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Bone Loss (bone + loss)
Kinds of Bone Loss Selected AbstractsBiochemical Markers of Bone Turnover, Hip Bone Loss, and Fracture in Older Men: The MrOS Study,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2009Douglas C Bauer Abstract We used data from the Osteoporotic Fractures in Men (MrOS) study to test the hypothesis that men with higher levels of bone turnover would have accelerated bone loss and an elevated risk of fracture. MrOS enrolled 5995 subjects >65 yr; hip BMD was measured at baseline and after a mean follow-up of 4.6 yr. Nonspine fractures were documented during a mean follow-up of 5.0 yr. Using fasting serum collected at baseline and stored at ,190°C, bone turnover measurements (type I collagen N-propeptide [PINP]; , C-terminal cross-linked telopeptide of type I collagen [,CTX]; and TRACP5b) were obtained on 384 men with nonspine fracture (including 72 hip fractures) and 947 men selected at random. Among randomly selected men, total hip bone loss was 0.5%/yr among those in the highest quartile of PINP (>44.3 ng/ml) and 0.3%/yr among those in the lower three quartiles (p = 0.01). Fracture risk was elevated among men in the highest quartile of PINP (hip fracture relative hazard = 2.13; 95% CI: 1.23, 3.68; nonspine relative hazard = 1.57, 95% CI: 1.21, 2.05) or ,CTX (hip fracture relative hazard = 1.76, 95 CI: 1.04, 2.98; nonspine relative hazard = 1.29, 95% CI: 0.99, 1.69) but not TRACP5b. Further adjustment for baseline hip BMD eliminated all associations between bone turnover and fracture. We conclude that higher levels of bone turnover are associated with greater hip bone loss in older men, but increased turnover is not independently associated with the risk of hip or nonspine fracture. [source] Impaired Energetic Metabolism After Central Leptin Signaling Leads to Massive Appendicular Bone Loss in Hindlimb-Suspended Rats,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2008Aline Martin Abstract We previously showed in rats that the leptin effects on bone were dose dependent. Positive effects were observed when serum leptin concentration was in a physiological range. In contrast, important increases in serum leptin levels led to negative effects on bone formation similar to those reported after intracerebroventricular leptin administration in mice. To clarify whether leptin effects on bone depend on administration route and/or animal model, female rats were hindlimb unloaded or not and treated either with intracerebroventricular infusion of leptin or vehicle for 14 days. By increasing cerebrospinal fluid (CSF) leptin concentration, intracerebroventricular infusion of leptin significantly reduced food intake and consequently body weight, abdominal fat, and lean mass of the animals. Leptin infusion inhibited bone elongation over the 14 days and blunted cortical bone thickening at the femoral diaphysis site. Interestingly, leptin effects were site dependent in the cancellous bone envelopes, because tibia metaphysis BMD was lower and lumbar spine BMD was higher under intracerebroventricular leptin. Treated groups showed reduced bone remodeling independently of hindlimb unloading. Multiple downstream pathways were implicated in the mediation of these negative leptin effects on bone including not only stimulation of the sympathetic nervous system but also a decrease in somatotropic axis activity. Therefore, the intracerebroventricular leptin-induced bone loss could be largely related to the concurrent alteration of energetic and metabolic status. In summary, our study supports the hypothesis of a concentration-dependent balance between peripheral and central control of leptin on bone. [source] Bone Loss, Weight Loss, and Weight Fluctuation Predict Mortality Risk in Elderly Men and WomenJOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2007Nguyen D Nguyen Abstract Low baseline BMD, rate of BMD loss, weight loss, and weight fluctuation are significant predictors of all-cause mortality in elderly men and women, independent of each other and of age, incident fracture, and concomitant diseases. Introduction: Although low BMD has been shown to be associated with mortality in women, the effect of BMD is affected by weight and weight change and the contribution of these factors to mortality risk, particularly in men, is not known. This study examined the association between baseline BMD, rate of bone loss, weight loss, and weight fluctuation and all-cause mortality risk in elderly men and women. Materials and Methods: Data from 1059 women and 644 men, ,60 years of age (as of 1989), of white background who participated in the Dubbo Osteoporosis Epidemiology Study were analyzed. All-cause mortality was recorded annually between 1989 and 2004. BMD at the femoral neck was measured by DXA (GE-LUNAR) at baseline and at approximately every 2 yr afterward. Data on incident osteoporotic fractures and concomitant diseases, including cardiovascular diseases, all types of cancer, and type I/II diabetes mellitus, was also recorded. Results: In the multivariable Cox's proportional hazards model with adjustment for age, incident fractures, and concomitant diseases, the following variables were independent risk factors of all-cause mortality in men: rate of BMD loss of at least 1%/yr, rate of weight loss of at least 1%/yr, and weight fluctuation (defined by the CV) of at least 3%. In women, in addition to the significant factors observed in men, lower baseline BMD was also an independent risk factor of mortality. In both sexes, baseline weight was not an independent and significant predictor of mortality risk. Approximately 36% and 22% of deaths in women and men, respectively, were attributable to the four risk factors. Conclusions: These data suggest that, although low BMD was a risk factor of mortality in women, it was not a risk factor of mortality in men. However, high rates of BMD loss, weight loss, and weight fluctuation were also independent predictors of all-cause mortality in elderly men and women, independent of age, incident fracture, and concomitant diseases. [source] Dendritic Cells at the Osteo-Immune Interface: Implications for Inflammation-Induced Bone Loss,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2007Mawadda Alnaeeli Abstract Within the past decade, the critical roles of T cells and T cell,mediated immunity in inflammation-induced osteoclastogenesis and subsequent bone loss have been extensively studied, thereby establishing the new paradigm of osteoimmunology. Therefore, dendritic cells (DCs), the most potent antigen-presenting cells, responsible for activation of naïve T cells and orchestration of the immune response, became critically situated at the osteo-immune interface. Today, emerging new evidence suggests that DC may be directly involved in inflammation-induced osteoclastogenesis and bone loss, by acting as osteoclast (OC) precursors that can further develop into DC-derived OCs (DDOC) under inflammatory conditions. These findings have tremendous implications, because in addition to DC's important roles in regulating innate and adaptive immunity, a direct contribution by these cells to inflammation-induced bone loss may provide a promising therapeutic target not only for controlling inflammation but also for modulating bone destruction. [source] Osteoblast Deletion of Exon 3 of the Androgen Receptor Gene Results