Comparison of the effects of raloxifene and low-dose hormone replacement therapy on bone mineral density and bone turnover in the treatment of postmenopausal osteoporosis

Objective. The aim of the present study was to compare the effects of raloxifene and low-dose hormone replacement therapy (HRT) on bone mineral density (BMD) and bone turnover markers in the treatment of postmenopausal osteoporosis.

Methods. Forty-two postmenopausal osteoporotic women, who were randomized to receive raloxifene 60 mg or estradiol 1 mg/norethisterone acetate 0.5 mg daily for 1 year, were studied. All women received calcium 600 mg/day and vitamin D 400 IU/day. BMD and markers of bone turnover were measured at baseline and at 12 months.

Results. After 12 months of treatment, there were statistically significant increases in BMD in both groups at all sites (all p < 0.05). For the lumbar spine, the increase in BMD was 2.3% for raloxifene compared with 5.8% for low-dose HRT and corresponding values for total body BMD were 2.9% for raloxifene and 4.6% for low-dose HRT; the increases being significantly greater in the low-dose HRT group (p < 0.001 and p = 0.02, respectively). Although the increase in BMD at the hip was significant for both raloxifene (2.1%) and low-dose HRT (3.2%) compared with baseline, the difference between the two regimens did not reach statistical significance. The decrease in serum C-terminal telopeptide fragment of type I collagen and serum osteocalcin levels for the low-dose HRT group (?53% and ?47%, respectively) was significantly greater than for the raloxifene group (?23% and ?27%, respectively; both p < 0.01).

Conclusions. In postmenopausal women with osteoporosis, low-dose HRT produced significantly greater increases in BMD of the lumbar spine and total body and greater decreases in bone turnover than raloxifene at 12 months.     

Veralipride administered in combination with raloxifene decreases hot flushes and improves bone density in early postmenopausal women.

We evaluated the administration of raloxifene and veralipride in postmenopausal women with high osteoporosis risk and hot flushes in whom hormone replacement therapy (HRT) was contraindicated. A group of early postmenopausal women (n = 29) (mean age 51.8 +/- 4.1), complaining of severe vasomotor symptoms and with a bone mineral density (BMD) T-score between -1.5 and -2.5 were evaluated. They were randomly assigned to two treatment groups: raloxfene (60 mg/day) continuously in association with veralipride (100 mg/day) on alternate days (n = 17); or on alternate months (n = 12). BMD, serum prolactin concentration and endometrial thickness were assessed at baseline and after 6 months of therapy. Kupperman Index and hot flushes were assessed before and after 3 and 6 months of therapy. BMD was significantly higher at the end of therapy with an increase of 1.1%. Kupperman Index was significantly reduced after 3 months and a further decrease at 6 months was observed with both protocols. Both treatments led to a significant reduction of hot flushes after 3 and 6 months. No signifcant changes of prolactin levels were observed in either protocol. We found that the combined raloxifene-veralipride treatment, both every other day and every other month, led to a significant improvement in bone density and was effective in hot flushes and other menopause-associated symptoms. These protocols could represent a new way to administer raloxifene in early postmenopausal women at high osteoporosis risk with HRT contraindication.     

A randomized trial of oral contraceptive and hormone replacement therapy on bone mineral density and coronary heart disease risk factors in postmenopausal women

