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Visfatin is a positive predictor of bone mineral density in young survivors of acute lymphocytic leukemia.
Siviero-Miachon, AA, Spinola-Castro, AM, de Martino Lee, ML, Calixto, AR, Geloneze, B, Lazaretti-Castro, M, Guerra-Junior, G
Journal of bone and mineral metabolism. 2017;(1):73-82
Abstract
Bone mass acquisition may be compromised in survivors of childhood acute lymphocytic leukemia due to various factors, including adiposity. Fat accumulation can affect bone through the direct effect of adipokines or indirectly through the state of chronic inflammation. The aim of this study was to evaluate the effect of body composition and adipokines on bone mass in survivors of acute lymphocytic leukemia. This was a cross-sectional study of 56 survivors aged between 15 and 24 years, 44.6 % of whom received cranial radiotherapy (18-24 Gy), assessed according to body fat, lean mass, and bone mineral density (dual energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, and adipokines by a multiple regression analysis. Both lumbar spine L1-L4 (trabecular bone) and total body (cortical bone) bone mineral density were positively correlated with visfatin (p < 0.050). Lean mass index was positively correlated, while waist-to-height ratio was negatively correlated with cortical bone (p < 0.010). Low bone mineral density for chronological age was detected in 5.4 % of patients in total body, and 8.9 % at the lumbar spine. In survivors of acute lymphocytic leukemia, visfatin may play an important role in the complex relationship between body composition and bone. At present, visfatin may represent a model for further study of bone metabolism, and could possibly explain the unknown mechanisms linking bone metabolism and cancer.
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Refined Phenotyping of Modic Changes: Imaging Biomarkers of Prolonged Severe Low Back Pain and Disability.
Määttä, JH, Karppinen, J, Paananen, M, Bow, C, Luk, KDK, Cheung, KMC, Samartzis, D
Medicine. 2016;(22):e3495
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Low back pain (LBP) is the world's most disabling condition. Modic changes (MC) are vertebral bone marrow changes adjacent to the endplates as noted on magnetic resonance imaging. The associations of specific MC types and patterns with prolonged, severe LBP and disability remain speculative. This study assessed the relationship of prolonged, severe LBP and back-related disability, with the presence and morphology of lumbar MC in a large cross-sectional population-based study of Southern Chinese.We addressed the topographical and morphological dimensions of MC along with other magnetic resonance imaging phenotypes (eg, disc degeneration and displacement) on the basis of axial T1 and sagittal T2-weighted imaging of L1-S1. Prolonged severe LBP was defined as LBP lasting ≥30 days during the past year, and a visual analog scale severest pain intensity of at least 6/10. An Oswestry Disability Index score of 15% was regarded as significant disability. We also assessed subject demographics, occupation, and lifestyle factors.In total, 1142 subjects (63% females, mean age 53 years) were assessed. Of these, 282 (24.7%) had MC (7.1% type I, 17.6% type II). MC subjects were older (P = 0.003), had more frequent disc displacements (P < 0.001) and greater degree of disc degeneration (P < 0.001) than non-MC subjects. In adjusted models, any MC (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.01-2.18), MC affecting whole anterior-posterior length (OR 1.62, 95% CI 1.04-2.51), and MC affecting 2/3 posterior length (OR 2.79, 95% CI 1.17-6.65) were associated with prolonged severe LBP. Type I MC tended to associate with pain more strongly than type II MC (OR 1.80, 95% CI 0.94-3.44 vs OR 1.36, 95% CI 0.88-2.09, respectively). Any MC (OR 1.47, 95% CI 1.04-2.10), type II MC (OR 1.56, 95% CI 1.06-2.31), MC affecting 2/3 posterior length (OR 2.96, 95% CI 1.27-6.89), and extensive MC (OR 1.95, 95% CI 1.21-3.15) were associated with disability. The strength of the associations increased with the number of MC.This large-scale study is the first to definitively note MC types and specific morphologies to be independently associated with prolonged severe LBP and back-related disability. This proposed refined MC phenotype may have direct implications in clinical decision-making as to the development and management of LBP. Understanding of these imaging biomarkers can lead to new preventative and personalized therapeutics related to LBP.
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The SNAP trial: a double blind multi-center randomized controlled trial of a silicon nitride versus a PEEK cage in transforaminal lumbar interbody fusion in patients with symptomatic degenerative lumbar disc disorders: study protocol.
