Age-related reference data of bone microarchitecture, volumetric bone density, and bone strength parameters in a population of healthy Brazilian men: an HR-pQCT study.

In a cross-sectional cohort of 340 healthy Brazilian men aged 20 to 92 years, data on density, structure, and strength of the distal radius and tibia were obtained using high-resolution peripheral quantitative computed tomography (HR-pQCT) to develop age- and site-specific reference curves. Age-dependent changes differed between the sites and bone compartments (trabecular and cortical). INTRODUCTION: The aim of this study was to establish age-related reference curves for bone densities, microarchitectural properties, and estimated failure load measured by HR-pQCT (distal radius and tibia) in men. Also, to correlate bone stiffness with the other HR-pQCT parameters, areal bone mineral density (BMD) by DXA and trabecular bone score (TBS). METHODS: Healthy Brazilian men (n = 340) between the ages of 20 and 92 years were recruited. Non-dominant radius and left tibia were scanned using HR-pQCT (Xtreme CT I). Standard and automated segmentation methods were performed, and bone strength estimated by FE analysis. Bone mineral density at lumbar spine, total hip, femoral neck, and TBS were measured using DXA (Hologic, QDR4500). RESULTS: Age-related reference curves were constructed at the distal radius and tibia for volumetric bone density, morphometry, and estimated bone strength parameters. There was a linear relationship with age only for thickness measurements of distal radius (trabecular: R2 0.108, p<0.001; cortical: R2 0.062, p=0.002) and tibia (trabecular: R2 0.109, p<0.001; cortical: R2 0.063, p=0.010), and bone strength at distal radius (R2 0.157, p<0.001). The significant correlations (p <0.05) found by Pearson's correlations (r) between bone stiffness and all other variables measured by HR-pQCT and DXA showed to be stronger at the tibia site than the distal radius. CONCLUSION: The current study expands the HR-pQCT worldwide database and presents an adequate methodology for the construction of reference data in other populations. Moreover, the correlation of bone strength estimated by FEA with other bone microstructural parameters provided by HR-pQCT helps to determine the contribution of each of these variables to fracture risk prediction in men.

Incidence and risk factors for osteoporotic non-vertebral fracture in low-income community-dwelling elderly: a population-based prospective cohort study in Brazil. The São Paulo Ageing and Health (SPAH) study.

We ascertained the incidence of non-vertebral fracture in a low-income Brazilian elderly cohort. To the best of our knowledge, this is the first population-based study to demonstrate the frequency of non-vertebral fracture in elderly Latin Americans. Age, prior fracture, and bone mineral density (BMD) at hip were predictors of fracture. INTRODUCTION: No data on incidence of osteoporotic non-vertebral fracture have been reported in low-income countries where the population's aging has been faster. Even in developed countries, currently available prospective data on major fracture rates beyond hip are scarce. The aim of this study is to describe the incidence and risk factors for non-vertebral fracture in a longitudinal prospective Brazilian population-based elderly cohort. METHODS: Seven hundred seven older adults (449 women, 258 men) were evaluated at baseline and after a mean follow-up of 4.3 ± 0.8 years. Clinical questionnaire, bone mineral density (BMD), and laboratory tests were performed at baseline. New non-vertebral fracture (hip, proximal humerus, rib, forearm) was determined during the follow-up. Multivariate Poisson regression models were used to identify independent predictors of fracture. RESULTS: The age-standardized incidence of non-vertebral fracture was 1562.3/100,000 (1085.7-2248.1/100,000) person-years (pyr) in women and 632.8/100,000 (301.7-1327.3/100,000) in men. Concerning to hip fractures, the incidence was 421.2/100,000 (210.7-842.3/100,000) pyr in women and 89.9/100,000 (12.7-638.5/100,000) in men. In a multivariate analysis, age (RR 2.07, 95% CI 1.13-3.82, p = 0.019, each 10-year increase), prior non-vertebral fracture (RR 3.08, 95% CI 1.36-6.95, p = 0.007), and total hip BMD (RR 1.68, 95% CI 1.11-2.56, p = 0.015, each 1 SD decrease) were predictors of new non-vertebral fracture. In men, fitting a model of risk factors for fracture was prevented by the limited number of events in male sample. CONCLUSION: This is the first population-based study to ascertain the incidence of major non-vertebral fractures in elderly Latin Americans, confirming the high frequency of the disorder. Age, prior fracture, and hip BMD were predictors of the short-term incidence of fracture.

Risk factors for bone loss in juvenile-onset systemic lupus erythematosus: a prospective study.

