Changes In Bone Mass Research Articles

Longitudinal bone mineral content and density in Rett syndrome and their contributing factors

Bone mass and density are low in females with Rett syndrome. This study used Dual energy x-ray absorptiometry to measure annual changes in z-scores for areal bone mineral density (aBMD) and bone mineral content (BMC) in the lumbar spine and total body in an Australian Rett syndrome cohort at baseline and then after three to four years. Bone mineral apparent density (BMAD) was calculated in the lumbar spine. Annual changes in lean tissue mass (LTM) and bone area (BA) were also assessed. The effects of age, genotype, mobility, menstrual status and epilepsy diagnosis on these parameters were also investigated.The baseline sample included 97 individuals who were representative of the total live Australian Rett syndrome population under 30years in 2005 (n=274). Of these 74 had a follow-up scan. Less than a quarter of females were able to walk on their own at follow-up. Bone area and LTM z-scores declined over the time between the baseline and follow-up scans. Mean height-standardised z-scores for the bone outcomes were obtained from multiple regression models. The lumbar spine showed a positive mean annual BMAD z-score change (0.08) and a marginal decrease in aBMD (−0.04). The mean z-score change per annum for those ‘who could walk unaided’ was more positive for LS BMAD (p=0.040). Total body BMD mean annual z-score change from baseline to follow-up was negative (−0.03). However this change was positive in those who had achieved menses prior to the study (0.03, p=0,040). Total body BMC showed the most negative change (−0.60), representing a decrease in bone mineral content over time. This normalised to a z-score change of 0.21 once adjusted for the reduced lean tissue mass mean z-score change (−0.21) and bone area mean z-score change (−0.14).Overall, the bone mineral content, bone mineral density, bone area and lean tissue mass z-scores for all outcome measures declined, with the TB BMC showing significant decreases.Weight, height and muscle mass appear to have impacts on bone formation and we recommend that nutritional intake should be closely monitored and a physical activity plan developed to optimise bone health. Pubertal progression should also be assessed in conjunction with serial densitometry assessments to track bone mass and density changes over time.

RANK pathway in giant cell tumor of bone: pathogenesis and therapeutic aspects.

Giant cell tumor is a relatively uncommon but painful tumor of bone, which can metastasize to the lungs. The RANK pathway is often reported to be involved in the pathogenesis of giant cell tumor of bone (GCTB). This pathway is a key signaling pathway of bone remodeling that plays a critical role in differentiation of precursors into multinucleated osteoclasts, and activation of osteoclasts leading to bone resorption. Dysregulation of RANK ligand (RANKL)-RANK-osteoprotegerin (OPG) signaling cascade induces the imbalance between bone formation and bone resorption, which leads to the changes in bone mass, increases osteoclast-mediated bone destruction, bone metastasis, and the progression of existing skeletal tumors. Recent evidences have shown that targeting the components of RANKL-RANK-OPG signaling pathway is a promising approach in the treatment of GCTB. This review study has focused on the association of RANKL-RANK-OPG pathway in the pathogenesis and progression of GCTB as well as discussed the possible therapeutic strategies by targeting this pathway.

Changes in vertebral bone marrow fat and bone mass after gastric bypass surgery: A pilot study

Bone marrow fat may serve a metabolic role distinct from other fat depots, and it may be altered by metabolic conditions including diabetes. Caloric restriction paradoxically increases marrow fat in mice, and women with anorexia nervosa have high marrow fat. The longitudinal effect of weight loss on marrow fat in humans is unknown. We hypothesized that marrow fat increases after Roux-en-Y gastric bypass (RYGB) surgery, as total body fat decreases. In a pilot study of 11 morbidly obese women (6 diabetic, 5 nondiabetic), we measured vertebral marrow fat content (percentage fat fraction) before and 6months after RYGB using magnetic resonance spectroscopy. Total body fat mass declined in all participants (mean±SD decline 19.1±6.1kg or 36.5%±10.9%, p<0.001). Areal bone mineral density (BMD) decreased by 5.2%±3.5% and 4.1%±2.6% at the femoral neck and total hip, respectively, and volumetric BMD decreased at the spine by 7.4%±2.8% (p<0.001 for all). Effects of RYGB on marrow fat differed by diabetes status (adjusted p=0.04). There was little mean change in marrow fat in nondiabetic women (mean +0.9%, 95% CI −10.0 to +11.7%, p=0.84). In contrast, marrow fat decreased in diabetic women (−7.5%, 95% CI −15.2 to +0.1%, p=0.05). Changes in total body fat mass and marrow fat were inversely correlated among nondiabetic (r=−0.96, p=0.01) but not diabetic (r=0.52, p=0.29) participants. In conclusion, among those without diabetes, marrow fat is maintained on average after RYGB, despite dramatic declines in overall fat mass. Among those with diabetes, RYGB may reduce marrow fat. Thus, future studies of marrow fat should take diabetes status into account. Marrow fat may have unique metabolic behavior compared with other fat depots.

