Affect Bone Density Research Articles

The atypical anti-psychotic clozapine decreases bone mass in rats in vivo

Background Fracture risk is increased in patients with schizophrenia, who often receive long-term therapy with anti-psychotic drugs. The mechanisms by which skeletal fragility is increased in patients with psychosis include increased risk of falling, but direct skeletal toxicity of anti-psychotic drugs is a possibility that has not been investigated. Methods We examined the skeletal effects, in vivo and in vitro, of a typical anti-psychotic drug, haloperidol, which primarily inhibits dopaminergic signaling, and an atypical anti-psychotic drug, clozapine, which predominantly inhibits serotonergic signaling. Results In growing rats, 42 days of clozapine treatment reduced whole body bone mineral density by 15% (P < 0.01 vs vehicle), and trabecular and cortical bone volume, as assessed by microcomputed tomography, by 29% and 15%, respectively (P < 0.05 vs vehicle for each). Treatment with haloperidol did not affect bone density. Clozapine, but not haloperidol, transiently increased levels of serum corticosterone, and decreased levels of serum testosterone. In vitro, clozapine dose-dependently decreased osteoblast mitogenesis, osteoblast differentiation and osteoclastogenesis, while haloperidol did not affect any of these parameters. Conclusions These data demonstrate that clozapine, but not haloperidol, exerts adverse skeletal effects in rodents, and that this effect may be attributable to direct actions to reduce osteoblast growth and function. Long-term administration of clozapine may therefore negatively affect bone health, and clinical studies to investigate this possibility are warranted.

Association of Long-Term Proton Pump Inhibitor Therapy with Bone Fractures and Effects on Absorption of Calcium, Vitamin B12, Iron, and Magnesium

Proton pump inhibitors (PPI) are one of the most widely used classes of drugs. PPIs have a very favorable safety profile, and it is unusual for a patient to stop them because of side effects. However, with increasing numbers of patients chronically taking PPIs for gastroesophageal reflux disease and other common, persistent conditions, the long-term potential adverse effects are receiving increasing attention. An insufficiently studied area receiving much attention is the long-term effect of chronic acid suppression on the absorption of vitamins and nutrients. This increased attention results from the reported potential adverse effect of chronic PPI treatment leading to an increased occurrence of bone fractures. Interest in this area has led to examination of the effects of PPIs on calcium absorption/metabolism and numerous cohort, case-control, and prospective studies of their ability to affect bone density and cause bone fractures. In this article, these studies are systematically examined, as are studies of the effects of chronic PPI use on absorption of VB(12), iron, and magnesium. Studies in each area have led to differing conclusions, but when examined systematically, consistent results of several studies support the conclusion that long-term adverse effects on these processes can have important clinical implications.

Polymorphisms in the macrophage migration inhibitory factor gene and bone loss in postmenopausal women

Osteoporosis is a severe condition in postmenopausal women and a common cause of fracture. Osteoporosis is a complex disease with a strong genetic impact, but susceptibility is determined by many genes with modest effects and environmental factors. Only a handful of genes consistently associated with osteoporosis have been identified so far. Inflammation affects bone metabolism by interfering with the interplay between bone resorption and formation, and many inflammatory mediators are involved in natural bone remodeling. The cytokine macrophage migration inhibitory factor (MIF) has been shown to affect bone density in rodents, and polymorphisms in the human MIF promoter are associated with inflammatory disorders such as rheumatoid arthritis. We investigated the association of polymorphisms in the MIF gene with bone mineral density (BMD) and bone loss in 1002 elderly women using MIF promoter polymorphisms MIF-CATT 5 – 8 and rs755622(G/C) located −794 and −173 bp upstream of the transcriptional start site. Bone loss was estimated both by the change in BMD over 5 years and by the levels of bone resorption markers in serum measured at four occasions during a 5-year period. The MIF-CATT 7/rs755622(C) haplotype was associated with increased rate of bone loss during 5 years at the femoral neck ( p < 0.05) and total hip ( p < 0.05). In addition, the MIF-CATT 7/rs755622(C) haplotype carriers had higher levels of the bone turnover marker serum C-terminal cross-linking telopeptide of type I collagen (S-CTX-I, p < 0.01) during the 5 year follow-up period. There was no association between MIF-CATT 7/rs755622(C) and baseline BMD at femoral neck, total hip or lumbar spine. We conclude that MIF promoter polymorphisms have modest effects on bone remodeling and are associated with the rate of bone loss in elderly women.

