The effect of clodronate and antioestrogens on bone loss associated with oestrogen withdrawal in postmenopausal women with breast cancer

In this study we report bone mineral density (BMD) changes during clodronate and antioestrogen treatment in women with breast cancer having discontinued hormone replacement therapy (HRT) at the time of operation compared to women who had not used HRT immediately before the operation. 61 postmenopausal women with operable breast cancer were treated with the adjuvant antioestrogen tamoxifen 20 mg or toremifene 60 mg daily for 3 years. All patients were randomized to clodronate (1.6 g daily orally) or control groups for 3 years. 23 patients had recently (recent users) and 38 never or not for at least 1 year before operation used HRT (non-users). BMD of lumbar spine and femoral neck were measured before antiresorptive therapy (antioestrogens and clodronate) and at 1, 2, 3 and 5 years thereafter. All patients were disease-free at the time of BMD measurements. Patients who had recently used HRT had more significant bone loss as compared to HRT non-users at 3 years in lumbar spine - 3.0% vs. + 1.2% (P< 0.001), but not in femoral neck - 0.4% vs. + 1.7% (P = 0.27). Adding 3-year clodronate treatment to antioestrogen therapy improved BMD marginally at 3 years: lumbar spine + 1.0% vs. -1.7% (P = 0.01) and femoral neck + 2.4% vs. -0.4% (P = 0.12). This was also seen at 5 years of follow-up, 2 years after termination of the antiresorptive therapy: HRT recent users vs. HRT non-users in lumbar spine -6.5% vs. +0.5% (P< 0.0001) and in femoral neck -4.8% vs. -1.5% (P = 0.38); and clodronate vs. controls in lumbar spine -1.0% vs. -3.2% (P = 0.06) and in femoral neck -0.1% vs. -5.2% (P = 0.001, respectively). The type of endocrine therapy (tamoxifen and toremifene) had no significant influence on BMD changes. We conclude from this study that postmenopausal women who have recently discontinued HRT experience more rapid bone loss than HRT non-users. Neither 3-year antioestrogen therapy alone nor antioestrogen together with clodronate could totally prevent the bone loss related to HRT withdrawal in lumbar spine, even though clodronate seemed to retard it.     

Clodronate improves bone mineral density in post-menopausal breast cancer patients treated with adjuvant antioestrogens.

The effect of clodronate on bone mineral density (BMD) was studied in 121 post-menopausal breast cancer women without skeletal metastases. In addition, two antioestrogens, tamoxifen and toremifene, were compared in their action on bone mineral density. Patients were randomized to have an adjuvant antioestrogen treatment either 20 mg of tamoxifen or 60 mg of toremifene daily for 3 years. In addition all patients were randomized to have 1600 mg of oral clodronate daily or to act as control subjects. BMD of the lumbar spine and femoral neck were measured by dual-energy radiographic absorptiometry before therapy and at 1 and 2 years. At 2 years, clodronate with antioestrogens markedly increased BMD in the lumbar spine and femoral neck by 2.9% and 3.7% (P = 0.001 and 0.006 respectively). There were no significant changes in BMD in the patients given antioestrogens only. No significant differences were found between tamoxifen and toremifene on bone mineral density. Clodronate with antioestrogens significantly increased bone mass in the lumbar spine and femoral neck. Both antioestrogens, tamoxifen and toremifene, similarly prevented bone loss in the lumbar spine and femoral neck.     