OBJECTIVE: To identify the effects of oral contraceptive (OC) and hormone replacement therapy (HRT) on bone mineral density and coronary heart disease risk factors in postmenopausal women. METHODS: Eighty healthy postmenopausal women were randomly assigned to a cyclic regimen of OC containing 30 microg of ethinyl estradiol and 150 microg of desogestrel or HRT containing 0.625 mg of conjugated equine estrogens 21 days per cycle and 5 mg of medrogestone 10 days per cycle for 12 months. Bone mineral density of lumbar spine and hip, biochemical markers of bone turnover, lipid-lipoprotein profiles, coagulation profiles, fasting plasma glucose, and blood pressure were evaluated. RESULTS: Both regimens caused significant increase in bone mineral density of lumbar spine, trochanter, intertrochanteric region, total hip, and Ward triangle. Only OC therapy was associated with a significant increase in femoral neck bone mineral density (mean score +/- standard error 2.5% +/- 0.7%, P < .01). Biochemical markers of bone turnover, total cholesterol, and low-density lipoprotein cholesterol decreased significantly in both groups. Posttreatment levels of those bone markers and lipid-lipoprotein were significantly lower after OC therapy than HRT. Fasting plasma glucose and systolic blood pressure decreased significantly in both groups; however, only the OC group showed a significant decrease in diastolic blood pressure. CONCLUSION: Both OC and HRT increased bone mineral density of lumbar spine and hip, but OC suppressed bone turnover more than HRT. Both methods favorably affected lipid-lipoprotein metabolism, fasting plasma glucose, and blood pressure during the 12 months of treatment.     

Statins have additive effects to vertebral bone mineral density in combination with risedronate in hypercholesterolemic postmenopausal women

BACKGROUND: Recent data suggest that statins used in the treatment of hypercholesterolaemia decrease fracture risk. In this study, we aimed to investigate prospectively whether statins have an additive effect to bisphosphonates (risedronate) according to the primary hypothesis that the addition of atorvastatin to risedronate would produce an increase, from baseline, in lumbar vertebrae and total hip BMD that was greater than that observed with risedronate alone. METHODS: A total of 120 hypercholesterolaemic postmenopausal women with osteoporosis or osteopenia were randomized to receive risedronate (5 mg/day) or risedronate (5 mg/day) plus atorvastatin (20 mg/day). Changes in bone mineral density in the lumbar spine and hip, and serum lipid and glucose metabolism changes were assessed. RESULTS: Compared with risedronate alone, at 6 months, risedronate plus atorvastatin produced significantly greater increases in the bone mineral density of the lumbar spine (1.58% versus 0.75%, p < 0.05). We found no difference after therapy in BMD of the total hip (1.2% versus 1.1%). Risedronate plus atorvastatin therapy had favorable effects on the serum lipid profile: LDL and total cholesterol. Serum fasting glucose and HbA1c levels were not affected during the treatments. CONCLUSION: Statins have modest additive effects to bisphosphonates in improving lumbar spine bone mineral density in hypercholesterolaemic postmenopausal women with established osteoporosis-osteopenia. A long-term study with adequate sample size is necessary to assess the effects of statins -- in combination or alone -- on the bones and prevention of fractures.     

The effects of short-term hormone replacement therapy on long-term bone mineral density.

INTRODUCTION: Short-term hormone replacement therapy (HRT) relieves menopausal symptoms and increases bone mineral density (BMD), but bone loss reoccurs upon discontinuation. This study assesses whether short-term HRT provides long-term BMD benefits. METHOD: This was a prospective study of women aged 50-54 years followed up for 9 years. Women were categorized into three groups according to the treatment they received: No-HRT (n = 340), Short-term HRT (2-4 years, n = 60), and Long-term HRT (9 years, n = 187). RESULTS: BMD increased significantly at the hip (2.4%, p < 0.001) and spine (8.0%, p < 0.001) over 9 years in the Long-term HRT group. Women without treatment lost BMD at the hip (-4.2%, p < 0.001) and spine (-3.5%, p < 0.001). Women in the Short-term HRT group had no significant loss of BMD at the hip (-1.6%, p = 0.08) or spine (-1.4%, p = 0.18) over 9 years. BMD in the Short-term HRT group was significantly higher at 9 years than in the No-HRT group at both spine (difference 0.023 g/cm(2), p = 0.048) and hip (difference 0.016 g/cm(2), p = 0.042). CONCLUSION: After 9 years, women who had taken short-term HRT had no significant loss of BMD and were better off in terms of BMD than those left untreated. Short-term HRT in the early postmenopausal period provides long-term BMD benefits.     

