P D Delmas

..The decreased vertebral fracture risk in yr 4 alone was not different from that observed in the first 3 yr...

..Non-pharmacological interventions include adequate calcium intake and diet, selected exercise programmes, reduction of other risk factors for osteoporotic fractures, and reduction of the risk of falls in elderly individuals...

..These discrepancies stress the differences in the pathogenesis of vertebral and nonvertebral fractures as discussed below, and the need to further investigate the mechanisms of action of various antiresorptive agents...

..Our data suggest that bone turnover markers can be used to monitor the BMD response to HRT at the individual level. Whether such monitoring could improve long-term compliance to HRT should be tested prospectively...

..A relative margin of non-inferiority of 20-30% is suggested, to be discussed on a case by case basis...

..These effects on cortical bone were reflected by changes in biochemical markers. MDL markedly reduces bone turnover and increases BMD suggesting that this new agent may prevent postmenopausal bone loss...

..The clinical performance of these two new markers was compared with that of a panel of other established biochemical markers of connective tissue metabolism...

..After the age of 60 years, bone resorption markers--but not bone formation markers--increase in some men and are associated with lower BMD, suggesting that this imbalance is responsible for increasing bone loss in elderly men...

..If DXA is not available, the combination of history of fracture and urinary CTX performs as well as hip BMD to assess hip fracture risk in elderly women...

..This property of cathepsin K is unique among mammalian proteinases and is reminiscent of bacterial collagenases. It is likely to be responsible for the key role of cathepsin K in bone resorption...

..Teriparatide is a bone formation agent that increases bone turnover and mass, resulting in an increase in bone strength and a decrease in fracture risk...

..Bone formation appears to be reduced both in patients with and without joint destruction, whereas resorption is increased only in patients with joint destruction in relation to disease activity...

..Thus, intermittent ibandronate has potential to become an important alternative to currently licensed bisphosphonates in postmenopausal osteoporosis...

..The delayed decrease in bone formation observed with intranasal E2 compared to oral E2 may be related to different effects on serum IGF-I levels...

..Thus, vertebral fragility may not only be due to alterations in bone architecture but also to modification of collagen cross-link patterns thereby influencing bone's mechanical behavior...

..Tibolone increased lumbar spine and total hip BMD to a statistically significantly greater extent than raloxifene after two years of treatment...

..Grade 1 deformities are often either false positive or deformities related to nonosteoporotic disease of the spine...

..The aim of this study was to assess age-related apparent net and endosteal bone loss as well as their morphological basis and age-related changes during a prospective follow-up in a large cohort of elderly men...

..Measurement of type II collagen breakdown by a new urinary biochemical marker may be useful for in vivo assessment of the effects of drugs that potentially inhibit cartilage destruction...

..We assessed the association of bone microarchitecture with calcium intake and serum concentrations of 25-hydroxycholecalciferol (25OHD) and parathyroid hormone (PTH) in men...

..CONCLUSION: Glc-Gal-PYD may be useful for the clinical investigation of patients with joint disease...

..Our aim was to evaluate the technical and clinical performances of a new, fully automated assay for serum C-terminal cross-linking telopeptide of type I collagen (CTX), a marker of bone resorption...

..The aim of this study was to investigate the associations between serum 25-hydroxyvitamin D (25-OH D), bone turnover markers, bone mineral density (BMD), radius bone loss and incidence of fracture in postmenopausal women...

..Changes in bone mineral density and bone turnover markers were similar between treatments. Risedronate 75 mg twice monthly was effective and safe suggesting a new, convenient dosing schedule...

..6 x 10(6) cells/ml).(ABSTRACT TRUNCATED AT 400 WORDS)..

..The bisphosphonate risedronate prevents anastrozole induced bone loss...

....

..Strontium was shown to be dose-dependently deposited into this newly formed bone with preservation of the mineralization...

..The aim was to analyse data on the use of biochemical bone turnover markers (BTM) in postmenopausal osteoporosis...

..Thus, the independent contribution of the external diameter of the femoral neck to the risk of hip fracture cannot be reliably estimated by this technique...

..The morphological basis of such a relationship is unknown. The objective of this study was to evaluate the association between baseline BTM levels and subsequent bone loss and fracture risk in men...

