Osteoporosis in Sickle Cell/β-Thalassemia Is Primarily Caused by an Imbalance at the RANKL/OPG Pathway.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3173-3173
Author(s):  
Ersi Voskaridou ◽  
Ioannis Papassotiriou ◽  
Evangelos Premetis ◽  
John Meletis ◽  
Dimitris Loukopoulos ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Renal Function ◽  
Bone Resorption ◽  
Bone Loss ◽  
Sickle Cell ◽  
Type I ◽  
Mineral Density ◽  
T Score ◽  
Tracp 5B ◽  
Marrow Expansion

Abstract Bone involvement is the commonest clinical manifestation of sickle cell disease (SCD) including chronic disorders, such as osteopenia/osteoporosis. The aim of the present study is to evaluate the bone mineral density (BMD) of patients with SCD/β-thalassemia (S/β-th) in parallel with markers of bone turnover in an attempt to better understand the pathophysiology of bone loss in these patients. We studied 52 patients with S/β-th (23M/29F; median age 40 y). The BMD of the lumbar spine (L) and femoral neck (F) was evaluated by DEXA. Bone remodeling was assessed using the following serum indices: (a) bone resorption markers [C-telopeptide of type-I collagen (CTX), tartrate-resistant acid phosphatase isoform-5b (TRACP-5b)], (b) bone formation markers [bone-alkaline phosphatase (bALP), osteocalcin (OC), and C-terminal propeptide of collagen type-I (CICP)], and (c) osteoclast stimulating factors [soluble receptor activator of nuclear factor κB ligand (sRANKL), and osteoprotegerin (OPG)]. Moreover, all patients had a thorough evaluation of their renal function (creatinine clearance, and cystatin-C serum levels), bone marrow expansion (soluble transferin receptors, sTfR), serum erythropoietin (Epo) and parathyroid hormone (PTH) levels. The same biochemical parameters were also determined in 25 age- and gender-matched controls. According to WHO criteria, 17 patients (32.6%; 8M/9F, median age 45 y) had osteopenia or osteoporosis (median L/T-score: −2.26; L/BMD: 0.9 g/cm2; F/T-score: −1.86; F/BMD: 0.68 g/cm2). In contrast, 30 patients (57.6%; 12M/18F, median age 40 y) had osteosclerosis (median L/T-score: +3.15; L/BMD: 1550.5 g/m2; F/T-score: +0.52; F/BMD: 1113.5 g/cm2). Renal function, Epo, Hb and sTfR levels and the number of crises/year were similar between both groups. All patients displayed increased levels of OPG, bALP, and CICP compared with controls (p<0.02). CTX levels in the osteosclerotic patients were significantly lower than those of both controls (p<0.0001) and osteopenic/osteoporotic patients (p<0.003); this finding implies a diminished bone resorption. Moreover, bALP and PTH in the osteopenia/osteoposis group were higher than those of the osteosclerosis group (p<0.01, and <0.03, respectively). BMD of the osteopenic/osteoporotic patients showed a strong correlation with OPG and CTX levels (p=0.01, and 0.008, respectively). This result, in combination with the significant correlations observed between OPG and sRANKL, TRACP-5b, and bALP in these patients suggests that osteopenia/osteoporosis in S/β-th results mainly from an imbalance at the RANKL/OPG axis. Conversely, considering the absence of correlation between BMD and sTfR in the same patient group, the potential contribution of bone marrow expansion in the development of osteopenia appears much weaker. No correlation between BMD and bone indices observed in osteosclerotic group. In conclusion, this study suggests that the development of bone loss in S/β-th patients is mainly due to an imbalance in RANKL/OPG pathway. Novel agents that target this system, as well as bisphosphonates, maybe useful in the management of this common SCD complication.

scholarly journals Ethanolic Extract of Rubus coreanus Fruits Inhibits Bone Marrow-Derived Osteoclast Differentiation and Lipopolysaccharide-Induced Bone Loss

2017 ◽  
Vol 12 (12) ◽  
pp. 1934578X1701201
Author(s):  
Tae-Ho Kim ◽  
Chae Gyeong Jeong ◽  
Hyeong-U Son ◽  
Man-Il Huh ◽  
Shin-Yoon Kim ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Resorption ◽  
Bone Loss ◽  
Osteoclast Differentiation ◽  
Ethanolic Extract ◽  
Type I ◽  
Mineral Density ◽  
Induced Differentiation ◽  
Rubus Coreanus

