Changes in bone mineral density during and after 3 years' use of tamoxifen or toremifene

OBJECTIVES: To study the effects of tamoxifen and toremifene on bone mineral density (BMD) in postmenopausal women with breast cancer. METHODS: Seventy patients with stage II-III breast cancer were randomized to start either tamoxifen (n = 36; 20 mg per day) or toremifene (n = 34; 40 mg per day) for 3 years. BMD in the lumbar spine and in the proximal femur was measured by dual-energy X-ray absorptiometry both before and during the treatment and 1 year after the discontinuation of the anti-estrogens. RESULTS: The baseline BMD measurements were comparable between the groups. In 3 years, lumbar BMD decreased by 1.7% in tamoxifen (P = 0.048) and 3.0% in toremifene (P = 0.001) users (ns between the groups), and femoral neck BMD by 0.9% (P = 0.040) and 1.3% (P = ns), respectively. The use of hormone replacement therapy (HRT) until the diagnosis of breast cancer was associated with decreases in lumbar BMD during anti-estrogen regimen (4% at 3 years) in contrast to unchanged lumbar BMD in women with no previous use of HRT. During the 1st year after the cessation of anti-estrogen, lumbar BMD did not change at all in either group whereas femoral BMD decreased in both the groups at the rate of 1.5-3.2%, as expected. CONCLUSIONS: We conclude that tamoxifen (20 mg) and toremifene (40 mg) have similar bone-sparing efficacy that in lumbar spine extends up to 1 year after the cessation of these regimens. This effect is not seen in lumbar spine BMD in those postmenopausal women who discontinue HRT at the time of breast cancer diagnosis.     

不同治疗方法对绝经后乳腺癌患者骨密度的影响

目的 探讨不同治疗方法 对绝经后乳腺癌患者骨密度(BMD)的影响.方法 研究分为健康对照组(50例)、肿瘤组[48例,其中24例再行他莫昔芬(TAM)组治疗].采用双能X线骨密度仪(DEXA)测定所有研究对象的基线BMD.肿瘤组术后均进行辅助化疗,其中24例(TAM组)化疗后继续使用TAM行内分泌治疗.用DEXA测量腰椎和左髋部位的BMD,比较肿瘤组化疗前、后以及TAM组行内分泌治疗8个月后BMD变化.结果 肿瘤组化疗后腰椎部位BMD(0.87±0.15)g/cm2比化疗前(0.93±0.15)g/cm2明显降低(P<0.05);TAM组行内分泌治疗8个月后腰椎BMD(0.90±0.04)g/cm2和股骨颈(0.74±0.05)g/cm2等左髋部位的BMD均有明显增加(P<0.05).结论 化疗可能导致绝经后乳腺癌患者BMD的下降,而TAM治疗能缓解化疗引起的BMD降低.     

Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer

BACKGROUND: Treatment with a gonadotropin-releasing hormone agonist decreases bone mineral density and increases the risk of fracture in men with prostate cancer. We conducted a controlled study of the prevention of osteoporosis in men undergoing treatment with a gonadotropin-releasing hormone agonist. METHODS: In a 48-week, open-label study, we randomly assigned 47 men with advanced or recurrent prostate cancer and no bone metastases to receive either leuprolide alone or leuprolide and pamidronate (60 mg intravenously every 12 weeks). Bone mineral density of the lumbar spine and the proximal femur was measured by dual-energy x-ray absorptiometry. Trabecular bone mineral density of the lumbar spine was measured by quantitative computed tomography. Forty-one men completed the study. RESULTS: In men treated with leuprolide alone, the mean (+/-SE) bone mineral density decreased by 3.3+/-0.7 percent in the lumbar spine, 2.1+/-0.6 percent in the trochanter, and 1.8+/-0.4 percent in the total hip, and the mean trabecular bone mineral density of the lumbar spine decreased by 8.5+/-1.8 percent (P<0.001 for each comparison with the base-line value). In contrast, the mean bone mineral density did not change significantly at any skeletal site in men treated with both leuprolide and pamidronate. There were significant differences between the two groups in the mean changes in bone mineral density at 48 weeks in the lumbar spine (P<0.001), trochanter (P = 0.003), total hip (P=0.005), and trabecular bone of the lumbar spine (P=0.02). CONCLUSIONS: Pamidronate prevents bone loss in the hip and lumbar spine in men receiving treatment for prostate cancer with a gonadotropin-releasing hormone agonist.     