Bone mineral density and risk of postmenopausal breast cancer

To determine if higher bone mineral density (BMD) is a risk factor for breast cancer in women age 50 years and older. 37,860 women ≥50-year old with no previous breast cancer diagnosis had baseline BMD assessment between January 1999 and December 2007. Cox proportional hazards models were created for time to a new breast cancer as a function of lumbar spine or femoral neck BMD quartile (1st = lowest as reference) with adjustment for relevant covariates. A secondary analysis was performed to look for an association with estrogen receptor-positive (ER-positive) breast cancers. 794 invasive and in situ breast cancers (484 ER-positive) occurred with a median follow up of 5.4 years. Increased breast cancer risk was seen for the 3rd and 4th quartiles of lumbar spine BMD with hazard ratios (HRs) of 1.26 (95% CI, 1.01–1.58) and 1.45 (95% CI, 1.16–1.81), respectively and for the 3rd quartile of femoral neck BMD with a HR of 1.33 (95% CI, 1.07–1.64). A test for linear trend showed that lumbar spine BMD (P < 0.001) and femoral neck BMD (P = 0.04) were associated with increased risk. Higher lumbar spine BMD was also associated with increased risk of ER-positive breast cancer with HR of 1.45 (95% CI, 1.08–1.94), and 1.68 (95% CI, 1.24–2.27) for women in the 2nd and 4th quartiles, respectively. A test for linear trend showed lumbar spine BMD was associated with increasing risk of ER-positive breast cancer (P = 0.003). Increased ER-positive breast cancer risk was seen for the 3rd quartile of femoral neck BMD with a HR of 1.43 (95% CI, 1.08–1.89). Higher lumbar spine and femoral neck BMD are associated with higher risk of breast cancer in women ≥50-year old. Lumbar spine and femoral neck BMD are associated with increased risk of ER-positive breast cancer.     

Aminoterminal propeptide of type I procollagen (PINP) correlates to bone loss and predicts the efficacy of antiresorptive therapy in pre- and post-menopausal non-metastatic breast cancer patients.

The aim of this study was to determine the correlation between changes in collagen metabolites (ICTP, mature cross-linked carboxy-terminal telopeptide of type I collagen; PINP, the amino-terminal propeptide of type I procollagen) and bone mineral density (BMD) in 206 pre- and post-menopausal breast cancer patients with non-metastatic disease. All patients received adjuvant cancer treatment--premenopausal patients chemotherapy and post-menopausal patients anti-oestrogens. In addition, the patients were also randomized to receive oral clodronate 1600 mg daily for 3 years. BMD was measured at baseline and at 1 and 2 years, the collagen metabolites at baseline and at 1 year. There was a highly significant negative correlation between the changes in PINP and BMD in lumbar spine and femoral neck from baseline to 12 months in all patients (r(s) = -0.68, P < 0.0001, and -0.45, P < 0.0001, respectively), and in pre- and post-menopausal patients separately. The changes in PINP levels at 12 months predict further changes in BMD at 24 months (r = -0.70, P < 0.0001, and -0.51, P < 0.0001, respectively). ICTP and BMD changes correlated significantly only in lumbar spine of premenopausal patients who developed rapid bone loss due to chemotherapy-induced amenorrhoea (r(s) = -0.34, P = 0.0003). The PINP levels at 12 months were significantly lower in the clodronate group than in the control group (P < 0.0001). Our results indicate that PINP is a sensitive marker of bone turnover rate. Changes in PINP levels significantly predicted changes in BMD and correlated with the antiresorptive efficacy of clodronate treatment.     

Off-treatment bone mineral density changes in postmenopausal women receiving anastrozole for 5 years: 7-year results from the IBIS-II prevention trial

Background Anastrozole has been associated with substantial accelerated bone mineral density (BMD) loss during active treatment.Methods One thousand four hundred and ten women were included in a BMD substudy and stratified into three strata according to their baseline T-score at spine or femoral neck. The primary objective of this analysis was to investigate whether DXA BMD at the spine and hip changed two years after treatment cessation (between years 5 and 7) in those who did not receive risedronate.Results Five- and seven-year BMD data were available for a total of 528 women who did not receive risedronate. In women with normal BMD at baseline, an increase in BMD at the lumbar spine after anastrozole withdrawal was observed 1.25% (95% CI 0.73 to 1.77) (P = 0.0004), which was larger than in those on placebo (0.14% (−0.29 to 0.56))). At the hip, BMD remained unchanged between years 5 and 7 for those previously on anastrozole but continued to a decrease in those who had been randomised to placebo (−1.35% (−1.70 to −0.98)).Conclusions These are the first results reporting BMD changes after stopping anastrozole in a breast cancer prevention setting. Our results show that the negative effects of anastrozole on BMD in the preventive setting are partially reversible.Subject terms: Breast cancer, Randomized controlled trials     

Reduced bone mineral density in men following chemotherapy for Hodgkin's disease.

