| 1. |
- Engert, Andreas, et al.
(författare)
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The European Hematology Association Roadmap for European Hematology Research : a consensus document
- 2016
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Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
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Tidskriftsartikel (refereegranskat)abstract
- The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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| 2. |
- Skliris, Antonis, et al.
(författare)
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Serglycin inhibits the classical and lectin pathways of complement via its glycosaminoglycan chains: Implications for multiple myeloma
- 2011
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Ingår i: European Journal of Immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 41:2, s. 437-449
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Tidskriftsartikel (refereegranskat)abstract
- Serglycin (SG) is a proteoglycan expressed by hematopoietic cells and is constitutively secreted by multiple myeloma (MM) cells. SG participates in the regulation of various inflammatory events. We found that SG secreted by human MM cell lines inhibits both the classical and lectin pathways of complement, without influencing alternative pathway activity. The inhibitory effect of SG is due to direct interactions with C1q and mannose-binding lectin (MBL). C1q-binding is mediated through the glycosaminoglycan moieties of SG, whereas MBL binds additionally to SG protein core. Interactions between SG and C1q as well as MBL are diminished in the presence of chondroitin sulfate type E. In addition, we localized the SG-binding site to the collagen-like stalk of C1q. Interactions between SG and C1q as well as MBL are ionic in character and only the interaction with MBL was found to be partially dependent on the presence of calcium. We found the serum levels of SG to be elevated in patients with MM compared to healthy controls. Moreover, we found that SG expressed from myeloma plasma cells protects these cells from complement activation induced by treatment with anti-thymocyte immunoglobulins. This might protect myeloma cells during immunotherapy and promote survival of malignant cells.
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| 3. |
- Terpos, Evangelos, et al.
(författare)
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Bortezomib-based therapy for relapsed/refractory multiple myeloma in real-world medical practice
- 2018
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Ingår i: European Journal of Haematology. - : WILEY. - 0902-4441 .- 1600-0609. ; 101:4, s. 556-565
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The efficacy and safety of bortezomib-based therapy for relapsed/refractory multiple myeloma (RRMM) in clinical trials may differ from the oncology practice experience. The electronic VELCADE (R) OBservational Study was designed to prospectively evaluate bortezomib for multiple myeloma (MM) in real-world medical practice. Method: Patients scheduled to receive intravenous bortezomib for MM were eligible. The primary objective was to evaluate clinical outcomes, including response, time to response, time to next therapy, treatment-free interval, progression-free survival (PFS), and overall survival (OS). Secondary objectives included safety and healthcare resource utilization. Results: In total, 873 patients with a median of two therapy lines prior to initiating bortezomib were included. The overall response rate (amp;gt;= partial response) was 69%, including 37% complete response/near-complete response. Median time to response was 1.8 months, median time to next therapy was 9.7 months, and median treatment-free interval was 7.9 months. After 22.6 months median follow-up, median PFS was 12.0 months and median OS was 36.1 months. The most common adverse events (AEs) were neuropathy not otherwise specified (19%), diarrhea NOS, and thrombocytopenia (each 17%); 230 (26%) patients discontinued bortezomib due to AEs. Of 689 (79%) patients without baseline peripheral neuropathy (PN), the rate of new-onset any-grade PN increased to 51% (12% grade 3/4) by cycle 8. Overall, 244 (28%) patients were hospitalized, 372 (43%) attended an outpatient visit, and 341 (39%) underwent a diagnostic/therapeutic procedure during bortezomib treatment. Conclusion: These prospective real-world data demonstrate the effectiveness and safety of bortezomib-based therapy for RRMM and confirm high response rates and long OS for this population.
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| 4. |
- Terpos, Evangelos, et al.
