Bone Marrow Stromal Damage after Chemo/Radiotherapy: Occurrence, Consequences and Possibilities of Treatment

Banfi, Andrea; Bianchi, Giordano; Galotto, Maria; Cancedda, Ranieri; Quarto, Rodolfo

doi:10.3109/10428190109097705

Cited by 102 publications

(77 citation statements)

References 61 publications

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“…15 It has been suggested that the failure of serum markers of bone formation to increase in the period after increased bone resorption is due to the selective impairment of the osteoblastic compartment after HDT. 16,17 Our results could indicate that osteoblasts may resume their function when the inhibitory effect of DKK-1 is no longer present.…”

Section: Dkk-1 and Asctmentioning

confidence: 72%

Serum concentrations of Dickkopf‐1 protein are increased in patients with multiple myeloma and reduced after autologous stem cell transplantation

Politou¹,

Heath²,

Rahemtulla³

et al. 2006

Intl Journal of Cancer

142

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Dickkopf-1 (DKK-1) protein, a soluble inhibitor of Wnt signalling, has been implicated in the pathogenesis of myeloma bone disease through the suppression of osteoblast differentiation. In this study, serum concentrations of DKK-1 were measured in 50 myeloma patients (32 at diagnosis and 18 before and after autologous stem cell transplantation (ASCT), 18 patients with monoclonal gammopathy of undetermined significance (MGUS), and 22 healthy controls. Serum DKK-1 levels were increased in MM at diagnosis compared with MGUS (mean 6 SD: 67 6 54 ng/mL vs. 38 6 13 ng/mL; p 5 0.006) and controls (31 6 11 ng/mL; p 5 0.02), while there was no difference between MGUS patients and controls. Although patients with stage 2 and 3 myeloma had higher DKK-1 values than stage 1 patients (79 6 63 vs. 40 6 13; p 5 0.005), no significant correlation between serum DKK-1 and myeloma bone disease was observed. Myeloma patients before ASCT also had increased levels of DKK-1 (63 6 77 ng/mL; p 5 0.03) compared with controls, supporting the notion that DKK-1 may be responsible for the suppressed osteoblast activity even in patients with low tumor burden. After ASCT, there was a sustained decrease in DKK-1 levels over time, while bone formation markers elevated, suggesting that the reduction of DKK-1 levels after ASCT may correlate with the normalization of osteoblast function. These results could provide the basis for developing agents that block DKK-1, thus restoring osteoblast function and counteracting the increased osteoclastogenesis observed in myeloma. ' 2006 Wiley-Liss, Inc.

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Section: Dkk-1 and Asctmentioning

confidence: 72%

Serum concentrations of Dickkopf‐1 protein are increased in patients with multiple myeloma and reduced after autologous stem cell transplantation

Politou¹,

Heath²,

Rahemtulla³

et al. 2006

Intl Journal of Cancer

142

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“…Superimposed on previous cancer treatment, these factors include the direct effects on the bone and the effects of impaired growth hormone (GH) and sex hormone secretion. 1,2 In addition, after allo-SCT chronic GVHD (cGVHD) may ensue, entailing long-term glucocorticoid and CYA treatment. [3][4][5] SCT survivors are often underweight and may be prone to physical inactivity.…”

Section: Introductionmentioning

confidence: 99%

Decreased bone mineral density in young adults treated with SCT in childhood: the role of 25-hydroxyvitamin D

Frisk

Arvidson

Ljunggren

et al. 2011

Bone Marrow Transplant

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We measured bone mineral density (BMD) with dualenergy X-ray absorptiometry in the total body, at the lumbar spine, at the femoral neck and in the total hip, in 18 young adults with a median of 18.2 years after SCT. Fifteen patients had undergone auto-SCT and all patients had received TBI. The patients had significantly lower BMD in the total body, at the femoral neck, and in the total hip compared with age-and sex-matched controls. Six of 18 patients (33%) had low bone mass (z-score oÀ1) at one or more measurement sites, as opposed to two of the controls (11%, P ¼ 0.29). We found no significant influence of growth hormone levels or of untreated hypogonadism on BMD variables. Levels of 25-hydroxy (25(OH)) vitamin D were lower among the patients (35.2 vs 48.8 nmol/L, P ¼ 0.044) and were significantly correlated with total body BMD in the patient group (r ¼ 0.55, P ¼ 0.021). All six patients with low bone mass had hypovitaminosis D (p37 nmol/L as opposed to 4 of the 11 (36%) patients without low bone mass (P ¼ 0.035). In conclusion, we found decreased BMD in SCT survivors, which may in part be caused by 25(OH) vitamin D deficiency.

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“…However little is known on the extent of this damage and on the regeneration ability of the stromal cells. It usually takes a much longer time to regenerate stromal cells, if possible, than to regenerate hematopoietic cells [32]. The difficulties inherent in experimental and clinical studies of stromal cell alterations make it difficult to assess their contribution to BM regeneration.…”

Section: Bm Regeneration After Radiotherapy and Chemotherapymentioning

confidence: 99%

Local signals in stem cell-based bone marrow regeneration

Wang

Liu

2006

Cell Res

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The cellular basis of bone marrow (BM) tissue development and regeneration is mediated through hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). Local interplays between hematopoietic cells and BM stromal cells (BMSCs) determine the reconstitution of hematopoiesis after myelosuppression. Here we review the BM local signals in control of BM regeneration after insults. Hematopoietic growth factors (HGFs) and cytokines produced by BMSCs are primary factors in regulation of BM hematopoiesis. Morphogens which are critical to early embryo development in multiple species have been added to the family of HSCs regulators, including families of Wnt proteins, Notch ligands, BMPs, and Hedgehogs. Global gene expression analysis of HSCs and BMSCs has begun to reveal signature groups of genes for both cell types. More importantly, analysis of global gene expression coupled with biochemical and biological studies of local signals during BM regeneration have strongly suggested that HGFs and cytokines may not be the primary local regulators for BM recovery, rather chemokines (SDF-1, FGF-4) and angiogenic growth factors (VEGF-A, Ang-1) play instructive roles in BM reconstitution after myelosuppression. A new direction of management of BM toxicity is emerging from the identification of BM regenerative regulators.

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Bone Marrow Stromal Damage after Chemo/Radiotherapy: Occurrence, Consequences and Possibilities of Treatment

Cited by 102 publications

References 61 publications

Serum concentrations of Dickkopf‐1 protein are increased in patients with multiple myeloma and reduced after autologous stem cell transplantation

Serum concentrations of Dickkopf‐1 protein are increased in patients with multiple myeloma and reduced after autologous stem cell transplantation

Decreased bone mineral density in young adults treated with SCT in childhood: the role of 25-hydroxyvitamin D

Local signals in stem cell-based bone marrow regeneration

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