OBJECTIVE: Juvenile-onset systemic lupus erythematosus (JoSLE) is associated with low bone mass for age and fractures; nevertheless, risk factors for bone impairment are poorly understood. The aim of this study was to evaluate risk factors for bone mass loss in JoSLE patients. METHODS: Forty-nine female JoSLE patients were evaluated at baseline and after a 3.5-year follow-up regarding clinical, laboratory (including bone turnover markers), areal bone mineral density (aBMD) and bone microarchitecture parameters using high-resolution peripheral quantitative computed tomography (HR-pQCT). Based on the difference between final and baseline aBMD value, the patients were divided into three groups: aBMD gain (BG), aBMD loss (BL) and aBMD no change (NC). RESULTS: The mean patient age was 18.7 ± 3.3 years. Sixty-one percent of patients presented with aBMD gain, 18.4% aBMD loss, and 20.4% remained stable during this follow-up period. Comparing the BL with the BG group, there was a higher frequency of alcohol consumption (p = 0.009), a higher frequency of inadequate calcium intake (p = 0.047) and lower levels of baseline procollagen type 1 amino-terminal propeptide (P1NP) (p = 0.036) in the BL group. Moreover, worsening of HR-pQCT parameters trabecular volumetric density (p = 0.003) and cortical thickness (p = 0.009) was observed in the BL group. In addition, a higher frequency of renal activity was observed comparing the BL + NC with the BG group (p = 0.036). CONCLUSIONS: This is the first longitudinal study that has analyzed the risk factors of bone loss in JoSLE patients. The authors emphasize the importance of evaluating lifestyle habits and renal disease activity in these young women. Furthermore, this study suggests that trabecular and cortical compartments deteriorated, and low levels of P1NP may be a predictor of bone impairment in JoSLE.

Monocytes from male patients with ankylosing spondylitis display decreased osteoclastogenesis and decreased RANKL/OPG ratio.

The present study investigates the osteoclastogenic capacity of peripheral blood mononuclear cells (PBMCs) in male patients with ankylosing spondylitis (AS). We demonstrated that monocytes from these patients display a lower capacity to generate osteoclasts compared to cells from healthy controls, and osteoclastogenesis was negatively correlated with disease duration. INTRODUCTION: Ankylosing spondylitis (AS) is a disease characterized by new bone growth that leads to syndesmophyte formation but AS patients frequently present with low bone mineral density/fractures. Osteoclastogenesis in AS patients is poorly studied and controversial. The aim of this study is to determine if the osteoclastogenic capacity of PBMCs is different in AS patients compared to controls and the relationship between osteoclastogenesis and clinical/laboratory parameters. METHODS: PBMCs from 85 male AS patients and 59 controls were tested for CD16+ cells and induced to differentiate into osteoclasts over 3 weeks in vitro. Serum levels of RANKL, osteoprotegerin (OPG), C-terminal telopeptide of type I collagen (CTX), and amino-terminal pro-peptide of type I collagen (P1NP) were also evaluated. RESULTS: PBMCs from AS patients had fewer CD16+ cells and produced fewer osteoclasts compared to controls. Apoptosis occurred less frequently in osteoclasts obtained from AS patients than in osteoclasts from the controls. A lower RANKL/OPG and CTX/P1NP were observed in AS patients compared to controls. AS patients taking NSAIDs presented no difference regarding the number of OCs produced and the percentage of CD16+ cells compared to controls. However, patients taking TNF inhibitors (TNFi) presented lower OC numbers than controls. A negative correlation was demonstrated between the number of osteoclasts generated from PBMCs of AS patients and disease duration. CONCLUSION: Monocytes from male AS patients display a lower capacity to generate osteoclasts in vitro compared to cells from controls. Osteoclastogenesis was negatively correlated with disease duration. This finding supports the idea that osteoclasts play a role in the physiopathology of bone disease in AS patients.

Increased visceral adipose tissue and altered adiposity distribution in premenopausal lupus patients: correlation with cardiovascular risk factors.

Objective Visceral adipose tissue (VAT) correlates with cardiovascular risk factors and has never been assessed in systemic lupus erythematosus (SLE). Our aim was to evaluate VAT in premenopausal SLE patients. Methods Sixty-three premenopausal SLE patients and 186 age-matched healthy women were included. Demographic, anthropometric, disease and treatment parameters were evaluated. VAT was measured by dual X-ray absorptiometry (DXA) with APEX 4.0 software. Results SLE patients had a disease duration of 5.25 ± 3.80 years, SLEDAI activity score of 4.35 ± 5.13, SLICC/ACR-DI of 0.70 ± 0.80, current prednisone dose of 11.60 ± 12.10 mg/day and cumulative glucocorticoid dose of 22.34 ± 12.94 g. Overweight/obese SLE patients and controls had similar VAT parameters ( p > 0.05). Among individuals with BMI <25 kg/m2, SLE patients and controls had similar weight, fat mass and fat percentage ( p > 0.05) but patients had higher values of VAT parameters (VAT mass: 260.60 ± 117.23 vs. 194.77 ± 71.42 g, p = 0.001; VAT area: 54.05 ± 24.30 vs. 40.40 ± 14.82 cm2, p = 0.001; VAT volume: 281.75 ± 126.81 vs. 210.61 ± 77.29 cm3, p = 0.001) and trunk/limb fat mass ratio (0.78 ± 0.21 vs. 0.67 ± 0.12, p = 0.002) compared to controls. In SLE, VAT area correlated with weight ( r = 0.66, p < 0.001), non-HDL cholesterol ( r = 0.53, p < 0.001), LDL cholesterol ( r = 0.48, p < 0.001) and triglycerides ( r = 0.33, p = 0.008), but not with disease duration, SLEDAI, SLICC/ACR-DI or current glucocorticoid use ( p > 0.05). Conclusion This study provides original evidence that SLE is associated with increased VAT and altered adiposity distribution. The correlation with traditional risk factors for cardiovascular disease, independent of current glucocorticoid dose and disease activity, suggests the role of visceral fat as an additional tool for risk assessment in these young patients.

