Bone mineral density, vitamin D, and nutritional status of children submitted to hematopoietic stem cell transplantation

doi:10.1016/j.nut.2013.10.014

Nutrition

Volume 30, Issue 6, June 2014, Pages 654-659

https://doi.org/10.1016/j.nut.2013.10.014 Get rights and content

Abstract

Objective

The aim of the study was to evaluate the effect of allogeneic hematopoietic stem cell transplantation (HSCT) on bone mineral density (BMD), serum vitamin D levels, and nutritional status of 50 patients between ages 4 and 20 y.

Methods

We conducted pre-HSCT and 6-mo post-HSCT evaluations. We measured BMD at the lumbar spine (LS) and total body (TB) by dual energy x-ray absorptiometry (DXA); body composition by bioimpedance analysis, and dietary intakes of calcium and vitamin D using the 24-h recall and semiquantitative food frequency questionnaire methods.

Results

We observed a significant reduction in BMD 6 mo post-HSCT. Nearly half (48%) of patients had reductions at the LS (average −9.6% ± 6.0%), and patients who developed graft-versus-host disease (GVHD) had the greatest reductions (−5.6% versus 1.2%, P < 0.01). We also found reductions in serum levels of 25-hydroxyvitamin D (25-OHD), from 25.6 ± 10.9 ng/dL to 20.4 ± 11.4 ng/dL (P < 0.05), and in body weight. Corticosteroid treatment duration, severity of chronic GVHD, serum 25-OHD levels, and family history of osteoporosis were all risk factors associated with variations in BMD at the LS.

Conclusion

HSCT in children and adolescents negatively effects their BMD, nutritional status, and vitamin D levels. We suggest that early routine assessment be done to permit prevention and treatment.

Introduction

The advancement of scientific knowledge has led to increases in the number of hematopoietic stem cell transplants (HSCTs), as well as in the disease-free survival rate and, consequently, a larger number of patients with HSCT late complications. Endocrine organs are sensitive to the cytotoxic drugs and radiation therapy commonly used during the pre-HSCT conditioning stage, thus, low bone mass, impaired growth, gonadal and thyroid dysfunction, metabolic syndrome, and changes in nutrient metabolism can develop after transplantation [1], [2]. Additionally, there is the negative influence of drugs used post-HSCT because cyclosporine and corticosteroids cause muscular atrophy and reductions in bone formation [3], [4]. Other factors also can be involved in bone mass reduction post-HSCT, including reduced physical activity and lean body mass, low sun exposure, and vitamin D deficiency, which is a required vitamin in the development and maintenance of bone mass [5].

Reductions in bone mineral density (BMD) are observed both at early (few months) and late stages (up to 10 y) post-HSCT [6], [7], [8]. Bone metabolism changes have been more widely studied in adults, but fewer studies have been done with children and adolescents, showing a prevalence of osteopenia and osteoporosis post-HSCT between 24% and 57% [7], [9], [10], [11], [12], [13], [14], [15]. A prospective study assessing BMD pre- and post-HSCT in young patients found 5% reduction in BMD 6 mo post-HSCT [12].

Children and adolescents are growing and developing their bone mass; by age 20, 95% of bone mineral mass has been acquired [16]. Peak bone mass reached at this stage is inversely related to fracture risk in adult life, which is associated with high morbidity and mortality [7], [17]. Additionally, children submitted to HSCT have nutrient deficiencies leading to impaired development, cognitive function, and delayed linear growth. Nutrition deficiencies are also associated with early mortality post-HSCT [18], [19]. Our hypothesis is that HSCT and its complications lead to reduced levels of 25-hydroxyvitamin D (25-OHD), changes in BMD and significant loss of weight and lean mass.

The objective of this study was to evaluate the effect of allogeneic HSCT on BMD, serum levels of vitamin D, and the nutritional status of children and adolescents.

Section snippets

Study population

All patients between ages 4 and 20 y receiving allogeneic HSCT between August 2006 and September 2008 at the Bone Marrow Transplant Unit at Hospital de Clínicas da Universidade Federal do Paraná were consecutively included in the study. We excluded those patients with osteometabolic bone disorders before HSCT and those with any impossibility to have a bone densitometry exam performed.

Out of the 80 patients selected, 68 were included. Of those, 17 (25%) died before the sixth-month post-HSCT, and

Bone mineral density

In the pre-HSCT stage, 7 patients (14%) reported a previous history of fracture, and 13 (26%) reported a family history of osteoporosis.

In the initial assessment, patients and controls had similar BMD values (Table 2); however, we observed that 7 patients (14%), but no controls, had a low BMD for their age (P = 0.05).

