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Assessment of age and risk factors on bone density and bone turnover in healthy premenopausal women.

The influence of age and risk factors on bone density and bone turnover was evaluated in 249 healthy premenopausal women. Risk factors were assessed by standardized questionnaires and included reproductive history and lifestyle factors (intake of calcium and vitamin D supplements, consumption of caffeine, smoking habits and physical activity). Bone mineral density (BMD) measurements were obtained in the distal forearm, the lumbar spine and the proximal femur. Bone turnover were assessed by plasma bone Gla proteins (pBGP) and fasting urinary hydroxyproline corrected for creatinine (fUHPr/Cr). Peak bone density seems to be achieved before the age of 30 years, whereafter we found no appreciable bone loss at any skeletal site. Accordingly, the levels of pBGP and fUHPr/Cr were increased before the age of 30, whereafter the values stabilized at a lower level. A dairy calcium intake above 660 mg/day significantly increased BMD in the spine and proximal femur by 3%-5%. Physical activity alone had no influence on BMD, but in combination with calcium intake an additive effect was observed. Women who had an active lifestyle (corresponding to at least 1 h of daily walking) and a dairy calcium intake above 660 mg/day had a 3%-7% increase in BMD compared with more sedentary women with a calcium intake below this limit. Vitamin D supplements, caffeine, smoking and reproductive history did not consistently influence BMD or bone turnover. Only pBGP was selectively reduced by smoking and current use of oral contraceptives, respectively. We conclude that there is no appreciable change in BMD before the menopause once skeletal maturity has been reached.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

Bone density and bone area in Canadian Aboriginal women: the First Nations Bone Health Study.

INTRODUCTION: Canadian Aboriginal women are at increased risk of fracture compared with the general population. HYPOTHESIS: There is disproportionately reduced bone density in Aboriginal women as compared to white females of similar age. METHODS: A random age-stratified (25-39, 40-59 and 60-75) sample of Aboriginal women (n=258) and white women (n=181) was recruited. All subjects had calcaneus and distal forearm bone density measurements, and urban participants (n=397 [90.4%]) also had measurements of the lumbar spine, hip and total body. RESULTS: Unadjusted measurements were similar in the two groups apart from the distal forearm which showed a significantly lower mean Z-score in the Aboriginal women (p=0.03). Aboriginal women were heavier than white women (81.0+/-18.0 kg vs. 76.0+/-18.0 kg, p=0.02). Weight was directly associated with BMD at all measurement sites (p<0.00001) and potentially confounded the assessment of ethnicity on bone mass measurements. Weight-adjusted ANCOVA models demonstrated significantly lower bone density in Aboriginal than white women for the calcaneus, distal forearm, and total body (all p<0.05), but not at the other sites. ANCOVA models (adjusted for age, height and weight) were used to explore differences in bone area and bone mineral content (BMC). There was a significant effect of ethnicity on bone area with Aboriginal women having larger adjusted mean values than white women (lumbar spine p=0.038, total hip p=0.0004, total body p=0.020). In contrast, there was no detectable effect of ethnicity on BMC (all p>0.2). CONCLUSIONS: We identified significant site-specific differences in age-and weight-adjusted bone density for Aboriginal and white women. Larger bone area, rather than a reduction in BMC, appeared to be primarily responsible. Further work is needed to define how these differences in bone density and geometry affect indices of bone strength.

Adult↗

Highly precise peripheral quantitative computed tomography for the evaluation of bone density, loss of bone density and structures. Consequences for prophylaxis and treatment.

