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PubMed2002

A congenic mouse and candidate gene at the Chromosome 13 locus regulating bone density.

Previously, we identified two significant quantitative trait loci (QTLs) specifying the peak relative bone mass (bone mass corrected for bone size) on chromosomes (Chrs) 11 and 13 by interval mapping in two mouse strains, SAMP2 and SAMP6. The latter strain is an established murine model of senile osteoporosis and exhibits a significantly lower peak relative bone mass than SAMP2 mice. We recently designated the Chr 13 locus as Pbd2 (Peak bone density 2) and constructed a congenic strain, P6.P2-Pbd2(b), which carried a single genomic interval from the Chr 13 of SAMP2 on a SAMP6-derived osteoporotic background. In this study, we have constructed a congenic strain, P2.P6-Pbd2(a), carrying a SAMP6-derived susceptible interval on a SAMP2-derived resistance background. This congenic strain had a lower bone density than the background strain, SAMP2, based on three measurement methods, each utilizing a different principle for evaluating bone density: MD, DXA, and pQCT. Next, a candidate gene approach was used to find polymorphisms of Bmp6 (bone morphogenetic protein 6). The CAG trinucleotide repeat numbers in exon 1 of this gene differ among SAM strains. We found an association of CAG repeat length with relative peak bone mass in mice.

Animals↗

PubMed2001

The metabolic and bone density effects of continuous combined 17-beta estradiol and noresthisterone acetate treatments in Thai postmenopausal women: a double-blind placebo-controlled trial.

OBJECTIVE: To compare the changes of lipid parameters, liver function tests, fasting plasma glucose and bone density in Thai postmenopausal women who received this combined hormonal treatment and placebo. STUDY DESIGN: Double-blinded, randomized controlled trial study. MATERIAL AND METHOD: Sixty postmenopausal women attending the menopause clinic at Chulalongkorn Hospital from July, 1996 to December, 1996, were enrolled in the study. The patients were randomized to receive the placebo or drug (17 beta-estradiol 2 mg and norethisterone acetate 1 mg) continuously. Patient characteristics, physical examination, liver function tests, fasting plasma glucose, lipid parameters (fasting total cholesterol, low density lipoprotein cholesterol (LDL), high density lipoprotein (HDL) and triglyceride level) and bone densitometry were performed before beginning the study. The lipid parameters were repeated at 3, 6 and 12 months. Fasting plasma glucose, liver function tests and bone densitometry were repeated at 12 months. RESULTS: In the drug group, there were significant changes in the cholesterol at 3, 6 and 12 months when compared to the baseline. There were significant differences at 3, 6 and 12 months when compared between groups. The HDL values were not significantly different within groups. The LDL values at 3, 6, 12 months were significantly lower than the baseline in the drug group when compared within groups and at 6, 12 months in the placebo group. The triglyceride values were not significantly different between groups and within groups. There was no significant change between groups and within groups of fasting plasma glucose, total bilirubin, direct bilirubin, AST, ALT, albumin and globulin. The alkaline phosphatase values were significantly decreased at 12 months in the drug group. The bone density of total BMD and T-score at the spine of the drug group increased significantly at 12 months. The per cent change per year was +5.1. In contrast, the values in the placebo group decreased significantly, the per cent change per year was -0.9. The same pattern was also found in the bone density of the total hip. But when focused to the femoral neck, we found no significant change in both groups. CONCLUSION: This continuous combined treatment resulted in beneficial changes of bone density and lipid profiles. The therapy prevented bone loss and the changes in serum lipoprotein were concordant with a lipid profile associated with a decreased risk of coronary heart disease in Thai postmenopausal women.

Aged↗

PubMed1993

An evaluation of bone density and turnover in premenopausal women with type 1 diabetes mellitus.

Measurement of bone density and turnover was assessed in 20 premenopausal females with Type 1 diabetes mellitus and 27 age-sex-matched controls. Measurement was made of spinal (L2-4) and neck of femur bone density by dual-energy X-ray absorptiometry. L2-4 density was significantly higher in the diabetic patients compared with controls (1.224 +/- 0.021 g cm-2 vs. 1.161 +/- 0.020 g cm-2: p = 0.016). No significant difference was noted between the groups in neck of femur density. Measurement of bone formation was assessed by serum alkaline phosphatase and bone resorption by fasting urinary hydroxyproline/creatinine ratio. Alkaline phosphatase was significantly higher in the diabetic patients (185 +/- 16 Ul-1 vs 135 +/- 10 Ul-1: p < 0.01) as was hydroxyproline/creatinine ratio (0.028 +/- 0.003 vs 0.017 +/- 0.002: p = 0.002). No significant correlation was found between L2-4 density and glycated haemoglobin, duration of diabetes or daily dose of insulin taken. These data suggest that osteopenia is not associated with Type 1 diabetes mellitus; however these patients do have evidence of increased bone turnover and may therefore be at risk of osteoporosis in later life, particularly after the menopause.