in Trabecular Bone Loss in Adult Male Mice,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2007Amanda J Notini Abstract The mechanism of androgen action on bone was studied in male mice with the AR deleted in mature osteoblasts. These mice had decreased trabecular bone volume associated with a decrease in trabecular number, suggesting that androgens may act directly on osteoblasts to maintain trabecular bone. Introduction: Androgens modulate bone cell activity and are important for the maintenance of bone mass. However, the mechanisms by which they exert these actions on bone remain poorly defined. The aim of this study was to investigate the role of androgens acting through the classical androgen receptor (AR) signaling pathways (i.e., DNA-binding dependent pathways) in osteoblasts using male mice in which exon 3 of the AR gene was deleted specifically in mature osteoblasts. Materials and Methods: Mice with a floxed exon 3 of the AR gene were bred with Col 2.3-cre transgenic mice, in which Cre recombinase is expressed in mineralizing osteoblasts. The skeletal phenotype of mutant mice was assessed by histomorphometry and quantitative ,CT at 6, 12, and 32 weeks of age (n = 8 per group). Wildtype, hemizygous exon 3 floxed and hemizygous Col 2.3-cre male littermates were used as controls. Data were analyzed by one-way ANOVA and Tukey's posthoc test. Results: ,CT analysis of the fifth lumbar vertebral body showed that these mice had reduced trabecular bone volume (p < 0.05) at 32 weeks of age compared with controls. This was associated with a decrease in trabecular number (p < 0.01) at 12 and 32 weeks of age, suggesting increased bone resorption. These effects were accompanied by a reduction in connectivity density (p < 0.01) and an increase in trabecular separation (p < 0.01). A similar pattern of trabecular bone loss was observed in the distal femoral metaphysis at 32 weeks of age. Conclusions: These findings show that inactivation of the DNA binding,dependent functions of the AR, specifically in mature osteoblasts in male mice, results in increased bone resorption and decreased structural integrity of the bone, leading to a reduction in trabecular bone volume at 32 weeks of age. These data provide evidence of a role for androgens in the maintenance of trabecular bone volume directly through DNA binding,dependent actions of the AR in mature osteoblasts. [source] Accentuated Ovariectomy-Induced Bone Loss and Altered Osteogenesis in Heterozygous N-Cadherin Null Mice,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2006Chung Fang Lai Abstract Ovariectomy-induced bone loss is accentuated in mice with germline Cdh2 haploinsufficiency, the result of a decreased osteoblastogenesis in the face of normal osteoclast number. Reduced N-cadherin abundance in these mice decreases cell,cell adhesion and alters signaling pathways important for osteoblast commitment and differentiation, thus providing in vivo evidence that N-cadherin,mediated cell,cell interactions are involved in homeostatic responses to increased bone remodeling. Introduction: We have shown that targeted expression of a dominant negative truncated form of N-cadherin (Cdh2) delays acquisition of peak bone mass in mice and retards osteoblast differentiation. We tested the role of this molecule in the skeletal homeostatic response to ovariectomy in mice with germline Cdh2 haploinsufficiency. Materials and Methods: Heterozygous Cdh2 null (Cdh2+/,) and wildtype mice were ovariectomized and followed up to 13 weeks by in vivo radiodensitometric and ex vivo histologic assessment of bone mass and turnover. Cells isolated from wildtype and Cdh2+/, mice were used to determine the alterations in bone cell function produced by partial loss of N-cadherin. Results: Bone mass was not significantly different between Cdh2+/, and wildtype littermates, but on ovariectomy, bone loss in Cdh2+/, mice was initially slower, but with time it became significantly greater than in wildtype mice. This accentuated bone loss was associated with lower osteoblast number and serum osteocalcin levels, with no differences in bone resorption. Although development of calcified nodules was faster in calvaria cells isolated from Cdh2+/, mice relative to Cdh2+/+ cells, bone marrow osteogenic precursors were lower in the former than in the latter genotypes. Cdh2 expression was downregulated with differentiation in wildtype calvaria cells, whereas cadherin-11 abundance remained unchanged. Furthermore, cell,cell adhesion (postconfluence) was decreased among heterozygous calvaria cells, as was cell proliferation (preconfluence), relative to wildtype cells. Finally, the abundance and cellular distribution of ,-catenin was minimally decreased in Cdh2+/, cells, whereas mitogen-activated protein kinase (MAPK) signaling was more active in Cdh2 insufficient cells. Conclusions:Cdh2 is involved in the homeostatic bone formation response to ovariectomy, presumably by regulating osteoprogenitors number and differentiation through stabilization of cell,cell adhesion and/or signaling modulation. [source] Perspective: On Genetic Studies of Bone Loss,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2006Fang Yang No Abstracts. [source] Ovariectomy-Induced Bone Loss Varies Among Inbred Strains of Mice,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2005Mary L Bouxsein PhD Abstract There is a subset of women who experience particularly rapid bone loss during and after the menopause. However, the factors that lead to this enhanced bone loss remain obscure. We show that patterns of bone loss after ovariectomy vary among inbred strains of mice, providing evidence that there may be genetic regulation of bone loss induced by estrogen deficiency. Introduction: Both low BMD and increased rate of bone loss are risk factors for fracture. Bone loss during and after the menopause is influenced by multiple hormonal factors. However, specific determinants of the rate of bone loss are poorly understood, although it has been suggested that genetic factors may play a role. We tested whether genetic factors may modulate bone loss subsequent to estrogen deficiency by comparing the skeletal response to ovariectomy in inbred strains of mice. Materials and Methods: Four-month-old mice from five inbred mouse strains (C3H/HeJ, BALB/cByJ, CAST/EiJ, DBA2/J, and C57BL/6J) underwent ovariectomy (OVX) or sham-OVX surgery (n = 6-9/group). After 1 month, mice were killed, and ,CT was used to compare cortical and trabecular bone response to OVX. Results: The effect of OVX on trabecular bone varied with mouse strain and skeletal site. Vertebral trabecular bone volume (BV/TV) declined after OVX in all strains (,15 to ,24%), except for C3H/HeJ. In contrast, at the proximal tibia, C3H/HeJ mice had a greater decline in trabecular BV/TV (,39%) than C57BL/6J (,18%), DBA2/J (,23%), and CAST/EiJ mice (,21%). OVX induced declines in cortical bone properties, but in contrast to trabecular bone, the effect of OVX did not vary by mouse strain. The extent of trabecular bone loss was greatest in those mice with highest trabecular BV/TV at baseline, whereas cortical bone loss was lowest among those with high cortical bone parameters at baseline. Conclusions: We found that the skeletal response to OVX varies in a site- and compartment-specific fashion among inbred mouse strains, providing support for the hypothesis that bone loss during and