(författare)
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Circulating Levels of the Wnt Inhibitors Dickkopf-1 and Sclerostin In Different Phases of Multiple Myeloma: Alterations Post-Therapy with Lenalidomide and Dexamethasone with or without Bortezomib
- 2010
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 116:21, s. 2963-2963
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Tidskriftsartikel (refereegranskat)abstract
- Dickkopf-1 (Dkk-1) and sclerostin are inhibitors of the Wingless-type and integrase 1 (Wnt) signaling and they are implicated in the pathogenesis of multiple myeloma (MM) bone disease through inhibition of osteoblast function. There is very limited information for the circulating levels of Dkk-1 and sclerostin in different phases of MM and their alterations post therapies with novel agents. Therefore, we studied 284 MM patients (153M/131F, median age 66 years): 167 consecutive patients were newly-diagnosed (20 had asymptomatic MM and 147 symptomatic MM), 29 patients were at the plateau phase of MM and 88 patients had relapsed/refractory MM and received therapy with the combination of lenalidomide plus dexamethasone with or without bortezomib (VRD or RD; Dimopoulos et al, Leukemia 2010). For newly diagnosed patients, serum was stored at the time of diagnosis, while for patients at the plateau phase serum was collected at the time of confirmation of the plateau (at least 6 months with stable M-protein without criteria confirming progression) and for relapsed/refractory patients on day 1 of cycles 1, 4 and 7 of VRD or RD administration. Circulating levels of Dkk-1 and sclerostin were measured using ELISA methodology (R&D Systems, Minneapolis, MN, USA and Biomedica Medizinprodukte, Vienna, Austria, respectively) in all patients and in 20 gender- and age- matched healthy controls. Circulating Dkk-1 and sclerostin concentrations of newly diagnosed symptomatic patients (median: 1383 pg/mL, range:274-32, 862 pg/mL and 415 pg/mL, 0–3,340 pg/mL respectively) were increased compared to controls (1069 pg/mL, 540-2, 709 pg/mL; p<0.001 and 250 pg/mL, 0–720 pg/mL; p=0.03, respectively) and to asymptomatic patients at diagnosis (1044 pg/mL, 480-2, 335 pg/mL; p<0.001 and 140 pg/mL, 0–1,100 pg/mL; p=0.001, respectively). Patients at plateau phase had increased circulating levels of sclerostin (704 pg/mL, 68–2000 pg/mL; p <0.001) compared to controls (p=0.002) as well as to MM patients at diagnosis (p=0.02). In contrast, they had lower serum levels of Dkk-1 (1013 pg/mL, 414–1729 pg/mL) compared to MM patients at diagnosis (p<0.001) and no difference compared to controls. Patients with ISS-3 myeloma at diagnosis had higher values of Dkk-1 and sclerostin than ISS-1 and ISS-2 patients [median Dkk-1 values for ISS-1, ISS-2 and ISS-3 were: 1059 pg/mL, 1290 pg/mL and 2649 pg/mL, respectively; p(ANOVA)=0.031; median sclerostin values for ISS-1, ISS-2 and ISS-3 were: 394 pg/mL, 392 pg/mL and 714 pg/mL, respectively; p(ANOVA)=0.001]. Patients with lytic disease at diagnosis (n=116) had increased levels of Dkk-1 compared with patients with no lytic disease (n=51): 1475 pg/mL, 327-32, 862 pg/mL vs. 840 pg/mL, 274–1112 pg/mL; p=0.002. There was no difference in sclerostin levels between these patients; however, patients with advanced bone disease (>3 lytic lesions and/or a fracture) had a borderline increase in their circulating sclerostin compared to all others (p=0.072). Dkk-1 circulating levels correlated weakly with sclerostin (r=0.201, p=0.05). Relapsed patients had increased Dkk-1 (1218 pg/mL, 161-19, 325 pg/mL) and sclerostin (886 pg/mL, 90-6, 272 pg/mL) levels compared to controls and to asymptomatic patients at diagnosis (p<0.001 for all comparisons). In patients who received RD, Dkk-1 was increased and sclerostin was decreased after 6 cycles of therapy. Responders to RD had a median increase of 9% in Dkk-1 serum levels after 6 cycles of therapy, while non-responders had a median increase of 91% compared to baseline values (p<0.01). Patients who did not respond to RD showed an increase in bone resorption marker CTX (p=0.021) after 6 cycles of therapy. VRD administration resulted in a significant reduction of sRANKL (p=0.024) and increase of bone formation marker, osteocalcin (p=0.01) after 6 cycles, but showed only minimal reduction of Dkk-1 (p=0.08) and no alterations on sclerostin. In conclusion our study suggests that Dkk-1 is elevated in active myeloma, while sclerostin is elevated even in the plateau phase of the disease. Both correlated with adverse disease features. The increase of Dkk-1 by RD seems to be balanced by a reduction effect of bortezomib on Dkk-1 in VRD. Furthermore, the reduction of sclerostin in RD patients may represent a modulatory effect of lenalidomide on marrow microenvironment. These results further support the rationale for the use of drugs targeting Dkk-1 and sclerostin in MM.