Correlations of serum prolidase activity between bone turnover markers and mineral density in postmenopausal osteoporosis

Prolidase is a specific imidodipeptidase involved in collagen degradation. The increase in the enzyme activity is believed to be correlated with the increased intensity of collagen degradation. The aim of this study was to evaluate the serum prolidase activity and its relationship between bone turnover markers and bone mineral density (BMD) in postmenopausal osteoporosis. The study included 45 postmenopausal osteoporotic, 55 postmenopausal nonosteoporotic and 38 premenopausal healthy women. BMD was measured at the femoral neck and lumbar spine with DEXA. T score was more than 2.5 SD below the normal at the lumbar spine or femoral neck in postmenopausal osteoporotic patients. Serum levels of prolidase, C-terminal telopeptide of type I collagen (C-telopeptide), total alkaline phosphatase (ALP), osteocalcin (OC), urinary deoxypyridinoline (Dpd) and urinary creatinine were also assayed. C-telopeptide, total ALP, OC, urinary Dpd levels were significantly higher in postmenopausal osteoporotic group compared with premenopausal women. However, there was no statistical difference in serum prolidase activity between the three groups. There were also no significant correlations between serum prolidase and any biomarkers of bone turnover as well as BMD. To conclude, in postmenopausal osteoporotic women with increased bone turnover, serum prolidase concentration was not correlated with the biomarkers of bone formation or bone resorption and with BMD.     

Comparison of bone mineral density and its variables between premenopausal and postmenopausal women

Objectives

To compare the bone mineral density (BMD) and its variables in premenopausal and postmenopausal women.

Methods

In this cross sectional study, 62 premenopausal and 62 postmenopausal apparently healthy women were evaluated by a questionnaire. The dietary intake of calcium was evaluated by 24 hours recall method and using table for proximate principle of common Indian food by Indian Council of Medical Research (ICMR). BMD at lumbar spine, femoral neck and Ward’s triangle were measured by dual energy X-ray absorptiometry (DXA). A correlation between BMD and various variables were calculated for each of the two groups.

Results

The mean age of premenopausal and postmenopausal women was 32.46±7.8 and 51.74±7.1 years respectively. The body mass index (BMI), height and weight were comparable in both the groups. The daily intake of calcium was significantly higher in premenopausal women (p<0.01). Approximately, 17% of the postmenopausal women and 9.6% of the premenopausal women were having osteoporosis; 28.56% of the postmenopausal women and 43.54% of the premenopausal women were having osteopenia at the lumbar spine. The BMD at lumber spine was found to be statistically significantly higher in premenopausal women than that in postmenopausal women (p=0.03). BMD at lumbar spine, femoral neck and Ward’s triangle were positively correlated with height, weight, BMI in premenopausal as well in postmenopausal women.

Conclusion

A significant number of women had osteopenia during premenopausal period and osteoporosis in postmenopausal phase. By increasing awareness towards bone health in second and third decade, morbidity of osteoporosis can be reduced.     

Long-term postmenopausal hormone replacement therapy effects on bone mass: differences between surgical and spontaneous patients.

BACKGROUND: Hormone Replacement Therapy (HRT) begun soon after spontaneous menopause or oophorectomy minimizes or even reverses the loss of bone that occurs normally during those years. The persistence of this HRT protective effect at long-term on bone density, however, is not well documented. AIM: to evaluate the effects of 5 years of HRT in postmenopausal women on bone mineral density of the lumbar spine. SUBJECTS AND METHODS: The 5-year prospective study enrolled 154 postmenopausal women, of them 136 completed the first year and were considered electible to continue the follow-up. These 136 postmenopausal women were allocated to two groups according their origin: surgical (n=68) and spontaneous (n=68). HRT was prescribed and bone mineral density (BMD) was measured at the lumbar spine prior to commencement of therapy, and then yearly for the duration of the study. All patients received a continuous therapy with standard dose (0.625 mg/day) of conjugated equine estrogen (CEE) or 50 microg/day of 17-beta-Estradiol in transdermal therapeutic systems (TTS). Subjects who experienced natural menopause also received 5 mg/day of medroxyprogesterone acetate sequentially added to the last 12 days of estrogen therapy. Treated groups were compared with two non-treated control groups (surgical n=77; spontaneous n=53). RESULTS: Our data showed that HRT increased the BMD of women who had experienced spontaneous menopause. Comparison with a control group revealed that HRT also protected against bone loss in women who had undergone surgical menopause. CONCLUSION: Long term hormone replacement therapy increases bone mineral density in women who have experienced natural menopause, and protects against bone loss in surgically postmenopausal women.     

