The effects of intermittent androgen deprivation therapy (ADT) and zoledronic acid administration on bone density in patients with prostate cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15593-15593 ◽  
Author(s):  
L. Katznelson ◽  
K. Kent ◽  
S. Srinivas
Keyword(s):  
Prostate Cancer ◽  
Lumbar Spine ◽  
Zoledronic Acid ◽  
Bone Loss ◽  
Femoral Neck ◽  
Previous Treatment ◽  
Osteonecrosis Of The Jaw ◽  
Recurrent Prostate Cancer ◽  
Mineral Density ◽  
Acid Administration

15593 Background: Intermittent ADT is commonly used in men with recurrent prostate cancer. Bone loss associated with ADT is well described. Bisphosphonate use in men undergoing ADT results in improvement in bone mineral density (BMD), although the utility and duration of bisphosphonate use in men undergoing intermittent ADT are unclear. Objective:To evaluate the effect of zoledronic acid administration every 3 months on BMD in men with prostate cancer undergoing intermittent ADT, and whether BMD is maintained upon discontinuation of both ADT and zoledronic acid. Methods: Patients with recurrent prostate cancer starting ADT were eligible to participate. Subjects received ADT for 9 months in addition to 3 doses of zoledronic acid every 3 months. At 9 months, patients who achieved an undetectable serum PSA were taken off ADT and then randomized either to continuing zoledronic acid every 3 months for an additional 3 doses vs. observation. BMD, assessed by DEXA scan, was determined at baseline, 9 months, and between 18 -24 months at hip, trochanter, femoral neck and lumbar spine sites. Results: Twenty two patients were treated with ADT and zoledronic acid between 2003–2006. Seven of these subjects had bone metastases and had previous treatment with ADT.There was one infusion related reaction, and one patient developed osteonecrosis of the jaw and was removed from the study. At baseline, 3 patients had osteoporosis at the lumbar spine. All patients who received zoledronic acid for 9 months had an improvement in BMD at all 3 sites. In the 7 subjects who had previously received ADT, BMD of the femoral neck increased significantly by approximately 1.9%. Among the 6 patients randomized to continuing zoledronic acid after discontinuing ADT at 9 months, all had a further, significant increase in BMD. Those randomized to observation were unable to maintain their BMD and had continued bone loss despite stopping ADT. Conclusions: This small study demonstrated an increase/maintenance of BMD in men receiving intermittent ADT and zoledronic acid. Only those men who continued zoledronic acid for up to a total of 9 mos after discontinuing ADT maintained BMD No significant financial relationships to disclose.

scholarly journals Randomized Controlled Trial of Annual Zoledronic Acid to Prevent Gonadotropin-Releasing Hormone Agonist–Induced Bone Loss in Men With Prostate Cancer

2007 ◽  
Vol 25 (9) ◽  
pp. 1038-1042 ◽  
Author(s):  
M. Dror Michaelson ◽  
Donald S. Kaufman ◽  
Hang Lee ◽  
Francis J. McGovern ◽  
Philip W. Kantoff ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lumbar Spine ◽  
Zoledronic Acid ◽  
Bone Loss ◽  
Gnrh Agonist ◽  
Controlled Trial ◽  
Gonadotropin Releasing Hormone ◽  
Mineral Density ◽  
Releasing Hormone ◽  
Increase Fracture Risk

Purpose Gonadotropin-releasing hormone (GnRH) agonists decrease bone mineral density (BMD) and increase fracture risk in men with prostate cancer. Annual zoledronic acid increases BMD in postmenopausal women, but its efficacy in hypogonadal men is not known. Patients and Methods In a 12-month study, 40 men with nonmetastatic prostate cancer who were receiving a GnRH agonist and had T scores more than −2.5 were randomly assigned to zoledronic acid (4 mg intravenously on day 1 only) or placebo. BMD of the posteroanterior lumbar spine and proximal femur were measured by dual-energy x-ray absorptiometry. Results Mean (± SE) BMD of the posteroanterior lumbar spine decreased by 3.1% ± 1.0% in men assigned to placebo and increased by 4.0% ± 1.0% in men assigned to zoledronic acid (P < .001). BMD of the total hip decreased by 1.9% ± 0.7% in men assigned to placebo and increased by 0.7% ± 0.5% in men assigned to zoledronic acid (P = .004). Similar between-group differences were observed for the femoral neck and trochanter. Serum N-telopeptide, a marker of osteoclast activity, decreased significantly after zoledronic acid treatment. Conclusion In men receiving a GnRH agonist, a single treatment with zoledronic acid significantly increased BMD and durably suppressed serum N-telopeptide levels for 12 months. Annual zoledronic acid may be a convenient and effective strategy to prevent bone loss in hypogonadal men.

