Estimation of bone mineral density and architectural parameters of the distal radius in hemodialysis patients using peripheral quantitative computed tomography

We analyzed bone changes in a series of hemodialysis patients followed up for a maximum of 299 months by assessing bone mineral density (BMD) and architectural parameters of the distal radius using peripheral quantitative computed tomography (pQCT), and determined the predictors of skeletal changes in these patients. No significant differences in trabecular BMD (BMD(T)) were found compared with BMD(T) of the normal control. In contrast, cortical BMD (BMD(C)) was significantly decreased compared with BMD(C) of the normal controls. Hemodialysis patients had significantly lower values for cortical bone area, cortical thickness, moment of inertia, and polar moment of inertia than the age-matched controls. From single and multiple regression analysis, the most significant predictor of metabolic bone disease in these cases was found to be duration of hemodialysis. In addition, increases in serum alkaline phosphatase and intact parathyroid hormone in secondary hyperparathyroidism were found to correlate with a decrease in pQCT values in cortical bone; as such, these increases were also found to be a predictive. The present study confirms that the reduction in both BMD(C) and architectural parameters in hemodialysis patients occurs partly because of prolonged hemodialysis and secondary hyperparathyroidism. In addition, immobilization, dietary factors, daily intake of calcium or vitamin D, and so on must be taken into account when clarifying the causes of skeletal complications resulting from hemodialysis.     

Macroscopic anisotropic bone material properties in children with severe osteogenesis imperfecta

Children with severe osteogenesis imperfecta (OI) typically experience numerous fractures and progressive skeletal deformities over their lifetime. Recent studies proposed finite element models to assess fracture risk and guide clinicians in determining appropriate intervention in children with OI, but lack of appropriate material property inputs remains a challenge. This study aimed to characterize macroscopic anisotropic cortical bone material properties and investigate relationships with bone density measures in children with severe OI. Specimens were obtained from tibial or femoral shafts of nine children with severe OI and five controls. The specimens were cut into beams, characterized in bending, and imaged by synchrotron radiation X-ray micro-computed tomography. Longitudinal modulus of elasticity, yield strength, and bending strength were 32–65% lower in the OI group (p < 0.001). Yield strain did not differ between groups (p ≥ 0.197). In both groups, modulus and strength were lower in the transverse direction (p ≤ 0.009), but anisotropy was less pronounced in the OI group. Intracortical vascular porosity was almost six times higher in the OI group (p < 0.001), but no differences were observed in osteocyte lacunar porosity between the groups (p = 0.086). Volumetric bone mineral density was lower in the OI group (p < 0.001), but volumetric tissue mineral density was not (p = 0.770). Longitudinal OI bone modulus and strength were correlated with volumetric bone mineral density (p ≤ 0.024) but not volumetric tissue mineral density (p ≥ 0.099). Results indicate that cortical bone in children with severe OI yields at the same strain as normal bone, and that their decreased bone material strength is associated with reduced volumetric bone mineral density. These results will enable the advancement of fracture risk assessment capability in children with severe OI.     

Measurement of bone mineral density (BMD) with quantitative computed tomography (QCT) in postmenopausal osteoporosis: effect of estrogen.

To determine the efficacy of the estrogen replacement therapy (ERT) on the bone mineral density (BMD) measured with quantitative computed tomography (QCT) in postmenopausal osteoporosis 16 women aged 46-72 were examined. They were divided into two groups: 8 women treated with conjugated estrogens (Group I) and 8 who did not received ERT (Group II). In all 16 patients the serum hormonal concentrations (LH, FSH and estradiol) were measured with radioimmunological methods. The bone densitometry was performed in all of them using the single-energy computed tomography (QCT) with the computer Picker 1200. Bone mineral density was measured in three lumbar vertebra (L1-L3) and expressed in milligrams K2HPO4 per ml. The bone mineral density (BMD) was statistically significantly higher in the estrogen treated group (Group I) in every vertebra compared with that of controls (Group II). The serum FSH concentration was statistically significantly lower in the ERT group (Group I) and a statistically significant correlation between FSH level and average BMD (Lmean) was present. In conclusion: 1. the ERT is very efficacious in preventing bone loss in postmenopausal women; 2. measurement of BMD in lumbar vertebra L1 or L3 may be a sufficiently reliable and accurate, cost-effective and time-saving method of screening for osteoporosis; 3. the serum FSH determination seems to be useful in monitoring of the estrogen therapy for postmenopausal osteoporosis.     

