRASSO) on the evaluation of body composition by densitometry: part I (technical aspects)-general concepts, indications, acquisition, and analysis.

OBJECTIVE: To review the technical aspects of body composition assessment by dual-energy X-ray absorptiometry (DXA) and other methods based on the most recent scientific evidence. MATERIALS AND METHODS: This Official Position is a result of efforts by the Scientific Committee of the Brazilian Association of Bone Assessment and Metabolism (Associação Brasileira de Avaliação Óssea e Osteometabolismo, ABRASSO) and health care professionals with expertise in body composition assessment who were invited to contribute to the preparation of this document. The authors searched current databases for relevant publications. In this first part of the Official Position, the authors discuss the different methods and parameters used for body composition assessment, general principles of DXA, and aspects of the acquisition and analysis of DXA scans. CONCLUSION: Considering aspects of accuracy, precision, cost, duration, and ability to evaluate all three compartments, DXA is considered the gold-standard method for body composition assessment, particularly for the evaluation of fat mass. In order to ensure reliable, adequate, and reproducible DXA reports, great attention is required regarding quality control procedures, preparation, removal of external artifacts, imaging acquisition, and data analysis and interpretation.

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.

Bone Evaluation by High-Resolution Peripheral Quantitative Computed Tomography in Patients With Adrenal Incidentaloma.

CONTEXT: Data regarding high-resolution peripheral quantitative computed tomography (HR-pQCT) in patients with adrenal incidentaloma (AI) are unknown. PURPOSE: To evaluate the areal bone mineral density (aBMD), microstructure, and fractures in patients with nonfunctioning AI (NFAI) and autonomous cortisol secretion (ACS). METHODS: We evaluated 45 patients with NFAI (1 mg dexamethasone suppression test [DST] ≤1.8 µg/dL) and 30 patients with ACS (1 mg DST 1.9-5.0 µg/dL). aBMD was measured using dual-energy X-ray absorptiometry; vertebral fracture by spine X-ray; and bone geometry, volumetric bone mineral density (vBMD), and microstructure by HR-pQCT. RESULTS: Patients with ACS showed lower aBMD values at the spine, femoral neck, and radius 33% than those with NFAI. Osteoporosis was frequent in both groups: NFAI (64.9%) and ACS (75%). Parameters at the distal radius by HR-pQCT were decreased in patients with ACS compared to those with NFAI: trabecular vBMD (Tb.vBMD, P = 0.03), inner zone of the trabecular region (Inn.Tb.vBMD, P = 0.01), the bone volume/tissue volume ratio (BV/TV, P = 0.03) and trabecular thickness (P = 0.04). As consequence, a higher ratio of the outer zone of the trabecular region/inner zone vBMD (Meta/Inn.vBMD, P = 0.003) was observed. A correlation between the cortisol levels after 1 mg DST and Meta/Inn.vBMD ratio was found (r = 0.29; P = 0.01). The fracture frequency was 73.7% in patients with ACS vs 55.6% in patients with NFAI (P = 0.24). CONCLUSION: Our findings point to an association between trabecular bone microarchitectural derangement at the distal radius and ACS. Our data suggest that AI have a negative impact on bone when assessed by HR-pQCT, probably associated to subclinical hypercortisolism.

Impact of Weight Loss With Intragastric Balloon on Bone Density and Microstructure in Obese Adults.

The historical concept that obesity protects against bone fractures has been questioned. Weight loss appears to reduce bone mineral density (BMD); however, the results in young adults are inconsistent, and data on the effects of weight loss on bone microstructure are limited. This study aimed to evaluate the impact of weight loss using an intragastric balloon (IGB) on bone density and microstructure. Forty obese patients with metabolic syndrome (mean age 35.1 ± 7.3 yr) used an IGB continuously for 6 mo. Laboratory tests, areal BMD, and body composition measurements via dual-energy X-ray absorptiometry, and volumetric BMD and bone microstructure measurements via high-resolution peripheral quantitative computed tomography were conducted before IGB placement and after IGB removal. The mean weight loss was 11.5%. After 6 mo, there were significant increases in vitamin D and carboxyterminal telopeptide of type 1 collagen levels. After IGB use, areal BMD increased in the spine but decreased in the total femur and the 33% radius. Cortical BMD increased in the distal radius but tended to decrease in the distal tibia. The observed trabecular bone loss in the distal tibia contributed to the decline in the total volumetric BMD at this site. There was a negative correlation between the changes in leptin levels and the measures of trabecular quality in the tibia on high-resolutionperipheral quantitative computed tomography. Weight loss may negatively impact bone microstructure in young patients, especially for weight-bearing bones, in which obesity has a more prominent effect.

Impact of 6 months of treatment with intragastric balloon on body fat and quality of life in obese individuals with metabolic syndrome.

