scholarly journals AI-related BMD variation in actual practice conditions: A prospective cohort study

2016 ◽  
Vol 23 (4) ◽  
pp. 303-312 ◽  
Author(s):  
María Rodríguez-Sanz ◽  
Daniel Prieto-Alhambra ◽  
Sonia Servitja ◽  
Natalia Garcia-Giralt ◽  
Laia Garrigos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cohort Study ◽  
Bone Loss ◽  
Fragility Fractures ◽  
Vitamin D Supplementation ◽  
Actual Practice ◽  
First Year ◽  
Breast Cancer Patients ◽  
Mineral Density ◽  
25 Hydroxy Vitamin D

Abstract The aim of the study was to evaluate the progression of bone mineral density (BMD) during 3 years of aromatase inhibitors (AI) therapy in actual practice conditions. This prospective, clinical cohort study of Barcelona–Aromatase induced Bone Loss in Early breast cancer (B-ABLE) assessed BMD changes during 3 years of AI treatment in women with breast cancer. Patients with osteoporosis (T score < −2.5 or T score ≤ −2.0) and a major risk factor and/or prevalent fragility fractures were treated with oral bisphosphonates (BPs). Of 685 women recruited, 179 (26.1%) received BP treatment. By the third year of AI therapy, this group exhibited increased BMD in the lumbar spine (LS; 2.59%) and femoral neck (FN; 2.50%), although the increase was significant only within the first year (LS: 1.99% and FN: 2.04%). Despite BP therapy, however, approximately 15% of these patients lost more than 3% of their baseline bone mass. At 3 years, patients without BP experienced BMD decreases in the LS (−3.10%) and FN (−2.79%). In this group, BMD changes occurred during the first (LS: −1.33% and FN: −1.25%), second (LS: −1.19% and FN: −0.82%), and third (LS: −0.57% and FN: −0.65%) years of AI treatment. Increased BMD (>3%) was observed in just 7.6% and 10.8% of these patients at the LS and FN, respectively. Our data confirm a clinically relevant bone loss associated with AI therapy amongst nonusers of preventative BPs. We further report on the importance of BMD monitoring as well as calcium and 25-hydroxy vitamin D supplementation in these patients.

10-year follow-up of the efficacy of clodronate on bone mineral density (BMD) in early stage breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 676-676 ◽  
Author(s):  
T. Saarto ◽  
L. Vehmanen ◽  
C. Blomqvist ◽  
I. Elomaa
Keyword(s):  
Breast Cancer ◽  
Bone Loss ◽  
Postmenopausal Women ◽  
Cancer Patients ◽  
Early Stage ◽  
Statistical Significance ◽  
Lumbar Vertebrae ◽  
Breast Cancer Patients ◽  
Mineral Density

676 Background: We have previously reported that clodronate prevents bone loss in breast cancer patients (JCO 1997;15:1341, BJC 1997;75(4):602 and EJC 2001;37:2373). Here we report the 10-year follow-up data. Methods: 268 pre- (PRE) and postmenopausal (POST) node positive breast cancer patients were randomized to clodronate (CL), orally 1.6 g daily, or control groups for 3 years. PRE were treated with adjuvant chemotherapy and POST with antiestrogens (AE), tamoxifen 20 mg or toremifene 60 mg, for 3 years. The BMD of the lumbar vertebrae L1–4 (BMDLS) and femoral neck (BMDFN) was measured before the treatment and at 1, 2, 3, 5 and 10 years. 93 patients were eligible for 10-year analyses: 53 PRE and 40 POST. 132 patients had metastatic disease or died and 39 were either lost to follow-up or had to be excluded because having diseases or medications that influences bone metabolism. Results: PRE: BMDLS decreased -12.4% in the control and −8.7% in the CL group in 10 years: from 0 to 3 years −6.9 % vs. −4.2% and from 3 to 10 years −5.5% and −4.5%, respectively. BMDFN decreased −8.8% and −7.2%: from 0 to 3 years −2.9% vs. −2.6% and from 3 to 10 years −5.9% vs. −4.6%, respectively. POST: BMDLS decreased −3.0% in the AE and −1.7% in the AE+CL group in 10 years: from 0 to 3 years −1.5% vs. + 1.2% and from 3 to 10 years −1.5% vs. −2.9%, respectively. BMDFN decreased −7.7% and −6.0%: from 0 to 3 years −0.1% vs. +1.9% and from 3 to 10 years −7.6% vs. −7.9%, respectively. These differences do not reach statistical significance. At 10-years 18 patients had osteoporosis in LS and 15 in FN. Only 4 patients who had osteoporosis at 10 years had normal BMD before the therapy. Conclusions: As reported previously, clodronate prevents the bone loss during treatment in pre- and postmenopausal women. This beneficial effect seems to be maintained at least for 7 years after treatment termination in premenopausal. In postmenopausal women the effect seems to diminish within time. Due to small numbers of patients these differences are no longer statistically significant. Patients at risk of developing osteoporosis are among those who has pretreatment osteopenia i.e. baseline BMD measurement has predictive value. No significant financial relationships to disclose.

