Ovarian steroid treatment blocks a postmenopausal increase in blood monocyte interleukin 1 release.

In previous studies, we showed that blood monocyte elaboration of interleukin 1 (IL-1), a known stimulator of bone resorption, was higher in osteoporotic patients with rapid bone turnover than in those with slow turnover and in nonosteoporotic subjects. Since an acceleration of bone loss following menopause contributes to the risk of osteoporosis in women, we have studied the effects of menopause and ovarian steroid treatment on IL-1 release by monocytes obtained from nonosteoporotic and osteoporotic women. IL-1 activity in the monocyte culture medium derived from untreated postmenopausal women (nonosteoporotic and osteoporotic) was higher than in the medium derived from either untreated premenopausal or estrogen/progesterone-treated postmenopausal women. A significant negative correlation was found between IL-1 and years since menopause in both the healthy (r = -0.75; P less than 0.005) and the osteoporotic (r = -0.61; P less than 0.01) untreated postmenopausal women. The difference between the two slopes was significant at P less than 0.05. Premenopausal IL-1 levels were achieved within 8 years of menopause in the nonosteoporotic, but not in the osteoporotic, subjects in whom increases were evident as long as 15 years after menopause. IL-1 also correlated inversely with vertebral mineral density (r = -0.37; P less than 0.05), as measured by quantitative computed tomography. In prospective studies, treatment with estrogen/progesterone for 1 month caused a substantial highly significant decrease in IL-1 activity in each of three nonosteoporotic and five osteoporotic women, confirming the apparent effect of hormone therapy observed in the cross-sectional analysis. Although a cause-effect relationship has not been established, it is our hypothesis, based on these data, that alterations in IL-1 production may underlie the postmenopausal acceleration in bone loss and its inhibition by ovarian steroids. Persistent elevation of IL-1 secretion appears to be a feature of postmenopausal osteoporosis.     

Treatment of postmenopausal hyperparathyroidism with norethindrone. Long-term effects on forearm mineral content

In 15 postmenopausal women with mild primary hyperparathyroidism, the long-term effect of norethindrone therapy (5 mg/d) on forearm bone mineral content (FMC) was evaluated. The FMC rose from 810 +/- 39 (SEM) mg/cm at baseline to 841 +/- 41 mg/cm after 2 years of treatment, representing a mean bone mineral gain of 1.9% per year. The majority of this bone gain occurred during the first 6 months of treatment. The rate of increase in FMC in the first 6 months was +3.71 +/- 0.12 mg/cm per month compared with -0.35 +/- 0.51 mg/cm per month during the second year. Fat-corrected FMC was measured to determine whether the bone gain was real or reflected a decrease in fat mass. There was a similar rise in fat-corrected FMC (from 885 +/- 36 mg/cm at baseline to 909 +/- 39 mg/cm at 2 years). The difference between fat-corrected and uncorrected FMC, however, decreased slightly on norethindrone treatment (from 75.2 +/- 11.9 mg/cm at baseline to 67.8 +/- 11.8 mg/cm at 12 months), indicating a reduction in the subcutaneous fat layer. We conclude that norethindrone therapy in postmenopausal women with mild primary hyperparathyroidism produces a gain in bone mass that is sustained for at least 2 years.     

Safety and efficacy of estrogen therapy in preventing bone loss in primary biliary cirrhosis

OBJECTIVE: Estrogen therapy has been found to be useful in the treatment of postmenopausal osteoporosis. However, concern about its potential for worsening cholestasis has limited its use in postmenopausal women with primary biliary cirrhosis. The aim of the present study was to determine the safety as well as the efficacy of estrogen replacement therapy with respect to bone mass in postmenopausal women with primary biliary cirrhosis. METHODS: Bone mineral density of the lumbar spine (measured using dual energy x-ray absorptiometry) of 46 unselected postmenopausal women with primary biliary cirrhosis receiving estrogen replacement therapy was compared with 46 age-matched women with primary biliary cirrhosis not receiving estrogen replacement therapy, and with the expected normal bone mineral density adjusted for age and ethnic group. RESULTS: The mean duration of follow-up was 4.8 +/- 0.4 yr. Treatment with estrogens resulted in a significantly lower rate of bone loss (0.002 g/cm(2)/yr +/- 0.028 vs 0.009 g/cm(2)/yr +/- 0.020, p = 0.05). Worsening cholestasis attributable to estrogen replacement therapy did not occur in any patient. One patient (2%) discontinued therapy because of side effects. CONCLUSIONS: Estrogen replacement therapy in postmenopausal patients with primary biliary cirrhosis is safe and may be effective in decreasing the rate of bone loss.     

