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Serum CTX (serum + ctx)
Selected AbstractsPerspective: Assessing the Clinical Utility of Serum CTX in Postmenopausal Osteoporosis and Its Use in Predicting Risk of Osteonecrosis of the Jaw,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2009Sanford Baim Abstract Bone turnover markers (BTMs) have become increasingly important in the management of postmenopausal osteoporosis (PMO). In bisphosphonate-treated women with PMO, BTMs can provide early indications of treatment efficacy, are predictors of BMD response and fracture risk reduction, and are potentially useful for monitoring patient compliance. The bone resorption marker serum C-telopeptide cross-link of type 1 collagen (sCTX) has shown high sensitivity and specificity for the detection of increased bone resorption. Recently, sCTX has been singled out as a potential indicator of risk of osteonecrosis of the jaw (ONJ) in patients receiving oral bisphosphonates who require oral surgery. However, whether BTMs are capable of predicting ONJ risk and whether sCTX is usable for this purpose are controversial questions. This article presents an overview of the current literature regarding critical issues affecting the clinical utility of BTMs (including variability and reference ranges) and the current applications of BTMs in PMO management, with a focus on sCTX. Last, the appropriateness of using sCTX to predict ONJ risk in women receiving oral bisphosphonates for PMO is evaluated. [source] Effect of Blockade of TNF-, and Interleukin-1 Action on Bone Resorption in Early Postmenopausal Women,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2007Natthinee Charatcharoenwitthaya Abstract After acute estrogen withdrawal in postmenopausal women, administration of anakinra or etanercept, specific blockers of IL-1 and TNF-,, respectively, reduced the rise in bone resorption markers to about one half of that in controls. This is consistent with an important role for these immune cytokines in mediating the effect of estrogen deficiency on bone. Introduction: Studies in rodents have implicated increased production of interleukin (IL)-1, and TNF-, as mediators of bone loss after ovariectomy, but their roles are unclear in humans whose immune system differs markedly from that of rodents. Materials and Methods: We administered transdermal estradiol, 0.1 mg/d, for 60 days to 42 early postmenopausal women. Estrogen treatment was discontinued, and subjects were randomly assigned to intervention groups receiving 3 wk of injections with 0.9% saline, anakinra 100 mg/d, or etanercept 25 mg/twice weekly. Bone turnover was assessed by measuring serum carboxyl-terminal telopeptide of type 1 collagen (CTX) and amino-terminal telopeptide of type 1 collagen (NTX), markers for bone resorption, and serum amino-terminal propeptide of type 1 collagen (P1NP), a marker for bone formation. Results were expressed as percent change in markers from baseline (last 2 days of estrogen treatment and days 20 and 21 of intervention). Results: The percent changes from baseline during intervention for serum CTX, urine NTX, and serum PINP, respectively, were 43.3 ± 8.0%, 12.0 ± 7.1%, and ,41.0 ± 2.5% for the control group; 25.9 ± 6.3%, 9.5 ± 4.0%, and ,37.8 ± 3.0% for the anakinra group; and 21.7 ± 5.0%, 0.32 ± 3.82%, and ,34.5 ± 3.9% for the etanercept group. Compared with the control group, the blunting of the increase in serum CTX fell just below the level of significance (p = 0.10) after anakinra treatment, whereas the blunting of the increase in serum CTX (p = 0.034) and in urine NTX (p = 0.048) were significant after etanercept treatment. Other changes were not significant. Conclusions: The data are consistent with a role for TNF-,, and possibly for IL-1,, in mediating increased bone resorption during estrogen deficiency in women. Although either cytokine blocker reduced serum CTX by about one half, the effect of combined blockade could not be tested because of concerns about toxicity. The data do not exclude direct or indirect contributory roles for RANKL or for other cytokines. [source] Cholesterol-Sensing Receptors, Liver × Receptor , and ,, Have Novel and Distinct Roles in Osteoclast Differentiation and ActivationJOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2006Kirsten M Robertson Abstract The liver × receptor (,,,) is responsible for regulating cholesterol homeostasis in cells. However, our studies using the LXR,,/,, LXR,,/,, and LXR,,/,,,/, mice show that both LXR, and , are also important for bone turnover, mainly by regulating osteoclast differentiation/activity. Introduction: The liver × receptors (,,,) are primarily responsible for regulating cholesterol homeostasis within cells and the whole body. However, as recent studies show that the role for this receptor is expanding, we studied whether the LXRs could be implicated in bone homeostasis and development. Materials and Methods: pQCT was performed on both male and female LXR,,/,, LXR,,/,, LXR,,/,,,/,, and WT mice at 4 months and 1 year of age. Four-month-old female mice were additionally analyzed with reference to qPCR, immunohistochemistry, histomorphometry, transmission electron microscopy, and serum bone turnover markers. Results: At the mRNA level, LXR, was more highly expressed than LXR, in both whole long bones and differentiating osteoblast-like MC3T3-E1 and osteoclast-like RAW 264.7 cells. Four-month-old female LXR,,/, mice had a significant increase in BMD because of an increase in all cortical parameters. No