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.

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.

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&lt;0.02). CTX levels in the osteosclerotic patients were significantly lower than those of both controls (p&lt;0.0001) and osteopenic/osteoporotic patients (p&lt;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&lt;0.01, and &lt;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 Raloxifene Has No Efficacy in Reducing the High Bone Turnover and the Risk of Spontaneous Vertebral Fractures after Denosumab Discontinuation

2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Elena Gonzalez-Rodriguez ◽  
Delphine Stoll ◽  
Olivier Lamy
Keyword(s):  
Bone Loss ◽  
Bone Turnover ◽  
Aromatase Inhibitors ◽  
Vertebral Fractures ◽  
Bone Markers ◽  
Rebound Effect ◽  
High Bone Turnover ◽  
Antiresorptive Agent ◽  
High Bone

At denosumab discontinuation, an antiresorptive agent is prescribed to reduce the high bone turnover, the rapid bone loss, and the risk of spontaneous vertebral fractures. We report the case of a woman treated with aromatase inhibitors and denosumab for 5 years. Raloxifene was then prescribed to prevent the rebound effect. Raloxifene was ineffective to reduce the high bone turnover and to avoid spontaneous clinical vertebral fractures. We believe that among the antiresorptive treatments, the most powerful bisphosphonates should be favored, and their administration adapted according to the serial follow-up of bone markers.

Zoledronic Acid Prevents Cancer Treatment–Induced Bone Loss in Premenopausal Women Receiving Adjuvant Endocrine Therapy for Hormone-Responsive Breast Cancer: A Report From the Austrian Breast and Colorectal Cancer Study Group

2007 ◽  
Vol 25 (7) ◽  
pp. 820-828 ◽  
Author(s):  
Michael F.X. Gnant ◽  
Brigitte Mlineritsch ◽  
Gero Luschin-Ebengreuth ◽  
Stephan Grampp ◽  
Helmut Kaessmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Zoledronic Acid ◽  
Bone Loss ◽  
Endocrine Therapy ◽  
Premenopausal Women ◽  
Adjuvant Endocrine Therapy ◽  
Phase Iii ◽  
Endocrine Treatment ◽  
Mineral Density ◽  
T Score

Purpose Adjuvant therapy for breast cancer can be associated with decreased bone mineral density (BMD) that may lead to skeletal morbidity. This study examined whether zoledronic acid can prevent bone loss associated with adjuvant endocrine therapy in premenopausal patients. Patients and Methods This study is a randomized, open-label, phase III, four-arm trial comparing tamoxifen (20 mg/d orally) and goserelin (3.6 mg every 28 days subcutaneously) ± zoledronic acid (4 mg intravenously every 6 months) versus anastrozole (1 mg/d orally) and goserelin ± zoledronic acid for 3 years in premenopausal women with hormone-responsive breast cancer. In a BMD subprotocol at three trial centers, patients underwent serial BMD measurements at 0, 6, 12, 24, and 36 months. Results Four hundred one patients were included in the BMD subprotocol. Endocrine treatment without zoledronic acid led to significant (P < .001) overall bone loss after 3 years of treatment (BMD, −14.4% after 36 months; mean T score reduction, −1.4). Overall bone loss was significantly more severe in patients receiving anastrozole/goserelin (BMD, −17.3%; mean T score reduction, −2.6) compared with patients receiving tamoxifen/goserelin (BMD, −11.6%; mean T score reduction, −1.1). In contrast, BMD remained stable in zoledronic acid–treated patients (P < .0001 compared with endocrine therapy alone). No interactions with age or other risk factors were noted. Conclusion Endocrine therapy caused significant bone loss that increased with treatment duration in premenopausal women with breast cancer. Zoledronic acid 4 mg every 6 months effectively inhibited bone loss. Regular BMD measurements and initiation of concomitant bisphosphonate therapy on evidence of bone loss should be considered for patients undergoing endocrine therapy.

