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In vitro effects of combination chemotherapy on osteoblasts: implications for osteopenia in childhood malignancy

In vitro effects of combination chemotherapy on osteoblasts: implications for osteopenia in childhood malignancy
In vitro effects of combination chemotherapy on osteoblasts: implications for osteopenia in childhood malignancy
Clinical studies suggest that combination chemotherapy adversely affects bone metabolism and in vitro studies have demonstrated that a reduction in osteoblast numbers results in diminished bone formation. The aim of this study was to investigate the in vitro effects of combinations of chemotherapeutic agents on primary human osteoblast-like (hOB) cell numbers and apoptosis, and to assess the ability of hOBs and osteoprogenitor (HCC1) cells to recover from prior treatment with chemotherapy. As glucocorticoids are frequently administered during treatment with cytotoxic agents, we evaluated whether glucocorticoids influence the chemosensitivity of hOB and human osteosarcoma (MG63) cells. Culture with clinically relevant concentrations of the individual chemotherapeutic agents reduced hOB cell numbers compared with control (p < 0.01) and also increased the numbers of apoptotic cells (p < 0.05). Potentiation of cytotoxicity was observed when agents were given in combination, thus further reducing cell numbers, and this effect was greatest when vincristine was given in combination with asparaginase. Following culture with a chemotherapeutic agent, there was greater recovery of hOB compared with HCC1 cell numbers (p < 0.01). Pretreatment with glucocorticoids ameliorated the adverse effects of chemotherapeutic agents on hOB and MG63 cell numbers and apoptosis (p < 0.05). We conclude that the use of combination chemotherapy contributes to osteopenia in childhood malignancy by a reduction in osteoblast numbers. However, this effect may be attenuated by the concomitant use of glucocorticoids.
metabolic, research support, affect, agents, treatment, antineoplastic combined chemotherapy protocols, osteoblasts, daunorubicin, etoposide, prevention & control, drug therapy, bone diseases, asparaginase, combination, adolescent, tumor cells, hematologic neoplasms, apoptosis, chemically induced, bone, cultured, research, wales, adverse effects, metabolism, osteosarcoma, in vitro, vincristine, pharmacology, pathology, health, stem cells, drug effects, humans, culture, child, childhood, glucocorticoids, female, human, in-vitro
8756-3282
319-326
Davies, J.H.
9f18fcad-f488-4c72-ac23-c154995443a9
Evans, B.A.
2679ef85-28bc-4ee9-8c3f-8550d40e5f63
Jenney, M.E.
4aa4993c-7f3f-4662-8f52-d084d67a1540
Gregory, J.W.
f14bbe24-2378-4a70-991d-4bbf8fa66ac5
Davies, J.H.
9f18fcad-f488-4c72-ac23-c154995443a9
Evans, B.A.
2679ef85-28bc-4ee9-8c3f-8550d40e5f63
Jenney, M.E.
4aa4993c-7f3f-4662-8f52-d084d67a1540
Gregory, J.W.
f14bbe24-2378-4a70-991d-4bbf8fa66ac5

Davies, J.H., Evans, B.A., Jenney, M.E. and Gregory, J.W. (2002) In vitro effects of combination chemotherapy on osteoblasts: implications for osteopenia in childhood malignancy. Bone, 31 (2), 319-326. (doi:10.1016/S8756-3282(02)00822-0).

Record type: Article

Abstract

Clinical studies suggest that combination chemotherapy adversely affects bone metabolism and in vitro studies have demonstrated that a reduction in osteoblast numbers results in diminished bone formation. The aim of this study was to investigate the in vitro effects of combinations of chemotherapeutic agents on primary human osteoblast-like (hOB) cell numbers and apoptosis, and to assess the ability of hOBs and osteoprogenitor (HCC1) cells to recover from prior treatment with chemotherapy. As glucocorticoids are frequently administered during treatment with cytotoxic agents, we evaluated whether glucocorticoids influence the chemosensitivity of hOB and human osteosarcoma (MG63) cells. Culture with clinically relevant concentrations of the individual chemotherapeutic agents reduced hOB cell numbers compared with control (p < 0.01) and also increased the numbers of apoptotic cells (p < 0.05). Potentiation of cytotoxicity was observed when agents were given in combination, thus further reducing cell numbers, and this effect was greatest when vincristine was given in combination with asparaginase. Following culture with a chemotherapeutic agent, there was greater recovery of hOB compared with HCC1 cell numbers (p < 0.01). Pretreatment with glucocorticoids ameliorated the adverse effects of chemotherapeutic agents on hOB and MG63 cell numbers and apoptosis (p < 0.05). We conclude that the use of combination chemotherapy contributes to osteopenia in childhood malignancy by a reduction in osteoblast numbers. However, this effect may be attenuated by the concomitant use of glucocorticoids.

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More information

Published date: 2002
Keywords: metabolic, research support, affect, agents, treatment, antineoplastic combined chemotherapy protocols, osteoblasts, daunorubicin, etoposide, prevention & control, drug therapy, bone diseases, asparaginase, combination, adolescent, tumor cells, hematologic neoplasms, apoptosis, chemically induced, bone, cultured, research, wales, adverse effects, metabolism, osteosarcoma, in vitro, vincristine, pharmacology, pathology, health, stem cells, drug effects, humans, culture, child, childhood, glucocorticoids, female, human, in-vitro

Identifiers

Local EPrints ID: 59650
URI: http://eprints.soton.ac.uk/id/eprint/59650
ISSN: 8756-3282
PURE UUID: 3800e71a-363d-4381-90b4-11ebce0d8240

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Date deposited: 03 Sep 2008
Last modified: 13 Mar 2019 20:30

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