Therapeutic equivalence of alendronate 35 milligrams once weekly and 5 milligrams daily in the prevention of postmenopausal osteoporosis

OBJECTIVE: To evaluate the efficacy and safety of alendronate 35 mg once weekly compared with alendronate 5 mg daily in the prevention of osteoporosis. METHODS: We compared the efficacy and safety of treatment with alendronate 35 mg once weekly (n = 362) and alendronate 5 mg daily (n = 361) in a 1-year, double-blind, multicenter study of postmenopausal women (6 months or greater), aged 40-70 years, with lumbar spine and femoral neck bone mineral density T-scores between -2.5 and 1. The primary efficacy end point was the comparability of lumbar spine bone mineral density increases, defined by strict prespecified criteria. RESULTS: Mean increases in lumbar spine bone mineral density at 12 months were equivalent (difference between the alendronate 35-mg once-weekly group and the alendronate 5-mg daily group [90% confidence interval] at month 12 was -0.3% [-0.6, 0.1], well within the prespecified bounds of +/-1.0%). Bone mineral density increases at other skeletal sites and effects on bone turnover were also virtually identical for the two dosing regimens. Both treatment regimens were well tolerated, and the larger weekly unit dose was not associated with an increased frequency of upper gastrointestinal events. CONCLUSION: Alendronate 35 mg once weekly is therapeutically equivalent to alendronate 5 mg daily and provides patients with greater dosing convenience, in addition to the proven efficacy of alendronate and good tolerability.     

Risedronate prevents bone loss in early postmenopausal women: a prospective randomized, placebo-controlled trial.

OBJECTIVES: To assess the efficacy and tolerability of risedronate, a pyridinyl bisphosphonate, in preventing loss of bone mineral density (BMD) of the lumbar spine and proximal femur in early postmenopausal women. METHODS: A total of 383 patients were randomly assigned to receive risedronate 2.5 or 5 mg or placebo once daily for 24 months. All patients received 1 g elemental calcium daily. BMD was measured by dual X-ray absorptiometry at baseline and at 3, 6, 12, 18, and 24 months. RESULTS: Risedronate 5 mg significantly increased BMD at the lumbar spine and femoral neck and trochanter in early postmenopausal women. Significant results were observed as early as 3 months. In the control calcium-supplemented group, BMD decreased steadily at each site throughout the study. The mean percentage change from baseline in BMD in the risedronate 5 mg group was significantly different from that in the control group at each determination at each site. At 24 months, the differences were 4.5 +/- 0.45% at the lumbar spine, 3.3 +/- 0.49% at the femoral neck, and 4.3 +/- 0.67% at the femoral trochanter. Risedronate 2.5 mg maintained BMD at each site, although the effect was less pronounced than that of risedronate 5 mg. Risedronate was well tolerated and was not associated with an increased incidence of overall or upper gastrointestinal adverse events. CONCLUSIONS: Risedronate 5 mg prevents bone loss in early postmenopausal women, is well tolerated, and represents an effective choice to maintain bone mass and prevent osteoporosis.     