scholarly journals Bisphosphonates and the prevention of osteoporosis in the adjuvant setting

2005 ◽  
Vol 8 (11) ◽  
Author(s):  
Michael Gnant
Keyword(s):  
Breast Cancer ◽  
Bone Mineral Density ◽  
Vitamin D ◽  
Bone Loss ◽  
Bisphosphonate Treatment ◽  
Breast Cancer Patients ◽  
Adjuvant Setting ◽  
Mineral Density ◽  
Prevention Of Osteoporosis

Endocrine adjuvant therapy for breast cancer has been associated with a decrease in bone mineral density (BMD) and bone loss. For aromatase inhibitors, this bone loss is likely to be the most significant limitation to their long-term use. Treatments traditionally used to counteract his effect include exercise and supplementation with calcium and vitamin D. A newer treatment is the use of bisphosphonates, a class of drugs that reduce osteoclast activity. Clinical trials currently underway to examine the effect of bisphosphonate treatment on breast cancer patients have shown improvement in bone strength. Additional benefits of bisphosphonates, currently under study, give this class of drugs an important role to play in the treatment of cancer treatment-induced bone loss.

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.

scholarly journals Osteoporosis in Postmenopausal Women with Breast Cancer

2020 ◽  
Vol 05 (03) ◽  
pp. 1-1
Author(s):  
Jacqueline Lamond ◽  
◽  
Charles L. Shapiro ◽  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Bone Loss ◽  
Postmenopausal Women ◽  
Osteoporotic Fracture ◽  
Fragility Fractures ◽  
Osteoporosis Prevention ◽  
Mineral Density ◽  
Cancer Treatments ◽  
The Mean

Breast cancer and osteoporosis are both diseases of aging. The "one in eight" lifetime risks of breast cancer occur primarily in the sixth, seventh, eighth, and ninth decades of life. One-third of postmenopausal women will experience an osteoporotic fracture. It is the coalescence of osteoporosis, breast cancer, and breast cancer treatments that, in some cases, increases the risks of osteoporotic fracture. That makes it imperative to assess risk factors, screen, and prevent or treat osteoporosis in postmenopausal women with breast cancer. Osteoporosis is primarily a genetic disease with a few modifiable risk factors. These risk factors include greater than two to three alcoholic drinks per day, current smoking, and decreased physical activity. The standard screening tool for osteoporosis is dual-energy x-ray absorptiometry (DXA) that gives a readout of T-scores of the lumbar spine, total hip, and femoral neck. The T-score is the number of standard deviations (SD) above or below the mean bone mineral density (BMD) of an average young adult of the same sex. For every SD below the mean BMD, the fracture risks double. Osteoporosis prevention and treatment do not differ in women with or without breast cancer. The difference is in breast cancer treatments, such as aromatase inhibitors (AI), which cause two to three-fold higher bone loss than average postmenopausal bone loss. Two classes of drugs for osteoporosis are oral and intravenous (iv) bisphosphonates and the receptor activator of nuclear factor kappa B ligand (RANKL) ligand inhibitor, subcutaneous (sc) denosumab. All three prevent bone loss and reduce the likelihood of fragility fractures. The treatment choice depends upon patient and provider preferences, specific contraindications (e.g., renal insufficiency), compliance, and costs. Despite guidelines and algorithms for AI-induced bone loss, the screening and treatment of osteoporosis remain suboptimal in postmenopausal women with breast cancer.

scholarly journals Quantifying the effects of mechanical signals on musculoskeletal quality in a model of complete estrogen deprivation

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Reid Wilson ◽  
Gabriel M. Pagnotti, PhD ◽  
Khalid S. Mohammad, MD, PhD ◽  
Theresa A. Guise, MD
Keyword(s):  
Breast Cancer ◽  
Bone Mineral Density ◽  
Bone Loss ◽  
Cancer Patients ◽  
Cortical Thickness ◽  
Bone Area ◽  
Breast Cancer Patients ◽  
Mineral Density ◽  
Estrogen Deprivation ◽  
Mechanical Signals