difference was seen regarding trabecular BMD. Quantitative histomorphometry showed that these mice had significantly more endosteal osteoclasts in the cortical bone; however, these cells appeared less active than normal cells as suggested by a significant reduction in serum levels of cross-linked carboxyterminal telopeptides of type I collagen (CTX) and a reduction in bone TRACP activity. Conversely, the female LXR,,/, mice exhibited no change in BMD, presumably because a significant decline in the number of the trabecular osteoclasts was compensated for by an increase in the expression of the osteoclast markers cathepsin K and TRACP. These mice also had a significant decrease in serum CTX, suggesting decreased bone resorption; however, in addition presented with an increase in the expression of osteoblast associated genes, bone formation markers, and serum leptin levels. Conclusions: Our findings show that both LXRs influence cellular function within the bone, with LXR, having an impact on osteoclast activity, primarily in cortical bone, whereas LXR, modulates trabecular bone turnover. [source] Glucocorticoid-induced bone loss in mice can be reversed by the actions of parathyroid hormone and risedronate on different pathways for bone formation and mineralizationARTHRITIS & RHEUMATISM, Issue 11 2008Wei Yao Objective Glucocorticoid excess decreases bone mineralization and microarchitecture and leads to reduced bone strength. Both anabolic (parathyroid hormone [PTH]) and antiresorptive agents are used to prevent and treat glucocorticoid-induced bone loss, yet these bone-active agents alter bone turnover by very different mechanisms. This study was undertaken to determine how PTH and risedronate alter bone quality following glucocorticoid excess. Methods Five-month-old male Swiss-Webster mice were treated with the glucocorticoid prednisolone (5 mg/kg in a 60-day slow-release pellet) or placebo. From day 28 to day 56, 2 groups of glucocorticoid-treated animals received either PTH (5 ,g/kg) or risedronate (5 ,g/kg) 5 times per week. Bone quality and quantity were measured using x-ray tomography for the degree of bone mineralization, microfocal computed tomography for bone microarchitecture, compression testing for trabecular bone strength, and biochemistry and histomorphometry for bone turnover. In addition, real-time polymerase chain reaction (PCR) and immunohistochemistry were performed to monitor the expression of several key genes regulating Wnt signaling (bone formation) and mineralization. Results Compared with placebo, glucocorticoid treatment decreased trabecular bone volume (bone volume/total volume [BV/TV]) and serum osteocalcin, but increased serum CTX and osteoclast surface, with a peak at day 28. Glucocorticoids plus PTH increased BV/TV, and glucocorticoids plus risedronate restored BV/TV to placebo levels after 28 days. The average degree of bone mineralization was decreased after glucocorticoid treatment (,27%), but was restored to placebo levels after treatment with glucocorticoids plus risedronate or glucocorticoids plus PTH. On day 56, RT-PCR revealed that expression of genes that inhibit bone mineralization (Dmp1 and Phex) was increased by continuous exposure to glucocorticoids and glucocorticoids plus PTH and decreased by glucocorticoids plus risedronate, compared with placebo. Wnt signaling antagonists Dkk-1, Sost, and Wif1 were up-regulated by glucocorticoid treatment but down-regulated after glucocorticoid plus PTH treatment. Immunohistochemistry of bone sections showed that glucocorticoids increased N-terminal Dmp-1 staining while PTH treatment increased both N- and C-terminal Dmp-1 staining around osteocytes. Conclusion Our findings indicate that both PTH and risedronate improve bone mass, degree of bone mineralization, and bone strength in glucocorticoid-treated mice, and that PTH increases bone formation while risedronate reverses the deterioration of bone mineralization. [source] Late Low-Dose Steroid Withdrawal in Renal Transplant Recipients Increases Bone Formation and Bone Mineral DensityAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2006C.K.T. Farmer Corticosteroids have been the most widely used immunosuppressive agents since the first clinical transplantation in the 1950s. There are few studies of late steroid withdrawal in renal transplantation and none have prospectively assessed bone mineral density (BMD). The study aim was to assess the impact of corticosteroid withdrawal, in stable renal transplant recipients, on BMD and bone turnover. BMD, osteocalcin (OC) and cross-linked telopeptide of type I collagen (CTx) were measured in 92 patients randomized into a trial of steroid withdrawal. Patients with functioning renal transplants for more than 1 year with a serum creatinine below 200 ,mol/L entered the trial. All patients were on triple immunosuppression (Cyclosporin microemulsion, Azathioprine and prednisolone), corticosteroids were withdrawn at 1 mg/month. BMD was measured twice annually with serum CTx and OC. One year following withdrawal of glucocorticoids there was no significant difference in creatinine. BMD increased in the withdrawal group (2.54% per year L1-L4, p < 0.01), there was a slight reduction in the control group. Mean OC increased from 5.3 to 12.2 ng/mL (p < 0.05) in the withdrawal group, but was unchanged in the controls. No change was seen in CTx. Corticosteroid withdrawal in renal transplant recipients results in an increase in BMD with a corresponding increase in serum OC. [source] | ||||||||||