The role of interleukin-1 in postmenopausal bone loss

Interleukin-1 (IL-1), a cytokine best known for its ability to stimulate lymphocyte proliferation, has recently been shown to stimulate bone resorption and modulate bone formation in vivo. Consequently, the authors have devised a series of studies to investigate the relationship between bone remodeling, menopause, and monocyte IL-1-secretion. In a first study, monocytes from osteoporotic patients were found to produce more IL-1 than monocytes from control subjects. IL-1 activity was also found to reflect histomorphometric indices of bone formation, but not of bone resorption. In a second study, devised to assess the effect of menopause on the relationship between IL-1 and bone turnover, a significant correlation was found between IL-1 and BGP in premenopausal osteoporotic women and osteoporotic men, but not in both postmenopausal osteoporotic subjects and normal subjects of either sex. In a third study, IL-1 from untreated postmenopausal women was found to be higher than in either untreated premenopausal or estrogen/progesterone-treated postmenopausal women. A significant negative correlation was found between IL-1 and years since menopause in both the healthy and osteoporotic postmenopausal women. Premenopausal IL-1 levels were achieved within eight years of menopause in the healthy but not in the osteoporotic subjects. In osteoporotic women, high IL-1 levels were evident as long as 15 years after menopause. IL-1 also correlated inversely with mineral density as measured by quantitative computer tomography. In prospective study, treatment with estrogen/progesterone caused a significant increase in IL-1 activity. This data indicates that monocyte IL-1 production mirrors the rate of bone turnover in both the healthy and osteoporotic patient, and that alteration in IL-1 production may underlie the postmenopausal acceleration of bone loss and its inhibition by ovarian steroids.     

High habitual calcium intake attenuates bone loss in early postmenopausal Chinese women: an 18-month follow-up study

This study assessed the association of habitual dietary calcium intake and bone loss in early postmenopausal women. Four hundred fifty-four healthy postmenopausal Chinese women were enrolled for this 18-month cohort study. The subjects were 48-62 yr of age and within 12 yr of natural menopause. Dietary intake was assessed by the food frequency method, and bone mass was measured using dual energy x-ray absorptiometry at baseline and 9 and 18 months. The association between mean habitual dietary intake over the follow-up period and the rate of bone loss was examined. During the 18-month follow-up, the total loss rates of BMD at the whole body, lumber spine, femoral neck, and total hip were 1.28, 0.60, 1.54, and 0.56% (all P < 0.01). Subjects were stratified into four quartiles according to calcium intake during the period of follow-up. Quartiles I-IV had median intakes of 341, 505, 682, and 934 mg Ca/d. Subjects in quartile IV had significantly less BMD loss at the whole body and less BMD/bone mineral content loss at Ward's triangle, even after adjustments for confounding factors (by analysis of covariance). Multiple linear regression analyses showed significant positive associations between calcium intake and BMD change at the whole body (P = 0.006) and Ward's triangle (P = 0.021). Calcium intake was significantly associated with bone mineral content change at the trochanter (P = 0.025) and Ward's triangle (P < 0.001). No significant effect of calcium intake at the spine was found. In conclusion, habitual dietary calcium intake had a beneficial effect on bone loss at the whole body and some regions of the hip. Our findings suggest that an intake exceeding 900 mg calcium/d was helpful in the prevention of cortical bone loss among early postmenopausal Chinese women.     