Effect of age on bone mineral density and micro architecture in the radius and tibia of horses: An Xtreme computed tomographic study

Background

The effect of age on the bone mineral density and microarchitecture of the equine radius and tibia was investigated. Fifty-six bones from 15 horses aged four to 21 years were used. There were nine geldings and six mares, and none of the horses had any disease influencing bone properties. Xtreme computed tomography was used to evaluate a 9-mm segment of the diaphysis and metaphysis of each bone. The following variables were determined: length of the bone, circumference and diameter in the frontal and sagittal planes in the middle of the bone.Diaphysis: total volume, bone volume, bone volume ratio, slice area, bone area, marrow area, cortical and marrow thickness, bone mineral density, polar moment of inertia of the cortex.Metaphysis: total area, bone area, cortical bone area, cortical thickness, bone mineral density, bone mineral density in the cortex, bone mineral density in the trabecular region, trabecular number, trabecular thickness, trabecular separation, polar moment of inertia of the metaphysis, polar moment of inertia of the cortex of the metaphysis.

Results

Bone density and microarchitecture were not affected by breed or gender. However, the microarchitecture varied with the age of the horse; the number of trabeculae decreased significantly and the distance between trabeculae increased significantly with increasing age. There were no significant differences between bones of the left and right limbs or between the radius and tibia.

Conclusion

The variables investigated did not differ between geldings and mares. However, there were age-related changes in the microstructure of the bones. Further experimental studies are necessary to determine whether these changes reduce bone strength. Age-related changes in the bones were seen and may explain the higher incidence of fractures and fissures in older horses.

     

Altered ratio of collagen chains in bone of a patient with non-lethal osteogenesis imperfecta.

Bone from a patient with osteogenesis imperfecta contained type III collagen which was absent in control bone. The ratio of alpha 1(I)/alpha 2(I) in type I collagen of patient's bone was increased (2.9 vs. 2.3 +/- 0.2 in controls) and the ratio of dimers beta 11/beta 12/beta 22 was altered due to the increased beta 22 content. No abnormality was observed in collagen from the patient's skin. The altered composition of collagen in bone, but the normal composition in skin suggests that the disease in the patient is due to impaired regulation of the synthesis of collagens in bone, rather than by a mutation in one of the two type I collagen genes. Unlike in skin, all the type III collagen in patient's bone was pepsin-soluble indicating an inability of the bone to incorporate type III collagen into mature highly cross-linked extracellular matrix.     

Material matters: a mechanostat-based perspective on bone development in osteogenesis imperfecta and hypophosphatemic rickets

This perspective paper presents a hypothesis that links abnormalities of bone material with densitometric findings in two congenital metabolic bone disorders, osteogenesis imperfecta type I (OI) and X-linked hypophosphatemic rickets (XLH). Analyses of iliac bone samples from OI patients have shown that material bone density is elevated and that the bone material is abnormally stiff in this disorder. Therefore, a given mechanical load on an OI bone will generate a smaller than normal deformation. This in turn should lead osteocytes, the putative mechanosensing cells, to systematically underestimate the prevailing mechanical forces. According to the mechanostat model, bone strength should then be adapted to the underestimated mechanical loads, which means that bone architecture and mass remain below requirements. Available densitometric studies are in accordance with this hypothesis. In XLH, a mild mineralization defect persists despite treatment. This mineralization defect should lead to soft bone material. In analogy to the above model for OI, mechanical loads should be overestimated, resulting in increased densitometric parameters of bone strength. Indeed, lumbar spine areal bone mineral density is usually elevated in such patients.     