The inhibition of osteoclast differentiation/bone resorption is a well-known therapeutic strategy for controlling pathological and postmenopausal bone loss. Natural products that specifically inhibit osteoclastogenesis could therefore be developed as antiresorptive drugs for the treatment of metabolic bone disorders characterized by excessive osteoclastic bone resorption. We therefore examined the effects of Rubus coreanus extract (eeRc) on receptor activator of nuclear factor kappa-B ligand (RANKL)-induced differentiation of bone marrow macrophages (BMMs) into osteoclasts and pit formation in vitro. Additionally, the in vivo effects of the eeRc were observed in mice with lipopolysaccharide (LPS)-induced bone erosion. In this study, we found that the ethanolic extract of Rubus coreanus fruits considerably suppressed the RANKL-induced differentiation of primary BMMs into osteoclasts and bone-resorbing activity of mature osteoclasts. Oral administration of eeRc attenuated LPS-induced bone loss in vivo, as demonstrated by the reversal of LPS-induced reduction in bone volume per tissue volume, bone mineral density, and trabecular number to some extent in eeRc-treated mice. In addition, eeRc slightly decreased the serum levels of C-terminal telopeptide fragments of type I collagen, the collagen-breakdown product generated by osteoclasts. Collectively, our results indicate that eeRc has the potential to inhibit bone loss by blocking osteoclast differentiation and could therefore be a promising natural product for the prevention and/or treatment of inflammatory bone loss.

Increased Bone Resorption Is Implicated in the Pathogenesis of Bone Loss in Hemophilia Patients: Correlations with Severity of Hemophilic Arthropathy and HIV Infection.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 493-493 ◽  
Author(s):  
O. Katsarou ◽  
Evangelos Terpos ◽  
P. Hatzismalis ◽  
S. Provelengios ◽  
T. Adraktas ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Turnover ◽  
Hiv Infection ◽  
Clinical Score ◽  
Hiv Positive ◽  
T Score ◽  
Hemophilic Arthropathy ◽  
Tracp 5B ◽  
Radiological Score

Abstract Osteoporosis has been recently recognized as a comorbidity factor, which affects significantly the quality of life in hemophilia patients. Prolonged immobilization and severity of arthropaphy have been considered as the major factors contributing to the pathogenesis of osteoporosis in hemophilia. However, the exact mechanisms of bone loss have not been fully clarified in this disorder. The aim of this study was to evaluate the incidence of osteoporosis in hemophilia patients, and investigate the possible correlations with clinical and laboratory data in an attempt to better understand the pathogenetic mechanisms that are involved in its development. Ninety-three hemophilia patients were evaluated. Their median age was 36 years (range: 24–46 years). Eighty patients (86%) had severe and 13 patients (13%) moderate haemophilia. Fifty-seven patients (61%) were HIV negative and 36 (38%) HIV positive. The severity of hemophilic arthropahty was assessed using WFH clinical score and Petterson radiological score in all patients. Bone mineral density of the lumbar spine(LS) and the femoral neck(FN) was measured using DEXA technique in 78 out of 93 patients. Bone turnover was studied by the measurement of a series of serum indices: bone resorption markers [N- and C-telopeptide of type-I collagen (NTX and CTX, respectively), and tartrate-resistant acid phosphatase isoform-5b (TRACP-5b)], bone formation markers [bone-alkaline phosphatase (bALP), and osteocalcin], and osteoclast stimulating factors [receptor activator of nuclear factor-kB ligand (RANKL), osteoprotegerin (OPG), and tumor necrosis factor-alpha]. Osteopenia(−2,5<T-score<−1.5) or osteoporosis (T-score<−2,5) was found in 83.9% and 60% of the patients in the FN and LS respectively. Osteoporosis was more common among HIV positive patients in both FN (65.3%vs.41.6%; p=0.007) and LS (17.86%vs.5.41%, p=0.004).The severity of osteoporosis in the FN correlated with patients’ total clinical and radiological score (p=0.001). Hemophilia patients showed increased serum levels of all markers of bone resorption and bALP compared with 15 controls of similar gender and age (median NTX: 19.4 vs. 17.4 nM BCE, p=0.018; CTX: 0.61 vs. 0.47 ng/mL, p=0.028; TRACP-5b: 2.7 vs. 1.3 U/L, p<0.01; and bALP: 20.0 vs. 16.9 U/L, p=0.048; for patients and controls, respectively). This increased osteoclastic activity was not found to be mediated by RANKL/RANK/OPG system as we observed no difference in terms of sRANKL/OPG ratio between patients and controls. Therefore it seems that other factors are involved in the increased bone resorption observed in hemophiliacs. In multivariate analysis, HIV infection (p=0.05) and total clinical score (p=0.001), were found to be independent prognostic factors for developing osteoporosis. Our study has shown that the incidence of osteoporosis is high among hemophilia patients and is related to the severity of hemophilic arthropathy. We report for the first time that hemophilia patients have high bone turnover, which seems not to be due to an imbalance of the RANKL/OPG system. HIV infection increases the negative effects of hemophilia on bone metabolism and may contribute to the pathogenetic mechanisms involved in osteoporosis development.

