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A prospective case-control pilot study to evaluate bone microarchitecture in children and teenagers on long-term parenteral nutrition using HR-pQCT.

ABSTRACT: Long-term parenteral nutrition (PN) may induce bone complications. Tridimensional bone imaging techniques such as high-resolution peripheral quantitative computed tomography (HR-pQCT) allow the assessment of both compartmental volumetric densities and microarchitecture. Our aim was to evaluate these parameters in children and teenagers receiving long-term PN. This cross-sectional, case-control study included children older than 9 years undergoing PN for at least 2 years. They were age-, gender- and puberty-matched with healthy controls (1:2). Evaluation included biological assessment of bone metabolism (serum calcium, phosphate, and albumin; urinary calcium and creatinine; 25-OH vitamin D, osteocalcin and PTH), dual X-ray absorptiometry (DXA) and HR-pQCT at the ultradistal tibia and radius. Results are presented as median [range]. Eleven patients (3 girls) with a median age of 16 [9-19] years were included. Bone parameters assessed by HR-pQCT at the ultradistal radius and tibia were similar in patients and controls. Parathyroid hormone (PTH) levels were higher (14 [7-115] vs 16 [12-27]) and osteocalcin levels were lower (44 [15-65] vs 65 [38-142]) in patients than in controls, although within the normal range. Conclusions: there were no differences for compartmental bone densities and microarchitecture in patients undergoing chronic PN. Further longitudinal studies are required to confirm these quite reassuring preliminary results.

SUBMITTER: Louazon T

PROVIDER: S-EPMC8080803 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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A prospective case-control pilot study to evaluate bone microarchitecture in children and teenagers on long-term parenteral nutrition using HR-pQCT.

Louazon Typhaine T Poinsot Pierre P Restier Lioara L Belmalih Abdelouahed A Loras-Duclaux Irène I Marotte Stéphanie S Heissat Sophie S Barnoud Didier D Chambrier Cécile C Confavreux Cyrille B CB Lachaux Alain A Bacchetta Justine J Peretti Noel N

Scientific reports 20210428 1

Long-term parenteral nutrition (PN) may induce bone complications. Tridimensional bone imaging techniques such as high-resolution peripheral quantitative computed tomography (HR-pQCT) allow the assessment of both compartmental volumetric densities and microarchitecture. Our aim was to evaluate these parameters in children and teenagers receiving long-term PN. This cross-sectional, case-control study included children older than 9 years undergoing PN for at least 2 years. They were age-, gender- ...[more]

PMID: 33911128

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Project description:Older adults with type 2 diabetes (T2D) tend to have normal or greater areal bone mineral density (aBMD), as measured by DXA, than those who do not have diabetes (non-T2D). Yet risk of fracture is higher in T2D, including 40% to 50% increased hip fracture risk. We used HR-pQCT to investigate structural mechanisms underlying skeletal fragility in T2D. We compared cortical and trabecular bone microarchitecture, density, bone area, and strength in T2D and non-T2D. In secondary analyses we evaluated whether associations between T2D and bone measures differed according to prior fracture, sex, and obesity. Participants included 1069 members of the Framingham Study, who attended examinations in 2005 to 2008 and underwent HR-pQCT scanning in 2012 to 2015. Mean age was 64 ± 8 years (range, 40 to 87 years), and 12% (n = 129) had T2D. After adjustment for age, sex, weight, and height, T2D had lower cortical volumetric BMD (vBMD) (p < 0.01), higher cortical porosity (p = 0.02), and smaller cross-sectional area (p = 0.04) at the tibia, but not radius. Trabecular indices were similar or more favorable in T2D than non-T2D. Associations between T2D and bone measures did not differ according to sex or obesity status (all interaction p > 0.05); however, associations did differ in those with a prior fracture and those with no history of fracture. Specifically, cortical vBMD at the tibia and cortical thickness at the radius were lower in T2D than non-T2D, but only among those individuals with a prior fracture. Cortical porosity at the radius was higher in T2D than non-T2D, but only among those who did not have a prior fracture. Findings from this large, community-based study of older adults suggest that modest deterioration in cortical bone and reductions in bone area may characterize diabetic bone disease in older adults. Evaluation of these deficits as predictors of fracture in T2D is needed to develop prevention strategies in this rapidly increasing population of older adults. © 2017 American Society for Bone and Mineral Research.