Comparison of the Spine and Hip BMD Assessments Derived from Quantitative Computed Tomography.

Quantification of bone mineral density (BMD) is being used as the main method to diagnose osteoporosis. Dual-energy X-ray absorptiometry (DXA) is the most common tools for measuring BMD. Compared to DXA, quantitative computed tomography (QCT) can determine in three dimensions the true volumetric BMD (vBMD) at any skeletal site. In addition to the spine, the hip is an important site for axial BMD measurement. This study examines lumbar spine and hip BMD of Chinese adults by QCT. Age related changes in bone mass derived by QCT measurements were determined. The osteoporosis QCT detection rates at the spine and hip are assessed in both female and male, and agreement of skeletal status category between the spine and hip in older adults is also assessed.

The Impact of Different Amounts of Calcium Intake on Bone Mass and Arterial Calcification in Ovariectomized Rats.

Reduced estrogen secretion and low calcium (Ca) intake are risk factors for bone loss and arterial calcification in female rodents. To evaluate the effects of Ca intake at different amounts on bone mass changes and arterial calcification, 8-wk-old female Wistar rats were randomly placed in ovariectomized (OVX) control and OVX with vitamin D3 plus nicotine (VDN) treatment groups. The OVX with VDN rats were then divided into six groups to receive different amounts of Ca in their diets: 0.01%, 0.1%, 0.3%, 0.6%, 1.2%, or 2.4% Ca. After 8 wk of administration, low Ca intake groups with 0.01% and 0.1% Ca diets had significantly reduced bone mineral density (BMD) and bone mechanical properties as compared with those of the other groups, whereas high Ca intake groups with 1.2% and 2.4% Ca diets showed no differences as compared with the 0.6% Ca intake group. For both the 0.01% and 2.4% Ca intake groups, Ca levels in their thoracic arteries were significantly higher as compared with those of the 0.6% Ca diet group, and that was highly correlated with serum PTH levels. An increase in relative BMP-2 mRNA expression in the arterial tissues of the 0.01% and 2.4% Ca diet groups was also observed. These results suggested that extremely low Ca intake during periods of estrogen deficiency may be a possible risk for the complications of reduced BMD and arterial calcification and that extremely high Ca intake may promote arterial calcification with no changes in BMD.

Quantitative ultrasonometry during pregnancy and lactation: a longitudinal study.

This study describes bone mass changes during pregnancy and lactation measured by a special ultrasound method. Pregnant women showed a decrease of bone mass followed by a stable bone mass while breast-feeding afterwards. Later in life, there is a recovery of bone mass loss. The aim of this study was to evaluate bone changes during pregnancy using the radiation-free method of quantitative ultrasonometry (QUS). One hundred twenty-five pregnant women who underwent prenatal care were included in this study. Ultrasound measurement of the calcaneus was performed in each trimester and then 6 weeks, 3 months, and 1 year postpartum. The calcaneal QUS measurements were carried out using the Achilles plus device (GE/Lunar Corporation, Madison, WI). Three ultrasound variables were measured: speed of sound (SOS, m/s), broadband ultrasound attenuation (BUA, dB/MHz), and the "stiffness index" (expressed as the percentage of the mean value in young adults). SOS and BUA raw data result in the t-score and z-score. A complete panel of six measurements was acquired over the time period in 101 patients (80.8%). Forty-two percent of the included patients were primipara, while 58% had given birth to at least one child (47%) previously. There was a statistically significant change of the t-score (tv = 2.14, p = 0.035) and the stiffness index (tv = 2.46, p = 0.016) from the second to the third trimester, followed by a plateau during lactation. Interestingly, the t-score remained stable during lactation, regardless of the duration of lactation (<3 months, 3-6 months, and >6 months). Young primiparas who had a sedentary adolescence were at the highest risk of bone loss during pregnancy. Bone loss that occurred during pregnancy was typically recovered later on, based on unknown molecular and biochemical mechanisms that must be elucidated with further studies.

