Bone marrow fat accumulation after 60 days of bed rest persisted 1 year after activities were resumed along with hemopoietic stimulation: the Women International Space Simulation for Exploration study

2009 ◽  
Vol 107 (2) ◽  
pp. 540-548 ◽  
Author(s):  
Guy Trudel ◽  
Michael Payne ◽  
Burkhard Mädler ◽  
Nanthan Ramachandran ◽  
Martin Lecompte ◽  
...  

Immobility in bed and decreased mobility cause adaptations to most human body systems. The effect of immobility on fat accumulation in hemopoietic bone marrow has never been measured prospectively. The reversibility of marrow fat accumulation and the effects on hemopoiesis are not known. In the present study, 24 healthy women (age: 25–40 yr) underwent −6° head-down bed rest for 60 days. We used MRI to noninvasively measure the lumbar vertebral fat fraction at various time points. We also measured hemoglobin, erythropoietin, reticulocytes, leukocytes, platelet count, peripheral fat mass, leptin, cortisol, and C-reactive protein during bed rest and for 1 yr after bed rest ended. Compared with baseline, the mean (± SE) fat fraction was increased after 60 days of bed rest (+2.5 ± 1.1%, P < 0.05); the increase persisted 1 yr after the resumption of regular activities (+2.3 ± 0.8%, P < 0.05). Mean hemoglobin levels were significantly decreased 6 days after bed rest ended (−1.36 ± 0.20 g/dl, P < 0.05) but had recovered at 1 yr, with significantly lower mean circulating erythropoietin levels (−3.8 ± 1.2 mU/ml, P < 0.05). Mean numbers of neutrophils and lymphocytes remained significantly elevated at 1 yr (+617 ± 218 neutrophils/μl and +498 ± 112 lymphocytes/μl, both P < 0.05). These results constitute direct evidence that bed rest irreversibly accelerated fat accumulation in hemopoietic bone marrow. The 2.5% increase in fat fraction after 60 days of bed rest was 25-fold larger than expected from historical ambulatory controls. Sixty days of bed rest accelerated by 4 yr the normal bone marrow involution. Bed rest and marrow adiposity were associated with hemopoietic stimulation. One year after subjects returned to normal activities, hemoglobin levels were maintained, with 43% lower circulating erythropoietin levels, and leukocytes remained significantly elevated across lineages. Lack of mobility alters hemopoiesis, possibly through marrow fat accumulation, with potentially wide-ranging clinical consequences.

2012 ◽  
Vol 112 (11) ◽  
pp. 1824-1831 ◽  
Author(s):  
Guy Trudel ◽  
Elizabeth Coletta ◽  
Ian Cameron ◽  
Daniel L. Belavý ◽  
Martin Lecompte ◽  
...  

Fat accumulates in the bone marrow of lumbar vertebrae with bed rest. Exercise with or without whole body vibration may counter this effect. Our objectives were to measure 1) the vertebral fat fraction (VFF) of men subjected to bed rest who performed resistive exercises with (RVE, n = 7) or without whole body vibration(RE, n = 8) or no exercise (CTR, n = 9) using three MRI techniques; and 2) changes in peripheral blood counts. Twenty-four healthy men (age: 20–45 yr) underwent −6° head-down tilt (HDT) bed rest for 60 days. MRI was performed using three techniques (fat saturation, proton spectroscopy, and in and out of phase) to measure the fat fraction of L3, L4, and/or L5 at baseline, mid-HDT, and end-HDT. Erythrocytes and leukocytes were counted at HDT days 19, 33, 47, 54, and 60. The mean absolute VFF was increased in the CTR group at mid-HDT and end-HDT (+3.9 ± 1.3 and +3.6 ± 1.2%, respectively, both P < 0.05). The RE group had a smaller VFF change than the CTR group at mid-HDT (−0.9 ± 1.2 vs. +3.9 ± 1.3%, P < 0.05). The RVE group had a smaller VFF change than the CTR group at end-HDT (−2.6 ± 1.9 vs. +3.5 ± 1.2%, P < 0.05). Erythrocyte counts were increased in all groups at HDT day 19 and HDT day 33 and in the RE group at HDT day 54 (all P < 0.05). Bed rest for 60 days at −6° HDT increased lumbar VFF in men beyond natural involution. RVE and RE regimens effectively prevented VFF accumulation. Higher erythrocyte counts were not altered by RVE or RE. Whole body vibration, along with RE administered to people with prolonged immobility, may prevent fat accumulation in their bone marrow.