The effect of circulating androgens on bone mineral density in postmenopausal women

BACKGROUND: Osteoporosis is a common problem in postmenopausal period. Recent studies have suggested that endogenous and exogenous androgens may influence the bone mineral density in women. There is limited data about the effect of circulating androgens on bone density in postmenopausal women. AIM: The aim of this study was to evaluate the effect of circulating androgens of ovarian and adrenal origin on bone mineral density in postmenopausal women. MATERIALS AND METHODS: This cross-sectional study included 178 postmenopausal women, who had never been treated with hormonal therapy or calciotropic agents. Serum free testosterone, dehydroepiandrosterone sulfate and androstenedione levels and their relationship with bone mass (dual X-ray absorptiometry) were evaluated. RESULTS: Serum free testosterone and DHEAS levels were correlated positively with bone mineral density at lumbar spine and femoral neck (P < 0.001). However, stepwise linear regression analyses revealed a differential effect of androgens on bone density. Serum free testosterone was among the independent predictor of bone density at lumbar spine (trabecular bone), whereas serum DHEAS level was of bone density at femoral neck (cortical bone). CONCLUSION: This study suggests that endogenous androgens are influential on bone density in postmenopausal women. However, regression analyses revealed a differential effect of androgens on different bone types.     

Bone mineral density in postmenopausal women treated with a vaginal ring delivering systemic doses of estradiol acetate

OBJECTIVE: To evaluate the effect on bone mineral density of vaginal rings delivering estradiol acetate at two systemic doses versus a locally active vaginal ring in healthy postmenopausal women. DESIGN: A total of 174 postmenopausal women (younger than age 65 years) were randomly assigned to a 0.05 mg/day vaginal ring, 0.1 mg/day vaginal ring, or 0.0075 mg/day vaginal ring (active comparator), and treated for 96 weeks. Of these, 170 took a study drug; 85 taking the study drug had data at 96 weeks, and 132 women were included in the intent-to-treat analysis. Non-hysterectomized women received 1 mg of norethisterone taken on the last 12 days of each 28-day monthly cycle. The primary endpoint was change in lumbar spine bone mineral density (L2-L4); change in total hip bone mineral density was a secondary endpoint. RESULTS: At 96 weeks, mean lumbar spine bone mineral density increased 2.7% and 3.3% from baseline, respectively, in the 0.05-mg and 0.1-mg groups (P < 0.001 for both) compared with an 0.3% increase in the 0.0075-mg group (P = 0.56). Mean total hip bone mineral density increased 1.7% and 1.8% from baseline, respectively, in both the 0.05-mg and 0.1-mg groups (P < 0.001) and decreased 1.2% in the 0.0075-mg group (P = 0.001). All vaginal ring doses were well tolerated. CONCLUSIONS: Vaginal rings delivering systemic doses of estradiol increase bone mineral density of the lumbar spine and total hip in healthy postmenopausal women. Safety and acceptability were similar to existing estradiol therapies.     

