Incidence of hip and knee osteonecrosis and their associations with bone mineral density in children with acute lymphoblastic leukaemia.
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ABSTRACT:
SUBMITTER: Inaba H
PROVIDER: S-EPMC7444687 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The attention to treatment-related toxicity has increased since the survival of children with acute lymphoblastic leukemia (ALL) has improved significantly over the past few decades. Intensive ALL treatment schedules including corticosteroids and asparaginase have been shown to give rise to skeletal abnormalities such as osteonecrosis and low bone mineral density (BMD), which may lead to debilitating sequelae in survivors. Although osteonecrosis and low BMD are different entities with suggested separate pathophysiological mechanisms, recent studies indicate that osteonecrosis is associated with accelerated BMD decline. Common underlying mechanisms for osteonecrosis and BMD decline are considered, such as an enhanced sensitivity to corticosteroids in children who suffer from both osteonecrosis and low BMD. In addition, restriction of weight-bearing activities, which is generally advised in patients with osteonecrosis, could aggravate BMD decline. This induces a clinical dilemma, since bone stimulation is important to maintain BMD but alternative interventions for osteonecrosis are limited. Furthermore, this recent finding of accelerated BMD decline in children with osteonecrosis emphasizes the need to develop effective preventive measures for osteonecrosis, which may include targeting BMD decline.
| S-EPMC8265561 | biostudies-literature
Project description:Bone mineral density (BMD) is heavily relied upon to reflect structural changes affecting hip strength and fracture risk. Strong correlations between BMD and strength are needed to provide confidence that structural changes are reflected in BMD and, in turn, strength. This study investigated how variation in bone structure gives rise to variation in BMD and strength and tested whether these associations differ with external bone size. Cadaveric proximal femurs (n = 30, White women, 36-89+ years) were imaged using nanocomputed tomography (nano-CT) and loaded in a sideways fall configuration to assess bone strength and brittleness. Bone voxels within the nano-CT images were projected onto a plane to create pseudo dual-energy X-ray absorptiometry (pseudo-DXA) images consistent with a clinical DXA scan. A validation study using 19 samples confirmed pseudo-DXA measures correlated significantly with those measured from a commercially available DXA system, including bone mineral content (BMC) (R 2 = 0.95), area (R 2 = 0.58), and BMD (R 2 = 0.92). BMD-strength associations were conducted using multivariate linear regression analyses with the samples divided into narrow and wide groups by pseudo-DXA area. Nearly 80% of the variation in strength was explained by age, body weight, and pseudo-DXA BMD for the narrow subgroup. Including additional structural or density distribution information in regression models only modestly improved the correlations. In contrast, age, body weight, and pseudo-DXA BMD explained only half of the variation in strength for the wide subgroup. Including bone density distribution or structural details did not improve the correlations, but including post-yield deflection (PYD), a measure of bone material brittleness, did increase the coefficient of determination to more than 70% for the wide subgroup. This outcome suggested material level effects play an important role in the strength of wide femoral necks. Thus, the associations among structure, BMD, and strength differed with external bone size, providing evidence that structure-function relationships may be improved by judiciously sorting study cohorts into subgroups. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
| S-EPMC10020918 | biostudies-literature
Project description:ObjectiveTo address knowledge gaps regarding the relationship between bone mineral density (BMD) and incident hip or knee osteoarthritis (OA); specifically, lack of information regarding hip OA or symptomatic outcomes.MethodsUsing data (n = 1,474) from the Johnston County Osteoarthritis Project's first (1999-2004) and second (2005-2010) followup of participants ages ?45 years, we examined the association between total hip BMD and both hip and knee OA. Total hip BMD was measured using dual x-ray absorptiometry, and participants were classified into sex-specific quartiles (low, intermediate low, intermediate high, and high). Radiographic OA (ROA) was defined as development of Kellgren/Lawrence grade ?2. Symptomatic ROA (sROA) was defined as onset of both ROA and symptoms. Weibull regression modeling was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs).ResultsMedian followup time was 6.5 years (range 4.0-10.2 years). In multivariate models, and compared with participants with low BMD, those with intermediate high and high BMD were less likely to develop hip sROA (HR 0.52 [95% CI 0.31-0.86] and 0.56 [95% CI 0.31-0.86], respectively; P = 0.024 for trend); high BMD was not associated (HR 0.69 [95% CI 0.45-1.06]) with risk of hip ROA. Compared with participants with low BMD, those with intermediate low and intermediate high total hip BMD were more likely to develop knee sROA (HR 2.15 [95% CI 1.40-3.30] and 1.65 [95% CI 1.02-2.67], respectively; P = 0.325 for trend); similar associations were seen with knee ROA.ConclusionOur findings suggest that higher BMD may reduce the risk of hip sROA, while intermediate levels may increase the risk of both knee sROA and ROA.