雷洛昔芬对绝经后妇女骨密度、骨代谢生化指标和血脂影响的随机对照研究

目的　确定盐酸雷洛昔芬 (RLX)对中国绝经后妇女骨密度、骨代谢生化指标及血脂的影响。方法　将来自 3所医院的 2 0 4例绝经后妇女 [平均年龄 (6 0± 5 )岁 ,平均体重 (6 3± 9)kg]随机分组 ,进行双盲安慰剂对照的临床研究 ,受试者每天接受RLX 6 0mg(n =10 2 ,RLX组 )或安慰剂 (n =10 2 ,安慰剂组 )治疗 12个月 ,并于服药前及服药 12个月后各进行一次骨密度、骨代谢生化指标及血脂的测定。结果　与安慰剂相比 ,RLX使腰椎和髋部骨密度显著升高 ,RLX组腰椎的骨密度增加2 30 % ,而安慰剂组降低 0 0 8% ,两组比较 ,差异有极显著性 (P <0 0 0 1) ;RLX组髋部骨密度增加2 4 6 % ,安慰剂组增加 1 0 7% ,两组比较 ,差异有显著性 (P <0 0 5 )。RLX组骨代谢生化指标血清骨钙素和血清C端交联肽分别降低 2 7 6 %和 2 4 0 % ,而安慰剂组则分别降低 10 6 %和升高 15 8% ,两组比较 ,差异有极显著性 (P <0 0 0 1)。RLX组总胆固醇和低密度脂蛋白胆固醇分别降低 6 4 %和34 6 % ,而安慰剂组则分别升高 1 4 %和降低 19 1% ,两组比较 ,差异有极显著性 (P <0 0 0 1)。两组间高密度脂蛋白胆固醇和甘油三酯水平未见差异。仅有 5例因不良事件而提前退出研究 (RLX组 3例 ,安慰剂组 2例 )。结论　RLX能增加绝经后中国妇女     

A randomized controlled trial of four doses of transdermal estradiol for preventing postmenopausal bone loss. Transdermal Estradiol Investigator Group.

OBJECTIVE: To determine the effects of four doses of a 7-day transdermal 17beta-estradiol (E2) delivery system, including 0.025 mg/day, on bone loss in postmenopausal women. METHODS: This was a multicenter, double-masked, randomized, placebo-controlled study of the effects of transdermal E2 at doses of 0.025, 0.05, 0.06, and 0.1 mg/day for the prevention of postmenopausal osteoporosis. Efficacy was evaluated from bone mineral density of lumbar vertebrae L2-L4, radius, proximal femur, and total hip measured with dual-energy x-ray absorptiometry. Serum osteocalcin and urinary pyridinoline and deoxypyridinoline concentrations were measured. RESULTS: At 24 months, E2 doses of 0.025, 0.05, 0.06, and 0.1 mg/day resulted in mean increases in bone mineral density of the lumbar spine of 2.37%, 4.09%, 3.28%, and 4.70%, respectively, and increased bone mineral density of the total hip by 0.26%, 2.85%, 3.05%, and 2.03%, respectively. All increases were statistically significantly greater than placebo, which decreased bone mineral density by 2.49% at the spine and 2.04% at the hip. Consistent and significant improvements in biochemical markers of bone turnover also were noted at various intervals in all treatment groups. The most frequent adverse events were local reactions from the transdermal drug-delivery system, effects of estrogen, and menopausal symptoms. CONCLUSION: Transdermal E2 at doses of 0.025, 0.05, 0.06, and 0.1 mg/day effectively prevented bone loss in postmenopausal women.     

Clinical efficacy of raloxifene in postmenopausal women.

A new class of compounds known as selective estrogen receptor modulators (SERMs) may possess the optimal combination of characteristics desirable in a drug designed for use in postmenopausal women. Among this class of compounds, raloxifene is the most studied and is currently available for clinical use in some countries for the prevention of osteoporosis in post-menopausal women. Raloxifene is a non-steroidal benzotiophene derivative shown to prevent bone loss at axial and appendicular sites and reduce serum cholesterol, like estrogen, in oophorectomized rats and in postmenopausal women. In animal models, unlike estrogen, raloxifene does not stimulate breast or uterine tissues. These appealing attributes make raloxifene a potential treatment for osteoporosis and other menopause related risks in middle aged and elderly women. Multicenter studies have been performed in early postmenopausal women, randomly assigned to receive raloxifene 30, 60, or 150 mg/day or placebo. All subjects received a calcium supplement. Bone mineral density, which was measured twice a year over 24 months by dual X-ray absorptiometry, decreased significantly at all skeletal sites with placebo, and significantly increased with raloxifene at the spine, hip, and total body at the three doses. At 24 months, the mean increase with raloxifene 60 mg compared with placebo was 2.4% at the lumbar spine and at the total hip, and 2% at the total body. Markers of bone formation (serum osteocalcin and bone specific alkaline phosphatase) and of resorption (urinary CrossLaps) decreased significantly to the premenopausal range within 3-6 months of treatment with raloxifene. In addition, total serum and low-density lipoprotein cholesterol decreased significantly in all raloxifene therapy groups in a dose-related fashion. Serum HDL-cholesterol and triglycerides were not significantly changed by therapy. The most commonly observed side-effect was hot flushes, with patients taking raloxifene reporting a slightly higher rate of flushes (25%) than those on placebo (18%). This adverse event usually occurred within the first few months of therapy, was generally mild, and did not result in excess study dropout (raloxifene 1.5%, placebo 2.1%). Preliminary 2-year data indicated that raloxifene is not associated with an increased risk of breast cancer. In summary, the clinical efficacy and safety of raloxifene is very promising and this compound will offer a particularly attractive choice for postmenopausal women.     