Absorptiometry, Photon↗

PubMed1992

Distribution of subchondral bone density and cartilage thickness in the human patella.

Subchondral bone density (by means of CT osteoabsorptiometry), and cartilage thickness (directly measured on photocopies of frozen sections), were examined in 30 human patellae, with an age range from 47 to 90 y. A surface demonstration of the distribution was prepared, and representative pictures produced by summation with a computer. Subchondral bone-density maxima were found in the proximal part of the lateral facet, and the density pattern interpreted as the expression of the long-term distribution of stress in the joint. It is reasonable to assume that cartilage thickness, of which two-thirds of the maximum values occupy a lateral position, is also dependent on the local stress. The 2 distributions show correlation coefficients > 0.5 in approximately a third of the cases we examined. Displacement of the higher values of cartilage thickness relative to the subchondral density maxima is attributed to incongruence in the medial part of the joint.

Aged↗

PubMedDate not supplied

[Genetic determination of bone density].

Osteoporosis is a very common disease that concerns every forth postmenopausal white woman. The loss of bone density leads to fractures, mainly to fractures of the neck of the femur. A hereditary genesis of the idiopathic osteoporosis seems to be sure. The vitamin D receptor (VDR) has an important role for the mineralisation of the bones. His allelic variants can be used for a prediction of bone density. These alleles are correlated with endonuclease restriction areas for Bsm-1, Apa-1 and Taq-1. Among these Bsm-1 has the highest incidence for prediction. In this study the allelic variants of the VDR gene correlated with the bone density of the lumbar spine (p < 0.009).

Adult↗

PubMed1990

Quantitative determination of alveolar bone density using digital image analysis of microradiographs.

Horizontal 100 microns ground sections of 20 alveolar bone specimens from adult human mandibles obtained from autopsies were prepared for microradiography. Quantitative analysis of bone density of the alveolar cortex was performed using a semiautomatic digital image analysis system (KONTRON). The results demonstrated that bone density was higher in the lingual than in the labial alveolar cortex (p less than 0.05). In addition, the coronal portion of alveolar cortical bone was significantly more porous than the medical and apical ones (p less than 0.05). These variances were primarily due to increased canal size rather than to an increased number of canals. No significant age dependent changes in bone density could be determined.

Adolescent↗

PubMed2002

Sacral and iliac articular cartilage thickness and cellularity: relationship to subchondral bone end-plate thickness and cancellous bone density.

OBJECTIVES: To measure the thickness and cellularity of adult human sacral and iliac articular cartilages and the thickness and density of the subchondral bones. METHODS: The right sacroiliac joints of 15 adult patients were examined post-mortem. HOME (Highly Optimized Microscope Environment) microscopy was used to measure articular cartilage and subchondral bone end-plate thickness. Conventional morphometric techniques were employed to estimate cartilage cellularity and cancellous bone density. RESULTS: Sacral articular cartilage was thicker than iliac (1.81 vs 0.80 mm, P<0.001). Iliac cartilage cell density in all zones was higher than sacral. The overall mean was 31.19 x 10(-3) vs. 23.23 x 10(-3)/mm(3), P<0.001. Superficial zones contained more cells than middle and deep zones but there were large differences between the cell numbers of the middle and deep zones of both sacral and iliac cartilages. Iliac subchondral bone end-plates were thicker than sacral (0.36 vs 0.23 mm, P<0.001). The thickness of these plates was related inversely to that of the overlying articular cartilages. Iliac subchondral cancellous bone was twice as dense as sacral (22.07 vs. 12.05%, P<0.001), a ratio recognized anteriorly, centrally and posteriorly. CONCLUSIONS: Adult human sacral cartilage is thick and of low cell density. It rests upon a thin bone end-plate supported by porous, cancellous bone. Iliac cartilage and bone display the converse proportions. The identification of these variables may assist understanding of normal sacroiliac joint function and the interpretation of tissue changes in the spondylarthropathies.