First-Line Chemotherapy Leads to High Bone Turnover and Reduced Bone Mass in Patients with Non-Hodgkin's Lymphoma (NHL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1951-1951 ◽  
Author(s):  
Konstantinos Anargyrou ◽  
Theodoros P. Vassilakopoulos ◽  
Konstantinos Tsionos ◽  
Panayiotis Kokkoris ◽  
Georgios Boutsikas ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Cell Lymphoma ◽  
Lumbar Vertebra ◽  
First Line ◽  
High Bone Turnover ◽  
T Score ◽  
Tracp 5B ◽  
High Bone ◽  
Line Chemotherapy

Abstract Abstract 1951 Poster Board I-974 Chemotherapy associated osteoporosis is a severe problem in patients with malignant diseases as it increases the risk for fractures and deteriorates quality of life. There are very limited data in the literature for the effect of chemotherapy on bone metabolism of adult patients with NHL. To elucidate this issue we scheduled a prospective study in which patients with newly-diagnosed NHL had a thorough evaluation of bone remodeling pre- and post- first-line chemotherapy. As of June 2009, 33 (20M/13F, median age 61 years, range: 28-90 years) of 52 patients, who were entered into this study, had completed their chemotherapeutic scheme: 19 patients (57%) had diffuse large B-cell lymphoma, 5 (15%) follicular lymphoma (grade III), 4 (12%) mantle-cell lymphoma, 4 marginal-zone lymphoma and one T-cell NHL. Twelve (36%) of those had stage IV disease and 17 (51%) had B-symptoms before therapy. Twenty-six patients (78%) received R-CHOP (25 every 21 days and 5 every 14 days), 2 received R-COP and one CHOP as first-line therapy for their disease. Bone mineral density (BMD) of the lumbar spine (L1-L4, antero-posterior view), and femoral neck (FN) was measured by dual energy X-ray absorptiometry (DXA) using a Hologic QDR-1000 scanner on day 1 of cycle 1 (baseline) and on day 30 post the last cycle of chemotherapy. The following serum indices of bone metabolism were measured on the days of DXA: i) osteoclast stimulators [sRANKL and osteoprotegerin (OPG)], ii) osteoblast inhibitor dickkopf-1 (Dkk-1), iii) bone resorption markers [C-telopeptide of collagen type-I (CTX) and tartrate-resistant acid phosphatase-5b (TRACP-5b)], and iv) bone formation markers [bone alkaline phosphatase (bALP) and osteocalcin (OC)]. The above markers were also evaluated in 24 healthy controls of similar gender and age. Patients were assessed for skeletal-related events (SREs) throughout the period of the study. At baseline, NHL patients had a median T-score of L1-L4 BMD of -0.65 (range -4.27 to +3.68) and of FN BMD of -1.1 (-4.01 to +0.2). The median T-score of the lumbar vertebra with the major bone loss was -1.44 (-4.6 to +3.03). At baseline patients had increased levels of Dkk-1 (p=0.036) and reduced levels of OC (p<0.001) compared to controls. In terms of bone resorption, CTX, TRACP-5b and sRANKL/OPG ratio did not differ between patients and controls. There was a strong correlation between L1-L4 and FN BMD (r=0.64, p<0.0001) as well as between L1-L4 BMD and Dkk-1 (r=-0.617, p<0.0001) and between CTX with TRACP-5b (r=0.65, p<0.0001) and sRANKL (r=0.413, p=0.036). There was no correlation between BMD and NHL stage. The administration of chemotherapy resulted in a dramatic reduction of BMD in L1-L4 (median T-score: -1.32; range -4.6 to +3.04; p=0.001 and median T-score of the lumbar vertebra with the major loss: -1.95; range: -4.84 to +2.72; p=0.002) and in a less impressive reduction in FN BMD (median T-score: -1.2; range: -3.68 to +0.38; p=0.022) compared to baseline values. The reduction of L1-L4 BMD post-chemotherapy was more profound in males (p=0.01) than in females (p=0.05) and in patients of >55 years (p=0.007) compared to all others (p=0.059). This reduction was irrespective of the NHL stage (I/II vs. III/IV), while patients who received 8 cycles of chemotherapy had a greater reduction of L1-L4 (p<0.0001) and FN (p=0.044) BMD compared to all others. The administration of chemotherapy also resulted in a dramatic increase of CTX (p=0.019) which was mainly due to a similar increase of sRANKL/OPG ratio (p=0.005). Both markers of bone formation, bALP (p=0.001) and OC (p<0.0001) were increased, while Dkk-1 showed a borderline increase post-therapy (p=0.1). All studied markers of bone remodeling were increased in NHL patients post-chemotherapy compared to controls (p<0.01 for CTX, TRACP-5b, bALP, Dkk-1, sRANKL and OPG; p=0.04 for OC and sRANKL/OPG ratio). There was a greater increase of CTX (p=0.04), sRANKL/OPG (p=0.015), TRACP-5b (p=0-.03), bALP (p=0.003) and OC (p<0.0001) in patients who received 8 cycles of chemotherapy compared to all others. During study period, one patient had a pathological fracture in his right FN. Our on-going study suggests that first-line chemotherapy results in high bone turnover, which leads to increased bone loss and reduced BMD of L1-L4 and FN in NHL patients. The confirmation of these results in a larger cohort of patients may lead to the prophylactic use of anti-resorptive agents, such as bisphosphonates in these patients. Disclosures: No relevant conflicts of interest to declare.

