The effect of long-term oestradiol implantation on bone mineral density in postmenopausal women who have undergone hysterectomy and bilateral oophorectomy

Twelve women who had received oestradiol implantation on demand for at least 15 years following hysterectomy with bilateral oophorectomy, underwent bone densitometry of hip and spine. Bone mass of hip and spine was significantly elevated above that of both the age matched mean to a degree hitherto undocumented. This suggests that oestrogen in high doses or over a long period may produce a true anabolic effect on bone mass.     

Hysterectomy with ovarian conservation: effect on bone mineral density

The results of a questionnaire-based investigation involving 126 oncologists who treat mastopathy are presented. The study failed to establish any significant decrease in breast cancer morbidity as a result of treating mastopathy by medication. It was found that the whole problem of treatment and follow-up of dibraodenoma mammae needs to be re-considered.     

Calcium supplements increase bone mineral density in women with low serum calcium levels during long-term estrogen therapy

In order to clarify whether the long-term effect of estrogen on bone mineral density (BMD) is reinforced by low dose calcium supplements, 600-800 mg of calcium lactate was administered to postmenopausal or oophorectomized women who had been undergoing unopposed estrogen therapy for at least 2 years and whose serum calcium level was suppressed to below the normal range. To patients whose serum calcium levels had been within the normal range, the same dose of estrogen alone was continued. Changes in lumbar spine BMD before and after calcium supplementation was measured by dual-energy X-ray absorptiometry. Lumbar spine BMD decreased by -0.37% for 2 years in women treated with estrogen alone, while that of women treated with estrogen and calcium increased by 2.78% (P = 0.003). These results indicate that low dose calcium supplements potentiate the effect of estrogen in women with decreased serum calcium during long-term hormone replacement therapy.     

Association of bone mineral density with vitamin D receptor gene polymorphism--changes in radial bone mineral density with long-term follow-up: longitudinal study

Recent studies have shown that genetic effects on bone mineral density (BMD) and bone turnover are related to vitamin D receptor (VDR) gene polymorphism. However, discordant studies have been published and it is still not clear whether VDR genotypes influence bone mass accretion and/or postmenopausal bone loss. To assess allelic influence of the VDR gene on BMD, we determined changes in 1/6-radial-BMD by several repeat measurements in the same subjects for about ten years and analyzed VDR polymorphism of BsmI restriction enzyme in 53 normal healthy Japanese women (age: 50.3 +/- 4.7 years, mean +/- SD). Twenty-seven (age: 53.2 +/- 4.7 years) of the subjects were post-menopausal (POST group). Among these 53 subjects, the distribution of bb, Bb and BB genotypes was 64.2%, 34% and 1.9%, respectively. The genotype frequencies in this study were very similar to those in previous reports concerning other Japanese women. There was no difference between the b group (women with bb genotype) and B group (women with BB or Bb genotype) in age, body weight, height, body mass index (BMI), years since menopause, serum osteocalcin and serum alkaline phosphatase values. In the POST group, BMD of the B group at menopause was lower than that of the b group (p < 0.05). About ten years after menopause, BMD did not differ significantly between these groups because the decrease in BMD in the b group was larger than that in the B group. Regarding changes in BMD in the POST group for four years after menopause, BMD of the b group was significantly decreased compared with the B group (p < 0.01). Our findings suggest that the differences in BMD by VDR genotype were larger among pre- and pri-menopausal women and seemed to decrease with years after menopause. It is suggested that there are other factors influencing BMD and postmenopausal bone loss in elderly women.     

