Bone Loss In Postmenopausal Women Research Articles

The effects of soluble interleukin-6 receptor and soluble glycoprotein 130 on bone loss in postmenopausal women

The effects of soluble interleukin-6 receptor and soluble glycoprotein 130 on bone loss in postmenopausal women

Prevention of Bone Loss With Tibolone in Postmenopausal Women: Results of Two Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Studies

Tibolone is a synthetic agent with tissue-specific effects, including an antiresorptive effect on bone. Clinical trials have documented prevention of bone loss in postmenopausal women; a daily oral dose of 2.5 mg has generally been used. The present study evaluated tibolone therapy over 2 years with daily doses of 0.3, 0.625, 1.25, or 2.5 mg of tibolone as compared with placebo in 770 generally healthy women who were 1 to 4 years past menopause and who had normal bone density for their age. All of them took supplemental calcium carbonate as well in a daily dose of 500 mg. Bone mineral density (BMD) was measured in the lumbar spine and right proximal femur by dual-energy x-ray absorptiometry for up to 2 years. The patient population was drawn from two identically designed randomized, placebo-controlled, dose-finding studies. A total of 519 women completed the 2-year studies. Tibolone led to a progressive increase in spinal and total hip BMD over 2 years of treatment in all doses except 0.3 mg. Hip BMD was maintained by the 0.3-mg dose. Only doses of 1.25 or 2.5 mg daily progressively increased BMD at the femoral neck. Differences in mean percentage of change from baseline in spinal and total hip BMD were significant for all dose groups compared with placebo. The rise in BMD at the lumbar spine over baseline, with 1.25 or 2.5 mg daily, was 2.0 to 2.6% at 2 years, a statistically significant and clinically meaningful effect. Increasing BMD was not limited to the first year of tibolone therapy. All tibolone doses except the lowest were associated with decreased serum osteocalcin levels, whereas in placebo recipients osteocalcin increased over baseline. Comparable reductions in bone-specific alkaline phosphatase were noted in patients given 1.25 and 2.5 mg of tibolone. Total cholesterol levels decreased in all tibolone dose groups, but declines in high-density lipoprotein cholesterol, triglycerides, and apolipoprotein A-1 seemed to be dose-related. All doses of tibolone were generally well tolerated during the 2 years of administration. No deep venous thrombosis or pulmonary embolism was observed. Hot flashes were less frequent with tibolone therapy than with placebo and were at their lowest with the 2.5-mg dose. Average body weight changes were similar in the actively treated and placebo groups. Endometrial hyperplasia was comparably frequent in the two groups. Vaginal bleeding became less prevalent with continued tibolone treatment. A 1.25-mg daily dose of tibolone is recommended for preventing osteoporosis. The ability of this drug to dose-dependently increase BMD in the lumbar spine and total hip should allow individualized antiresorptive treatment for postmenopausal women according to their clinical response.

Combination of Intermittent Cyclical Etidronate and Hormone Replacement Therapy for Postmenopausal Non-Responders to Estrogen

To investigate whether the addition of etidronate to conventional hormone replacement therapy (HRT) is effective against bone loss in postmenopausal women whose lumbar bone mineral density (BMD) cannot be maintained by HRT. Single-centre, placebo-controlled randomised study. Among 1138 patients on conventional HRT, 30 postmenopausal women were considered to be non-responders to estrogen, since their BMDs continued to decrease by more than 1% per year in spite of the HRT. The BMD of all the included patients was less than 70% of the young adult mean. PATIENTS were randomly divided into two groups: group A (n = 15) treated with conventional HRT and placebo, and group B (n = 15) treated with combined intermittent cyclical etidronate therapy (ICT-etidronate) and conventional HRT. Measurement of lumbar BMD was performed at baseline and at 6 and 12 months using dual energy x-ray absorptiometry (DEXA). Biochemical markers of bone resorption and formation were also measured during the visits. ICT-etidronate combined with HRT increased the lumbar BMD at 6 months (p < 0.05) and 12 months (p < 0.05) compared with baseline. Lumbar BMDs of the combined treatment group were significantly increased at 12 months (p < 0.05) compared with the HRT-only group. Bone resorption was suppressed by combined therapy at 6 months (p < 0.05). Bone formation did not change in either group. ICT-etidronate combined with HRT seems to be effective in preventing loss of BMD in postmenopausal women who do not respond to estrogen, and may be useful in preventing fractures in this group.

Usual dietary isoflavone intake, bone mineral density, and bone metabolism in postmenopausal women.

