Adverse events and bone health during anastrozole therapy in postmenopausal Japanese breast cancer patients.

BACKGROUND: Although anastrozole (ANA), an aromatase inhibitor (AI), has been widely used for breast cancer patients; adverse events during ANA therapy in Japanese patients have not been reported. METHODS: The study included 656 postmenopausal breast cancer patients receiving ANA as postoperative adjuvant therapy in our hospital. Adverse events during ANA therapy, such as musculoskeletal effects and cerebro- and cardiovascular accidents, were investigated over a 5-year period. The percentage changes in lumbar (L2-4) spine bone mineral density (BMD) were determined in 71 patients receiving ANA alone and 26 patients receiving bisphosphonate in combination with ANA for 7-24 months. RESULTS: The follow-up period ranged from 6 to 60 months (median 23 months). Joint pain, the most common adverse event, was observed in 3.6% (24/656) of the patients. Cerebral infarctions occurred in 0.3% (2/656) of the patients, and no cardiovascular accidents occurred. Bone fractures occurred in nine patients receiving ANA alone. The mean age and BMD of the nine patients were 67.6 years and 71.8% (compared to the young adult mean BMD), respectively. Accumulated and annual fracture rates were 1.3 and 0.8%, respectively. A decrease in BMD was observed in 62.0% (44/71) of the ANA group compared to 26.9% (7/26) of the combination bisphosphonate group (P < 0.01). CONCLUSION: Incidence of adverse events during AI therapy in this Japanese postmenopausal population appears to be lower than that of the ATAC trial. The incidence of bone fractures during AI therapy is lower in Japan, and the addition of bisphosphonates enhances bone health. We should perform a prospective trial in the future to investigate the precise risk of bone fractures in Japanese patients.

Aromatase inhibitor-induced bone mineral loss and its prevention by bisphosphonate administration in postmenopausal breast cancer patients.

AIM: To investigate aromatase inhibitor-induced bone mineral loss and its prevention by bisphosphonate administration in postmenopausal breast cancer patients. METHODS: Subjects were 17 postmenopausal breast cancer patients (mean age, 63.3 +/- 9.9 years) receiving non-steroidal aromatase inhibitor (AI; anastrozole, 1 mg daily) only and 10 such patients (mean age, 65.0 +/- 5.1 years) receiving AI + bisphosphonate (risedronate sodium, 2.5 mg daily) for 6 months. All of the subjects had undergone surgical resection and had positive estrogen receptor tumor status. Age, age at menopause, years since menopause, height, weight, and body mass index (Wt/Ht(2)) were recorded. Lumbar spine (L2-4) bone mineral density (BMD), T-, and Z-scores were assessed on dual-energy X-ray absorptiometry before and after therapy. RESULTS: In the AI-only group BMD, T-, and Z-scores significantly decreased from the baseline during the 6-month therapy period (P < 0.05). Mean decreases in L2-4 BMD and Z-score were 2.5% and 3.0%, respectively. In the AI + bisphosphonate group, however, BMD, T-, and Z-scores significantly increased from the baseline values (P < 0.01). Mean increases in L2-4 BMD and Z-score were 4.5% and 3.3%, respectively. CONCLUSION: AI carries a potential risk of bone mineral loss despite the short therapy duration. Bisphosphonate has a preventive effect on this loss.

Bone mineral density in breast cancer patients with positive estrogen receptor tumor status.

AIM: The aim was to investigate bone mineral density (BMD) in breast cancer patients with positive estrogen receptor (ER) tumor status. METHODS: The participants were 110 postmenopausal breast cancer patients with positive estrogen receptor (ER+) tumor status. Two hundred and sixty-one age-matched, healthy postmenopausal women, all of whom were selected from our pooled data, served as controls. Age, age at menopause, years since menopause (YSM), height, weight, and body mass index (BMI, wt/ht(2)) were recorded. Lumbar spine (L2-4) BMD and Z-score were assessed by dual-energy X-ray absorptiometry. RESULTS: Bone mineral density in breast cancer patients was significantly higher than that in controls (0.89+/-0.12 g/cm(2) versus 0.84+/-0.16 g/cm(2), P<0.01). The Z-score in breast cancer patients was also higher than that in controls (110+/-13.6% versus 100+/-9.8%, P<0.001). Higher BMD and Z-score in breast cancer patients remained significant after adjusting for age, YSM, and BMI (P<0.05). CONCLUSIONS: Postmenopausal breast cancer patients with positive ER tumor status have higher BMD. Positive ER tumor status may be associated with higher cumulative exposure to estrogen.