Avances en el estudio de los mecanismos involucrados en la modulación de la expresión de esclerostina en células humanas

Summary Sclerostin plays an important role in the regulation of bone metabolism, as is shown in the dramatic changes in bone mass which occur when its activity is inhibited by means of monoclonal antibodies. However, the mechanisms which regulate its expression are still not well-understood. Various studies have shown an association between polymorphisms of the SOST gene promoter (which codes for sclerostin) and bone mineral density. Also, the degree of methylation of a CpG island near the start of the transcription is associated with marked changes in the expression of the gene. Therefore, it appears that the production of sclerostin is influenced by both genetic and epigenetic mechanisms, in addition to other hormonal and mechanical factors. A greater knowledge of these mechanisms would not only contribute to a better understanding of bone biology, but could open up new therapeutic opportunities.

Bone And Soft Tissue Changes In Patients With Spinal Cord Injury And Multiple Sclerosis

In patients with spinal cord injury and multiple sclerosis, deterioration of body composition (changes in bone, fat and muscle mass) is associated with increased risk for diseases such as coronary artery heart disease, non-insulin dependent diabetes mellitus, lipid metabolism abnormalities, and osteoporotic fractures in these patients. Immobility leads to a changing pattern of loading in the paralyzed areas, and secondary alteration in structure. However, bone and soft tissue changes in these patients are usually neglected. The purpose of this article is to update on the pathophysiological mechanisms leading to bone and soft tissue changes, and to increase the awareness of the treating physicians with respect to bone, muscle and fat loss and their consequences aiming to obtain measures to prevent bone and soft tissue loss in these patients.

Skeletal maturity leads to a reduction in the strain magnitudes induced within the bone: A murine tibia study

Bone adapts to changes in the local mechanical environment (e.g. strains) through formation and resorption processes. However, the bone adaptation response is significantly reduced with increasing age. The mechanical strains induced within the bone by external loading are determined by bone morphology and tissue material properties. Although it is known that changes in bone mass, architecture and bone tissue quality occur with age, to what extent they contribute to the altered bone adaptation response remains to be determined. This study investigated alterations in strains induced in the tibia of different aged female C57Bl/6J mice (young, 10-week-old; adult, 26-week-old; and elderly, 78-week-old) subjected to in vivo compressive loading. Using a combined in vivo/in silico approach, the strains in the bones were assessed by both strain gauging and finite element modeling experiments. In cortical bone, strain magnitudes induced at the mid-diaphysis decreased by 20% from young to adult mice and by 15% from adult to elderly mice. In the cancellous bone (at the proximal metaphysis), induced strains were 70% higher in young compared with adult and elderly mice. Taking into account previous studies showing a reduced bone adaptation response to mechanical loading in adulthood, these results suggest that the diminished adaptive response is in part due to a reduction in the strains induced within the bone.

Bone remodelling in humans is load-driven but not lazy

During bone remodelling, bone cells are thought to add and remove tissue at sites with high and low loading, respectively. To predict remodelling, it was proposed that bone is removed below and added above certain thresholds of tissue loading and within these thresholds, called a 'lazy zone', no net change in bone mass occurs. Animal experiments linking mechanical loading with changes in bone density or microstructure support load-adaptive bone remodelling, while in humans the evidence for this relationship at the micro-scale is still lacking. Using new high-resolution CT imaging techniques and computational methods, we quantify microstructural changes and physiological tissue loading in humans. Here, we show that bone remodelling sites in healthy postmenopausal women strongly correlate with tissue loading following a linear relationship without a 'lazy zone' providing unbiased evidence for load-driven remodelling in humans. This suggests that human and animal bones both react to loading induced remodelling in a similar fashion.