Visceral fat measured by DXA is associated with increased risk of non-spine fractures in nonobese elderly women: a population-based prospective cohort analysis from the São Paulo Ageing & Health (SPAH) Study.

The present study investigates the relationship between visceral fat measured by dual-energy X-ray absorptiometry (DXA) and the incidence of non-spine fractures in community-dwelling elderly women. We demonstrated a potential negative effect of visceral fat on bone health in nonobese women. INTRODUCTION: The protective effect of obesity on bone health has been questioned because visceral fat has been demonstrated to have a deleterious effect on bone. The aim of this study was to investigate the association of visceral fat measured by DXA with the incidence of non-spine fractures in community-dwelling elderly women. METHODS: This longitudinal prospective population-based cohort study evaluated 433 community-dwelling women aged 65 years or older. A specific clinical questionnaire, including personal history of a fragility fracture in non-spine osteoporotic sites, was administered at baseline and after an average of 4.3 years. All incidences of fragility fractures during the study period were confirmed by affected-site radiography. Visceral adipose tissue (VAT) was measured in the android region of a whole-body DXA scan. RESULTS: The mean age was 72.8 ± 4.7 years, and 28 incident non-spine osteoporotic fractures were identified after a mean follow-up time of 4.3 ± 0.8 years. According to the Lipschitz classification for nutritional status in the elderly, 38.6 % of women were nonobese (BMI ≤ 27 kg/m2) and 61.4 % were obese/overweight. Logistic regression models were used to estimate the relationship between VAT and non-spine fractures in elderly women. After adjusting for age, race, previous fractures, and BMD, VAT (mass, area, volume) had a significant association with the incidence of non-spine fractures only in nonobese elderly women (VAT mass: OR, 1.42 [95 % CI, 1.09-1.85; p = 0.010]; VAT area: OR, 1.19 [95 % CI, 1.05-1.36; p = 0.008]; VAT volume: OR, 1.40 [95 % CI, 1.09-1.80; p = 0.009]). CONCLUSION: This study suggests a potential negative effect of visceral adiposity on bone health in nonobese women.

Associations between OPG and RANKL polymorphisms, vertebral fractures, and abdominal aortic calcification in community-dwelling older subjects: the Sao Paulo Ageing & Health Study (SPAH).

This is the first study analyzing concomitantly osteoprotegerin (OPG)/receptor activator of nuclear factor kappa B ligand (RANKL) polymorphisms and OPG/RANKL serum levels and their association with bone mineral density (BMD), vertebral fractures, and vascular aortic calcification in a cohort of 800 subjects in community-dwelling older individuals. INTRODUCTION: Osteoprotegerin (OPG) and RANKL play an important role in osteoclast activation and differentiation as well as in vascular calcification. At present, there are no studies of OPG or RANKL gene polymorphisms in Brazilian older populations. The aim of this study was to evaluate OPG/RANKL polymorphism and their association with vertebral fractures (VFs) and aortic calcification. METHODS: Eight hundred subjects (497 women/303 men) were genotyped for the OPG 1181G>C (rs2073618), 163C>T (rs3102735), 245T>G (rs3134069), and 209G>A (rs3134070) and RANKL A>G (rs2277438) single-nucleotide polymorphisms (SNPs). VFs were evaluated by spine radiography (Genant's method). Aortic calcification was quantified using Kauppila's method. RESULTS: The isolated genotype analyses and single-allele frequency data showed association of OPG 163C, 245G, and 209A alleles with presence of VFs (P < 0.05). Multiple logistic regression of subjects with absence of VFs vs. those with VFs (grades II/III) revealed only OPG 209A homozygosity as a risk factor for higher-grade VFs (odds ratio (OR) = 4.17, 95 % CI 1.03-16.93, P = 0.046). Regarding aortic calcification, the isolated genotype analysis frequency data revealed a significant association of OPG 1181G, 163C, 245G, and 209A alleles with absent aortic calcification (P < 0.05). Multiple logistic regression data confirmed that the OPG 209A allele was protective for aortic calcification (OR = 0.63, 95 % CI 0.45-0.88, P = 0.007) and the OPG 1181C allele was a risk factor for aortic calcification (OR = 1.26, 95 % CI 1.00-1.58, P = 0.046). CONCLUSION: This study showed that the OPG 209AA genotype was a risk factor for higher-grade VFs, the OPG 209A allele was protective for aortic calcification, and the OPG 1181C was a risk factor for aortic calcification, supporting the involvement of OPG polymorphisms in the analyzed phenotypes and the concept that the related pathogenesis is multifactorial.

Lower P1NP serum levels: a predictive marker of bone loss after 1 year follow-up in premenopausal systemic lupus erythematosus patients.