Annual zoledronic acid to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer: A randomized placebo-controlled trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4515-4515 ◽  
Author(s):  
M. D. Michaelson ◽  
H. Lee ◽  
D. S. Kaufman ◽  
P. W. Kantoff ◽  
J. Finkelstein ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Mineral Density ◽  
Lumbar Spine ◽  
Zoledronic Acid ◽  
Bone Loss ◽  
Bone Mineral ◽  
Gnrh Agonist ◽  
Gonadotropin Releasing Hormone ◽  
Mineral Density ◽  
Total Hip

4515 Background: Gonadotropin-releasing hormone (GnRH) agonists decrease bone mineral density (BMD) and increase fracture risk in men with prostate cancer. Zoledronic acid (4 mg IV every 3 months) increases BMD in GnRH agonist treated men. Intermittent zoledronic acid (4 mg IV once annually) increases BMD in postmenopausal women with osteoporosis but the efficacy of the annual treatment schedule in hypogonadal men is unknown. Methods: In a 12-month open-label study, men with nonmetastatic prostate cancer (n = 44) who were receiving a GnRH agonist were assigned randomly to zoledronic acid (4 mg IV × 1) or placebo. BMD of the posteroanterior lumbar spine and total hip were measured by dual energy x-ray absorptiometry at baseline and month 12. Serum N-telopeptide, a marker of osteoclast activity, was measured every 3 months. Results: Mean (± SE) BMD of the posteroanterior lumbar spine increased by 4.0 ± 0.9 in men treated with zoledronic acid and decreased by 3.1 ± 0.9 percent in men who received placebo (P < 0.001 for between-group comparison). BMD of the total hip decreased by 0.7 ± 0.6 percent in men treated with zoledronic acid and decreased by 1.9 ± 0.7 percent in men who received placebo (P = 0.005). Compared to placebo, zoledronic acid significantly decreased serum N-telopeptide throughout the 12-month study (P < 0.05). Conclusions: In men receiving a GnRH agonist for prostate cancer, a single treatment of zoledronic acid significantly increased bone mineral density of the total hip and spine at 12 months. Annual zoledronic acid may provide a convenient and effective strategy to prevent bone loss in hypogonadal men. This study was supported in part by Novartis Oncology and by the Prostate Cancer Foundation. [Table: see text]

Bisphosphonate risedronate prevents bone loss in women with artificial menopause due to chemotherapy of breast cancer: a double-blind, placebo-controlled study.

1997 ◽  
Vol 15 (3) ◽  
pp. 955-962 ◽  
Author(s):  
P D Delmas ◽  
R Balena ◽  
E Confravreux ◽  
C Hardouin ◽  
P Hardy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lumbar Spine ◽  
Bone Loss ◽  
Femoral Neck ◽  
White Women ◽  
Treatment Withdrawal ◽  
Controlled Study ◽  
Treatment Needs ◽  
Mineral Density ◽  
Double Blind

PURPOSE To determine the effectiveness and safety of the bisphosphonate risedronate in preventing bone loss in young women with breast cancer and early menopause induced by chemotherapy who are at major risk for the development of postmenopausal osteoporosis. PATIENTS AND METHODS Fifty-three white women, aged 36 to 55 years, with breast cancer and artificially induced menopause were stratified according to prior tamoxifen use. Thirty-six patients received tamoxifen (20 mg/d). Within each stratum, patients were randomly assigned to receive risedronate (n = 27) or placebo (n = 26). Treatment consisted of eight cycles oral risedronate 30 mg/d or placebo daily for 2 weeks followed by 10 weeks of no drug (12 weeks per cycle). Patients were monitored for a third year without treatment. RESULTS Main outcomes of the study were changes in lumbar spine and proximal femur (femoral neck, trochanter, and Ward's triangle) bone mineral density (BMD), and biochemical markers of bone turnover. In contrast to a significant decrease of BMD at the lumbar spine and hip in the placebo group, there was an increase in BMD in the risedronate group. On treatment withdrawal, bone loss ensued, which suggests that treatment needs to be continuous to maintain a protective effect on bone mass. At 2 years, the mean difference (+/- SEM) between groups was 2.5% +/- 1.2%, (95% confidence interval [CI], 0.2 to 4.9) at the lumbar spine (P = .041) and 2.6% +/- 1.1%, (95% CI, 0.3 to 4.8) at the femoral neck (P = .029). Similar results were observed at the hip trochanter. Results by stratum indicate a beneficial, although partial, effect of tamoxifen in reducing bone loss. Risedronate was well tolerated and showed a good safety profile, with no evidence of laboratory abnormalities. CONCLUSION Risedronate appears to be a safe treatment that prevents both trabecular and cortical bone loss in women with menopause induced by chemotherapy for breast cancer.

