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I M A A van Roessel Department of Pediatric Neuro-oncology, Princess Máxima Center, Heidelberglaan, CS Utrecht, The Netherlands
Department of Pediatric Endocrinology, Wilhelmina Children’s Hospital, University Medical Center, Lundlaan, EA Utrecht, The Netherlands

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J E Gorter Department of Pediatric Neuro-oncology, Princess Máxima Center, Heidelberglaan, CS Utrecht, The Netherlands
Department of Pediatric Endocrinology, Wilhelmina Children’s Hospital, University Medical Center, Lundlaan, EA Utrecht, The Netherlands

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B Bakker Department of Pediatric Neuro-oncology, Princess Máxima Center, Heidelberglaan, CS Utrecht, The Netherlands
Department of Pediatric Endocrinology, Wilhelmina Children’s Hospital, University Medical Center, Lundlaan, EA Utrecht, The Netherlands

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M M van den Heuvel-Eibrink Princess Máxima Center, Heidelberglaan, CS Utrecht, The Netherlands
Wilhelmina Children’s Hospital, University Medical Center, Lundlaan, EA Utrecht, The Netherlands

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M H Lequin Department of Radiology, Princess Máxima Center, Heidelberglaan, CS Utrecht, The Netherlands
Department of Radiology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands

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J van der Lugt Department of Pediatric Neuro-oncology, Princess Máxima Center, Heidelberglaan, CS Utrecht, The Netherlands

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L Meijer Department of Pediatric Neuro-oncology, Princess Máxima Center, Heidelberglaan, CS Utrecht, The Netherlands

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A Y N Schouten-van Meeteren Department of Pediatric Neuro-oncology, Princess Máxima Center, Heidelberglaan, CS Utrecht, The Netherlands

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H M van Santen Department of Pediatric Neuro-oncology, Princess Máxima Center, Heidelberglaan, CS Utrecht, The Netherlands
Department of Pediatric Endocrinology, Wilhelmina Children’s Hospital, University Medical Center, Lundlaan, EA Utrecht, The Netherlands

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Objective

Children with a supratentorial midline low-grade glioma (LGG) may be at risk for impaired bone health due to hypothalamic-pituitary dysfunction, obesity, exposure to multiple treatment modalities, and/or decreased mobility. The presence of impaired bone health and/or its severity in this population has been understudied. We aimed to identify the prevalence and risk factors for bone problems in children with supratentorial midline LGG.

Materials and methods

A retrospective study was performed in children with supratentorial midline (suprasellar or thalamic) LGG between 1 January 2003 and 1 January 2022, visiting the Princess Máxima Center for Pediatric Oncology. Impaired bone health was defined as the presence of vertebral fractures and/or very low bone mineral density (BMD).

Results

In total, 161 children were included, with a median age at tumor diagnosis of 4.7 years (range: 0.1–17.9) and a median follow-up of 6.1 years (range: 0.1–19.9). Five patients (3.1%) had vertebral fractures. In 99 patients, BMD was assessed either by Dual Energy X-ray Absorptiometry (n = 12) or Bone Health Index (n = 95); 34 patients (34.3%) had a low BMD (≤ −2.0). Impaired visual capacity was associated with bone problems in multivariable analysis (OR: 6.63, 95% CI: 1.83–24.00, P = 0.004).

Conclusion

In this retrospective evaluation, decreased BMD was prevalent in 34.3% of children with supratentorial midline LGG. For the risk of developing bone problems, visual capacity seems highly relevant. Surveillance of bone health must be an aspect of awareness in the care and follow-up of children with a supratentorial midline LGG.

Significance statement

Patients with supratentorial midline LGG may encounter various risk factors for impaired bone health. Bone problems in survivors of childhood supratentorial midline LGG are, however, understudied. This is the first paper to address the prevalence of bone problems in this specific patient population, revealing visual problems as an important risk factor. Diencephalic syndrome historyand/or weight problems associated with hypothalamic dysfunction were related to bone problems in univariate analyses. The results of this study can be used in the development of guidelines to adequately screen and treat these patients to subsequently minimizing bone problems as one of the endocrine complications.

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J Van Schaik Division of Pediatric Endocrinology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
Division of Pediatric Oncology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

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M Burghard Division of Pediatric Oncology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Department of Exercise Physiology, Child Development & Exercise Center, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands

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M H Lequin Division of Pediatric Oncology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Department of Radiology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands

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E A van Maren Division of Pediatric Oncology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Department of Radiology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands

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A M van Dijk Department of Dietetics, University Medical Center Utrecht, Utrecht, The Netherlands

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T Takken Division of Pediatric Oncology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Department of Exercise Physiology, Child Development & Exercise Center, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands

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L B Rehorst-Kleinlugtenbelt Division of Pediatric Oncology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

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B Bakker Division of Pediatric Endocrinology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
Division of Pediatric Oncology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

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L Meijer Division of Pediatric Oncology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

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E W Hoving Division of Neurosurgery, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

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M Fiocco Division of Pediatric Oncology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Institute of Mathematics, Leiden University, Leiden, The Netherlands

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A Y N Schouten-van Meeteren Division of Pediatric Oncology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

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W J E Tissing Division of Pediatric Oncology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Division of Pediatric Oncology, University Medical Centre Groningen, Groningen, The Netherlands

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H M van Santen Division of Pediatric Endocrinology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
Division of Pediatric Oncology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

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Objective

Children with suprasellar brain damage are at risk of hypothalamic dysfunction (HD). HD may lead to decreased resting energy expenditure (REE). Decreased REE, however, is not present in all children with HD. Our aim was to assess which children suspect for HD have low REE, and its association with clinical severity of HD or radiological hypothalamic damage.

Patients and methods

A retrospective cohort study was performed. Measured REE (mREE) of children at risk of HD was compared to predicted REE (pREE). Low REE was defined as mREE <90% of predicted. The mREE/pREE quotient was associated to a clinical score for HD symptoms and to radiological hypothalamic damage.

Results

In total, 67 children at risk of HD (96% brain tumor diagnosis) with a mean BMI SDS of +2.3 ± 1.0 were included. Of these, 45 (67.2%) had low mREE. Children with severe HD had a significant lower mean mREE/pREE quotient compared to children with no, mild, or moderate HD. Mean mREE/pREE quotient of children with posterior hypothalamic damage was significantly lower compared to children with no or anterior damage. Tumor progression or tumor recurrence, severe clinical HD, and panhypopituitarism with diabetes insipidus (DI) were significant risk factors for reduced REE.

Conclusion

REE may be lowered in children with hypothalamic damage and is associated to the degree of clinical HD. REE is, however, not lowered in all children suspect for HD. For children with mild or moderate clinical HD symptoms, REE measurements may be useful to distinguish between those who may benefit from obesity treatment that increases REE from those who would be better helped using other obesity interventions.

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