Exercise and bone mineral density

A decrease in physical activity may lead to an increased loss of bone and an increase in the incidence of osteoporotic fractures. Studies have demonstrated increases in bone formation in animals and increases in bone mineral density in humans. Studies of animals show that bone has enhanced physical and mechanical properties following periods of increased stress. Strains which are high in rate and magnitude, and of abnormal distribution, but not necessarily long in duration, are best for inducing new bone formation, resulting in the strengthening of bone by increased density. Cross-sectional studies show that athletes, especially those who are strength-trained, have greater bone mineral densities than nonathletes, and that strength, muscle mass and maximal oxygen uptake correlate with bone density. Longitudinal training studies indicate that strength training and high impact endurance training increase bone density. Strain induction, the deformation that occurs in bone under loading, may cause a greater level of formation and an inhibition of resorption within the normal remodelling cycle of bone, or it may cause direct activation of osteoblastic bone formation from the quiescent state. Various mechanisms have been proposed for the transformation of mechanical strain into biochemical stimuli to enhance bone formation. These include prostaglandin release, piezoelectric and streaming potentials, increased bone blood flow, microdamage and hormonally mediated mechanisms. These mechanisms may act on their own or in concert, depending on the loading situation and the characteristics of the bone.     

The effect of a low-fat, high-carbohydrate diet on serum high density lipoprotein cholesterol and triglyceride

OBJECTIVE: To determine whether substituting carbohydrate for saturated fat has any adverse effects on serum high density lipoprotein (HDL) cholesterol and triglycerides in free-living individuals. DESIGN: Randomised crossover trial. SETTING: General community. SUBJECTS: Volunteer sample of 38 healthy free-living men with mean (s.d.) age 37 (7) y, moderately elevated serum total cholesterol 5.51 (0.93) mmol/l and body mass index 26.0 (3.6) kg/m2. INTERVENTIONS: Participants completed two six week experimental periods during which they consumed either a traditional Western diet (36%, 18%, and 43% energy from total, saturated, and carbohydrate, respectively) or a low-saturated fat high-carbohydrate diet (22%, 6% and 59% energy from total, saturated, and carbohydrate, respectively). Dietary principles were reinforced regularly, but food choices were self-selected during each experimental period. MAIN OUTCOME MEASURES: Serum lipids, body weight and plasma fatty acids. RESULTS: Reported energy and nutrient intakes, plasma fatty acids, and a drop in weight from 79.1 (12.5) kg on the Western diet to 77.6 (12.0) kg on the high-carbohydrate diet (P < 0.001) confirmed a high level of compliance with experimental diets. Total and low density lipoprotein (LDL) cholesterol fell from 5.52 (1.04) mmol/l and 3.64 (0.88) mmol/l, respectively on the Western diet to 4.76 (1.10) mmol/l and 2.97 (0.94) mmol/l on the high-carbohydrate diet (P < 0.001). HDL cholesterol fell from 1.21 (0.27) mmol/l on the Western diet to 1.07 (0.23) mmol/l on the high-carbohydrate diet (P = 0.057), but the LDL:HDL cholesterol ratio improved from 3.17 (1.05) on the Western diet to 2.88 (0.97) on the high-carbohydrate diet (P = 0.004). Fasting triglyceride levels were unchanged throughout the study. CONCLUSIONS: Replacement of saturated fat with carbohydrate from grains, vegetables, legumes, and fruit reduces total and LDL cholesterol with only a minor effect on HDL cholesterol and triglyceride. It seems that when free living individuals change to a fibre rich high-carbohydrate diet appropriate food choices lead to a modest weight reduction. This may explain why the marked elevation of triglyceride and reduction of HDL cholesterol observed on strictly controlled high-carbohydrate diets may not occur when such diets are followed in practice.     

Effect of vitamin D receptor gene polymorphism and lifestyle on bone mineral density and bone mineral density decrement rate

