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 | 2020 May
REPOSITORIES: biostudies-literature
Publications
Incidence of hip and knee osteonecrosis and their associations with bone mineral density in children with acute lymphoblastic leukaemia.
Inaba Hiroto H Cao Xueyuan X Chang Jennifer Y JY Karol Seth E SE Panetta John C JC Ness Kirsten K KK Cheng Cheng C Pui Ching-Hon CH Relling Mary V MV Kaste Sue C SC
British journal of haematology 20200324 4
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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:Osteonecrosis (ON) is a well-known sequela of paediatric acute lymphoblastic leukaemia (ALL) treatment. Incidence differs substantially among studies and the clinical significance of radiological findings is not fully established. We analysed 256 consecutive patients with ALL treated in our Institution between October 2010 and December 2016. Within the cohort, 41 developed ON, with a mean 5-year cumulative incidence of 18.5 (standard error, SE, 5.7)% overall. The mean (SE) 5-year cumulative incidence of ON was 12.7 (2.1)% after censoring upon stem cell transplantation (SCT) and/or relapse. Patients aged ≥10 years and patients allocated to the high-risk stratum had a 10-fold and fivefold higher risk of ON respectively. The risk of ON was more than double in relapsed patients, whereas no significant impact of gender, immunophenotype and SCT was demonstrated. Multiple lesions (median four joints involved per patient) were detected by magnetic resonance imaging in all but one patient, with the knee being the most affected joint. Lesions affecting convex joint surfaces experienced the worst evolution, whereas most lesions on diaphyses and concave surfaces remained radiologically stable or disappeared during follow-up. ON has a high prevalence in paediatric ALL, presenting with multiple lesions. Lesions involving convex surfaces were at higher risk of radiological deterioration.
| S-EPMC9323502 | 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:BackgroundOsteonecrosis (ON) is a debilitating orthopedic condition characterized by bone cell death due to impaired blood supply, leading to structural changes and disability. Osteoporosis (OP), a systemic skeletal disease, results in reduced bone density and quality, making bones fragile and prone to fractures. Although distinct, OP and ON share several risk factors such as corticosteroid use and smoking. This study aims to investigate the causal relationships between OP, bone mineral density (BMD), and ON using a bidirectional two-sample Mendelian randomization (MR) approach.MethodsThis study utilized genome-wide association study (GWAS) data for OP from the FinnGen database, and BMD data for the lumbar spine and femoral neck from the Genetic Factors for Osteoporosis (GEFOS) consortium. ON data were also obtained from the FinnGen database. All participants were of European descent. Genetic instruments were selected based on genome-wide significance, linkage disequilibrium, and strength (F-statistic). Bidirectional MR analysis was performed using inverse-variance weighted (IVW), MR-Egger regression, and weighted median methods to assess causality. Sensitivity analyses, including Cochran's Q test and MR-PRESSO, were conducted to evaluate heterogeneity and pleiotropy.ResultsMR analysis demonstrated a positive causal effect of OP on ON using the IVW method, with an odds ratio (OR) of 1.223 (95% CI: 1.026-1.459, P = 0.025). The weighted median method also confirmed this result with an OR (95% CI) 1.290 (1.021-1.630), P = 0.033. No significant causal effects were found between BMD (lumbar spine and femoral neck) and ON. Furthermore, ON did not exhibit a causal effect on OP or BMD. Sensitivity analyses confirmed the robustness of the results, showing no evidence of heterogeneity or pleiotropy.ConclusionThis study provides evidence of a unidirectional causal relationship between OP and ON, suggesting that individuals with a genetic predisposition to OP have an increased risk of developing ON. These findings highlight the importance of early OP detection and management to potentially reduce ON incidence. The lack of a significant causal relationship between BMD and ON indicates that factors other than bone density, such as vascular health, may play a crucial role in ON development. Future research should explore these mechanisms further to inform clinical interventions.
| S-EPMC11863788 | biostudies-literature