Effects of aging, menopause, and hormone replacement therapy on forearm skin elasticity in women

OBJECTIVES: To investigate the decline per year in skin elasticity in postmenopausal women and how much hormone replacement therapy (HRT) increased elasticity over 12 months. DESIGN: Observational study of convenience sample. SETTING: The Cardiovascular Hospital of Central Japan, a cardiovascular medical center. PARTICIPANTS: One hundred seventy-six postmenopausal subjects, mean age+/-standard deviation=61.3+/-9.1. MEASUREMENTS: In Study 1, skin elasticity was measured in the right forearm using a suction device. Comparisons also were made with 45 premenopausal subjects (aged 34.5+/-9.9). Skin elasticity in the right forearm was measured using the same device at baseline and 12 months after initiation of HRT. INTERVENTIONS: In Study 2, 12 postmenopausal subjects (mean age=57.1+/-7.4, range 49-71) received conjugated equine estrogen (0.625 mg/d) in combination with medroxyprogesterone acetate (2.5 mg/d) for 12 months. RESULTS: In Study 1, significant negative correlations between skin elasticity and age and years since menopause were found (r=-0.60, P<.001 for each), as well as a 0.55% decline per year in skin elasticity. In Study 2, 12 months of HRT significantly increased skin elasticity in postmenopausal subjects, by 5.2%. CONCLUSION: After menopause, skin elasticity declined 0.55% per year; 12 months of HRT increased elasticity by 5.2%.     

上海地区绝经后妇女骨质疏松症危险因素流行病学研究

目的通过绝经后骨质疏松症的分布特征和易发因素相关性分析,探讨绝经后骨质疏松症的病因机理和危险因素。方法选取社区50～69岁绝经1年以上妇女,以问卷调查,结合DXA测量BMD值,以及血清1α,25（OH）2D3等骨代谢指标测定,分析与骨丢失的相关性。结果骨质疏松症的发生率随增龄和绝经年限的延长而上升,绝经年龄早、生育胎数多、哺乳时间长是低骨量的重要危险因素,而使用雌激素、长期饮用牛奶、维持一定体重对骨量值有保护作用。此外,绝经后OP妇女的血清1α,25（OH）2D3和25（OH）D3含量均明显低于非OP妇女,血清1α,25（OH）2D3含量与BMD值呈高度相关（r=0．693,P〈0．01）。骨代谢相关指标分析表明,绝经后OP表现为高骨转换型,维生素D与PTH状态,以及DPD／Cr等均是评价绝经后OP患者的重要指标。结论妇女绝经后有一个快速的骨丢失过程,而血清1α,25（OH）2D3水平的低下是绝经后骨量丢失的一个重要原因。为维护骨骼健康,应维持其底物25（OH）D3在正常范围内。     

Anabolic effect of estrogen replacement on bone in postmenopausal women with osteoporosis: histomorphometric evidence in a longitudinal study

It is well recognized that estrogen (E(2)) prevents postmenopausal bone loss by suppressing bone resorption. Despite evidence that E(2) may also stimulate bone formation in animals, an anabolic effect in humans is still controversial. To investigate this, we studied 22 older postmenopausal females, with a mean age of 65.4 yr and mean interval of 16.9 yr since menopause and low bone mineral density. Transcortical iliac bone biopsies were performed before and 6 yr after E(2) replacement therapy (ERT) [75 mg percutaneous E(2) replaced 6-monthly plus oral medroxy progesterone acetate (5 mg daily) for 10 days each calendar month]. The mean serum E(2) level after 6 yr of treatment was 1077 (range, 180-2568) pmol/L. Bone mineral density improved in every patient, with a median increase of 31.4% at the lumbar spine and 15.1% at the proximal femur. Bone histomorphometry showed an increase in cancellous bone volume from 10.75% to 17.31% (P < 0.001). The wall thickness after 6 yr of E(2) treatment was 38.30 micrometer compared with 31.20 micrometer before commencement of ERT (P < 0.0005), indicating net bone gain. This is the first report showing histological evidence for an increase in cancellous bone volume, together with an increase in wall thickness, in a longitudinal follow-up study of ERT in older postmenopausal women. Our results show that E(2) is capable of exerting an anabolic effect in women with osteoporosis, even when started well into the menopause.     