..We conclude that the generation of ICTP and CTX depends on different collagenolytic pathways. This finding may explain why these two markers may discriminate between different bone pathologies...

..To illustrate the role of the crosslinking process of collagen in bone strength, clinical disorders associated with bone collagen abnormalities and bone fragility, such as osteogenesis imperfecta and osteoporosis, are described...

..Vitamin D receptor (VDR) gene polymorphisms explain only a small part of the genetic influence on the level of bone mineral density (BMD), whereas their effect on fracture remains uncertain...

..Because this model is independent of the study design, it should be broadly applicable...

....

..These results suggest a possible new mechanism for regulating osteoclast activity and indicate that excitatory amino acids such as glutamate may be important local regulators of bone cell functions...

..Identification of older men at high risk of peripheral fracture can be improved by assessing prevalent fractures (men aged ≤ 65), history of falls (men aged >65), bone width, and aortic calcifications...

..Bone microhardness is linked to Young's modulus of bone and is strongly correlated to mineralization, but the organic matrix accounts for about one third of its variance...

..83, P = 0.015). These findings indicate that post-translational modifications of type I collagen have an impact on skeletal fragility...

....

....

..In addition, we investigated circulating forms recognized by antiserum IIA in pools of serum from healthy adults, patients with OA and patients with RA...

..In contrast, they do not reflect the periosteal bone formation, probably because the periosteal surface is smaller and has a slower remodelling rate than the endosteal surface...

....

..AGE concentration did not influence bending mechanical properties; however, the simple 3-point bending test we used was likely inadequate to demonstrate effects of AGEs on mechanical properties...

....

..2 pmol for the pyridimium crosslinks and 0.02 pmol for the pentosidine. The inter- and intra-assay coefficients of variation were as low as 5% and 2%, respectively, for all crosslinks...

..Furthermore, the spatial distribution of the trabeculae differs between OP and OA whereas cortical thinning is homogenous...

..In the next five years, new SERMs and inhibitors of RANK-ligand might be new treatment options...

..Osteoporosis in men is less studied than in women. Few data concern biochemical bone turnover markers (BTM) in men and their potential use...

..Given methodological limitations, these results need to be confirmed in a younger and more representative group of men...

..After adjustment for age, there was no significant relation between the plasma level of homocysteine and the subsequent risk of fracture...

..Observations in patients and in animal models provide insights on the biomechanical consequences of these illnesses and the nature of the qualities of bone that determine its strength...

..The test was a sensitive indicator of the antiresorptive effects of bisphosphonate and estrogens in postmenopausal women. This new bone resorption marker should be useful for the clinical investigation of patients with osteoporosis...

..Thus, antiresorptive therapy may be of interest in the prevention and treatment of osteoporosis in men. Further studies are necessary to determine if bone resorption markers predict the risk of fragility fractures in elderly men...

..The bone formation rate (BFR/B.Pm) also decreased by 84% and the adjusted apposition rate (Aj.AR) by 80%. The increase in the total formation period was mainly due to an increase in the inactive period.(ABSTRACT TRUNCATED AT 250 WORDS)..

..6 - 12-fold even after adjusting for BMD. We examined the possibility that biochemical marker levels were associated with this unexplained BMD-independent element of fracture risk...

..Expression patterns suggest Plexin-A3/Neuropilin-1 as a candidate receptor in target cells for the regulation of bone innervation by Semaphorin-3A...

....

..To compare type II collagen degradation using a new urinary specific marker in patients with rapidly destructive and those with slowly progressive hip OA...

..Further studies in osteoporosis should explore the changes in these biochemical parameters of bone matrix as they may represent a key component of bone quality...

..These fractures may reflect architectural deterioration, independent of BMD, leading to increased skeletal fragility...

..It is the clinician's responsibility to attend to and recognize that nonspinal, nonhip fractures are usually associated with osteoporosis and should be treated...

..Many factors may affect the outcome of such analyses. Our work explores some of these factors and illustrates the need for caution in interpreting the results of meta-analyses...

..dermatan-sulfate chains), and is independent of a steric hindrance effect exerted by its glycosaminoglycan side chains...