Six months post-HSCT, there was a significant reduction in BMD at the LS and TB (Table 2 and Fig. 1), with 24 patients (48%) having reductions at the LS (average −9.6% ± 6.0%). Age

Discussion

This study was conducted by the need to know the changes in BMD, in 25-OHD levels and nutritional status resulting from HSCT in children and adolescents, as, to our knowledge, these data were not yet known in the Brazilian population. Although the study was conducted in a single Brazilian public hospital, patients came from different regions of the country.

Among adults, the prevalence of osteopenia and osteoporosis pre-HSCT ranged from 19% to 39% [29], [30], [31], [32], [33]. A previous study

Conclusion

We found that HSCT in children leads to negative effects on BMD, nutritional status, and serum vitamin D levels, with unknown consequences for their final development. All children receiving HSCT should undergo routine assessments of BMD, vitamin D levels, and body composition, so that negative changes can be detected and treated early.

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Cited by (26)

Ultra-High Dose Vitamin D in Pediatric Hematopoietic Stem Cell Transplantation: A Nonrandomized Controlled Trial
2021, Transplantation and Cellular Therapy
Citation Excerpt :
Pediatric patients experience a significant decrease in their bone mineral density the first 6 months after hematopoietic stem cell transplantation (HSCT) [1,2].
Vitamin D is essential for bone health and has immunomodulatory properties. Most pediatric patients are vitamin D insufficient (<30 ng/mL) before hematopoietic stem cell transplantation (HSCT). Standard supplementation strategies fail to achieve vitamin D sufficiency in the acute post-transplantation period, and there are scarce data to support optimal vitamin D supplementation in this patient population. This study aimed to evaluate whether a single, oral, weight-based ultra-high dose of vitamin D (Stoss dosing) was more effective than standard supplementation to achieve pre-HSCT vitamin D sufficiency and reduce the incidence of HSCT-related complications (acute graft-versus-host disease, veno-occlusive disease, and/or transplant-associated thrombotic microangiopathy) that are associated with immune-mediated endothelial damage. Secondary endpoints examined the immunomodulatory properties of vitamin D. We conducted a nonrandomized controlled clinical trial of Stoss-dosed vitamin D in pediatric patients receiving HSCT. The study prospectively enrolled 33 patients, 29 of whom successfully received Stoss-dosed vitamin D and were compared to 136 patients in a historical control. Patient characteristics were compared using Fisher's exact test or t-test. The one-sided Fisher's exact test was used for cohort comparison of the primary endpoints. Logistic regression was used to examine the association between patient-specific factors and total 25-hydroxy vitamin D (25-OHD) levels and the compiled HSCT complications. In the Stoss cohort, 97% (n = 28/29) of patients achieved pre-HSCT vitamin D sufficiency compared to 67% (n = 10/15) of patients in the historical control who were on standard supplementation at the time the total 25-OHD level was assessed (P = .013). The mean total 25-OHD level in the Stoss cohort was significantly higher than patients in the historical control who received standard supplementation (72.2 ng/mL versus 35.8 ng/mL, P < .001). Nine patients in the Stoss cohort maintained vitamin D sufficiency throughout the first 100 days after HSCT, and the remaining 19 patients maintained sufficiency for a median of 63 days (range 6-105 days) from the Stoss dose. Patients receiving Stoss-dosed vitamin D developed a lower combined incidence of HSCT-related complications than the historical control (25% [n = 7/28] versus 42% [n = 57/136], P = .055). After Stoss dosing, immunophenotyping studies found a significant decrease in subsets of CD8+ T cells and mononuclear cells (P = .040 and.013, respectively), and, in a subset of cells, larger decreases in phosphoprotein expression were seen with greater increases in total 25-OHD levels. Inflammatory cytokines did not change significantly after Stoss dosing. Stoss dosing is therefore a safe and effective approach to maintain vitamin D sufficiency in the immediate post-HSCT period and may be associated with decreased HSCT-related complications. Randomized studies are warranted to further investigate the efficacy of Stoss-dosed vitamin D to improve bone health and reduce complications in pediatric patients receiving HSCT.
Nutritional challenges in children with primary immunodeficiencies undergoing hematopoietic stem cell transplant
2020, Clinical Nutrition
Nutritional profile and management of patients with primary immunodeficiencies (PID) undergoing hematopoietic stem cell transplant (HSCT) has not been described in the literature. We aim to report the nutritional challenges and practices peculiar to this population before and after HSCT and suggest clinical pathways for their management.
We conducted a single-centre retrospective study. Inclusion criteria were children aged less than 20 years with a diagnosis of PID who have undergone HSCT at the Royal Children's Hospital Melbourne since April 2014 with a minimal follow-up of 1 year. Nutritional parameters were collected in the pre-transplant period, at conditioning, and at 1, 3, 6 and 12 months post-HSCT. Descriptive analysis were used.
Between April 2014 and December 2018, 27 children received 31 HSCT. Before transplant, 33% had a weight and/or height ≤ −2 standard deviations (SD). Forty percent required nutritional support before transplant: 33% had enteral nutrition (EN) while 7% required long-term parenteral nutrition (PN) due to intestinal failure. After transplant, although most children were started on EN, 82% required PN with a mean duration of 67 days. Mean time to full oral diet was 154 days. Pre-transplant mean weight and height were −0.57 SD and −0.88 SD respectively. After a decrease in anthropometric parameters the first 3 months post-transplant, progressive catch up was noticeable for weight (−0.27 SD) with no catch up for height at 1 year (−0.93 SD).
Our work highlights the nutritional challenges and specificities of children with PID in the peri-transplant period. An approach to nutrition assessment and management in the pre- and post-transplant period is proposed.
Vitamin D deficiency and graft-versus-host disease in hematopoietic stem cell transplant population
2019, Hematology/ Oncology and Stem Cell Therapy
Vitamins are the organic compounds that have long been known to play a significant role in our body by functioning as hormones and antioxidants. Vitamin D, a fat-soluble vitamin, is the main regulator of calcium hemostasis in our body. At the same time, it is also known to show its potential effects on the immune system by modulating the differentiation, activation, and proliferation of T and B lymphocytes. The immunomodulatory properties of vitamin D are also known to have a crucial role in the prevention and treatment of graft-versus-host disease. Patients undergoing hematopoietic stem cell transplantation are particularly at risk of vitamin D deficiency. This review article expands our understanding of vitamin D, its immunomodulatory effects, and its role in prevention and treatment of graft-versus-host disease.