G.P.170: Bone mineral density and body composition in 39 Duchenne muscular dystrophy patients: A two-years follow up

Individuals affected with Duchenne muscular dystrophy (DMD) show significantly altered whole-body composition compared with normal control population. We assessed for at least two years 39 DMD-patients to evaluate how their bone mass and body composition change during time. All patients underwent clinical evaluation and dual-energy-X-ray-absorptiometry (DXA) assessment every six months. By DXA we obtained subtotal total body (without head) and spine bone mineral density (BMD), lean tissue mass (LTM) and body fat percentage (PFAT). We compared data using Wilcoxon tests. At baseline visit the average age was 7 ± 1.62 (range 4–11) years, 11 patients were already treated with steroids since a mean of 3 years, 17 started therapy after that visit and 4 about 1 year later. At baseline we found significant Spearman correlations between all four DXA parameters each other and with weight, height and BMI. We observed an increasing trend (with statistically significant differences) in all DXA parameters during the two-years follow-up, especially in PFAT. Comparing boys over 10 years old with others we found significant differences in all parameters. These results confirm usefulness of DXA as tool both for DMD follow up and for treatment adjustment. Correlation with clinical outcome measures will be presented.

Peak bone strength is influenced by calcium intake in growing rats

In this study we investigated the effect of supplementing the diet of the growing male rat with different levels of calcium (from low to higher than recommended intakes at constant Ca/P ratio), on multiple factors (bone mass, strength, size, geometry, material properties, turnover) influencing bone strength during the bone accrual period. Rats, age 28days were supplemented for 4weeks with high Ca (1.2%), adequate Ca (0.5%) or low Ca level (0.2%). Bone metabolism and structural parameters were measured. No changes in body weight or food intake were observed among the groups. As anticipated, compared to the adequate Ca intake, low-Ca intake had a detrimental impact on bone growth (33.63 vs. 33.68mm), bone strength (−19.7% for failure load), bone architecture (−58% for BV/TV) and peak bone mass accrual (−29% for BMD) due to the hormonal disruption implied in Ca metabolism. In contrast, novel, surprising results were observed in that higher than adequate Ca intake resulted in improved peak bone strength (106 vs. 184N/mm for the stiffness and 61 vs. 89N for the failure load) and bone material properties (467 vs. 514mPa for tissue hardness) but these effects were not accompanied by changes in bone mass, size, microarchitecture or bone turnover. Hormonal factors, IGF-I and bone modeling were also evaluated. Compared to the adequate level of Ca, IGF-I level was significantly lower in the low-Ca intake group and significantly higher in the high-Ca intake group. No detrimental effects of high Ca were observed on bone modeling (assessed by histomorphometry and bone markers), at least in this short-term intervention. In conclusion, the decrease in failure load in the low calcium group can be explained by the change in bone geometry and bone mass parameters. Thus, improvements in mechanical properties can be explained by the improved quality of intrinsic bone tissue as shown by nanoindentation. These results suggest that supplemental Ca may be beneficial for the attainment of peak bone strength and that multiple factors linked to bone mass and strength should be taken into account when setting dietary levels of adequate mineral intake to support optimal peak bone mass acquisition.

Influence of angulation on metacarpal bone mineral density measurements using digital X-ray radiogrammetry.

Digital X-ray radiogrammetry (DXR) is a computer-assisted technique used to quantify cortical bone density of the metacarpals. The influence of metacarpal bone rotation and type of cast material on bone mineral density (BMD) measurements using the DXR technique was tested. The bone mineral density of the hand was measured by DXR, and rotation error (DXR-RE) as coefficients of variation were calculated, to verify reliability and reproducibility of this radiogeometric technique to assess in particular minor disease-related changes in the metacarpal bone mass. The reproducibility of the DXR measurements was also investigated using different cast materials (mull, elastic, and plastic). There were no significant changes in absolute values of DXR-BMD observed between 0 to [Formula: see text] angulation. The relative DXR-RE ranged between 0 % (degree 1) and 0.70 % (degrees 15 and 19) for DXR-BMD. Regarding the different cast materials, DXR-BMD revealed a coefficient of variation with 0.41 % (mull cast) and 0.21 % (elastic cast). For the plastic cast, the DXR technique was not able to perform an analysis of DXR-BMD. The study revealed no significant influence of metacarpal rotation on the measurements of metacarpal bone mineral density as estimated by DXR. DXR measurements are not optimal when cast material is used. DXR can accurately quantify periarticular cortical bone mass. This is significant especially for rheumatoid arthritis and related conditions where X-ray imaging of arthritic hands with varying degrees of deformity is performed.