Risk of bone loss in men with multiple sclerosis

2004 ◽  
Vol 10 (2) ◽  
pp. 170-175 ◽  
Author(s):  
Bianca Weinstock-Guttman ◽  
Eileen Gallagher ◽  
Monika Baier ◽  
Lydia Green ◽  
Joan Feichter ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Lumbar Spine ◽  
Bone Loss ◽  
Femoral Neck ◽  
Bone Mass ◽  
Multivariate Linear Regression Analysis ◽  
Mineral Density ◽  
Factors Associated ◽  
Dexa Scan

Context: O steoporosis and the increased fracture risk associated with osteoporosis become apparent in men appro ximately 10 years later than women. However, in recent studies, appro ximately 20% of healthy men in the age range 55-64 years were found to be osteopenic. Emerging data suggest a significantly increased prevalence of osteoporosis in men and women with multiple sclerosis (MS) compared to age-matched controls, but no specific clinical testing recommendations are available for men. Objective: To determine the proportion of male MS patients with osteoporosis and to identify the factors associated with the reduction in bone mass. Design: C onsecutive male MS patients seen at our MS clinic were screened with dual-X-ray absorptiometry (DEXA) scan for determining the bone mineral density (BMD). A ll patients had neurological Expanded Disability Status Scale (EDSS) evaluation. The results were compared to healthy age-matched male reference population using the Z score and to a cohort of women MS patients and women controls. C alcium, total testosterone, sex-hormone binding globulin (SHBG), 25-hydro xy-vitamin-D, and parathyroid hormone (PTH) were evaluated in male patients with decreased BMD. Relevant data on body mass index (BMI), medicatio n, alcohol consumption, smoking, and sexual dysfunction were recorded. Setting: Academic MS C entre. Patients and other participants: Forty consecutive male MS patients, age mean 51.2±8.7 years, and mean EDSS of 5.8±1.9 were evaluated with DEXA scan. O f these, 17.5% patients were relapsing - remitting (RR) MS, 57.5% were secondary progressive (SP) MS and 25% were primary progressive (PP) MS. Main outcome measure: Proportion of male MS patients with reduced BMD at the lumbar spine and femoral neck. Results: Thirty-two (80%) of our patients had a reduced bone mass of either lumbar spine or the femoral neck; of these 17 patients (42.5%) had osteopenia and 15 patients (37.5%) had osteoporosis. Twenty-o ne per cent (eight out of 38 patients) had vertebral, rib or extremities fractures. Multivariate linear regression analysis indicated that the EDSS (P B-0.0001) and BMI (P =0.0004) were the important factors associated with low BMD at the femoral neck and the EDSS was the important factor (P =0.0017) associated with low BMD at the lumbar spine. The same factors emerged as significantly associated with the corresponding Z scores, which are corrected for age and sex. No clear association between intravenous steroid therapy and BMD was evident in the multivariate analysis. Low levels of 25-hydroxy-vitamin-D were seen in 37.5% of patients. Conclusions: The proportion of male MS patients with reduced bone mass is high and disproportionate to their age and ambulation, consistent with an association between the MS disease process and patho logical bone loss. Increased awareness and bone density screening of male and female MS patients over 40 years of age is warranted.

scholarly journals Impact of Monthly 120 Mg Denosumab on Bone Metabolism in Bone-metastatic Prostate Cancer Undergoing Androgen Deprivation Therapy