2020 ◽  
Vol 52 (1) ◽  
pp. 298-306 ◽  
Author(s):  
Alan Bainbridge ◽  
Timothy J.P. Bray ◽  
Raj Sengupta ◽  
Margaret A. Hall‐Craggs

2019 ◽  
Vol 7 (7_suppl5) ◽  
pp. 2325967119S0028 ◽  
Author(s):  
Patrick Allan Massey ◽  
Andrew Zhang ◽  
Christine Bayt Stairs ◽  
Stephen Hoge ◽  
Trevor Carroll ◽  
...  

Objectives: The purpose of the current study is to review the results of meniscus repairs with and without bone marrow aspiration concentrate (BMAC). It is hypothesized that with BMAC, meniscus repair outcomes will be improved when compared to without BMAC at 1 year after surgery. Methods: This is a prospective case control study performed from August 2014 until August 2017. Patients were included if they had a meniscus repair performed with no history of prior meniscus surgery to the operative knee. Patients were excluded if there was a full thickness cartilage tear or International Cartilage Repair Society (ICRS) Grade IV cartilage tear not treated in a single staged surgery. Patients were also excluded if they did not reach the one year follow-up, had a multi-ligamentous knee injury requiring multiple staged procedures. From August 2014 until November 2015, patients had meniscus repair without BMA. Menisci were all repaired arthroscopically using inside-out, outside-in and all-inside techniques. After November 2015, all meniscus repairs were augmented with BMAC. In the BMAC group, all bone marrow was obtained from the ipsilateral femur during the time of surgery. The Biocue BMAC system (Zimmer Biomet, Warsaw Indiana) was used for bone marrow aspiration and BMAC was injected directly into the tear site after repair. Numerical data such as VAS, lysholm and IKDC was analyzed using a 2 sample T-test. Categorical data such as sex, tear location, type of tear and zone of tear were analyzed using a chi-square. Results: A total of 150 patients were initially included in the study. The average age in the control group was 26.3 versus 29.4 in the BMAC group (P=0.27). Thirty seven percent of the control group had an ACL reconstruction versus 40% in the BMAC group (P= .77). The control group improved from an average pain level of 6.1 to 1.2 and the BMAC group improved from an average pain level of 5.9 to 0.7 at the 1 year end point. Both the control group and BMAC group improved with respect to pain with no difference at the 1 year end point (P=.19). There was, however a significantly larger reduction in pain at the 6 week and 3 month time point with BMAC compared to the control group (P=.02 and P=.02 respectively). At the 1-year follow-up, the mean lysholm score improved from 43 to 92 in the control group and 43 to 90 in the BMAC group. The mean IKDC score improved from 37 to 87 in the control group and 36 to 83 in the BMAC group at the one year follow-up. Conclusion: Meniscus repair outcomes were improved at 6 weeks and 3 months post-operatively, when BMAC is used to augment meniscus repair compared to repair without BMAC. Both groups, control group and BMAC meniscus repair group had improved outcomes at 1 year post-operatively with respect to VAS, lysholm and IKDC, with no difference in complication rate.


2015 ◽  
Vol 28 (4) ◽  
pp. 432-439 ◽  
Author(s):  
Michael Dieckmeyer ◽  
Stefan Ruschke ◽  
Christian Cordes ◽  
Samuel P. Yap ◽  
Hendrik Kooijman ◽  
...  