BACKGROUND: Obesity is a worldwide public health issue with a negative impact on quality of life. Different weight loss interventions have demonstrated improvements in quality of life. The aim of this study was to investigate the effect of 6 months of treatment with an intragastric balloon (IGB) on health-related quality of life (HRQOL) and its relation to changes in body fat in obese individuals with metabolic syndrome (MS). METHODS: Fifty obese patients with MS aged 18-50 were selected for treatment with IGB for 6 months. Body fat was assessed with anthropometric measures and dual-energy X-ray absorptiometry (DXA) at baseline and after removal of the IGB. HRQOL was evaluated with the short form of the World Health Organization Quality of Life (WHOQOL-BREF) at baseline and soon after removal of the IGB. RESULTS: Thirty-nine patients completed the study. After 6 months, there was a significant improvement in quality of life (p = 0.0009) and health (p < 0.0001) perceptions, and in the Physical (p = 0.001), Psychological (p = 0.031), and Environmental domains (p = 0.0071). Anthropometric measures and total fat determined by DXA were directly and significantly related to an improvement in general aspects of quality of life. The decrease in the percentage of total fat was the parameter that better correlated with improvements in quality of life perception after regression (p = 0.032). CONCLUSIONS: In obese individuals with MS, weight loss parameters were associated with short-term improvements in HRQOL after 6 months of treatment with IGB. However, only total fat was independently related to HRQOL perception. TRIAL REGISTRATION: ClinicalTrials.gov NCT01598233 .

Bone Density Is Directly Associated With Glomerular Filtration and Metabolic Acidosis but Do Not Predict Fragility Fractures in Men With Moderate Chronic Kidney Disease.

Hyperparathyroidism, vitamin D deficiency, increased fibroblast growth factor-23 (FGF-23), and metabolic acidosis promote bone fragility in chronic kidney disease (CKD). Although useful in predicting fracture risk in the general population, the role of dual-energy X-ray absorptiometry (DXA) in CKD remains uncertain. This cross-sectional study included 51 men aged 50-75 yr with moderate CKD. The stage 4 CKD patients had higher levels of parathyroid hormone (p<0.001), FGF-23 (p=0.029), and lowest 25-hydroxyvitamin D (p=0.016), bicarbonate (p<0.001), total femur (p=0.003), and femoral neck (p=0.011) T-scores compared with stage 3 CKD patients. Total femur and femoral neck T-scores were directly correlated with serum bicarbonate (p=0.003, r=0.447 and p=0.005, r=0.427, respectively) and estimated glomerular filtration rate (p=0.024, r=0.325 and p=0.003, r=0.313, respectively) but were not significantly associated with parathyroid hormone, 25-hydroxyvitamin D, or FGF-23. Only 3.9% of the participants had osteoporosis on DXA scan, whereas 31.4% reported a low-impact fracture. Our data point to a pivotal role of metabolic acidosis for bone impairment and to the inadequacy of DXA to evaluate bone fragility in CKD patients.

Bone density and microarchitecture in endogenous hypercortisolism.

OBJECTIVE: Osteoporosis is a serious and underestimated complication of endogenous hypercortisolism that results in an increased risk of fractures, even in patients with normal or slightly decreased bone mineral density (BMD). Alterations in bone microarchitecture, a very important component of bone quality, may explain bone fragility. The aim of this study was to investigate bone density and microarchitecture in a cohort of patients with endogenous Cushing's syndrome (CS). DESIGN: Cross-sectional study. PATIENTS: Thirty patients with endogenous active CS and fifty-one age-, sex- and body mass index-matched controls were included. MEASUREMENTS: Participants were studied for areal BMD (dual-energy X-ray absorptiometry) of the lumbar spine (LS), femoral neck (FN), total femur (TF) and radius (33%), and for volumetric bone density (vBMD) and structure using high-resolution peripheral quantitative computed tomography (HR-pQCT) of the distal radius and distal tibia. RESULTS: Patients with active CS exhibited lower areal BMD and Z-score values in the LS, FN and TF (P < 0·003 for all comparisons). At HR-pQCT, the patients with CS also had lower cortical area (P = 0·009 at the radius and P = 0·002 at the tibia), lower cortical thickness (P = 0·02 at the radius and P = 0·002 at the tibia), lower cortical density (P = 0·008 at the tibia) and lower total vBMD (P = 0·002 at the tibia). After the exclusion of hypogonadal individuals, the patients with CS maintained the same microarchitectural and densitometric alterations described above. CONCLUSIONS: Endogenous hypercortisolism has deleterious effects on bone, especially on cortical bone microstructure. These effects seem to be a more important determinant of bone impairment than gonadal status.

Bone mineral density in children and adolescents with congenital adrenal hyperplasia.