The effect of glucocorticoids on bone mass in rheumatoid arthritis patients. Influence of menopausal state

We studied 97 patients with definite or classic rheumatoid arthritis (RA). Fifty-four patients (19 premenopausal women, 25 postmenopausal women, and 10 men) had been treated with low-dose glucocorticoids for at least 12 months (mean dose less than 10 mg/day). The remaining 43 patients (15 premenopausal women, 17 postmenopausal women, and 11 men) had been treated with penicillamine, and served as a patient control group. The distal forearm bone mineral content (BMC) was measured in all patients by single photon absorptiometry using 125I, and the total body bone mineral (TBBM) was measured in 61 patients by dual photon absorptiometry using 153Gd. Compared with normal controls, both treatment groups had significantly decreased BMC and TBBM (0.01 less than P less than 0.001). When the patients were stratified according to pre- and postmenopausal state, we found significantly lower BMC and TBBM values in the premenopausal glucocorticoid-treated women than in penicillamine-treated women. However, no differences in BMC and TBBM values were found in the corresponding postmenopausal groups. In the premenopausal women treated with glucocorticoids, the duration of treatment and cumulative dose correlated with BMC. No such correlations were found in the postmenopausal women. We conclude that 1) RA is associated with loss of bone mass, 2) systemic glucocorticoid treatment further aggravates the bone loss, 3) in postmenopausal RA patients, the bone loss resulting from menopause and from the disease itself is not accelerated by low-dose glucocorticoids, and 4) in premenopausal RA patients, however, the bone mass is significantly affected by glucocorticoid treatment. We therefore suggest that these factors be considered when prescribing glucocorticoids, in order to minimize the bone loss.     

Alendronate and estrogen-progestin in the long-term prevention of bone loss: four-year results from the early postmenopausal intervention cohort study. A randomized, controlled trial

BACKGROUND: Up to 3 years of treatment with alendronate, 5 mg/d, prevents postmenopausal bone loss. OBJECTIVE: To determine whether the effect of alendronate is sustained at 4 years of treatment and persists after treatment is discontinued. DESIGN: Randomized, controlled trial. SETTING: United States and Europe. PARTICIPANTS: 1609 postmenopausal women 45 to 59 years of age. INTERVENTION: Participants were randomly assigned to receive oral alendronate, 5 mg/d or 2.5 mg/d; placebo; or open-label estrogen-progestin. Women in the alendronate groups received alendronate for the first 2 years of the study. Treatment was then continued without change or replaced with placebo for the last 2 years of the study. MEASUREMENTS: Annual measurement of bone mineral density. RESULTS: By year 4, the bone mineral density of participants in the placebo group had decreased by 1% to 6% (P < 0.001). Four years of treatment with 5 mg of alendronate per day increased bone mineral density at the spine (mean change [+/-SE], 3.8%+/-0.3%), hip (mean, 2.9%+/-0.2%), and total body (mean, 0.9%+/-0.2%) (P < 0.001 overall). By year 4, bone mineral density at most skeletal sites was greater in participants who switched from alendronate to placebo than in those who continuously received placebo. In years 3 and 4, bone loss in participants who switched from alendronate to placebo was similar to that seen during years 1 and 2 in those who continuously received placebo. Compared with 5 mg of alendronate per day, estrogen-medroxyprogesterone acetate produced similar increases in bone mineral density and estradiol-norethisterone acetate produced increases that were substantially greater. CONCLUSIONS: Four years of treatment with alendronate or estrogen-progestin prevented postmenopausal bone loss. A residual effect was seen 2 years after alendronate therapy was stopped; however, continuous alendronate treatment was more effective in preventing postmenopausal bone loss than 2 years of alendronate followed by 2 years of placebo.     

Relative contributions of years since menopause, age, and weight to vertebral density in postmenopausal women.

