Bone Marrow Changes Research Articles

Sharing and Helping: Regularity and Characteristics of Pathogenesis of a Widely Used Transgene Initiated Murine Acute Promyelocytic Leukemia Model.

A transgenic acute promyelocytic leukemia (APL) murine model established by Michael Bishop by cloning a human PML-RARα cDNA into the hMRP8 expression cassette has been widely used in the all-trans retinoid acid and arsenic preparations for the research of APL. However, in the existing literature, the data of regularity and characteristics of the pathogenesis of this model were still missing, which hinder the development of many studies, especially application of new technologies such as single-cell sequencing. Therefore, in this article, we have made up this part of the missing data using an improved APL murine model. We clarified the effects of different inoculation doses on the onset time, latency, morbidity, life span, and proportion of APL cells in peripheral blood (PB), spleen, bone marrow, and so on. The relationship between the proportion of APL cells in the bone marrow, spleen, and PB and organ histological changes was also revealed. These results were a supplement and refinement of this APL model. It would add to the knowledge base of the field and aid in ensuring that accurate models are used for directed interventions. It also provides a great convenience for the researchers who will carry out similar research.

Cytogenetic abnormalities and morphological changes of bone marrow in multiple myeloma: a pathological analysis of 151 cases

Objective: To investigate the relationship between six common cytogenetic abnormalities and bone marrow pathomorphology in multiple myeloma (MM). Methods: Bone marrow biopsy was performed on 151 newly-diagnosed MM patients. Meanwhile, myeloma cells were enriched by CD138 immunomagnetic beads, and then lq+, 13q-, 17p-, t(4;14), t (11;14), t (14;16) and other common genetic abnormalities were detected using interphase fluorescence in situ hybridization (FISH). The relationship between different genetic abnormalities and biopsy morphology was compared. Results: Of the 151 patients, 15 had extramedullary infiltration (9.9%). The rate of cytogenetic abnormalities was 76.2% (115/151), of which 1q+ accounted for 49.7% (75/151), 13q-39.1% (59/151), 17p-8.6% (13/151), t(4;14) 21.2% (32/151), t(11;14) 19.2% (29/151), and t(14;16) 2.0% (3/151). The proliferation patterns of MM plasma cells were nodular (48.3%, 73/151), interstitial (33.8%, 51/151) and diffuse (17.9%, 27/151). The morphology of plasma cells was mainly mature type (58.3%, 88/151), followed by juvenile type (20.5%, 31/151), intermediate type (15.9%, 24/151) and plasmacyte type (5.3%, 8/151). According to the mSMART risk stratification system, the proliferation pattern of myeloma cells in the high-risk group was mainly diffuse type, and the morphology was mainly immature and plasmacyte type. In the middle-risk group, mature type myeloma cells were mainly nodular proliferating. In the low-risk and negative group, mature type myeloma cells were mainly interstitial proliferating. There was no difference in the probability of different proliferation modes of intermediate type plasma cells in each group. Conclusions: The proliferation pattern and morphology of plasma cells in bone marrow biopsy combined with cytogenetic markers can more accurately predict the severity and prognosis of MM.

COVID-19: B-Cell Depletion and Sepsis Related Changes in Bone Marrow and Spleen

COVID-19: B-Cell Depletion and Sepsis Related Changes in Bone Marrow and Spleen

Focal, Symptomatic Bone Marrow Lesions in Waldenström Macroglobulinaemia Characterised By Dense Infiltration with Lymphoplasmacytic Lymphoma: A Newly Defined Indication for Systemic Treatment