Chronic glucocorticoid therapy is associated with reduced bone mineral density. In paediatric patients with congenital adrenal hyperplasia, increased levels of androgens could not only counteract this effect, but could also advance bone age, with interference in the evaluation of densitometry. We evaluate bone mineral density in paediatric patients with classic congenital adrenal hyperplasia taking into account chronological and bone ages at the time of the measurement. Patients aged between 5 and 19 years underwent radiography of the hand and wrist followed by total body and lumbar spine densitometry. Chronological and bone ages were used in the scans interpretation. In fourteen patients, mean bone mineral density Z-score of total body to bone age was -0.76 and of lumbar spine to bone age was -0.26, lower than those related to chronological age (+0.03 and +0.62, resp.). Mean Z-score differences were statistically significant (P = 0.004 for total body and P = 0.003 for lumbar spine). One patient was classified as having low bone mineral density only when assessed by bone age. We conclude that there was a reduction in the bone mineral density Z-score in classic congenital adrenal hyperplasia paediatric patients when bone age was taken into account instead of chronological age.

Six-month intragastric balloon treatment for obesity improves lung function, body composition, and metabolic syndrome.

BACKGROUND: The purpose of this study is to establish whether the use of an intragastric balloon (IGB) for 6 months improves lung function, metabolic parameters, and body fat distribution in patients with overweight/obesity and metabolic syndrome (MS). METHODS: This is a longitudinal and interventional study on 40 adults, whose anthropometric, laboratory, and lung function parameters were assessed and who underwent dual-energy X-ray absorptiometry (DXA) before implantation and after removal of IGB. RESULTS: The total lung capacity (TLC) (p = 0.0001), functional residual capacity (FRC) (p = 0.0001), residual volume (p = 0.0005), and expiratory reserve volume (ERV) (p = 0.0001) were significantly reduced by IGB. The body mass index (BMI) significantly decreased from a median of 39.1 kg/m(2) at the beginning of the study to 34.5 kg/m(2) at the end of the 6-month period (p = 0.0001). At the end of the study, 31 participants (77.5%) no longer met the diagnostic criteria of MS. The percentage of truncal, android, gynoid, and total fat investigated by DXA exhibited significant reductions (p = 0.0001). Significant correlations were found between delta TLC and delta waist circumference (ρ = -0.34; p = 0.03), delta FRC and delta IMC (ρ = -0.39; p = 0.01), delta ERV and delta BMI (ρ = -0.44; p = 0.005), and delta ERV and delta high-density lipoprotein (HDL) (ρ = -0.37; p = 0.02). Significant correlations were also found between delta ERV and delta truncal (ρ = -0.51; p = 0.004), android (ρ = -0.46; p = 0.01), gynoid (ρ = -0.55; p = 0.001), and total fat (ρ = -0.59; p = 0.0005). CONCLUSIONS: IGB efficiently induced weight loss and promoted the improvement of lung function parameters, with a reduction of the restrictive ventilatory defect. It also promoted improvements of MS and the pattern of body fat distribution.

Lean mass as a predictor of bone density and microarchitecture in adult obese individuals with metabolic syndrome.

The effects of obesity and metabolic syndrome (MS) on bone health are controversial. Furthermore, the relationship between body composition and bone quality has not yet been determined in this context. The aim of this study was to investigate the correlations between body composition and bone mineral density (BMD) and bone microstructure in obese individuals with MS. This cross-sectional study assessed 50 obese individuals with MS with respect to their body composition and BMD, both assessed using dual X-ray absorptiometry, and bone microarchitecture, assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) of the distal tibia and radius. Several HR-pQCT measurements exhibited statistically significant correlations with lean mass. Lean mass was positively correlated with parameters of better bone quality (r: 0.316-0.470) and negatively correlated with parameters of greater bone fragility (r: -0.460 to -0.310). Positive correlations were also observed between lean mass and BMD of the total femur and radius 33%. Fat mass was not significantly correlated with BMD or any HR-pQCT measurements. Our data suggest that lean mass might be a predictor of bone health in obese individuals with MS.

The prevalence of disordered eating and possible health consequences in adolescent female tennis players from Rio de Janeiro, Brazil.

The aim of this study was to estimate the prevalence of disordered eating and possible health consequences in adolescent female tennis players. This cross-sectional controlled study investigated the pubertal development (Tanner stages); body composition (dual energy X-ray absorptiometry-DXA); dietary intake (food record); presence of disordered eating (EAT-26, BITE and BSQ); menstrual status (questionnaire) and bone mineral density (DXA). The Female Athlete Triad (FAT) was divided into two severity stages. The study included 45 adolescents (24 athletes and 21 controls) at some pubertal developmental stage. The athletes exhibited better body composition profiles. We found that 91.7%, 33.3% and 25% of athletes and 71.4%, 9.5% and 33.3% of controls met criteria for disordered eating and/or low energy availability, menstrual irregularities and low bone mass, respectively. A greater percentage of athletes than controls presented with 1 and 2 FAT components (stage I), and 4.2% presented with the full syndrome. In conclusion, tennis players appear to present with more severe disorders than controls and should be monitored to avoid damage to their performance and health.