Precedence of bone loss over changes in body composition and body fat distribution within a few years after menopause.

OBJECTIVE: The present study investigated the sequence of certain phenomena with a few years after menopause: bone mineral loss, decrease in lean body mass, increase in body fat mass, or the shift toward upper body fat distribution. METHODS: Subjects were 64 postmenopausal women aged 50-53 years with right side dominance (mean age+/-S.D., 51.4+/-1.1 years), and 59 age-matched regularly menstruating premenopausal women (51.7+/-1.2 years) serving as controls. Height, weight, body mass index (BMI, wt./ht.(2)), age at menopause (in postmenopausal women), and years since menopause (YSM) were recorded. Anthropometries, bone mineral density (BMD), and body fat distribution were assessed by dual-energy X-ray absorptiometry. RESULTS: Age at menopause and YSM in postmenopausal women were 51.7+/-1.2 and 2.3+/-1.7 years, respectively. Age, height, weight, BMI did not differ between the two groups. BMD of the bilateral arm, lumbar spine (L2-4), pelvis, and total body were significantly lower in postmenopausal women. However, leg BMD, trunk-leg fat ratio, body fat mass, and the lean body mass did not differ between the two groups. CONCLUSION: Within a few years after menopause, bone mineral loss precedes lean mass loss, increase in body fat mass, and a shift toward upper body fat distribution. We can say that bone tissue is more sensitive to hypogonadism than lean and fat tissues are.

Leptin production in pre- and postmenopausal women.

OBJECTIVES: To investigate the differences in leptin production between pre- and postmenopausal women. METHODS: Subjects were 75 pre- and 75 postmenopausal women. Age, height, weight, and body mass index (BMI, wt/ht(2)) were recorded. Serum leptin levels were measured by RIA. Total body fat mass and percentage of body fat mass were measured by whole-body scanning with dual-energy X-ray absorptiometry. Serum leptin levels, the ratio of serum leptin levels to total body fat mass (leptin-fat mass ratio), baseline characteristics, and anthropometric variables were compared between the two groups. In all subjects (n=150), relationship of serum leptin levels with menopausal status (pre- and postmenopause) was investigated by univariate and multiple regression analysis. RESULTS: Serum leptin levels in premenopausal women 8.4+/-4.8 ng/ml, which did not differ from that in postmenopausal women (9.2+/-7.1 ng/ml). Total body fat mass, percentage of body fat mass, and BMI did not differ between the two groups. Leptin-fat mass ratio in premenopausal women was 0.43+/-0.17 ng/ml/kg, which did not differ from that in postmenopausal women (0.44+/-0.24 ng/ml/kg). On both univariate and multiple regression analysis, serum leptin levels were not correlated with menopausal status. CONCLUSIONS: Menopausal status does not have a significant impact on leptin production.

Effects of vitamin K(2) on bone of ovariectomized rats and on a rat osteoblastic cell line.

The effects of vitamin K(2) on bone mineral density (BMD) and bone metabolic markers of ovariectomized rats, and those on mRNA expression of osteocalcin and IL-6 on a rat osteoblastic cell line, were investigated. BMD and bone metabolic markers were examined in ovariectomized rats after 2 months' treatment with vitamin K(2), and mRNA expression of osteocalcin and IL-6 were measured in the cell line after 24-hour treatment with vitamin K(2). Vitamin K(2) attenuated the decline in BMD after ovariectomy in the rats, and suppressed serum deoxypyridinoline levels of the ovariectomized rats. No effect on osteocalcin and IL-6 mRNA expression on the cell line was observed. In conclusion, vitamin K(2) has a bone-protective effect on ovariectomized rats.