Tofogliflozin, a sodium/glucose cotransporter 2 inhibitor, attenuates body weight gain and fat accumulation in diabetic and obese animal models.

Objective:Tofogliflozin, a highly selective inhibitor of sodium/glucose cotransporter 2 (SGLT2), induces urinary glucose excretion (UGE), improves hyperglycemia and reduces body weight in patients with Type 2 diabetes (T2D). The mechanisms of tofogliflozin on body weight reduction were investigated in detail with obese and diabetic animal models.Methods:Diet-induced obese (DIO) rats and KKAy mice (a mouse model of diabetes with obesity) were fed diets containing tofogliflozin. Body weight, body composition, biochemical parameters and metabolic parameters were evaluated.Results:In DIO rats tofogliflozin was administered for 9 weeks, UGE was induced and body weight gain was attenuated. Body fat mass decreased without significant change in bone mass or lean body mass. Food consumption (FC) increased without change in energy expenditure, and deduced total calorie balance (deduced total calorie balance=FC−UGE−energy expenditure) decreased. Respiratory quotient (RQ) and plasma triglyceride (TG) level decreased, and plasma total ketone body (TKB) level increased. Moreover, plasma leptin level, adipocyte cell size and proportion of CD68-positive cells in mesenteric adipose tissue decreased. In KKAy mice, tofogliflozin was administered for 3 or 5 weeks, plasma glucose level and body weight gain decreased together with a reduction in liver weight and TG content without a reduction in body water content. Combination therapy with tofogliflozin and pioglitazone suppressed pioglitazone-induced body weight gain and reduced glycated hemoglobin level more effectively than monotherapy with either pioglitazone or tofogliflozin alone.Conclusion:Body weight reduction with tofogliflozin is mainly due to calorie loss with increased UGE. In addition, tofogliflozin also induces a metabolic shift from carbohydrate oxidation to fatty acid oxidation, which may lead to prevention of fat accumulation and inflammation in adipose tissue and liver. Tofogliflozin may have the potential to prevent obesity, hepatic steatosis and improve insulin resistance as well as hyperglycemia.

Effects of microgravity on bone marrow mesenchymal stem cells into osteogenic differentiation

Bone marrow mesenchymal stem cells (BMSCs) is a kind of multipotent adult stem cells,which is one of the most important seed sources of tissue engineering.Microgravity has inhibitory effects on osteogenic differentiation of BMSCs,which will cause bone mass reduction and changes of bone micro-structure that finally lead to osteoporosis.This process is regulated by multiple signaling pathways such as mitogen-activated protein kinase (MAPK) pathway,Notch pathway and Wnt/β-catenin pathway which co-regulated BMSCs osteogenic differentiation under microgravity.Studying the effects of microgravity on BMSCs into osteogenic differentiation can clarify the mechanism of bone loss,put forward new targets for the treatment of diseases and provide a useful reference for the development of China's space industry. Key words: Microgravity; Bone marrow mesenchymal stem cells; Osteogenic differentiation

Vaccination with DKK1-derived peptides promotes bone formation and bone mass in an aged mouse osteoporosis model.