Kersten, RF, van Gaalen, SM, Arts, MP, Roes, KC, de Gast, A, Corbin, TP, Öner, FC
BMC musculoskeletal disorders. 2014;:57
Abstract
BACKGROUND Polyetheretherketone (PEEK) cages have been widely used in the treatment of lumbar degenerative disc disorders, and show good clinical results. Still, complications such as subsidence and migration of the cage are frequently seen. A lack of osteointegration and fibrous tissues surrounding PEEK cages are held responsible. Ceramic implants made of silicon nitride show better biocompatible and osteoconductive qualities, and therefore are expected to lower complication rates and allow for better fusion.Purpose of this study is to show that fusion with the silicon nitride cage produces non-inferior results in outcome of the Roland Morris Disability Questionnaire at all follow-up time points as compared to the same procedure with PEEK cages. METHODS/DESIGN This study is designed as a double blind multi-center randomized controlled trial with repeated measures analysis. 100 patients (18-75 years) presenting with symptomatic lumbar degenerative disorders unresponsive to at least 6 months of conservative treatment are included. Patients will be randomly assigned to a PEEK cage or a silicon nitride cage, and will undergo a transforaminal lumbar interbody fusion with pedicle screw fixation. Primary outcome measure is the functional improvement measured by the Roland Morris Disability Questionnaire. Secondary outcome parameters are the VAS leg, VAS back, SF-36, Likert scale, neurological outcome and radiographic assessment of fusion. After 1 year the fusion rate will be measured by radiograms and CT. Follow-up will be continued for 2 years. Patients and clinical observers who will perform the follow-up visits will be blinded for type of cage used during follow-up. Analyses of radiograms and CT will be performed independently by two experienced radiologists. DISCUSSION In this study a PEEK cage will be compared with a silicon nitride cage in the treatment of symptomatic degenerative lumbar disc disorders. To our knowledge, this is the first randomized controlled trial in which the silicon nitride cage is compared with the PEEK cage in patients with symptomatic degenerative lumbar disc disorders. TRIAL REGISTRATION NCT01557829.
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Dietary acid load is associated with lower bone mineral density in men with low intake of dietary calcium.
Mangano, KM, Walsh, SJ, Kenny, AM, Insogna, KL, Kerstetter, JE
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2014;(2):500-6
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High dietary acid load (DAL) may be detrimental to bone mineral density (BMD). The objectives of the study were to: (1) evaluate the cross-sectional relation between DAL and BMD; and (2) determine whether calcium intake modifies this association. Men (n = 1218) and women (n = 907) aged ≥60 years were included from the National Health and Nutrition Examination Survey 2005-2008. Nutrient intake from 2, 24-hour recalls was used to calculate net endogenous acid production (NEAP) and potential renal acid load (PRAL) (mEq/d). PRAL was calculated from dietary calcium (PRALdiet ) and diet + supplemental calcium (PRALtotal ). Tests for linear trend in adjusted mean BMD of the hip and lumbar spine were performed across energy-adjusted NEAP and PRAL quartiles. Modification by calcium intake (dietary or total) above or below 800 mg/d was assessed by interaction terms. Overall, mean age was 69 ± 0.3 years. Among women, there was no association between NEAP and BMD. PRALdiet was positively associated with proximal femur BMD (p trend = 0.04). No associations were observed with PRALtotal at any BMD site (p range, 0.38-0.82). Among men, no significant associations were observed between BMD and NEAP or PRAL. However, an interaction between PRALdiet and calcium intake was observed with proximal femur BMD (p = 0.08). An inverse association between PRALdiet and proximal femur BMD was detected among men with <800 mg/d dietary calcium (p = 0.02); no associations were found among men with ≥800 mg/d (p = 0.98). A significant interaction with PRALtotal was not observed. In conclusion, when supplemental calcium is considered, there is no association between DAL and BMD among adults. Men with low dietary calcium showed an inverse relation with PRAL at the proximal femur; in women no interaction was observed. This study highlights the importance of calcium intake in counteracting the adverse effect of DAL on bone health. Further research should determine the relation between DAL and change in BMD with very low calcium intake.
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Influence of preoperative leg pain and radiculopathy on outcomes in mono-segmental lumbar total disc replacement: results from a nationwide registry.