We have measured bone mineral density (BMD) in 29 men, mean age 35.0 (range 19.7-58.0) years, with testicular damage following MVPP or hybrid chemotherapy for Hodgkin''s disease. Forearm cortical bone mineral content (BMC) and lumbar spine and femoral neck integral BMD were measured 3.4 (1.1-6.8) years after completion of chemotherapy, and results expressed as Z (standard deviation) scores. There was a significant reduction in forearm cortical BMC (median BMC 1.727 g cm-1, median Z-score -0.8, P < 0.0005), in lumbar spine integral BMD (median BMD 1.141 g cm-2, median Z-score -0.6, P < 0.0005) and in femoral neck integral BMD (median BMD 0.991 g cm-2, median Z-score -0.4, P < 0.05). There was no significant correlation between Z-score and time elapsed since completion of chemotherapy, and no significant difference in Z-score according to type of chemotherapeutic regimen or number of cycles of chemotherapy received. In conclusion, men who are in complete remission following treatment of Hodgkin''s disease have reduced cortical and trabecular BMD. Possible causes include mild hypogonadism secondary to chemotherapy-induced impairment of Leydig cell function, a direct effect of chemotherapy on bone, an effect of high-dose glucocorticoid on bone or an effect of Hodgkin''s disease per se.     

Effect of Diphosphonates on Bone Mineral Density in Men Receiving Androgen Deprivation Therapy for Prostate Cancer

Patients receiving androgen deprivation therapy are associated with increasing loss of bone mineral density (BMD) and higher risk of skeletal-related events. We reviewed and analyzed the influence of diphosphonates on BMD change. A systemic literature research was conducted in PubMed and related bibliographies. The focus of data extraction was BMD percentage change of lumbar spine, total hip, and femoral neck after 12 months. Standardized mean difference (SMD) was pooled with the random-effects model, and metaregression and subgroup analysis were performed to explore heterogeneity. Nine articles (n = 920) were included and finally analyzed after screening 118 articles. We found significant improvement in BMD percentage changes of the lumbar spine, total hip, and femoral neck at 1 year (respectively, SMD = 6.379, 95% confidence interval [CI] = 3.740-9.018, P < .001, I² = 98.8%, P < .001; SMD = 4.870, 95% CI, 2.256-7.485, P < .001, I² = 98.9%, P < .001; SMD = 3.634, 95% CI, 1.989-5.279, P < .001, I² = 97.3%, P < .001). In individual variable metaregression analysis, application zoledronic acid or not showed a statistically significant influence on BMD percentage change of total hip (P = .018). In subgroup analyses, both zoledronic acid and alendronate showed a significant improvement in BMD percentage changes. Diphosphonates significantly increased BMD percentage changes of the lumbar spine, total hip, and femoral neck in men receiving androgen deprivation therapy for prostate cancer. Patients with androgen deprivation therapy should be evaluated BMD loss, and timely therapy with diphosphonates may be an appropriate strategy to prevent osteoporosis.     

Effect of oral clodronate on bone mass,bone turnover and subsequent metastases in women with primary breast cancer

Breast cancer treatments have been associated with accelerated bone loss and increased osteoporosis risk. In a subgroup analysis of a randomised, double-blind, placebo-controlled study, we compared the changes in spine and total hip bone mineral density (BMD) and biochemical markers of bone turnover in women with primary breast cancer who had received standard therapy plus either oral clodronate 1600 mg/d (n = 419) or placebo (n = 432) for 2 years. After 2 years, spine BMD was 1.92% higher in patients who received clodronate instead of placebo (P < 0.0001) and total hip BMD was 1.29% higher (P = 0.002 versus placebo). Patients who received clodronate had a median 26% reduction in levels of serum N-terminal pro-peptide of type I procollagen (PINP) – a marker of bone turnover – after 2 years of therapy. This compares with a median 5% increase in patients who received placebo (P < 0.0001). Effects on BMD, but not biochemical markers, persisted for up to 3 years post-treatment. Early changes in PINP were associated with changes in BMD and the likelihood of developing bone metastases. This study shows the use of oral clodronate during primary breast cancer treatment is associated with reduced bone turnover and protection against bone metastases.     