Zoledronic Acid Increases Bone Mineral Density in Patients with Thalassemia Intermedia-Induced Osteoporosis Regardless of the Incessant Bone Marrow Expansion.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3813-3813
Author(s):  
Ersi Voskaridou ◽  
Dimitrios Christoulas ◽  
Lito Antoniadou ◽  
Panagiotis Tsaftaridis ◽  
Eleni Plata ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Marrow ◽  
Placebo Group ◽  
Zoledronic Acid ◽  
Bone Loss ◽  
Bone Pain ◽  
Bone Remodelling ◽  
Erythropoietic Activity ◽  
Mineral Density ◽  
Marrow Expansion

Abstract Osteoporosis represents an important cause of morbidity in adult patients with thalassemia. Its pathogenesis is multifactorial, and includes mainly bone marrow expansion, endocrine dysfunction and iron overload. Patients with thalassaemia intermedia (TI) seem to have a more expanded bone marrow with pressure on cortical bone, which causes pain and bone loss in several cases. The measurement of soluble transferrin receptor (sTfR) and erythropoietin (Epo) in the serum is considered as accurate marker of erythropoietic activity in thalassemia. Bisphosphonates are potent inhibitors of osteoclast activity and have been used for the management of thalassemia-induced osteoporosis. The aim of this study was to evaluate the effect of zoledronic acid, the most potent aminobisphosphonate, on bone mineral density (BMD) of patients with TI and explore possible correlations with bone marrow expansion and erythropoietic activity. Thirty-five patients with TI and osteopenia or osteoporosis (13M/22F, median age 45 years) were evaluated. Twenty-three were randomized to receive zoledronic acid, 4 mg, IV, every 3 months (n=12) or every 6 months (n=11) for one year, while 12 patients received placebo every 3 months. There was no difference in terms of the presence of gonadal dysfunction between the three studied groups. BMD of the lumbar spine (L), femoral neck and forearm was determined in all patients, using DEXA, before and 12 months after treatment. Bone marrow expansion was assessed by the measurement of sTfR and Epo serum levels, using an ELISA methodology (R&D Systems, Minneapolis, MN, USA), before and 12 months post zoledronic acid or placebo administration. In all patients markers of bone remodelling, such as C-telopeptide of collagen type-I (CTX) and bone specific alkaline phosphatase (bALP) were also measured by ELISA (Nordic Bioscience Diagnostics, Herlev, Denmark, and Quidel, San Diego, CA, USA, respectively). Patients were asked to quantify their degree of bone pain on Huskisson’s visual analogue scale and the McGill-Melzack scoring system before and 12 months post-therapy. All patients had increased values of sTfR, Epo, CTX, and bALP compared with 40 controls of similar age and gender (p&lt;0.001). Patients who received zoledronic acid showed a significant increase in their L-BMD (p=0.01), which was accompanied by a dramatic reduction in CTX and bALP values ((p&lt;0.001). There was no difference in terms of L-BMD changes between zoledronic acid groups. Placebo group showed an aggravation of L-BMD (p=0.041) and markers of bone remodelling at 12 months. No other changes were observed in the BMD of other sites. Zoledronic acid reduced bone pain, which remained stable in placebo group during the study period. There was only weak correlation between baseline sTfR levels and L-BMD, while there was no correlation between Epo or hemolytic parameters (indirect bilirubin, reticulocytes counts, and LDH) with BMD of all studied sites. Serum sTfR and Epo values showed a significant elevation after 12 months of therapy in all studied groups (p&lt;0.01, p&lt;0.02, and p&lt;0.01, respectively); this elevation was irrespective of the L-BMD changes. This study suggests that the increase of BMD produced by zoledronic acid in TI is irrespective of the continuous increase of bone marrow expansion, which is considered a major cause of bone loss in this hemoglobinopathy.

scholarly journals Serum Concentrations of Cross-Linked N-Telopeptides of Type I Collagen: New Marker for Bone Resorption in Hemodialysis Patients

