Chemical castration induced by adjuvant cyclophosphamide, methotrexate, and fluorouracil chemotherapy causes rapid bone loss that is reduced by clodronate: a randomized study in premenopausal breast cancer patients.

Saarto, Tiina; Blomqvist, Carl; Välimäki, M; Mäkelä, Pekka; Sarna, Seppo; Elomaa, Inkeri

doi:10.1200/jco.1997.15.4.1341

Cited by 250 publications

(156 citation statements)

References 26 publications

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“…During the period of chemotherapy (6 months), the reductions in BMD at the lumbar spine and total hip in this study were approximately 4% and 2% respectively. These data are consistent with those of previous studies for pre-menopausal women 10 receiving adjuvant chemotherapy [1,[9][10][11]. Although this change is relatively small, given that a reduction of 1 in T-score is approximately equivalent to a 10% reduction in BMD, it may be seen that the direct chemotherapy-induced reduction in BMD could be sufficient to push osteopenic patients into the osteoporotic range and may be clinically significant in terms of increased fracture risk in the longer term in these relatively young women.…”

Section: Discussionsupporting

confidence: 93%

“…There are a number of studies that link the use of adjuvant cyclophosphamide, methotrexate and fluorouracil (CMF), amenorrhoea and loss of BMD [1,2]. For example, Saarto et al [1] showed that CMF induced ovarian failure and rapid bone loss in premenopausal breast cancer patients, with women over 40 years at particular risk.…”

Section: Introductionmentioning

confidence: 99%

“…For example, Saarto et al [1] showed that CMF induced ovarian failure and rapid bone loss in premenopausal breast cancer patients, with women over 40 years at particular risk. BMD changes at 2 years in the lumbar spine and femoral neck were -5.9% and -2.0%…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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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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“…At 24 months, the difference in bone mineral density between the two groups was 2.5% at the spine and 2.6% at the femoral neck. Other studies have examined the efficacy of clondronate, [16][17][18][19] which is unavailable in the United States. Our study is the first to examine the US Food and Drug Administration-approved dose of the oral bisphosphonate risedronate once weekly for this indication.…”

Section: Discussionmentioning

confidence: 99%

Risedronate Prevents Bone Loss in Breast Cancer Survivors: A 2-Year, Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Greenspan

Brufsky

Lembersky

et al. 2008

JCO

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Purpose-Limited data are available on the efficacy of oral bisphosphonate therapy in breast cancer survivors. Our goal was to examine prevention of breast cancer-related bone loss in this cohort.Patients and Methods-Eighty-seven postmenopausal women after chemotherapy for breast cancer were randomly assigned to once-weekly risedronate 35 mg or placebo for 24 months. Outcomes included bone mineral density (BMD) and turnover markers. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTAlthough all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptResults-At study initiation, 13% of patients were on an aromatase inhibitor (AI). After 24 months, there were differences of 1.6 to 2.5% (P < .05) at the spine and hip BMD between the placebo and risedronate groups. At study completion, 44% were on an AI. Adjusting for an AI, women on placebo plus AI had a decrease in BMD of (mean ± SE) 4.8% ± 0.8% at the spine and 2.8% ± 0.5% at the total hip (both P < .001). In women on risedronate + AI, the spine decreased by 2.4% ± 1.1% (P < .05) and was stable at the hip. Women in the placebo group not on an AI, maintained BMD at the spine, and had a 1.2% ± 0.5% loss at the total hip (P < .05). Women who received risedronate but no AI had the greatest improvement in BMD of 2.2% ± 0.9% (P < .05) at the total hip. Bone turnover was reduced with risedronate. There were no differences in adverse events between the groups.Conclusion-We conclude that in postmenopausal women with breast cancer with or without AI therapy, once-weekly oral risedronate was beneficial for spine and hip BMD, reduced bone turnover, and was well tolerated.

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“…Cancer-Bisphosphonates, including intravenous pamidronate and zoledronic acid, oral risedronate, and oral clodronate, have been shown to prevent bone loss in premenopausal women experiencing ovarian failure in the setting of chemotherapy for breast cancer [50•, 51,52] and in those with leukemia who are undergoing stem cell transplant [53]. Additionally, in a randomized study of 401 premenopausal women with breast cancer who were receiving adjuvant endocrine-suppressive therapy with either goserelin and tamoxifen or goserelin and anastrazole, bone loss seen with these therapies was prevented in those receiving zoledronic acid (4 mg every 6 months) [54••].…”

Section: Bisphosphonatesmentioning

confidence: 99%

Treatment of premenopausal women with low bone mineral density

Cohen

Shane²

2008

Curr Osteoporos Rep

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Interpretation of bone mineral density (BMD) results in premenopausal women is particularly challenging, because the relationship between BMD and fracture risk is not the same as for postmenopausal women. Z scores rather than T scores should be used to define "low BMD" in premenopausal women. The finding of low BMD in a premenopausal woman should prompt an evaluation for secondary causes of bone loss. If a secondary cause is found, management should focus on treatment of this condition. In some cases in which the secondary cause cannot be addressed, such as glucocorticoid therapy or cancer chemotherapy, treatment with a bone-active agent to prevent bone loss should be considered. In women with no fractures and no known secondary cause, low BMD may not signify compromised bone strength. BMD is likely to remain stable in these women, and pharmacologic therapy is rarely justified. Assessment of markers of bone turnover and follow-up bone density measurements can help to identify those with an ongoing process of bone loss that may indicate a higher risk for fracture, and possible need for pharmacologic intervention.

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Chemical castration induced by adjuvant cyclophosphamide, methotrexate, and fluorouracil chemotherapy causes rapid bone loss that is reduced by clodronate: a randomized study in premenopausal breast cancer patients.

Abstract: Chemotherapy-induced ovarian failure causes rapid bone loss in premenopausal breast cancer patients. Women older than 40 years are at particularly high risk. Clodronate significantly reduces this bone loss.

Cited by 250 publications

References 26 publications

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

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

Risedronate Prevents Bone Loss in Breast Cancer Survivors: A 2-Year, Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Treatment of premenopausal women with low bone mineral density

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