| S-EPMC5529272 | biostudies-literature
Project description:BackgroundChildren with acute lymphoblastic leukemia (ALL) can develop reduced bone mineral density (BMD). However, data from patients who received treatment on a frontline regimen without cranial irradiation are limited, and no genome-wide analysis has been reported.MethodsLumbar BMD was evaluated by quantitative computed tomography at diagnosis, after 120 weeks of continuation therapy, and after 2 years off therapy in pediatric patients with ALL (ages 2-18 years at diagnosis) who were treated on the St. Jude Total XV Protocol. Clinical, pharmacokinetic, and genetic risk factors associated with decreased BMD Z-scores were evaluated.ResultsThe median BMD Z-score in 363 patients was 0.06 at diagnosis, declined to -1.08 at week 120, but partly recovered to -0.72 after 2 years off therapy; BMD in patients with low BMD Z-scores at diagnosis remained low after therapy. Older age (≥10 years vs 2-9.9 years at diagnosis; P < .001), a higher BMD Z-score at diagnosis (P = .001), and a greater area under the plasma drug concentration-time curve for dexamethasone in weeks 7 and 8 of continuation therapy (P = .001) were associated with a greater decrease in BMD Z-score from diagnosis to week 120. Single-nucleotide polymorphisms in 2 genes important in osteogenesis and bone mineralization (COL11A1 [reference single-nucleotide polymorphism rs2622849]; P = 2.39 × 10-7 ] and NELL1 [rs11025915]; P = 4.07 × 10-6 ]) were associated with a decreased BMD Z-score. NELL1 (P = .003) also was associated with a greater dexamethasone area under the plasma drug concentration-time curve.ConclusionsBMD Z-scores decreased during therapy, especially in patients who had clinical, pharmacokinetic, and genetic risk factors. Early recognition of BMD changes and strategies to optimize bone health are essential. Cancer 2018;124:1025-35. © 2017 American Cancer Society.
| S-EPMC5821586 | biostudies-literature
Project description:BackgroundMuscle weakness is a key factor in the increase risk of falls and might also play a significant role in the increase of risk of hip fracture. Computed tomography-measured muscle size and muscle density are well-established imaging biomarkers used in studies of physical function, frailty or cancer, but limited to hip fracture. In particular, it is warranted to have a better understanding of the performance of muscle size and density in the discrimination of acute hip fractures. We also aim to determine age-related differences of muscle size and density in healthy controls and hip fracture patients.MethodsFour hundred thirty-eight low-energy acute hip fracture cases and 316 healthy controls from the China Action on Spine and Hip Status study were included in the study. Muscle cross-sectional area and density were measured for the gluteus maximus and gluteus medius and minimus. Areal bone mineral density (aBMD) of the femoral neck and total hip was measured. Using propensity score matching, we generated three samples with cases and controls matched for age, body mass index, and gender: femoral neck fracture (FNF), intertrochanteric fracture (ITF), and any hip fracture vs. controls, respectively.ResultsHandgrip strength, gluteus muscle area and density, and bone parameters of the matched hip fracture groups were lower than those of the correspondence control groups, respectively (P < 0.05). The univariate analysis showed that associations of aBMD with FNF and with ITF were significantly weaker than associations between fracture and muscle parameters. Gluteus medius and minimus muscle density showed the highest areas under the curve (AUC) with FNF (0.88, 95% confidence interval, 0.85-0.92) and trochanteric fracture (0.95, 95% confidence interval, 0.92-0.97). The model including all muscle and bone parameters provided the highest AUC (FNF: AUC 0.912; ITF: AUC 0.958), and AUC results of another selected model without muscle density showed that association with fracture significantly dropped (FNF: AUC 0.755; ITF: AUC 0.858). Separate results for the two age groups younger and older than 70 years showed no age-related significant differences in discriminate models.ConclusionsMuscle density performs better than aBMD from hip computed tomography X-ray absorptiometry and muscle size in discrimination of hip fracture. Combination of aBMD and muscle density provided the best discrimination. The integration of muscle assessments may trigger a paradigm shift in hip fracture prediction. Gluteus muscle density should also be evaluated as treatment outcome.