Clinical trials of isoflavone supplementation and bone density have been of relatively short duration and yielded inconsistent results. Few studies examined the effects of usual dietary isoflavone intake on bone density, and none examined the effects on markers of bone turnover. This cross-sectional study examines the association of usual, unsupplemented dietary soy intake with bone density at the lumbar spine and hip and markers of bone turnover in postmenopausal women. Participants were 208 postmenopausal Southern California women aged 45-74 years. Information on behavioral and lifestyle factors was obtained, and dietary intake of isoflavones over the past year was assessed with a standardized questionnaire. Bone density was measured at the spine and hip with dual energy x-ray absorptiometry (DEXA). Urinary type I collagen cross-linked N-telopeptides (N-Tx) and pyridinium cross-links (PYR), both markers of bone resorption, and bone alkaline phosphatase (BAP), a marker of bone formation, were assayed. After adjustment for age and obesity, women with the highest daily intake of dietary genistein had N-Tx concentrations 18% lower than those of women who reported no daily genistein consumption (mean 37.29 vs. 45.44, respectively, p = 0.01). After adjustment for all covariates, there were trends toward significant differences in N-Tx (p = 0.09) and spine bone density (p = 0.07), whereby women with the highest level of isoflavone consumption had greater bone density at the spine. These results suggest that usual, unsupplemented dietary isoflavone consumption may be protective against bone loss in postmenopausal women through a reduction in bone resorption.

Ten years of treatment with tibolone 2.5 mg daily: effects on bone loss in postmenopausal women

Objectives: To assess the effects of tibolone 2.5 mg daily over a 10-year period on bone loss and other efficacy parameters in postmenopausal women, and to confirm its long-term safety and tolerability.Methods: A 10-year, open, non-randomized, prospective study was conducted in 110 postmenopausal women; 59 women received tibolone 2.5 mg daily and 51 were entered into an untreated control group.After 10 years, 31 women in the tibolone group (53%) and 26 (51%) in the control group remained in the study.Results: After 10 years, tibolone had significantly (p < 0.0001) increasedthe mean bone mineral density in the lumbar spine and femoral neck by 4.8% and 3.7%, respectively, compared with baseline. The corresponding changes in the control group were -8.5% and -8.9% (p <0.0001 vs. baseline), respectively. The incidence and intensity of hot flushes were reduced in the tibolone group and there were improvements in vaginal cytology parameters. Tibolone was well tolerated.Conclusion: Tibolone 2.5 mg daily maintains its beneficial effects on bone loss over 10 years, while remaining well tolerated.

Low-dose hormone replacement therapy: effects on bone

Hormone replacement therapy (HRT) is considered the mainstay for postmenopausal osteoporosis prevention. However, at the standard doses, HRT preparations can induce bothersome hormone-related side-effects,in both sequential and continuous combined regimens. Lower-dose HRT schedules are reported to be highly effective in the relief of climacteric symptoms, inducing minimal endometrial stimulation with verylow rates of unscheduled bleeding. Moreover, low-dose HRT associated with an adequate calcium supplement can spare bone by preventing the increase in bone turnover and the resultant bone loss in postmenopausalwomen. Low-dose regimens may be considered as a starting dose not only in elderly subjects, but also in early postmenopausal women to allow for adjustment to HRT. In older women, these may minimize theoccurrence of side-effects and improve compliance, while preventing the long-term consequences of estrogen deprivation.

The periodontal-systemic connection: implications for treatment of patients with osteoporosis and periodontal disease.

Osteoporosis and osteopenia may influence periodontal disease and tooth loss. Medications such as hormone replacement therapy and nutritional supplements that are used to prevent or treat osteoporosis have been evaluated for beneficial effects on oral health in a small number of human studies. Hormone replacement therapy (HRT), which slows the rate of bone loss at skeletal sites such as the hip and spine, also appears to reduce the rate of alveolar bone loss in postmenopausal women. HRT use is consistently associated with greater tooth retention and a reduced likelihood of edentulism in studies of elderly women. The number of studies on the effects of calcium or vitamin D intake on oral outcomes is limited, but suggest that higher intake levels are associated with reduced prevalence of clinical attachment loss and lower risk of tooth loss. Data from a prospective study of oral health in men show a similar association between higher calcium intake and reduced alveolar bone loss. The number of teeth with progression of alveolar bone loss over a 7-year period was significantly lower among men whose calcium intake was at least 1,000 mg per day, compared to men with a calcium intake below this level. Future studies should confirm these findings and evaluate the oral effects of new medications for osteoporosis. If confirmed, the implications for dental professionals may include an expanded array of medications for the treatment of periodontal disease and a greater emphasis on nutrition education for patients.

