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Serum Dickkopf-1 is increased and correlates with reduced bone mineral density in patients with thalassemia-induced osteoporosis. Reduction post-zoledronic acid administration.

ABSTRACT: Dickkopf-1 is an inhibitor of Wnt signaling, which is crucial for osteoblast differentiation. We evaluated serum levels of Dickkopf-1 in 66 patients with thalassemia-induced osteoporosis who received therapy with zoledronic acid in a placebo-controlled, randomized trial. At baseline, thalassemia patients had increased serum levels of Dickkopf-1 that correlated with reduced bone mineral density of the lumbar spine and the distal radius. High Dickkopf-1 also correlated with increased bone resorption and reduced bone formation markers. Zoledronic acid produced a reduction in serum Dickkopf-1, which was associated with bone mineral density increase after 12 months of therapy. On the contrary, placebo group showed a borderline increase of Dickkopf-1, which was higher in patients who showed deterioration in pain scores. These results suggest that Dickkopf-1 is implicated in the pathogenesis of osteoporosis in thalassemia and reveal Dickkopf-1 as a possible target for the development of novel agents for the management of thalassemia-induced osteoporosis.

SUBMITTER: Voskaridou E

PROVIDER: S-EPMC2675686 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Serum Dickkopf-1 is increased and correlates with reduced bone mineral density in patients with thalassemia-induced osteoporosis. Reduction post-zoledronic acid administration.

Voskaridou Ersi E Christoulas Dimitrios D Xirakia Charoula C Varvagiannis Konstantinos K Boutsikas Georgios G Bilalis Antonios A Kastritis Efstathios E Papatheodorou Athanasios A Terpos Evangelos E

Haematologica 20090501 5

Dickkopf-1 is an inhibitor of Wnt signaling, which is crucial for osteoblast differentiation. We evaluated serum levels of Dickkopf-1 in 66 patients with thalassemia-induced osteoporosis who received therapy with zoledronic acid in a placebo-controlled, randomized trial. At baseline, thalassemia patients had increased serum levels of Dickkopf-1 that correlated with reduced bone mineral density of the lumbar spine and the distal radius. High Dickkopf-1 also correlated with increased bone resorpti ...[more]

PMID: 19407319

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Project description:Introduction: Periprosthetic bone mineral density (BMD) loss following total hip arthroplasty (THA) may threaten the survival of the implant, especially in patients with osteoporosis. Zoledronic acid (ZA) is the representative of the third generation of bisphosphonates, which were effective in reducing bone loss in conditions associated with accelerated bone turnover. The aim of this study was to evaluate the efficacy and safety of ZA in patients with osteoporosis after THA. Methods: Randomized controlled trials (RCTs) associated with ZA and THA were searched from the MEDLINE, PubMed, EMBASE, Wanfang database, and the Web of Science (August 2021). Other methods, such as hand search and email request were also tried. The methodological quality was assessed by the Risk of Bias (RoB) 2.0. Relevant data were abstracted from the included RCTs and authors were contacted when necessary. Results: In this study, six RCTs involving a total of 307 patients were finally included and analyzed. The pooled data demonstrated that significantly less periprosthetic BMD loss in Gruen zone seven had occurred in the ZA-treated patients than in the control patients at 3 months (mean difference [MD] = 4.03%; 95% CI: 0.29-7.76%; P = 0.03), 6 months (MD = 7.04%; 95% CI: 2.12-11.96%; P = 0.005), and 12 months (MD = 7.12%; 95% CI: 0.33-13.92%; P = 0.04). The Harris Hip Score (HHS) was also significantly increased in ZA group at 6 and 12 months after operation (P = 0.03 and P = 0.02, respectively). Influenza-like symptom was found related to the usage of ZA [relative risk (RR) = 7.03, P < 0.0001]. Conclusion: A meta-analysis of six RCTs suggested that ZA was beneficial in maintaining the periprosthetic BMD in patients with osteoporosis at 6 and 12 months after THA. In addition, the HHS was significantly improved in patients treated with ZA. However, the short length of follow-up of the available studies resulted in the lack of analyses regarding the survival of implants including the rate of aseptic loosing, periprosthetic fracture, and revision. It still needs to be determined in research with longer follow-up period. Clinical Trial Registration: Researchregistry.com, identifier: reviewregistry1087.

Project description:Osteoporosis, a disease characterized by low bone mineral density (BMD), increases the risk for fractures. Conventional risk factors alone do not completely explain measured BMD or osteoporotic fracture risk. Metabolomics may provide additional information. We aim to identify BMD-associated metabolomic markers that are predictive of fracture risk. We assessed 209 plasma metabolites by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in 1552 Framingham Offspring Study participants, and measured femoral neck (FN) and lumbar spine (LS) BMD 2 to 10 years later using dual-energy X-ray absorptiometry. We assessed osteoporotic fractures up to 27-year follow-up after metabolomic profiling. We identified 27 metabolites associated with FN-BMD or LS-BMD by LASSO regression with internal validation. Incorporating selected metabolites significantly improved the prediction and the classification of osteoporotic fracture risk beyond conventional risk factors (area under the curve [AUC] = 0.74 for the model with identified metabolites and risk factors versus AUC = 0.70 with risk factors alone, p = .001; net reclassification index = 0.07, p = .03). We replicated significant improvement in fracture prediction by incorporating selected metabolites in 634 participants from the Hong Kong Osteoporosis Study (HKOS). The glycine, serine, and threonine metabolism pathway (including four identified metabolites: creatine, dimethylglycine, glycine, and serine) was significantly enriched (false discovery rate [FDR] p value = .028). Furthermore, three causally related metabolites (glycine, phosphatidylcholine [PC], and triacylglycerol [TAG]) were negatively associated with FN-BMD, whereas PC and TAG were negatively associated with LS-BMD through Mendelian randomization analysis. In summary, metabolites associated with BMD are helpful in osteoporotic fracture risk prediction. Potential causal mechanisms explaining the three metabolites on BMD are worthy of further experimental validation. Our findings may provide novel insights into the pathogenesis of osteoporosis. © 2021 American Society for Bone and Mineral Research (ASBMR).

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Dataset Information

Serum Dickkopf-1 is increased and correlates with reduced bone mineral density in patients with thalassemia-induced osteoporosis. Reduction post-zoledronic acid administration.

Publications

Serum Dickkopf-1 is increased and correlates with reduced bone mineral density in patients with thalassemia-induced osteoporosis. Reduction post-zoledronic acid administration.

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