Double-blind, placebo-controlled study of the effects of tibolone on bone mineral density in postmenopausal osteoporotic women with and without previous fractures.

A 2-year placebo-controlled, randomized, two-center prospective study was carried out to assess the effects of tibolone (Org OD14, Livial) on trabecular and cortical bone mass and bone biochemistry parameters in elderly postmenopausal women with and without previous fractures. In total, 107 subjects, 71 with fractures and 36 without fractures, were randomized to tibolone (n = 64) or placebo (n = 43). Their mean age was 63.1 years. Bone mineral density (BMD) (g/cm2) was assessed at baseline and every 6 months for 2 years by dual-energy X-ray absorptiometry (DXA). Mean baseline values were 0.79 and 0.80 for the lumbar spine in the tibolone and placebo groups, respectively, and for the femoral neck 0.64 in both groups. Serum and urinary bone biochemistry parameters were measured concurrently. An analysis of variance (ANOVA) model including center and group was applied. The completers' group was the primary subset for the analysis; the intention-to-treat (ITT) group was also analyzed. Results are expressed as the percentage change at 24 months and the annual rate of change percentage year. The tibolone group showed an overall mean increase (vs. placebo) in BMD at the lumbar spine of 7.2% (p < 0.001) and for the femoral neck 2.6% (p < 0.001). In subjects with previous fractures increases were 6.0% and 4.0% for the lumbar spine and femoral neck, while in those with no fractures, respective changes were 8.9% and 1.1%. Overall changes in the placebo group were 0.9% and -1.6% for the lumbar spine and femoral neck, respectively. A significant fall in bone biochemistry parameters showed that tibolone inhibits osteoclastic activity. In conclusion we have found that tibolone 2.5 mg induces significant increases of trabecular and cortical bone mass in elderly postmenopausal osteoporotic women with and without previous fractures.     

New possibilities for diagnosis and treatment of osteoporosis

Postmenopausal osteoporosis is preventable and treatable. Women need not lose bone mineral density (BMD) after the menopause. Without intervention, all women lose bone after menopause, regardless of the amount of calcium, vitamin D, and exercise they undertake. Postmenopausal women need estrogen replacement, a selective estrogen receptor modulator (SERM), or a bisphosphonate to prevent bone loss. Alendronate, risedronate (bisphosphonates) and raloxifene (SERM) are approved for the prevention of bone loss. The diagnosis of at-risk postmenopausal women can best be accomplished by measuring BMD in all postmenopausal women age 65 years and older regardless of their risk profile and in all postmenopausal women under 65 years with one or more risk factors. Treatment guidelines direct physicians to treat postmenopausal women with T-scores lower than -2.0 SD regardless of their risk profile and postmenopausal women with T-scores lower than -1.5 SD with one or more risk factors. The lower the BMD, the greater the fracture risk, particularly in individuals with increased age, existing fragility fractures, or high bone turnover. The best intervention for a patient should be individually selected, based on careful clinical assessment. Although calcitonin is not approved for prevention, it is approved for treatment. The labeling of estrogens has been modified to state that they may be used to "manage" osteoporosis. The lack of efficacy of calcitonin to prevent bone loss during the first 5 years after menopause, and the lack of prospective fracture reduction data for estrogen, have resulted in these labeling restrictions. Alendronate, risedronate, and raloxifene are currently approved for the treatment of osteoporosis. Both of these compounds have been shown to increase BMD and decrease fracture risk. Monitoring of a patient's response to treatment may be accomplished using serial BMD testing and biomarkers of bone turnover.     