Zweig, T, Aghayev, E, Melloh, M, Dietrich, D, Röder, C, ,
European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. 2012;(Suppl 6):S729-36
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PURPOSE Currently, many pre-conditions are regarded as relative or absolute contraindications for lumbar total disc replacement (TDR). Radiculopathy is one among them. In Switzerland it is left to the surgeon's discretion when to operate if he adheres to a list of pre-defined indications. Contraindications, however, are less clearly specified. We hypothesized that, the extent of pre-operative radiculopathy results in different benefits for patients treated with mono-segmental lumbar TDR. We used patient perceived leg pain and its correlation with physician recorded radiculopathy for creating the patient groups to be compared. METHODS The present study is based on the dataset of SWISSspine, a government mandated health technology assessment registry. Between March 2005 and April 2009, 577 patients underwent either mono- or bi-segmental lumbar TDR, which was documented in a prospective observational multicenter mode. A total of 416 cases with a mono-segmental procedure were included in the study. The data collection consisted of pre-operative and follow-up data (physician based) and clinical outcomes (NASS form, EQ-5D). A receiver operating characteristic (ROC) analysis was conducted with patients' self-indicated leg pain and the surgeon-based diagnosis "radiculopathy", as marked on the case report forms. As a result, patients were divided into two groups according to the severity of leg pain. The two groups were compared with regard to the pre-operative patient characteristics and pre- and post-operative pain on Visual Analogue Scale (VAS) and quality of life using general linear modeling. RESULTS The optimal ROC model revealed a leg pain threshold of 40 ≤ VAS > 40 for the absence or the presence of "radiculopathy". Demographics in the resulting two groups were well comparable. Applying this threshold, the mean pre-operative leg pain level was 16.5 points in group 1 and 68.1 points in group 2 (p < 0.001). Back pain levels differed less with 63.6 points in group 1 and 72.6 in group 2 (p < 0.001). Pre-operative quality of life showed considerable differences with an 0.44 EQ-5D score in group 1 and 0.29 in group 2 (p < 0.001, possible score range -0.6 to 1). At a mean follow-up time of 8 months, group 1 showed a mean leg pain improvement of 3.6 points and group 2 of 41.1 points (p < 0.001). Back pain relief was 35.6 and 39.1 points, respectively (p = 0.27). EQ-5D score improvement was 0.27 in group 1 and 0.41 in group 2 (p = 0.11). CONCLUSIONS Patients labeled as having radiculopathy (group 2) do mostly have pre-operative leg pain levels ≥ 40. Applying this threshold, the patients with pre-operative leg pain do also have more severe back pain and a considerably lower quality of life. Their net benefit from the lumbar TDR is higher and they do have similar post-operative back and leg pain levels as well as the quality of life as patients without pre-operative leg pain. Although randomized controlled trials are required to confirm these findings, they put leg pain and radiculopathy into perspective as absolute contraindications for TDR.
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Loss of hip bone mineral density over time is associated with spine and hip fracture incidence in osteoporotic postmenopausal women.
Bruyere, O, Varela, AR, Adami, S, Detilleux, J, Rabenda, V, Hiligsmann, M, Reginster, JY
European journal of epidemiology. 2009;(11):707-12
Abstract
The objective of the study assess the relationship between bone mineral density (BMD) loss over time and fracture incidence in postmenopausal women. This is a posthoc analysis that includes women from the placebo group of two large randomized controlled trials having assessed the efficacy of a new anti-osteoporotic drug. BMD was assessed every 6 months during 3 years at the lumbar spine, the femoral neck and the total proximal femur. Vertebral fractures were assessed using a semiquantitative method. Hip fractures were based on written documentation. All patients received calcium and vitamin D. In the present study that included 1,775 patients (with complete data at baseline and after 3 years), the logistic regression analysis, adjusted for covariates, showed that 3-year change in lumbar BMD was not statistically associated with the new vertebral fractures after 3 years. However, femoral neck and total proximal femur BMD changes was statistically correlated with the incidence of new vertebral fractures (P < 0.001). When considering change in BMD after the first year of follow-up, a decrease in total proximal femur BMD was statistically associated with an increase in the incidence of new vertebral fractures during the last 2 years of follow-up (P = 0.048). The 3-year change in femoral neck and total proximal BMD was statistically correlated with the incidence of hip and fragility fracture after 3 years (all P < 0.001). In this elderly osteoporotic population receiving calcium and vitamin D, a decrease in hip BMD after 1 or 3 year of follow-up, is associated with an increased risk of fracture incidence. However, spine BMD changes do not influence vertebral fracture incidence.
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Effective inhibition of aromatase inhibitor-associated bone loss by zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: ZO-FAST Study results.