after the menopause is partly genetically regulated. [source] An Uncoupling Agent Containing Strontium Prevents Bone Loss by Depressing Bone Resorption and Maintaining Bone Formation in Estrogen-Deficient RatsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2005Pierre J. Marie Ph.D. Trabecular bone loss in estrogen deficiency is associated with enhanced bone resorption with a smaller increase in bone formation. We previously reported that low doses of strontium can increase trabecular bone volume in rodents by affecting bone resorption and formation. In this study we determined the effect of a new divalent strontium salt (S12911) on bone loss induced by E2 deficiency. Sprague-Dawley female rats (230 g, n = 15,25 per group) were sham operated or ovariectomized (OVX) and treated with 17,-estradiol (E2, 10 ,g/kg/day, sc) or S12911 by gavage at the dose of 77, 154, or 308 mg/kg/day or the vehicle. Treatment for 60 days with S12911 resulted in a dose-dependent increase in plasma, urine, and bone strontium concentrations without any deleterious effect on total or skeletal growth. OVX rats were osteopenic compared to sham rats as shown by decreased femoral dry bone weight and mineral content measured on bone ash and by DXA. Treatment of OVX rats with S12911 prevented bone loss as bone ash and bone mineral content were restored to the values in sham rats. Trabecular bone volume measured by histomorphometry on the tibial metaphysis was decreased by 46% in OVX rats and was corrected by E2. Treatment of OVX rats with S12911 increased the trabecular bone volume by 30,36%. Histomorphometric indices of bone resorption (osteoclast surface and number) were increased in OVX rats and were reduced by S12911 to the levels in sham rats. In contrast to this inhibitory effect on bone resorption, the osteoid surface, osteoblast surface, mineral apposition rate, and bone formation rate were as high in OVX rats treated with S12911 as in untreated OVX rats. In addition, plasma osteocalcin (OC) and alkaline phosphatase (ALP) levels remained elevated or were further increased in OVX rats treated with S12911. In contrast, treatment with E2 reduced both bone resorption and formation and plasma ALP and OC to the levels in sham rats. The data indicate that the divalent strontium salt S12911 is acting as an uncoupling agent that can prevent the femoral osteopenia and partially prevent the trabecular bone loss in E2-deficient rats by inhibiting bone resorption without reducing bone formation. [source] Management of Bone Loss After Organ Transplantation,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2004Adi Cohen Organ transplant recipients experience rapid bone loss and high fracture rates, particularly during the early post-transplant period. Early rapid bone loss occurs in the setting of uncoupled bone turnover with increased bone resorption and decreased bone formation. Because there are no clinical factors that reliably predict post-transplant bone loss and fractures in the individual patient, all transplant recipients should be considered candidates for early preventive therapy for osteoporosis. Long-term transplant recipients with densitometric osteoporosis and/or fractures should also receive treatment. Although active metabolites of vitamin D and bisphosphonates have both shown efficacy, data from clinical trials suggest that bisphosphonates are the safest and most consistently effective agents for the prevention and treatment of post-transplantation osteoporosis in adults. Kidney transplant recipients represent a special population, and more research is needed to delineate the risks and benefits of treating bone disease in these patients. [source] Prevention of Postmenopausal Bone Loss by a Low-Magnitude, High-Frequency Mechanical Stimuli: A Clinical Trial Assessing Compliance, Efficacy, and Safety,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2004Clinton Rubin Abstract A 1-year prospective, randomized, double-blind, and placebo-controlled trial of 70 postmenopausal women demonstrated that brief periods (<20 minutes) of a low-level (0.2g, 30 Hz) vibration applied during quiet standing can effectively inhibit bone loss in the spine and femur, with efficacy increasing significantly with greater compliance, particularly in those subjects with lower body mass. Introduction: Indicative of the anabolic potential of mechanical stimuli, animal models have demonstrated that short periods (<30 minutes) of low-magnitude vibration (<0.3g), applied at a relatively high frequency (20,90 Hz), will increase the number and width of trabeculae, as well as enhance stiffness and strength of cancellous bone. Here, a 1-year prospective, randomized, double-blind, and placebo-controlled clinical trial in 70 women, 3,8 years past the menopause, examined the ability of such high-frequency, low-magnitude mechanical signals to inhibit bone loss in the human. Materials and Methods: Each day, one-half of the subjects were exposed to short-duration (two 10-minute treatments/day), low-magnitude (2.0 m/s2 peak to peak), 30-Hz vertical accelerations (vibration), whereas the other half stood for the same duration on placebo devices. DXA was used to measure BMD at the spine, hip, and distal radius at baseline, and 3, 6, and 12 months. Fifty-six women completed the 1-year treatment. Results and Conclusions: The detection threshold of the study design failed to show any changes in bone density using an intention-to-treat analysis for either the placebo or treatment group. Regression analysis on the a priori study group demonstrated a significant effect of compliance on efficacy of the intervention, particularly at the lumbar spine (p = 0.004). Posthoc testing was used to assist in identifying various subgroups that may have benefited from this treatment modality. Evaluating those in the highest quartile of compliance (86% compliant), placebo subjects lost 2.13% in the femoral neck over 1 year, whereas treatment was associated with a gain of 0.04%, reflecting a 2.17% relative benefit of treatment (p = 0.06). In the spine, the 1.6% decrease observed over 1 year in the placebo group was reduced to a 0.10% loss in the active group, indicating a 1.5% relative benefit of treatment (p = 0.09). Considering the interdependence of weight, the spine of lighter women (<65 kg), who were in the highest quartile of compliance, exhibited a relative benefit of active treatment of 3.35% greater BMD over 1 year (p = 0.009); for the mean compliance group, a 2.73% relative benefit in BMD was found (p = 0.02). These preliminary results indicate the potential for a noninvasive, mechanically mediated intervention for osteoporosis. This non-pharmacologic approach represents a physiologically based means of inhibiting the decline in BMD that follows menopause, perhaps most effectively in the spine of lighter women who are in the greatest need of intervention. [source] Disorders Associated With Acute Rapid and Severe Bone Loss,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2003Solomon Epstein We describe a constellation of bone diseases characterized by the common feature of acute, rapid, and severe bone loss accompanied by dramatic fracture rates. These disorders are poorly recognized, resulting mainly from systemic diseases, frailty, immobilization, and immunosuppressive drugs, such as glucocorticoids and the calcineurin inhibitors. The opportunity to prevent or