Reduced bone mass in daughters of women with osteoporosis

To determine whether premenopausal daughters of women with postmenopausal osteoporosis have lower bone mass than other women of the same age, we measured the bone mineral content of the lumbar spine and femoral neck and midshaft, using dual-photon absorptiometry, in 25 postmenopausal women with osteoporotic compression fractures and in 32 of their premenopausal daughters; we then compared the results with those in normal controls. As compared with normal postmenopausal women, women with osteoporosis had lower bone mineral content in the lumbar spine, femoral neck, and femoral midshaft by 33, 24, and 15 percent, respectively (P less than 0.001 for each comparison by the one-tailed t-test). As compared with normal premenopausal women, the daughters of women with osteoporosis had lower bone mineral content at these sites by 7, 5, and 3 percent, respectively (P = 0.03, 0.07, and 0.15, respectively, by the one-tailed t-test). In terms of a standardized score, we calculated that the mean (+/- SEM) relative deficits in bone mineral content in the daughters of women with osteoporosis were 58 +/- 18 percent (lumbar spine) and 34 +/- 16 percent (femoral neck) of the relative deficits in their mothers. We conclude that daughters of women with osteoporosis have reduced bone mass in the lumbar spine and perhaps in the femoral neck; this reduction in bone mass may put them at increased risk for fractures. We also conclude that postmenopausal osteoporosis may result partly from a relatively low peak bone mass rather than from excessive loss of bone.     

High Serum Osteopontin Levels Are Associated with Low Bone Mineral Density in Postmenopausal Women

Osteopontin (OPN) is an acidic, noncollagenous matrix protein produced by the bone and kidneys. It is reportedly involved in bone resorption and formation. We examined the association between serum OPN levels and bone mineral density in postmenopausal women. Premenopausal women (n=32) and postmenopausal women (n=409) participated in the study. We measured serum osteopontin levels and their relationships with bone mineral density and previous total fragility fractures. The postmenopausal women had higher mean serum OPN levels compared to the premenopausal women (43.6±25.9 vs 26.3±18.6 ng/mL; P<0.001). In the postmenopausal women, high serum OPN levels were negatively correlated with mean lumbar bone mineral density (BMD) (r=-0.113, P=0.023). In a stepwise multiple linear regression model, serum OPN levels were associated with BMD of the spine, femoral neck, and total hip after adjustment for age, body mass index, smoking, and physical activity in postmenopausal women. However, serum OPN levels did not differ between postmenopausal women with and without fractures. Postmenopausal women exhibit higher serum OPN levels than premenopausal women and higher serum OPN levels were associated with low BMD in postmenopausal women.     

Trimegestone in a low-dose, continuous-combined hormone therapy regimen prevents bone loss in osteopenic postmenopausal women

OBJECTIVE: To determine the efficacy of estrogen + progestogen therapy with 1 mg 17beta-estradiol and 0.125 mg trimegestone in the prevention of postmenopausal osteoporosis. DESIGN: For this study, 360 healthy, postmenopausal women with osteopenia [lumbar spine bone mineral density (BMD) between -1.0 and -2.5 SD of the premenopausal mean value] were enrolled in a 2-year prospective, randomized study, and 70% completed. Treatments were 1 mg 17beta-estradiol + 0.125 mg trimegestone (n = 179) or placebo (n = 181), given as daily oral therapy. All received a daily supplement of 500 mg calcium and 400 IU vitamin D. BMD measurements at the lumbar spine, total hip, and femoral neck as well as blood and urinary biochemical markers of bone turnover (serum osteocalcin), serum bone-specific alkaline phosphatase, serum CrossLaps, and urinary CrossLaps took place regularly. RESULTS: BMD increases relative to placebo were 6.3%, 3.9%, and 3.8% at the lumbar spine, total hip, and femoral neck, respectively (all P < 0.001). The biochemical markers of bone turnover were suppressed accordingly. Serum CrossLaps and urinary CrossLaps decreased rapidly, by 52% and 54%, respectively, whereas serum osteocalcin and serum bone-specific alkaline phosphatase revealed a more retarded decrease of 40% and 33%, respectively. Of the women receiving hormone therapy, 75% had amenorrhea from the first cycle, and 5% withdrew prematurely due to metrorrhagia or mastalgia. CONCLUSION: This new estrogen + progestogen therapy is efficient in increasing BMD in an osteopenic postmenopausal population. Furthermore, it is well tolerated, with few adverse events and an early bleeding control, which is likely to improve compliance to the treatment over the long term.     

Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis

Although fluoride increases bone mass, the newly formed bone may have reduced strength. To assess the effect of fluoride treatment on the fracture rate in osteoporosis, we conducted a four-year prospective clinical trial in 202 postmenopausal women with osteoporosis and vertebral fractures who were randomly assigned to receive sodium fluoride (75 mg per day) or placebo. All received a calcium supplement (1500 mg per day). Sixty-six women in the fluoride group and 69 women in the placebo group completed the trial. As compared with the placebo group, the treatment group had increases in median bone mineral density of 35 percent (P less than 0.0001) in the lumbar spine (predominantly cancellous bone), 12 percent (P less than 0.0001) in the femoral neck, and 10 percent (P less than 0.0001) in the femoral trochanter (sites of mixed cortical and cancellous bone), but the bone mineral density decreased by 4 percent (P less than 0.02) in the shaft of the radius (predominantly cortical bone). The number of new vertebral fractures was similar in the treatment and placebo groups (163 and 136, respectively; P not significant), but the number of nonvertebral fractures was higher in the treatment group (72 vs. 24; P less than 0.01). Fifty-four women in the fluoride group and 24 in the placebo group had side effects sufficiently severe to warrant dose reduction; the major side effects were gastrointestinal symptoms and lower-extremity pain. We conclude that fluoride therapy increases cancellous but decreases cortical bone mineral density and increases skeletal fragility. Thus, under the conditions of this study, the fluoride-calcium regimen was not effective treatment for postmenopausal osteoporosis.     

Esterified estrogen therapy in postmenopausal women. Relationships of bone marker changes and plasma estradiol to BMD changes: a two-year study

OBJECTIVE: To determine the relationships among bone mineral density changes, bone marker changes, and plasma estrogens in postmenopausal women receiving estrogen replacement therapy. DESIGN: A total of 406 postmenopausal women received 1,000 mg calcium and continuous esterified estrogens (0.3 mg, 0.625 mg, or 1.25 mg) or placebo daily for up to 24 months. Bone mineral density and bone marker measurements were determined at 6-month intervals; plasma estrogens were measured in a subset after 12, 18, and 24 months. RESULTS: Esterified estrogens produced significant increases in bone mineral density (lumbar spine, hip) compared with baseline and placebo at 6, 12, 18, and 24 months. Bone markers decreased from baseline with all esterified estrogen doses relative to placebo. Bone marker changes at 6 months correlated negatively with bone mineral density changes at 24 months (correlation coefficient range = -0.122 to -0.439). The strongest correlation was noted for spine bone mineral density changes and serum osteocalcin. Mean plasma estrogen levels increased with esterified estrogen dose, and bone mineral density changes correlated positively with plasma estrogen levels. Positive bone mineral density changes were noted in treatment groups with plasma estradiol levels at and above 25 pg/mL. CONCLUSIONS: Esterified estrogens, at doses from 0.3 mg to 1.25 mg/day, unopposed by progestin, increase bone mineral density of the spine and hip in postmenopausal women. These bone mineral density changes correlated significantly with bone marker changes at 6 months and with plasma estrogens at 12, 18, or 24 months. Data variability minimizes the predictive value of the bone marker changes in monitoring individual therapy.     

Relationship between self-reported periodontal status and skeletal bone mineral density in Japanese postmenopausal women