..All tested doses were well tolerated; the 2 g/d dose was considered to offer the best combination of efficacy and safety. In conclusion, SR therapy increased vertebral BMD and reduced the incidence of vertebral fractures...

..Microdamage accumulation due to fatigue loading may lead to fracture. In addition, several studies using animal models have suggested in recent years that bisphosphonates might increase microdamage accumulation...

....

..This finding raises the intriguing possibility that protein-S might play a role in bone turnover and bone mass...

..Larger long-term studies are necessary to assess adequately the relationships between IL-6 genotype, rate of bone loss, and risk of fracture...

..Hence, these effects may explain the decreased fracture rate...

....

..To evaluate the relationship between bone mass and risk of breast cancer and to determine the effect of raloxifene therapy on breast cancer incidence in women categorized by bone mass into low bone mass and osteoporosis subgroups...

....

..This randomized, double-blind, multi-center study was designed to assess the efficacy and safety of a single 150 mg risedronate once-a-month oral dose compared with the 5 mg daily regimen...

..Zoledronic acid reduced bone turnover by 63% and preserved bone structure and volume, with evidence of ongoing bone remodeling in 99% of biopsies obtained...

..We sought whether microdamage could rise in postmenopausal osteoporotic women on long-term bisphosphonates, as suggested by recent animal studies. We found few microcracks in iliac bone biopsies, despite a marked reduction in bone turnover...

..Altogether, our results indicate that osteoclast precursors express NMDAR that are involved in the osteoclast differentiation process through activation of the NF-kappa B pathway...

..Seventy percent to 80% of women classified as having high bone turnover at baseline were similarly classified by the same methods 4 years later...

..In this Review, we will use the recently proposed BIPED (i.e. burden of disease, investigative, prognostic, efficacy of intervention and diagnostic) classification of OA markers to describe the potential usage of a given marker...

..Osteoporosis is an increasingly common health concern in postmenopausal women. In a 2-yr phase III study, bazedoxifene prevented bone loss, reduced bone turnover, and was well tolerated in early postmenopausal women with normal or low BMD...

..This is the first double-blind, randomized, placebo-controlled study to assess the efficacy of ibandronate, a third-generation amino-bisphosphonate, in preventing SREs in advanced-stage multiple myeloma patients...

..This suggests that alterations of type I collagen isomerization/racemization that can be detected by changes in urinary CTX ratios may be associated with increased skeletal fragility...

..In a randomised study, alendronate increased BMD and reduced the incidence of vertebral fractures. Alendronate and risedronate were also effective in the prevention and treatment of cortisone-induced osteoporosis in men...

..Tibolone has estrogenic, progestogenic, and androgenic effects. Although tibolone prevents bone loss, its effects on fractures, breast cancer, and cardiovascular disease are uncertain...

..v. every 3 months. Thus, ibandronate can be considered as a promising new option for the treatment of postmenopausal osteoporotic women...

..This study was undertaken to assess the effect of strontium ranelate on nonvertebral and vertebral fractures in postmenopausal women with osteoporosis in a 5-year, double-blind, placebo-controlled trial...

..The results of these human trials will also be discussed...

..We report the effects on lumbar spine and proximal femur bone mineral density (BMD) and bone resorption markers over 2 years...

..To evaluate the effects of discontinuing or continuing alendronate (ALN) therapy on bone mineral density (BMD) after patients on a long-term regimen of glucocorticoids (GCs) completed a 1-year treatment period with ALN...

....

....

..We assessed the effects of annual infusions of zoledronic acid on fracture risk during a 3-year period...

..After adjustment of each significant baseline variable, the percent change in OC was better able to predict the reduction in vertebral fracture risk than the percent change in femoral neck BMD in patients treated with raloxifene...

..Further studies are needed to define the structural basis of the fracture risk reduction...

....

..In 671 postmenopausal women from the OFELY cohort, we found that the rate of bone loss was significantly associated with fracture risk independently of other well-known predictors including BMD and previous fractures...

..Odds ratio estimates (95% CI) were 0.60 (0.49, 0.74) for RLX60 and 0.51 (0.41, 0.64) for RLX120/150. From these data we infer that raloxifene consistently reduces the risk of vertebral fracture in postmenopausal women...