treat fractures is commonly missed because they are often not detected. Ideally, patients need to be identified early and preventative therapy initiated promptly to avoid the rapid bone loss and fractures. The most effective therapy at present seems to be the bisphosphonates, particularly when bone resorption is predominant. However, more severe forms of bone loss that result from an osteoblastic defect and reduced bone formation may benefit potentially more from newer anabolic agents, such as recombinant human parathyroid hormone (rhPTH). [source] Tibolone Exerts Its Protective Effect on Trabecular Bone Loss Through the Estrogen ReceptorJOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2001A. G. H. Ederveen Abstract Tibolone (Org OD14) has estrogenic, progestogenic, and/or androgenic activity depending on the tissue. In postmenopausal women, tibolone prevents bone loss without stimulating the endometrium. Tibolone is effective in preventing trabecular bone loss from the peripheral and axial skeleton of young and old ovariectomized (OVX) rats by reducing bone turnover, that is, bone resorption, like estrogens. We evaluated the contribution of the various hormonal activities to tibolone's bone-conserving effect. Three-month-old OVX rats received tibolone (125 ,g/rat or 500 ,g/rat, twice daily), alone or combined with an antiestrogen, antiandrogen, or antiprogestogen, and the effects on trabecular bone mass and bone turnover were evaluated. Sham-operated and control OVX groups were treated with vehicle. The remaining OVX groups received oral doses of tibolone twice daily, alone or with twice daily (a) antiestrogen ICI 164.384, (b) antiandrogen flutamide, or (c) antiprogestogen Org 31710. For comparison, the effects of 17,-estradiol and testosterone were examined also. After 4 weeks, trabecular bone mineral density (BMD) in the distal femur, plasma osteocalcin, and urinary deoxypyridinoline/creatinine ratio (Dpyr/Cr) were measured. Tibolone or 17,-estradiol significantly blocked ovariectomy-induced loss of trabecular BMD and inhibited bone resorption and bone turnover as judged by reduced Dpyr/Cr ratio and osteocalcin, respectively. These effects of both compounds were counteracted by the antiestrogen. This suggests a major involvement of the estrogen receptor in the action of tibolone on bone metabolism. However, the antiandrogen and the antiprogestogen did not counteract the effects of tibolone, excluding a major role of the androgenic and progestogenic activities of tibolone in its action against trabecular bone loss. The results indicate that tibolone acts on bone almost entirely through activation of the estrogen receptor. [source] Female Estrogen Receptor ,,/, Mice Are Partially Protected Against Age-Related Trabecular Bone LossJOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2001Sara H. Windahl Abstract Recently, it has been shown that inactivation of estrogen receptor , (ER-,) by gene targeting results in increased cortical bone formation in adolescent female mice. To study the possible involvement of ER-, in the regulation of the mature skeleton, we have extended the analyses to include 1-year-old ER-, knockout mice (ER-,,/,). Male ER-,,/, mice did not express any significant bone phenotypic alterations at this developmental stage. However, the increase in cortical bone parameters seen already in the adolescent female ER-,,/, mice was maintained in the older females. The aged female ER-,,/, mice further exhibited a significantly higher trabecular bone mineral density (BMD) as well as increased bone volume/total volume (BV/TV) compared with wild-type (wt) mice. This was caused by a less pronounced loss of trabecular bone during adulthood in female ER-,,/, mice. The growth plate width was unaltered in the female ER-,,/, mice. Judged by the expression of the osteoclast marker tartrate-resistant acid phosphatase (TRAP) and cathepsin K (cat K; reverse-transcription-polymerase chain reaction [RT-PCR]) as well as the serum levels of C-terminal type I collagen cross-linked peptide, bone resorption appeared unaffected. However, an increase in the messenger RNA (mRNA) expression levels of the osteoblast marker core-binding factor ,1 (Cbfa1) suggested an anabolic effect in bones of old female ER-,,/, mice. In addition, the mRNA expression of ER-, was augmented, indicating a role for ER-, in the development of this phenotype. Taken together, the results show that ER-, is involved in the regulation of trabecular bone during adulthood in female mice and suggest that ER-, acts in a repressive manner, possibly by counteracting the stimulatory action of ER-, on bone formation. [source] Mice Lacking the Plasminogen Activator Inhibitor 1 Are Protected from Trabecular Bone Loss Induced by Estrogen DeficiencyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2000E. Daci Abstract Bone turnover requires the interaction of several proteases during the resorption phase. Indirect evidence suggests that the plasminogen activator/plasmin pathway is involved in bone resorption and turnover, and recently we have shown that this cascade plays a role in the degradation of nonmineralized bone matrix in vitro. To elucidate the role of the plasminogen activator inhibitor 1 (PAI-1) in bone turnover in vivo, bone metabolism was analyzed in mice deficient in the expression of PAI-1 gene (PAI-1,/,) at baseline (8-week-old mice) and 4 weeks after ovariectomy (OVX) or sham operation (Sham) and compared with wild-type (WT) mice. PAI-1 inactivation was without any effect on bone metabolism at baseline or in Sham mice. However, significant differences were observed in the response of WT and PAI-1,/, mice to ovariectomy. The OVX WT mice showed, as expected, decreased trabecular bone volume (BV/TV) and increased osteoid surface (OS/BS) and bone formation rate (BFR), as assessed by histomorphometric analysis of the proximal tibial metaphysis. In contrast, no significant change in any of the histomorphometric variables studied was detected in PAI-1,/, mice after ovariectomy. As a result, the OVX PAI-1,/, had a significantly higher BV/TV, lower OS/BS, lower mineral apposition rate (MAR) and BFR when compared with the OVX WT mice. However, a comparable decrease in the cortical thickness was observed in OVX PAI-1,/, and WT mice. In addition, the cortical mineral content and density assessed in the distal femoral metaphysis by peripheral quantitative computed tomography (pQCT), decreased significantly after ovariectomy, without difference between PAI-1,/, mice and WT mice. In conclusion, basal bone turnover and bone mass are only minimally affected by PAI-1 inactivation. In conditions of estrogen deficiency, PAI-1 inactivation protects against trabecular bone loss but does not affect cortical bone loss, suggesting a site-specific role for PAI-1 in bone turnover. [source] Biochemical Markers as Predictors of Rates of Bone Loss After MenopauseJOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2000A. Rogers Abstract Biochemical markers of bone turnover may correlate with rates of bone loss in a group of postmenopausal women, but it is uncertain how useful they are in predicting rates of bone loss in the individual. The aim of this study was to determine the value of measurements of biochemical markers for the prediction of rates of bone loss in the individual. We studied 60 postmenopausal women (ages, 49,62 years), 43 of whom had