The effects of genetic and environmental factors on bone mineral density (BMD) were investigated in 108 healthy Japanese women. Of the 108 subjects, BMD (from the second to forth lumbar vertebrae) was measured in 1992 in 103, in 1993 in 100, and in both years in 95 by dual energy X-ray absorptiometry. Vitamin D receptor (VDR) gene polymorphism in intron 8 was used as a genetic marker. Information on menstruation, health status, lifestyle, quantities of nutrient intake and frequencies of food intake was obtained by questionnaire. The frequency of allele B (825bp), whose polymerase chain reaction (PCR) products cannot be cut with BsmI, was 0.259 and the frequency of allele b (650bp), whose PCR products can be cut with BsmI, was 0.741. The subjects in our study obeyed the Hardy-Weinberg law. While the frequency of allele B was 0.448 in European whites as reported by Morrison et al, it was 0.259 in our Japanese subjects, suggesting a racial difference. Z score values (average value 0, standard deviation 1) increased in the order BB, Bb and bb. This result indicates that allele B is associated with the lower BMD in Japanese, as in European whites. The BMD decrement rate increased in the order bb, Bb and BB, indicating that VDR gene polymorphism may be a regulatory factor for losing BMD. Most of lifestyle variables, calcium intake and vitamin D intake were not correlated with BMD, but the food frequency score (which was defined as values weighted in each of three food categories obtained by factor analysis) was significantly correlated with BMD. Multiple regression analysis showed significant influences of years after menopause, the food frequency score and VDR genotype on BMD. VDR genotype and years after menopause influenced the BMD decrement rate significantly in multiple regression analysis. Neither a relationship between BMD and calcium intake nor between BMD and vitamin D intake by VDR genotype was found. These results suggest that the VDR gene is a genetic factor in BMD and the BMD decrement rate in Japanese.     

Effect of carbamazepine and valproate on bone mineral density

OBJECTIVE: To examine the effect of carbamazepine and valproate monotherapy on bone mineral density in children. METHODS: Axial (second, third, and fourth lumbar vertebrae) and appendicular (distal third of radius) bone mineral density was measured by dual-energy x-ray absorptiometry in 27 healthy children and 26 children with uncomplicated idiopathic epilepsy treated with either carbamazepine (n = 13) or valproate (n = 13) for more than 18 months. Control subjects and patients were similar with respect to age, race (all white), and geographic area, and had no dietary restrictions, neurologic impairment, or physical handicaps. RESULTS: Subjects were seizure-free for more than 6 months on a regimen of carbamazepine or valproate therapy, and had mean serum trough levels of 6.88 +/- 2 micrograms/ml and 72.04 +/- 45.6 micrograms/ml, respectively. Dietary calcium intake was similar in control and treated groups. After correction for gender and age, children treated with valproate had a 14% (p = 0.003) and 10% (p = 0.005) reduction in bone mineral density at the axial and appendicular sites, respectively. The reduction in bone mineral density increased with the duration of valproate therapy. Carbamazepine did not significantly reduce bone mineral density. CONCLUSION: Valproate montherapy, but not carbamazepine therapy, significantly reduces axial and appendicular bone mineral density in children with idiopathic epilepsy and may increase their risk of osteoporotic fractures.     

Premature hair graying and bone mineral density

In a recent case-control study, premature hair graying was found to be associated with osteopenia, suggesting that this might be a clinically useful risk factor for osteoporosis. We report a reexamination of this possibility in 293 healthy postmenopausal women. Subjects experiencing onset of hair graying in their 20s tended to have lower bone mineral density throughout the skeleton (adjusted for age and weight) than those with onset of graying later in life. The same was true for those in whom the majority of their hair was gray by the age of 40 yr (n = 16), in whom bone density was reduced by 7% in the femoral neck, 8% in the femoral trochanter, and 4% in the total body (P < 0.05) when compared with those not prematurely gray. Bone density at the lumbar spine and Ward's triangle showed similar trends that were not significant. However, premature hair graying explained only 0.6-1.3% of the variance in bone mineral density within the population. We conclude that premature hair graying is associated with low bone density, but that its infrequency in the normal postmenopausal population leads to its accounting for only a tiny fraction of the variance of bone density.     