scholarly journals Evaluation of Bone Mineral Density in Subjects with Primary Hyperparathyroidism by Dual Energy X-Ray Absorptiometry

2018 ◽  
Vol 20 (2) ◽  
pp. 129
Author(s):  
Rezwana Haque ◽  
Raihan Hussain ◽  
Shamim MF Begum
Keyword(s):  
Bone Loss ◽  
Femoral Neck ◽  
Primary Hyperparathyroidism ◽  
Dual Energy ◽  
Mineral Density ◽  
X Ray ◽  
T Score ◽  
Group A ◽  
Group B ◽  
Bone Condition

<p><strong><em>Objective:</em></strong><strong> </strong>Bone loss is a major complication of primary hyperparathyroidism (PHPT), and the extent of bone loss is an important factor for parathyroidectomy. Studies focused on this issue of bone loss in subjects with PHPT are quite rare in our country. This study will help the physicians to take proper action by giving an exact reflection of bone condition in subjects with PHPT. The purpose of this study was to evaluate the bone condition by measuring Bone Mineral Density (BMD), in subjects with PHPT using Dual Energy X-ray Absorptiometry (DEXA) and compare these findings with individuals without PHPT.</p><p><strong><em>Patients and Methods:</em></strong><strong> </strong>It was an analytic cross sectional study (group comparison) carried out at National Institute of Nuclear Medicine and Allied Sciences (NINMAS) BSMMU campus, Dhaka from July 2015-December 2016. Subjects of PHPT diagnosed by biochemical evaluation (increased serum calcium and parathyroid hormone concentrations), between age ranges 15-45 years were selected as group-A. Individuals without biochemical evidence of PHPT or other major illness causing bone loss were selected as comparison group or as group-B. The subjects underwent BMD test by DEXA at lumbar spines from L1-L4 vertebra and the left femoral neck using Norland XR-46 densitometer. BMD was classified according to WHO criteria. Data presented on categorical form were analyzed using chi-squared test. While the data presented on continuous scale were analyzed using student’s t-test. In each analysis, level of significance was 5% and P value &lt;0.05 was considered significant. Data were processed and analyzed with the help of computer software SPSS, version 20.</p><p><strong><em>Results:</em></strong><strong> </strong>Total number of 90 subjects were selected for this study, 45 subjects with PHPT were in group-A and equal number of subjects without PHPT were in group-B. The findings derived from data analysis showed, a significantly more male participants in group-A. The mean age of group-A and group-B was 37.24 ± 8.03 years and 38.20 ± 5.74 years respectively. Mean BMI of group-A was 25.10 ± 4.35 kg/m<sup>2  </sup>in compare to 29.43 ± 5.17 kg/m<sup>2</sup> in group-B. Higher BMI was noted in both groups. PHPT subjects with high BMI had low BMD. BMD expressed in absolute value (gm/cm<sup>2</sup>) and T score. BMD was significantly low in group-A (with PHPT) than in group-B (without PHPT), (p&lt;0.0001). In group-A, prevalence of low BMD was 62.2% (osteopenia 37.8%  and osteoporosis 24.4%)  at lumbar spine and 84.5% (osteopenia 35.6% and osteoporosis 48.9%) at femoral neck. PHPT subjects had significant difference in both T score and BMD between lumbar spine and femoral neck.</p><p><strong><em>Conclusion:</em></strong><strong> </strong>Primary hyperparathyroidism (PHPT) is shown to be associated with significantly reduced BMD especially at femoral neck. Thus, an increased fracture risk should consider if it is left untreated.</p><p>Bangladesh J. Nuclear Med. 20(2): 129-135, July 2017</p>

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.