gone through a natural menopause 1,20 years previously and 17 of whom had undergone hysterectomy 3,22 years ago. Lumbar spine bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA) over 2,4 years. Bone formation markers (bone-specific alkaline phosphatase [ibAP] and amino terminal of type I collagen [PINP] and osteocalcin [OC]) were measured in serum. Bone resorption markers (N-telopeptide of type 1 collagen [NTx] and immunoreactive free deoxypyridinoline [iFDpd]) were measured in urine and corrected for creatinine (Cr). Rates of bone loss were calculated as percent change per year. We found significant negative correlations (Spearman rank) between all measured biochemical markers and rate of change in bone density with r values ranging from ,0.35 to ,0.52. When markers and rates of bone loss were divided into tertiles, prediction of bone loss in an individual was poor (, < 0.2). There was an exponential relationship between rate of bone loss and years since menopause (YSM) in the 43 women having a natural menopause (r2 = 0.44; p = 0.008) indicating higher rates of loss in the early postmenopausal period. Levels of NTx, iFDpd, and PINP also showed a significant negative correlation with YSM. We conclude that there is a strong relationship between rates of spinal bone loss and levels of bone turnover markers. Although this is a small study, the results also suggest that using DXA measurements of the lumbar spine as the "gold standard," it is not possible to use biochemical markers to predict rate of bone loss in the individual. [source] Making Rats Rise to Erect Bipedal Stance for Feeding Partially Prevented Orchidectomy-Induced Bone Loss and Added Bone to Intact RatsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2000Wei Yao Abstract The objectives of this study were to investigate the different effects on muscle mass and cancellous (proximal tibial metaphysis [PTM]) and cortical (tibial shaft [TX]) bone mass of sham-operated and orchidectomized (ORX) male rats by making rats rise to erect bipedal stance for feeding. Specially designed raised cages (RC) were used so that the rats had to rise to erect bipedal stance to eat and drink for 12 weeks. Dual-energy X-ray absorptiometry (DEXA) and peripheral quantitative computerized tomography (pQCT) were used to estimate the lean leg mass and bone mineral. Static and dynamic histomorphometry were performed on the triple-labeled undecalcified sections. We found that making the intact rats rise to erect bipedal stance for feeding increased muscle mass, cortical bone volume, and periosteal bone formation. Orchidectomy increased net losses of bone next to the marrow by increasing bone turnover. Making the ORX rats rise to erect bipedal stance increased muscle mass, partially prevented cancellous bone loss in the PTM, and prevented net cortical bone loss in TX induced by ORX by depressing cancellous and endocortical high bone turnover and stimulating periosteal bone formation. The bone-anabolic effects were achieved mainly in the first 4 weeks in the PTM and by 8 weeks in the TX. These findings suggested that making the rats rise to erect bipedal stance for feeding helped to increase muscle mass and cortical bone mass in the tibias of intact rats, increase muscle mass, and partially prevented cancellous and net cortical bone loss in ORX rats. [source] Protein Undernutrition-Induced Bone Loss Is Associated with Decreased IGF-I Levels and Estrogen DeficiencyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2000Patrick Ammann M.D. Abstract Protein undernutrition is a known factor in the pathogenesis of osteoporotic fracture in the elderly, but the mechanisms of bone loss resulting from this deficiency are still poorly understood. We investigated the effects of four isocaloric diets with varying levels of protein content (15, 7.5, 5, and 2.5% casein) on areal bone mineral density (BMD), bone ultimate strength, histomorphometry, biochemical markers of bone remodeling, plasma IGF-I, and sex hormone status in adult female rats. After 16 weeks on a 2.5% casein diet, BMD was significantly decreased at skeletal sites containing trabecular or cortical bone. Plasma IGF-I was decreased by 29,34% and no estrus sign in vaginal smear was observed. To investigate the roles of estrogen deficiency and protein undernutrition, the same protocol was used in ovariectomized (OVX) or sham-operated (SHAM) rats, pair-fed isocaloric diets containing either 15 or 2.5% casein. Trabecular BMD was decreased by either manipulation, with effects appearing to be additive. Cortical BMD was decreased only in rats on a low-protein diet. This was accompanied by an increased urinary deoxypyridinoline excretion without any change in osteocalcin levels, suggesting an uncoupling between resorption and formation. Isocaloric protein undernutrition decreased bone mineral mass and strength. This effect might be related to decreased plasma IGF-I and/or estrogen deficiency with a consequent imbalance in bone remodeling. [source] Alcohol-Induced Disruption of Endocrine SignalingALCOHOLISM, Issue 8 2007Martin J. J. Ronis This article contains the proceedings of a symposium at the 2006 ISBRA Meeting in Sydney Australia, organized and cochaired by Martin J. Ronis and Thomas M. Badger. The presentations were (1) Effect of Long-Term Ethanol Consumption on Liver Injury and Repair, by Jack R. Wands; (2) Alcohol-Induced Insulin Resistance in Liver: Potential Roles in Regulation of ADH Expression, Ethanol Clearance, and Alcoholic Liver Disease, by Thomas M. Badger; (3) Chronic Gestational Exposure to Ethanol Causes Brain Insulin and Insulin-Like Growth Factor Resistance, by Suzanne M de la Monte; (4) Disruption of IGF-1 Signaling in Muscle: A Mechanism Underlying Alcoholic Myopathy, by Charles H. Lang; (5) The Role of Reduced Plasma Estradiol and Impaired Estrogen Signaling in Alcohol-Induced Bone Loss, by Martin J. Ronis; and (6) Short-Term Influence of Alcohol on Appetite-Regulating Hormones in Man, by Jan Calissendorff. [source] Marginal Bone Loss at Implants: A Retrospective, Long-Term Follow-Up of Turned Brånemark System® ImplantsCLINICAL IMPLANT DENTISTRY AND RELATED RESEARCH, Issue 1 2009Odont Lic, Solweig Sundén Pikner DDS ABSTRACT Background: Lately, presence of progressive bone loss around oral implants has been discussed. Purpose: The aim of this study was to report in a large patient group with different prosthetic restorations marginal bone level and its change as measured in radiographs obtained from prosthesis insertion up to a maximum 20 years in service. Further, it also aimed to study the impact of gender, age, jaw, prosthetic restoration, and calendar year of surgery. Materials and Methods: Out of 1,716 patients recorded for clinical examination during 1999, 1,346 patients (78.4%) could be identified. A total of 640 patients (3,462 originally installed Brånemark System® implants, Nobel Biocare, Göteborg, Sweden) with a follow-up of ,5 years were included in the study, while patients with continuous overdentures and augmentation procedures were not. Distance between the fixture/abutment junction (FAJ) and the marginal bone level was recorded. Results: The number of implants with a mean bone level of ,3 mm below FAJ increased from 2.8% at prosthesis insertion to 5.6% at year 1, and 10.8% after 5 years. Corresponding values after 10, 15, and 20 years were 15.2, 17.2, and 23.5%, respectively. Implant-based