Project description:Bone changes in patients undergoing pelvic radiotherapy remain unclear. This study initially utilized high-resolution peripheral quantitative computed tomography (HR-pQCT) to assess the dynamic changes in bone microarchitecture and volumetric bone mineral density (BMD) in patients with cervical cancer before and after concurrent chemoradiotherapy. This prospective, observational study included patients with squamous carcinoma of the cervix scheduled for concurrent chemoradiotherapy. Patients underwent HR-pQCT, dual-energy X-ray absorptiometry (DXA) and laboratory tests before chemoradiotherapy, and at three and six months post-chemoradiotherapy. DXA, serving as the clinical standard for measuring BMD, was employed alongside HR-pQCT to provide complementary insights into bone micro-changes. The primary endpoint comprised changes in total (Tt.vBMD), trabecular (Tb.vBMD) and cortical (Ct.vBMD) volumetric BMD at the distal radius and tibia between pre-chemoradiotherapy and 6 months post-chemoradiotherapy. A total of 21 patients were enrolled, and one patient chose to withdraw (median age: 54.5 years). Tt.vBMD significantly decreased three months (distal radius: -1.65%, P = 0.008; distal tibia: -2.4%, P < 0.001) and six months (distal radius: -3.03%, P = 0.003; distal tibia: -2.69%, P = 0.002) post-chemoradiotherapy compared to baseline. Similarly, Tb.vBMD and Ct.vBMD demonstrated a significant downward trend post-chemoradiotherapy, with mean percent changes at three months of -0.73% and - 1.59% for the distal radius, and - 1.95% and - 1.50% for the distal tibia, respectively. The trends in BMD changes measured by DXA align with those observed using HR-pQCT. Regarding the laboratory tests, estradiol levels significantly decreased post-chemoradiotherapy, while follicle stimulating hormone and luteinizing hormone levels significantly increased. The results found that concurrent chemoradiotherapy was associated with the changes in bone volume, microstructure and BMD, especially in BMD three months post-chemoradiotherapy. Most of the bone micro-changes had not reverted by six months. This study explored the feasibility of early fracture risk identification post-chemoradiotherapy, aiding physicians in taking timely measures to improve prognosis.

Project description:Quantifying precision error for DXA, peripheral QCT (pQCT), and HR-pQCT is crucial for monitoring longitudinal changes in body composition and musculoskeletal outcomes. Agreement and associations between bone variables assessed using pQCT and second-generation HR-pQCT are unclear. This study aimed to determine the precision of, and agreement and associations between, bone variables assessed via DXA, pQCT, and second-generation HR-pQCT. Thirty older adults (mean age: 64.2 ± 8.0 yr; women: 67%) were recruited. DXA scans were performed at the total hip, lumbar spine, and whole body. Distal (4%) and proximal (30%/33%/66%) skeletal sites at the radius and tibia were scanned with pQCT and/or HR-pQCT. Root-mean-squared coefficients of variation (%CVRMS) were calculated to define precision errors, and Bland-Altman plots assessed agreement between densitometric estimates. Pearson correlations and linear regression explored relationships between bone variables at different skeletal sites and proportional bias, respectively. Precision errors ranged between 0.55% and 1.6% for DXA, 0.40% and 4.8% for pQCT, and 0.13% and 30.7% for HR-pQCT. Systematic bias was identified between pQCT- and HR-pQCT-determined radius and tibia volumetric BMD (vBMD) estimates (all p<.001). Proportional bias was not observed between vBMD measures at any skeletal site (all p>.05). pQCT- and HR-pQCT-determined total, trabecular, and cortical vBMD and estimates of bone strength at the radius and tibia were strongly correlated (all p<.05). Precision error was low for most bone variables and within the expected range for all imaging modalities. We observed significant systematic bias, but no proportional bias, between pQCT- and second-generation HR-pQCT-determined vBMD estimates at the radius and tibia. Nevertheless, measures of bone density and strength were strongly correlated at all skeletal sites. These findings suggest that although bone density and strength estimates from both imaging modalities are not interchangeable, they are strongly related and likely have similar fracture prediction capabilities.