BACKGROUND Waldenström Macroglobulinaemia (WM) is an indolent, IgM-producing lymphoplasmacytic lymphoma (LPL) that infiltrates bone marrow (BM) and other tissues. Only symptomatic patients (with IgM-related complications, cytopenias, constitutional symptoms, bulky extramedullary disease) require treatment. Symptomatic BM lesions are not a recognised manifestation of WM and, if present, may raise the possibility of high-grade transformation. AIMS To characterise the clinical, radiological and histological features of focal bone marrow lesions (FBML) identified in WM patients with unrelenting pain in bones and/or joints, and outline implications for treatment. METHODS This study retrospectively reviewed investigations performed at the time of FBMLpresentation, including MRI of the site of pain, total body FDG-PET/CT, review of histology from BM trephine biopsy of the posterior superior iliac spine (PSIS) and CT-guided core biopsy of the identified FBML, and routine blood panels. RESULTS The 6 patients identified (Table 1) presented with localised skeletal pain at different stages of their WM disease course: 1 at initial WM diagnosis, 1 after 10 years of observation, 3 in remission following R-chemotherapy, and 1 during active treatment with R-chemotherapy. Median age at diagnosis of WM was 57 years (41-64 years). Median time from diagnosis to presentation with FBML was 28 months (0-120 months). MRI demonstrated well-defined areas of abnormal signal within the medullae of symptomatic bones and no evidence of cortical or trabecular bone involvement (Fig. 1A), with T1 hypointensity, diffusion restriction and mild STIR hyperintensity in excess of background BM changes. The FBML showed a predilection for the lower limbs (knees, ankles and/or feet involvement in 3 patients, 50%) and periarticular spaces (5 patients, 83%). They were CT-occult and only mildly FDG-avid. In all cases, core biopsies of the FBML showed heavy BM infiltration with diffuse interstitial infiltrate of small, mature lymphocytes (Fig. 1B, 1C) expressing CD20, CD79a and IgM; CD138 staining highlighted scattered interstitial plasma cells (<10%). There was no evidence of infarct or high-grade transformation. When compared to contemporaneous PSIS biopsies (Fig. 1D, 1E), all FBML demonstrated significantly higher proportions of lymphoid infiltration into the haematopoietic space (80-100% vs 0-80%, p=0.03), confirming FBML represent heavier disease infiltrationthan the background BM disease burden. On blood panels, LDH, ALP and platelet count were normal and Hb was >100g/L in all but the 1 patient with active WM (who had Hb 79g/L and ALP 149IU/L). There was no corresponding rise in paraprotein at the time of FBML presentation. In all cases, the detection of FBML prompted initiation/escalation of systemic treatment despite no evidence of progression using conventional criteria; this resulted in resolution of pain and disappearance of the T1 hypointense lesions on MRI in all cases. CONCLUSION Painful, LPL-dense, infiltrative lesions confined to the BM of affected appendicular bones are an unreported manifestation in WM. They are clinicopathologically different from the osteolytic lesions seen in myeloma and the painless, diffuse BM infiltration seen in low-grade lymphomas and can induce unrelenting focal skeletal pain. Based on our findings, such cases should be evaluated for focal bone marrow lesions; MRI is the preferred modality as lesions are CT-occult. They do not necessarily represent high-grade transformation. This small yet comprehensive series suggests they constitute a hitherto undescribed novel indication for systemic therapy irrespective of the general disease status. Disclosures D'Sa: Janssen:Honoraria, Research Funding;BeiGene:Honoraria, Research Funding;Sanofi:Honoraria.

Evaluation of Necrotic, Edematous and Inflammatory Changes in Bone Marrow and Soft Tissue After Irrigation with Different Concentrations of NaOCl Solution: An Experimental Study in Rat Tibia.

We aimed to investigate effects of different concentrations (0.5-5%) of Sodium Hypochlorite (NaOCl) solution on healthy tissues, and determine the optimal concentration that does not harm to tissue. 30 tibias of 15 male Wistar albino rats were used. The tibias were randomly divided into 5 groups (Salin, 0.5%, 1%, 2.5%, and 5% NaOCl). Tibias were reamed intramedullary, and irrigated with 20 ml of saline or increasing concentrations of (0.5-5%) NaOCl. The tibias were embedded in paraffin and the sections were stained with hematoxylin-eosin. All sections were assessed for edema, acute inflammation, or necrosis according to their density, in bone marrow and soft tissues. Pairwise comparisons revealed that irrigation of tibia with saline or 0.5% NaOCl solutions was not statistically significant in terms of necrosis in the bone marrows (p=0.320). However, irrigation of rat tibia with saline caused less necrosis in the bone marrows compared to high concentrations (1%, 2.5%, and 5%) of NaOCl (saline and 1% NaOCl, p=0.017; saline and 2.5% NaOCl, p=0.0007; saline and 5% NaOCl, p=0.001). As an irrigation solution, the effects of 0.5% NaOCl are similar to those of saline in terms of edema, inflammation, and necrosis. There is a need for evaluation of necrosis for extended periods such as one week or one month by immunohistochemical methods and flow cytometry.

Changes in histidine decarboxylase expression influence extramedullary hematopoiesis in postnatal mice.