Vertebral mineral density (VMD) was measured by quantitative computerized tomography (QCT) in 16 premenopausal and 243 untreated postmenopausal women without vertebral compression. The mean VMD in the premenopausal group was 157 +/- 10.1 mg/mL, which is close to previously reported values. In the postmenopausal women, VMD fell significantly with age and years since menopause (YSM) separately and together, but the relation to YSM was more significant than that to age. After logarithmic transformation of YSM, the fall in bone density with logYSM was highly significant (P less than 0.001), and that with age was not quite significant. In 36 pairs of women matched for YSM, there was no significant difference in VMD between the subjects up to and over 55 yr of age. In 32 pairs matched for age, VMD was significantly lower in those over 55 yr than in those up to 55 yr (P = 0.005). There was also a significant correlation between VMD and body weight. After this was allowed for, the correlation between VMD and logYSM remained highly significant, but the correlation with age was not significant. We conclude that the fall in vertebral body trabecular bone in postmenopausal women is self-limiting, amounts to about 35% bone loss in 25 yr (most of it in the first 5 yr), and corresponds to but is proportionately greater than the trabecular component in postmenopausal forearm bone loss.     

The association between low bone mass at the menopause and cardiovascular mortality

BACKGROUND: Low bone mineral density in late postmenopausal women has been associated with increased nontrauma mortality. We investigated whether bone mass in women soon after menopause was also associated with the risk of mortality in later life. METHODS: Between 1977 and 1988, two samples of healthy women were enrolled; one group soon after the menopause (age 50 +/- 2 years [mean +/- SD], n = 309) and another later after menopause (age 70 +/- 2 years, n = 754). The baseline visit included a medical examination and a measurement of bone mineral content in the distal forearm. In 1994, vital status was checked. All causes of death were registered, excluding those that were due to trauma or suicide. Multivariate relative risks (RR) and 95% confidence intervals (CI) were determined. RESULTS: In the early postmenopausal group, each decrease of one SD (0.4 g/cm) in bone mineral content was associated with a 43% increase in mortality (RR = 1.4; 95% CI 1.0 to 2.0; P < 0.05). When only cardiovascular death was considered, the relative risk of dying within 17 years of the menopause was increased 2.3-fold (95% CI 1.0 to 5.3; P < 0.05). Correspondingly, a 70-year-old woman with a bone mineral content 1 SD below the mean for her age had a 1.8-fold increased risk of dying from cardiovascular disease (95% CI 1.0 to 3.2; P = 0.06). Expressed as quartiles, women with bone mass in the lowest quartile had twice the risk of cardiovascular death compared with those in the highest quartile. A prevalent vertebral compression fracture in the late postmenopausal group was independently associated with cardiovascular death (RR = 2.0; 95% CI 1.4 to 3.3; P = 0.004). CONCLUSION: Low bone mineral content at the menopause is a risk factor for increased mortality in later life, especially from cardiovascular disease.     

Treatment of postmenopausal osteoporosis with transdermal estrogen.

OBJECTIVE: To evaluate the tolerance and effectiveness of transdermal estrogen for women with established postmenopausal osteoporosis and vertebral fractures. DESIGN: Double-blind, randomized, placebo-controlled clinical trial lasting 1 year. SETTING: Referral-based outpatient clinic. PATIENTS: Seventy-five postmenopausal women, 47 to 75 years of age, with one or more vertebral fractures due to osteoporosis. INTERVENTIONS: Thirty-nine women received dermal patches delivering 0.1 mg of 17 beta-estradiol for days 1 to 21 and oral medroxyprogesterone acetate for days 11 to 21 of a 28-day cycle. Another 39 women received placebo. MEASUREMENTS: Bone turnover assessed by biochemical markers and iliac bone histomorphometry; bone loss assessed by serial measurement of bone density; and vertebral fracture rate. RESULTS: Compared with the placebo group, the median annual percentage change in bone mineral density in the estrogen group reflected increased or steady-state bone mineral density at the lumbar spine (5.3 compared with 0.2; P = 0.007), femoral trochanter (7.6 compared with 2.1; P = 0.03), and midradius (1.0 compared with -2.6, P less than 0.001) but showed no significant difference at the femoral neck (2.6 compared with 1.4; P = 0.17). Estrogen treatment uniformly decreased bone turnover as assessed by several methods including serum osteocalcin concentration (median change, -0.35 compared with 0.02 nmol/L; P less than 0.001). Histomorphometric evaluation of iliac biopsy samples confirmed the effect of estrogen on bone formation rate per bone volume (median change, -12.9 compared with -6.2% per year; P = 0.004). Also, 8 new fractures occurred in 7 women in the estrogen group, whereas 20 occurred in 12 women in the placebo group, yielding a lower vertebral fracture rate in the estrogen group (relative risk, 0.39; 95% CI, 0.16 to 0.95). CONCLUSIONS: Transdermal estradiol treatment is effective in postmenopausal women with established osteoporosis.     

