High-dose chemotherapy shows a dose-dependent toxicity to bone marrow osteoprogenitors

Banfi, Andrea; Podestà, Marina; Fazzuoli, Laura; Sertoli, Mario Roberto; Venturini, M.; Santini, G; Cancedda, Ranieri; Quarto, Rodolfo

doi:10.1002/1097-0142(20011101)92:9<2419::aid-cncr1591>3.0.co;2-k

Cited by 125 publications

(62 citation statements)

References 52 publications

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“…The changes seen in serum markers of bone metabolism appear to reflect the rapid initial decline in BMD observed in recipients following transplantation. It has been suggested that the failure of serum markers of bone formation to increase during a period of bone resorption, may reflect a selective impairment of the osteoblastic compartment (Banfi et al, 2001). Unfortunately, bone resorption markers were not assessed in the present study.…”

Section: Discussionmentioning

confidence: 80%

“…Possible factors implicated include physical inactivity, nutritional deficiencies, secondary hypogonadism induced by the preparatory regimen, direct toxicity to the bone microenvironment by high-dose chemoradiotherapy (Hamanishi et al, 1994;Withold et al, 1996;Banfi et al, 2001) and, lastly, the influence of the malignancy (e.g. myeloma) itself.…”

Section: Discussionmentioning

confidence: 99%

“…The pathogenesis of bone loss after SCT is not completely understood (Weilbaecher, 2000). Several factors have been implicated, including low bone mass prior to transplant, secondary hyperparathyroidism due to vitamin D deficiency, immobilization, graft-versus-host disease (GVHD) and its treatment (Katz & Epstein, 1992;Laan et al, 1993;Carlson et al, 1994;Weinstein et al, 1998), malignancy-related mechanisms, ovarian insufficiency in women, and altered cellular or cytokine-mediated bone marrow function (Hamanishi et al, 1994;Withold et al, 1996;Banfi et al, 2001).…”

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confidence: 99%

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Significant and persistent loss of bone mineral density in the femoral neck after haematopoietic stem cell transplantation: long‐term follow‐up of a prospective study

Gandhi¹,

Lekamwasam

Inman³

et al. 2003

Br J Haematol

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Summary. Reduced bone mineral density (BMD) has been reported following allogeneic stem cell transplantation (alloSCT) but the effects of autologous SCT (autoSCT) are less well characterized. We performed a prospective study of BMD changes and its determinants in 44 SCT recipients (38 auto and six allo; 30 peripheral blood SCT and 14 bone marrow transplantation). Serial measurements of BMD at the lumbar spine and femoral neck were performed at baseline and at 3, 6, 12 and 24 months, and spinal radiographs were performed at baseline and 12 months. Mean baseline BMD values at the femoral neck and spine were within normal limits. At 3 months, there was a significant decline of BMD at the femoral neck (P ¼ 0AE011) and a nonsignificant trend towards reduction at the spine. BMD loss persisted for up to 2 years at the femoral neck (P ¼ 0AE005), but values returned to baseline at the spine. Reflecting the rapid initial decline in BMD, bone-specific alkaline phosphatase (a serum marker of bone formation) showed a significant initial decline at 1 month but had recovered to pretransplant levels by 3 months. No new fractures were detected at 1 year post transplant. Sex, diagnosis, use of total body irradiation, stem cell source and type of graft (auto versus allo) did not significantly predict BMD change over the first 12 months. In conclusion, significant and persistent bone loss at the femoral neck was demonstrated in this group of patients following stem cell transplantation. The implications of these findings for future fracture risk require further study.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Significant and persistent loss of bone mineral density in the femoral neck after haematopoietic stem cell transplantation: long‐term follow‐up of a prospective study

Gandhi¹,

Lekamwasam

Inman³

et al. 2003

Br J Haematol

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“…A more likely explanation is the known direct cytotoxic effect of chemotherapy agents on bone cells [19]. This has been demonstrated particularly in the growing skeleton [20][21], but there appears to be little data on the mechanisms of the direct toxic effects of chemotherapy agents on bone especially for the newer regimens [22].…”

Section: Discussionmentioning

confidence: 99%

Bone mineral density loss during adjuvant chemotherapy in pre-menopausal women with early breast cancer: is it dependent on oestrogen deficiency?