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| 5. |
- Terpos, Evangelos, et al.
(författare)
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Elevated circulating sclerostin correlates with advanced disease features and abnormal bone remodeling in symptomatic myeloma: Reduction post-bortezomib monotherapy
- 2011
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 131:6, s. 1466-1471
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Tidskriftsartikel (refereegranskat)abstract
- Sclerostin is a Wingless and Int-1 inhibitor, which is produced by osteocytes and inhibits osteoblast-driven bone formation. Sclerostin is implicated in the pathogenesis of bone loss in metabolic bone disorders but there is no information for its effect on multiple myeloma (MM)-related osteolytic disease. We evaluated circulating sclerostin in 157 newly diagnosed patients with symptomatic myeloma, in 25 with relapsed myeloma who received bortezomib monotherapy, in 21 patients with monoclonal gammopathy of undetermined significance (MGUS), and in 21 healthy controls. Patients with active myeloma had elevated circulating sclerostin compared to MGUS patients and controls (p < 0.01). MM patients who presented with fractures at diagnosis (n = 34) had very high levels of circulating sclerostin compared with all others (p < 0.01), whereas sclerostin correlated negatively with bone specific alkaline phosphatase (a bone formation marker; r = -0.541, p < 0.0001) and positively with C-telopeptide of collagen type-1 (a bone resorption marker; r = 0.524, p < 0.0001). Patients with International Staging System (ISS)-3 disease had higher circulating sclerostin compared to ISS-1 and ISS-2 MM (p = 0.001). Furthermore, patients with high sclerostin (upper quartile, n = 40) had a median survival of 27 months versus 98 months of all others (p = 0.031). Relapsed MM patients had higher levels of circulating sclerostin even compared to newly diagnosed patients (p < 0.01). Bortezomib monotherapy resulted in a reduction of sclerostin by almost 50% in both responders and non-responders. These results suggest that patients with active myeloma have elevated circulating sclerostin, which correlated with advanced disease features including severe bone disease. Our study indicates sclerostin as a possible target for the development of novel therapies to enhance osteoblast function in myeloma.
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| 6. |
- Terpos, Evangelos, et al.
(författare)
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High Serum Sclerostin Correlates with Advanced Stage, Increased Bone Resorption, Reduced Osteoblast Function, and Poor Survival in Newly-Diagnosed Patients with Multiple Myeloma.