2020 ◽  
Vol 30 (6) ◽  
pp. 3417-3428 ◽  
Author(s):  
Robert C. Bertheau ◽  
Roberto Lorbeer ◽  
Johanna Nattenmüller ◽  
Elke Wintermeyer ◽  
Jürgen Machann ◽  
...  

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Michael Dieckmeyer ◽  
Stefan Ruschke ◽  
Alexander Rohrmeier ◽  
Jan Syväri ◽  
Ingo Einspieler ◽  
...  

Abstract Background Quantification of vertebral bone marrow (VBM) water–fat composition has been proposed as advanced imaging biomarker for osteoporosis. Estrogen deficiency is the primary reason for trabecular bone loss in postmenopausal women. By reducing estrogen levels aromatase inhibitors (AI) as part of breast cancer therapy promote bone loss. Bisphosphonates (BP) are recommended to counteract this adverse drug effect. The purpose of our study was to quantify VBM proton density fat fraction (PDFF) changes at the lumbar spine using chemical shift encoding-based water-fat MRI (CSE-MRI) and bone mineral density (BMD) changes using dual energy X-ray absorptiometry (DXA) related to AI and BP treatment over a 12-month period. Methods Twenty seven postmenopausal breast cancer patients receiving AI therapy were recruited for this study. 22 subjects completed the 12-month study. 14 subjects received AI and BP (AI+BP), 8 subjects received AI without BP (AI-BP). All subjects underwent 3 T MRI. An eight-echo 3D spoiled gradient-echo sequence was used for CSE-based water-fat separation at the lumbar spine to generate PDFF maps. After manual segmentation of the vertebral bodies L1-L5 PDFF values were extracted for each vertebra and averaged for each subject. All subjects underwent DXA of the lumbar spine measuring the average BMD of L1-L4. Results Baseline age, PDFF and BMD showed no significant difference between the two groups (p > 0.05). There was a relative longitudinal increase in mean PDFF (∆relPDFF) in both groups (AI+BP: 5.93%; AI-BP: 3.11%) which was only significant (p = 0.006) in the AI+BP group. ∆relPDFF showed no significant difference between the two groups (p > 0.05). There was no significant longitudinal change in BMD (p > 0.05). Conclusions Over a 12-month period, VBM PDFF assessed with CSE-MRI significantly increased in subjects receiving AI and BP. The present results contradict previous results regarding the effect of only BP therapy on bone marrow fat content quantified by magnetic resonance spectroscopy and bone biopsies. Future longer-term follow-up studies are needed to further characterize the effects of combined AI and BP therapy.


Bone ◽  
2014 ◽  
Vol 64 ◽  
pp. 39-46 ◽  
Author(s):  
Maya Styner ◽  
William R. Thompson ◽  
Kornelia Galior ◽  
Gunes Uzer ◽  
Xin Wu ◽  
...  

2021 ◽  
Vol 22 (20) ◽  
pp. 10988
Author(s):  
Ya-Li Zhang ◽  
Liang Liu ◽  
Yu-Wen Su ◽  
Cory J. Xian

