Juliet Compston

..In iliac crest biopsy specimens from 57 healthy subjects 19-80 yr of age, no correlations were shown between these variables, an observation that challenges the use of activation frequency as an estimate of remodeling rate...

..The evidence base for strategies to prevent fractures in obese individuals is weak and is an important area for future research...

..Anti-resorptive therapy after PTH therapy maintains or increases the gains in BMD. Further research is required to establish the cost-effectiveness and safety of combined and sequential regimens...

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..These results indicate that although weight gain in young anorexics is associated with linear growth, bone mineral density does not increase. Whether this deficit can be corrected subsequently requires longer-term prospective studies...

..Nevertheless, the mechanisms by which estrogen exerts its beneficial skeletal effects remain a major area of research that has important implications for the development of novel therapies...

..These results demonstrate that strontium ranelate is a new therapeutic option in the prevention of osteoporotic vertebral fractures in postmenopausal women...

..This review considers the challenges involved in the development and implementation of guidelines and proposes a paradigm for the unification of guidelines in the future...

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..In other glucocorticoid-treated individuals, the decision to treat should be based on bone densitometry...

..Better definition of the effects of intermittent PTH administration on cancellous and cortical bone remodelling and structure at different skeletal sites may inform these speculations and is an important area for future research...

..New techniques to assess these components of bone quality are being developed and should produce important insights into determinants of fracture risk in untreated and treated disease...

..To investigate the prevalence and incidence of clinical fractures in obese, postmenopausal women enrolled in the Global Longitudinal study of Osteoporosis in Women (GLOW)...

..Other possible pathogenetic factors include suppression of bone turnover, altered immune status and adverse effects of bisphosphonates on the oral mucosa...

..Calcium and vitamin D supplements should be co-prescribed unless there is evidence of an adequate dietary calcium intake and vitamin D status...

..Finally, there is a discussion of the recent advances in fracture risk prediction and the use of independent clinical risk factors to improve bone mineral density-based prediction...

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..Compliance and persistence with long-term treatment is poor but may be improved by less frequent dosing regimens...

..University of Sheffield Press; 2008], a practical summary of which is detailed below. The management algorithms are underpinned by a health economic analysis applied to the epidemiology of fracture in the UK...

..Nevertheless, further research is required to establish the optimal duration of treatment with antiresorptive agents...

..Organized care programs together with the use of evidence-based guidelines have the potential to improve significantly the management of this serious complication of glucocorticoid therapy...

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..The aim of this study was to establish whether there were abnormalities in bone turnover and remodelling in a group of symptomatic subjects who had served in the Gulf War...

..The absence of receptor expression in osteoclasts also suggests that the effects of glucocorticoids on bone resorption may be mediated indirectly...

..Participants from the trial also volunteered for trans-iliac bone biopsy, to assess the early effects of stroke and zoledronate on iliac bone remodelling...

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..This is also the first demonstration of the presence of TRbeta2 mRNA in bone. The role of TRbeta2 in mediating the actions of thyroid hormones in bone is not known and requires further investigation...

..RANKL-independent osteoclastogenesis also occurs, though IL1 is required for resorptive function in most studies. These inflammatory cytokines have a pivotal role in rheumatoid arthritis,..

..There was also a trend toward higher wall width with increasing dose of oestrogen, consistent with the previously reported anabolic effect in cancellous bone...

..Since the young and old-donor hOBs were cultured under identical conditions, our results indicate that the response of hOBs to estrogen is largely dependent on intracellular mechanisms that control the timing of cellular differentiation...

..ERalpha mRNA but not ERbeta expression was up-regulated by estrogen. Our results suggest that estrogen may exert its anti-resorptive effects on bone, at least in part, by stimulating ER and OPG expression in osteoblasts...

..These data provide further evidence that megakaryocytes may play an important role in bone remodeling...

..These results show that MKs inhibit osteoclast formation and activity. The most pronounced effects were seen when MKs and osteoclasts were co-cultured from day 0, suggesting that MKs act primarily on osteoclast precursors...

..These data demonstrate the widespread expression of PDGF-A and its receptor in forming human bone and indicate that this growth factor may exert autocrine and paracrine effects to regulate osteogenesis during skeletal development...