| S-EPMC7749550 | biostudies-literature
Project description:In the absence of clinically recognized cardiovascular disease, increased carotid artery intimal medial thickness was associated with higher hip fracture risk in older adults, despite its association with higher bone mineral density (BMD). Low ankle brachial index and aortic wall thickness were not associated with fracture risk or BMD. INTRODUCTION:Clinically recognized cardiovascular disease (CVD) is associated with osteoporosis and hip fracture risk, but the relationship of subclinical atherosclerosis to bone health is not certain. METHODS:We followed 3385 participants from the Cardiovascular Health Study (mean age 74.7 ± 5.3 years) with a median time to fracture of 12.1 years who underwent baseline carotid artery and aortic wall ultrasound scanning and ankle brachial blood pressure index (ABI) determinations. A subset underwent bone mineral density (BMD) testing. RESULTS:There were 494 hip fractures during follow-up. Among persons without clinical CVD, an average standard-deviation increase in a composite score of maximal common and internal carotid artery intimal medial thickness (cIMT) was associated with increased risk of hip fracture [(HR 1.18 [1.04, 1.35]), even though cIMT was positively associated with BMD. Neither aortic wall thickness nor ABI were associated with hip fracture risk or BMD. Among participants with clinical CVD, cIMT and aortic wall thickness, but not ABI, were associated with increased hip fracture risk. CONCLUSION:Subclinical cIMT is associated with an increased risk of hip fractures despite being associated with increased BMD. This finding suggests that vascular health, even in its early stages, is linked to bone health, by pathways other than BMD.
| S-EPMC6487649 | biostudies-literature
Project description:ObjectiveTo assess the relationship between chronic obstructive pulmonary disease (COPD) severity and bone mineral density (BMD) in the whole body and different body areas.MethodsThis retrospective, cross-sectional study included patients with COPD. Demographic and lung function data, COPD severity scales, BMD, and T scores were collected. Patients were grouped by high (≥-1) and low (<-1) T scores, and stratified by body mass index, airway obstruction, dyspnoea, and exercise capacity (BODE) index. The relationship between whole-body BMD and BODE was evaluated by Kendall's tau-b correlation coefficient. Risk factors associated with COPD severity were identified by univariate analyses. BMD as an independent predictor of severe COPD (BODE ≥5) was verified by multivariate logistic regression. BMD values in different body areas for predicting severe COPD were assessed by receiver operating characteristic curves.ResultsOf 88 patients with COPD, lung-function indicators and COPD severity were significantly different between those with high and low T scores. Whole-body BMD was inversely related to COPD severity scales, including BODE. Multivariate logistic regression revealed that BMD was independently associated with COPD severity. The area under the curve for pelvic BMD in predicting severe COPD was 0.728.ConclusionBMD may be a novel marker in predicting COPD severity, and pelvic BMD may have the strongest relative predictive power.