Cameron

Douglas

Brown

et al. 2010

Breast Cancer Res Treat

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mineral density loss during adjuvant chemotherapy in pre-menopausal women with early breast cancer: is it dependent on oestrogen deficiency?. Breast Cancer Research and Treatment, Springer Verlag, 2010, 123 (3) Pre-menopausal women given adjuvant chemotherapy for breast cancer experience both premature ovarian failure and loss of bone mineral density (BMD), and this study was designed to see if these observations are causally linked. MethodsChemotherapy was administered to 41 pre-menopausal women with early breast cancer enrolled prospectively in a study of ovarian function and BMD in such women given systemic therapy. After giving written informed consent, all patients underwent baseline and regular on-treatment measurements of BMD by dual-energy x-ray absorptiometry (DXA) scan, bone turnover and ovarian function by analysis of serum hormone levels and self-reported menstrual diaries. ResultsBaseline lumbar spine BMD in the 41 women given chemotherapy was higher than the normal population (Z score 0.28±0.14 (mean±sem), p=0.047), and fell significantly over the first six months from a mean of 1.05 to 1.01 g/m 2 , p <0.0001, and similar but smaller changes were demonstrated in hip BMD. This fall was independent of age at diagnosis, type of chemotherapy, development of amenorrhoea or either baseline or on-treatment estradiol concentration. During the six months after completion of adjuvant chemotherapy, BMD fell further only in those women with low estradiol or experiencing amenorrhoea during the first six months, although all groups showed evidence of increased bone turnover. ConclusionsThis study demonstrates loss of both spine and hip BMD in pre-menopausal women during six months' adjuvant systemic chemotherapy to be independent of changes in ovarian function. Ovarian function was however related to BMD changes after chemotherapy ceased.3

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“…Various studies to date have evaluated the toxic effects of HDC and demonstrated severe and irreversible damage on mature bone marrow stromal compartments in vivo and in vitro [5][6][7][8][9][10][11][12][13][14]. These effects are relevant not only in patients treated with HDC without allogeneic stem cells but also in recipients of allogeneic stem cell transplants in whom bone marrow stroma remains recipient in origin after the transplant [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Chemotherapy-induced mesenchymal stem cell damage in patients with hematological malignancy

et al. 2010

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Hematopoietic recovery after high-dose chemotherapy (HDC) in the treatment of hematological diseases may be slow and/or incomplete. This is generally attributed to progressive hematopoietic stem cell failure, although defective hematopoiesis may be in part due to poor stromal function. Chemotherapy is known to damage mature bone marrow stromal cells in vitro, but the extent to which marrow mesenchymal stem cells (MSCs) are damaged by HDC in vivo is largely unknown. To address this question, the phenotype and functional properties of marrow MSCs derived from untreated and chemotherapeutically treated patients with hematological malignancy were compared. This study demonstrates a significant reduction in MSC expansion and MSC CD44 expression by MSCs derived from patients receiving HDC regimens, thus implicating potential disadvantages in the use of autologous MSCs in chemotherapeutically pretreated patients for future therapeutic strategies. The clinical importance of these HDCinduced defects we have observed could be determined through prospective randomized trials of the effects of MSC cotransplantation on hematopoietic recovery in the setting of HDC with and without hematopoietic stem cell rescue.

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High-dose chemotherapy shows a dose-dependent toxicity to bone marrow osteoprogenitors

Cited by 125 publications

References 52 publications

Significant and persistent loss of bone mineral density in the femoral neck after haematopoietic stem cell transplantation: long‐term follow‐up of a prospective study

Significant and persistent loss of bone mineral density in the femoral neck after haematopoietic stem cell transplantation: long‐term follow‐up of a prospective study

Bone mineral density loss during adjuvant chemotherapy in pre-menopausal women with early breast cancer: is it dependent on oestrogen deficiency?

Chemotherapy-induced mesenchymal stem cell damage in patients with hematological malignancy

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