Effect of measuring bone mineral density on calcium intake

The diet in Japan has improved, but calcium intake has not increased for the past ten years, and it remains insufficient. To prevent osteoporosis, instruction in nutrition is directed at increasing calcium intake. We studied the effect of measuring bone mineral density on calcium intake in people receiving nutrition education. Intake of other nutrients was also measured. The subjects were 87 healthy women living in an agricultural region (Yamanashi Prefecture). They were members of a group formed to improve the diet of people in their area. For three days in October 1992 and in August 1994 food-weight records were obtained. A total of 76 of the 87 women chose to have their bone mineral density measured. The measurements before the first nutrition assessment in 1992. The intake of almost all nutrients tended to be greater in 1994 than in 1992. Calcium intake exceeded the minimum daily requirement (600mg). Calcium intake increased between 1992 and 1994 only in the subjects whose bone mineral density had been measured. Calcium intake decreased in the other subjects. Therefore, nutrition education programs aimed at preventing osteoporosis may be more effective if bone mineral density is measured. In addition, an appropriate balance of other nutrients can be maintained as the intake of calcium is increased.     

Predicting clinical discordance of bone mineral density

OBJECTIVE: To identify clinical and lifestyle factors that may predict clinical discordance of bone mineral density (BMD) in otherwise healthy perimenopausal and postmenopausal women referred for bone densitometry. MATERIAL AND METHODS: Data from 304 white women referred for bone densitometry were retrospectively reviewed in order to determine predictors of BMD status at the lumbar spine, femoral neck, and distal radius. In addition, a cross-validation study in a further independent sample of 50 patients was undertaken. Dual-energy x-ray absorptiometry of all three sites was performed, and T-scores were determined with use of standard criteria established by the World Health Organization. Covariables including age, postmenopausal status, years since menopause, use of alcohol and cigarettes, family history of osteoporosis, exercise, height, weight, and body mass index were analyzed by canonical discriminant functions. RESULTS: Seventy-six patients (25%) had normal BMD at all three sites (group A); 55 patients (18%) had osteopenia or osteoporosis at all sites (group B); and 173 patients (57%) showed regional discordance of BMD (group C). Menopausal status, years since menopause, use of alcohol and cigarettes, exercise levels, and weight allowed distinct separation of these three groups by using the plot of one canonical discriminant function against the other. When tested, this method of assignment correctly predicted the regional BMD status in 38 of 50 women (76%) in the independent sample. CONCLUSION: Thus, the combination of certain clinical and lifestyle factors may be helpful in predicting variations in the clinical classification of BMD in an ambulatory healthy perimenopausal or postmenopausal woman.     

Nutrition and bone mineral density in premenopausal women

Environmental factors have an important role in osteoporosis. Diet and, in particular, nutrients like calcium, vitamin D or phosphorus were extensively studied as determinants of bone mineral density, but the results remain conflicting and there is no clear evidence for an independent effect of such factors in the bone density of premenopausal women. We studied 66 healthy premenopausal women (20-40 years-old) aiming to relate bone mineral density, as measured in three different sites (distal forearm, lumbar spine and femoral neck) using single X ray and dual energy X-ray absorptiometry, with nutritional intake as estimated by a semi-quantitative food frequency questionnaire. Demographic, anthropometric and other life style variables were also assessed. There was a significant correlation between distal forearm and femoral neck (r = 0.57) or lumbar spine (r = 0.45) bone mineral density. No significant effect of age was observed for distal forearm bone mineral density in these women. In a stepwise multiple linear regression model, evaluating the contribution of all the variables studied, only body mass index (p=0.038) and vitamin A ingestion (p = 0.020) had an independent contribution for the variation in distal forearm bone mineral density. Mean bone mineral density, assessed in the femoral neck (p = 0.003) or the lumbar spine (p = 0.056) was different across tertiles of alcohol ingestion, being higher in non-drinkers. However, among regular drinkers there was a significant positive correlation between alcohol ingestion and femoral neck bone mineral density (Spearman's r = 0.53, p = 0.015). This study shows that the effect of nutrition seems dependent on the anatomical site assessed and that there is a weak correlation between nutritional intake and the actual bone mineral density.     

