Bone mineral density in children with acute lymphoblastic leukemia

Inaba, Hiroto; Cao, Xueyuan; Han, Alice Q.; Panetta, John C.; Ness, Kirsten K.; Metzger, Monika L.; Rubnitz, Jeffrey E.; Ribeiro, Raul C.; Sandlund, John T.; Jeha, Sima; Cheng, Cheng; Pui, Ching Hon; Relling, Mary V.; Kaste, Sue C.

doi:10.1002/cncr.31184

Cited by 29 publications

(24 citation statements)

References 43 publications

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“…Low BMD in pediatric cancer survivors has been reported previously, but the majority have been reported in ALL cases . Inaba et al reported reduced BMD Z ‐scores in patients with ALL during therapy and only partly recovered after 2 years off therapy. Although the BMD Z ‐scores were enhanced after completing treatment, they remained lower than those at diagnosis .…”

Section: Discussionmentioning

confidence: 92%

“…A specific diagnosis referring to metabolic bone disease in the preterm infant is osteopenia of prematurity, which is not based on BMD Z ‐score . One radiological study defined BMD Z ‐scores < −2 and between −1 and −2 as severe and mild osteopenia, respectively, while a recent St. Jude cohort regarding BMD in childhood ALL defined BMD Z ‐scores < −1.5 as low BMD . In our study, we gave denosumab therapy only for the patients who had persistently BMD Z ‐scores < −1.5 even after calcium and vitamin D supplementation.…”

Section: Discussionmentioning

confidence: 95%

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Efficacy and safety of denosumab therapy for low bone mineral density in childhood cancer survivors: A report of preliminary experience

Huang

Liu

Hou

et al. 2019

Pediatric Blood & Cancer

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Background:In childhood cancer survivors, low bone mineral density (BMD) is a bone-related consequence. Efficacy of denosumab, an effective therapy for adult patients with osteoporosis, remains unclear in children. This study aimed to investigate denosumab therapy efficacy for low BMD in childhood cancer survivors. , we monitored lumbar BMD of children with cancer using dual-energy X-ray absorptiometry after completing chemotherapy with a 6month interval. For patients with low BMD, defined as height-adjusted Z-scores of BMD < −1.5 in this study, calcium carbonate and vitamin D supplements were initially administered. When low BMD continued for at least 6 months, denosumab therapy was introduced. Calcium and vitamin D supplementation were continued in patients on denosumab. We investigated BMD change and adverse effects during denosumab therapy. Results:During the study period, 20 patients received denosumab treatment. Mean heightadjusted Z-score of BMD before denosumab treatment was −2.68 but increased to −2, −1.96, and −1.33 at 0.5, 1, and 1.5 years after denosumab treatment, respectively (P = .012). In addition, hypocalcemia occurred in 40% (8/20) of patients; three patients had hypocalcemic symptoms with numbness in all four limbs. All hypocalcemic patients, except one patient who died due to relapsed leukemia, recovered well after continuous calcium supplementation. Conclusions:Denosumab is an effective treatment for low BMD in childhood cancer survivors.However, the complication of hypocalcemia might develop posttreatment. K E Y W O R D Sbone mineral density, cancer, children, denosumab, osteoporosis

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 95%

Efficacy and safety of denosumab therapy for low bone mineral density in childhood cancer survivors: A report of preliminary experience

Huang

Liu

Hou

et al. 2019

Pediatric Blood & Cancer

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“…Examination of Masson's Trichrome-stained sections of MTX-treated group showed thin discontinuous bony trabeculae which were formed mostly of unmineralized bone matrix with few areas of mineralized bone matrix. Previous findings were reported by [25] who confirmed that, children with ALL showed a significant decrease in the bone mineral density (BMD) after MTX-chemotherapy. [26] explained that MTX-induced osteoblastic damage caused diminished mineralizing surface, mineral apposition rate and bone formation rate.…”

Section: Discussionmentioning

confidence: 67%

Comparative Histological Study on the Protective Effect of Folinic Acid versus Fish Oil on the Growing Bone of Methotrexate-Treated Young Rats

