Untreated osteoporosis and higher FRAX as risk factors for tooth loss: a 5-year prospective study.

INTRODUCTION: Studies have shown that an impaired bone condition, represented by osteoporosis and increased fracture risk, may potentially aggravate periodontal disease and, consequently, the risk of tooth loss. This 5-year prospective study aimed to investigate whether systemic bone condition represents risk factor for tooth loss due to periodontal disease amongst elderly women. MATERIAL AND METHODS: Seventy-four participants, aged ≥ 65 years, who attended the 5-years recall for periodontal evaluation were involved. Baseline exposures were osteoporosis and fracture risk probabilities (FRAX). Women were grouped according to bone mineral density (BMD) and years of bone treatment for osteoporosis. The primary outcome at a 5-year follow-up was the number of tooth loss due to periodontal disease. Periodontitis staging and grading, and causes of tooth loss were recorded. RESULTS: The multivariate Poisson regression models showed that women with untreated/shortly treated osteoporosis were 4 times more likely to present higher number of tooth loss due to periodontal disease than those with normal BMD or treated for ≥ 3 years (risk ratio (RR) = 4.00, 95% CI 1.40-11.27). Higher FRAX was also linked to tooth loss (RR = 1.25, 95% CI 1.02-1.53). Receiver-operating characteristic (ROC) curve suggested that women with history of ≥ 1 tooth losses have higher chances of worse major FRAX (sensitivity = 72.2%; specificity = 72.2%). CONCLUSION: In this 5-year study, higher FRAX and untreated osteoporosis were risk factors for tooth loss. Women with normal BMD or treated for osteoporosis for ≥ 3 years did not show increased risk. Management of skeletal conditions should be emphasized with periodontal care for the prevention of tooth loss in elderly women.

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.

Inhaled glucocorticoids are associated with vertebral fractures in COPD patients.

Chronic obstructive pulmonary disease (COPD) is an independent risk factor for osteoporosis. Oral glucocorticoids are deleterious to bone; however, the impact of inhaled glucocorticoids (ICS) remains unclear. Our objective was to determine whether ICS contribute to osteoporosis and fragility fractures. Sixty-one COPD patients, 35 current users of ICS and 26 who had never received glucocorticoids, were evaluated for bone mineral density (BMD) and body composition and underwent vertebral fracture assessment (VFA). The risk factors for bone disease considered for analysis were age, gender, ICS use, body mass index (BMI), muscle mass index (MMI), and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) category. The Fracture Risk Assessment Tool (FRAX) calculation tool for the Brazilian population was also employed. The groups did not differ regarding gender, BMI, MMI, GOLD class, lowest values of the BMD T-score and Z-score, prevalence of osteoporosis, or low BMD for age. Vertebral fractures were identified via VFA in seven patients using ICS and in none of those not receiving glucocorticoids (p = 0.02). There was a trend for an association between MMI and osteoporosis (p = 0.05) and for a progressive decrease in the BMD Z-score according to the COPD severity assessed via the GOLD score (p = 0.08). Vertebral fractures were not associated with osteoporosis (p = 0.69) or low MMI (p = 0.12). The fracture risk was not estimated by FRAX. ICS may lead to bone fragility before a significant decrease in BMD. Low muscle mass and COPD severity may contribute to bone disease.

Vitamin D Deficiency and Its Influence on Bone Metabolism and Density in a Brazilian Population of Healthy Men.

Vitamin D supplementation is universal for postmenopausal women, but not for elderly men, in whom osteoporosis is also commonly neglected. This study aimed to evaluate vitamin D deficiency and its association with secondary hyperparathyroidism, bone resorption, and bone density in Brazilian men. A total of 120 men, 20-93 years, were evaluated for serum calcium, phosphorus, creatinine, 25-hydroxyvitamin D (25(OH)D), parathyroid hormone, biochemical markers of bone resorption (carboxy-terminal telopeptide, carboxy-terminal peptide of type I collagen), and bone mineral density (dual-energy X-ray absorptiometry). Glomerular filtration rate (GFR) below 30 mL/min/1.73 m2, chronic diseases, and medications affecting bone were the exclusion criteria. No participant reported previous low-impact fractures. In the overall population, 25(OH)D levels were below 30 ng/mL in 46.7%, and below 20 ng/mL in 27.6%. Among the 93 patients 50 years and older, 28 had osteoporosis. In those 70 years and older, the prevalence of vitamin D deficiency (42.1%), secondary hyperparathyroidism (46.4%), high bone resorption (39.6%), decreased GFR (39.2%), and osteoporosis (41.4%) was significantly higher than in the younger subjects (p < 0.005 for all comparisons). Serum parathyroid hormone increased with aging and declining GFR, but was not significantly associated with 25(OH)D or bone mineral density. There was a clear contribution of vitamin D deficiency to increased bone resorption and osteoporosis. Binary logistic regression model considering age, 25(OH)D, and bone resorption identified age ≥70 years as the main determinant of osteoporosis. Our data demonstrate a high prevalence of vitamin D deficiency in a male population living in Rio de Janeiro, and emphasize its participation on the pathogenesis of age-related bone loss. (Vitamin D deficiency and osteoporosis are common in elderly Brazilian men.).

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.

Vitamin D status in a Brazilian cohort of adolescents and young adults with perinatally acquired human immunodeficiency virus infection.