bone loss was as a mean 0.8 mm (SD 0.8) after 5 years, followed by only minor average changes. Mean bone loss on patient level followed a similar pattern. Disregarding follow-up time, altogether 183 implants (107 patients) showed a bone loss ,3 mm from prosthesis insertion to last examination. Significantly larger bone loss was found the older the patient was at surgery and for lower jaw implants. Conclusions: Marginal bone support at Brånemark implants was with few exceptions stable over years. [source] Ovariectomy-Induced Bone Loss Varies Among Inbred Strains of Mice,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2005Mary L Bouxsein PhD Abstract There is a subset of women who experience particularly rapid bone loss during and after the menopause. However, the factors that lead to this enhanced bone loss remain obscure. We show that patterns of bone loss after ovariectomy vary among inbred strains of mice, providing evidence that there may be genetic regulation of bone loss induced by estrogen deficiency. Introduction: Both low BMD and increased rate of bone loss are risk factors for fracture. Bone loss during and after the menopause is influenced by multiple hormonal factors. However, specific determinants of the rate of bone loss are poorly understood, although it has been suggested that genetic factors may play a role. We tested whether genetic factors may modulate bone loss subsequent to estrogen deficiency by comparing the skeletal response to ovariectomy in inbred strains of mice. Materials and Methods: Four-month-old mice from five inbred mouse strains (C3H/HeJ, BALB/cByJ, CAST/EiJ, DBA2/J, and C57BL/6J) underwent ovariectomy (OVX) or sham-OVX surgery (n = 6-9/group). After 1 month, mice were killed, and ,CT was used to compare cortical and trabecular bone response to OVX. Results: The effect of OVX on trabecular bone varied with mouse strain and skeletal site. Vertebral trabecular bone volume (BV/TV) declined after OVX in all strains (,15 to ,24%), except for C3H/HeJ. In contrast, at the proximal tibia, C3H/HeJ mice had a greater decline in trabecular BV/TV (,39%) than C57BL/6J (,18%), DBA2/J (,23%), and CAST/EiJ mice (,21%). OVX induced declines in cortical bone properties, but in contrast to trabecular bone, the effect of OVX did not vary by mouse strain. The extent of trabecular bone loss was greatest in those mice with highest trabecular BV/TV at baseline, whereas cortical bone loss was lowest among those with high cortical bone parameters at baseline. Conclusions: We found that the skeletal response to OVX varies in a site- and compartment-specific fashion among inbred mouse strains, providing support for the hypothesis that bone loss during and after the menopause is partly genetically regulated. [source] Overweight Postmenopausal Women Lose Bone With Moderate Weight Reduction and 1 g/day Calcium Intake,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2005Claudia S Riedt Abstract Overweight postmenopausal women may be more susceptible to bone loss with weight reduction than previously studied obese women. The influence of energy restriction and Ca intake on BMD was assessed in 66 individuals. Weight reduction resulted in bone loss at several sites in women consuming 1 g Ca/day and was mitigated with higher calcium intake at 1.7 g/day. Introduction: Bone loss is associated with weight loss in obese postmenopausal women and can be prevented with calcium (Ca) supplementation. However, because bone loss caused by weight loss may be greater in overweight than obese women, it is not clear whether Ca supplementation is also beneficial in overweight women. Materials and Methods: We assessed the influence of caloric restriction at two levels of Ca intake on BMD and BMC in 66 overweight postmenopausal women (age, 61 ± 6 years; body mass index, 27.0 ± 1.8 kg/m2). Subjects completed either a 6-month energy-restricted diet (WL, n = 47) and lost 9.3 ± 3.9 % weight or maintained weight (WM; 1 g Ca/day, n = 19). Participants in the WL group were randomly assigned to either normal (1 g/day; WL NL-Ca) or high (1.7 g/day; WL Hi-Ca) Ca intake. Regional BMD and BMC were measured at baseline and after 6 months. Results: During normal Ca intake, trochanter BMD and BMC and total spine BMD were decreased more in WL than WM women (p < 0.05). The WL NL-Ca group lost more trochanter BMD (,4.2 ± 4.1%) and BMC (,4.8 ± 7.1%) than the WL Hi-Ca group (,1.4 ± 5.6% and ,1.1 ± 8.1%, respectively; p < 0.05). There were no significant changes in BMD or BMC at the femoral neck in any group. Weight loss correlated with trochanter BMD loss (r = 0.687, p < 0.001) in the WL NL-Ca group. Conclusion: Despite an intake of 1 g Ca/day, bone loss occurred at some sites because of weight loss. Calcium intake of 1.7 g/day will minimize bone loss during weight loss in postmenopausal overweight women. [source] ApoE Gene Polymorphisms, BMD, and Fracture Risk in Elderly Men and Women: The Rotterdam Study,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2004Mariette WCJ Schoofs Abstract To study the association between the ApoE gene polymorphism and osteoporosis, we performed an association study in 5857 subjects from the Rotterdam Study. We did not observe an association between the ApoE polymorphism and osteoporosis in this study, which is thus far the largest study on ApoE and osteoporosis. Introduction: The E4 allele of the E2, E3, E4 protein isoform polymorphism in the gene encoding apolipoprotein E (ApoE) has previously been associated with an increased fracture risk. We investigated the association between the ApoE polymorphism and BMD, bone loss, and incident fractures as part of the Rotterdam Study a prospective population-based cohort study of diseases in the elderly. Materials and Methods: The study population consisted of 5857 subjects (2560 men; 3297 women) for whom data on ApoE genotypes, confounding variables, and follow-up of nonvertebral fractures were available. Data on femoral neck and lumbar spine BMD were available for 4814 participants. Genotype analyses for bone loss (defined as annualized percent change in BMD at the hip and lumbar spine) and BMD were performed using ANOVA. Fractures were analyzed using a Cox proportional-hazards model and logistic regression. All relative risks were adjusted for age and body mass index. Results and Conclusions: The genotype distribution of the study population was in Hardy-Weinberg equilibrium (p = 0.98) and did not differ by gender. At baseline, mean BMD of the lumbar spine and femoral neck did not differ between the ApoE genotypes of men and women. Bone loss (mean follow-up, 2.0 years) did not differ by ApoE genotype for women and men. During a mean follow-up of 6.6 years, 708 nonvertebral fractures (198 hip fractures and 179 wrist fractures) and 149 incident vertebral fractures occurred. No consistent differences in the distribution of alleles could be observed between subjects with or without these fractures. Our data do not support the hypothesis that the ApoE4 risk allele is associated with BMD, increased bone loss, or an increased risk of osteoporotic fractures. [source] Stimulation of macrophage TNF, production by orthopaedic wear particles requires activation of the ERK1/2/Egr-1 and NF-,B pathways but is independent of p38 and JNKJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2008Michelle A. Beidelschies Bone loss that causes aseptic