Histidine decarboxylase (HDC), histamine synthase, is expressed in hematopoietic stem cells and in lineage-committed progenitors in the bone marrow (BM). However, the role of histamine in hematopoiesis is not well described. To evaluate the role of histamine in hematopoiesis, we analyzed the changes in HDC expression at hematopoietic sites, the BM, spleen, and liver of 2-, 3-, and 6-week-old wild-type mice. We also performed morphological analyses of the hematopoietic sites using HDC-deficient (HDC-KO) mice. In wild-type adults, HDC expression in the BM was higher than that in the spleen and liver and showed an age-dependent increase. Histological analysis showed no significant change in the adult BM and spleen of HDC-KO mice compared to wild-type mice. In the liver, HDC expression was temporarily increased at 3 weeks and decreased at 6 weeks of age. Morphological analysis of the liver revealed more numerous hematopoietic colonies and megakaryocytes in HDC-KO mice compared to wild-type mice at 2 and 3 weeks of age, whereas no changes were observed in adults. Most of these hematopoietic colonies consisted of B220-positive B-lymphocytes and TER119-positive erythroblasts and were positive for the cell proliferation marker PCNA. Notably, these hematopoietic colonies declined in HDC-KO mice upon N-acetyl histamine treatment. A significant increase in the expression of hematopoiesis-related cytokines, Il3, Il7, Epo, Gcsf, and Cxcl12 mRNA was observed in the liver of 3-week-old HDC-KO mice compared to wild-type mice. These results suggest that histamine-deficiency may maintain an microenvironment suitable for hematopoiesis by regulating hematopoiesis-related cytokine expression in the liver of postnatal mice.

The bone marrow niche components are adversely affected in sepsis

Multiple organ dysfunction is an important cause of death in patients with sepsis. Currently, few studies have focused on the impact of sepsis on bone marrow (BM), especially on the cell components of BM niche. In this study, we performed mouse sepsis models by intraperitoneal injection of LPS and cecal ligation and puncture (CLP). The changes of niche major components in the mouse BM among vascular structures, mesenchymal stem cells and Treg cells were observed and analyzed. The results showed that pathological changes in BM was earlier and more prominent than in other organs, and various cell components of the BM niche changed significantly, of which vascular endothelial cells increased transiently with vascular remodeling and the regulatory T cells decreased over a long period of time. These results indicated that the components of the BM niche underwent series of adaptive changes in sepsis.

Radioprotective Activity of the Nitric Oxide Synthase Inhibitor T1023. Toxicological and Biochemical Properties, Cardiovascular and Radioprotective Effects.

In this work, studies were performed to investigate the toxicological, biochemical, vasotropic and radiomodifying properties of the new nitric oxide synthase (NOS) inhibitor, compound T1023. Toxicological studies included the estimation of acute toxicity in mice after i.p. administration of T1023. Radiometric analysis and electron paramagnetic resonance spectroscopy were used to study NOS-inhibitory properties of T1023 in vitro and in vivo, respectively. T1023 vasoactive properties were studied in rat central hemodynamics. Radiobiological experiments were performed using endogenous and exogenous spleen colony formation as well as 30-day survival tests. The morphological changes in peripheral blood and bone marrow (BM) induced with T1023 were analyzed in mice during hematopoietic acute radiation syndrome (H-ARS). It was shown that T1023 is a sufficiently safe compound (LD10 of 317 mg/kg; LD50 of 410 mg/kg). It is an effective competitive NOS-inhibitor that is 10-to-15-fold selective to endothelial and inducible NOS (IC50 for nNOS, iNOS, eNOS: 52.3, 3.2 and 5.1 µM, respectively). Its NOS-inhibitory activity is realized in vivo and is accompanied by an increase in vascular tone. Its single i.p. administration in doses greater than 1/8 LD10 provides significant (40-50%) and long-lasting (more than 90 min) weakening of cardiac output, which can cause transient hypoxia. In radiobiological studies, T1023 proved to be a hypoxic radioprotector. Its radioprotective effect was observed only when administered prophylactically [single i.p dose, 5-120 min before total-body irradiation (TBI)] and only in doses that reduced cardiac output (1/8 LD10 and more, 40 mg/kg for mice), and was correlated in time with the dynamics of circulatory depression. Its radioprotective effect was not observed when administered in vitro and in the first 4 h after TBI. The optimal radioprotective doses of T1023 are relatively safe (1/ 5-1/4 LD10). In addition, T1023 effectively prevents H-ARS and gastrointestinal acute radiation syndrome (G-ARS) in experimental animals in vivo: dose modifying factor of 1.6-1.9. In the H-ARS mouse model, the prophylactic effect of T1023 (75 mg/kg, single i.p. injection) was accompanied by clinically significant effects. There was an express decrease in the degree of indicators of early BM devastation (by 40%) and maximal neutropenia and thrombocytopenia (2-2.5 times), in addition to a reduction in recovery time (by 30-40%). The obtained experimental results and literature data indicate that NOS inhibitors are an independent class of vasoactive radioprotectors with a specific hypoxic mechanism of action. NOS inhibitors provide new opportunities for developing effective and safe tools for the prevention of ARS.