Background and Hypothesis:  Post-menopausal, estrogen-receptor positive breast cancer patients are treated with aromatase inhibitors (AIs) to limit tumor progression; however, this causes adverse musculoskeletal effects. Zoledronic acid (ZA) is prescribed to inhibit bone resorption. Mechanical signals, delivered via low intensity vibration (LIV), stimulate bone formation. We hypothesize that combining LIV with ZA will mitigate bone loss in a murine model of complete estrogen-deprivation more effectively than either treatment alone.  Project Methods:  21-week-old C57BL/6 mice (n=20/group) were ovariectomized, receiving daily letrozole injections (OVX/AI) with LIV (OVX/AI+LIV), ZA (OVX/AI+ZA), LIV and ZA (OVX/AI+LIV/ZA) or underwent sham surgery with daily PBS (vehicle) injections (SH-OVX) for 22 weeks. Longitudinal dual energy X-ray absorptiometry (DEXA) and micro-computed tomography scans were analyzed for changes in body composition and bone microarchitecture, respectively.  Results:  OVX/AI reduced whole body (p< 0.0001) and lumbar spine (p<0.0001) bone mineral density (BMD) as compared to SH-OVX by 11% and 28%, respectively, as measured via DEXA. At 22w, OVX/AI+LIV/ZA had greater BMD across both regions-of-interest relative to OVX/AI (p<0.0001). Cortical bone area fraction (p<0.0001) and cortical thickness (p[Symbol]0.001) in distal femora decreased by 8% and 9%, respectively, in OVX/AI relative to SH-OVX. In OVX/AI+LIV/ZA, these parameters were greater relative to OVX/AI (p[Symbol]0.0001). OVX/AI+ZA and OVX/AI+LIV groups were not significantly different from OVX/AI in either cortical bone area fraction or cortical thickness.  Conclusion and Potential Impact:  Complete estrogen-deprivation reduced bone mineral density and altered microarchitecture. Mechanical signals provided via LIV combined with ZA prevent bone loss in aged estrogen-deprived mice. Combining these treatment strategies may reduce skeletal morbidity in breast cancer patients.

scholarly journals Osteoporosis in Postmenopausal Women with Breast Cancer

2020 ◽  
Vol 05 (02) ◽  
pp. 1-1
Author(s):  
Jacqueline Lamond ◽  
◽  
Charles L. Shapiro ◽  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Bone Loss ◽  
Postmenopausal Women ◽  
Osteoporotic Fracture ◽  
Fragility Fractures ◽  
Osteoporosis Prevention ◽  
Mineral Density ◽  
Cancer Treatments ◽  
The Mean

Breast cancer and osteoporosis are both diseases of aging. The "one in eight" lifetime risks of breast cancer occur primarily in the sixth, seventh, eighth, and ninth decades of life. One-third of postmenopausal women will experience an osteoporotic fracture. It is the coalescence of osteoporosis, breast cancer, and breast cancer treatments that, in some cases, increases the risks of osteoporotic fracture. That makes it imperative to assess risk factors, screen, and prevent or treat osteoporosis in postmenopausal women with breast cancer. Osteoporosis is primarily a genetic disease with a few modifiable risk factors. These risk factors include greater than two to three alcoholic drinks per day, current smoking, and decreased physical activity. The standard screening tool for osteoporosis is dual-energy x-ray absorptiometry (DXA) that gives a readout of T-scores of the lumbar spine, total hip, and femoral neck. The T-score is the number of standard deviations (SD) above or below the mean bone mineral density (BMD) of an average young adult of the same sex. For every SD below the mean BMD, the fracture risks double. Osteoporosis prevention and treatment do not differ in women with or without breast cancer. The difference is in breast cancer treatments, such as aromatase inhibitors (AI), which cause two to three-fold higher bone loss than average postmenopausal bone loss. Two classes of drugs for osteoporosis are oral and intravenous (iv) bisphosphonates and the receptor activator of nuclear factor kappa B ligand (RANKL) ligand inhibitor, subcutaneous (sc) denosumab. All three prevent bone loss and reduce the likelihood of fragility fractures. The treatment choice depends upon patient and provider preferences, specific contraindications (e.g., renal insufficiency), compliance, and costs. Despite guidelines and algorithms for AI-induced bone loss, the screening and treatment of osteoporosis remain suboptimal in postmenopausal women with breast cancer.

