Effect of 1,25(OH)2—Vitamin D on Bone Mass in Children With Acute Lymphoblastic Leukemia

Diaz, P.; Neira, L; Fischer, Sylvia; Torres, María C. Teresa; Milinarsky, Aída; Giadrosich, Vinka; Arriagada, M; Arinoviche, R; Casanova, D.

doi:10.1097/mph.0b013e318159a522

Cited by 15 publications

(22 citation statements)

References 19 publications

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“…Nonetheless, the early changes to bone found in this study emphasize the need to develop effective interventions and raises the question of whether preventive measures beginning at the time of diagnosis may be necessary to mitigate the adverse influence of osteotoxic chemotherapy. Previous studies to positively influence bone density using Vitamin D[39] or exercise [40] were both implemented subsequent to Induction and were not successful. However, using a combination approach of both Vitamin D and exercise, as is typically recommended [41], and beginning the intervention concurrent with Induction therapy, may provide benefit where the previous studies did not.…”

Section: Discussionmentioning

confidence: 99%

Early injury to cortical and cancellous bone from induction chemotherapy for adolescents and young adults treated for acute lymphoblastic leukemia

Orgel

Mueske

Wren

et al. 2016

Bone

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Diminished bone density and skeletal fractures are common morbidities during and following therapy for acute lymphoblastic leukemia (ALL). While cumulative doses of osteotoxic chemotherapy for ALL have been reported to adversely impact bone density, the timing of onset of this effect as well as other changes to bone structure are not well characterized. We therefore conducted a prospective cohort study in pre-adolescent and adolescent patients (10-21 years) newly diagnosed with ALL (n=38) to explore leukemia-related changes to bone at diagnosis and the subsequent impact of the first phase of chemotherapy (“Induction”). Using quantitative computerized tomography (QCT), we found that pre-chemotherapy bone properties were similar to age- and sex-matched controls. Subsequently over the one month Induction period, however, cancellous volumetric bone mineral density (vBMD) decreased markedly (-26.8%, p<0.001) with sparing of cortical vBMD (tibia -0.0%, p=0.860, femur -0.7%, p=0.290). The tibia underwent significant cortical thinning (average cortical thickness -1.2%, p<0.001; cortical area -0.4%, p=0.014), while the femur was less affected. Areal BMD (aBMD) concurrently measured by dual-energy X-ray absorptiometry (DXA) underestimated changes from baseline as compared to vBMD. Biochemical evidence revealed prevalent Vitamin D insufficiency and a net resorptive state at start and end of Induction. Our findings demonstrate for the first time that significant alterations to cancellous and cortical bone develop during the first month of treatment, far earlier during ALL therapy than previously considered. Given that osteotoxic chemotherapy is integral to curative regimens for ALL, these results provide reason to re-evaluate traditional approaches toward chemotherapy-associated bone toxicity and highlight the urgent need for investigation into interventions to mitigate this common adverse effect.

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Section: Discussionmentioning

confidence: 99%

Early injury to cortical and cancellous bone from induction chemotherapy for adolescents and young adults treated for acute lymphoblastic leukemia

Orgel

Mueske

Wren

et al. 2016

Bone

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“…Nineteen trials examined the effect of calcitriol on changes in BMD across a variety of populations [65, 67, 70–72, 74–76, 78, 82–91]. BMD was assessed at various anatomical sites, including the hip, spine, femur, radius, and total body.…”

Section: Monotherapy Calcitriol Therapy Bmd and Fracturesmentioning

confidence: 99%

“…Of the 19 trials, 11 reported statistically significant increases in BMD at one or more sites for the calcitriol group when compared to the placebo group [65, 67, 70, 71, 74, 75, 84, 87–90]. Five trials reported no difference in BMD changes between those receiving calcitriol therapy and those in the placebo group [72, 78, 82, 85, 91]. The final three trials found that calcitriol therapy was equivalent to proven bone therapies, such as bisphosphonates [76], high-dose vitamin D [83], and alfacalcidol (a calcitriol prodrug) [86].…”

Section: Monotherapy Calcitriol Therapy Bmd and Fracturesmentioning

confidence: 99%

“…This study also found no difference in BMD change at the femur and hip between those receiving alendronate and calcitriol. Three studies administered calcitriol to patients who had experienced bone loss as a result of corticosteroid therapy [71, 88, 91]. Lambrinoudaki et al [71] found significantly increased lumbar BMD, and Mirzaei et al [88] found significantly increased femoral BMD for those in the calcitriol arm when compared to those in the control arm.…”