Differential effect of triiodothyronine and thyroxine on liposomes containing cholesterol: physiological speculations

Chemopreventive effects of the antioxidants 1-O-hexyl-2,3,5- trimethylhydroquinone (HTHQ), 3-O-ethylascorbic acid (EAsA), 3-O-dodecylcarbomethylascorbic acid (DAsA), green tea catechins (GTC) and ellagic acid on 2-amino-1-methyl-6- phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary carcinogenesis were examined in female F344 rats. Groups of 20-21 6-week-old rats were maintained on a powdered diet containing 0.02% PhIP alone, PhIP together with 0.5% HTHQ, 1% EAsA, 1% DAsA, 1% GTC or 0.1% ellagic acid, these antioxidants alone or basal diet alone without supplement for 52 weeks. The survival rates of PhIP plus antioxidant groups at the end of the experiment were higher than that of the PhIP alone group. Sequential observation of palpable mammary tumors demonstrated only one tumor by week 52 in the PhIP plus HTHQ group, whereas 40% of the rats receiving PhIP alone had tumors by this time point. The final incidence of mammary adenocarcinomas was significantly decreased in the PhIP plus HTHQ group (4.8%, P < 0.01) as compared to the PhIP alone value (40%). Although statistically not significant, incidences of adenocarcinomas in the other antioxidant-treated groups (23.8-28.6%) were also lower than in the PhIP alone group. Furthermore, the incidence of large intestinal tumors in the PhIP plus HTHQ group (0%) showed a tendency to decrease relative to the PhIP alone group (16.7%). These results indicate that antioxidants, particularly HTHQ, exert a potent chemopreventive action against PhIP-induced carcinogenesis.     

Bone mineral density in patients on long-term therapy with levothyroxine

The aim of the study was to determine the influence of replacement and suppressive thyroxine therapy on bone mineral density (BMD). 30 postmenopausal women; 19 on replacement therapy (dose 1.22 +/- 0.35 micrograms/kg; duration 11.4 +/- 7.2 years) and 11 on suppressive therapy (dose 1.45 +/- 0.71 micrograms/kg; duration 9.5 +/- 7.2 years). Controls were 60 healthy women matched for age and menopausal status. BMD at the lumbar spine (L2-L4), femoral neck, Ward's triangle and trochanter was measured by dual-energy absorptiometry. Forearm BMD at distal site was measured by single-photon absorptiometry. Mean thyroid hormone values and TSH were within normal limits, although the patients on suppressive therapy had significantly higher T3 (p < 0.05) than the patients on replacement therapy. BMD on each site was significantly lower in the replacement treated group than in controls. BMD in patients on suppressive therapy was lower, but not significantly, compared to controls. Thyroxine therapy could have an adverse effect on BMD. The magnitude of bone loss depends on the serum level of thyroid hormones and on the functional state of thyroid hormone receptor in bone tissue, as well.     

Evaluation of periprosthetic bone using dual-energy x-ray absorptiometry: precision of the method and effect of operation on bone mineral density

To assess the perioperative bone loss of femur during total hip arthroplasty (THA), periprosthetic bone mineral density (BMD) of the seven regions of interests (Gruen zones) was determined with dual-energy x-ray absorptiometry (DXA) preoperatively in both proximal femurs and postoperatively in the involved side in 53 patients with degenerative hip osteoarthrosis. The mean (standard deviation, SD) precision error (coefficient of variation percent, CV%) in various regions of interest (ROIs) based on two consecutive measurements (n = 16) were 2.3 (0.8)%, 2.5 (1.5)%, and 2.8 (1.6)% for uncemented stems, cemented stems, and control sides, respectively. Furthermore, the mean variability caused by the rotation of femur was 3.5 (1.4)%. The most significant perioperative bone loss (13.5-19.2%) was found in the calcar area (zone 7) after noncemented THA. Zone 4, representing the bone below the prosthesis, also showed BMD decreases. These decreases suggest perioperative bone loss owing to rasping and reaming the calcar and bone canal. However, after cemented THA, highly significant BMD increases were found in all the lateral zones. The calcar area was the only site where significant perioperative bone loss was detected (12.8%). In conclusion, DXA is a precise method for quantifying bone mass and density changes in the follow-up of THA. However, when interpreting the results, the preoperative BMD, differences between the femurs and the effect of operation on bone mass should be taken into account. We suggest that the best reference for BMD follow-up is the periprosthetic BMD of the involved side measured soon after the THA.     