The importance of serial examinations over time with peripheral quantitative computed tomography (pQCT) is that they enable the detection of patients at high risk of osteoporosis, and the individualisation of prophylaxis and treatment. We have shown that postmenopausal patients with high bone turnover evaluated by biochemical markers are identical to fast bone losers as determined by pQCT. As a consequence, we use agents that inhibit bone resorption in patients who are fast bone losers and agents that stimulate bone formation in patients who are slow bone losers. To visualise bone microarchitecture, and to evaluate bone density and the rate of bone loss, we used a highly sensitive pQCT system (DENSISCAN 1000, reproducibility of 0.3% in a mixed population of normal individuals and patients with osteopenia or osteoporosis). This system enabled us to separately assess trabecular and cortical bone density in the radius and tibia, and to differentiate between fast and slow bone losers within a few months (threshold: 3% loss of trabecular bone density in the radius per year). We have shown that the lower the trabecular bone density in the distal radius, the higher the relative bone loss. To classify patients as slow and fast losers in the future, we may need only one measurement. With this highly precise measurement method, we have shown that calcitonin and etidronate are more effective in fast than in slow bone losers, and that vitamin D metabolites (calcitriol or 1 alpha-calcidol) and estrogens can halt fast bone loss. In conclusion, highly sensitive pQCT enables us to adapt the treatment to different forms of osteoporosis and bone turnover, resulting in an increase in the number of patients successfully treated and also in patient compliance. Because our treatment is based on precise, objective measurements, treatment modifications--especially in those who change from a slow to a fast bone-loser state--can be easily justified.

Adult↗

Effect of testosterone on bone density and bone metabolism in adolescent male hypogonadism.

To assess the influence of gonadal steroid testosterone (T) on bone mineral status in males during puberty, we observed the response of cortical bone density and serum biochemical parameters of bone metabolism to T treatment in 12 adolescent patients with hypogonadotropic hypogonadism (11 with both gonadotropin and growth hormone deficiency and one with isolated gonadotropin deficiency). The 12 patients aged 15 to 21 years (Tanner stage I to II) were divided into two groups: group 1 (n = 6) given T treatment for 2 consecutive years, and group 2 (n = 6) without T treatment for the first year and then with T treatment for the second year. Cortical bone density measured in the radius was less than the age-matched mean value for normal subjects in all 12 patients (groups 1 and 2) at the start of the study. Bone density in group 1 increased significantly during the 2-year T treatment period, but did not increase in group 2 during the first year without T treatment, although an increase was observed during the subsequent year with T treatment. Among circulating biochemical factors such as osteocalcin, parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OHD), and 1,25-dihydroxyvitamin D [1,25-(OH)2D], only osteocalcin showed an increase in response to T treatment in both groups. Levels of insulin-like growth factor-I (IGF-I) remained consistently low and did not change in any patients except one with isolated gonadotropin deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effect of calcium supplementation to undernourished mothers during pregnancy on the bone density of the bone density of the neonates.

Eighty seven pregnant women belonging to poor socioeconomic groups of population were investigated to find out the effect of calcium supplementation during pregnancy on the bone density of the mother as well as of the neonate. Supplements of 300 and 600 mg of elemental calcium administered daily from the 20th week of gestation onward until term, brought about a significant increase in the bone density of the neonates born of such mothers compared to that of the neonates born to unsupplemented mothers. Although no significant difference was observed between the initial and final values for bone densities among the mothers, there was a tendency for an increase in the bone density of the mothers who received 600 mg of calcium supplements. Individual variation of different neonatal bones in their response to maternal calcium supplements was observed. Bone density of the neonate was not related to the birth weight, crown-heel, or crown-rump lengths.

Adolescent↗

The CAG repeat polymorphism in the androgen receptor gene affects bone density and bone metabolism in healthy males.