Iron Status Independently Associates With Bone Mineral Density At Population Level. Insights From The Val Borbera Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4672-4672
Author(s):  
Nicola Martinelli ◽  
Michela Traglia ◽  
Fabiana Busti ◽  
Marcella Sirtori ◽  
Natascia Campostrini ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Mass ◽  
Iron Overload ◽  
Bone Metabolism ◽  
Iron Status ◽  
Population Level ◽  
Mineral Density ◽  
Major Health Problem ◽  
T Score ◽  
Serum Hepcidin

Background and Aims Osteoporosis is a multifactorial major health problem affecting over 200 million people worldwide. It is long known as a complication of marked iron overload, both primary (i.e. genetic hemochromatosis) and secondary (i.e. transfusional iron overload), but only recently cellular and animal models have shed some light on the pathogenetic link between iron and bone metabolism. Iron has been shown to activate osteoclasts (Ishii KA, Nat Med 2009) and to inhibit osteoblasts (Yamasaki K, Toxicol Lett 2009), which express ferroportin regulated by hepcidin (Xu Y, Inflammation 2012). A murine model has shown that iron overload causes bone loss through induction of Reactive Oxygen Species (ROS) (Tsay J, Blood 2010). Of note, a recent longitudinal study in a Korean population has demonstrated that serum ferritin, even at concentrations generally not considered as “iron overload”, is an independent predictor of bone mass deterioration and incident vertebral fractures (Kim BJ, J Bone Miner Res 2012), an effect most prominent in women ≥ 45 years of age (Kim BJ, Osteoporos Int 2013). Taking advantage from the recently completed iron section of the Val Borbera Study (Traglia M, J Med Genet 2011), this study aimed to evaluate for the first time the association between iron status (including serum hepcidin levels) and bone mass in a Caucasian population. Subjects and Methods This survey included 921 subjects (564 females, 357 males) aged 53.8 ± 16.3 years for whom complete data regarding bone mass (measured by transportable Quantitative Ultrasonography, QUS-based approach) and iron status (including serum hepcidin-25 levels measured by Mass Spectrometry) were available. Subjects with known inflammatory and renal disorders, as well as hereditary hemochromatosis had been previously excluded. Analyses were performed separately in males and females, due to known gender-related differences in either iron or bone metabolism. Main Results No significant association was found in males, while in females both ferritin (r= -0.42, P<0.001) and hepcidin (r= -0.30, P<0.001) were inversely correlated with T-score at univariate analyses. However, after including both ferritin and hepcidin in an age-adjusted linear regression model, only ferritin remained a significant predictor of T-score variability (beta coefficient= -0.115, P=0.042). Subsequent regression models adjusted for age, BMI, and C-Reactive Protein highlighted ferritin levels as independent predictors of T-score in females. After stratification for age and ferritin categories, T-score decreased linearly with increasing ferritin levels especially in females aged 50-75 years (n=293), i.e. the age known to be at major risk of accelerated bone loss (P<0.001 – Figure 1). Conclusions This study confirms that iron status significantly associates with bone loss at population level even in Caucasians, particularly in post-menopausal women. Increasing iron stores, even not clearly “pathologic”, may influence bone metabolism through increased ROS and/or hepcidin-mediated altered iron handling of osteoblasts and osteoclasts. Disclosures: No relevant conflicts of interest to declare.

The effect of aromatase inhibitors on bone mineral density measured by serial DXA scans

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11065-11065 ◽  
Author(s):  
K. J. Whannel ◽  
J. C. Doughty ◽  
C. R. Wilson ◽  
A. McLellan
Keyword(s):  
Bone Mineral Density ◽  
Endocrine Therapy ◽  
Bone Mineral ◽  
Aromatase Inhibitors ◽  
Fracture Rate ◽  
Mineral Density ◽  
First Line ◽  
Dxa Scan ◽  
T Score ◽  
Dxa Scans