Vertebral fracture assessment in acromegaly.

Most vertebral fractures (VFs) are asymptomatic and incidentally found on X-rays. The effects of acromegaly on bone mineral density (BMD) are still controversial, and the prevalence of VFs in this specific population remains uncertain. The objective of this study was to assess VFs in acromegaly through vertebral fracture assessment (VFA) by dual-energy X-ray absorptiometry (DXA). Seventy-five acromegalic patients from the same center (53 female; age: 48.9±14.5yr) were enrolled in this study. None of them referred previous fragility fracture. They were divided according to the presence or absence of moderate or severe VFs on VFA, a densitometric spine imaging. Age, gender, estimated duration of disease, insulin-like growth factor I levels, disease control and gonadal status, as well as BMD and body composition (analyzed by DXA) were compared between these 2 groups. A prevalence of 10.6% of clinically unapparent VFs was observed. Eight patients had 13 moderate or severe VFs, and only one of them had osteoporosis at densitometry. There was a trend to longer duration of acromegaly before diagnosis, higher prevalence of hypogonadism, and higher BMD Z-score at lumbar spine and femoral neck in fractured patients, without reaching statistical significance. There is a significant prevalence of moderate and severe VFs in acromegalic patients, independently of BMD. More longitudinal and controlled studies are needed to recommend the use of VFA in all acromegalic patients submitted to DXA scan. VFA is simple, practical, uses low radiation, and may provide important information in the management of acromegaly.

Intragastric balloon for the treatment of obesity: evaluation of pulmonary function over a 3-month period.

BACKGROUND: Obesity has become a global epidemic in the 21st century, and the placement of an intragastric balloon (IB) is a therapeutic modality used to treat it. Our objectives for this study were to evaluate changes in lung function resulting from IB use and to correlate the pattern of body fat distribution with changes in lung function. METHODS: This was an interventional study with 30 overweight and obese patients with metabolic syndrome. All of the subjects underwent anthropometric measurements, assessment of their body fat distribution pattern by dual-energy X-ray absorptiometry, and pulmonary function testing before implantation of the IB. RESULTS: During the initial evaluations, the main pulmonary function abnormalities observed were decreased expiratory reserve volume (ERV), decreased total lung capacity (TLC), and increased diffusing capacity of carbon monoxide (DL(CO)), which occurred in 56.7, 40, and 23.3 % of patients, respectively. We observed a statistically significant positive correlation between the DL(CO) and the percentage of trunk fat mass (ρ = 0.42; p < 0.01). Three months after placement of the IB, there was a significant reduction in the body mass index (p < 0.0001) and the maximal inspiratory pressure (p < 0.009). We also observed a significant increase in the forced vital capacity (p < 0.0001), TLC (p < 0.001), and ERV (p < 0.0001). CONCLUSIONS: Weight loss as a result of IB causes increased static lung volumes and decreased inspiratory muscle strength. Additionally, being overweight and obese is related to increased DL(CO), especially in individuals with truncal obesity.

Risk factors for decreased total body and regional bone mineral density in hemodialysis patients with severe secondary hyperparathyroidism.

Hyperparathyroidism contributes significantly to decreased bone mineral density (BMD) in end-stage renal disease patients, but this negative influence is not homogeneous throughout the skeleton. We studied the BMD by dual-energy X-ray absorptiometry on total body and on different regions of the skeleton in 42 patients with severe hyperparathyroidism on hemodialysis. We also evaluated the relationship between different risk factors and BMD found on the regions examined in these patients. The legs and other sites where cortical bone predominate were mostly affected, whereas trabecular bone was relatively preserved. This is probably the result of the different effects of hyperparathyroidism on cortical and trabecular bone, but we cannot rule out the interference of ectopic calcifications and sclerotic lesions of vertebral end-plates falsely increasing lumbar spine BMD. The main determinants of low total-body BMD were, in order of importance, immobility, high intact parathyroid hormone levels, low body mass index, and low albumin. Eleven patients presented with pathologic fractures, mainly in the legs, and BMD was lower in this group than in patients without fractures. In conclusion, our study makes clear that hyperparathyroidism is a great threat to bone density in hemodialysis patients, mainly in the legs, the site mostly affected by fragility fractures in our patients. Physicians must worry not only with high parathyroid hormone levels, but also with the nutritional state of these patients.