Summary
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:
R
2
0.108,
p
<0.001; cortical:
R
2
0.062,
p
=0.002) and tibia (trabecular:
R
2
0.109,
p
<0.001; cortical:
R
2
0.063,
p
=0.010), and bone strength at distal radius (
R
2
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.
Summary
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.
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.
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.
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).
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.
Summary
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.
Summary 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.
Introduction
Evidence-based data suggest that under inflammatory conditions, classical monocytes are the main source of osteoclasts and might be involved in bone erosion pathophysiology. Here, we ...analyze the transcriptomic profile of classical monocytes in erosive and non-erosive rheumatoid arthritis patients in order to better understand their contribution to bone erosion.
Methods
Thirty-nine premenopausal RA patients were consecutively enrolled and divided into two groups based on the presence of bone erosions on hand joints. Classical monocytes were isolated from peripheral blood through negative selection, and RNA-seq was performed using a poly-A enrichment kit and Illumina® platform. Classical monocytes transcriptome from healthy age-matched women were also included to identify differentially expressed genes (DEGs). Therefore, gene sets analysis was performed to identify the enriched biological pathways.
Results
RNA-seq analysis resulted in the identification of 1,140 DEGs of which 89 were up-regulated and 1,051 down-regulated in RA patients with bone erosion compared to those without bone erosions. Among up-regulated genes, there was a highlighted expression of
IL18RAP
and
KLF14
related to the production of pro-inflammatory cytokines, innate and adaptive immune response. Genes related to collagen metabolism (
LARP6
) and bone formation process (
PAPPA
) were down-regulated in RA patients with erosions. Enriched pathways in patients with erosions were associated with greater activation of immune activation, and inflammation. Interestingly, pathways associated with osteoblast differentiation and regulation of Wnt signaling were less activated in RA patients with erosions.
Conclusion
These findings suggest that alterations in expression of monocyte genes related to the inflammatory process and impairment of bone formation might have an important role in the pathophysiology of bone erosions in RA patients.
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.
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.
Summary
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/m
2
) 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.
Summary
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.
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