Low bone mineral density is related to atherosclerosis in postmenopausal Moroccan women.

BackgroundSome studies have implicated several possible metabolic linkages between osteoporosis and vascular calcification, including estrogen deficiency, vitamin D excess, vitamin K deficiency and lipid oxidation products. Nevertheless, it remains unclear whether osteoporosis and atherosclerosis are related to each other or are independent processes, both related to aging. The aim of this cross-sectional study was to evaluate the correlation between arterial thickening and bone status in a sample of apparently healthy Moroccan women.MethodsSeventy-two postmenopausal women were studied. All patients were without secondary causes that might affect bone density. Bone status was assessed by bone mineral density (BMD) in lumbar spine and all femoral sites. Arterial wall thickening was assessed by intima-media thickness (IMT) in carotid artery (CA) and femoral artery (FA). Prevalent plaques were categorized into four groups ranging from low echogenicity to high echogenicity.ResultsThe mean age was 59.2 ± 8.3 years. 84.7% had at least one plaque. By Spearman Rank correlation, CA IMT was negatively correlated to Femoral total BMD (r = -0.33), Femoral neck BMD (r = -0.23), Ward triangle BMD (r = -0.30) and Trochanter BMD (r = -0.28) while there was no association with lumbar BMD. In multiple regression analysis, CA IMT emerged as an independent factor significantly associated with all femoral sites BMD after adjusting of confounding factors. FA IMT failed to be significantly associated with both Femoral and Lumbar BMD. No significant differences between echogenic, predominantly echogenic, predominantly echolucent and echolucent plaques groups were found concerning lumbar BMD and all femoral sites BMDConclusionOur results demonstrate a negative correlation between bone mineral density (BMD) qnd carotid intima-media thickness (IMT) in postmenopausal women, independently of confounding factors. We suggest that bone status should be evaluated in patients with vascular disease to assess whether preventive or therapeutic intervention is necessarry.

Diet Calcium Level but Not Calcium Supplement Particle Size Affects Bone Density and Mechanical Properties in Ovariectomized Rats ,

Calcium (Ca) supplements, especially Ca carbonate (CaCO3), are the main alternative sources of dietary Ca and an important part of a treatment regimen for osteoporosis, the most common metabolic bone disorder of aging and menopause. In a female ovariectomized (OVX) rat model for studying postmenopausal osteoporosis, we tested the hypothesis that a small compared with a large particle size of CaCO3 (13.0- vs. 18.5-μm geometric diameter) would result in increased Ca balance and subsequently bone mass and that this would be affected by dietary Ca level. We used 6-mo-old rats that were OVX either at 6 or 3 mo of age as models of early or stable menopausal status, respectively. The rats received semipurified diets that contained either 0.4 or 0.2% dietary Ca provided from CaCO3 of 2 particle sizes. A group of Sham-operated rats with intact ovaries served as control and were fed 0.4% dietary Ca from large particles. Estrogen deficiency as a result of ovariectomy had an adverse effect on bone density, mineral content, and bone mechanical properties (P < 0.001). Reducing dietary Ca from 0.4 to 0.2% resulted in significant adverse effects on bone density and mechanical properties (P < 0.001). The particle size of CaCO3 did not affect total Ca balance, bone dual energy X-ray absorptiometry and peripheral quantitative computed tomography indices, bone ash and Ca content, or the mechanical determinants of bone strength. We conclude that a decrease in particle size of CaCO3 to 70% of that typically found in Ca supplements does not provide a benefit to overall Ca metabolism or bone characteristics and that the amount of Ca consumed is of greater influence in enhancing Ca nutrition and skeletal strength.