Intensive methotrexate (MTX) treatment for childhood malignancies decreases osteogenesis but increases adipogenesis from the bone marrow stromal cells (BMSCs), resulting in bone loss and bone marrow adiposity. However, the underlying mechanisms are unclear. While microRNAs (miRNAs) have emerged as bone homeostasis regulators and miR-542-3p was recently shown to regulate osteogenesis in a bone loss context, the role of miR-542-3p in regulating osteogenesis and adipogenesis balance is not clear. Herein, in a rat MTX treatment-induced bone loss model, miR-542-3p was found significantly downregulated during the period of bone loss and marrow adiposity. Following target prediction, network construction, and functional annotation/ enrichment analyses, luciferase assays confirmed sFRP-1 and Smurf2 as the direct targets of miR-542-3p. miRNA-542-3p overexpression suppressed sFRP-1 and Smurf2 expression post-transcriptionally. Using in vitro models, miR-542-3p treatment stimulated osteogenesis but attenuated adipogenesis following MTX treatment. Subsequent signalling analyses revealed that miR-542-3p influences Wnt/β-catenin and TGF-β signalling pathways in osteoblastic cells. Our findings suggest that MTX treatment-induced bone loss and marrow adiposity could be molecularly linked to miR-542-3p pathways. Our results also indicate that miR-542-3p might be a therapeutic target for preserving bone and attenuating marrow fat formation during/after MTX chemotherapy.


Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1926
Author(s):  
Ya-Li Zhang ◽  
Liang Liu ◽  
Yu-Wen Su ◽  
Cory J. Xian

Methotrexate (MTX) treatment for childhood malignancies has shown decreased osteogenesis and increased adipogenesis in bone marrow stromal cells (BMSCs), leading to bone loss and bone marrow adiposity, for which the molecular mechanisms are not fully understood. Currently, microRNAs (miRNAs) are emerging as vital mediators involved in bone/bone marrow fat homeostasis and our previous studies have demonstrated that miR-6315 was upregulated in bones of MTX-treated rats, which might be associated with bone/fat imbalance by directly targeting Smad2. However, the underlying mechanisms by which miR-6315 regulates osteogenic and adipogenic differentiation require more investigations. Herein, we further explored and elucidated the regulatory roles of miR-6315 in osteogenesis and adipogenesis using in vitro cell models. We found that miR-6315 promotes osteogenic differentiation and it alleviates MTX-induced increased adipogenesis. Furthermore, our results suggest that the involvement of miR-6315 in osteogenesis/adipogenesis regulation might be partially through modulating the TGF-β/Smad2 signalling pathway. Our findings indicated that miR-6315 may be important in regulating osteogenesis and adipogenesis and might be a therapeutic target for preventing/attenuating MTX treatment-associated bone loss and marrow adiposity.


2020 ◽  
Vol 49 (11) ◽  
pp. 1753-1763
Author(s):  
Yayun Ji ◽  
Weifeng Hong ◽  
Mouyuan Liu ◽  
Yuying Liang ◽  
YongYan Deng ◽  
...  

Abstract Objective To investigate the potential clinical application of quantitative MRI in assessing the correlation between lumbar vertebrae bone marrow fat deposition and intervertebral disc degeneration. Materials and methods A total of 104 chronic lower-back pain volunteers underwent 3.0-T MRI with T2-weighted imaging, T2 mapping, and iterative decomposition of water and fat with echo asymmetry and least squares estimation (IDEAL-IQ) between August 2018 and June 2019. Each disc was assessed with T2 value by T2 mapping, and the L1-S1 vertebral bone marrow fat fraction was assessed by IDEAL-IQ. The differences and relationship between T2 value and the adjacent vertebral bone marrow fat fraction values within the five Pfirrmann groups, five age groups, and five lumbar levels were statistically analyzed. Results The vertebral bone marrow fat fraction had a significant negative correlation with T2 values of nucleus pulposus’ T2 values (p < 0.001). However, the significant negative correlation was only found between T2 values of nucleus pulposus and adjacent vertebral bone marrow fat in Pfirrmann II–III, L1/2-L5/S1 level, and 40–49 years’ age groups. Pfirrmann grades of the intervertebral disc were positively correlated with adjacent vertebrae bone marrow fat fraction (p < 0.05). Conclusion Lumbar bone marrow fat deposition significantly increases during the early stages of intervertebral disc degeneration. Quantitative measurements of bone marrow fat deposition and water content of intervertebral discs have a predictive value and are an important supplement to the qualitative traditional classification strategies for the early stages of intervertebral disc degeneration.


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