..In situ zymography demonstrates that SL-2 is produced in an active form with associated degradation, whereas SL-1, in a matrix-bound proenzyme form, may act as a reservoir for later activation...

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..Furthermore, TIMP-1 may play a role in the regulation of bone modeling and remodeling in normal developing human bone...

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..The ability of MKs to express ERs and synthesise TGFbeta, a potent mitogen in osteoblast differentiation, suggests that these cells may play a role in mediating estrogen-induced effects on bone...

..The distribution of Ang-1, Ang-2, and VEGF indicate these factors may play key roles in the regulation of angiogenesis at sites of endochondral ossification, intramembranous ossification, and bone turnover in the growing human skeleton...

..Effects of the underlying disease on bone remodeling may also contributed to these changes and could not be excluded in the present study; since control subjects were not matched in terms of disease status...

..001). Thus, E stimulates megakaryocytopoiesis and modulates OPG and RANKL expression, providing evidence that MKs may play a role in bone remodelling and, in particular, in E-induced changes in osteoclastogenesis and bone resorption...

..The data suggest that increasing concentrations of glucocorticoid, including concentrations similar to plasma levels in patients receiving oral glucocorticoid therapy, increase the rate of cellular differentiation...

..This finding together with the stimulation of ER protein and mRNA expression adds to the increasing evidence for a role for MKs in estrogen-induced bone formation...

..The low incidence of fracture and absence of spinal bone loss indicate that bone disease after liver transplantation may be less common than previously reported...

..Thus, the use of combination therapy for treatment of osteoporosis cannot be recommended on the basis of currently available evidence...

..Osteoporosis is among the chronic problems emerging as the human immunodeficiency virus (HIV)-positive population ages...

..We conclude that, as the most usual indication for bone densitometry is to aid the determination of an individual's fracture risk, both proximal femur and lumbar spine should continue to be assessed...

..These results indicate that pre-operative administration of pamidronate in patients with chronic liver disease prevents, at least in part, the increase in bone turnover which occurs in untreated patients after transplantation...

..Providing that the relationship between fracture rates and BMD is the same in Britain and the US, it would still be appropriate to apply the reference data in fracture risk assessment in the UK...

..With the exception of increasing age and lower body weight in women, no independent risk factors were found, emphasizing the importance of BMD measurements in these patients and the need for prophylactic measures to optimize bone health...

..We assessed osteoclast number and activity during infective exacerbations and examined their relationship to serum inflammatory cytokines and bone turnover markers...

..Thus, Ostn provides a marker of osteoblast lineage cells and appears to correlate with osteoblast activity...

..We conclude that corticosteroid therapy is an independent risk factor for osteoporosis in patients with Crohn's disease and should be used as little as possible...

..CONCLUSION: These data suggest that, through attenuation of bone loss, isoflavones have a potentially protective effect on the lumbar spine in women...

..In conclusion, significant and persistent bone loss at the femoral neck was demonstrated in this group of patients following stem cell transplantation. The implications of these findings for future fracture risk require further study...

..Adults with cystic fibrosis (CF) are at increased risk of developing osteoporosis. During infective exacerbations, increased production of proinflammatory cytokines and markers of bone resorption have been reported...

..In Addison's disease, glucocorticoid and mineralocorticoid deficiencies require lifelong replacement, but the associated near-total failure of DHEA synthesis is not typically corrected...

..05). The eightfold elevation of urinary free cortisol excretion, low osteoblast number, decreased resorptive surface, and reduced markers of osteoblast differentiation are all consistent with an acute glucocorticoid effect on bone...

..Osteomalacia was diagnosed in one patient. This condition should be excluded as a cause of low bone mineral density in patients with CF and vitamin D insufficiency corrected...

..However, this increase was about two-fold lower than that observed after alendronate therapy (10 mg/day/3 years) in postmenopausal osteoporotic women...

..This study provides evidence for gender-specific, site-specific and age-specific QTL, which regulate BMD in humans, and illustrates the importance of conducting subgroup analysis to detect these loci...

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..006) and total body less head BMD (P = 0.02), corrected for age and gender, confirming the family findings. These findings suggest a role for PTHR1 variation in determining peak BMD...