SUMMARY: Predictors of bone mineral density (BMD) loss are additional tools in the management of osteoporosis in premenopausal women with systemic lupus erythematosus (SLE). This study provides original evidence that N-terminal propeptide of type 1 collagen (P1NP), the most specific bone formation marker, is a predictor of BMD loss in this group of women. INTRODUCTION: SLE is associated with a high risk of low bone mass/fractures but this risk is still controversial in premenopausal women. Our aim was to determine the 1 year incidence of BMD loss in premenopausal SLE women and the value of bone turnover markers as predictors of this complication. METHODS: This study enrolled a convenience sample of 63 premenopausal SLE patients. BMD was evaluated by dual X-ray absorptiometry at lumbar spine and hip at baseline and after 12 months. BMD changes above the least significant change were considered significant. Serum levels of P1NP and CTX (electrochemiluminescence), OPG, and RANKL (ELISA) were determined at baseline. RESULTS: Mean age was 31.1±6.8 years, and disease duration was 5.25±3.8 years. 36.5 % of patients presented BMD loss and 17.5 % BMD gain at lumbar spine and/or hip. Patients were divided in three groups: BMD loss (BL), no BMD change (NC), and BMD gain (BG). Patients with BL and NC received similar cumulative/mean/maximum glucocorticoid doses during the study, but patients with BG received lower doses (p<0.05). Baseline P1NP levels were different in the groups (BL: 36.95±23.37 vs. NC: 54.63±30.82 vs. BG: 84.09±43.85 ng/mL; p=0.031 BL vs. NC, p<0.001 BL vs. BG, and p=0.039 NC vs. BG). There was no difference in CTX, OPG, or RANKL levels. After multivariate analysis, P1NP remained as an independent risk factor for BMD loss (p<0.03). CONCLUSIONS: This study provides original evidence that lower levels of P1NP, the most specific bone formation marker, are predictive of BMD loss over 12 months in premenopausal SLE patients.

Incidence and risk factors for osteoporotic vertebral fracture in low-income community-dwelling elderly: a population-based prospective cohort study in Brazil. The São Paulo Ageing & Health (SPAH) Study.

UNLABELLED: We ascertained the incidence and predictors of radiographic vertebral fracture in a Brazilian elderly cohort, since no data in this field have been reported in low-income countries. This is the first population-based study to demonstrate the high frequency of vertebral fracture in elderly Latin Americans. Age, prior fracture, BMD, and bone turnover were predictors of fracture. INTRODUCTION: Vertebral fractures are associated with increased future fracture risk and mortality. No data on incidence of osteoporotic vertebral fracture have been reported in low-income countries where the population's aging has been faster. Thus, we sought to describe the incidence and risk factors for radiographic vertebral fracture in a longitudinal prospective Brazilian population-based elderly cohort. METHODS: 707 older adults (449 women and 258 men) were evaluated with spinal radiographs obtained at baseline and after a mean follow-up of 4.3 ± 0.8 years. New vertebral fracture was defined as distinct alteration in the morphology of vertebrae resulting in higher grade of deformity on the second radiograph when compared to the baseline radiograph. Clinical questionnaire, bone mineral density (BMD), and laboratory tests were performed at baseline. Multivariate Poisson regression models were used to identify independent predictors of fracture. RESULTS: The age-standardized incidence of vertebral fracture was 40.3/1,000 person-years in women and 30.6/1,000 in men. In women, three models of risk factors for fracture were fitted: (1) age (relative risks (RR) 2.46, 95 % confidence interval (CI) 1.66-3.65), previous osteoporotic fracture (RR 1.65, 95 % CI 1.00-2.71), and lumbar spine BMD (RR 1.21, 95 % CI 1.03-1.41); (2) age (RR 2.25, 95 % CI 1.52-3.34) and femoral neck BMD (RR 1.42, 95 % CI 1.11-1.81); (3) age (RR 2.11, 95 % CI 1.41-3.15) and total hip BMD (RR 1.56, 95 % CI 1.21-2.0). In men, the highest quartile of cross-linked C-telopeptide (CTx) (RR 1.96, 95 % CI 0.98-3.91) and prior fracture (RR 2.10, 95 % CI 1.00-4.39) were predictors of new vertebral fracture. CONCLUSIONS: This is the first population-based study to ascertain the incidence of vertebral fracture in elderly Latin Americans, confirming the high frequency of the disorder. Age, prior fracture, BMD, and bone turnover were predictors of the short-term incidence of vertebral fracture.

Prevalence of sarcopenia and associated risk factors by two diagnostic criteria in community-dwelling older men: the São Paulo Ageing & Health Study (SPAH).