loosening of orthopedic implants is initiated by pro-inflammatory cytokines produced by macrophages in response to implant-derived wear particles. MAPK and NF-,B signaling pathways are activated by the particles; however, it is not clear which of the signaling pathways are important for the initial response to the wear particles and which are only involved at later steps in the process, such as osteoclast differentiation. Here, we show that the ERK1/2, p38, JNK, and NF-,B pathways are rapidly activated by the wear particles but that only the ERK1/2 and NF-,B pathways are required for the initial response to the wear particles, which include increases in TNF, promoter activity, TNF, mRNA expression, and secretion of TNF, protein. Moreover, ERK1/2 activation by wear particles is also required for increased expression of the transcription factor Egr-1 as well as Egr-1's ability to bind to and activate the TNF, promoter. These results, together with our previous studies of the PI3K/Akt pathway, demonstrate that wear particles coordinately activate multiple signaling pathways and multiple transcription factors to stimulate production of pro-inflammatory cytokines, such as TNF,. The current study also demonstrates that the signaling pathways are activated to a much greater extent by wear particles with adherent endotoxin than by "endotoxin-free" wear particles. These results, together with those demonstrating the requirement for ERK1/2/Egr-1 and NF-,B, show that activation of these signaling pathways is responsible for the ability of adherent endotoxin to potentiate cytokine production, osteoclast differentiation, and bone loss induced by wear particles. J. Cell. Physiol. 217: 652,666, 2008. © 2008 Wiley-Liss, Inc. [source] Hypoxia suppresses runx2 independent of modeled microgravityJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2004Christopher Ontiveros Bone loss is a consequence of skeletal unloading as seen in bed rest and space flight. Unloading decreases oxygenation and osteoblast differentiation/function in bone. Previously we demonstrated that simulation of unloading in vitro, by culturing differentiating mouse osteoblasts in a horizontal rotating wall vessel (RWV), results in suppressed expression of runx2, a master transcriptional regulator of osteoblast differentiation. However, the RWV is able to reproduce in a controlled fashion at least two aspects of disuse that are directly linked, model microgravity and hypoxia. Hypoxia in the RWV is indicated by reduced medium oxygen tension and increased expression of GAPDH and VEGF. To uncouple the role of model microgravity from hypoxia in suppressed runx2 expression, we cultured osteoblasts under modeled microgravity (oxygenated, horizontal RWV rotation), hypoxia (vertical RWV rotation), or both conditions (horizontal RWV rotation). The expression, DNA binding activity and promoter activity of runx2, was suppressed under hypoxic but not normoxic modeled microgravity RWV conditions. Consistent with a role for hypoxia in suppression of runx2, direct exposure to hypoxia alone is sufficient to suppress runx2 expression in osteoblasts grown in standard tissue culture plates. Taken together, our findings indicate that hypoxia associated with skeletal unloading could be major suppressor of runx2 expression leading to suppressed osteoblast differentiation and bone formation. © 2004 Wiley-Liss, Inc. [source] Periodontal conditions in patients with coronary heart disease: a case,control studyJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 3 2008Carin Starkhammar Johansson Abstract Aim: This study examined periodontal conditions in patients with coronary heart disease (CHD) and subjects with no history of CHD. Material and Methods: Participants were 161 patients (40,75) with severe angina pectoris (diagnosed as CHD by coronary angiography) who subsequently underwent percutaneous coronary intervention and 162 control subjects with no history of CHD. Periodontal status was recorded. Bone loss was determined on radiographs. Periodontal disease experience was classified into five groups according to Hugoson & Jordan. Results: Periodontal disease experience groups 4 and 5 were more common in the CHD group (25%) compared with the control group (8%). The mean bone level (the distance from the CEJ to the most coronal level of the alveolar bone) was 3.0±1.0 mm in CHD subjects and 2.6±0.8 mm in controls. CHD patients had significantly lower numbers of natural teeth, higher numbers of periodontal pockets 4,6-mm and higher bleeding on probing (%). In a stepwise regression analysis, the factor periodontal disease experience groups 4+5 gave an odds ratio of 5.74 (2.07,15.90) for having CHD after controlling for smoking and age. Conclusion: Severe periodontal disease expressed by several clinical and radiographic parameters was more prevalent among subjects with CHD than among controls. Analysis, the factor periodontal disease experience groups 4+5 gave an odds ratio of 5.74 (2.07,15.90) for having CHD after controlling for smoking and age. [source] Absence of a specific subgingival microflora in adults with Down's syndromeJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 11 2001W. Reuland-Bosma Abstract Background: Periodontal disease in Down's syndrome (DS) is generally characterized by a high degree of bone loss. Bone loss of 5 mm or more is observed in 70% of these subjects. Among DS subjects, considerable differences in disease progression occur. So far, no studies have been conducted in which specific properties of the subgingival microflora have been related to the condition observed. Aims: To investigate (1) the subgingival microflora in DS subjects and other mentally retarded (control) individuals which were matched to the utmost and (2) to investigate the subgingival microflora of a "low-risk" and a " high-risk" group formed in DS subjects. Material and Methods: 17 DS subjects and 17 control subjects were matched with respect to age, plaque level and bleeding on probing. In addition, the DS group was divided in a "low-risk" group (0,2 teeth lost due to periodontal disease n=6) and a "high-risk"group (6,13 teeth lost due to periodontal disease n=11). Prevalence and proportions of the putative periodontal pathogens Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Bacteroides forsythus, Peptostreptococcus micros, Fusobacterium nucleatum and Campylobacter rectus in the subgingival plaque were determined using anaerobic culture techniques. No differences in the prevalence of distinct suspected periodontopathic bacteria and bacterial subgingival composition between the DS group and the control group could be established. Also no differences in the prevalence of the seven investigated microbial species between the "low-risk" and the "high-risk" group were observed. Conclusions: Because of the lack of differences in microflora between the DS group and the control group, a specific effect of the microbiological composition in the periodontal status of subjects with DS can be excluded in this population. Host factors constitute the more likely explanation of the differences observed in DS. Zusammenfassung Basis: Die parodontale Erkrankung beim Down Syndrom (DS) ist allgemein durch einen hohen Grad von Knochenverlust charakterisiert. Knochenverlust von 5 mm und mehr wird bei 70% der Personen beobachtet. Unter den DS Personen bestehen beträchtliche Differenzen