Lateral bone density variations in the scoliotic spine

Adolescent Idiopathic Scoliosis (AIS) is the most common deformity of the spine, affecting 2–4% of the population. Previous studies have shown that the vertebrae in scoliotic spines undergo abnormal shape changes, however there has been little exploration of how scoliosis affects bone density distribution within the vertebrae. In this study, existing CT scans of 53 female idiopathic scoliosis patients with right-sided main thoracic curves were used to measure the lateral (right to left) bone density profile at mid-height through each vertebral body. Five key bone density profile measures were identified from each normalized bone density distribution, and multiple regression analysis was performed to explore the relationship between bone density distribution and patient demographics (age, height, weight, body mass index (BMI), skeletal maturity, time since Menarche, vertebral level, and scoliosis curve severity). Results showed a marked convex/concave asymmetry in bone density for vertebral levels at or near the apex of the scoliotic curve. At the apical vertebra, mean bone density at the left side (concave) cortical shell was 23.5% higher than for the right (convex) cortical shell, and cancellous bone density along the central 60% of the lateral path from convex to concave increased by 13.8%. The centre of mass of the bone density profile at the thoracic curve apex was located 53.8% of the distance along the lateral path, indicating a shift of nearly 4% toward the concavity of the deformity. These lateral bone density gradients tapered off when moving away from the apical vertebra. Multi-linear regressions showed that the right cortical shell peak bone density is significantly correlated with skeletal maturity, with each Risser increment corresponding to an increase in mineral equivalent bone density of 4–5%. There were also statistically significant relationships between patient height, weight and BMI, and the gradient of cancellous bone density along the central 60% of the lateral path. Bone density gradient is positively correlated with weight, and negatively correlated with height and BMI, such that at the apical vertebra, a unit decrease in BMI corresponds to an almost 100% increase in bone density gradient.

Factors that affect bone density in premenopausal women

Factors that affect bone density in premenopausal women

Osteoporosis and Cardiovascular Risk Among Premenopausal Women in Sri Lanka

We examined the association between bone mineral density (BMD) and cardiovascular risk in a group of premenopausal women selected from the Southern province of Sri Lanka. One hundred six previously healthy premenopausal volunteers (aged 30–54 yr) were recruited by open invitations. Subjects with previous history of diabetes, hypertension, epilepsy, chronic renal or liver disease, hyperlipidemia, ischemic heart disease, endocrine diseases, or prolonged inflammatory conditions were excluded. Subjects who were taking medications that can affect bone density, blood sugar, serum lipids, or blood pressure (BP) were also excluded. Women with the history of previous fractures were not excluded. BMDs in the spine, hip, and total body (TB) were measured using a Hologic Discovery scanner (Hologic Inc, Bedford, MA). BP, fasting glucose, and fasting lipids were also measured. Independent of body mass index (BMI) and age, TB bone mineral content (BMC) and spine BMD showed inverse and significant correlations with total cholesterol (TC), low density cholesterol, and the ratio between TC and high density lipoprotein cholesterol ( r ranged from −0.24 to −0.27, p < 0.05 for all). The highest mean lipid levels were seen among the women in the lowest third of spine BMD, whereas women in the upper third of spine BMD had the lowest lipid levels. The number of women with metabolic syndrome in the 3 tirtiles of spine BMD was not significantly different. Fasting glucose or BP had no association with either BMD or BMC. In conclusion, our data demonstrates an association, independent of age and BMI, between BMD and BMC or lipid levels among previously healthy, premenopausal women. This may explain the high cardiovascular risk seen in women with osteoporosis in old age.

Osteoporosis in developing countries

Osteoporosis poses a huge challenge in developing countries due to demographic transition and aging of the population coupled with limited availability of resources. The exact disease burden is difficult to quantify because of the paucity of data. Ethnicity affects bone density as well as fracture risk. Population-specific normative data for bone density are lacking in large parts of the world. Vitamin D deficiency is common even in sunny countries. The WHO has developed an algorithm for estimation of 10-year fracture risk which may be used even in the absence of bone mineral density.