UNLABELLED: Sarcopenia is an aging syndrome that can be characterized by many criteria adjusted or not by fat mass. This study suggested that the optimal criteria should be selected according to body mass index (BMI) in older men and identified age, BMI, race, smoking, physical activity, hip bone mineral density (BMD) as risk factors for this syndrome. INTRODUCTION: This study aims to analyze the prevalence of sarcopenia and associated risk factors using appendicular skeletal mass (ASM)/height(2) and ASM adjusted for total fat mass criteria in older men from community. METHODS: Three hundred ninety-nine men were included and answered a questionnaire about lifestyle and medical history. Individuals were classified by their BMI using the classification adjusted by age. Body composition and bone mineral density were measured by dual X-ray absorptiometry. Sarcopenia was classified according to both criteria. Logistic regression models were used to analyze risk factors associated with sarcopenia. RESULTS: The mean BMI was 26.46 kg/m(2): 12.5 % underweight, 43.6 % normal, and 43.9 % overweight/obese. Fifty-four (13.5 %) were considered sarcopenic by ASM/height(2) and 79 (19.8 %) by ASM adjusted for fat (p = 0.001). Fifty-one (12.8 %) individuals had discordant sarcopenia classification: 13 were classified only by ASM/height(2) and 38 only by ASM adjusted for fat. Of the 13 subjects classified as sarcopenic only by ASM/height(2), 84.6 % (11/13) were underweight and solely one (7.7 %) was considered overweight/obese. In contrast, of those 38 older men classified as sarcopenic only by ASM adjusted for fat, none were underweight and 53 % (20/38) were overweight/obese. Subjects classified as sarcopenic according to both criteria had the same risk factors in the final model analyses (age, BMI, race, smoking, physical activity, hip BMD; p < 0.05). CONCLUSION: This study suggested that the optimal criteria for sarcopenia should be selected according to BMI in community-dwelling older men.

Discriminating sarcopenia in community-dwelling older women with high frequency of overweight/obesity: the São Paulo Ageing & Health Study (SPAH).

SUMMARY: The criteria most used for the definition of sarcopenia, those based on the ratio between the appendicular skeletal muscle mass (ASM) and the square of the height (h(2)) underestimate prevalence in overweight/obese people whereas another criteria consider ASM adjusted for total fat mass. We have shown that ASM adjusted for fat seems to be more appropriate for sarcopenia diagnosis. INTRODUCTION: Since the prevalence of overweight and obesity is a growing public health issue, the aim of this study was to evaluate the prevalence and risk factors associated with sarcopenia, based on these two criteria, among older women. METHODS: Six hundred eleven community-dwelling women were evaluated by specific questionnaire including clinical data. Body composition and bone mineral density were evaluated by dual X-ray absorptiometry. Logistic regression models were used to identify factors independently related to sarcopenia by ASM/h(2) and ASM adjusted for total fat mass criteria. RESULTS: The prevalence of overweight/obesity was high (74.3 %). The frequency of sarcopenia was lower using the criteria of ASM/h(2) (3.7 %) than ASM adjusted for fat (19.9 %) (P < 0.0001). We also note that less than 5 %(1/23) of sarcopenic women, according to ASM/h(2), had overweight/obesity, whereas 60 % (74/122) of sarcopenic women by ASM adjusted for fat had this complication. Using ASM/h(2), the associated factors observed in regression models were femoral neck T-score (OR = 1.90; 95 % CI 1.06-3.41; P = 0.03) and current alcohol intake (OR = 4.13, 95 % CI 1.18-14.45, P = 0.03). In contrast, we have identified that creatinine (OR = 0.21; 95 % CI 0.07-0.63; P = 0.005) and the White race (OR = 1.81; 95 % CI 1.15-2.84; P = 0.01) showed a significant association with sarcopenia using ASM adjusted for fat. CONCLUSIONS: In women with overweight/obesity, ASM adjusted for fat seems to be the more appropriate criteria for sarcopenia diagnosis. This finding has relevant public health implications, considering the high prevalence of overweight/obesity in older women.

Prevalence and risk factors of radiographic vertebral fracture in Brazilian community-dwelling elderly.

UNLABELLED: The prevalence and risk factors of radiographic vertebral fracture were determined among Brazilian community-dwelling elderly. Vertebral fractures were a common condition in this elderly population, and lower hip bone mineral density was a significant risk factor for vertebral fractures in both genders. INTRODUCTION: The aim of the study was to estimate the prevalence of radiographic vertebral fracture and investigate factors associated with this condition in Brazilian community-dwelling elderly. METHODS: This cross-sectional study included 943 elderly subjects (561 women and 382 men) living in São Paulo, Brazil. Thoracic and lumbar spine radiographs were obtained, and vertebral fractures were evaluated using Genant's semiquantitative method. Bone mineral density (BMD) was measured by dual X-ray absorptiometry, and bone biochemical markers were also evaluated. Female and male subjects were analyzed independently, and each gender was divided into two groups based on whether vertebral fractures were present. RESULTS: The prevalence of vertebral fracture was 27.5% (95% CI 23.8-31.1) in women and 31.8% in men (95% CI 27.1-36.5) (P = 0.116). Cox regression analyses using variables that were significant in the univariate analysis showed that age (prevalence ratio = 1.03, 95% CI 1.01-1.06; p = 0.019) and total femur BMD (PR = 0.27, 95% CI 0.08-0.98; p = 0.048) were independent factors in predicting vertebral fracture for the female group. In the male group, Cox regression analyses demonstrated that femoral neck BMD (PR = 0.26, 95% CI 0.07-0.98; p = 0.046) was an independent parameter in predicting vertebral fractures. CONCLUSIONS: Our results suggest that radiographic vertebral fractures are common in Brazilian community-dwelling elderly and that a low hip BMD was an important risk factor for this condition in both genders. Age was also significantly correlated with the presence of vertebral fractures in women.

Primary antiphospholipid syndrome in premenopausal women: low vitamin D, high fat mass and maintained bone mineral mass.