OBJECTIVE: Bone metabolism and bone density (BD) are influenced by sex hormones. Testosterone (T) action is exerted through the androgen receptor (AR). We investigated the potential impact of the CAG repeat (CAGR) polymorphism within the AR gene on BD and bone metabolism in healthy younger males. PATIENTS AND MEASUREMENTS: The number of CAGRs in 110 healthy men aged 20-50 years was determined by sequence analysis. We assessed BD by the radiation-free method of quantitative ultrasound (QUS) of the phalanges. Serum levels of bone-specific alkaline phosphatase (BAP) and urine secretion of free deoxypyridinoline (DPD, corrected for creatinine), serum levels of sex hormones, body fat content and lifestyle factors were determined. RESULTS: In stepwise multiple regression models controlling for age, body fat content and lifestyle factors, the number of CAGRs was an independent negative predictor of BD (partial r = - 0.286, P = 0.001), whereas it was positively associated with markers of bone turnover (for BAP: partial r = 0.32, P= 0.001; for DPD: partial r = 0-241, P = 0.013). Levels of free T and oestradiol showed an independent and positive association with BD; age contributed significantly to lower BD. Age and free T were negatively associated with markers of bone turnover, whereas oestradiol showed a positive correlation with BAP and DPD. ANOVA in groups according to age and the CAGR length suggested an increased age-dependent bone loss in subjects with a CAGR length of 22-31 compared with 14-21 CAGRs (overall P < 0.01). CONCLUSIONS: A high number of CAG repeats within the androgen receptor gene attenuates testosterone effects on bone density and bone metabolism. This seems to be associated with accelerated age-dependent bone loss.

Adult↗

Effects of gonadotrophin-releasing hormone agonist on uterine fibroids and bone density.

Bone density (BD) was evaluated by single photon absorptiometry (SPA) in 18 women treated with Buserelin a gonadotrophin-releasing hormone (LHRH) analogue, for uterine fibroids. Buserelin was administered for a period of 6 mth. Amenorrhoea and oestradiol levels in the follicular-phase range were recorded in all patients during treatment. Fibroid volume was evaluated by means of ultrasound. SPA was performed at the 1/3 proximal radius and at the 1/10 distal radius sites before starting therapy and every 2 mth subsequently for 12 mth. BD was also measured in a control group of 18 normally-menstruating premenopausal women, matched for age and body mass index. No significant changes in BD at the proximal or distal radius sites were observed in either the cases or the controls during the study. Moreover, comparison of the data on the cases and the controls revealed no differences in BD at 0, 6 or 12 mth. Thus, although LHRH analogue treatment proved effective in reducing fibroids, it did not cause any significant changes in BD.

Adult↗

Contributions of chronological age, age at menarche and menopause and of anthropometric parameters to axial and peripheral bone densities.

Bone mineral density (BMD) was measured in 128 normal postmenopausal women at different skeletal sites: lumbar spine and proximal femur, using dual-energy X-ray absorptiometry (DXA), and the cancellous and cortical envelopes of the distal third of radius and tibia, using precise low-dose quantitative computed tomography (QCT). Multivariate analysis included chronological age, ages related to menstrual history (menopause and menarche) and anthropometric factors, e.g. height and weight, as independent predictive variables. Weight is a much-studied predictor of bone density. At sites of high bone turnover, i.e. cancellous envelope, the effect of weight appeared overshadowed by estrogen-related parameters: age-past-menopause was the first predictor of BMD in the cancellous compartment of radius and in Ward's triangle, and the number of reproductive years was the strongest predictor of BMD in the cancellous compartment of tibia and in the spine (L2-4). This suggests that in addition to menopause, the length of menstrual life should be considered as an explanation for the variations in current bone mass in postmenopausal women. At the cortical level of radius, the effect of chronological age was predominant. At the cortical level of tibia, height and weight were the best predictors of BMD. We conclude that the influence of parameters related to menstrual history is predominant in sites with mainly cancellous tissue and that anthropometric factors constitute the best predictors of BMD in the cortical sites of weight-bearing bones.

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Longitudinal changes of bone density and bone resorption in hyperthyroid girls during treatment.