Section: Monotherapy Calcitriol Therapy Bmd and Fracturesmentioning

confidence: 99%

“…Lambrinoudaki et al [71] found significantly increased lumbar BMD, and Mirzaei et al [88] found significantly increased femoral BMD for those in the calcitriol arm when compared to those in the control arm. Diaz et al [91] administered calcitriol to 24 children aged two to 11 with acute lymphoblastic leukemia. Overall, no significant change in lumbar BMD was found, but a significant increase in lumbar BMD was reported in the calcitriol arm for those with a low baseline BMD.…”

Section: Monotherapy Calcitriol Therapy Bmd and Fracturesmentioning

confidence: 99%

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The efficacy of calcitriol therapy in the management of bone loss and fractures: a qualitative review

et al. 2009

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Summary Osteoporosis, a skeletal disorder characterized by a reduction in bone strength, increases fracture risk. Primary osteoporosis is usually a result of reduced bone mineral density as a consequence of natural aging. Secondary osteoporosis is usually a result of a disease, such as cystic fibrosis, or medical treatment, such as corticosteroids or cancer treatment. Introduction Currently, ten million Americans are osteoporotic and an additional 34 million have the precursor condition, osteopenia. Osteoporosis leads to 1.5 million fractures and 500,000 hospitalizations annually. Osteoporosis-related fractures increase mortality and reduce quality of life. Calcitriol, the active form of vitamin D, regulates intestinal calcium absorption, among other actions. During the past four decades, many clinical trials investigating the effect of calcitriol on bone loss have been performed. Methods We conducted a systematic qualitative review of clinical trials that assessed calcitriol for the treatment of osteoporosis and bone loss. In these clinical trials, calcitriol was used as a monotherapy and in combination with other therapeutic bone agents. Results and conclusion Studies using calcitriol monotherapy, although not conclusive, found that calcitriol slowed the rate of bone loss in a variety of populations. Calcitriol in combination with other therapeutic bone agents was shown to have additional bone-preserving effects when compared to the use of therapeutic bone agents alone. A common side-effect of calcitriol therapy was hypercalcemia and hypercalciuria, but the degree of hypercalcemia was mild. Recent research found that intermittent dosing can reduce hypercalcemia rates. Calcitriol, alone or in combination with other agents, should be considered for the therapy of osteoporosis.

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Vitamin D supplementation for children with cancer: A systematic review and consensus recommendations

et al. 2021

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Background Prevalent vitamin D deficiency (VDD) and low bone mineral density (BMD) have led to vitamin D supplementation for children with cancer, regardless vitamin D status. However, it remains unsettled whether this enhances bone strength. We sought to address this issue by carrying out a systematic review of the literature. Methods We conducted a literature search using PubMed, Embase, and Cochrane databases. Studies including children up to 5 years after cancer therapy were assessed for the association between 25‐hydroxyvitamin D (25OHD) levels and BMD Z‐scores or fractures, and the effect of vitamin D supplementation on BMD or fractures. Evidence quality was assessed using the GRADE methodology. Results Nineteen studies (16 observational and 3 interventional, mainly involving children with hematologic malignancies) were included. One study which analyzed 25OHD as a threshold variable (≤10 ng/ml) found a significant association between 25OHD levels and BMD Z‐scores, while 25OHD as a continuous variable was not significantly associated with BMD Z‐scores in 14 observational studies. We found neither a significant association between lower 25OHD levels and fractures (2 studies), nor between vitamin D (and calcium) supplementation and BMD or fracture frequency (3 studies) (very low quality evidence). Conclusion There is a lack of evidence for an effect of vitamin D (and calcium) supplementation on BMD or fractures in children with cancer. Further research is needed; until then, we recommend dietary vitamin D/calcium intake in keeping with standard national guidelines, and periodic 25OHD monitoring to detect levels <20 ng/ml. Vitamin D/calcium supplementation is recommended in children with low levels, to maintain levels ≥20 ng/ml year‐long.

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Effect of 1,25(OH)2—Vitamin D on Bone Mass in Children With Acute Lymphoblastic Leukemia

Abstract: One-year calcitriol administered to recently diagnosed ALL children did not show impact on bone mass. Greater increment in lumbar spine bone mass was observed in patients who received calcitriol and had lower baseline BMD.

Cited by 15 publications

References 19 publications

Early injury to cortical and cancellous bone from induction chemotherapy for adolescents and young adults treated for acute lymphoblastic leukemia

Early injury to cortical and cancellous bone from induction chemotherapy for adolescents and young adults treated for acute lymphoblastic leukemia

The efficacy of calcitriol therapy in the management of bone loss and fractures: a qualitative review

Vitamin D supplementation for children with cancer: A systematic review and consensus recommendations

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