Changes in trabecular bone score and bone mineral density following allogeneic hematopoietic stem cell transplantation
2019, Bone
Citation Excerpt :
Dual-energy X-ray absorptiometry (DXA)-based studies have demonstrated substantial bone deficits within the first 6 to 12 months after alloHSCT at all skeletal sites. Risk factors for bone loss after alloHSCT include old age, prolonged immunosuppression [2], hypogonadism [3], low body weight [4], total body irradiation (TBI) [5], and glucocorticoid therapy [4,6,7]. The rapid impairment of bone formation and the increase in bone resorption might play a role in post-HSCT bone loss.
It has been demonstrated that bone mineral density (BMD) loss is substantial within the first 12 months after allogeneic hematopoietic stem cell transplantation (alloHSCT). Declines in BMD showed a disproportionate cortical bone loss even though trabecular bone is metabolically more active than cortical bone. This finding suggests a unique mechanism. However, the structural bone deficits after alloHSCT have not been well characterized. The trabecular bone score (TBS) has emerged as a method to assess bone microarchitecture. The aim of this study was to evaluate the changes in BMD and TBS in patients who received alloHSCT with follow-up of two years.
All patients 18 years and older who received alloHSCT between 2009 and 2015 at Seoul St. Mary's Hospital, Korea were included. They were segregated into a first group (A, n = 24) that was evaluated for BMD at the time of alloHSCT and 12 months posttransplant and a second group (B, n = 44) that was evaluated for BMD at 12 and 24 months following alloHSCT.
Subjects in group A experienced a decrease in BMD at the femoral neck and total hip between the time of transplantation and 12 months posttransplantation: 0.056 ± 0.057 (5.48%) and 0.072 ± 0.063 (6.84%), respectively. Subjects in group B experienced an increase in BMD at the lumbar spine and total hip between 12 and 24 months post-alloHSCT: 0.047 ± 0.064 (4.90%) and 0.017 ± 0.045 (2.16%), respectively. In group A, TBS at 12 months post-alloHSCT decreased 0.028 ± 0.067 (1.92%) from the baseline (p = 0.086). In group B, TBS at 24 months post-alloHSCT increased 0.010 ± 0.049 (0.78%) from the 12 months post-alloHSCT evaluation (p = 0.149). TBS change was positively associated with BMD changes at all measured sites. The cumulative dose of glucocorticoid therapy was associated with loss of BMD at all measured sites and TBS. In addition, the dose of total body irradiation (TBI) was negatively associated with TBS.
In summary, this study delineated longitudinal microarchitectural changes in bone structure occurring in the context of alloHSCT. TBS change per 12 months was insignificant during the two years following alloHSCT. Therefore, our data represented disproportionate cortical bone loss in the context of the microarchitecture.
Body composition, dietary intake and physical activity of young survivors of childhood cancer
2019, Clinical Nutrition
Citation Excerpt :
In this study the only clinical variable that was associated with body composition, was that having received a BMT was related to low BCMI and FFMI. The conditioning regimens, mucositis and gut graft-versus-host disease can result in poor functional integrity of the gastrointestinal tract during BMT, which affects nutritional status in the short term [44,45]. Our study demonstrates that having had a BMT continues to influence nutritional status in the long term and that consequently nutritional support should be an important consideration before, during and after BMT.
To describe the body composition, dietary intake and physical activity and of paediatric, adolescent and young adult childhood cancer survivors (CCS) and examine the factors that impact body composition after treatment.
This prospective cross-sectional study involved 74 subjects who were at least three years post treatment. Measurements included anthropometry, whole body potassium counting, air displacement plethysmography, and three day physical activity and diet diaries.
The CCS had significantly reduced body cell mass index Z-scores compared to controls (p = 0.0001), with 59% considered undernourished. The CCS had a significantly higher percent fat (p = 0.002) than the controls, with 27% classified as obese. The intake of 60% of CCS met estimated energy requirements, but the CCS consumed high amount of energy from fat and low amount of energy from carbohydrates. A high percentage of CCS did not meet their dietary requirements for calcium (61%), magnesium (46%), folate (38%) and iodine (38%). The CCS group had a light active lifestyle with 64% spending more than 2 h daily on screen time. Receiving a bone marrow transplant (r = −0.27; p = 0.02) and physical activity level (r = 0.49; p = 0.0001) were significantly correlated with body cell mass index.
This study demonstrates that increased fat mass and decreased body cell mass is a concern for CCS and that CCS have poor health behaviours including light active lifestyles, excessive screentime, high fat intake, and poor intake of essential nutrients. This study has highlighted that CCS are at risk of both obesity and undernutrition and that increasing body cell mass as well as decreasing fat mass should be a focus of energy balance interventions in survivorship. There is a need for parents and children undergoing treatment for cancer to be educated about diet quality and importance of daily physical activity to ensure healthy habits are established and maintained into survivorship.
Importance of Nutrition in the Treatment of Leukemia in Children and Adolescents
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Citation Excerpt :
A form of nutritional morbidity of particular concern in children and adolescents who undergo HSCT is loss of bone mineral that risks fractures, which may be asymptomatic (73). Reduced bone mineral density is a common occurrence that has been described in 50% of children by 6 months after HSCT, correlating with a significant drop in serum levels of the active metabolite 1, 25-dihydroxy vitamin D (72). Others have reported similar findings despite vitamin D supplementation (74).
Malnutrition has been identified as a prognostic factor in children and adolescents with leukemia.
A review of the data available on this topic has been carried out.
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: DJC, VAMF, and VCZB were responsible for the conception and design of the study. DJC and VCZB generated, collected, assembled, analyzed, and interpreted the data. LB, CMSB, CMAK, RP, and VCZB drafted or revised the manuscript and approved of the final version of the manuscript.