Effects of zoledronic acid on bone mineral density during aromatase inhibitor treatment of Korean postmenopausal breast cancer patients

The age distribution of breast cancer patients in Korea, where most are less than 60 years of age and have recently entered menopause, differs from that in the West. The aim of this study was to evaluate bone mineral density (BMD) changes in Korean breast cancer patients treated with an aromatase inhibitor (AI) either alone or in combination with zoledronic acid (ZA). Changes in BMD of the lumbar spine and hip were evaluated in 107 patients receiving AI treatment, of which 59 were treated in combination with ZA. The mean age of the patients was 54.9 years, and the median follow-up period was 38.2 months. With AI treatment alone, BMD loss was significant (all P < 0.0001) in the lumbar spine and hip 12 months (4.18 and 3.95%, respectively), 24 months (6.28 and 5.44%), and 36 months (8.17 and 6.82%) after treatment. In contrast, the combination treatment resulted in increased BMD in the lumbar spine and hip 12 months (2.45 and 0.89%, respectively), 24 months (3.51 and 1.03%), and 36 months (3.85 and 1.80%) after treatment. BMD loss in the lumbar spine was significantly greater in AI alone-treated women who had entered menopause within the past year compared with those who had entered menopause more than 1 year ago, when measured 12 and 24 months after treatment (P = 0.017 and 0.021, respectively). Importantly, ZA effectively inhibited AI-associated bone loss, independent of the postmenopausal interval. Because the proportion of patients in this study who had recently entered menopause was high, bone loss in Korean breast cancer patients treated with AI alone was higher than data reported from the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial. In conclusion, we have shown that ZA is very effective in preventing AI-induced bone loss in Korean postmenopausal breast cancer patients.     

Body composition and bone mineral density in breast cancer survivors and non‐cancer controls: A 12‐ to 15‐month follow‐up

While prognosis for breast cancer in women has improved, adverse side effects of treatments may negatively affect body composition and bone mineral density (BMD). This study assessed body composition and BMD changes in breast cancer survivors (BCS) (n = 10, 57.9 ± 5.7 years) and age‐matched women (non‐cancer, n = 10, 56.5 ± 4.3 years) over a 12‐ to 15‐month period via dual‐energy X‐ray absorptiometry. No differences were observed between groups at baseline except forearm BMD values were lower in BCS (BCS: 0.462 ± 0.070 g/cm²; Control: 0.539 ± 0.052 g/cm², p = .012). Body fat increased in both groups compared to baseline (BCS: 38.3–39.6 kg, p = .013; Control: 38.2–39.5 kg, p = .023) at the follow‐up. Significant decreases in BMD at the lumbar spine, femoral neck, total femur and ulna were observed in both groups. Breast cancer survivors had a greater decrease in left femoral neck BMD. While BCS demonstrated lower baseline forearm BMD values and a greater decrease in left femoral neck BMD, both groups showed an increase in body fat and decrease in forearm BMD. These findings support the implementation of interventions to improve body composition and BMD in both BCS and women without cancer.     