Sources of interracial variation in bone mineral density

Many studies have demonstrated significant differences in bone mineral density between various racial groups. Although it has been suggested that differences in body weight contribute to such interracial variation, the artifactual effect of the skeletal size inherent in projectional absorptiometry methods has been largely ignored. We have measured bone mineral density by dual-energy X-ray absorptiometry in the lumbar spine and at three femoral sites in 200 premenopausal women of Chinese, Indian, European, or Polynesian origin (50 of similar mean age in each group). In the Chinese and Indian women the measured bone mineral density measurements (g/cm2) were similar, but significantly less, at all sites, than those of European women (p < or = 0.005). The European women were, however, significantly taller than both the Chinese and Indian women (p < 0.0001), and when the scale artifact of absorptiometry was removed by dividing the measured bone mineral density either by the height of the subject, or by the square root of the area over which the X-ray beam was projected, then the differences in mean bone mineral density between the Chinese, Indian, and European women were almost completely eliminated. The Polynesian women were significantly more obese (as judged from mean body mass index) than all the other groups (p < 0.0001) and had significantly greater bone mineral density at all sites than all the other groups both before (p < 0.0001) and after (p < 0.0001) correcting for the scale artifact.(ABSTRACT TRUNCATED AT 250 WORDS)     

Calcium supplementation and bone mineral density in adolescent girls

OBJECTIVE: To evaluate the effect of calcium supplementation on bone acquisition in adolescent white girls. DESIGN: A randomized, double-blind, placebo-controlled trial of the effect of 18 months of calcium supplementation on bone density and bone mass. SUBJECTS: Ninety-four girls with a mean age of 11.9 + 0.5 years at study entry. SETTING: University hospital in a small town. INTERVENTIONS: Calcium supplementation, 500 mg/d calcium as calcium citrate malate; controls received placebo pills. MAIN OUTCOME MEASURES: Bone mineral density and bone mineral content of the lumbar spine and total body were measured by dual-energy x-ray absorptiometry and calcium excretion from 24-hour urine specimens. RESULTS: Calcium intake from dietary sources averaged 960 mg/d for the entire study group. The supplemented group received, on average, an additional 354 mg/d of calcium. The supplemented group compared with the placebo group had greater increases of lumbar spine bone density (18.7% vs 15.8%; P = .03), lumbar spine bone mineral content (39.4% vs 34.7%; P = .06), total body bone mineral density (9.6% vs 8.3%; P = .05), and 24-hour urinary calcium excretion (90.4 vs 72.9 mg/d; P = .02), respectively. CONCLUSIONS: Increasing daily calcium intake from 80% of the recommended daily allowance to 110% via supplementation with calcium citrate malate resulted in significant increases in total body and spinal bone density in adolescent girls. The increase of 24 g of bone gain per year among the supplemented group translates to an additional 1.3% skeletal mass per year during adolescent growth, which may provide protection against future osteoporotic fracture.     

Vitamin-D-receptor-gene polymorphisms and change in lumbar-spine bone mineral density

Common vitamin-D-receptor (VDR) gene allelic variants predict bone mineral density. We analysed VDR alleles and rate of change of lumbar-spine bone mineral density over 18 months in 72 elderly subjects. 9 BB homozygotes lost bone mineral density but 26 homozygotes for the alternative genotype (bb) did not (mean change -2.3 [SE 1.0] vs 0.9 [0.7]% per year, p < 0.05), irrespective of calcium intake. Among 37 heterozygotes (Bb), however, change in bone mineral density correlated with calcium intake (r = 0.35, p < 0.03). This association between a genetic marker and rate of bone loss in the elderly suggests that the effect of calcium intake on maintenance of bone mass could relate to VDR gene polymorphisms.