OBJECTIVE: Several investigators have linked periodontal disease progression and low skeletal bone mineral density in postmenopausal women. However, little is known about whether self-reported periodontal status is the reflection of skeletal bone mineral density. We investigated whether self-reported poor periodontal status is associated with low skeletal bone mineral density in postmenopausal women. DESIGN: Relationships among self-reported periodontal status, number of teeth remaining, and bone mineral density of the lumbar spine and the femoral neck were evaluated in 253 Japanese postmenopausal women (mean +/- SD, 56.6 +/- 7.7) recruited from the patients who visited our clinic for bone mineral assessment between 1997 and 2003. Self-reported periodontal symptoms included gingival swelling, gingival bleeding, purulent discharge, and tooth mobility at the time of bone mineral assessment. RESULTS: Analysis of covariance adjusted for age, height, weight, years since menopause, duration of estrogen use, and regular oral care revealed that subjects without periodontal symptoms had significantly higher BMD of the lumbar spine than did those with periodontal symptoms (mean +/- SEM, 0.962 +/- 0.014 vs 0.921 +/- 0.013; P = 0.038); however, there were no significant differences in the number of remaining teeth and bone mineral density of the femoral neck between them. The odds of low spine bone mineral density in subjects with periodontal symptoms was 2.01 (95% CI = 1.15 to 3.50). CONCLUSION: Our results suggest that self-reported poor periodontal status may be associated with low bone mineral density of the lumbar spine in postmenopausal women.     

Factors affecting bone loss around menopause in women without HRT: a prospective study

OBJECTIVES: The present study evaluated the effects of menopause and other putative bone loss modifying factors on bone mineral density (BMD) change. METHODS: The study population, 396 healthy women aged 48-59 years with no history of hormone replacement therapy (HRT) use or any bone affecting disease or medications, was selected from a random sample (n=2025) of the OSTPRE-study cohort (n=13100) in Kuopio, Finland. BMD at lumbar spine (LS) and three areas of proximal femur (femoral neck (FN), Ward's triangle (W), trochanter (T)) was measured with dual X-ray absorptiometry at baseline in 1989-1991 and at 5 years in 1994-1997. RESULTS: 116 women who reported the beginning of menopause during the follow-up (perimenopausal) had the greatest mean annual bone loss (-1.22%/year (LS), -0.87% year (FN), -1.14%/year (W), -0.36%/year (T)). In women under 5 years postmenopausal at baseline (early postmenopausal, n=172) bone loss rate was significantly lower than in perimenopausal women. In women over 5 years postmenopausal at baseline (late postmenopausal, n=108) bone loss rate was significantly further decreased only at lumbar spine. In peri- and postmenopausal women the annual BMD change was best described as a trinomial function of the duration of menopause at all sites (P<0.03). Of the life-style factors studied protective effects were found in weight increase in both spinal and femoral bone (P=0.010/P<0.001), high baseline weight in spine (P<0.001) and high grip strength in femoral neck (P=0.002). CONCLUSION: The beginning of menopause is accompanied by significant bone loss, which decreases in later menopause. Few other physiological and life-style factors were found to significantly contribute to this phenomenon.     

Osteocalcin and bone alkaline phosphatase in the serum of women with liver disease

To identify the types of liver disease in which osteopenia is a prominent feature and to understand the mechanisms of bone loss, bone mineral density was measured in the lumbar spine and hip, bone alkaline phosphatase, osteocalcin, and biochemical markers of calcium homeostasis were measured in 42 women, aged 33 to 52, with chronic liver disease and in 299 healthy women of similar age. In control women, bone alkaline phosphatase and osteocalcin correlated negatively with bone density at all sites (p less than 0.05). In women with liver disease, osteocalcin correlated negatively with bone density in the lumbar spine (p less than 0.007), whereas bone alkaline phosphatase did not correlate with bone density at any site. Bone alkaline phosphatase correlated positively with osteocalcin in control women (p = 0.001) and negatively with osteocalcin in women with liver disease (p = 0.03). Serum bone alkaline phosphatase in women with liver disease was increased significantly over serum bone alkaline phosphatase of control women, probably because of decreased clearance owing to defective function or decreased numbers of hepatic asialoglycoprotein receptors. Bone density was lower in the lumbar spines and hips of women with primary sclerosing cholangitis, primary biliary cirrhosis, and chronic active hepatitis or fibrosis without cirrhosis than in the lumbar spine and hips of control women. However, the differences were not significant, possibly because of the small sample size. It is concluded that, in liver disease, osteocalcin is a more reliable marker of osteoblastic function than bone alkaline phosphatase. Although our results show that bone density may decrease in women with cholestatic liver disease, larger studies are needed to determine the degree of osteopenia.     