The aim of this study was to analyze vitamin D levels and their association with bone mineral density and body composition in primary antiphospholipid syndrome. For this cross-sectional study 23 premenopausal women with primary antiphospholipid syndrome (Sapporo criteria) and 23 age- and race-matched healthy controls were enrolled. Demographic, anthropometric, clinical and laboratorial data were collected using clinical interview and chart review. Serum 25-hydroxyvitamin D levels, parathormone, calcium and 24-hour urinary calcium were evaluated in all subjects. Bone mineral density and body composition were studied by dual X-ray absorptiometry. The mean age of patients and controls was 33 years. Weight (75.61 [20.73] vs. 63.14 [7.34] kg, p = 0.009), body mass index (29.57 [7.17] vs. 25.35 [3.37] kg, p = 0.014) and caloric ingestion (2493 [1005.6] vs. 1990 [384.1] kcal/day, p = 0.03) were higher in PAPS than controls. All PAPS were under oral anticoagulant with INR within therapeutic range. Interestingly, biochemical bone parameters revealed lower levels of 25-hydroxyvitamin D [21.64 (11.26) vs. 28.59 (10.67) mg/dl, p = 0.039], serum calcium [9.04 (0.46) vs. 9.3 (0.46) mg/dl, p = 0.013] and 24-hour urinary calcium [106.55 (83.71) vs. 172.92 (119.05) mg/d, p = 0.027] in patients than in controls. Supporting these findings, parathormone levels were higher in primary antiphospholipid syndrome than in controls [64.82 (37.83) vs. 44.53 (19.62) pg/ml, p = 0.028]. The analysis of osteoporosis risk factors revealed that the two groups were comparable (p > 0.05). Lumbar spine, femoral neck, total femur and whole body bone mineral density were similar in both groups (p > 0.05). Higher fat mass [28.51 (12.93) vs. 20.01 (4.68) kg, p = 0.005] and higher percentage of fat [36.08 (7.37) vs. 31.23 (4.64)%, p = 0.010] were observed in PAPS in comparison with controls; although no difference was seen regarding lean mass. In summary, low vitamin D in primary antiphospholipid syndrome could be secondary to higher weight and fat mass herein observed most likely due to adipocyte sequestration. This weight gain may also justify the maintenance of bone mineral density even with altered biochemical bone parameters.

Premature coronary artery calcification is associated with disease duration and bone mineral density in young female systemic lupus erythematosus patients.

Our objective was to evaluate the relevance of traditional and disease-related cardiovascular risk factors and of bone mineral density for premature coronary artery calcification in young patients with systemic lupus erythematosus. Ninety-four female patients with systemic lupus erythematosus with disease durations >5 years and <45 years were consecutively selected. Cardiovascular risks (diabetes mellitus, arterial hypertension, dyslipoproteinemia, smoking, family history, body mass index, ovarian and renal insufficiency) and systemic lupus erythematosus-related risk factors (disease duration, ACR criteria, modified SLICC/ ACR, SLEDAI and treatment) were evaluated. Bone mineral density was assessed by dual X-ray absorptiometry. Coronary artery calcification was determined by computed tomography. Coronary artery calcification was identified in 12 (12.7%) patients and was associated with a higher frequency of patients with cardiovascular risks (p = 0.001), higher number of cardiovascular risks (p = 0.002), age (p = 0.025), disease duration (p = 0.011) and SLICC (p=0.011). Individual analysis of cardiovascular risks demonstrated that menopause (p = 0.036), dyslipidemia (p = 0.003) and hypertension (p = 0.006) were significantly associated with coronary artery calcification. In addition, coronary artery calcification was associated with a lower whole body bone mineral density (p = 0.013). Multiple logistic regression analysis using cardiovascular risks, age, disease duration, SLICC and whole body bone mineral density revealed that only disease duration (p = 0.038) and whole body bone mineral density (p = 0.021) remained significant for coronary artery calcification. In conclusion, we found that disease duration and decreased bone mineral density are independent predictors for premature coronary calcification in young women with systemic lupus erythematosus, suggesting a common underlying mechanism.

A single dose of zoledronic acid reverses the deleterious effects of glucocorticoids on titanium implant osseointegration.