Low bone mineral density (BMD) and increased bone turnover are common features of untreated hyperthyroidism in adult patients. The effect of treatment on BMD is still controversial. BMD and bone metabolism in hyperthyroid children have not been thoroughly investigated. In the present study, we measured spinal and whole body BMD by dual-energy X-ray absorptiometry in a group of 13 girls (aged 5.0-14.9 years) at diagnosis of hyperthyroidism. The bone resorption rate was assessed by urine measurement of N-terminal telopeptide of type I collagen (NTX). Hyperthyroid patients have been studied longitudinally during treatment. BMD values and NTX urine concentrations have been also determined in 155 healthy Caucasian girls (aged 2.4-24.2 years). Spinal and whole body bone density measurements were significantly lower compared with healthy controls in untreated hyperthyroid girls, after correction for differences in age and anthropometric measurements (p </= 0.033). Bone density measurements obtained after 12 and 24 months of treatment were no longer different from those of healthy girls. NTX urine levels at diagnosis of thyrotoxicosis were significantly higher than those found in healthy controls (p < 0.0001); 6 months after treatment, the urine levels did not show significant differences, and they remained stable after 12 and 24 months of therapy. Inverse correlations at diagnosis were found between serum-free thyroxine (FT4) serum levels and spinal (r = -0.42) and whole body bone density (r = -0.41); FT4 and free triiodothyronine serum levels directly correlated with the NTX concentration (r = 0. 77, and r = 0.71, respectively). In conclusion, the results of the present study demonstrate that low bone density values and high bone resorption rates are found in hyperthyroid children and adolescents at diagnosis of the disease. Our data also demonstrate that antithyroid treatment is able to reduce dramatically the bone resorption and to increase significantly both spinal and total body BMD, granting physiologic conditions for the achievement of the best obtainable peak bone mass.

Adolescent↗

Discontinuing antiresorptive therapy one year after cardiac transplantation: effect on bone density and bone turnover.

BACKGROUND: We have previously reported that subjects randomized to alendronate or calcitriol immediately after cardiac transplantation sustained minimal bone loss during the first year, significantly less than a concurrently transplanted reference group that received calcium and parent vitamin D. In this extension, we evaluated the effect of discontinuing alendronate or calcitriol on bone loss and biochemical markers of bone turnover during the second year. We hypothesized that subjects who discontinued alendronate, which has a long half-life in bone, would not sustain significant bone loss. As the half-life of calcitriol is short, we hypothesized that there would be significant bone loss after discontinuing calcitriol. METHODS: We measured bone density (BMD), calciotropic hormones and bone turnover markers at 12, 18, and 24 months after transplantation in adherent subjects who completed the randomized trial on alendronate or calcitriol, and in reference subjects who had received no preventive therapy. RESULTS: In all, 75 subjects (34 alendronate, 25 calcitriol, 16 reference) participated. During the second year, the bone resorption marker, serum N-telopeptide, rose by 27% in the calcitriol group (P< or =0.001). Bone alkaline phosphatase, a bone formation marker, increased by 54% in the calcitriol group (P< or =0.001) and by 32% in the alendronate group (P< or =0.001). BMD did not change significantly at any site in either randomized group. CONCLUSIONS: After discontinuing alendronate or calcitriol, BMD remained stable during the second year after cardiac transplantation, despite a significant increase in a biochemical marker of bone resorption in the calcitriol group. This suggests that antiresorptive therapy may be discontinued at the end of the first posttransplantation year in cardiac transplant recipients without resumption of rapid bone loss. However, as increased bone turnover may predict future bone loss and fractures, such patients warrant observation to ensure that BMD remains stable long-term.

Adult↗

[Bone density and bone metabolism regulated by vitamin D receptor allele polymorphism in a German study sample].