Body mass and composition affect bone density in recently diagnosed inflammatory bowel disease: The Manitoba IBD cohort study

This prospective study was undertaken to clarify the role of body mass and composition as a determinant of bone mineral density (BMD) in recently diagnosed inflammatory bowel disease (IBD). A nested subgroup of 101 adult subjects of the population-based Manitoba IBD Cohort Study were enrolled. Baseline BMD and body composition were measured and repeated 2.3 +/- 0.3 years later. Greater weight, height, and body mass measurements were positively correlated with bone density at all sites (P < 0.01). Although both fat tissue and lean tissue showed positive relationships with BMD, lean tissue showed a much stronger correlation than fat tissue, especially for the total hip (r = 0.66, P < 0.001 versus r = 0.23, P < 0.05) and total body measurements (r = 0.59, P < 0.001 versus r = 0.04, P NS). Increase (or decrease) in hip bone density was strongly associated with an increase (or decrease) in all body mass variables (r = 0.49-0.54, P < 0.001). Measures of body mass are important determinants of baseline BMD in recently diagnosed IBD patients. Furthermore, change in body mass is correlated with change in BMD, especially at the total hip. Early optimization and maintenance of nutrition and body weight, particularly toward lean tissue mass, may play an important role in preventing IBD-related bone disease.

Do gender and torus mandibularis affect mandibular cortical index? A cross-sectional study

BackgroundThe interactions between torus and several factors such as age, gender, and dental status have not been studied comprehensively. The purpose of this study was to determine the effect of gender on the mandibular cortical index (MCI) and to investigate a possible association between torus mandibularis (TM) and MCI.MethodsThe study consisted of 189 consecutive patients referred to Department of Oral Diagnosis and Radiology of Hacettepe University within 30 workdays. Patients who did not have systemic disorders affecting bone density were included; and the age, gender, dental status and existing TM of the patients were recorded. Morphology of the mandibular inferior cortex was determined according to Klemitti's classification on panoramic radiographs.ResultsMCI was affected by age and gender (P < 0.05). No significant relationship was found between TM and MCI (P > 0.05).ConclusionIn the study population, MCI was affected by age and gender. As age increased, semilunar defects could be seen on the cortex of the mandible and MCI values increased. Women appeared to have higher MCI values than men.

Relationship between body composition and bone mineral density in women with and without osteoporosis: relative contribution of lean and fat mass

To assess the relationship of total fat mass (TFM) and total lean mass (TLM) with bone mineral density (BMD) and bone mineral content (BMC), we studied 770 postmenopausal white women after total body measurements by dual-energy X-ray absorptiometry. Height-independent bone mineral density (HIBMD) was also tested. The effects of TFM and TLM on the dependent variables HIBMD, BMD, and BMC were assessed by the univariate general linear model (UGLM). Age, age at menopause, height, and bone area were entered in the models as controlling variables when appropriate. In the total population, TLM and TFM were associated with BMD, BMC, and HIBMD (P < 0.001). Taking the T-score cut-off as -2.5, women without (463) and with (307) osteoporosis were then tested separately. In nonosteoporotic women, TLM was significantly associated with BMD, BMC, and HIBMD (P < 0.001), while TFM was not. In osteoporotic women, both TLM and TFM were associated with BMD to the same extent (P < 0.05), but not with HIBMD. Women without osteoporosis were then tested according to whether their TFM/TLM fraction was less than or greater than 1. In those with TFM/TLM less than 1, both TLM (P < 0.001) and TFM (P < 0.01), tested separately, were associated with BMD and BMC, but not with HIBMD. When TLM and TFM were tested at the same time and assessed by the same UGLM, only TLM (P < 0.001) still affected these three bone parameters. In women with TFM/TLM greater than 1, testing the body components both separately and at the same time and using the UGLM showed that TFM affected both BMC and BMD (P < 0.05), while TLM did not. In conclusion, our data indicate that both TFM and TLM affect bone density, with different physiological/pathological conditions modulating this relationship.