| S-EPMC9127852 | biostudies-literature
Project description:Factors related to mortality after osteoporotic hip fracture (HF) have been investigated intensively, except for proximal femoral bone mineral density (BMD), which is also the primary cause of osteoporosis. In this study, we aimed to investigate the association of hip BMD with mortality risk after HF. Four hundred and eleven elderly patients with HF in Beijing, China, were included and prospectively followed up with a median time of 3 years. At baseline, quantitative CT technique (QCT) was used to measure areal BMD (aBMD) of the unaffected hip. Areal BMDs of the total hip (TH), femoral neck (FN), trochanter (TR), and intertrochanter were analyzed with postoperative mortality as the primary outcome. A total of 394 patients (78.59 ± 7.59 years, 75.4% female) were included in our final analysis, with 86 (82.23 ± 7.00 years, 81.4% female) dead. All hip bone densities demonstrated a significant association with mortality risks in the unadjusted model, but only TR aBMD remained significantly correlated after adjusting for all covariates. Compared to the lower TR aBMD group, the higher TR aBMD group yielded significantly lower death risks (HR 0.21 95% CI 0.05-0.9, P = 0.036). Higher survival probabilities were observed for higher TH and TR aBMD in survival analysis (P < 0.001). Hip BMD, especially TR BMD assessed by QCT, is an independent risk factor for postoperative mortality following HF. QCT may present a promising avenue for opportunistic analysis in immobilized patients, providing valuable information for early detection and personalized interventions to enhance patient outcomes.
| S-EPMC10449952 | biostudies-literature
Project description:Bone mineral density (BMD) and lean body mass (LBM) not only have a considerable heritability each, but also are genetically correlated. However, common genetic determinants shared by both traits are largely unknown. In the present study, we performed a bivariate genome-wide association study (GWAS) meta-analysis of hip BMD and trunk lean mass (TLM) in 11,335 subjects from 6 samples, and performed replication in estimated heel BMD and TLM in 215,234 UK Biobank (UKB) participants. We identified 2 loci that nearly attained the genome-wide significance (GWS, p?<?5.0?×?10-8) level in the discovery GWAS meta-analysis and that were successfully replicated in the UKB sample: 11p15.2 (lead SNP rs12800228, discovery p?=?2.88?×?10-7, replication p?=?1.95?×?10-4) and 18q21.32 (rs489693, discovery p?=?1.67?×?10-7, replication p?=?1.17?×?10-3). The above 2 pleiotropic loci may play a pleiotropic role for hip BMD and TLM development. So our findings provide useful insights that further enhance our understanding of genetic interplay between BMD and LBM.
| S-EPMC7880826 | biostudies-literature
Project description:Studying dietary patterns is often more informative than individual nutrients or foods. We found that a Prudent dietary pattern (rich in vegetables and fish) was associated with reduced loss of total hip BMD in older men. A Prudent dietary pattern may be a potential lifestyle strategy for minimizing bone loss. INTRODUCTION:This study aimed to identify baseline dietary patterns using factor analysis in a cohort of older men and to evaluate whether the dietary patterns were associated with bone mineral density change (%ΔBMD) at the total hip and femoral neck over time. METHODS:Participants (n = 4379; mean age 72.9 ± 5.5 years) were from the Osteoporotic Fractures in Men (MrOS) prospective cohort study and had dietary data collected at baseline (March 2000-April 2002) and BMD measured at baseline and Visit 2 (March 2005-May 2006). Dietary intake was assessed with a brief Block food frequency questionnaire (FFQ); factor analysis was used to derive dietary patterns. BMD was measured by dual-energy x-ray absorptiometry (DXA); %ΔBMD was calculated from baseline to Visit 2. We used generalized linear regression to estimate least square (LS) means of %ΔBMD in quartiles of the dietary pattern scores adjusted for potential confounding factors. RESULTS:Two major dietary patterns were derived: Prudent (abundant in vegetables, salad, and non-fried fish) and Western (rich in hamburger, fries, processed meats, cheese, and sweets/desserts). There was an inverse association between adherence to the Prudent pattern and total hip %ΔBMD (p-trend = 0.028 after adjusting for age and clinical site; p-trend = 0.033 after further adjustment for smoking, calcium supplement use, diabetes, hypertension, and total energy intake). No other consistent associations between dietary patterns and %ΔBMD were observed. CONCLUSIONS:Greater adherence to a Prudent dietary pattern may attenuate total hip BMD loss (%ΔBMD) in older men.
| S-EPMC6842326 | biostudies-literature