The investigation of agents for the treatment of osteoporosis has been a long-standing effort. The Wnt pathway plays an important role in bone formation and regeneration, and expression of Wnt pathway inhibitors, Dickkopf-1 (DKK1), appears to be associated with changes in bone mass. Inactivation of DKK1 leads to substantially increased bone mass in genetically manipulated animals. DKK1-derived peptides (DDPs) were added to BMP2-stimulated MC3T3-E1 preosteoblastic cells in vitro to evaluate inhibitory activity of DDPs in MC3T3-E1 cell differentiation. Study was extended in vivo on old female mice to show whether or not inhibition of endogenous DKK1 biological activity using DDPs vaccination approach leads to increase of bone formation, bone density, and improvement of bone microstructure. We reported that synthetic DDPs were able to reduce alkaline phosphatase activity, prevent mineralization and inhibit the differentiation of MC3T3-E1 cells in vitro. Furthermore, vaccination with these DDPs in aged female mice 4 times for a total period of 22weeks promoted bone mass and bone microstructure. 3D microCT and histomorphometric analysis showed that there were significant increase in bone mineral densities, improvement of bone microstructure and promotion of bone formation in the vaccinated mice, especially in the mice vaccinated with DDP-A and DDP-C. Histological and scanning electron microscopy image analysis also indicated that vaccination increased trabecular bone mass and significantly decreased fragmentation of bone fibers. Taken together, these preclinical results suggest that vaccination with DDPs represents a promising new therapeutic approach for the treatment of bone-related disorders, such as osteoporosis.

Reduced tissue-level stiffness and mineralization in osteoporotic cancellous bone.

Osteoporosis alters bone mass and composition ultimately increasing the fragility of primarily cancellous skeletal sites; however, effects of osteoporosis on tissue-level mechanical properties of cancellous bone are unknown. Dual-energy X-ray absorptiometry (DXA) scans are the clinical standard for diagnosing osteoporosis though changes in cancellous bone mass and mineralization are difficult to separate using this method. The goal of this study was to investigate possible difference in tissue-level properties with osteoporosis as defined by donor T scores. Spine segments from Caucasian female cadavers (58-92years) were used. A T score for each donor was calculated from DXA scans to determine osteoporotic status. Tissue-level composition and mechanical properties of vertebrae adjacent to the scan region were measured using nanoindentation and Raman spectroscopy. Based on T scores, six samples were in the Osteoporotic group (58-74years) and four samples were in the Not Osteoporotic group (65-92years). The indentation modulus and mineral to matrix ratio (mineral:matrix) were lower in the Osteoporotic group than the Not Osteoporotic group. Mineral:matrix ratio decreased with age (r (2)=0.35, p=0.05), and the indentation modulus increased with areal bone mineral density (r (2)=0.41, p=0.04). This study is the first to examine cancellous bone composition and mechanical properties from a fracture prone location with osteoporosis. We found differences in tissue composition and mechanical properties with osteoporosis that could contribute to increased fragility in addition to changes in trabecular architecture and bone volume.

FRI0063 Changes in Bone Mass over Time in Subjects with Rheumatoid Arthritis: an Observational Study

BackgroundIt is widely accepted that patients with rheumatoid arthritis (RA) lose bone mass more rapidly those without such history over time due to a number of factors including systemic inflammation...

SAT0442 Subchondral Bone Remodeling, but not Bone Mass, is Increased in Local Early Stage Lesions of the Osteoarthritic Human Hip Joint as Studied by Stereological Histology

BackgroundOsteoarthritis (OA) is a common joint disease, but the pathology is not fully understood. It has been suggested that bone changes are important for the pathogenesis of OA. However, only...

Evaluación de la densidad mineral ósea en la monitorización de los efectos del tratamiento de cáncer de mama con inhibidores de la aromatasa: la importancia del cambio mínimo significativo

Aromatase inhibitors (IAs) have shown great efficacy in the treatment of estrogen receptor positive breast cancer in postmenopausal women, however they may lead to a reduction of estrogen concentration which is associated with a significant increase in bone loss, increasing incidence of fractures in patients treated with these drug, compared to those treated with tamoxifen (11% vs 8%).Osteopenia induced by aromatase inhibitors can be prevented by concomitant use of bisphosphonates (BIS), which can reduce bone loss due to induced menopause. It is essential to evaluate minimal changes in bone mass over time in order to monitor the effectiveness of the therapy. This can be done by means of dual energy absorptiometry (DEXA), relating these variations to the “least significant change” (LSC).Proper monitoring of bone mineral density in women on treatment with IAs and BIS is reliable only if always performed with the same equipment, in the same facility (even better when performed by the same technologist), provided that the LSC is maintained at the lowest achievable values.