Hormone replacement therapy: the benefits in tailoring the regimen and dose

Despite the clear benefits of long-term hormone replacement therapy (HRT), the majority of patients tend to undergo short-term treatment. The cyclical bleedings induced by the sequential progestogen administration are often unacceptable namely in the elderly postmenopausal women. At the standard doses HRT preparations can also induce annoying hormone-related side effects, both in sequential and continuous combined regimens. Lower HRT schedules are reported to be highly effective in the relief of climacteric symptoms, inducing minimal endometrial stimulation with high rates of amenorrhea. Continuous administration of low doses of progestins is safe for endometrium protection and minimizes progestin-related side effects. Indeed, it has been demonstrated that low dose HRT can prevent the increase in bone turnover and the consequent bone loss in postmenopausal women. The choice of lower HRT dosages can also be useful for the number of potential disadvantages of standard HRT doses, mainly for long-term treatments. Low dose regimens should be considered as a starting dose to minimize the occurrence of side effects, improving compliance and, therefore, HRT effects on the prevention of long-term consequences of estrogen deprivation.

Evaluation of lumbar spine bone mineral density in the anteroposterior and lateral projections by dual-energy X-ray absorptiometry.

Dual-energy x-ray absorptiometry (DXA) is an established method for estimating bone mineral density (BMD) of the lumbar spine. In a prospective study, the sensitivity of BMD measurements between anteroposterior and lateral projections were evaluated in 204 postmenopausal women based on their DXA analysis. Patients were divided into two groups according to the absence or presence of lumbar scoliosis. Lateral projection DXA measurements were more sensitive than AP projection measurements for early detection of bone loss in postmenopausal women. Lateral projection DXA analysis is not recommended in spines with lumbar scoliosis.

Reply

We thank Dr. Kamel for his comments on our recently published study of the effect of thiazide diuretics on normal postmenopausal bone loss ( 1 Reid I.R. Ames R.W. Orr-Walker B.J. et al. Hydrochlorothiazide reduces loss of cortical bone in normal postmenopausal women a randomized controlled trial. Am J Med. 2000; 109: 362-370 Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar ). In general, we agree with his conclusions but have some further minor comments. Changes in renal tubular absorption of calcium probably contribute to the increase in urine calcium after the menopause, as does the nearly twofold increase in the rate of bone resorption that also occurs then. Dr. Kamel comments that calcium supplements “restore serum calcium levels.” That is not really correct, as serum calcium levels are higher in postmenopausal women than in premenopausal women, and the effect of serum calcium supplementation is to suppress parathyroid hormone and bone resorption, rather than to change serum calcium levels themselves ( 2 Reid I.R. Ames R.W. Evans M.C. et al. Effect of calcium supplementation on bone loss in postmenopausal women. N Engl J Med. 1993; 328: 460-464 Crossref PubMed Scopus (448) Google Scholar ). He repeats the long-held view that the actions of thiazides on bone are principally by way of changing tubular resorption of calcium. That is likely to be substantially true, although a significant finding of our recent study was that thiazides might also directly inhibit bone resorption, possibly through their known inhibition of carbonic anhydrase in the osteoclast ( 1 Reid I.R. Ames R.W. Orr-Walker B.J. et al. Hydrochlorothiazide reduces loss of cortical bone in normal postmenopausal women a randomized controlled trial. Am J Med. 2000; 109: 362-370 Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar ). Dr. Kamel concludes that thiazides should be preferentially given to women with high urine calcium excretion. It should be noted, however, that in our study, the size of the therapeutic benefit was not related to the baseline urine calcium excretion. The key finding of our study—that thiazides produce small but detectable beneficial effects on bone density—has recently been supported by data from a similar study by LaCroix et al ( 3 LaCroix A.Z. Ott S.M. Ichikawa L. Scholes D. et al. Low-dose hydrochlorothiazide and preservation of bone mineral density in older adults. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2000; 133: 516-526 Crossref PubMed Scopus (185) Google Scholar ). Dr. Kamel is probably correct in concluding that the principal relevance of these trials is to the selection of antihypertensive therapy for postmenopausal women, as there are obviously much more potent agents that can be used to increase bone density in women with osteoporosis. What role would thiazide diuretics have in the prevention of postmenopausal osteoporosis?The American Journal of MedicineVol. 111Issue 2Preview Full-Text PDF