UNLABELLED: This study evaluates the effect of zoledronic acid (ZOL) on the osseointegration of titanium implants in rabbits with glucocorticoid (GC)-induced bone loss, and our findings demonstrated that a single dose of ZOL is able to reverse the detrimental effects of GCs on the osseointegration of titanium implants. INTRODUCTION: The purpose of this study is to evaluate the effect of ZOL on the osseointegration of titanium implants in rabbits with GC-induced bone loss. METHODS: Three groups of six NZW rabbits were treated for 18 weeks with saline (SALINE), GC (methylprednisolone, 0.35 mg/kg three times a week), or GC + ZOL (methylprednisolone + single dose of ZOL, 0.1 mg/kg). The animals received a titanium implant in the left tibia after 6 weeks and were killed at the 18th week. Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry at baseline, eighth week (W8), and 18th week (W18) after treatment to determine the change upon treatment (BMD). Histomorphometric and serum bone alkaline phosphatase analysis (BAP) were also performed. RESULTS: At W8, GC group had a significant reduction in lumbar spine and tibia BMD compared with SALINE (p = 0.003 and p = 0.000), as also observed for GC + ZOL group (p = 0.014 and p = 0.003) just 2 weeks after ZOL treatment. In contrast, at W18, the GC + ZOL had an evident BMD rescue with similar lumbar spine and tibia BMD compared with SALINE (0.043 +/- 0.006 vs. 0.055 +/- 0.009 g/cm(2), p = 0.457 and 0.027 +/- 0.003 vs. 0.041 +/- 0.011 g/cm(2), p = 0.232) and a significantly higher BMD compared with the GC (p = 0.024 and p = 0.001). Histomorphometry revealed that osseointegration was significantly reduced in GC (tibia cortical thickness and diameter, bone-implant contact, total and peri-implant bone area) whereas GC + ZOL had these parameters similar to SALINE (p > 0.05). Likewise, ZOL reversed the BAP alteration induced by GC. CONCLUSIONS: Our findings demonstrated that a single dose of ZOL is able to reverse the detrimental effects of glucocorticoids on the osseointegration of titanium implants, suggesting that ZOL therapy may improve the outcome of bone implants in patients with glucocorticoid-induced osteoporosis.

Osteoprotegerin/RANKL system imbalance in active polyarticular-onset juvenile idiopathic arthritis: a bone damage biomarker?

OBJECTIVE: To evaluate the importance of receptor activator of nuclear factor kappaB (RANK)/receptor activator of nuclear factor kappaB ligand (RANKL)/osteoprotegerin (OPG) modulation in active polyarticular juvenile idiopathic arthritis (pJIA) patients with and without bone erosions. METHODS: Thirty female patients (mean age 11.07+/-3.77 years, range 4-17 years) with active pJIA and 30 healthy gender- and age-matched controls were consecutively selected for this study. All involved articulations were assessed by X-ray and examined for the presence of bone erosions. The serum levels of RANKL and OPG were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Patients with active pJIA had higher levels of serum RANKL than controls [2.90 (0.1-37.4) vs. 0.25 (0.1-5.7) pg/mL, p = 0.007] and a lower OPG/RANKL ratio [21.25 (1.8-897.6) vs. 347.5 (9-947.8), p = 0.005]. However, levels of OPG were comparable in both groups [55.24 (28.34-89.76) vs. 64.42 (30.68-111.28) pg/mL, p = 0.255]. Higher levels of serum RANKL and a lower OPG/RANKL ratio were also observed in active pJIA patients with bone erosions compared to controls [3.49 (0.1-37.4) vs. 0.25 (0.1-5.7) pg/mL, p = 0.0115 and 14.3 (1.8-897.6) vs. 347.5 (9-947.8), p = 0.016]. However, RANKL levels and OPG/RANKL ratio were similar in pJIA patients without bone erosion and controls [1.75 (0.1-10.9) vs. 0.25 (0.1-5.7) pg/mL, p = 0.055 and 29.2 (3.3-756.8) vs. 347.5 (9-947.8), p = 0.281]. CONCLUSION: These data suggest that active pJIA with bone erosions is associated with high serum levels of RANKL and a low OPG/RANKL ratio, indicating that these alterations may reflect bone damage in this disease.

Bone mineral apparent density in juvenile dermatomyositis: the role of lean body mass and glucocorticoid use.

OBJECTIVE: To analyse bone mineral density (BMD) in juvenile dermatomyositis (JDM) and its possible association with body composition, disease activity, duration of disease, glucocorticoid (GC) use, and biochemical bone parameters, including osteoprotegerin (OPG) and receptor activator of nuclear factor kappaB (RANKL). METHODS: Twenty girls with JDM and 20 controls matched for gender and age were selected. Body composition and BMD were analysed by dual-energy X-ray absorptiometry (DXA) and bone mineral apparent density (BMAD) was calculated. Duration of disease, cumulative GC, and GC pulse therapy use were determined from medical records. Disease activity and muscle strength were measured by the Disease Activity Score (DAS), the Childhood Myositis Assessment Scale (CMAS), and the Manual Muscle Test (MMT). Inflammatory and bone metabolism parameters were also analysed. OPG and RANKL were measured in patients and controls using an enzyme-linked immunosorbent assay (ELISA). RESULTS: A lower BMAD in the femoral neck (p<0.001), total femur (p<0.001), and whole body (p = 0.005) was observed in JDM patients compared to controls. Body composition analysis showed a lower lean mass in JDM compared to controls (p = 0.015), but no difference was observed with regard to fat mass. A trend of lower serum calcium was observed in JDM (p = 0.05), whereas all other parameters analysed, including OPG and RANKL, were similar. Multiple linear regression analysis revealed that, in JDM, lean mass (p<0.01) and GC pulse therapy use (p<0.05) were independent factors for BMAD in the hip region. CONCLUSIONS: This study has identified low lean mass and GC pulse therapy use as the major factors for low hip BMAD in JDM patients.

Decreased in vitro osteoblast proliferation and low turnover bone disease in nonuremic proteinuric patients.