2017 ◽  
Vol 2 (3) ◽  
pp. 41-46
Author(s):  
Jimpei Miyakawa ◽  
Satoru Taguchi ◽  
Motofumi Suzuki ◽  
Kaori Endo ◽  
Yorito Nose ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lumbar Spine ◽  
Femoral Neck ◽  
Bone Metabolism ◽  
Androgen Deprivation Therapy ◽  
Metastatic Prostate Cancer ◽  
Androgen Deprivation ◽  
Mineral Density ◽  
Bone Metabolism Markers ◽  
The Impact

Background: While semiannual 60 mg denosumab is a common treatment for osteoporosis, impact of monthly 120 mg denosumab, the common treatment protocol for bone metastases from solid tumors, on bone metabolism is unclear.Materials and Methods: We reviewed 15 patients with bone-metastatic prostate cancer who initiated monthly 120 mg denosumab in conjunction with androgen deprivation therapy between 2013 and 2014. Bone mineral density (BMD) was measured at lumbar spine and femoral neck using dual energy X-ray absorptiometry (DXA), before treatment and annually thereafter. Bone metabolism markers, including urine N-terminal telopeptide (uNTx) and bone type alkaline phosphatase (BAP), were monitored monthly.Results: Twelve of 15 (80%) patients had evaluable DXA before treatment, and of them, eight underwent DXA after a year of initiation without discontinuation of denosumab. Percent changes in BMD from baseline were +6.2% at lumbar spine and +7.6% at femoral neck, both of which were significant increases (both P<0.01). Bone metabolism markers were evaluable in 11 (73%) patients: uNTx decreased rapidly, while BAP declined gradually after initiating denosumab. These effects were similar to those seen by the standardized dose for osteoporosis in previous literature. There were no denosumab-related severe adverse events during the follow-up period. Conclusions: The impact of monthly 120 mg denosumab on bone metabolism was significant, but almost equivalent to that of the standard dose for osteoporosis (60mg semiannually) in bone-metastatic prostate cancer undergoing androgen deprivation therapy. Whereas the higher dose has reportedly reduced skeleton-related events, the effect on bone metabolism seemed plateaued or showed no dose-dependency.

Effect of Zoledronic Acid on Bone Mineral Density in Thalassemia-Induced Osteoporosis: Results of a Phase II Clinical Trial.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3826-3826
Author(s):  
Ali Taher ◽  
Sami Azar ◽  
Wael Shamseddeen ◽  
Dany Habr ◽  
Adlette Inati ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Lumbar Spine ◽  
Zoledronic Acid ◽  
Femoral Neck ◽  
Adverse Events ◽  
Bone Mineral ◽  
Beta Thalassemia ◽  
Mineral Density ◽  
Significant Change

Abstract Background: Osteoporosis is an important cause of morbidity in beta-thalassemia patients. Bisphosphonates are potent inhibitors of osteoclast activity and have been recently used for the treatment of osteoporosis in beta-thalassemia. The aim of this study is to assess the efficacy and safety of zoledronic acid in Lebanese thalassemics with osteoporosis. Methods: Eighteen thalassemic patients (13 thalassemia major and 5 intermedia) with osteoporosis defined as Z-score &lt;−2.5 were given zoledronic acid 4 mg i.v. every 3 months over a period of 12 months (Total of 4 doses administered). The efficacy of treatment was assessed by measuring Bone Mineral Density (BMD) at the lumbar spine, femoral neck and hip at baseline, 6 and 12 months. Other efficacy measurements included markers of bone formation and resorption (bone alkaline phosphatase (BAP), osteocalcin (OC), and urinary deoxypyridinoline (Dpd)), assessment of pain score, analgesic score, and performance score measured at baseline and at 3-month intervals. Safety assessment included regular physical exams, standard hematology and clinical chemistry tests, and adverse events recording. All patients were on Ca/Vitamin D supplementation prior to and during the study. Ten thalassemic osteoporotic patients were followed up only with serial BMDs as controls. Results: The characteristics of all patients are shown in Table 1. Both groups had no significant difference with respect to age, gender and baseline BMD. Patients taking zoledronic acid had a significant increase in their spine, femoral neck, trochanter and total hip BMD measurements over the 12-month period (all p-values&lt;0.05). Patients in the control group, on the other hand, did not have any significant change except in the spine BMD. The BMD values are presented in Table 2. There was a significant change in the levels of the OC and BAP over the 12-month follow-up in the treatment group (p=0.00 for both). Dpd levels did not significantly change overall (p=0.06) although they decreased throughout the study. Reported adverse events included joint pain in 9 patients (50%) after the 1st dose and in 2 (11.1%) after the 2nd dose and responding very well to oral analgesics. Two patients (11.1%) had perioral numbness and 3 (16.7%) had low grade fever after the 1st dose. No treatment-related adverse events were reported after the 3rd and 4th doses. No patients withdrew from the study. Conclusions: Treatment of Lebanese thalassemic osteoporotic patients with zoledronic acid 4 mg every 3 months is effective in increasing BMD at the lumbar spine and hip and is well-tolerated. Well-controlled studies with longer follow-up are needed to determine the fracture-reduction benefits and the most optimal zoledronic acid treatment dose and frequency in this patient population. Table 1: Main characteristics of the studied groups Table 2: BMD values of the treatment and control groups