2005 ◽  
Vol 51 (12) ◽  
pp. 2312-2317 ◽  
Author(s):  
Yoshifumi Maeno ◽  
Masaaki Inaba ◽  
Senji Okuno ◽  
Tomoyuki Yamakawa ◽  
Eiji Ishimura ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Type I Collagen ◽  
Bone Alkaline Phosphatase ◽  
Bone Resorption Marker ◽  
Type I ◽  
Serum Concentrations ◽  
Mineral Density ◽  
Intact Osteocalcin ◽  
Bone Formation Markers

Abstract Background: Urinary cross-linked N-telopeptide of type I collagen (NTX) is a reliable bone resorption marker in patients with metabolic bone disease. We assessed a clinically available serum NTX assay suitable for anuric patients on hemodialysis (HD). Methods: Serum concentrations of NTX, C-terminal telopeptide of type I collagen (β-CTX), pyridinoline (PYD), and deoxypyridinoline (DPD) were determined as bone resorption markers, and those of bone alkaline phosphatase (BAP) and intact osteocalcin (OC) as bone formation markers, in 113 male HD patients (mean age, 59.3 years; mean HD duration, 67.7 months). Each patient’s bone mineral density (BMD) in the distal third of the radius was measured twice, with a 2-year interval between measurements, by dual-energy x-ray absorptiometry. Results: Serum NTX correlated significantly with β-CTX, PYD, DPD, BAP, and intact OC. NTX, as well as β-CTX, PYD, DPD, BAP, and intact OC, correlated significantly with BMD at the time of measurement. NTX, β-CTX, and DPD correlated significantly with the annual change in BMD during the 2-year period thereafter, in contrast to PYD, BAP, and intact OC. Patients in the highest quartile of serum NTX concentrations showed the fastest rate of bone loss. The sensitivity and specificity for detecting rapid bone loss were 48% and 83%, respectively, for serum NTX. Conclusion: Serum NTX may provide a clinically relevant serum assay to estimate bone turnover in HD patients.

scholarly journals Rhus javanicaGall Extract Inhibits the Differentiation of Bone Marrow-Derived Osteoclasts and Ovariectomy-Induced Bone Loss

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Tae-Ho Kim ◽  
Eui Kyun Park ◽  
Man-Il Huh ◽  
Hong Kyun Kim ◽  
Shin-Yoon Kim ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Resorption ◽  
Bone Loss ◽  
Bone Turnover ◽  
Bone Remodeling ◽  
Bone Mineral ◽  
Osteoclast Differentiation ◽  
Protective Effects ◽  
Mineral Density ◽  
Femoral Bone Mineral Density

Inhibition of osteoclast differentiation and bone resorption is a therapeutic strategy for the management of postmenopausal bone loss. This study investigated the effects ofRhus javanica(R. javanica) extracts on bone marrow cultures to develop agents from natural sources that may prevent osteoclastogenesis. Extracts ofR. javanica(eGr) cocoons spun byRhus javanica(Bell.) Baker inhibited the osteoclast differentiation and bone resorption. The effects of aqueous extract (aeGr) or 100% ethanolic extract (eeGr) on ovariectomy- (OVX-) induced bone loss were investigated by various biochemical assays. Furthermore, microcomputed tomography (µCT) was performed to study bone remodeling. Oral administration of eGr (30 mg or 100 mg/kg/day for 6 weeks) augmented the inhibition of femoral bone mineral density (BMD), bone mineral content (BMC), and other factors involved in bone remodeling when compared to OVX controls. Additionally, eGr slightly decreased bone turnover markers that were increased by OVX. Therefore, it may be suggested that the protective effects of eGr could have originated from the suppression of OVX-induced increase in bone turnover. Collectively, the findings of this study indicate that eGr has potential to activate bone remodeling by inhibiting osteoclast differentiation and bone loss.

AB0840 INFLUENCE OF PSORIATIC ARTHRITIS (PsA) ON BONE LOSS AND ANALYSIS BETWEEN AXIAL AND PERIPHERAL PsA IN JAPANESE PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1726.1-1726
Author(s):  
S. Tsuji ◽  
T. Tomita ◽  
M. Higashiyama ◽  
T. Noguchi ◽  
T. Mouri ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Lumbar Spine ◽  
Bone Loss ◽  
Bone Remodeling ◽  
Japanese Patients ◽  
Type I ◽  
Effector Molecules ◽  
T Score ◽  
Asas Classification Criteria ◽  
Tracp 5B