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Applied nutritional investigationBone mineral density, vitamin D, and nutritional status of children submitted to hematopoietic stem cell transplantation

Abstract

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Study population

Bone mineral density

Discussion

Conclusion

Biol Blood Marrow Transplant

Biol Blood Marrow Transplant

Biol Blood Marrow Transplant

Am J Clin Nutr

J Clin Densitom

Bone

Biol Blood Marrow Transplant

Blood

Biol Blood Marrow Transplant

Endocrine dysfunction and parameters of the metabolic syndrome after bone marrow transplantation during childhood and adolescence

Bone Marrow Transplant

Endocrinological late complications after hematopoietic SCT in children

Bone Marrow Transplant

Longitudinal follow-up of body composition in hematopoietic stem cell transplant patients

Bone Marrow Transplant

Post-transplantation osteoporosis

Arq Bras Endocrinol Metab

Variations in 1 alpha,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 serum levels during allogeneic bone marrow transplantation [letter]

Bone Marrow Transplant

Bone mineral density and osteonecrosis in survivors of childhood allogenic bone marrow transplantation

Bone Marrow Transplant

Screening, prevention and management of osteoporosis and bone loss in adult and pediatric hematopoietic cell transplant recipients

Bone Marrow Transplant

Bone mineral density in patients undergoing bone marrow transplantation for myeloid malignances

Bone Marrow Transplant

Bone mass after allogenic BMT for childhood leukemia or lymphoma

Bone Marrow Transplant

Bone mineral density in pediatric transplant recipients

Transplantation

Prospective study of changes in bone mineral density and turnover in children after hematopoetic cell transplantation

J Clin Endocrinol Metab

Applied nutritional investigation
Bone mineral density, vitamin D, and nutritional status of children submitted to hematopoietic stem cell transplantation