Bone Loss in Patients with Previously Untreated Lymphoma: The Effect of Periodontal Disease on the Use of Zoledronic Acid

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5297-5297
Author(s):  
Vince D. Cataldo ◽  
Michael A. Thompson ◽  
Bela B. Toth ◽  
Perpetua Sanjorjo ◽  
B. Nebiyou Bekele ◽  
...  
Keyword(s):  
Vitamin D ◽  
Calcium Carbonate ◽  
Zoledronic Acid ◽  
Bone Loss ◽  
Femoral Neck ◽  
Periodontal Disease ◽  
Osteonecrosis Of The Jaw ◽  
Phase Iii ◽  
Exclusion Criterion ◽  
One Year

Abstract Treatment of lymphoma with alkylating agents and steroids is known to cause bone loss and increased fracture risk. These effects result from multiple causes including systemic lymphoma-related cytokine activity, steroid-mediated bone loss, and therapy-induced hypogonadism. Furthermore, over half of all untreated lymphoma patients are either osteopenic or osteoporotic at the time of diagnosis.1,2 Pamidronate is known to reduce bone loss and risk of vertebral fractures in lymphoma patients undergoing chemotherapy. However, the effects of the more potent bisphosphonate zoledronic acid in this setting are unknown. Therefore, we report on an ongoing phase III trial designed to evaluate the effect of zoledronic acid on the change in bone mineral density (BMD) in patients with newly-diagnosed lymphoma undergoing chemotherapy. In total, 72 patients will be randomized to either the control arm consisting of therapy with calcium carbonate (1200 mg orally per day) plus vitamin D (400 mg orally per day), or the bisphosphonate arm consisting of therapy with calcium carbonate and vitamin D as in the control arm plus zoledronic acid (4 mg IV given at baseline and at 6 months). The primary endpoint of the study is to compare the absolute change between the baseline and 12-month measures of BMD at the lumbar spine and femoral necks. Thus far, 97 patients have been screened for enrollment. Twenty-four patients (24.7%) failed screening due to periodontal disease, a predetermined exclusion criterion of the study. Twenty-three patients have been randomized to the control arm, and 18 patients have been randomized to the bisphosphonate arm. To date, 11 patients in the control arm and 7 patients in the bisphosphonate arm have completed the one-year follow up period including baseline and one-year BMD evaluations. In comparing the change in BMD at one year of patients in the control arm to that of patients in the bisphosphonate arm, the average change in T scores at the lumber spine was −0.482 vs. 0, at the left femoral neck was −0.218 vs. 0.057, and at the right femoral neck was −0.309 vs. 0.243, respectively. There have been no therapy-related serious adverse events in either arm of the study. In addition, no occurrences of osteonecrosis of the jaw have been noted. In conclusion, treatment with the bisphosphonate zoledronic acid in combination with calcium carbonate and vitamin D supplementation appears to provide prevention of bone loss or improvement in the BMD of patients with lymphoma undergoing chemotherapy. Given the large number of patients with below-average BMD prior to therapy and the known deleterious effects of lymphoma therapy on bone density, baseline BMD evaluation may be warranted in all lymphoma patients. In addition, the unexpectedly high rate of periodontal disease in this patient population further supports the need for careful dental evaluation prior to the consideration of bisphosphonate therapy given the well-described, albeit rare, risk of osteonecrosis of the jaw from zoledronic acid.