Diabetes and premature menopause: is their co-existence detrimental to the skeleton?

OBJECTIVE: Premature menopause is a known risk factor for osteoporosis, whilst the influence of type 2 diabetes on bone mineral density (BMD) is still controversial. DESIGN AND METHODS: BMD values assessed by dual-energy X-ray absorptiometry (DXA) in L2-L4 vertebrae and the femoral neck (FN) of 40 diabetic women with premature menopause (D-EMP) were compared with those of 60 non-diabetic, prematurely menopausal women (EMP) and 60 diabetic women with normal menopause (D-NMP) who had been matched by age and body mass index (BMI). In all women, the time elapsed since menopause ranged between 10 and 25 years and the duration of diabetes exceeded 75% of the postmenopausal time period. The age of D-EMP women was 58.7+/-5 years (mean+/-1 s.d.), age at menopause 39.5+/-2.7, years since menopause 18.6+/-4.9, BMI 27.8+/-4.3 kg/m(2) and duration of diabetes 13.9+/-3.9 years. RESULTS: Vertebral BMD values of D-EMP women were significantly higher than those of EMP women (0.908+/-0.135 vs. 0.817+/-0.14 g/cm(2), P = 0.002), although there was no significant difference between D-EMP and D-NMP women (0.886+/-0.15 g/cm(2)). No significant differences were observed in FN BMD values between all groups. Age-adjusted BMD values (Z scores) of D-EMP women were higher than EMP women in both anatomic sites (P < 0.01), but did not differ from D-NMP women. In contrast to the other two groups, no statistically significant correlation was observed in D-EMP women between the BMD values of either anatomic area and the time elapsed since menopause. HbA(1c) values were positively correlated only to vertebral BMD values of the D-EMP group (P < 0.05). No correlation was observed between the BMD values and the duration of diabetes either in D-EMP or in D-NMP women. CONCLUSIONS: Type 2 diabetes seems to positively affect the mineral density of the trabecular bone in women with premature menopause. The duration of diabetes does not appear to influence bone mass.     

Bone mass in totally thyroidectomized patients. Role of calcitonin deficiency and exogenous thyroid treatment

Calcitonin has an uncertain role in the preservation of bone mass. Since surgical thyroidectomy abolishes the calcitonin secretion in response to calcium, the bone mineral density at the radius shaft and lumbar spine was measured in 60 patients (5 men, 16 premenopausal, 34 postmenopausal euparathyroid and 5 postmenopausal hypoparathyroid women) who had undergone near total thyroidectomy for thyroid cancer 8.4 +/- 0.7 years before the study. All patients were maintained on suppressive doses of thyroid hormones. Bone mineral density values of the radius shaft (expressed as Z-score) of 34 postmenopausal euparathyroid women was significantly below the normal average (mean +/- SEM = -0.59 +/- 0.2; p = 0.01). Bone mineral density of the lumbar spine was also below the normal average although the difference only approached statistical significance (-0.36 +/- 0.2; 0.05 less than p less than 0.1). The bone mineral density of neither the radius nor the spine differed from normal levels in the premenopausal women and the postmenopausal hypoparathyroid women. Unexpectedly, the bone mineral density of the spine was significantly increased in the 5 thyroidectomized men. The results indicate that thyroidectomized women have a diminished bone mass after the menopause only if parathyroid function is normal. Since the patients were receiving thyroid hormone at suppressive doses, the present study is not able to separate the relative contributions of calcitonin deficit and exogenous thyroid on bone mass loss.     