Alterations in bone mineral density and bone turnover markers in newly diagnosed adults with lymphoma receiving chemotherapy: a 1-year prospective pilot study

BackgroundBone mineral density (BMD) loss is poorly defined in lymphoma patients. The aim of this study was to measure the extent of BMD loss in newly diagnosed lymphoma patients receiving chemotherapy.Patients and methodsThis was a prospective, single-center study conducted in patients aged ≥18 years with previously confirmed lymphoma treated by chemotherapy. Patients with low baseline BMD defined as Z/T-score less than or equal to -2.5 and/or history of osteoporotic fractures were excluded. BMD was measured at baseline before initiating chemotherapy and 1 year later. Predictive factors of BMD loss were investigated.ResultsForty-one lymphoma patients (31 males and 10 females) receiving chemotherapy were enrolled. The median age at diagnosis was 59 (range: 19–86) years. Histological subtypes were predominantly diffuse large B-cell lymphoma (58%), mostly stage III–IV (54%). All patients received chemotherapy and 22% of patients received second-line treatment due to relapse or progressive disease. Thirty-two patients were evaluable at 1 year. The mean BMD changes were: -2.7% ± 3.9% for lumbar spine (P < 0.001), -2.2% ± 7.6% for femoral neck (P < 0.01) and -2.6% ± 4.5% for total hip (P < 0.0001). In multivariate analysis, predictive factors of BMD loss at baseline were (i) at lumbar spine: female gender (P = 0.01), higher lactate dehydrogenase level (P = 0.04) and lower creatinine clearance (P = 0.01); (ii) at total hip: lower albumin (P = 0.01), higher corrected serum calcium (P < 0.01), lower alkaline phosphatase (AP) (P < 0.01) and autologous stem cell transplant (P = 0.03); and (iii) at femoral neck: higher corrected serum calcium (P = 0.02) and lower bone AP (P = 0.01).ConclusionAdult patients with known lymphoma receiving chemotherapy experienced significant BMD loss at 1 year.     

Long-term effects of anastrozole on bone mineral density: 7-year results from the ATAC trial

BackgroundThis ‘Arimidex’, Tamoxifen, Alone or in Combination (ATAC) trial sub-study examined the effects of anastrozole and tamoxifen on bone mineral density (BMD) following 5 years of treatment.Patients and methodsLumbar spine and total hip BMD were assessed at years 6 and 7 in a total of 71 eligible patients. In total, 50 patients had evaluable data.ResultsFollowing anastrozole treatment, the lumbar spine median BMD increased by 2.35% (P = 0.04) and 4.02% (P = 0.0004) at years 6 and 7, while total hip median BMD increased by 0.71% (P = 0.3) and 0.5% (P = 0.8). After tamoxifen treatment, lumbar spine median BMD decreased by 0.79% (P = 0.2) and 0.30% (P = 0.9) at years 6 and 7, while total hip median BMD decreased by 2.09% (P = 0.0003) and 2.52% (P = 0.0002). Patients with a normal BMD or who were osteopenic at 5 years did not become osteoporotic.ConclusionsAnastrozole treatment-related bone loss did not continue into the off-treatment follow-up period. The recovery in lumbar spine BMD and absence of further loss at the hip is consistent with the reduction in the annual rate of fracture observed after treatment cessation in the main ATAC trial.     

Immediate versus delayed zoledronic acid for prevention of bone loss in postmenopausal women with breast cancer starting letrozole after tamoxifen-N03CC

Postmenopausal women with breast cancer (BC) are at increased risk for bone loss. Bisphosphonates improve bone mineral density (BMD) in normal postmenopausal women. The purpose of this study was to determine if immediate treatment with zoledronic acid preserves BMD in postmenopausal women with BC starting letrozole after tamoxifen. Postmenopausal women with BC completing tamoxifen were treated with daily letrozole 2.5 mg/vitamin D 400 I.U., calcium 500 mg twice daily and were randomized to upfront or delayed zoledronic acid 4 mg every 6 months. Patients in the delayed arm were only given zoledronic acid if they developed a post-baseline BMD T score <?2.0 or had a fracture. The primary endpoint was the mean percent change in lumbar spine (LS) BMD at 1 year. About 558 women enrolled; 395 provided 1 year BMD data. The upfront arm experienced a mean change of +3.66% in LS BMD versus -1.66% for the delayed group (P < 0.001). Changes at the femoral neck/total hip were also greater for the upfront versus delayed arms (P < 0.001; P < 0.001) with differences persisting at 2 years. Patients in the delayed arm were more likely to experience a clinically meaningful 5% loss of BMD at all sites versus the upfront zoledronate group. Patients in the upfront arm were slightly more likely to report limb edema, fatigue, fever, nausea and jaw osteonecrosis(1%). Upfront zoledronic acid prevents bone loss in postmenopausal women with BC starting letrozole after tamoxifen.     