TRAIL inhibits osteoclastic differentiation by counteracting RANKL‐dependent p27Kip1 accumulation in pre‐osteoclast precursors

Experimental evidences indicate that the TNF family member TNF-related apoptosis inducing ligand (TRAIL) might be involved in modulating osteoclastic differentiation. The ability of recombinant soluble TRAIL to affect bone density in vivo was evaluated by using 4-week-old mice subcutaneously (s.c.) injected with TRAIL for 8 days. TRAIL injection induced a significant increase of tibia trabecular thickness and total bone mass in 4-week-old mice, accompanied by a significant decrease of TRAP serum levels, without modulation of osteocalcin and osteoprotegerin (OPG). Parallel experiments performed in vitro showed that inhibition of osteoclastic differentiation, induced by treatment of human peripheral blood osteoclast precursors with TRAIL, was associated to inhibition of receptor activator of nuclear factor kappa B ligand (RANKL)-induced accumulation of p27(Kip1). The potential role of p27(Kip1) pathway in mediating the anti-osteoclastic activity of TRAIL was further suggested by in vitro gene knock-down experiments performed in osteoclast precursor cultures. Taken together, our data strongly suggest that recombinant TRAIL inhibits osteoclastogenesis by inducing the ubiquitin-mediated degradation of p27(Kip1).

Repositioning hip global region of interest borders affects bone density measurements

When manufacturing firms venture into services, they often do so either in reaction to deteriorating performance or to further enhance their financial position. While extant literature argues that firms are most likely to succeed with strategic change processes out of a healthy position, the majority of manufacturers have started their service maneuver in reaction to deteriorating performance. To date, no empirical studies examine whether a healthy financial situation is a necessary requirement for successful service transition. Drawing on configuration theory and employing qualitative comparative analysis, the present study demonstrates that an increasing focus on services can lead to success for both types of firms. However, depending on their financial situation, firms should tap different resource and knowledge sources to implement the service transition: Whereas healthy companies should focus on customers as a knowledge source, companies in an inferior financial situation need strong links with suppliers to turn their services transition into financial success.

Selective deletion of fibronectin in osteoblasts affects bone density

Objectives: Bone extracellular matrix consists mainly of collagen (90%), with fibronectin (FN) being found in only small amounts (<2%). In vitro data however have established an absolute requirement for FN for the assembly of collagen to take place. We therefore postulated a defect in matrix assembly that may affect bone density in mice in which FN is deleted in the osteoblasts.

Advances in endocrinology of aging research, 2005–2006

The purpose of this brief review is to highlight some of the more important advances in endocrinology of aging research over the past year. Four advances were chosen and briefly described. First, exploration of the early steps in the generation of the internal steroidal hormonal signal involved in lifespan extension via the insulin/IGF-like signaling pathway in the nematode by two research groups revealed that the product of cholestanoic acid derivatives metabolized by a cytochrome P-450-like protein activates a protein with homology to the mammalian nuclear receptor superfamily, a process strikingly similar to the steroid hormone signaling pathway documented in mammalian systems. Second is the discovery that sirtuins, proteins that regulate lifespan in model organisms, enhance pancreatic insulin secretion in mice following a glucose challenge, suggesting the potential to regulate mammalian lifespan through regulation of the insulin signaling pathway. Third, the newly discovered hormone klotho, which also plays a role in regulating lifespan, in this case in mice, is reported to not only negatively affect insulin sensitivity but, perhaps more importantly, significantly affects calcium and phosphate metabolism as a required cofactor of Fgf-23 signaling. Finally the gonadotropin FSH is shown to directly affect bone density in mice separate from any direct effect of estrogen, suggesting that reproductive hormones other than estrogen can directly impact menopause-associated pathophysiology in non-reproductive tissues.