Effects of calcium and phosphorus intake and excretion on bone density in postmenopausal women in Hermosillo,Mexico

Calcium (Ca) is important in bone formation and as aging progresses, bone loss gradually occurs. With the onset of menopause, reduced estrogen levels and insufficient Ca in the diet often create serious problems with fractures. Since little is known about the diet and other factors related to risk factors in postmenopausal women in northern Mexico, it was the objective of this study to determine the effects of dietary Ca and phosphorus (P) and their excretion, anthropometric measurements, and blood serum estradiol on bone density in women aged 45-63 years. No studies are available on the dietary intake of Ca and P and the effects on bone mineral density (BMD) in postmenopausal women in northern Mexico, so this study reports some of the first data on this population. Women with an average age of 55 years showed a positive relation of Ca intake and Ca excretion, however, dietary intake of Ca and P had no relation to bone density. Age, urinary Ca, Ca/creatinine and years of postmenopause had the highest negative correlation. Weight and body mass index had a positive correlation with BMD in the forearm and heel. Only 15% of the women met the recommendation of 1,500 mg/day of Ca. A high Ca/creatinine ratio has been proposed to indicate excess Ca excretion and subsequent bone density loss. Thirty-five percent of the women exceed the Ca/creatinine indicator of >0.16. In this study, 1% of the subjects were classified as osteoporotic and 37% as osteopenic.     

Effects of hormone replacement therapy on bone mineral density in postmenopausal women with primary hyperparathyroidism: four-year follow-up and comparison with healthy postmenopausal women

BACKGROUND: Long-term treatment of patients with asymptomatic primary hyperparathyroidism remains controversial, but the presence of osteoporosis is regarded as an indication for parathyroidectomy. Hormone replacement therapy (HRT) is a possible alternative therapy in osteopenic postmenopausal women with the disorder, and results of short-term studies suggest a beneficial effect on bone mass comparable to that achieved by parathyroidectomy. Longer-term data are required to further assess the efficacy of this treatment in chronic stable primary hyperparathyroidism. METHODS: We report the results of the extension from 2 to 4 years of a randomized, placebo-controlled trial of HRT in postmenopausal women with primary hyperparathyroidism. Of 23 postmenopausal women with primary hyperparathyroidism, 11 received active HRT with conjugated equine estrogen, 0.625 mg/d, and medroxyprogesterone acetate, 5 mg/d, and 12 received placebo. Bone mineral density was measured throughout the skeleton at 6-month intervals using dual-energy x-ray absorptiometry in these women and in 50 normocalcemic age-matched control subjects. None of the 23 patients withdrew during the extension period. RESULTS: Changes in bone mineral density were more positive in those taking HRT than placebo, with the between-group differences at 4 years being 4.6% in the total body, 7.5% in the lumbar spine, 7.4% in the femoral neck, 8.2% in the femoral trochanter, 6.8% in the legs, and 7.0% in the forearm (P<.01). At skeletal sites composed predominantly of cortical bone, there was a progressive divergence of the 2 groups. Biochemical markers of bone turnover remained lower throughout the study in women taking HRT. When rates of bone loss were compared between the placebo group and healthy women of comparable age, bone loss tended to be more marked throughout the skeleton in women with hyperparathyroidism, but only in the total body and its legs subregion was this difference significant. CONCLUSIONS: Hormone replacement therapy is efficacious in the long-term management of osteopenia in postmenopausal women with primary hyperparathyroidism and thus represents an important new therapeutic option for asymptomatic patients who do not have other indications for surgery. Bone loss seems to be accelerated in untreated primary hyperparathyroidism.     