Safety and efficacy of drospirenone used in a continuous combination with 17beta-estradiol for prevention of postmenopausal osteoporosis.

OBJECTIVE: To evaluate the combination of 17beta-estradiol and continuous drospirenone for the prevention of postmenopausal osteoporosis. METHODS: A total of 180 (75%) healthy postmenopausal women aged 45-65 years completed a 2-year prospective study. Bone mineral density (BMD) at lumbar spine, hip and total body as well as endometrial thickness, markers of bone turnover and serum lipids were measured regularly. Treatment groups were given placebo or 1 mg 17beta-estradiol combined with 1, 2 or 3 mg drospirenone daily. RESULTS: BMD at the lumbar spine, hip and total body increased by 7, 4 and 3%, respectively, in all hormone groups versus placebo (all p < 0.001). Bone markers all decreased accordingly (serum osteocalcin 52%, serum bone specific alkaline phosphatase 36%, serum CrossLaps 67% and urinary CrossLaps 75% from baseline; all p < 0.001). Total cholesterol and low-density lipoprotein cholesterol decreased by 8% and 13%, respectively (both p < 0.001). High-density lipoprotein cholesterol and triglycerides remained unchanged. No significant dose-related effects were found. Endometrial thickness increased by 1.2 mm only in the 1-mg drospirenone group (p < 0.01 versus placebo). CONCLUSION: The combination of 17beta-estradiol and drospirenone has a positive effect on BMD and a potentially beneficial effect on lipids. Although endometrial thickness increased slightly, the safety of the endometrium was assured, as no cases of hyperplasia or cancer occurred.     

Association of tibolone and fluoride displays a pronounced effect on bone mineral density in postmenopausal osteoporotic women.

A double-blind, placebo-controlled, randomized, prospective two-center study was carried out to assess the effects of tibolone + fluoride versus placebo + fluoride therapy on trabecular and cortical bone in postmenopausal osteoporotic women. Ninety-four subjects (mean age 61.1 years, postmenopausal 13.5 years on average) with low bone mineral density (BMD) at baseline were randomized to 2.5 mg of tibolone (Org OD 14, Livial) plus 26.4 mg of fluoride (Fluocalcic) or placebo plus 26.4 mg of fluoride daily over 2 years; 55 (58.5%) subjects completed the study, the main reason for discontinuation being untoward gastrointestinal effects. BMD at the lumbar spine was measured by both dual photon absorptiometry (DPA) and dual-energy X-ray absorptiometry (DXA), and at the hip by DXA at 6-month intervals. Baseline values (DXA, g/cm2) for tibolone + fluoride and placebo + fluoride groups were 0.733 and 0.744 for the lumbar spine, and 0.761 and 0.788 for the hip. Change from baseline and percentage change from baseline were calculated for the intent-to-treat and completers groups. An analysis of variance (ANOVA) model or Wilcoxon test was used for statistical evaluation. There was a mean increase in BMD at the lumbar spine measured by DPA of 25.3% and 12.3% in tibolone + fluoride and placebo + fluoride groups, respectively (p = 0.01); with DXA, respective changes were 32.6% and 14.0% (p = 0.013). Data on BMD at the hip showed mean increases of 7.9% and 2.6% for the tibolone + fluoride and placebo + fluoride groups, respectively. We conclude that combined tibolone + fluoride treatment induces a highly significant increase in BMD at the lumbar spine without simultaneous loss of the cortical bone allowing for a meaningful reduction of the fluoride dose when given in combination with tibolone.     