Effects of exemestane and tamoxifen on bone health within the Tamoxifen Exemestane Adjuvant Multicentre (TEAM) trial: results of a German, 12-month,prospective, randomised substudy

Background: Adjuvant treatment of hormone receptor-positive breast cancer in postmenopausal women with aromatase inhibitors may be associated with increased bone loss.Patients and methods: Two hundred patients were randomised to receive exemestane or tamoxifen as adjuvant treatment of hormone receptor-positive breast cancer. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry at baseline and after 6 and 12 months treatment.Results: One hundred and sixty-one patients were assessable. Tamoxifen treatment resulted in a 0.5% increase from baseline in BMD at the spine, which was maintained at 12 months. Exemestane-treated patients experienced a 2.6% decrease from baseline in BMD at the spine at 6 months and a further 0.2% decrease at 12 months. There were significant differences in the changes in BMD between tamoxifen and exemestane at 6 and 12 months (P = 0.0026 and P = 0.0008, respectively). The mean changes in BMD from baseline at the total hip were also significantly different between exemestane and tamoxifen at 6 and 12 months (P = 0.0009 and P = 0.04, respectively). There was no difference between tamoxifen and exemestane in mean changes in BMD from baseline at the femoral neck.Conclusions: Exemestane treatment resulted in an increase in bone loss at 6 months; bone loss stabilised after 6- to 12-month treatment.     

Single infusion of zoledronic acid to prevent androgen deprivation therapy‐induced bone loss in men with hormone‐naive prostate carcinoma

BACKGROUND:

Androgen‐deprivation therapy (ADT) decreases bone mineral density (BMD) and increases fracture risk in patients with prostate carcinoma. The authors investigated the effectiveness of a single infusion of zoledronic acid initiated subsequent to ADT on BMD with hormone‐naive prostate carcinoma.

METHODS:

Forty men received either a single infusion of zoledronic acid (4 mg intravenously on Day 1) or no infusion during ADT. BMD of the proximal femur and posteroanterior lumbar spine was measured by dual‐energy x‐ray absorptiometry and urinary N‐telopeptide (u‐NTx) at 6 and 12 months.

RESULTS:

At baseline, the overall BMDs demonstrated no significant difference in lumbar spine and hip regions. At 6months, mean (±standard error) BMD of the posteroanterior lumbar spine decreased 4.6% ± 1.0% in control patients and increased 5.1% ± 1.2% in patients receiving zoledronic acid, a significant difference (P = .0002). At 12 months, the change in BMD between the 2 groups was statistically significantly different at the lumbar region (P = .0004), indicating that zoledronate preserved BMD. For u‐NTx, bone turnover was statistically significantly decreased in the zoledronate group compared with controls at 6 months (P < .0001), but returned to pretreatment levels at 12 months in the zoledronate group.

CONCLUSIONS:

Bone loss begins at 6 months with ADT. A single infusion of zoledronic acid in patients receiving ADT reduces bone mineral loss and maintains BMD at least at 12 months during ADT. Further study is needed to determine the best dosing schedule to prevent ADT‐induced bone loss in men with hormone‐naive prostate carcinoma. Cancer 2009. © 2009 American Cancer Society.     