Background:Osteoporosis is one of the major comorbidities in patients with psoriasis and psoriatic arthritis (PsA). It has been reported that PsA induces fragility bone structure1and high risk of osteoporosis2. However, there is no report about relationship between psoriatic arthritis and osteoporosis in Japanese patients and its mechanism has not been elucidated.Objectives:The objective of this study is to investigate influence of PsA on bone mineral density (BMD) and its mechanism including analysis between axial and peripheral PsA in Japanese patients.Methods:This study was retrospective study. We examined 58 cases of PsA and 29 cases of RA that underwent DXA tests at our facility from January 2017 to July 2019 (Table 1). The axial PsA was classified as axial SpA using the ASAS classification criteria. First, we investigated influence of PsA containing both axial (n=30,19 males, 11 females, mean age: 50.6 years) and peripheral (n=28, 19 males, 9 females, mean age: 58.0 years) subtypes on BMD measured by dual-energy X-ray absorptiometry. Second, we measured serum bone metabolism markers (P1NP: type I procollagen-N-propeptide, TRACP-5b: tartrate-resistant acid phosphatase 5b) and bone remodeling effector molecules (Dkk1: Dickkopf1, sclerostin, 25(OH)D: 25-hydroxyvitamin D) to elucidate differences in BMD between axial and peripheral PsA. Furthermore, rheumatoid arthritis (RA) (n=29, 2 males, 27 females, mean age: 66.2 years), as a reference disease, was also evaluated for comparison with axial and peripheral PsA.Osteoporosis and Osteopenia were defined as T-score ≤ -2.5 or %YAM ≤70%., -1.0< T-score >-2.5 or 80>%YAM >70% respectively.Results:58 patients with PsA indicated low T-score, Z-score and %YAM in both lumbar spine and proximal femur (Table 1). Axial PsA and peripheral PsA showed osteoporosis in 16.7% and 35.7%, and osteopenia in 20.0% and 32.1%, respectively, despite the fact that there were many middle-aged men. Comparison between axial and peripheral PsA, axial PsA showed higher BMDthan peripheral PsA. In bone remodeling makers, P1NP in both PsA were almost same, but TRACP-5b, bone resorption marker, in axial PsA was lower than that in peripheral PsA(Table 2). In bone remodeling influencer molecules, Dkk1, and sclerostin in axial PsA was slightly higher than those in peripheral PsA, whereas 25(OH)D is almost same as the both PsA. On the other hand, RA also indicated low T-score and %YAM in both lumbar spine. P1NP in RA showed slightly lower, but TRACP-5b and Homocysteine in RA higher than those in axial and peripheral PsA. Dkk1 and sclerostin in RA were slightly lower than those in both PsA.Conclusion:Peripheral PsA indicated more severe bone loss than axial PsA in our study. There were some differences in bone remodeling markers and bone remodeling effector molecules between axial and peripheral PsA, but the relationships between BMD and these parameters were not confirmed. Further studies are needed to elucidate bone loss mechanism in these PsA.References:[1]Zhu TY, et al. Osteoporosis Int. 2015; 26:261–272.[2]Kathuria R, et al. J Am Acad Dermatol. 2017;76:1045-53.Disclosure of Interests:Shigeyoshi Tsuji Grant/research support from: Eli Lilly, Speakers bureau: AbbVie, Asahi Kasei, Chugai, Daiichi Sankyo, Eli Lilly, Eisai, Mitsubishi Tanabe, Celgene, and Novartis Pharma K.K., Tetsuya Tomita Consultant of: Eli Lilly and Company, Mari Higashiyama: None declared, Takaaki Noguchi: None declared, Toshikazu Mouri: None declared, Jun Hashimoto Speakers bureau: AbbVie, Asahi Kasei, Chugai, Daiichi Sankyo, Eli Lilly, Eisai, Mitsubishi Tanabe, Celgene, and Novartis Pharma K.K.

Low Bone Mineral Density and High Bone Turnover In Patients with Non-Hodgkin's Lymphoma (NHL) Who Receive Frontline Therapy: Results of a Multicenter Prospective Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5071-5071 ◽  
Author(s):  
Konstantinos Anargyrou ◽  
Theodoros P. Vassilakopoulos ◽  
Konstantinos Tsionos ◽  
Panayiotis Kokkoris ◽  
Georgios Boutsikas ◽  
...  
Keyword(s):  
Bone Loss ◽  
Cell Lymphoma ◽  
Lumbar Vertebra ◽  
Mineral Density ◽  
First Line ◽  
High Bone Turnover ◽  
T Score ◽  
Tracp 5B ◽  
High Bone ◽  
Baseline Values