BACKGROUND: It has been reported that the spinal bone density is associated with vitamin-D-receptor (VDR) gene polymorphisms. The results of recent studies have been contradictory concerning the predictive power for low bone mineral density (BMD). Regional population-specific influences have been found to affect the vitamin-D-endocrinologic-system, diminishing the influence of VDR polymorphism on BMD and on bone turnover. We have examined the association of bone density, fracture predictivity and biochemical markers of bone turnover with VDR polymorphism in a German population. METHODS: Blood and urine were collected from a heterogeneous subset of 164 caucasian subjects with ethnic German background. Polymerase chain reaction and subsequent digestion with Bsm I were used to examine variations of VDR genotypes. The morning following initial specimen collections, both urinary excretion rate of pyridinoline crosslinks (Pyr) and serum levels of bone alkaline phosphatase (BAP) were determined. For determination of the bone mineral density, the well-established method of dual X-ray absorptiometry was used. FINDINGS: The VDR BB-genotype was associated with low bone mineral density for age-matched subjects (90.1 +/- 15.5%) versus the bb-genotype (100.8 +/- 10.8%) at the lumbar spine and at the Ward's triangle (91.8 +/- 17.9% versus 101.9 +/- 12.1%). 34.2% of BB-genotype subjects, 14.2% of bB-genotype subjects and 12.6% of bb-genotype subjects had Z-score related bone mineral density < 85%. The fracture rate at typical osteoporotic fracture sites was 23.6% for the BB-, 10.8% for the bB- and 0.0% for the bb-genotype. The urinary excretion rate of free pyridinoline crosslinks was higher for the BB-genotype than for the bB- or the bb-, however the difference was not significant. No genotype specific variations were seen for bone alkaline phosphatase. INTERPRETATION: The authors conclude from this study that bone mineral density at the axial skeleton is associated with the vitamin-D-receptor allele polymorphism and that there is an influence on bone turnover and fracture rate in a German subset. CLINICAL RELEVANCE: The analysis of the VDR-genotype can be considered as a new piece in the puzzle of the diagnostic of osteoporosis for we get prognostic hints concerning the rate of fracture.

Adult↗

Effect of glucocorticoids and calcium intake on bone density and bone, liver and plasma minerals in guinea pigs.

The purpose of this study was to see what effect glucocorticoids would have on bone density and mineral distribution in guinea pigs. Adult female guinea pigs were given prednisolone, a synthetic analogue of cortisol, for up to 24 weeks. Bone density and bone, liver and plasma levels of zinc, copper, iron, manganese, chromium, magnesium and calcium were studied in these animals. In one study, the effect of menopause was simulated by using ovariectomy. In another study, dietary calcium was varied to investigate its effect with glucocorticoids. Animals treated with 1 mg prednisolone/kg body weight showed increased femur density compared with controls, but no changes in tissue mineral concentrations. Animals fed 100 mg prednisolone/kg body weight experienced decreased femur density. Differences in effects were not observed between ovariectomized and intact animals. Bone loss was greatest in animals fed the cereal-based closed-formula diet and least in animals fed the low-calcium diet. Changes in mineral content of femurs observed in animals which lost bone mass were increased iron concentration and decreased magnesium concentration. Total liver stores of zinc and magnesium increased. Liver copper increased in concentration per gram as well as in total content. Liver concentration of manganese decreased. Plasma changes in animals fed the high level of drug were decreased iron and calcium, and increased copper. Hemoglobin and hematocrit increased with increasing drug levels. It is suggested that glucocorticoids have marked effects on mineral metabolism which may be related to the bone loss and that these effects may be modified by dietary changes.

Animals↗

Bone density and bone metabolic markers in active collegiate athletes: findings in long-distance runners, judoists, and swimmers.

We investigated the bone metabolic system status of 103 male and female volunteer collegiate athletes, who were actively pursuing one of three different sports: Long-distance running (LR); judo (JU); and swimming (SW). The following parameters were evaluated: total body bone mineral density (TMBD); bone-forming metabolic markers; serum procollagen type I C-peptide (PICP) levels; bone alkaline phosphatase (B-ALP) content; bone resorption markers, urinary pyridinoline (Pyd) and deoxypyridinoline (Dpd) levels. We found that the TBMD and urinary Dpd values in JU athletes were significantly higher (p < 0.001) than in athletes of the same sex in the other two groups. The urinary Pyd level in male JU athletes was also higher (p < 0.001) than that in the other two groups, but that in females JU athletes was only higher (p < 0.01) than that in female LR athletes. The PICP levels were similar to the TBMD values in all groups. No differences in bone density or in bone metabolic markers were seen in LR and SW athletes of the same sex. We thus conclude that differences in bone mineral density are in part due to the demands of the specific sport, and that they are reflected in bone metabolic markers. In addition, the status of bone metabolic turnover in male JU athletes in training may be hypermetabolic and as well as that of female JU athletes with regular menses cycles.