Forearm and vertebral bone mineral in treated and untreated hyperprolactinemic amenorrhea

To determine whether women with PRL-secreting pituitary tumors have similar decreases in cortical and trabecular bone and to determine whether bone loss associated with hyperprolactinemia is reversible, we measured forearm and vertebral bone mineral in normal women and in amenorrheic women with treated and untreated hyperprolactinemia. The mean spinal bone mineral content in hyperprolactinemic women [130 +/- 23 (+/- SD) mg/mL] was 25% lower than that in normal women (167 +/- 28 mg/mL), while the mean forearm bone mineral content (0.71 +/- 0.04 g/cm2) was similar to that in normal women (0.73 +/- 0.05 g/cm2). Women with normal serum PRL levels and regular menses after transsphenoidal surgery had slightly higher mean spinal bone mineral content (149 +/- 28 mg/mL) than women who remained amenorrheic after surgery (129 +/- 19 mg/mL), but the mean value in the cured women remained significantly lower than that in normal women. In contrast, women who had undergone successful transsphenoidal pituitary surgery had mean forearm bone mineral comparable to that in normal women. There was no correlation between vertebral and radial bone mineral in hyperprolactinemic women and no correlation between bone mineral and serum PRL, serum estradiol, or duration of amenorrhea when age was taken into account. These findings suggest that hyperprolactinemia and/or decreased gonadal function in women with PRL-secreting pituitary tumors are associated with more prominent effects on trabecular bone in the spine than on cortical bone in the wrist. In addition, the abnormal spinal bone mineral content after successful treatment suggest that normalization of estradiol and PRL secretion is not sufficient to restore bone mineral content to normal, although it may be stabilized.     

Postmenopausal bone loss is prevented by treatment with low-dosage estrogen with calcium

Bone mass was measured prospectively in 73 women during the period immediately after menopause. By comparing the rates of loss at three skeletal sites, we assessed the protective effects of calcium supplements given alone or combined with low-dosage estrogen therapy. After 2 years of follow-up, spinal trabecular mineral content, measured by quantitative computed tomography, decreased by a mean of 9.0% (p = 0.002 compared with baseline) in untreated women and a mean of 10.5% (p = 0.0001) in women given calcium supplements alone. By contrast, women given conjugated estrogens, 0.3 mg/d, with calcium supplements showed an insignificant increase of 2.3%. Significant losses of a lesser magnitude were seen in the appendicular cortical skeleton of women not receiving therapy and in those receiving calcium alone, but no significant changes were observed in women receiving estrogen with calcium.     

Prevention of early postmenopausal bone loss with cyclical etidronate

Cyclical etidronate has been shown to be effective in the treatment of established postmenopausal osteoporosis but less is known about its effects on early menopausal bone loss. The aim of the study was to establish the effects of cyclic etidronate therapy on spinal and proximal femoral bone mineral loss in early postmenopausal women. One hundred and seven women who were within 6 months to 3 years of the menopause were recruited into a 2-year, randomised, placebo-controlled, double-blind trial. Spinal bone mineral density was within 2 SD of the age-matched mean reference value at baseline. Bone mineral density in the lumbar spine and proximal femur was assessed by dual energy X-ray absorptiometry at baseline and thereafter at 6 monthly intervals for 2 years. Urinary collagen cross-links (deoxypyridinoline and pyridinoline) were measured at the same time points. Seventy-seven women completed the study. At the end of the treatment period, the mean bone mineral density change from baseline in the treated group was +0.14% and -0.06% in the lumbar spine and femoral neck, respectively, compared to -1.49 and -2.22 in the control group. Overall, there was a significant difference between the two groups at both these sites (p=0.01 and 0.001, respectively). No significant differences between the groups were demonstrated at the greater trochanter or Ward's triangle. The conclusion was that cyclical etidronate therapy prevents bone loss in the spine and femoral neck in early postmenopausal women. It provides a safe and effective therapeutic option for the prevention of postmenopausal osteoporosis in women who are unwilling or unable to tolerate hormone replacement therapy.