Adult↗

PubMedDate not supplied

Trabecular bone density and menstrual function in women runners.

Osteoporosis results in decreased bone mineral mass and reduced trabecular bone density. Although its etiology remains unknown, studies have revealed differential changes in the bone mineral densities of postmenopausal women, anorexic women, and amenorrheic female athletes. Correlations have also been made between estrogen deficiency and osteoporosis in both premenopausal and postmenopausal women. In order to examine the possibility of osteopenia, a group of 36 female runners between the ages of 15 and 44 years were evaluated for bone mineral density, menstrual function, and dietary habits. Serum calcium, phosphorus, and parathyroid hormone (PTH) levels were also determined for each participant, as were complete blood counts. Using dual photon absorptiometry, all participants underwent a 20 minute scan of the lumbar spine with specificity to the L1-14 vertebrae. The 36 subjects included 19 oligomenorrheic and 17 eumenorrheic women. Results of bone density analyses revealed that the oligomenorrheic runners had significantly lower calibrated bone mineral density (CBMD) than their eumenorrheic counterparts (P less than or equal to 0.01). Likewise, the PTH levels of the oligomenorrheic runners were also significantly lower (P less than or equal to 0.01). Analysis of dietary logs revealed no significant differences between the dietary habits, the calcium intake, or the caloric intake of the two groups. The data from this study indicate that there is a relationship between reduced serum PTH levels and the oligomenorrheic state. The loss of the protective effect of estrogen in the oligomenorrheic runners possibly contributed to their reduced bone mineral densities and could be a contributing factor in osteopenia.

Adolescent↗

PubMed1994

[Bone density in anorexia nervosa--with comments on prevention and therapy of osteoporosis].

Anorectic women often have reduced bone density, which may predispose them to osteoporosis and fractures. The mechanisms involved and their relative contribution are still a matter of discussion. Most studies have been done in young adults, but during the past few years children and adolescents have also been investigated. In this paper we present preliminary data on bone mineral parameters in young anorectic females during the first few months of inpatient treatment. Measurement of trabecular bone density (TBD), bone mineral density (BMD) and body composition were done by peripheral quantitative computed tomography (pQCT) at the distal end of the radius and by dual-energy X-ray absorptiometry (DEXA) in ap-projection. Hormonal parameters and clinical course were monitored. Baseline values of TBD and BMD seemed to be generally within the normal range. Follow-up measurements showed a significant reduction in TBD but not in BMD in most patients during the first two months of treatment despite clinical improvement. There was no clear correlation with hormonal or clinical parameters. Further evaluations are necessary. Possible therapeutic consequences are discussed.

Adolescent↗

PubMed2003

Effects of projective bone area size of the spine on bone density and the diagnosis of osteoporosis in healthy pre-menopausal women in China.

The aim of this study was to understand the effects of projective bone area (BA) size of the spine on bone density and the diagnosis of osteoporosis. Measurements of BA, bone mineral content (BMC), areal bone density (aBMD) and volumetric bone density (vBMD) at the posteroanterior (PA) lumbar spine (vertebrae L2-L4) followed by a paired PA/lateral spine (L2-L4) were made using a dual-energy X-ray absorptiometry (DXA) fan-beam bone densitometer (Hologic QDR 4500A) in 1436 healthy pre-menopausal women aged from 20 to 56-years-old. At the PA and lateral lumbar spine, there was a significant positive correlation between BA and BMC (r=0.762 and 0.762, p=0.000) and aBMD (r=0.370 and 0.352, p=0.000), but not vBMD (r=0.000 and 0.102, p=0.813 and 0.063). When BA at the PA spine changed by one standard deviation (SD), BMC and aBMD correspondingly changed by 12.6% and 4.3% on the basis of their respective means while vBMD indicated no change. When a variation of 1 SD was observed in BA at the lateral spine, BMC, aBMD and vBMD correspondingly changed by 13.8%, 4.4% and 1.73% on the basis of their respective means. Through an intercomparison among large, intermediate and small BA groups, significant differences were found in the means of subject's height, weight, BMC and aBMD at the PA and lateral spine as well as the detection rate of osteoporosis by aBMD (p=0.000). Detection rates of osteoporosis by aBMD at the PA, lateral spine and vBMD in healthy pre-menopausal women aged from 40 years to 56 years were 4.5%, 16.4% and 9.7%, respectively, in the small BA group; 1.3%, 6.4% and 7.3%, respectively, in the intermediate BA group; and 0, 0 and 5.5%, respectively, in the large BA group. No significant differences were found in the detection rates of osteoporosis by vBMD among the groups. The results of multiple linear regression revealed that the major factors influencing BA of the lumbar spine was height. In healthy pre-menopausal women of the same race and age, the BA size of the lumbar spine would have significant influence upon aBMD and the diagnosis of osteoporosis, i.e. the larger the BA, the greater the aBMD and the lower the osteoporosis detection rate while conversely, the smaller the BA, the smaller the aBMD and the higher the osteoporosis detection rate. Though vBMD does not change with BA sizes of the lumbar spine, it is a sensitive marker for diagnosing osteoporosis.