Influence of Muscle Strength and Body Weight and Composition on Regional Bone Mineral Density in Healthy Women Aged 60 Years and Over

Although weight, lean mass, fat mass and muscular strength are often found to be intercorrelated, the respective role of each parameter in bone mineral density (BMD) remains unknown in older women. The aim of the present study was to investigate the relationship between body weight and composition and quadriceps strength on femoral neck and lumbar spine BMD in healthy postmenopausal women. The relationship between isokinetic quadriceps strength measured by Biodex and BMD measured by dual energy X-ray absorptiometry was studied in 56 women aged 60–81 (70.5 ± 6.2) years in multiple regression models adjusted for age, body composition and menopausal treatment. Weight and age were associated with femoral neck BMD (33 and 10% of variance accounted for, respectively) and lumbar spine BMD (23 and 8% of its variance). When body weight and quadriceps strength were excluded from the model, lean mass and age were associated with femoral neck BMD (29 and 14% of variance explained, respectively) and lumbar spine BMD (28 and 11% of variance explained, respectively). When quadriceps strength was entered into the model, it was strongly associated with femoral neck BMD (30% of variance accounted for), in addition to lean mass (9%) and age (7%), whereas it was not associated with lumbar spine BMD. In conclusion, lean mass explains a great part of the strong association between body weight and femoral neck and lumbar spine BMD. Quadriceps strength explains a great part of the association between lean mass and BMD at the femoral neck site but not at the lumbar spine site. These results suggest a site-specific effect of muscular strength on bone and a potential role of the age-related decline of muscle strength in age-related bone loss in postmenopausal women.

RISEDRONATE: CLINICAL USAGE

SUMMARYRisedronate is a new bisphosphonate – a family of drugs that inhibit bone resorption – and thus can be used in various bone conditions involving increased levels of bone resorption, such as postmenopausal osteoporosis, glucocorticoid‐induced bone loss, and Paget's disease of bone. In placebo‐controlled clinical trials, risedronate has been shown to prevent bone loss in postmenopausal women, to decrease the incidence of vertebral and non vertebral (including hip) fractures in postmenopausal women with osteoporosis, and to prevent bone loss in men and women treated with moderate to high doses of glucocorticoids. Risedronate has also been shown substantially to decrease the severity of bone pain and the level of bone turnover in Paget's disease of bone, and to improve the radiographic lesions of this disease. Risedronate is safe and well tolerated. Thus, risedronate is a new option for the management of postmenopausal osteoporosis, Paget's disease of bone and corticosteroid‐induced bone loss.

Withdrawal of hormone replacement therapy is associated with significant vertebral bone loss in postmenopausal women.

This study aimed to assess the changes in vertebral bone mineral density (BMD) after cessation of hormone replacement therapy (HRT) in postmenopausal women who had been treated on a long-term basis. Fifty healthy postmenopausal women who had been followed both during the course of HRT and after cessation of treatment in our menopause clinic were included in this study. All women had started HRT within the first 3 years after the postmenopause and had received HRT (either 1.5 mg/day of 17 beta-estradiol given percutaneously or 50 micrograms/day of 17 beta-estradiol given as a transdermal patch, combined in all women with natural progesterone or a 19-norprogesterone derivative) for a mean 5 +/- 2.4 years. In all women, vertebral BMD was assessed during the course of HRT up to the last 6 months before estrogen withdrawal, then at least once within the first 18 months after cessation of treatment. Of the initial population, 30 women were additionally reviewed later on and up to 8 years after cessation of treatment (mean duration of follow-up for the whole population: 3.9 +/- 1.7 years). Rates of changes in vertebral BMD were compared with those determined in a group of healthy untreated women who had been followed within the first years of postmenopause during the same time period as the study population. In the study group, bone loss was found to accelerate within the first 2 years after HRT withdrawal and the annual rate of loss was identical to that which occurs within the first 2 years of postmenopause in untreated women (-1.64% +/- 1.3% vs -1.52 +/- 0.9%, NS). Beyond this first 2-year time period, the annual rate of bone loss decreased as a function of time following cessation of treatment, as was observed following the menopause in untreated women (between 3 and 5 years: -0.83% + 1.35% in the study group vs -0.70% +/- 0.8% in the control group, NS). On average, 3 years after cessation of HRT mean vertebral BMD when expressed as a Z-score was significantly higher (-0.13 vs -0.89, p < 0.01) than at baseline, before HRT was started, which suggested a lasting beneficial effect on bone mass. However, even though our findings do not support the hypothesis that bone loss might continue to be accelerated several years after cessation of treatment we cannot fully address the question as to whether any residual benefit on bone mass over a longer period of time may be observed. In conclusion, the pattern of bone loss observed after cessation of estrogen therapy was found to be comparable to that which occurs in younger women within the first years after the menopause. Such a pattern needs to be kept in mind when the decision to stop HRT is taken, especially in women who were given HRT to prevent osteoporosis. The issue of assessing their risk of fracture several years after cessation of treatment thus needs to be addressed.