Randomized trial of adjuvant zoledronic acid in postmenopausal women with high-risk breast cancer

PurposeWe present the results of a randomized multicenter clinical trial of adjuvant zoledronic acid (ZA) in postmenopausal women with high-risk breast cancer. The primary objective was change in bone mineral density (BMD) at the lumbar spine and femoral neck at 1 year. Secondary objectives included change in calcaneal BMD, disease-free survival (DFS), overall survival (OS), and toxicity.Patients and MethodsPostmenopausal women with stage II/III breast cancer diagnosed up to 5 years previous were eligible and randomized to either observation or ZA 4 mg intravenous every 3 months. Bone mineral density testing was performed at 0, 6, and 12 months.ResultsSixty-eight women were enrolled (36 ZA and 32 observation). The population was a median of 2 years from diagnosis and the majority received tamoxifen during the study. There was a significant difference in the mean change from baseline to 1 year follow-up for lumbar spine (increased by 4.28% ± 0.62%; P = .01), total femur (increased by 1.9% ± 0.4%; P = .03), trochanter (increased by 2.97% ± 0.69%; P = .03), and calcaneal BMD (increased by 2% ± 0.57%; P = .01) in favor of the ZA arm. No significant difference in the mean change for the femoral neck was seen. No significant differences in DFS or OS were observed.ConclusionZoledronic acid significantly improved the BMD at multiple skeletal sites in postmenopausal women largely on tamoxifen. No new safety signals were noted. There were insufficient events to comment on DFS or OS.     

Efficacy of zoledronic acid for prevention of bone loss in early-stage breast cancer patients receiving adjuvant therapy: A meta-analysis of 13 randomized controlled trials

Early-stage breast cancer (BC) patients receiving adjuvant therapy suffer from bone loss and increased fracture risk. Zoledronic acid (ZA) has been confirmed to inhibit bone metastasis and improve survival outcomes in early BC postmenopausal patients receiving adjuvant therapy. However, the efficacy of ZA for prevention of adjuvant therapy-induced bone loss from 2 different early BC groups, namely premenopausal and postmenopausal patients, still remain unclear. To obtain detailed characteristics, we performed this meta-analysis. PubMed, EMBASE, and Cochrane were searched. In premenopausal BC patients and postmenopausal BC patients, to assess bone loss, we calculated the weighted mean differences with 95% confidence intervals (CI) to evaluate lumbar spine (LS) bone mineral density (BMD), total hip (TH) BMD, and femoral neck (FN) BMD in ZA and non-ZA group with follow-up of 12 months. Thirteen randomized controlled trials (RCTs) encompassing 7375 patients were included. In a mixed population of early BC patients receiving adjuvant therapy, ZA significantly increased LS BMD (P < 0.00001), TH BMD (P < 0.00001), and FN BMD (P = 0.01) compared with non-ZA group. In premenopausal patient subgroup, LS BMD was greatly higher in patients with ZA compared to controls (0.06 g/cm²; 95% CI: 0.05-0.08), whereas there were no differences in TH BMD and FN BMD between patients with ZA and controls. In postmenopausal patient subgroup, both LS BMD (0.06 g/cm²; 95% CI: 0.05-0.07) and TH BMD (0.04 g/cm²; 95% CI: 0.03-0.04) were significantly higher in patients with ZA compared to controls, but there was no difference in FN BMD between patients with ZA and controls. To sum up, ZA prevents bone loss in early-stage BC patients receiving adjuvant therapy at different skeletal sites. In premenopausal patients, effectiveness of ZA in prevention of bone loss is confirmed at LS site, but not at TH and FN site. In postmenopausal patients, ZA has a satisfying efficacy for prevention of bone loss at LS and TH site, but not at FN site.     