CYP19A1 rs10046 Pharmacogenetics in Postmenopausal Breast Cancer Patients Treated with Aromatase Inhibitors: One-year Follow-up

2020 ◽  
Vol 26 (46) ◽  
pp. 6007-6012
Author(s):  
Karin Baatjes ◽  
Armand Peeters ◽  
Micheal McCaul ◽  
Maria M. Conradie ◽  
Justus Apffelstaedt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lumbar Spine ◽  
Bone Loss ◽  
Cancer Patients ◽  
Aromatase Inhibitors ◽  
Postmenopausal Breast Cancer ◽  
Breast Cancer Patients ◽  
Mineral Density ◽  
Er Positive ◽  
Positive Breast Cancer

Background: Significant individual variation in bone loss associated with aromatase inhibitors (AIs) emphasizes the importance of identifying postmenopausal breast cancer patients at high risk for this adverse effect. The study explores the clinical relevance of genetic variation in the Cytochrome P450 19A1 (CYP19A1) gene in a subset of South African patients during the first year of taking AIs for estrogen receptor (ER)-positive breast cancer. Methods: The study population consisted of ER-positive breast cancer patients on AIs, followed in real-life clinical practice. Body mass index was measured and bone mineral density (BMD) was determined at baseline and at month 12. CYP19A1 genotyping was performed using real-time polymerase chain reaction analysis of rs10046, extended to Sanger sequencing and whole exome sequencing in 10 patients with more than 5% bone loss at month 12 at the lumbar spine. Results: After 12 months of AI treatment, 72 patients had completed BMD and were successfully genotyped. Ten patients (14%) experienced more than 5% bone loss at the lumbar spine over the study period. Genotyping for CYP19A1 rs10046 revealed that patients with two copies of the A-allele were 10.79 times more likely to have an ordinal category change of having an increased percentage of bone loss or no increase at the lumbar spine, compared to patients with the GA or GG genotypes (CI of 1.771- 65.830, p=0.01). None of the 34 patients without lumbar spine bone loss at month 12 were homozygous for the functional CYP19A1 polymorphism. At the total hip region, patients with the AA genotype were 7. 37 times more likely to have an ordinal category change of having an increased percentage of bone loss or no increase (CI of 1.101- 49.336, p=0.04). Conclusions: Homozygosity for the CYP19A1 rs10046 A-allele may provide information, in addition to clinical and biochemical factors that may be considered in risk stratification to optimize bone health in postmenopausal breast cancer women on AIs. Further investigation is required to place the clinical effect observed for a single CYP19A1 gene variant in a genomic context.

scholarly journals Effect of Endocrine Therapies on Bone in Breast Cancer Patients

Endocrinology ◽  
2011 ◽  
Vol 152 (1) ◽  
pp. 332-332
Author(s):  
R. J. Santen
Keyword(s):  
Breast Cancer ◽  
Bone Mineral Density ◽  
Bone Density ◽  
Bone Loss ◽  
Bone Formation ◽  
Postmenopausal Women ◽  
Bone Mineral ◽  
Breast Cancer Patients ◽  
Mineral Density ◽  
Markers Of Bone Formation

Recent data suggest that AIs are more effective than tamoxifen in the adjuvant and advanced disease settings and are now being more commonly used. Tamoxifen, as a selective estrogen receptor modulator, exerts estrogenic effects to preserve bone, whereas the AIs profoundly lower estrogen levels and cause bone loss. Recent comparative studies of these agents provide extensive data on fracture rates, bone mineral density, and markers of bone formation and resorption. Objective: The aim of the study was to review the mechanistic effects of estrogen on bone and clinical data regarding bone density, bone turnover markers, and fracture rates in women with breast cancer taking tamoxifen or AIs. Evidence Acquisition and Synthesis: Data presented reflect a review of the literature and data integration from the perspective of the author’s knowledge of the field. Results: Tamoxifen increases bone density and reduces fractures in postmenopausal women with breast cancer, whereas AIs increase rate of fracture, accelerate loss of bone mineral density, and enhance levels of markers of bone formation and resorption. Bisphosphonates and denosumab counteract the effects of the AIs on bone. Guidelines for management of AI-induced bone loss are available from several sources, but a simple algorithm guides decision making most effectively. Conclusions: Endocrine therapy for postmenopausal women with breast cancer exerts substantial effects on bone, and guidelines are available to assist in the management of bone-related problems.

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