The purpose was to determine the prevalence and related factors of vitamin D (VitD) insufficiency in adolescents and young adults with perinatally acquired human immunodeficiency virus. A cohort of 65 patients (17.6 ± 2 years) at the Federal University of Rio de Janeiro, Brazil, were examined for pubertal development, nutrition, serum parathormone and serum 25-hydroxyvitamin D [s25(OH)D]. s25(OH)D levels < 30 ng/mL (< 75 nmol/L) were defined as VitD insufficiency. CD4+ T-cell counts and viral load, history of worst clinical status, immunologic status as nadir, current immunologic status, and antiretroviral (ART) regimen were also evaluated as risk factors for VitD insufficiency. Mean s25(OH)D was 37.7 ± 13.9 ng/mL and 29.2% had VitD insufficiency. There was no difference between VitD status and gender, age, nutritional status, clinical and immunological classification, and type of ART. Only VitD consumption showed tendency of association with s25(OH)D (p = 0.064). Individuals analysed in summer/autumn season had a higher s25(OH)D compared to the ones analysed in winter/spring (42.6 ± 14.9 vs. 34.0 ± 11.9, p = 0.011). Although, the frequency of VitD insufficiency did not differ statistically between the groups (summer/autumn 17.9% vs. winter/spring 37.8%, p = 0.102), we suggest to monitor s25(OH)D in seropositive adolescents and young adults, especially during winter/spring months, even in sunny regions.

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.

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.

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.

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.

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.

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.

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.

Active search of adult patients with persistently low serum alkaline phosphatase levels for the diagnosis of hypophosphatasia.

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.

Body composition, but not insulin resistance, influences postprandial lipemia in patients with Turner's syndrome.

OBJECTIVE: The aim of the present study was to examine the influence of body composition and insulin resistance on the magnitude of postprandial lipemia in patients with Turner's syndrome receiving oral versus transdermal estrogen replacement. METHODS: Twenty-five patients with Turner's syndrome receiving oral or transdermal estrogen replacement were evaluated for body mass index, waist-to-hip and waist-to-height ratios, fasting glycemia, insulin, body composition (dual-energy X-ray absorptiometry), and postprandial lipid metabolism. For statistical analysis, we used parametric tests to compare numeric variables between the two subgroups. RESULTS: We observed no difference in postprandial triglyceride levels between patients receiving oral versus transdermal hormone replacement therapy. The postprandial triglycerides increment correlated positively with the percentage of total fat mass (p=0.02) and android fat mass (p=0.02) in the transdermal group. In the oral estrogen group, a positive correlation was observed between the increment in postprandial triglycerides and waist-to-hip (p=0.15) and waist-to-height (p=0.009) ratios. No association was observed between the estrogen replacement route and insulin resistance evaluated by the homeostatic model assessment-insulin resistance (HOMA-IR) index (p=0.19 and p=0.65 for the oral and transdermal groups, respectively). CONCLUSION: We concluded that body composition and anthropometric characteristics possibly affect the extent of postprandial lipemia independently from the route of estrogen replacement.

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.

Cyclosporine A, but not tacrolimus, is associated with impaired proliferation and differentiation of human osteoblast-like cells in vitro.

BACKGROUND: The prevention of graft rejection after liver transplant with cyclosporine A (CyA) and tacrolimus has been associated to decreased bone mineral density. The aim of this study was to investigate the in vitro effects of increasing concentrations of CyA and tacrolimus on human osteoblasts. MATERIAL/METHODS: Human osteoblast-like cells obtained by the outgrowth of cells from bone chips were exposed to tacrolimus (10-1000 ng/mL) or CyA (1000-50,000 ng/mL). Alkaline phosphatase (ALP) activity was determined on days 2, 4, 6, and 8, and cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell counting on days 2, 4, 6, and 8. Cell death was investigated by flow cytometry with propidium iodine, and apoptosis was assessed by flow cytometry with fluorescently conjugated annexin V. RESULTS: No effects of tacrolimus were detected with respect to ALP activity or cell proliferation. In CyA-treated cultures, concentrations greater than 10 000 ng/mL were associated with decreased ALP activity after 8 days (P<0.05). In addition, a dose-dependent reduction in cell proliferation was detected after 6 days (P<0.05). This decreased cell proliferation was associated with increased apoptosis in response to 50 000 ng/mL CyA. CONCLUSIONS: Our results showed that CyA reduced, in a time- and concentration-dependent manner, the number of metabolically active cells via a decrease in proliferation and an increase in cell death, and induced impairment of osteoblast differentiation. These negative effects of CyA on human osteoblast-like cells might contribute to the bone loss reported in vivo.

Additional beneficial effects of recombinant growth hormone in alendronate-treated patients with idiopathic osteoporosis.

In order to study the benefit of adding recombinant human growth hormone (rhGH) to antiresorptive therapy, six patients with idiopathic osteoporosis (IO) receiving alendronate plus calcium and vitamin D were started on daily subcutaneous injections of rhGH 2.0 IU for one year. Fasting morning urine and serum samples were collected for N telopeptide of type-1 collagen (NTX), serum bone-specific alkaline phosphatase (BSAP) and insulin-like growth factor 1 (IGF-1) during the study. Bone mineral density (BMD) was determined by dual-energy x-ray absorptiometry at baseline and 01 year. The effect of rhGH was evaluated comparing the percentage changes in BMD during the last year on ALN with the results obtained with the combined therapy. Serum IGF-1 increased in all patients but variations were not significant (p=0.266). Serum BSAP did not significantly change (p=0.078) but median NTX increased at 45 days from 12.3 to 19.8 nMBCE/mMCr (p=0.012) and tended to return to baseline values at 12 months (15.2 nMBCE/mMCr). Comparing with isolated ALN therapy, a beneficial effect on bone density was observed in 2/3 of the patients at lumbar spine, and percentage change (median and quartiles) varied from -0.65% (-2.33 and 2.23) on ALN to 0.70% (-0.35 and 3.03) on ALN+GH. Although no bone gain occurred at the femoral neck, our data point to a positive effect of rhGH in patients with idiopathic osteoporosis.