Adult↗

Geometry and bone density.

Bone development is a key process in the growing child. It is, therefore, of paramount importance to survey this process, which is characterized by increasing length and size of the bone together with its progressive mineralization. The bone status can be evaluated by different techniques, each of them having its pros and cons. Furthermore, it should be underlined that the results of bone assessment depend not only from the employed technique but also from the auxological characteristics of the subjects. It is, therefore, the aim of this review to examine the characteristics of the various methods of bone evaluation, such as dual energy X-ray absorptiometry (DEXA), peripheral quantitative computed tomography (pQCT), ultrasound and metacarpal index and to explain how changes in bone structure and geometry may influence the results.

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Genetic predisposition for adult lactose intolerance and relation to diet, bone density, and bone fractures.

UNLABELLED: Evidence that genetic disposition for adult lactose intolerance significantly affects calcium intake, bone density, and fractures in postmenopausal women is presented. PCR-based genotyping of lactase gene polymorphisms may complement diagnostic procedures to identify persons at risk for both lactose malabsorption and osteoporosis. INTRODUCTION: Lactase deficiency is a common autosomal recessive condition resulting in decreased intestinal lactose degradation. A -13910 T/C dimorphism (LCT) near the lactase phlorizin hydrolase gene, reported to be strongly associated with adult lactase nonpersistence, may have an impact on calcium supply, bone density, and osteoporotic fractures in the elderly. MATERIALS AND METHODS: We determined LCT genotypes TT, TC, and CC in 258 postmenopausal women using a polymerase chain reaction-based assay. Genotypes were related to milk intolerance, nutritional calcium intake, intestinal calcium absorption, bone mineral density (BMD), and nonvertebral fractures. RESULTS: Twenty-four percent of all women were found to have CC genotypes and genetic lactase deficiency. Age-adjusted BMD at the hip in CC genotypes and at the spine in CC and TC genotypes was reduced by -7% to -11% depending on the site measured (p = 0.04). LCT(T/C-13910) polymorphisms alone accounted for 2-4% of BMD in a multiple regression model. Bone fracture incidence was significantly associated with CC genotypes (p = 0.001). Milk calcium intake was significantly lower (-55%, p = 0.004) and aversion to milk consumption was significantly higher (+166%, p = 0.01) in women with the CC genotype, but there were no differences in overall dietary calcium intake or in intestinal calcium absorption test values. CONCLUSION: The LCT(T/C-13910) polymorphism is associated with subjective milk intolerance, reduced milk calcium intake, and reduced BMD at the hip and the lumbar spine and may predispose to bone fractures. Genetic testing for lactase deficiency may complement indirect methods in the detection of individuals at risk for both lactose malabsorption and osteoporosis.

Age Factors↗

Bone density and bone turnover in patients with osteoarthritis and osteoporosis.

OBJECTIVE: Osteoarthritis (OA) and osteoporosis (OP) are reported to be rare in the same patient. We examined bone mass, bone turnover, and radiological presence of OA in a group of patients with OA with previous hip fractures and age matched controls. METHODS: Bone mass was assessed by bone mineral density (BMD), using dual energy x-ray absorptiometry (DEXA) of the hip and total body, and quantitative ultrasound of the os calcis, measuring broadband ultrasound attenuation and velocity of sound. Bone turnover was assessed by measuring urinary pyridinium crosslinks and serum osteocalcin. RESULTS: There were differences in bone density, the patients with OP having lower bone density, while patients with OA had similar or increased bone density compared to controls, Serum osteocalcin showed no significant differences among the 3 groups of patients. Urinary pyridinium crosslinks excretion was significantly elevated in the OA group but not in the OP group compared with controls. CONCLUSION: Increased bone turnover was restricted to the OA group.