The value of skin densitometry in diagnosis of decreased bone mass in the spine of women during the period around and post-menopause]

OBJECTIVE: In peri- and postmenopausal women, the association of skin thickness with bone mass is well described, and a low skin thickness is a useful predictor of osteoporosis. In this study the association between skin thickness and bone mass of lumbar spine in peri- and postmenopausal women was assessed; and the potential for skin thickness as a screening test for osteoporosis evaluated. DESIGN/METHODS: Skin thickness was measured at the arm by ultrasonography (probe 22 MHz). Bone mass was measured at lumbar spine by dual-energy X-ray absorptiometry. One hundred and three peri- and postmenopausal women were studied. RESULT: Successive decrease of skin thickness going along with the loss of lumbar spine bone mass was found. There was a statistically significant difference (p < 0.05) in skin thickness between group of females with normal bone mass and group with osteoporosis. CONCLUSIONS: Ultrasound skin measurement is a very simple method which can be used in the diagnostics of osteoporosis of the lumbar spine in peri- and postmenopausal women.     

Effects of hormone replacement therapy on bone mineral density in Turkish patients with or without COL1A1 Sp1 binding site polymorphism

AIM: To evaluate the effects of hormone replacement therapy (HRT) on bone mineral density (BMD) in patients with or without COL1A1 Sp1 binding site polymorphism. METHODS: Non-smoking otherwise healthy postmenopausal women (n=111), who had not received any kind of HRT for at least 3 years (between 2002 and 2005) at the onset of menopause, were included. All patients received 0.625 mg conjugated estrogen/2.5 mg medroxyprogesterone for 18 months. BMD by dual X-ray absorptiometry was measured at the lumbar spine and the femur neck initially and after 18th months of treatment. COL1A1 Sp1 binding site polymorphism was studied using the PCR-RFLP method. RESULTS: After having the results of COL1A1 Sp1 binding site polymorphism, 79 (71.2%) patients were SS, 30(27.0%) were Ss and two (1.8%) were homozygous for ss. The mean age, weight and length of menopausal period were similar between the SS and Ss patients. The Ss heterozygotes had lower BMD values both at the lumbar spine and at the femur neck compared with the SS patients. This difference was also reflected in post treatment measurements. The increase in BMD scores was higher in the SS homozygotes than in the Ss patients. CONCLUSION: Our preliminary data supports the fact that HRT had a lower increase in BMD scores following 18 months of treatment in COL1A1 s allele individuals compared with normal SS individuals. Therefore our study may provide evidence that the Sp1 polymorphism may ameliorate the effects of HRT on BMD, suggesting some additional regimens may be used to support bone strength and to decrease osteoporotic fractures.     

Tumor necrosis factor alpha, CYP 17, urokinase, and interleukin 10 gene polymorphisms in postmenopausal women: correlation to bone mineral density and susceptibility to osteoporosis

OBJECTIVE: Osteoporosis is a common disorder with a strong genetic component. We investigated the correlations between bone mineral density (BMD) and four gene polymorphisms (-308G>A tumor necrosis factor alpha (TNF-alpha), -34T>C CYP 17, *141T>C urokinase, and -627C>A interleukin 10 (IL-10) promoter), and their relationship to osteoporosis in postmenopausal women. STUDY DESIGN: These polymorphisms were determined using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) analysis. BMD of the lumbar spine and proximal femur were measured using dual-energy X-ray absorptiometry. RESULTS: The prevalence of each genotype was as follows: (1) 79.3% A/A, 16.6% A/G, and 4.1% G/G in -308G>A TNF-alpha; (2) 18.9% T/T, 52.1% T/C, and 29% C/C in -34T>C CYP 17; (3) 86.4% C/C and 13.6% C/T in *141T>C urokinase; (4) 46.2% A/A, 45% A/C, and 8.8% C/C in -627C>A IL-10 promoter. Subjects with genotype C/C in -627C>A IL-10 promoter had lower BMD values and a significantly greater risk for osteoporosis (OR 8.1, 95% CI 1.5-42.8) at the lumbar spine compared with subjects with genotype A/C in -627C>A IL-10 promoter, after adjustment for potential confounders. CONCLUSION: The RsaI IL-10 promoter gene polymorphism is associated with reduced BMD and predisposes women to osteoporosis at the lumbar spine.