Role of Estrogens in the Management of Postmenopausal Bone Loss

It is well known that estrogen deficiency is the major determinant of bone loss in postmenopausal women. Estrogen is important to the bone remodeling process through direct and indirect actions on bone cells. The largest clinical experience exists with estrogen therapy, demonstrating its successful prevention of osteoporosis as well as its positive influence on oral bone health, vasomotor and urogenital symptoms, and cardiovascular risk factors, which may not occur with other nonestrogen-based treatments. Compliance with HRT, however, is typically poor because of the potential side effects and possible increased risk of breast or endometrial cancer. Nevertheless, there is now evidence that lower doses of estrogens in elderly women may prevent bone loss while minimizing the side effects seen with higher doses of estrogen. Additionally, when adequate calcium, vitamin D, and exercise are used in combination with estrogen-based treatments, more positive increases occur in bone density. The benefits and risks of HRT must be assessed on a case-by-case basis, and the decision to use HRT is a matter for each patient in consultation with her physician. Estrogen-based therapy remains the treatment of choice for the prevention of osteoporosis in most postmenopausal women, and there may be a role for estrogen to play in the prevention of corticosteroid osteoporosis. Combination therapies using estrogen should probably be reserved for patients who continue to fracture on single therapy or should be used in patients who present initially with severe osteoporosis.

Calcium intake and bone mass

The deficiency of calcium intake during childhood blocks the attainment of normal peak bone mass. On the other hand, oral calcium supplement is effective for suppressing bone loss in postmenopausal women. This effect is prominent especially in older women as well as women with lower calcium intake, and in cortical bone, compared with cancellous bone. Thus, the deficiency of calcium intake is considered to be one of major risk factors for osteoporosis, but no clear evidence have been available in Japan.

Quality indicators for the management of osteoporosis in vulnerable elders.

Osteoporosis is a major cause of morbidity and death in older persons. For women who are 50 years of age, the estimated lifetime risk for osteoporotic fracture is 54%, and studies suggest that the ...

Prediction of bone loss in postmenopausal women.

Prediction of bone loss in postmenopausal women.

Risedronate Reverses Bone Loss in Postmenopausal Women With Low Bone Mass: Results From a Multinational, Double-Blind, Placebo-Controlled Trial

This study evaluated risedronate, a bisphosphonate used to treat Paget’s disease of bone, for effectiveness and safety when used to prevent or reverse loss of bone mineral density (BMD) in postmenopausal women with low bone mass. A total of 543 women up to age 80 years who were at least 1 year postmenopausal were entered into a randomized, double-blind, placebo-controlled study in which patients received risedronate in a dose of 2.5 or 5 mg. BMD was measured in the lumbar spine, femoral neck, and trochanter. The two treatment groups and placebo recipients had comparable BMD in the lumbar spine at baseline. At least 2 years of treatment were completed by 355 participants. BMD at the lumbar spine increased by 4 percent after 2 years in patients given 5 mg of risedronate, and a lesser increase was noted in those given 2.5 mg. Patients receiving placebo had no change. Benefit was not a function of time since menopause (Fig. 1). Changes in BMD at the femoral neck and trochanter were less impressive than in the spine except for a nearly 3 percent increase at the trochanter after 2 years of 5 mg of risedronate. Serum levels of bone-specific alkaline phosphatase decreased by nearly one-fourth after 2 years of treatment with 5 mg of risedronate and increased by 8 percent on average in patients taking the placebo (Fig. 2). The reduction in the N-telopeptide/creatinine ratio after 2 years on 5 mg of risedronate was substantially greater than in the placebo group. There were positive trends toward a reduction in vertebral fractures, mostly with the higher dose of risedronate. Adverse events, including gastrointestinal erosion and ulceration, were comparably frequent in all groups. Risedronate was a rapidly effective and well-tolerated treatment for postmenopausal osteoporosis in this trial, regardless of time since menopause.Fig. 1: Change in BMD at the lumbar spine during treatment with 5 mg of risedronate (▪), 2.5 mg of risedronate (▴), or placebo (○), stratified into: A) ≤5 years postmenopausal or B) >5 years postmenopausal. ***, P < .001 versus placebo. Values are means ± SEM.Fig. 2: Changes in A) serum concentrations of bone-specific alkaline phosphatase and B) NTx/creatinine during treatment with 5 mg of risedronate (▪) or placebo (○). ***, P < .001 versus placebo. Values are means ± SEM.J Clin Endocrinol Metab 2000;85:1895–1900