Project description:IntroductionBone fragility is a critical issue in the treatment of elderly people with type 2 diabetes (T2D). In the Canagliflozin Cardiovascular Assessment Study, the subjects with T2D who were treated with canagliflozin showed a significant increase in fracture events compared to a placebo group as early as 12 weeks post-initiation. In addition, it has been unclear whether sodium-glucose co-transporter 2 (SGLT2) inhibitors promote bone fragility. We used high-resolution peripheral quantitative computed tomography (HR-pQCT) to prospectively evaluate the short-term effect of the SGLT2 inhibitor luseogliflozin on bone strength and microarchitecture in elderly people with T2D.MethodsThis was a single-center, randomized, open-label, active-controlled pilot trial for ≥ 60-year-old Japanese individuals with T2D without osteoporosis. A total of 22 subjects (seven women and 15 men) were randomly assigned to a Lusefi group (added luseogliflozin 2.5 mg) or a control group (added metformin 500 mg) and treated for 48 weeks. We used the second-generation HR-pQCT (Xtreme CT II®, Scanco Medical, Brüttisellen, Switzerland) before and 48 weeks after the treatment to evaluate the subjects' bone microarchitecture and estimate their bone strength.ResultsTwenty subjects (Lusefi group, n = 9; control group, n = 11) completed the study, with no fracture events. As the primary outcome, the 48-week changes in the bone strength (stiffness and failure load) estimated by micro-finite element analysis were not significantly different between the groups. As the secondary outcome, the changes in all of the cortical/trabecular microarchitectural parameters at the radius and tibia from baseline to 48 weeks were not significantly different between the groups.ConclusionsIn the pilot trial, we observed no negative effect of 48-week luseogliflozin treatment on bone microarchitecture or bone strength in elderly people with T2D.Trial registrationUMIN-CTR no. 000036202 and jRCT 071180061.

Project description:Sex differences in bone strength and fracture risk are well documented. However, we know little about bone strength accrual during growth and adaptations in bone microstructure, density, and geometry that accompany gains in bone strength. Thus, our objectives were to (1) describe growth related adaptations in bone microarchitecture, geometry, density, and strength at the distal tibia and radius in boys and girls; and (2) compare differences in adaptations in bone microarchitecture, geometry, density, and strength between boys and girls. We used HR-pQCT at the distal tibia (8% site) and radius (7% site) in 184 boys and 209 girls (9 to 20 years old at baseline). We aligned boys and girls on a common maturational landmark (age at peak height velocity [APHV]) and fit a mixed effects model to these longitudinal data. Importantly, boys showed 28% to 63% greater estimated bone strength across 12 years of longitudinal growth. Boys showed 28% to 80% more porous cortices compared with girls at both sites across all biological ages, except at the radius at 9 years post-APHV. However, cortical density was similar between boys and girls at all ages at both sites, except at 9 years post-APHV at the tibia when girls' values were 2% greater than boys'. Boys showed 13% to 48% greater cortical and total bone area across growth. Load-to-strength ratio was 26% to 27% lower in boys at all ages, indicating lower risk of distal forearm fracture compared with girls. Contrary to previous HR-pQCT studies that did not align boys and girls at the same biological age, we did not observe sex differences in Ct.BMD. Boys' superior bone size and strength compared with girls may confer them a protective advantage. However, boys' consistently more porous cortices may contribute to their higher fracture incidence during adolescence. Large prospective studies using HR-pQCT that target boys and girls who have sustained a fracture are needed to verify this. © 2016 American Society for Bone and Mineral Research.