Vitamin d status and its relationship with bone mineral density and parathyroid hormone in southeast asian adults with low bone density

ObjectiveTo investigate the vitamin D sufficiency status and the relationships among serum 25-hydroxyvitamin D [25(OH)D] levels, intact parathyroid hormone (iPTH) levels, and bone mineral density (BMD) in patients attending an osteoporosis clinic in Singapore.MethodsIn total, 193 adults with or without prevalent fragility fractures and with low BMD at the femoral neck, total hip, or lumbar spine underwent assessment. Multivariate regression models were used to investigate the relationships among serum 25(OH)D, iPTH, and BMD.ResultsThe mean values (standard deviation) for age of the patients and serum 25(OH)D level were 61 (14) years and 26.05 (7.97) ng/mL, respectively. In 72% of patients, serum 25(OH)D levels were below 30 ng/mL. There was no association between 25(OH)D levels and BMD at the femoral neck, total hip, or lumbar spine(P = .568, .461, and .312, respectively). Serum iPTH levels were negatively associated with BMD at the total hip(P = .035) and the lumbar spine (P = .019). At levels < 30 ng/mL, 25(OH)D was negatively associated with iPTH (P = .036).ConclusionAmong this Southeast Asian population of patients with low BMD, no direct relationship between serum 25(OH)D levels and BMD was observed. A negative correlation existed, however, between iPTH and 25(OH)D at serum 25(OH)D concentrations < 30 ng/mL, and serum iPTH levels showed a significant negative association with BMD at the total hip and lumbar spine. These significant negative associations between iPTH levels and BMD at the total hip and lumbar spine underscore the critical role of this hormone in bone metabolism and health. (Endocr Pract. 2011;17:226-234)     

Association of interleukin 10 haplotype with low bone mineral density in Korean postmenopausal women

Osteoporosis is a disease characterized by exaggerated loss of bone mass, with as much as 50 to 85% of the variation in bone mineral density (BMD) commonly accepted as being genetically determined. Although intensive studies have attempted to elucidate the genetic effects of polymorphisms on BMD and/or osteoporosis in several genes, the genes involved are still largely unknown. The possible associations of genetic variants in five-candidate genes (IL10, CCR3, MCP1, MCP2 and GC) with spinal BMD were investigated in Korean postmenopausal women (n = 370). Fourteen SNPs in five candidate genes were genotyped, and the haplotypes of each gene constructed. The associations of adjusted spinal BMD by age, year since menopause (YSM) and body mass index (BMI), with genetic polymorphisms, were analyzed using multiple regression models. Genetic association analysis of Korean postmenopausal women revealed that IL10 -592A > C and/or IL10 ht2 were associated with decreased bone mass, whereas no significant associations were observed with all polymorphisms in other genes. The levels of spinal BMD in individuals bearing the IL10 -592CC genotype were lower (0.78 +/- 0.16) than those in others (0.85 +/- 0.17) (P = 0.02), and the BMD of IL10 ht2 bearing individuals were also lower (0.82 +/- 0.15) than those in others (0.85 +/- 0.17) (P = 0.04). Our results suggest that variants of IL10 might play a role in the decreased BMD, although additional study might need to be followed-up in a more powerful cohort.     

Strangulated diaphragmatic hernia in a patient with osteogenesis imperfecta.

Hernias are common in patients with osteogenesis imperfecta, but to our knowledge there have been no reports of diaphragmatic hernias in such patients. We describe a patient with osteogenesis imperfecta in whom a diaphragmatic hernia contained a strangulated segment of the splenic flexure of the colon. Resection of the necrotic tissue and transverse colostomy resulted in an uneventful recovery.     

Zinc status of women with low bone mineral density who receive calcium supplements

We evaluated whether a daily high-dose calcium supplement perturbs the zinc status in 23 postmenopausal women (mean age: 63yr) with low bone mineral density. Plasma and erythrocyte zinc concentrations, plasma bone-specific alkaline phosphatase (BSAP) and 5′-nucleotidase activities, and urinary zinc and calcium excretion were determined first at the end of 4 wk of daily oral calcium (1200 mg) and were measured again at the end of the subsequent 4 wk of daily cosupplementation with calcium (1200 mg) and zinc (30 mg). Mean plasma and erythrocyte zinc concentrations after 4 wk of calcium alone were not significantly different from concentrations after cosupplementation of calcium and zinc. Mean plasma BSAP activities before cosupplementation with zinc was significantly higher than that after zinc (p<0.02), whereas plasma 5′-nucleotidase activities were not affected by zinc supplementation. Urinary zinc excretion slightly, but significantly, increased after the supplementation of zinc (p<0.05), whereas calcium excretion remained similar. Our data indicate that a 4-wk zinc supplementation did not significantly improve zinc status. Although limited by the small sample size and short study duration, our data suggest that a daily calcium dose of 1200 mg had no effect on the zinc status of our subjects.     