Absorptiometry, Photon↗

PubMed2002

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.

Absorptiometry, Photon↗

PubMed1991

Determinants of forearm bone density in premenopausal women: a study in one general practice.

Predictors of distal and proximal forearm bone density, measured by photon absorbtiometry, were investigated in 248 premenopausal women aged 39-56 years. Only one strong predictor of lower bone density was found--history of previous fracture at any site (P less than 0.001). Two other factors showed a weaker association with density, but only at the distal site--history of diuretic use showed a positive association (P less than 0.02) whereas alkaline phosphatase level was inversely correlated with density (P less than 0.01). Other factors were not significant predictors: these included age, calcium intake, level of exercise, anthropometric measures of obesity, serum calcium level, parity, lactation history, a menopausal symptom history, use of the contraceptive pill, smoking and alcohol intake. These results contrast with the far stronger predictors found for postmenopausal women and suggest that genetic endowment rather than lifestyle may be the major determinant of bone density before the menopause.

Adult↗

PubMed2002

Effect of antiepileptic drugs on bone density in ambulatory patients.

BACKGROUND: Long-term antiepileptic drug (AED) use causes multiple abnormalities in calcium and bone metabolism that have been most extensively described in institutionalized patients. The objective is to determine the effect of AED on vitamin D levels and bone density in ambulatory patients and to compare the effects of enzyme-inducing and -noninducing AED and of single vs multiple therapy on bone density. METHODS: A cross-sectional evaluation was conducted of 71 patients (42 adults and 29 children/adolescents) on anticonvulsant therapy for at least 6 months who presented to neurologists at a tertiary referral center. Bone mineral density (BMD) as well as serum 25 hydroxy-vitamin D (25-OHD) levels were measured. A detailed questionnaire assessing calcium intake as well as previous and current intake of antiepileptic medications was administered to all patients. RESULTS: Over 50% of adults and children/adolescents had low 25-OHD levels, but this finding did not correlate with BMD. Antiepileptic therapy decreased BMD in adults. Generalized seizures, duration of epilepsy, and polypharmacy were significant determinants of BMD, more so at skeletal sites enriched in cortical bone. Subjects on enzyme-inducing drugs such as phenytoin, phenobarbital, carbamazepine, and primidone tended to have lower BMD than those on noninducers such as valproic acid, lamotrigine, clonazepam, gabapentin, topamirate, and ethosuximide. CONCLUSION: Epilepsy and its therapy, including the newer drugs, are risk factors for low bone density, irrespective of vitamin D levels. Skeletal monitoring with the institution of appropriate therapy is indicated in patients on chronic antiepileptic therapy.

Adolescent↗

PubMed1993

Chaos in the discrete-time algorithm for bone-density remodeling rate equations.

We compare the predictions of the differential equation form of a class of bone-density stress adaptation models with their associated discrete-time computational algorithms. Although our considerations apply to the class of adaptation models based on bulk or apparent bone-density remodeling, we focus attention on a particular model in this class, a model employed by Weinans et al. [Trans. Orthop. Res. Soc. 14, 310 (1989); Trans. First World Congress of Biomechanics, Vol. II, p. 75 (1990)]. We show that the discrete-time computational algorithm of that stress adaptation model has a well-known chaos mechanism for stress values of practical interest. Further, we obtain a condition on the discrete-time step that prevents the transition to chaos, and conditions that insure monotonic convergence. This chaos mechanism is only present in the discrete-time computational algorithm; we show that the corresponding differential equation form of the bone-density stress adaptation model is smooth, monotonic and nonchaotic.