Bassiouny

Amin

Ibrahim

et al. 2019

Egyptian Journal of Histology

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Background: Folinic acid (FA) is used to reduce Methotrexate (MTX) toxicity during treatment of childhood acute lymphoblastic leukemia (ALL). However, FA has been shown to reduce MTX treatment efficacy and cure rates of ALL. Recent studies suggested that fish oil (FO) supplementation may protect bone during MTX chemotherapy. Aim of Work: to compare the protective effect of FA versus FO on the growing bone of MTX-treated young rats monitored by histological, immunohistochemical, morphometric and laboratory methods. Materials and Methods: Forty two, 6 weeks-old-male albino rats were divided into: group I (control), group II (MTXtreated), group III (MTX and FA-treated) and group IV (MTX and FO-treated). MTX was injected subcutaneously, once daily for 5 consecutive days, 0.65 mg/kg, followed by 9 days of rest, then 1.3 mg/kg twice weekly for 4 weeks. FA was injected intraperitoneally, 6 hours after each dose of MTX, 0.87 mg/kg, then1.3 mg/kg twice weekly. FO was given orally daily for 6 weeks, 0.5 ml/100 gm. Left knee joints were processed for measuring RANKL/ OPG ratio (Receptor Activator of Nuclear factor Kapp-B Ligand/ Osteoprotegerin). Right knee joint sections were stained with H&E, Masson's Trichrome and immunohistochemical staining for Caspase-3. Morphometric measurements and statistical analysis were done. Results: MTX-treated group sections revealed disruption in the growth plate structure with subsequent reduction in endochondral bone formation. Supplementation with FA and FO preserved growth plate integrity and bone formation. Conclusion: Fish oil showed better effect than Folinic acid in ameliorating growth plate disruption and retarded bone formation encountered during MTX chemotherapy in young rats.

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“…По данным литературы, гемобластозы являются распространенным фактором риска развития вторичного остеопороза и низкоэнергетических переломов [5]. Остеопороз и остеопения, как осложнения терапии лимфопролиферативных заболеваний, чаще встречаются у больных ЛХ (до 88 % пациентов), чем у больных неходжкинскими лимфомами (67 %) и хроническим лимфоцитарным лейкозом (49 %) [7].…”

Section: Discussionunclassified

Assessment of Bone Mineral Density in Patients With Hodgkin’s Lymphoma

2019

SSMJ

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В настоящее время лимфома Ходжкина (ЛХ) признана высококурабельным заболеванием. Стандартом лечения являются протоколы полихимиотерапии (ПХТ), содержащие различные комбинации цитостатических препаратов и глюкокортикостероидов. На промежуточных этапах болезни используется комбинированный подход: ПХТ в сочетании с лучевой терапией на зоны исходного поражения. Достижение стойкой безрецидивной выживаемости поставило перед врачами вопрос обеспечения пациентов удовлетворительным качеством жизни и профилактики отдаленных последствий противоопухолевой терапии. Одним из таких последствий может быть изменение минеральной плотности костей (МПК) скелета. Цель исследования-оценить МПК и выявить факторы, влияющие на ремоделирование костной ткани, у больных с различными стадиями и гистологическими вариантами ЛХ. Материал и методы. Мы исследовали МПК у больных ЛХ с помощью двухэнергетической рентгеновской абсорбциометрии (DXA) на аппарате LunarProdigy (GE, США). Определение риска основных низкоэнергетических переломов проводили с помощью опросника FRAX (веб-версия 3.8, расчет по российской модели). Оценивали общий риск низкоэнергетических переломов (FRAX total) и риск переломов шейки бедра (FRAX hip). Результаты. По результатам DXA 36 больных ЛХ (48,6 %) имеют снижение МПК. Пациенты с остеопорозом в целом были старше, имели меньший индекс массы тела, чем больные с нормальной МПК (р < 0,05). Десятилетний риск основных низкоэнергетических переломов и переломов шейки бедра, согласно FRAX, оказался выше в группах больных с остеопорозом и остеопенией по сравнению с больными ЛХ с нормальной МПК (р < 0,05). При оценке денситометрических показателей у больных ЛХ, получавших комбинированную терапию, в большинстве случаев (χ 2 = 5,47; р = 0,0194) выявлялось снижение МПК в сравнении с пациентами, получавшими только ПХТ. Более чем у половины больных, получавших схемы ПХТ, содержащие глюкокортикостероиды (59,1 %), обнаружено уменьшение МПК. При сравнительном анализе установлено, что в группе пациентов моложе 50 лет МПК и величина Z-критерия поясничного отдела позвоночника на ранних стадиях заболевания были достоверно ниже, чем у больных с III-IV стадиями. В свою очередь, у больных старше 50 лет и женщин в постменопаузе на ранних стадиях заболевания зарегистрировано достоверное уменьшение МПК и величины Т-критерия шейки бедра в сравнении с пациентами с распространенными стадиями заболевания. Результаты настоящей работы позволяют предполагать, что снижение денситометрических показателей на I-II стадиях ЛХ также связано с применением лучевой терапии на зоны исходного поражения в качестве общепринятого стандарта лечения преимущественно ранних стадий заболевания. Ключевые слова: лимфома Ходжкина, минеральная плотность костной ткани, остеопороз, денситометрия, двухэнергетическая рентгеновская абсорбциометрия.

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Bone mineral density in children with acute lymphoblastic leukemia

Abstract: BMD 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.

Cited by 29 publications

References 43 publications

Efficacy and safety of denosumab therapy for low bone mineral density in childhood cancer survivors: A report of preliminary experience

Efficacy and safety of denosumab therapy for low bone mineral density in childhood cancer survivors: A report of preliminary experience

Comparative Histological Study on the Protective Effect of Folinic Acid versus Fish Oil on the Growing Bone of Methotrexate-Treated Young Rats

Assessment of Bone Mineral Density in Patients With Hodgkin’s Lymphoma

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