COL1A1 mutation analysis in Lithuanian patients with osteogenesis imperfecta

Osteogenesis imperfecta (OI) is a generalised disorder of connective tissue characterised by an increased fragility of bones and also manifested in other tissues containing collagen type I, by blue sclera, hearing loss, dentinogenesis imperfecta, hyperextensible joints, hernias and easy bruising. OI is dominantly inherited and results in >90% OI cases, caused by mutations in one of the two genes COL1A1 or COL1A2 coding for type I procollagen. The Lithuanian OI database comprises 147 case records covering the period of 1980 - 2001. Clinical and genealogical analysis of OI cases/families from Lithuania available for examination revealed 18 familial cases of OI type I and 22 sporadic cases: OI type II (3 cases), OI type III (11 cases) and OI type I (8 cases). As a result of their molecular genetic investigation, 11 mutations were identified in the COL1A1 gene in 13 unrelated patients. Of them, nine mutations (E500X, G481A, c.2046insCTCTCTAG, c.1668delT, c.1667insC, c.4337insC, IVS19+1G > A, IVS20-2A > G, IVS22-1G > T) appeared to be novel, i.e. not yet registered in the Human Type I and Type III Collagen Mutations Database (http://www.le.ac.uk/genetics/collagen).     

Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta

In principle, transplantation of mesenchymal progenitor cells would attenuate or possibly correct genetic disorders of bone, cartilage and muscle, but clinical support for this concept is lacking. Here we describe the initial results of allogeneic bone marrow transplantation in three children with osteogenesis imperfecta, a genetic disorder in which osteoblasts produce defective type I collagen, leading to osteopenia, multiple fractures, severe bony deformities and considerably shortened stature. Three months after osteoblast engraftment (1.5-2.0% donor cells), representative specimens of trabecular bone showed histologic changes indicative of new dense bone formation. All patients had increases in total body bone mineral content ranging from 21 to 29 grams (median, 28), compared with predicted values of 0 to 4 grams (median, 0) for healthy children with similar changes in weight. These improvements were associated with increases in growth velocity and reduced frequencies of bone fracture. Thus, allogeneic bone marrow transplantation can lead to engraftment of functional mesenchymal progenitor cells, indicating the feasibility of this strategy in the treatment of osteogenesis imperfecta and perhaps other mesenchymal stem cell disorders as well.     

Reduced quantitative ultrasound bone mineral density in HIV-infected patients on antiretroviral therapy in Senegal

Background

Bone status in HIV-infected patients on antiretroviral treatment (ART) is poorly documented in resource-limited settings. We compared bone mineral density between HIV-infected patients and control subjects from Dakar, Senegal.

Methods

A total of 207 (134 women and 73 men) HIV-infected patients from an observational cohort in Dakar (ANRS 1215) and 207 age- and sex-matched controls from the general population were enrolled. Bone mineral density was assessed by quantitative ultrasound (QUS) at the calcaneus, an alternative to the reference method (i.e. dual X-absorptiometry), often not available in resource-limited countries.

Results

Mean age was 47.0 (±8.5) years. Patients had received ART for a median duration of 8.8 years; 45% received a protease inhibitor and 27% tenofovir; 84% had undetectable viral load. Patients had lower body mass index (BMI) than controls (23 versus 26 kg/m², P<0.001). In unadjusted analysis, QUS bone mineral density was lower in HIV-infected patients than in controls (difference: −0.36 standard deviation, 95% confidence interval (CI): −0.59;−0.12, P = 0.003). Adjusting for BMI, physical activity, smoking and calcium intake attenuated the difference (−0.27, CI: −0.53;−0.002, P = 0.05). Differences in BMI between patients and controls explained a third of the difference in QUS bone mineral density. Among patients, BMI was independently associated with QUS bone mineral density (P<0.001). An association between undetectable viral load and QUS bone density was also suggested (β = 0.48, CI: 0.02;0.93; P = 0.04). No association between protease inhibitor or tenofovir use and QUS bone mineral density was found.