- 2009
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 114:22, s. 425-425
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Tidskriftsartikel (refereegranskat)abstract
- Multiple myeloma (MM) is characterized by the presence of lytic bone disease due to increased osteoclast activity which is accompanied by reduced osteoblast function. To-date dickkopf-1 (Dkk-1) is considered as the main osteoblast inhibitor which is overproduced by myeloma cells and inhibits Wnt signaling leading to osteoblast exhaustion. Sclerostin is another canonical Wnt antagonist through its binding to low-density lipoprotein-receptor-related protein 5/6. Sclerostin is specifically expressed by osteocytes and inhibits bone morphogenic protein-induced osteoblast differentiation and ectopic bone formation. Osteonectin (SPARC) is a multi-faceted protein that belongs to a family of matricellular proteins. It is secreted by osteoblasts during bone formation, initiating mineralization and promoting mineral crystal formation. SPARC shows affinity for collagen in addition to bone mineral calcium. The aim of this study contacted by the Greek Myeloma Study Group in collaboration with Biomarker Design Forschungs GmbH (BDF), Vienna, Austria was to evaluate, for the first time in the literature, the serum levels of sclerostin in patients with MM and explore possible correlations with clinical and laboratory data, including SPARC levels, ISS stage and survival. One hundred and fifty-seven patients (87M/70F, median age 68 years) with MM at diagnosis before the administration of any type of therapy, including bisphosphonates, were evaluated. Serum sclerostin and SPARC were measured using an ELISA methodology developed by BDF for Biomedica Medizinprodukte GmbH & Co KG (Vienna, Austria). Both assays are sandwich type ELISA using biotinylated antibodies/HRP-streptavidine for the detection of sclerostin and SPARC in the serum. The detection limit of the sclerostin ELISA was 0.18 ng/ml and the coefficient of variation (CV) 6%. The standard range was set from 0.3-3 ng/ml. For the SPARC ELISA we found a detection limit of 1.95 ng/ml and CVs of 8% using a standard range from 5-130 ng/ml. Serum sclerostin and SPARC were determined in MM patients, 21 patients with MGUS and 21 healthy controls, of similar gender and age. Bone remodeling was also studied by the measurement of a series of serum indices within one week from diagnosis: i) osteoclast regulators [sRANKL and osteoprotegerin (OPG)], ii) Dkk-1, iii) bone resorption markers [C-terminal cross-linking telopeptide of collagen type-I (CTX) and 5b-isoenzyme of tartrate resistant acid phosphatase (TRACP-5b)], and iv) bone formation markers [bone-specific alkaline phosphatase (bALP) and osteocalcin (OC)]. Patients with MM had increased levels of serum sclerostin compared with MGUS patients (mean value±SD: 0.48±0.46 vs. 0.26±0.29 ng/ml; p=0.004) and healthy controls (0.31±0.20 ng/ml, p=0.01). In contrast, both patients with MM and MGUS had reduced levels of serum SPARC (26.3±16.2 and 27.2±18.0 ng/ml, respectively) compared to controls (52.8±50.2 ng/ml; p<0.001). Sclerostin values strongly correlated with beta2-microglobulin (r=0.354, p<0.0001), cystatin-C (r=0.389, p<0.0001), serum creatinine (r=0.380, p<0.0001), and bALP (r=-0.541, p<0.0001). No correlations were observed between sclerostin with sRANKL, OPG, Dkk-1 or SPARC. Patients with advanced bone disease assessed by conventional radiography (>3 lytic lesions and/or a pathological fracture) had a borderline increase of sclerostin compared to all others (median value: 0.51 vs. 0.41 ng/ml, p=0.09). Patients with ISS-3 disease had increased levels of sclerostin compared to patients with ISS-1 and ISS-2 MM (ANOVA p=0.001). Median survival of MM patients was 48 months and median follow-up period was 20 months. Patients who had a serum sclerostin of ≥0.62 ng/ml (upper quartile, n=40 patients) had a median survival of 27 months, while median survival of all other patients was 98 months (p=0.031). In conclusion, our study provided evidence that sclerostin is increased in the serum of patients with MM and correlates with advanced ISS stage, increased bone resorption, reduced osteoblast function and poor survival. SPARC is reduced in MM possibly confirming the reduced osteoblast function observed in these patients. Sclerostin seems to participate in the biology of MM and thus it may be a possible target for the development of novel therapies that can both increase osteoblast function and target myeloma cells.
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| 7. |
- Terpos, Evangelos, et al.
(författare)
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International Myeloma Working Group Recommendations for the Treatment of Multiple Myeloma-Related Bone Disease.