Adaptation, Physiological↗

PubMedDate not supplied

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

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

Aged↗

PubMed2006

Peri-prosthetic bone density after implantation of a custom-made femoral component. A five-year follow-up.

Peri-prosthetic bone loss caused by stress shielding may be associated with aseptic loosening of femoral components. In order to increase primary stability and to reduce stress shielding, a three-dimensional, cementless individual femoral (Evolution K) component was manufactured using pre-operative CT scans. Using dual energy x-ray absorptiometry, peri-prosthetic bone density was measured in 43 patients, three months, six months, 3.6 and 4.6 years after surgery. At final follow-up there was a significant reduction in mean bone density in the proximal Gruen zones of -30.3% (zone 7) and -22.8% (zone 1). The density in the other zones declined by a mean of between -4% and -16%. We conclude that the manufacture of a three-dimensional, custom-made femoral component could not prevent a reduction in peri-prosthetic bone density.

Absorptiometry, Photon↗

PubMed2002

Alveolar and postcranial bone density in postmenopausal women receiving hormone/estrogen replacement therapy: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: We conducted a 3-year, double-blind, randomized, placebo-controlled study to determine whether the positive effects of hormone/estrogen replacement therapy (H/ERT) on postcranial bone density are accompanied by similar positive effects on oral bone mass. METHODS: A total of 135 postmenopausal women (aged 41-70 years) with no evidence of moderate or severe periodontal disease were randomized to receive daily oral conjugated estrogen (Premarin; 0.625 mg) alone or in combination with medroxyprogesterone acetate (Prempro; 0.625 and 2.5 mg, respectively) or placebo. All subjects received calcium carbonate (1000 mg/d) and cholecalciferol (400 [corrected] IU/d) supplements. The primary efficacy end points were the changes in alveolar crest height and alveolar bone density. Alveolar crest height was measured on bite-wing radiographs, and changes in alveolar bone mass were assessed by means of digital-subtraction radiography. Postcranial bone density was measured in the lumbar spine and left proximal femur by means of dual-energy x-ray absorptiometry. RESULTS: Hormone/estrogen replacement therapy significantly increased alveolar bone mass compared with placebo (+1.84% vs +0.95% [P =.04]), and tended to improve alveolar crest height (+4.83% vs +3.46% [P =.34]). Bone mineral density of the proximal femur significantly increased in the H/ERT compared with the placebo group (total proximal femur, +3.59% vs +0.22% [P =.001]; neck, +2.05% vs -0.34% [P =.02]; trochanter, +3.49% vs +0.08% [P<.001]), but not the lumbar spine (+1.01% vs +0.17% [P =.39]). Changes in alveolar bone mass correlated with bone density changes in the total femur (r = 0.28 [P =.02]) and femoral trochanter (r = 0.25 [P =.04]) in the H/ERT but not in the placebo group. CONCLUSIONS: Postcranial and oral bone mass were increased in postmenopausal women receiving H/ERT. Improvement in oral bone health constitutes an additional benefit of H/ERT.

Absorptiometry, Photon↗

PubMed2004

Seasonal variation in bone density in postmenopausal women.

We investigated seasonal variation in bone density by cross-sectional designs in two large cohorts of women (N = 2337) in Sweden. One cohort was strictly population-based (all 75 yr old, N = 1044), and one cohort was patient-based (age > or = 55 yr, mean age 68, N = 1293). Each woman was assessed once and the inclusion was continuous throughout almost all days of the year. Bone mineral density (BMD) of the total body, hip, and lumbar spine was determined by means of dual X-ray absorptiometry (DXA). For both cohorts, the BMD was similar in those assessed during the period April-September compared to those assessed during the period October-March. On the other hand, when women who had been assessed during July-December were compared with women assessed during January-June, we found the BMD to be up to 5% lower during July-December in all skeletal regions in the population-based sample, and 4% lower at the Ward's triangle and trochanter in the patient-based sample. After correction for small differences in age and weight, women of both cohorts who had been assessed during July-December still had lower BMD at the hip compared with women assessed during January-June. In conclusion, we found no variation in bone density during the period April-September compared to the period October-March in these two cohorts of postmenopausal women. In elderly women living at a northern latitude, BMD may be a few percent lower during the period July-December compared to the period January-June.

Absorptiometry, Photon↗