伊班膦酸钠间断静脉输注治疗北京绝经后骨质疏松症的疗效

 目的 评价新一代双膦酸盐类药物伊班膦酸钠间断静脉输注对北京绝经后骨质疏松症的疗效及安全性。方法 研究纳入绝经后骨质疏松女性60例,年龄48~74岁,绝经年限3~32年,随机分为2组,治疗组每3个月静脉输注伊班膦酸钠2mg,对照组每周口服阿仑膦酸钠70mg,疗程12个月。疗效指标为腰椎及髋部骨密度（采用双能X线骨密度仪测量）、骨吸收指标血I型胶原羧基末端肽（酶联免疫吸附法测量）及骨形成指标碱性磷酸酶（自动分析仪酶法检测）。安全性指标包括血尿生化指标、心电图及不良反应。结果 59例患者完成研究。治疗12个月后,伊班膦酸钠组腰椎2-4、股骨颈及大转子骨密度增幅达6.3%,2.5%和0.1% (腰椎P <0.001,股骨颈P <0.01)。阿仑膦酸钠组腰椎、股骨颈及大转子骨密度改变率为 3.7%,4.9和-0.5% (腰椎和股骨颈P <0.001)。两组间治疗前后骨密度均无明显差别。伊班膦酸钠和阿仑膦酸钠治疗后ALP及CTX浓度均快速、显著下降,ALP降低15.8%和17.2%,CTX降低78.1%及43.2%（均P <0.001）。两组血钙磷水平、肝肾功能在正常范围内,伊班膦酸钠组常见的不良反应是首次输液后肌肉疼痛和低热,占26.7%,反酸、上腹不适是阿仑膦酸钠组主要的不良反应,占13.3%,患者可以耐受这些轻度的不良反应。结论 新一代双膦酸类药物伊班膦酸钠对于治疗绝经后骨质疏松症是安全而有效的。     

Changes in the serum levels of osteoprotegerin and soluble receptor activator for nuclear factor kappaB ligand after estrogen-progestogen therapy and their relationships with changes in bone mass in postmenopausal women

OBJECTIVE: To investigate changes in the serum levels of osteoprotegerin (OPG) and soluble receptor activator for nuclear factor kappaB ligand (sRANKL) after estrogen plus progestogen therapy (EPT) and to determine their relationships with changes in bone mineral density (BMD) and bone turnover markers in postmenopausal women. DESIGN: Serum levels of OPG, sRANKL, and bone turnover markers, such as osteocalcin and type I C-telopeptide breakdown products, parathyroid hormone, calcitonin, calcium, and phosphorus, and BMD at the lumbar spine and proximal femur were measured in 297 postmenopausal Korean women. In all, 143 women were treated with sequential EPT for 1 year. RESULTS: Before EPT, serum OPG and sRANKL levels and RANKL/OPG ratios were not related to BMD at the lumbar spine and proximal femur, except for a negative correlation (r = -0.13, P < 0.05) between serum OPG and BMD at the trochanter. Of the bone markers, serum parathyroid hormone alone correlated negatively with serum OPG (r = -0.19, P < 0.005) and positively with serum sRANKL (r = 0.23, P < 0.001) and sRANKL/OPG ratios (r = 0.28, P < 0.001). After 6 months of EPT, serum OPG and sRANKL levels were unchanged, but sRANKL/OPG ratios and serum levels of bone turnover markers, such as osteocalcin, type I C-telopeptide breakdown products, and phosphorus decreased significantly. The 1-year change in BMD at the lumbar spine and proximal femur after EPT was not found to be correlated with basal levels of serum OPG, sRANKL, and sRANKL/OPG ratios and their changes at 6 months after EPT. After 6 months of EPT, changes in all bone markers were not associated with changes in circulating OPG, sRANKL levels, and sRANKL/OPG ratios. CONCLUSIONS: After EPT, sRANKL/OPG ratios in the circulation decreased, but changes in this OPG-sRANKL system have no association with changes in any bone marker or BMD. The OPG-sRANKL system in the circulation might be involved in reduced bone resorption after EPT, but does not seem to be clinically useful for predicting BMD or bone turnover status and bone response after hormone therapy.     