- 2013
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 31:18, s. 179-2347
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSEThe aim of the International Myeloma Working Group was to develop practice recommendations for the management of multiple myeloma (MM) -related bone disease.MethodologyAn interdisciplinary panel of clinical experts on MM and myeloma bone disease developed recommendations based on published data through August 2012. Expert consensus was used to propose additional recommendations in situations where there were insufficient published data. Levels of evidence and grades of recommendations were assigned and approved by panel members.RecommendationsBisphosphonates (BPs) should be considered in all patients with MM receiving first-line antimyeloma therapy, regardless of presence of osteolytic bone lesions on conventional radiography. However, it is unknown if BPs offer any advantage in patients with no bone disease assessed by magnetic resonance imaging or positron emission tomography/computed tomography. Intravenous (IV) zoledronic acid (ZOL) or pamidronate (PAM) is recommended for preventing skeletal-related events in patients with MM. ZOL is preferred over oral clodronate in newly diagnosed patients with MM because of its potential antimyeloma effects and survival benefits. BPs should be administered every 3 to 4 weeks IV during initial therapy. ZOL or PAM should be continued in patients with active disease and should be resumed after disease relapse, if discontinued in patients achieving complete or very good partial response. BPs are well tolerated, but preventive strategies must be instituted to avoid renal toxicity or osteonecrosis of the jaw. Kyphoplasty should be considered for symptomatic vertebral compression fractures. Low-dose radiation therapy can be used for palliation of uncontrolled pain, impending pathologic fracture, or spinal cord compression. Orthopedic consultation should be sought for long-bone fractures, spinal cord compression, and vertebral column instability.
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| 8. |
- Tsartsalis, Athanasios N., et al.
(författare)
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The role of biphosphonates in the management of thalassemia-induced osteoporosis: a systematic review and meta-analysis
- 2018
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Ingår i: HORMONES-INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM. - : SPRINGER. - 1109-3099. ; 17:2, s. 153-166
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Forskningsöversikt (refereegranskat)abstract
- Thalassemia Major (TM) is a clinical entity with a high prevalence of low bone mass. The aim of the present study was to perform a meta-analysis of all available data on the role of bisphosphonates (BPs) in the therapy of thalassemia major-induced osteoporosis. The PRISMA recommendations for reporting systematic reviews and meta-analyses were used to guide the present study. We searched PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL) through March 31, 2017 for articles related to thalassemia and BPs. To meta-analytically synthesize the primary endpoint, we used the standardized mean difference (SMD) after Hedgess g transformation under the scenario of a random effects model. Heterogeneity across studies was examined using the I (2) statistic. Nine randomized controlled trials (RCTs) containing original data were included in this review. Three studies were performed in Italy, one in Australia, three in Greece, one in Cyprus, and one in China. The BPs investigated included zoledronate, alendronate, pamidronate, clodronate, and neridronate. Zoledronate and alendronate showed a tendency to perform best as compared to neridronate and the placebo effect with respect to femoral neck, lumbar spine, total hip, and total body in terms of bone mass density (g/cm(2)). BPs and in particular, zolendronate, were quite effective in the treatment of osteoporosis. These findings suggested that bisphosphonates are still a front-line treatment of osteoporosis in TM. However, to draw more meaningful and significant conclusions for the use and efficacy of BP in TM, larger and more complete RCTs should be conducted.
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| 9. |
- Voskaridou, Ersi, et al.