The impact of clothing style on bone mineral density among post menopausal women in Morocco: a case-control study

BackgroundThe clothing style is an important factor that influences vitamin D production and thus bone mineral density. We performed a case-control study in order to evaluate the effect of veil wearing (concealing clothing) on bone mineral density in Moroccan post menopausal women.MethodsThe cases were osteoporotic women whose disease was assessed by bone mineral density measurement. Each patient was matched with a non osteoporotic woman for age, and body mass index. All our patients were without secondary causes or medications that might affect bone density. The veil was defined as a concealing clothing which covered most of the body including the arms, the legs and the head. This definition is this of the usual Moroccan traditional clothing style.Results178 post menopausal osteoporotic patients and 178 controls were studied. The mean age of the cases and the controls was 63.2 years (SD 7) and the mean body mass index was 32.1 (SD 8). The results of crude Odds Ratios analyses indicated that wearing a veil was associated with a high risk of osteoporosis: OR 2.29 (95% CI, 1.38–3.82). Multiparity or a history of familial peripheral osteoporotic fractures had also a significant effect on increasing the osteoporosis risk (ORs: 1.87 (95% CI, 1.05–3.49) and 2.01 (95% CI, 1.20–3.38)). After a multiple regression analysis, wearing the veil and a history of familial osteoporotic fractures remained the both independent factors that increased the osteoporosis risk (ORs: 2.20 (95% CI, 1.22–3.9) and 2.19 (95% CI, 1.12–4.29) respectively).Conclusionour study suggested that in Moroccan post menopausal women, wearing a traditional concealing clothing covering arms, legs and head increased the risk of osteoporosis. Further studies are required to evaluate the clinical impact of the above findings and to clarify the status of vitamin D among veiled women in Morocco.

Does individual response to androgen replacement therapy affect bone density?

Does individual response to androgen replacement therapy affect bone density?

Densidade óssea de frangos de corte alimentados com diferentes níveis de aminoácidos e cálcio durante a fase final de criação

Two experiments were carried out aiming at evaluating the effects of different dietary amino acid and calcium profiles on bone characteristics of two chicken strains (Avian Farms and Cobb) from 42 to 49 days of age. At the end of each experiment, two chickens of each replication were sacrificed and their tibiae were collected for analysis of bone characteristics: bone measurements (weight, length and thickness of the compact and spongy layers) and bone density (bone density). A total of 540 birds were used in each experiment, divided into fully randomized blocks with a 3 x 2 factorial scheme, that is, three amino acid profiles (methionine, lysine and threonine – 100, 125 and 150% of NRC recommendations, 1994) and two calcium levels (75 and 100% of NRC recommendations, 1994), with 30 birds per replication. There were not interactions between the two factors. The amino acid or calcium levels did not affect bone density and tibia variables in both strains.

Effect of Korean Oriental Medicine Extract on Bone Mass as Compared with Alendronate in Ovariectomized Rats

A number of alternative medicines (AMs) have often been used as traditional therapies for various diseases without scientific or clinical evidence supporting their use. The present study examined the pharmaceutical effects of an AM extract with a long history of use as a traditional medicine for various bone diseases. To evaluate it as a potential candidate for use as an anti-osteoporotic drug, we investigated the effects of the AM extract on the progression of bone loss in ovariectomized (OVX) rats fed a calcium (Ca)-deficient diet for 4 or 12 weeks. We also compared the AM extract with alendronate, an anti-resorptive drug. The AM extract did not influence bone turnover as indicated by biochemical markers [i.e., deoxypyridinoline (DPD)]. In contrast, alendronate treatment seemed to reduce bone turnover via inhibition of bone resorption as evidenced by reduced urinary DPD concentrations accompanied by a tendency for decreased serum tartrate-resistant acid phosphatase. Administration of alendronate or AM extracts did not significantly affect bone density, although both tended to increase bone mineral density (BMD) and bone strength of the femur. Although both treatments did not affect vertebral BMD and bone strength, histological analysis of vertebrae showed well-developed trabecular networking in OVX rats treated with alendronate or AM extract, in contrast to the thin and disconnected trabecule in OVX rats. In conclusion, the AM extract produced a very weak effect on the prevention of bone loss induced by OVX and Ca deficiency in rats, but was similar to the results observed with alendronate. Further verification is necessary to justify the use of the AM extract as a treatment for osteoporosis.