绝经前早期乳腺癌患者于内分泌治疗中采用钙及维生素D对减少骨量的作用分析

目的 探讨绝经前早期乳腺癌患者于内分泌治疗中采用钙及维生素D对减少骨量的作用.方法 截选78例绝经前早期乳腺癌患者作为本次研究对象.所有研究对象均采用内分泌治疗,并于治疗前检测2组腰椎、全髋及股骨颈处骨密度情况.按照随机数字表法将研究对象分为对照组与治疗组,各39例.对照组不采用任何补充治疗,治疗组采用钙及维生素D辅助治疗.2组均治疗12个月,并再次检测2组骨密度,观察治疗安全性.结果 治疗12个月后,对照组腰椎骨密度较治疗前明显下降,与治疗组比较,P<0.05.2组患者全髋关节骨密度均较治疗前显著下降,而对照组下降更显著,P<0.05.治疗组患者腰椎、股骨颈骨密度较治疗前比较,P>0.05.对照组患者治疗前、后股骨颈骨密度比较,P>0.05;且与治疗组比较,P>0.05.治疗期间未发生不良反应.结论 于内分泌治疗绝经前早期乳腺癌期间及时补充钙及维生素D可有效减少患者骨量丢失,尤其是腰椎,从而对预防患者骨质疏松症的发生具有重要意义.     

Zoledronic acid (zoledronate) for postmenopausal women with early breast cancer receiving adjuvant letrozole (ZO-FAST study): final 60-month results

BackgroundAromatase inhibitors are the preferred adjuvant endocrine therapy for the majority of postmenopausal women with hormone-responsive early breast cancer. Although generally more effective than tamoxifen, aromatase inhibitor therapy is associated with increased bone loss and fracture risk.Patients and methodsPostmenopausal women receiving adjuvant letrozole (2.5 mg/day for 5 years; N = 1065) were randomly assigned to immediate zoledronic acid (zoledronate) 4 mg every 6 months for 5 years, or delayed zoledronate (initiated for fracture or on-study bone mineral density [BMD] decrease). The primary end point was the change in lumbar spine BMD at 12 months. Lumbar spine and total hip BMD at subsequent follow-up, disease-free survival (DFS), and overall survival were assessed as secondary end points.ResultsAt 60 months (final analysis), the mean change in lumbar spine BMD was +4.3% with immediate zoledronate and -5.4% with delayed intervention (P < 0.0001). Immediate zoledronate reduced the risk of DFS events by 34% (hazard ratio [HR] = 0.66; P = 0.0375) with fewer local (0.9% versus 2.3%) and distant (5.5% versus 7.7%) recurrences versus delayed zoledronate. In the delayed group, delayed initiation of zoledronate substantially improved DFS versus no zoledronate (HR = 0.46; P = 0.0334).ConclusionsImmediate zoledronate in postmenopausal women receiving letrozole preserved BMD and is associated with improved DFS compared with letrozole alone.Clinical Trials Registration NoNCT00171340.     

Prospective Study Evaluating Changes in Bone Quality in Premenopausal Women With Breast Cancer Undergoing Adjuvant Chemotherapy

BackgroundOvarian suppression from chemotherapy results in bone loss in premenopausal women with breast cancer (BC). Less is known about bone microarchitecture changes. We used high-resolution peripheral quantitative computed tomography (HR-pQCT) to measure volumetric bone density and trabecular and cortical microarchitecture in this population.Materials and MethodsThe primary endpoint was to assess changes in cortical thickness and trabecular bone density by HR-pQCT. Premenopausal women with stage I to III BC undergoing adjuvant chemotherapy underwent a bone mineral density (BMD) dual energy x-ray absorptiometry scan and HR-pQCT (voxel size, 82 microns) at baseline and 12 months. Paired t tests were used to observe the change over time in bone microarchitecture and areal and volumetric density.ResultsEighteen patients were evaluated, of which 12 patients had baseline and matched 12-month imaging. The mean age was 45.2 years (range, 35-51 years), 17 (94%) patients had hormone receptor-positive BC, and 16 (89%) initiated tamoxifen. At 12 months, there was a significant decrease in femoral neck (P < .05) and lumbar spine and total hip (P < .01) BMD. Changes detected by HR-pQCT at 12 months included significant decreases in cortical thickness and area at the tibia (P < .05), and total and cortical volumetric BMD at the radius and tibia (P < .01), as well as an increase in tibial trabecular area (P < .05).ConclusionPremenopausal women undergoing chemotherapy experience BMD decline and trabecular and cortical bone microarchitecture deterioration. In this population, future efforts should focus on therapy-induced bone loss and optimizing bone density-related management.