(författare)
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High Circulating Levels of Sclerostin Correlate with Bone Mineral Density In Patients with Thalassemia and Osteoporosis: The Role of the Wnt Signaling In the Pathogenesis of Bone Loss In Thalassemia
- 2010
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 116:21, s. 1010-1010
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Tidskriftsartikel (refereegranskat)abstract
- Abstract 1010Osteoporosis represents an important cause of morbidity in adult patients with thalassemia. Osteoclast activity is elevated in thalassemia-induced osteoporosis, and thus bisphosphonates have been used for its management. Moreover, osteoblasts are also deregulated in thalassemia patients but there is very limited data for the underlying mechanisms of this deregulation. Osteocyte seems to be a key cell for the control of bone remodeling. Sclerostin is a secreted inhibitor of the wingless-type and integrase 1 (Wnt) canonical pathway which is produced by osteocytes and has inhibitory effects on bone formation by preventing the activation of lining cells as well as by inhibiting the function of active osteoblasts. The aim of this study was to evaluate, for the first time, the circulating levels of sclerostin in patients with thalassemia and osteoporosis who received therapy with zoledronic acid (ZOL) and explore possible correlations with clinical and laboratory data in an attempt to clarify if there is any role of sclerostin in the pathogenesis of bone loss in thalassemia. Sixty-six patients (22M/44F, median age 42 years) with thalassemia-induced osteoporosis who participated in a phase 2, randomized, placebo-controlled trial, which was previously published, were studied. In summary, patients were blindly randomized to receive ZOL at a dose of 4 mg, iv, in 15 min infusion, every 6 months (group A, n=23) or every 3 months (group B, n=21), or to receive placebo every 3 months (group C, n=22) for a 12-month period (Voskaridou et al, Hametologica 2006;91:1193-202). Bone mineral density (BMD) of the lumbar spine (L1-L4), femoral neck (FN) and distal radius (R) was determined using Dual-energy X-ray Absorptiometry before and 12 months post-ZOL treatment. Circulating sclerostin was measured in the serum of all patients at baseline and after 12 months of therapy, using an ELISA methodology developed by BDF for Biomedica Medizinprodukte (Vienna, Austria), along with a series of serum bone indices: i) bone resorption markers [C-terminal telopeptide of collagen type-1 (CTX) and tartrate resistant-acid phosphatase (TRACP-5b)]; ii) bone formation markers [bone-alkaline phosphatase (bALP), osteocalcin and C-terminal propeptide of collagen type-I (CICP)]; iii) osteoclast regulators [RANKL, osteoprotegerin (OPG) and osteopontin] and iv) dickkopf-1 (Dkk-1), which is another inhibitor of Wnt signaling, as previously described (Voskaridou et al, Haematologica 2009;94:725-8). The above bone markers were also evaluated in 30, age- and gender-matched, healthy controls (11M/19F, median age 44 years), while sclerostin was also measured in 62 women with post-menopausal osteoporosis (median age 63 years). At baseline, patients with thalassemia and osteoporosis had elevated circulating levels of sclerostin (median: 605 pg/mL, range: 22–1227 pg/mL) compared to healthy controls (250 pg/mL, 0–720 pg/mL, p<0.001) and reduced levels of sclerostin compared with postmenopausal women with osteoporosis (840 pg/mL, 181–1704 pg/mL, p<0.001). Patients with thalassemia had also increased values of CTX (p<0.001), Dkk-1 (p<0.001), bALP (p<0.001), CICP (p=0.003), TRACP-5b (p<0.01), and sRANKL/OPG ratio (p=0.001). Sclerostin levels correlated with BMD in all studied sites L1-L4 (r=0.454, p<0.001), R (r=0.324, p=0.01) and FN (r=0.268, p=0.035). Similar results were obtained for post-menopausal women with osteoporosis for L1-L4 BMD (r=0.501, p<0.001). The other Wnt inhibitor, Dkk-1 also correlated with BMD of L1-L4 (r=-0.290, p=0.022) and R (r=-0.415, p=0.001). Patients who received ZOL did not alter their sclerostin levels after 12 months of therapy, but reduced their circulating Dkk-1 (from 39.6±16.6 to 28.9±16.3 pmol/L, p=0.004). In contrast, placebo group patients showed an increase of sclerostin levels (p=0.01) and a borderline increase of Dkk-1 (p=0.08). In conclusion, the results of this study show that circulating sclerostin is elevated in thalassemia patients with osteoporosis and correlated with their BMD. Furthermore, the high Dkk-1 serum levels and their association with BMD observed in these patients support the notion of a disrupted Wnt signaling in patients with thalassemia and osteoporosis which leads, in turn, to osteoblast deregulation. These findings give the rationale for the use of novel drugs targeting sclerostin and Dkk-1 in patients with thalassemia-induced osteoporosis.
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