Abstract Abstract 5071 Chemotherapy-associated bone loss is a severe problem in patients with malignancies as it increases the risk for fractures and deteriorates quality of life. However, there are very limited reports in the literature describing the effects of chemotherapy on bone metabolism of adult patients with NHL. To elucidate this issue we scheduled a prospective study in which patients with newly-diagnosed non-Hodgkin's lymphoma (NHL) had a thorough evaluation of bone remodeling, pre- and post- frontline chemotherapy. As of June 2009, 53 patients (33M/20F, median age 59 years, range: 18–90 years) had completed their first-line treatment: 36 patients (67.9%) had diffuse large B-cell lymphoma, 5 (9.4%) follicular lymphoma (grade III), 4 (7.5%) mantle-cell lymphoma, 6 (11.3%) marginal-zone lymphoma and 2 (3.8%) T-cell NHL. Nineteen patients (35.8%) had stage IV disease and B-symptoms before therapy initiation. Forty-seven patients (88.7%) received R-CHOP (40 every 21 days and 7 every 14 days), 4 received R-COP and 2 received CHOP as first-line therapy for their disease. Bone mineral density (BMD) of the lumbar spine (L1-L4, antero-posterior view), and femoral neck (FN) was measured by dual energy X-ray absorptiometry (DXA) on day 1 of cycle 1 (baseline) and on day 30 of the last cycle of chemotherapy. The following serum indices of bone metabolism were measured on the days of DXA: i) osteoclast stimulators [sRANKL and osteoprotegerin (OPG)], ii) osteoblast regulators [parathyroid hormone, vitamin-D, and dickkopf-1 (Dkk-1)], iii) bone resorption markers [C-telopeptide of collagen type-I (CTX) and tartrate-resistant acid phosphatase-5b (TRACP-5b)], and iv) bone formation markers [bone alkaline phosphatase (bALP) and osteocalcin (OC)]. The above markers were also evaluated in 30 healthy controls of similar gender and age. Patients were assessed for skeletal-related events (SREs) throughout the period of the study. At baseline, NHL patients had a median T-score of L1-L4 BMD of -0.63 (range -4.27 to +3.68) and of FN BMD of -0.875 (-4.01 to +2.07). The median T-score of the lumbar vertebra with the major bone loss was -1.425 (-4.6 to +3.03). At baseline patients had reduced levels of OC (p=0.01) compared to controls, while CTX, TRACP-5b and sRANKL/OPG ratio did not differ between patients and controls. There was a strong correlation between L1-L4 and FN BMD (r=0.64, p<0.0001) as well as between CTX with TRACP-5b (r=0.467, p=0.001), sRANKL (r=0.479, p=0.001) and Dkk-1 (r=0.442, p=0.003). Strong correlations were also observed between bALP and sRANKL/OPG ratio (r=0.406, p=0.006), Dkk-1 and TRACP-5b, (r=0.421, p=0.004), sRANKL and CTX (r=0.479, p=0.001). There was no correlation between BMD and NHL stage. The administration of chemotherapy resulted in a dramatic reduction of BMD in L1-L4 (median T-score: -1.12; range -4.49 to +3.04; p<0.001 and median T-score of the lumbar vertebra with the major loss: -1.45; range: -4.84 to +2.72; p=0.001) and in FN BMD (median T-score: -1.115; range: -3.68 to +1.12; p<0.001) compared to baseline values. The reduction of L1-L4 and FN BMD post-chemotherapy was more profound in males (p=0.003 and p=0.001 respectively) than in females (p=0.011 and p=0.01) and in patients of >55 years (p=0.001 and p<0.001 respectively) compared to all others (p=0.037 and p=0.014). This reduction was irrespective of the NHL stage (I/II vs. III/IV), while patients who received 8 cycles of chemotherapy had a greater reduction of L1-L4 (p<0.001) and FN (p=0.001) BMD compared to all others. The administration of chemotherapy also resulted in a dramatic increase of CTX (p=0.017), TRACP-5b (p<0.001), bALP (p<0.001), OC (p<0.001) and Dkk-1 (p=0.022) compared to baseline values. All studied markers of bone remodeling, with the exception of OPG and sRANKL, were significantly increased in NHL patients post-chemotherapy compared to controls (p=0.05 for CTX, p<0.001 for TRACP-5b and Dkk-1, p=0.01 for bALP, p=0.015 for OC). During study period, one male patient had a pathological fracture in his right FN. We conclude that frontline treatment with the combination of chemotherapy and/or rituximab results in high bone turnover, which leads to increased bone loss and reduced BMD of L1-L4 and FN in NHL patients. The prophylactic use of anti-resorptive agents, such as bisphosphonates, or the administration of agents with anti-Dkk-1 activity may be useful for preventing bone loss in these patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Bone Benefits of Fish Oil Supplementation Depend on its EPA and DHA Content

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2701
Author(s):  
Haissam Abou-Saleh ◽  
Allal Ouhtit ◽  
Ganesh V. Halade ◽  
Md Mizanur Rahman
Keyword(s):  
Bone Marrow ◽  
Bone Resorption ◽  
Bone Loss ◽  
Fish Oil ◽  
Signaling Pathways ◽  
Dietary Intervention ◽  
High Dose ◽  
Chow Diet ◽  
Bone Resorption Marker ◽  
Mineral Density