Project description:BackgroundOlder patients with type 2 diabetes mellitus (T2DM) have an increased risk of bone fracture independent of their bone mineral density (BMD), which is explained mainly by the deteriorated bone quality in T2DM compared to that in non-diabetic adults. Sodium-glucose co-transporter (SGLT) 2 inhibitors have been studied in several trials in T2DM, and the Canagliflozin Cardiovascular Assessment Study showed an increased fracture risk related to treatment with the SGLT2 inhibitor canagliflozin, although no evidence of increased fracture risk with treatment with other SGLT2 inhibitors has been reported. The mechanism of the difference in the fracture risk between the SGLT2 inhibitors is unknown, but the differences among the SGLT2 inhibitors in the selectivity of SGLT2 against SGLT1 may affect bone metabolism, since among the SGLT2 inhibitors the selectivity of canagliflozin is lowest. We will investigate whether the SGLT2 inhibitor luseogliflozin, which has the higher SGLT2 selectivity, affects bone metabolism by using high-resolution, peripheral quantitative computed tomography (HR-pQCT) which provides direct in vivo morphometric information about the bone microarchitecture.Methods/designThis is a single-center, randomized, open-label, active-controlled, parallel pilot trial. Eligible participants are older (age ≥ 60 years) individuals with T2DM with HbA1c levels at 7.0-8.9%. A total of 24 participants will be allocated to either the luseogliflozin group (taking luseogliflozin) or the control group (taking metformin) in a 1:1 ratio to compare the groups' changes in bone microarchitecture of the radius and tibia which are analyzed by HR-pQCT before and at 48 weeks after the administration of each medication. The laboratory data associated with glycemic control and bone metabolism will be collected every 12 weeks during the study. Recruitment began in June 2019.DiscussionThe reason that we use metformin as an active control is to avoid yielding differences in glycemic control between the luseogliflozin and control groups. Besides, metformin is considered to have a neutral effect on bone. This trial should reveal the effect of luseogliflozin on bone metabolism in older patients with T2DM.Trial registrationThe study was registered with the University Hospital Medical Information Network (UMIN000036202) on 1 April 2019 and with the Japan Registry of Clinicla Trials (jRCTs071180061) on 14 March 2019.

Project description:Numerous clinical cohorts are exposed to reduced skeletal loading and associated bone loss, including surgical patients, stroke and spinal cord injury victims, and women on bed rest during pregnancy. In this context, understanding disuse-related bone loss is critical to developing interventions to prevent fractures and the associated morbidity, mortality, and cost to the health care system. The aim of this pilot study was to use high-resolution peripheral QCT (HR-pQCT) to examine changes in trabecular and cortical microstructure and biomechanics during a period of non weight bearing (WB) and during recovery following return to normal WB. Surgical patients requiring a 6-week non WB period (n=12, 34.8±7.7 yrs) were scanned at the affected and contralateral tibia prior to surgery, after the 6-week non WB period, and 6 and 13 weeks after returning to full WB. At the affected ultradistal tibia, integral vBMD (including both trabecular and cortical compartments) decreased with respect to baseline (-1.2%), trabecular number increased (+5.6%), while trabecular thickness (-5.4%), separation (-4.6%), and heterogeneity (-7.2%) decreased (all p<0.05). Six weeks after return to full WB, trabecular structure measures reverted to baseline levels. In contrast, integral vBMD continued to decrease after 6 (-2.0%, p<0.05) and 13 weeks (-2.5%, p=0.07) of full WB. At the affected distal site, the disuse period resulted in increased porosity (+16.1%, p<0.005), which remained elevated after 6 weeks (+16.8%, p<0.01) and after 13 weeks (+16.2%, p<0.05). A novel topological analysis applied to the distal tibia cortex demonstrated increased number of canals with surface topology ("slabs" +21.7%, p<0.01) and curve topology ("tubes" +15.0%, p<0.05) as well as increased number of canal junctions (+21.4%, p<0.05) following the disuse period. Porosity increased uniformly through increases in both pore size and number. Finite element analysis at the ultradistal tibia showed decreased stiffness and failure load (-2.8% and -2.4%, p<0.01) following non WB. These biomechanical predictions remained depressed following 6 and 13 weeks of full WB. Finite element analysis at the distal site followed similar trends. Our results suggest that detectable microstructural and biomechanical degradation occurs--particularly within the cortical compartment--as a result of non WB and persists following return to normal loading. A better understanding of these microstructural changes and their short- and long-term influence on biomechanics may have clinical relevance in the context of disuse-related fracture prevention.

Dataset Information

A prospective case-control pilot study to evaluate bone microarchitecture in children and teenagers on long-term parenteral nutrition using HR-pQCT.

Publications

A prospective case-control pilot study to evaluate bone microarchitecture in children and teenagers on long-term parenteral nutrition using HR-pQCT.

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