Long-term Exercise Using Weighted Vests Prevents Hip Bone Loss in Postmenopausal Women

Bone mineral density (BMD) is a primary risk factor for hip fracture. We studied the effect of long-term weighted vest plus jumping exercise on hip BMD in postmenopausal women as a strategy for reducing hip fracture risk. Eighteen postmenopausal women (age = 64.1 +/- 1.6 years at baseline, 69.9 +/- 1.6 years at post-testing) who had participated in a 9-month exercise intervention volunteered for the long-term trial. Nine of the original group engaged in weighted vest plus jumping exercise three times per week for 32 weeks of the year over a period of 5 years. Nine of the original controls were active but not enrolled in the exercise program. BMD of the proximal femur was assessed by dual energy x-ray absorptiometry at baseline and after 5 years. At baseline, groups were similar for age, weight, height, years past menopause, and BMD of the femoral neck, trochanter, and total hip. At follow-up, differences in BMD at all regions of the hip were higher in exercisers than controls. For exercisers, changes in BMD were + 1.54% +/- 2.37%, -0.24% +/- 1.02%, and -0.82% +/- 1.04% (means + SE) at the femoral neck, trochanter, and total hip, respectively; controls decreased at all sites (-4.43% +/- 0.93%. 3.43% +/- 1.09%, and -3.80% +/- 1.03%, respectively). A 5-year program of weighted vest plus jumping exercise maintains hip BMD by preventing significant bone loss in older postmenopausal women. Furthermore, this particular program appears to promote long-term adherence and compliance, as evidenced by the commitment of the exercisers for more than 5 years.

Prevention of bone loss by EM-800 and raloxifene in the ovariectomized rat

Some undesirable effects are associated with chronic estrogen and progestin administration used to prevent bone loss in postmenopausal women, thus leading to poor compliance and the need for improved therapeutic and preventive agents. We have thus studied the ability of the new antiestrogen EM-800 (SCH 57050) to prevent bone loss and lower serum cholesterol levels and compared its effects with those of raloxifene. Ovariectomized (OVX) female rats were treated by oral gavage for 37 weeks with increasing daily doses (0.01, 0.03, 0.1, 0.3 or 1 mg/kg) of EM-800 or raloxifene. At 35 weeks after OVX, lumbar spine bone mineral density (BMD) was 19% lower than in intact animals ( P<0.01), while the OVX animals given EM-800 or raloxifene had 90–93 and 85–90%, respectively, of the BMD values observed in intact rats. Similar effects were observed on femoral BMD. Bone histomorphometry measurements were performed on proximal tibia. At the 0.01 mg/kg dose, EM-800 prevented the effect of OVX on TBV by 34% ( P<0.01), while raloxifene had no detectable effect. Treatment with 1 mg/kg EM-800 and raloxifene resulted in, respectively, 68% ( P<0.01) and 64% ( P<0.01) prevention of the OVX-induced decrease in TBV. In addition, the administration of 0.01 and 0.03 mg/kg EM-800 caused, respectively, 54% ( P<0.01) and 56% ( P<0.01) inhibitions of serum cholesterol levels, while raloxifene administered at the same doses caused, respectively, 24% ( P<0.01) and 41% ( P<0.01) decreases of the value of the same parameter. At the highest doses used (0.1–1 mg/kg), both compounds lowered serum cholesterol levels by approximately 65% ( P<0.01). No stimulatory effect of EM-800 was observed on the endometrial epithelial cells at doses up to 1 mg/kg, while hypertrophy of uterine epithelium was observed with raloxifene. EM-800 and raloxifene achieve the same degree of effectiveness on bone and serum cholesterol at higher doses, but EM-800 is at least three to ten times more potent than raloxifene at lower concentrations and has no stimulatory effect on uterine epithelium. The present data show the potent effect of EM-800 preventing bone loss and lower serum cholesterol levels without the negative effect on the endometrium, thus suggesting the particular interest of this new fully tissue-specific selective estrogen receptor modulator.