scholarly journals Rates of Bone Loss Among Women Initiating Antidepressant Medication Use in Midlife

2013 ◽  
Vol 98 (11) ◽  
pp. 4355-4363 ◽  
Author(s):  
Susan J. Diem ◽  
Kristine Ruppert ◽  
Jane A. Cauley ◽  
YinJuan Lian ◽  
Joyce T. Bromberger ◽  
...  
Keyword(s):  
Lumbar Spine ◽  
Bone Loss ◽  
Femoral Neck ◽  
Serotonin Reuptake ◽  
The United States ◽  
Community Dwelling ◽  
Mineral Density ◽  
Total Hip ◽  
Antidepressant Medications ◽  
Rate Of Bone Loss

Context: Concern has been raised that medications that block serotonin reuptake may affect bone metabolism, resulting in bone loss. Objective: The aim of the study was to compare annual bone mineral density (BMD) changes among new users of selective serotonin reuptake inhibitors (SSRIs), new users of tricyclic antidepressants (TCAs), and nonusers of antidepressant medications. Design and Setting: We conducted a prospective cohort study at five clinical centers in the United States. Participants: The study included 1972 community-dwelling women, aged 42 years and older, enrolled in the Study of Women's Health Across the Nation (SWAN). Exposure: The use of antidepressant medications was assessed by interview and verified from medication containers at annual visits. Subjects were categorized as nonusers (no SSRI or TCA use at any examination), SSRI users (initiated SSRI use after the baseline SWAN visit), or TCA users (initiated TCA use after the baseline visit), using a computerized dictionary to categorize type of medication. Main Outcome Measures: BMD at the lumbar spine, total hip, and femoral neck was measured using dual-energy x-ray absorptiometry at annual visits. Results: BMD was compared among 311 new users of SSRIs, 71 new users of TCAs, and 1590 nonusers. After adjustment for potential confounders, including age, race, body mass index, menopausal status, and hormone therapy use, mean lumbar spine BMD decreased on average 0.68% per year in nonusers, 0.63% per year in SSRI users (P = .37 for comparison to nonusers), and 0.40% per year in TCA users (P = .16 for comparison to nonusers). At the total hip and femoral neck, there was also no evidence that SSRI or TCA users had an increased rate of bone loss compared with nonusers. Results were similar in subgroups of women stratified by the Center for Epidemiologic Studies Depression Scale (&lt;16 vs ≥16). Conclusions: In this cohort of middle-aged women, use of SSRIs and TCAs was not associated with an increased rate of bone loss at the spine, total hip, or femoral neck.

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.

1997 ◽  
Vol 15 (4) ◽  
pp. 1341-1347 ◽  
Author(s):  
T Saarto ◽  
C Blomqvist ◽  
M Välimäki ◽  
P Mäkelä ◽  
S Sarna ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lumbar Spine ◽  
Bone Loss ◽  
Femoral Neck ◽  
Cancer Patients ◽  
Skeletal Metastases ◽  
Control Group ◽  
Breast Cancer Patients ◽  
Mineral Density ◽  
Premenopausal Breast Cancer

PURPOSE In the majority of premenopausal breast cancer patients, an adjuvant chemotherapy-induced early menopause occurs, which is known to be a strong predictor of osteoporosis. We present data on the effect of adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) therapy on bone mineral density (BMD) and the efficacy of clodronate on the prevention of bone loss in 148 premenopausal breast cancer patients without skeletal metastases. MATERIALS AND METHODS Patients were randomized to receive oral clodronate 1,600 mg/d or to a control group. In addition, patients were treated with six cycles of CMF therapy. BMD of the lumbar spine and femoral neck was measured by dual-energy x-ray absorptiometry (DEXA) before therapy and at 1 and 2 years. RESULTS Changes in the BMD of lumbar spine and femoral neck were -5.9% and -2.0% without clodronate and -2.2% and +0.9% with clodronate at 2 years (P = .0005 and .017, respectively). Patients who developed amenorrhea after chemotherapy had a rapid bone loss, which was significantly reduced by clodronate. In controls, bone loss was 9.5% in the lumbar spine and 4.6% in the femoral neck, while in the clodronate group, bone loss was 5.9% and 0.4%, respectively, at 2 years. Patients with preserved menstruation had only marginal changes in BMD. CONCLUSION 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.

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