Bundred, NJ, Campbell, ID, Davidson, N, DeBoer, RH, Eidtmann, H, Monnier, A, Neven, P, von Minckwitz, G, Miller, JC, Schenk, NL, et al
Cancer. 2008;(5):1001-10
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BACKGROUND Letrozole is safe and effective in postmenopausal women with estrogen receptor-positive early breast cancer, but long-term aromatase inhibitor use may cause bone loss and increase fracture risk. This study evaluated an immediate or delayed strategy of bone protection therapy with zoledronic acid. METHODS A total of 1065 patients who were receiving adjuvant letrozole were randomized to immediate-start or delayed-start zoledronic acid (4 mg intravenously biannually for 5 years). The delayed group received zoledronic acid if lumbar spine or total hip T-score decreased below -2.0 or when a nontraumatic fracture occurred. The primary endpoint was change in lumbar spine bone mineral density (BMD) at Month 12. Secondary endpoints included changes in total hip BMD, serum bone turnover markers, and safety at Month 12. RESULTS Lumbar spine BMD increased from baseline in the immediate arm, while it decreased from baseline in delayed-arm patients. At Month 12, the differences between the groups in lumbar spine and total hip BMD were 5.7% (P < .0001; 95% confidence intervals [CI], 5.2% to 6.1%), and 3.6% (P < .0001; 95% CI, 3.3 to 4.0%), respectively. Both regimens were well tolerated with few serious adverse events. Bone pain was higher in the immediate group, as expected, because some patients experienced acute-phase reactions after zoledronic acid infusion. CONCLUSIONS At 12 months, immediate zoledronic acid therapy prevented bone loss in postmenopausal women who were receiving adjuvant letrozole.
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Alendronate once weekly for the prevention and treatment of bone loss in Canadian adult cystic fibrosis patients (CFOS trial).
Papaioannou, A, Kennedy, CC, Freitag, A, Ioannidis, G, O'Neill, J, Webber, C, Pui, M, Berthiaume, Y, Rabin, HR, Paterson, N, et al
Chest. 2008;(4):794-800
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BACKGROUND Patients with cystic fibrosis (CF) are at risk for early bone loss, and demonstrate increased risks for vertebral fractures and kyphosis. A multicenter, randomized, controlled trial was conducted to assess the efficacy, tolerability, and safety of therapy with oral alendronate (FOSAMAX; Merck; Whitehouse Station, NJ) in adults with CF and low bone mass. METHODS Participants received placebo or alendronate, 70 mg once weekly, for 12 months. All participants received 800 IU of vitamin D and 1,000 mg of calcium daily. Adults with confirmed CF with a bone mineral density (BMD) T score of < - 1.0 were eligible for inclusion. Participants who had undergone organ transplantation or had other reported contraindications were excluded from the study. The primary outcome measure was the mean (+/- SD) percentage change in lumbar spine BMD after 12 months. Secondary measures included the percentage change in total hip BMD, the number of new vertebral fractures (grade 1 or 2), and changes in quality of life. RESULTS A total of 56 participants were enrolled in the study (mean age, 29.1 +/- 8.78 years; 61% male). The absolute percentage changes in lumbar spine and total hip BMDs at follow-up were significantly higher in the alendronate therapy group (5.20 +/- 3.67% and 2.14 +/- 3.32%, respectively) than those in the control group (- 0.08 +/- 3.93% and - 1.3 +/- 2.70%, respectively; p < 0.001). At follow-up, two participants (both in the control group) had a new vertebral fracture (not significant), and there were no differences in quality of life or the number of adverse events (including serious and GI-related events). CONCLUSION Alendronate therapy was well tolerated and produced a significantly greater increase in BMD over 12 months compared with placebo.
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Oral ibandronate significantly reduces the risk of vertebral fractures of greater severity after 1, 2, and 3 years in postmenopausal women with osteoporosis.
Felsenberg, D, Miller, P, Armbrecht, G, Wilson, K, Schimmer, RC, Papapoulos, SE
Bone. 2005;(5):651-4
Abstract
In a recent multinational, double-blind, placebo-controlled, randomized, phase III study (BONE: IBandronate Osteoporosis Vertebral Fracture trial in North America and Europe), oral daily ibandronate (2.5 mg) significantly and substantially reduced the risk of new vertebral fractures by 62% relative to placebo after 3 years of treatment. The objective of the present study was to retrospectively analyze data from the BONE study to examine the efficacy of oral ibandronate in preventing incident vertebral fractures of greater severity. This analysis was conducted on the placebo and oral daily ibandronate (2.5 mg) arms of the BONE study, comprising a total of 1964 women (aged 55-80 years, >or=5 years postmenopause) with osteoporosis. Vertebral fractures on annual lateral radiographs of the spine were graded as mild, moderate, or severe, using criteria derived from an established semiquantitative technique. The findings demonstrate that in addition to being effective in significantly reducing the risk of new vertebral fractures of all severities, oral daily ibandronate has a pronounced effect on the more severe, most clinically relevant, vertebral fractures: a significant and sustained reduction of 59% in the relative risk of combined new moderate and severe vertebral fractures was observed at years 1 (P = 0.0164), 2 (P = 0.0004), and 3 (P < 0.0001).