The effect of low-dose conjugated equine estrogens and cyclic MPA on bone density

OBJECTIVE: to compare the effect of 0.3 and 0.625 mg conjugated equine estrogens on bone mineral density (BMD) in a private practice setting. METHODS: postmenopausal women interested in hormone replacement therapy were prescribed either 0.3 or 0.625 mg conjugated equine estrogens daily with 10 mg medroxyprogesterone acetate days 1-12 of the month. All women were given calcium citrate 1000 mg/day and vitamin D 400 IU/day. DEXA bone mineral density studies of the spine and hip were performed at baseline and 1 year. RESULTS: there was no significant difference in BMD at the spine, the trochanter or the femoral neck compared with baseline in either the 0.625 or 0.3 mg group. The mean percent increase in BMD for the 0.3 versus 0.625 mg group was: spine 2.6 versus 3.8%, femoral neck 1.8 versus 1.5%, and trochanter 0.5 versus 2.6%. CONCLUSION: both the 0.625 mg dose and the 0.3 mg dose of conjugated equine estrogens preserved BMD at the spine and hip over one year in early postmenopausal women who were also given cyclic medroxyprogesterone acetate, calcium citrate and vitamin D.     

Alendronate for the treatment of osteoporosis in men

BACKGROUND: Despite its association with disability, death, and increased medical costs, osteoporosis in men has been relatively neglected as a subject of study. There have been no large, controlled trials of treatment in men. METHODS: In a two-year double-blind trial, we studied the effect of 10 mg of alendronate or placebo, given daily, on bone mineral density in 241 men (age, 31 to 87 years; mean, 63) with osteoporosis. Approximately one third had low serum free testosterone concentrations at base line; the rest had normal concentrations. Men with other secondary causes of osteoporosis were excluded. All the men received calcium and vitamin D supplements. The main outcome measures were the percent changes in lumbar-spine, hip, and total-body bone mineral density. RESULTS: The men who received alendronate had a mean (+/-SE) increase in bone mineral density of 7.1+/-0.3 percent at the lumbar spine, 2.5+/-0.4 percent at the femoral neck, and 2.0+/-0.2 percent for the total body (P<0.001 for all comparisons with base line). In contrast, men who received placebo had an increase in lumbar-spine bone mineral density of 1.8+/-0.5 percent (P<0.001 for the comparison with base line) and no significant changes in femoral-neck or total-body bone mineral density. The increase in bone mineral density in the alendronate group was greater than that in the placebo group at all measurement sites (P<0.001). The incidence of vertebral fractures was lower in the alendronate group than in the placebo group (0.8 percent vs. 7.1 percent, P=0.02). Men in the placebo group had a 2.4-mm decrease in height, as compared with a decrease of 0.6 mm in the alendronate group (P=0.02). Alendronate was generally well tolerated. CONCLUSIONS: In men with osteoporosis, alendronate significantly increases spine, hip, and total-body bone mineral density and helps prevent vertebral fractures and decreases in height.     