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Ultralow-dose micronized 17beta-estradiol and bone density and bone metabolism in older women: a randomized controlled trial.

CONTEXT: Estrogen therapy is known to prevent osteoporosis, but studies have shown that conventional doses increase adverse events. Whether lower doses, one quarter of standard treatment, prevent bone loss is not known. OBJECTIVE: To examine the effect of 3 years of treatment with 0.25 mg/d of micronized 17beta-estradiol on bone mineral density (BMD) and bone turnover in healthy older postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled trial conducted from July 24, 1998, through June 14, 2002, at a university general clinical research center in the United States. Healthy, community-dwelling women (N = 167) who were older than 65 years at enrollment. INTERVENTION: Dosage of 0.25 mg/d of micronized 17beta-estradiol (n = 83) or placebo (n = 84); all women who had not had a hysterectomy received 100 mg/d of oral micronized progesterone for 2-week periods every 6 months. MAIN OUTCOME MEASURES: The BMD of the hip, spine, wrist, and total body measured annually for 3 years. Serum and urine biochemical markers of bone resorption and formation and sex hormones were measured at baseline, 3 months, and during years 1 and 3 of treatment. RESULTS: Mean BMD increased at all sites for participants taking low-dose estrogen (17beta-estradiol) compared with placebo (P<.001). Compared with participants receiving placebo, participants taking low-dose estrogen had BMD increases of 2.6% for the femoral neck; 3.6%, total hip; 2.8%, spine; and 1.2%, total body. Markers of bone turnover, N-telopeptides of type 1 collagen, and bone alkaline phosphatase decreased significantly (P<.001) in participants taking low-dose estrogen compared with placebo. Estradiol, estrone, and sex hormone-binding globulin levels increased in the estrogen-treated group compared with placebo. The adverse effect profile was similar; specifically, there were no statistically significant differences in breast tenderness, changes in endometrial thickness or pathological effects, or annual mammographic results between the 2 groups. The number of abnormal mammograms over 3 years was 15 for the low-dose estrogen group and 10 for the placebo group (8 occurred at baseline) (P =.26). There were no reports of breast cancer during the study. CONCLUSIONS: In older women, a dosage of 0.25 mg/d of 17beta-estradiol increased bone density of the hip, spine, and total body, and reduced bone turnover, with minimal adverse effects. Future studies evaluating the effect of low-dose estrogen on fractures are indicated.

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The roles of bone mineral density, bone turnover, and other properties in reducing fracture risk during antiresorptive therapy.

Osteoporosis is a skeletal disorder characterized by compromised bone strength and increased risk of fracture. Properties related to bone strength include rate of bone turnover, bone mineral density, geometry, microarchitecture, and mean degree of mineralization. These properties (with or without bone density) are sometimes collectively referred to as bone quality. Antiresorptive agents may reduce fracture risk by several separate but interrelated effects on these individual properties. For example, antiresorptive agents have been reported to reduce bone turnover, stabilize or increase bone density, preserve or improve microarchitecture, reduce the number or size of resorption sites, and improve mineralization. Although changes in bone architecture and mineralization are not currently measurable in clinical practice, bone turnover is assessed easily in vivo and affects the other bone properties. Moreover, antiresorptive therapies that produce larger decreases in bone turnover markers together with larger increases in bone mineral density are associated with greater reductions in fracture risk, especially at sites primarily composed of cortical bone such as the hip. Reductions in fracture risk are the most convincing evidence of good bone quality. Data from well-designed randomized clinical trials with up to 10 years of continuous antiresorptive therapy have shown that certain antiresorptive agents effectively reduce fracture risk and (together with extensive preclinical data) suggest no deleterious effects on bone quality.

Bone Density↗