Patients with proteinuria, even those with normal glomerular filtration rate, often present abnormal bone histology. We evaluated bone histology and the in vitro proliferation of osteoblasts in samples obtained from 17 proteinuric patients with primary glomerulopathies. Histomorphometric analysis of bone biopsies was performed, and bone fragments were obtained for osteoblast culture, in which we evaluated cell proliferation. In comparison to controls, patients presented lower trabecular bone volume (20.9+/-14.5% vs 26.8+/-5.9%; P=0.0008); lower trabecular number (1.7+/-0.2/mm vs 2.0+/-0.3/mm; P=0.004); and greater trabecular separation (475.5+/-96.4 microm vs 368.3+/-86.2 microm, P=0.0002). We also found alterations in bone formation and resorption: lower osteoid volume (0.9+/-0.7% vs 2.0+/-1.4%; P=0.0022); lower osteoid thickness (6.4+/-2.8 microm vs 11.5+/-3.2 microm; P<0.0001); less mineralizing surface (4.6+/-3.1% vs 13.5+/-6.0%; P<0.0001); lower bone formation rate (0.03+/-0.04 microm(3)/microm(2)/day vs 0.09+/-0.05 microm(3)/microm(2)/day; P<0.0001); and greater osteoclast surface (0.35+/-0.6 vs 0.05+/-0.1%, P=0.0016). Mean in vitro osteoblast proliferation was lower in patients than in controls (910.2+/-437.1 vs 2261.0+/-1121.0 d.p.m./well, P=0.0016). Serum concentrations of 25-hydroxyvitamin-D(3) correlated negatively with proteinuria and positively with in vitro osteoblast proliferation. Our results demonstrate that nonuremic proteinuric glomerulonephritic patients present bone structure disorder, low bone formation and high bone resorption, as well as low osteoblast proliferation.

Balance training program is highly effective in improving functional status and reducing the risk of falls in elderly women with osteoporosis: a randomized controlled trial.

INTRODUCTION: The purpose of this study was to investigate the effect of a 12-month Balance Training Program on balance, mobility and falling frequency in women with osteoporosis. METHODS: Sixty-six consecutive elderly women were selected from the Osteometabolic Disease Outpatient Clinic and randomized into 2 groups: the 'Intervention', submitted for balance training; and the 'Control', without intervention. Balance, mobility and falling frequency were evaluated before and at the end of the trial, using the Berg Balance Scale (BBS), the Clinical Test Sensory Interaction Balance (CTSIB) and the Timed "Up & Go" Test (TUGT). Intervention used techniques to improve balance consisting of a 1-hour session each week and a home-based exercise program. RESULTS: Sixty women completed the study and were analyzed. The BBS difference was significant higher in the Intervention group compared to Control (5.5 +/- 5.67 vs -0.5 +/- 4.88 score, p<0.001). Similarly, the number of patients in the Intervention group presented improvement in two conditions of CTSIB compared to Control (eyes closed and unstable surface condition: 13 vs one patient, p < 0.001 and eyes open, visual conflict and unstable surface condition: 12 vs one patient, p<0.001). Additionally, the differences between the TUGT were reduced in the Intervention group compared to Control (-3.65 +/- 3.61 vs 2.27 +/- 7.18 seconds, p< 0.001). Notably, this improvement was paralleled by a reduction in the number of falls/patient in the Intervention group compared to Control (-0.77 +/- 1.76 vs 0.33 +/- 0.96, p=0.018). CONCLUSION: This longitudinal prospective study demonstrated that an intervention using balance training is effective in improving functional and static balance, mobility and falling frequency in elderly women with osteoporosis.

Low bone density and low serum levels of soluble RANK ligand are associated with severe arterial calcification in patients with Takayasu arteritis.

OBJECTIVE: Takayasu arteritis (TA) is a chronic inflammatory disorder affecting the aorta and its branches. Vascular calcification has been described in 29-54% of cases of TA, although its aetiology remains unknown. Recently the osteoprotegerin/RANKL/RANK system has emerged as an important contributing factor to atherogenesis and osteogenesis. Our aim is to investigate the association between vascular calcification, bone mineral density (BMD) and the osteoprotegerin/RANK/RANKL system in TA. METHODS: Thirty pre-menopausal female TA patients and 30 age- and sex-matched controls were studied. BMD was measured by dual X-ray absorptiometry. Arterial calcification in TA patients was analysed by computed tomography in thoracic and abdominal sites. Serum levels of osteoprotegerin and soluble receptor activator of nuclear factor kappaB ligand (sRANKL) were quantified by enzyme-linked immunosorbent assay. RESULTS: Patients with severe arterial calcification showed lower BMD values than controls in lumbar spine (0.965 +/- 0.055 vs 1.126 +/- 0.153 g/cm2, P = 0.009) and total body (0.993 +/- 0.065 vs 1.085 +/- 0.082 g/cm2, P = 0.019). In contrast, TA patients without calcification presented BMD values similar to controls (P > 0.05). Interestingly, lower serum levels of sRANKL (1.89 +/- 2.35 vs 2.80 +/- 2.23 pg/ml, P = 0.031) and a longer disease duration (12.20 +/- 6.61 vs 3.56 +/- 5.33 yr, P = 0.004) were observed in TA patients with severe calcification compared with patients without calcification. CONCLUSIONS: Severe arterial calcification in TA is associated with low values of BMD and sRANKL, reinforcing the possible link between bone and vascular disease.