in der Erkrankungsprogression. Bis heute sind keine Studien durchgeführt worden, in welchen die spezifischen Eingenschaften der subgingivalen Mikroflora in Beziehung zu den Bedingungen beobachtet wurden. Ziele: Untersuchung (1) der subgingivalen Mikroflora bei DS Personen und anderen mental retardierten (Kontrollen) Personen, die zu einer größten gemischt wurden und (2) der subgingivalen Mikroflora von Gruppen mit "geringem Risiko" und Gruppen mit "hohem Risiko" bei DS Personen. Material und Methoden: 17 DS Personen mit 17 Kontrollpersonen wurden im Hinblick auf Alter, Plaquemenge und Blutung auf Provokation eingeteilt. Zusätzlich wurde die DS Gruppe in "geringes Risiko" (0,2 Zähne infolge von parodontaler Erkrankung verloren, n=6) und in "hohes Risiko" (6,13 Zähne infolge parodontaler Erkrankung verloren, n=11) eingeteilt. Das Vorkommen und die Relationen von putativen parodontalen Pathogenen Actinobacillus actinomycetemcomitants, Porphyromonas gingivalis, Prevotella intermedia, Bacteroides forsythus, Peptostreptococcus micros, Fusobacterium nucleatum und Campylobacter rectus in der subgingivalen Plaque wurden mit anaerober Kulturtechnik bestimmt. Ergebnisse: Es konnten keine Differenzen in der Prävalenz der bezeichneten parodontopathogenen Bakterien und der bakteriellen subgingivalen Zusammensetzung zwischen DS Gruppe und der Kontrollgruppe beobachtet werden. Auch zwischen der Gruppe "geringes Risiko" und "hohes Risiko" wurden keine Differenzen in der Prävalenz der 7 untersuchten Spezies beobachtet. Schlußfolgerungen: Weil keine Differenzen in der Mikroflora zwischen DS Gruppe und der Kontrollgruppe vorhanden sind, kann ein spezifischer Effekt der mikrobiologischen Zusammensetzung beim parodontalen Status der Personen mit DS in dieser Population ausgeschlossen werden. Für die Erklärung der Differenzen, die bei den DS Personen beobachtet werden, sind die Wirtsfaktoren mehr wahrscheinlich. Résumé Origine: La maladie parodontale lors du syndrôme de Down (DS) est généralement caractérisée par une importante perte osseuse. Cette perte osseuse atteint 5 mm ou plus chez 70% de ces malades. Parmi les sujets DS, des différences considérables dans la progression de cette maladie se manifestent. Aucune étude n'a encore été entreprise dans laquelle la microflore sous-gingivale a été mise en relation avec les conditions observées. But: Le but de cette étude a été (1) d'analyser la microflore sous-gingivale chez les sujets DS et d'autres retardés mentaux servant de contrôles et (2) mieux connaître la microflore sous-gingivale chez les groupes de patients DS avec faible et haut risques. Matériaux et méthodes: 17 sujets DS et 17 sujets contrôles ont été analysés de manière parallèle en fonction de l'âge, du niveau de plaque dentaire et du saignement au sondage. De plus, le groupe DS était scindé en deux sous-groupes: "petit risque" (0 à 2 dents perdues pour cause de maladie parodontale; n=6), et "haut risque" (6 à 13 dents perdues; n=11). La fréquence globale et les proportions de pathogènes parodontaux putatifs l'Actinobacillus actinomycetemcomitans, le Porphyromonas gingivalis, le Prevotella intermedia, le Bacteroides forsythus, le Peptostreptococcus micros, le Fusobacterium nucleatum et le Campylobacter rectus dans la plaque sous-gingivale ont été déterminés en utilisant des techniques de culture anaérobie. Résultats: Aucune différence dans la fréquence globlale de ces bactéries ni dans la composition de la flore sous-gingivale n'a été trouvée entre le groupe DS et le groupe contrôle. Il n'y avait également aucune différence entre les sous-groupes à faible et à haut risques. Conclusions: Parce qu'aucune différence n'a été décelée dans la microflore entre les groupes DS et contrôle, aucun effet spécifique de leur flore sous-gingivale ne pourrait être responsable; les facteurs de l'hôte constituent très vraisemblablement l'explication des différences observées chez les sujets DS. [source] Rehabilitation by means of osseointegrated implants in oral cancer patients with about four to six years follow-upJOURNAL OF ORAL REHABILITATION, Issue 3 2006J. SEKINE summary, This paper describes the reconstruction of mandibular defects in four oral cancer patients using iliac crest bone grafts and osseointegrated implants. In three patients, reconstructive surgery using a reconstruction plate and free forearm skin flap was performed following tumour and segmental mandibular resection. After 7,9 months, mandibular reconstruction with a free iliac bone graft was carried out. In one patient, reconstructive surgery was performed with vascularized iliac bone grafting with an anterolateral thigh flap at the same time as the tumour resection. Fixtures were placed in the transplanted bone, and abutments were connected 6,9 months later together with vestibuloplasty. Gingival grafts were used to replace the skin flap around abutments. All implants survived throughout the approximately 4,6 years observation time. Marginal bone loss of the graft was originally several millimetres but less than 1·5 mm. Bone loss as well as management of peri-implant soft tissue was also discussed. [source] Bone loss and osteoporosis: An anthropological perspectiveAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 2 2005Dawnie Wolfe Steadman No abstract is available for this article. [source] Local ex vivo gene therapy with bone marrow stromal cells expressing human BMP4 promotes endosteal bone formation in miceTHE JOURNAL OF GENE MEDICINE, Issue 1 2004Xiao S. Zhang Abstract Background Bone loss in osteoporosis is caused by an imbalance between resorption and formation on endosteal surfaces of trabecular and cortical bone. We investigated the feasibility of increasing endosteal bone formation in mice by ex vivo gene therapy with bone marrow stromal cells (MSCs) transduced with a MLV-based retroviral vector to express human bone morphogenetic protein 4 (BMP4). Methods We assessed two approaches for administering transduced MSCs. ,-Galactosidase (,-Gal) transduced C57BL/6J mouse MSCs were injected intravenously via tail vein or directly injected into the femoral bone marrow cavity of non-marrow-ablated syngenic recipient mice and bone marrow cavity engraftment was assessed. BMP4- or ,-Gal-transduced cells were injected into the femoral bone marrow cavity and effects on bone were evaluated by X-ray, peripheral quantitative computed tomography (pQCT), and histology. Results After tail-vein injection less than 20% of recipient mice contained ,-Gal-positive donor cells in femur, humerus or vertebra marrow cavities combined, and in these mice only 0.02,0.29% of injected cells were present in the bone marrow. In contrast, direct intramedullary injection was always successful and an average of 2% of injected cells were present in the injected femur marrow cavity 24 hours after injection. Numbers of donor cells decreased over the next 14 days. Intramedullary injection of BMP4-transduced MSCs induced bone formation. Trabecular bone mineral density (BMD) determined by pQCT increased 20.5% at 14 days and total BMD increased 6.5% at 14 days and 10.4% at 56 days. Conclusions The present findings support the feasibility of using ex vivo MSC-based retroviral gene therapy to induce relatively sustained new bone formation, with normal histological appearance, at endosteal bone sites. Copyright © 2004 John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||||||||||||||