Conclusion

Senegalese HIV-infected patients had reduced QUS bone mineral density in comparison with control subjects, in part related to their lower BMI. Further investigation is needed to clarify the clinical significance of these observations.     

Exercise and bone mineral density in men: a meta-analysis.

The purpose of this study was to use the meta-analytic approach to examine the effects of exercise on bone mineral density (BMD) in men. A total of 26 effect sizes (ES) representing 225 subjects from 8 studies met the criteria for inclusion. When BMD sites assessed were specific to the sites loaded during exercise, increases of approximately 2.6% (2.1% in the exercisers and -0.5% in the controls) were found. These results were statistically significant (ES = 0.213, 95% bootstrap confidence interval = 0.007-0.452). Statistically significant ES changes were found for older (>31 yr) but not younger (<31 yr) adults, with differences between groups statistically significant (P = 0.04). Statistically significant changes were also observed at the femur, lumbar, and os calcis sites. The results of this study suggest that site-specific exercise may help improve and maintain BMD at the femur, lumbar, and os calcis sites in older men. However, the biological importance of the small changes observed for most outcomes, quality of studies, and limited data pool prevent us from forming any firm conclusion regarding the use of exercise for maintaining and/or improving BMD in men. Clearly, a need exists for additional studies.     

BMI,hypertension and low bone mineral density in adult men and women

The aim of this work was to estimate the body mass index (BMI) at which risk of hypertension is lowest in men and women, while concurrently considering the protective role of adipose tissue in osteoporosis. Healthy, occupationally active inhabitants of the city of Wroc?aw, Poland, 1218 women and 434 men were studied. BMI, systolic and diastolic blood pressures, bone mineral density (BMD) of the trabecular compartment and distal radius of the non-dominant hand were recorded. Overweight in young women (≤45 years) was associated with increased risk of hypertension, whereas the risk of low bone mineral was decreased for the same BMI. In older women (>45 years), a BMI > 27 was the threshold for increased risk of hypertension. In this age group, extremely slim women (BMI < 21) had the highest risk of low bone mineral density. In younger males (≤45 years), risk of hypertension was lowest among the thinnest subjects (BMI < 21). Increase in BMI over 21 kg/m² increased the risk of hypertension. The probability of low bone mineral density was the same in all BMI categories of men. In older men (>45 years), the thinnest (BMI < 21) had higher risk of hypertension. To begin from BMI = 25 kg/m², there was a monotonous increase in risk of hypertension in men. Higher risk for low bone mineral density was observed in older men with the BMI < 23.Among younger adults, risk of hypertension and low bone mineral density increase at BMI ≥ 21 kg/m² in men and BMI ≥ 23 kg/m² in women. Among older men and women, the BMI threshold was 27 kg/m².     

Low areal bone mineral density values in adolescents and young adult turner syndrome patients increase after long-term transdermal estradiol therapy

OBJECTIVE: To study the effects of long-term estradiol therapy on areal bone mineral density (aBMD) values in young adult Turner syndrome patients. METHODS: The effects of 2-year transdermal estradiol administration on lumbar, L2-L4, aBMD values were evaluated in 12 Turner syndrome patients, 15.41-21.85 years old, who had reached adult height and had low aBMD values. Puberty was induced in all at a chronological age above 12 years and menarche appeared between 13.82 and 15.40 years. The patients were on oral estrogen/gestagen therapy from then until the start of the study. Adhesive patches of 17-beta-estradiol designed to be worn for 72 h and deliver 100 microg of estradiol per day, which results in a steady mean serum estradiol level of 75 pg/ml, were used for 21 days. From day 11 to day 21, 10 mg of oral didrogesterone were also added. Nutritional and physical activity habits were evaluated at the beginning, after 1 year and at the end of the study. RESULTS: aBMD values significantly increased from 0.910 +/- 0.065 to 1.005 +/- 0.086 g/cm2 (10.06 +/- 3.37%) and the z-score from -2.38 +/- 0.63 to -1.54 +/- 0.71 (0.81 +/- 0.30 z-score). No significant differences were observed in body mass index, calcium intake and physical activity habits at the start, during and at the end of the study. CONCLUSION: In summary, our results underline the importance of estrogens for bone mass peaking and suggest that this therapeutic protocol may be useful in the therapy of Turner syndrome patients with low bone mass.