绝经后妇女甲状旁腺素基因多态性与骨密度：福州地区的调查

背景：有研究证实,绝经后妇女骨密度与甲状旁腺素基因有密切关系,但在不同地区人群中结果存在差异性。 目的：探讨福州地区绝经后妇女甲状旁腺素基因(PTH)BstBⅠ多态性与骨密度的关系。 方法：用双能X射线骨密度仪检测福州地区150例绝经后妇女的腰椎、股骨颈,大转子和Ward’s三角骨密度,应用PCR-RFLP技术检测甲状旁腺素基因BstBⅠ多态性。 结果与结论：①甲状旁腺素基因型分布频率为BB型 68.8%、Bb型24.1%、bb 型7.1%。等位基因频率为B 81%,b 19%,基因型分布符合Hardy-Weinberg定律。②分析其基因型与骨密度的关系：BB、Bb、bb 3种基因型在股骨颈、大转子、Ward’s三角区4个部位骨密度差异均无显著意义(P > 0.05)。甲状旁腺素基因BstBⅠ位点多态性与骨密度间无关联,尚不能作为预测福州地区绝经后妇女发生骨质疏松危险的遗传标志。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

Relationship of osteocalcin and matrix Gla protein gene polymorphisms to serum osteocalcin levels and bone mineral density in postmenopausal Korean women

OBJECTIVE: To investigate the relationship of osteocalcin and matrix Gla protein (MGP) gene polymorphisms to serum osteocalcin levels, and bone mineral density (BMD) in postmenopausal Korean women. DESIGN: The osteocalcin gene Hind III and MGP gene cytosine-adenine polymorphisms were analyzed in 267 postmenopausal Korean women. Serum osteocalcin, bone alkaline phosphatase, C-telopeptide of type I collagen, and BMD at the lumbar spine and femoral neck were measured. RESULTS: No significant differences in BMD of the lumbar spine and femoral neck were observed across MGP genotypes, whereas a significant lower BMD at the lumbar spine (but not at the femoral neck) was observed in women with the (h) allele (lower case 'h' signifies the presence of the Hind III site) in a dose-response manner. Serum osteocalcin levels among bone turnover markers studied were significantly higher in women without the 210-bp MGP (cytosine-adenine) allele, or with the osteocalcin hh genotype. CONCLUSIONS: The osteocalcin gene Hind III polymorphism is a genetic factor that is associated with BMD of the lumbar spine in Korean women, and Gla gene polymorphisms are associated with higher osteocalcin levels.     

Association between breast cancer and bone mineral density: the Dubbo Osteoporosis Epidemiology Study

BACKGROUND: The association between bone mineral density and breast cancer was investigated in a nested case-control study, involving 30 breast cancer cases and 120 controls, aged 68+/-6 (mean +/-S.D.) years, as part of the Dubbo Osteoporosis Epidemiology Study (Australia). METHODS: Bone mineral density (BMD, g/cm(2)) at the femoral neck and lumbar spine was measured by dual energy X-ray absorptiometry. Anthropometric data and reproductive history were collected by direct interview using a structured questionnaire. RESULTS: In univariate conditional logistic regression analysis, lower age at menarche, longer overall duration of lifetime ovulation and higher bone density were associated with higher risk of breast cancer. Among the breast cancer cases, 20% of subjects had lumbar spine BMD greater than 1.20 g/cm(2) (or 2.5 S.D. above the mean) compared with less than 1% of the controls. After adjusting for the effects of duration of lifetime ovulation and body mass index, each 0.1 g/cm(2) increase in lumbar spine and femoral neck BMD was associated with a 2.1-fold (95% CI: 1.3-3.4) and 1.5-fold (1.0-2.4) respectively, higher risk of breast cancer. Further adjustment for age at menarche, hormone replacement therapy, and parity did not alter the result. Thus, postmenopausal BMD, which is affected by lifetime exposure to estrogen, is also related to risk of breast cancer. Importantly, it is estimated that estrogen therapy in osteoporotic women, even if raising the risk of breast cancer by 70% as suggested by some studies, would not elevate their risk to the level experienced by their non-osteoporotic counterparts. CONCLUSION: While the mechanism of this relationship remains to be explored, these data support the concept that lifetime exposure to estrogen is an indicator of risk of both breast cancer and osteoporosis. However, the use of estrogen in osteoporosis treatment would not elevate the risk of breast cancer in osteoporotic women up to the level experienced by their non-osteoporotic counterparts.