Effects of chemotherapeutic agents on bone. I. Short-term methotrexate and doxorubicin (adriamycin) treatment in a rat model.

Friedlaender, Gary E.; Tross, R B; Doganis, Andrew; Kirkwood, John M.; Baron, Roberta H.

doi:10.2106/00004623-198466040-00016

Cited by 239 publications

(82 citation statements)

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“…These include chemotherapeutic agents, such as doxorubicin and methotrexate, that have been shown to cause a decrease in trabecular bone volume in a rat model (13,62). Similarly, ethanol has been associated with the induction of cellular stress and enhances bone loss in vivo through the increase of osteoclast numbers (5).…”

Section: Discussionmentioning

confidence: 99%

Molecular Stress-inducing Compounds Increase Osteoclast Formation in a Heat Shock Factor 1 Protein-dependent Manner

Chai

Kouspou

Lang

et al. 2014

Journal of Biological Chemistry

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Background: HSP90 inhibitors increase osteoclast formation and bone loss. Results: Altered Hsf1 activity impacts the ability of stress-inducing compounds to modulate osteoclast formation. Conclusion: Hsf1 plays an important role in stress-associated osteoclast formation, potentially via MITF. Significance: We identified a novel pathway whereby agents inducing stress can enhance osteoclast formation.

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Section: Discussionmentioning

confidence: 99%

Molecular Stress-inducing Compounds Increase Osteoclast Formation in a Heat Shock Factor 1 Protein-dependent Manner

Chai

Kouspou

Lang

et al. 2014

Journal of Biological Chemistry

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“…[19][20][21] Similarly, some studies have demonstrated that some other individual chemotherapy drugs impair bone growth mechanisms and bone growth directly, including DNA-damaging agents cisplatin and doxorubicin and anti-metabolites 5-FU and methotrexate. [13][14]16,[36][37] …”

Section: Discussionmentioning

confidence: 99%

Effects of etoposide and cyclophosphamide acute chemotherapy on growth plate and metaphyseal bone in rats

Chen¹,

Cool²,

Gangelen³

et al. 2007

Cancer Biology & Therapy

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“…High-dose methotrexate (MTX), for example, has been associated with resultant osteopenia in adult animals. [19][20][21] The effect of high-dose MTX on bone density during rapid skeletal growth, however, has not been widely studied, nor has the potentially therapeutic effect of bisphosphonates in this specific setting. Van Leeuwen and colleagues found that long bone length and strength was reduced in growing rats by MTX, largely due to treatment-induced malnutrition.…”

Section: Introductionmentioning

confidence: 99%

Density and structural changes in the bone of growing rats after weekly alendronate administration with and without a methotrexate challenge

Spadaro¹,

Damron²,

Horton³

et al. 2006

Journal Orthopaedic Research

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Alendronate (ALN) and other bisphosphonates have been used successfully in pediatric patients with osteopenia secondary to connective tissue diseases. Loss of growth in height has not been reported, but concerns remain regarding the effect of these potent antiresorptive agents when used in children and adolescents. High-dose methotrexate (MTX) and other chemotherapy drugs have been implicated in osteoporosis and a high fracture incidence in survivors of childhood cancers and are also associated with osteopenia in adult animals. The effect of high dose MTX on bone density during rapid skeletal growth, however, has not been widely studied, nor has the potentially therapeutic effect of bisphosphonates in this setting. We examined the effects of ALN and MTX administration, alone and in combination, on bone density, morphology, mechanical strength, and longitudinal growth in normal growing rats. Sprague-Dawley rats were given ALN once weekly (0.3 mg/kg) from 5 to 11 weeks of age, with and without a course of methotrexate (MTX) given daily in weeks 1 and 3 (0.75 mg/kg/day). Twenty-four animals were randomly divided into four groups: Control (vehicle), ALN alone, ALN þ MTX, and MTX alone. After 6 weeks, the femora, tibiae, and lumbar spine were studied by dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, mechanical strength testing, microradiography, light microscopy, and by determination of ash weights and bone lengths. ALN treatment increased bone mineral density (BMD) by 23% to 68%. The largest increases in the femur occurred in the distal third where endochondral bone growth was greatest and included large increases in trabecular bone and total cross-sectional area. ALN þ MTX produced similar effects to ALN alone. MTX only reduced BMD by 8% in the vertebrae, but not significantly at other sites. MTX also led to femoral length reductions of 2.9%. The small reductions in BMD due to MTX were overwhelmed by the increases due to ALN, whereas the length loss was unaffected. Transverse density banding corresponding to weekly ALN administrations were clearly evident radiographically throughout the growing skeleton, likely due to decreased resorption and possibly increased mineralization in the bands. ALN or ALN þ MTX treatment also led to increases in mechanical strength in the femora. Although MTX administration during growth leads to some BMD reduction, ALN given with MTX eliminates this reduction and in fact bone density and strength increase above control levels. ß

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Effects of chemotherapeutic agents on bone. I. Short-term methotrexate and doxorubicin (adriamycin) treatment in a rat model.

Cited by 239 publications

References 0 publications

Molecular Stress-inducing Compounds Increase Osteoclast Formation in a Heat Shock Factor 1 Protein-dependent Manner

Molecular Stress-inducing Compounds Increase Osteoclast Formation in a Heat Shock Factor 1 Protein-dependent Manner

Effects of etoposide and cyclophosphamide acute chemotherapy on growth plate and metaphyseal bone in rats

Density and structural changes in the bone of growing rats after weekly alendronate administration with and without a methotrexate challenge

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