The preventive effect of high-dose (9%) regular-fish oil (FO) against bone loss during aging has been demonstrated, but the effects of a low-dose (1%–4%) of a highly purified concentrated FO (CFO) has not been elucidated. The aim of this study was to determine the dose-dependent effect of a CFO against bone loss in C57BL/6 female mice during aging. Twelve-month old mice were fed with 1% and 4% CFO and 4% safflower oil (SFO) diets, including a group with a 4% regular-FO diet and a group with a lab chow diet for 12 months. Bone mineral density (BMD) was analyzed by dual-energy x-ray absorptiometry (DXA) before and after the dietary intervention. At the end of dietary intervention, bone resorption markers in serum and inflammatory markers in bone marrow and splenocytes and inflammatory signaling pathways in the bone marrow were analyzed. As compared to the 4% SFO control, 4% CFO maintained higher BMD during aging, while 1% CFO offered only a mild benefit. However, the 1% CFO fed group exhibited slightly better BMD than the 4% regular-FO fed group. BMD loss protection by CFO was accompanied by reduced levels of the bone resorption marker, TRAP, and the osteoclast-stimulating-factor, RANKL, without affecting the decoy-receptor of RANKL, osteoprotegerin (OPG). Further, CFO supplementation was associated with an increase in the production of IL-10, IL-12, and IFN-γ and a decrease in the production of TNF-α and IL-6, and the activation of NF-κB, p38 MAPK, and JNK signaling pathways. In conclusion, the supplementation of 4% CFO is very efficient in maintaining BMD during aging, whereas 1% CFO is only mildly beneficial. CFO supplementation starting at middle age may maintain better bone health during aging.

Zoledronic Acid (ZOL) Markedly Improves Bone Mineral Density (BMD) for Patients (Pts) with Monoclonal Gammopathy of Undetermined Significance (MGUS) and Bone Loss.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3606-3606
Author(s):  
James R. Berenson ◽  
Ori Yellin ◽  
Ralph V. Boccia ◽  
Marshall S. Flam ◽  
Siu-Fun Wong ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Disease ◽  
Metastatic Bone Disease ◽  
Lymphocytic Leukemia ◽  
High Risk Population ◽  
Mineral Density ◽  
T Score ◽  
Increased Risk ◽  
Prior Use

Abstract MGUS occurs in 5% of individuals over 70 yrs of age and these pts have been found to have increased rates of bone resorption. Osteoporosis associated with MGUS have higher bone resorption compared to sex and aged-matched pts with osteoporosis but without evidence of MGUS. Not only do pts with MGUS have a higher prevalence of osteopenia/osteoporosis than the normal population but they also have an increased risk of fractures (fx). ZOL has been shown to increase BMD in the treatment of gonadotropin agonist-induced osteoporosis in men with prostate cancer without metastatic bone disease when administered every 3 mos at 4 mg. The rationale for the use of ZOL for pts with osteopenia/osteoporosis in the setting of MGUS is based on these studies coupled with the knowledge that pts with this disorder have a higher prevalence of bone loss and fx risk. To date, no agents have been formally studied in the treatment of osteopenia/osteoporosis associated with MGUS. A schedule of 4 mg every 6 mos has been shown to be safe and effective in increasing BMD for other cancer pts without metastatic bone disease but with significant bone loss. This open-label study was designed to evaluate the efficacy and safety of this dose and schedule of ZOL for MGUS pts with significant loss of bone. Pts had to have osteopenia/osteoporosis (T-score worse than -1) as verified by a DEXA scan and a diagnosis of MGUS. Pts with prior use of oral bisphosphonates (BIS) or fluorides for more than three mos within the last two yrs or prior use of intravenous (IV) BIS within the last two yrs were excluded. ZOL at 4 mg was administered IV at 0, 6, and 12 mos. To assess the efficacy of ZOL therapy, DEXA scans and skeletal surveys were conducted at screening and one mo after the final ZOL infusion (13 mos). Fifty-four pts were enrolled on this trial with an average age of 68 (range, 50 to 91 yrs). The starting L-spine T-scores ranged from −3.97 to −1.10 (mean = −2.16). After one year of ZOL therapy, T-scores improved by a mean of +0.55 (range, −0.40 to +3.90; P = 0.0042). This corresponded to a mean increase in BMD of +25.5% (range, −19.0% to +134%). Similar evaluation in the hip showed baseline T-scores of −3.50 to −1.00 (mean = −1.88). The mean change in T-score was +0.27 (range, −0.60 to +2.00; P = 0.0046) corresponding to a mean increase of +14.4% (range, −54.5% to +163%). One pt developed chronic lymphocytic leukemia while on study whereas no other pt showed progression to myeloma or a related B-cell disorder. No pt developed osteonecrosis of the jaw or a significant adverse renal event. During the study, no pt developed a new fx. This trial suggests that ZOL administered at 4 mg every 6 mos significantly improves BMD in MGUS pts with bone loss (osteopenia/osteoporosis); and, thus, suggests that this is a safe and effective treatment to prevent the development of new fxs in this high risk population.

Sign in / Sign up

Export Citation Format

Share Document