11065 Background: We are now using aromatase inhibitors (AI) in increasing numbers of women as treatment in the breast cancer care pathway. Studies have reported a loss of bone mineral density (BMD) with use of all AIs. It has been shown in our unit that 5 years of tamoxifen (T) in post-menopausal women prior to commencing an AI does not offer sufficient protection to prevent significant BMD loss when an AI is introduced, with 25% requiring concurrent bisphosphonate (BP) therapy. The aim of this study was to determine changes in serial DXA scan results over a 12month period in women taking AIs. Method: 62 women being considered for or in early stages of use of an AI attended for a DXA scan and re-scan at 12 months. Vertebral morphometry and fracture rate were assessed and risk factors for osteoporosis noted. Scan results were compared ( Table 1 ). Results: Mean age was 67yrs [standard deviation (SD) 9yrs]. The patients were grouped according to initial endocrine therapy. 13 (21%) switched from tamoxifen to arimidex after 2years, 3 (4.8%) switched from tamoxifen to exemestane after 3 years and 30 (48.4%) switched from tamoxifen to letrozole after 5 years. 11 (17.7%) had been on arimidex as first line endocrine therapy for <=2 years and 5 (8.1%) had been on letrozole as first line endocrine therapy for <=1 year. Mean t-score and SD was calculated at each site and results categorised by lowest t-score at any site. The overall decrease in BMD measured at 1.66% over the 12 months. Conclusion: We have demonstrated a decrease in BMD with AI treatment of 1.66% per year as well as an increase in fracture incidence and increased need for bisphosphonate therapy whilst on an AI. We would recommend that all patients on any AI receive annual DXA scans. [Table: see text] No significant financial relationships to disclose.

Bone mineral density and biochemical markers of bone metabolism in predialysis patients with chronic kidney disease

2016 ◽  
Vol 64 (4) ◽  
pp. 861-866 ◽  
Author(s):  
Nuri Fidan ◽  
Ayca Inci ◽  
Melahat Coban ◽  
Cevval Ulman ◽  
Seyhun Kursat
Keyword(s):  
Bone Mineral Density ◽  
Chronic Kidney Disease ◽  
Alkaline Phosphatase ◽  
Kidney Disease ◽  
Bone Loss ◽  
Bone Mineral ◽  
Serum Alkaline Phosphatase ◽  
Mineral Density ◽  
T Score ◽  
Z Scores

The aim of the study was to evaluate the usefulness of serum bone turnover markers (BTM) and bone mineral density (BMD) determined by dual-energy X-ray absorptiometry (DEXA) in predialysis patients with chronic kidney disease (CKD). We enrolled 83 patients with CKD, 41 (49.4%) males, 42 (50.6%) females, with mean estimated glomerular filtration rate (eGFR) 23.90±12 (range=6.0–56.0). BMD of the lumbar spine (LS) (anteroposterior, L2 through L4), femoral neck (FN) and femoral trochanter (FT) were measured by DEXA. Biochemical BTM, including calcium (Ca), phosphorus (P), intact parathyroid hormone (PTH), serum specific alkaline phosphatase (serum AP), bone-specific AP (BSAP), plasma bicarbonate and 25-hydroxy-vitamin D (25hD) were used for the prediction of BMD loss. T score results of LS and FN were worse than FT. BMD levels were lower in females than in males (all p<0.05). According to different BMD T score levels, patients with age ≥65 years and patients in menopause were significantly more osteopenic (p=0.026) and there was no relation between different BMD T scores and presence of diabetes (p=0.654). A positive correlation was identified between the BMD of FN T-Z scores (r=0.270, p=0.029, r=0.306, p=0.012), FT T-Z scores (r=0.220, p=0.076, r:0.250, p=0.043) and serum HCO3, while the correlation with serum alkaline phosphatase (AP) and BSAP was considered to be negative. No statistically significant association was found between BMD of all the measured skeletal sites and eGFR. Loss of BMD was identified mostly in females over ≥65 years of age and after menopause. Higher serum levels of BSAP and AP can be determined in the advanced stages of renal failure and they reflect fracture risk of the femur, but not spine. Measurements of BMD by DEXA are useful to demonstrate bone loss, but not technical enough to distinguish the quantity of bone loss between different stages of CKD.

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