Fat fraction quantification of lumbar spine: comparison of T1-weighted two-point Dixon and single-voxel magnetic resonance spectroscopy in diagnosis of multiple myeloma.

We aimed to investigate the value of T1-weighted two-point Dixon technique and single-voxel magnetic resonance spectroscopy (MRS) in diagnosis of multiple myeloma (MM) through quantifying fat content of vertebral marrow. A total of 30 MM patients and 30 healthy volunteers underwent T1-weighted two-point Dixon and single-voxel MRS imaging. The fat fraction map (FFM) was reconstructed from the Dixon images using the equation FFM = Lip/In, where Lip represents fat maps and In represents in-phase images. The fat fraction (FF) of MRS was calculated by using the integral area of Lip peak divided by the sum of integral area of Lip peak and water peak. FF values measured by the Dixon technique and MRS were significantly decreased in MM patients (45.99%±3.39% and 47.63%±4.38%) compared with healthy controls (64.43%±0.96% and 76.22%±1.91%) (P < 0.001 with both methods). FF values measured by Dixon technique were significantly positively correlated to those measured by MRS in MM (r = 0.837, P < 0.001) and healthy control group (r = 0.735, P < 0.001), respectively. There was no significant difference between area under the curve (AUC) obtained by the Dixon technique (0.878±0.047; range, 0.785 to 0.971; optimal cutoff, 56.35 for healthy controls vs. MM) and MRS (0.883±0.047; range, 0.791 to 0.974; optimal cutoff, 61.00 for healthy controls vs. MM). The ability of Dixon technique to differentiate MM group from healthy controls was equivalent to single-voxel MRS. Regarding detection of fat contents in vertebral bone, T1-weighted two-point Dixon technique exhibited equivalent performance to single-voxel MRS in the diagnosis of multiple myeloma. Moreover, two-point Dixon is a more convenient and stable technique for assessing bone marrow changes in MM patients than single-voxel MRS.

Caprylic acid (C8:0) promotes bone metastasis of prostate cancer by dysregulated adipo-osteogenic balance in bone marrow.

Prostate cancer (PCa) continues to be the most common, noncutaneous cancer in men. Bone is the most frequent site of PCa metastases, and up to 90% of patients with advanced PCa develop bone metastases. An altered bone marrow microenvironment, induced by obesity, is a significant mediator for the bone tropism of PCa. However, the specific molecular mechanisms by which obesity causes changes in the bone marrow microenvironment, leading to PCa bone metastasis, are not fully understood. Our results demonstrate that a high‐fat diet (HFD) leads to dyslipidemia and changes in bone marrow of nude mice: an increase in the area and number of adipocytes and a reduction in the area and number of osteoblasts. Moreover, a HFD promoted cyclooxygenase 2 (COX2) expression and inhibited osteoprotegerin (OPG) expression in the bone microenvironment. Additionally, the total level of free fatty acids (FFAs) and caprylic acid (C8:0) was significantly higher in PCa patients with bone metastases. In vitro, caprylic acid (C8:0) promoted bone mesenchymal stem cell (MSC)‐derived adipocytic differentiation, COX2 expression, and prostaglandin E2 (PGE2) secretion, whereas osteoblastic differentiation and OPG expression were reduced. Furthermore, caprylic acid (C8:0)‐treated adipocytes promoted the invasion and migration of PCa cells. Taken together, our findings suggest caprylic acid (C8:0) promotes bone metastasis of PCa by dysregulated adipo‐osteogenic balance of bone marrow.

Haematological profiles after Intensive phase of Anti Koch Treatment with special emphasis on bone marrow changes

BackgroundTuberculosis remains a major public health problem in various parts of the world. It leads to various haematological changes. Study of these haematological changes will help better patient management. Objective & methodsIt is to evaluate haematological changes in tuberculosis patients and compare the result with special emphasis to bone marrow changes as active case search is sharply decreasing the miliary tuberculosis. It is also to evaluate the patients with before and after the Intensive Phase of Anti Koch Treatment. Sputum positive and sputum negative tuberculosis patients confirmed by other ancillary techniques were included into this study. It is conducted at a tertiary level hospital in rural area. ResultIn this study bone marrow hypercellularity was of erythroid series with only 1.92% patients showed granuloma in bone marrow aspiration. In addition to bone marrow changes, significant changes were evident in haemoglobin level, Erythrocyte Sedimentation Rate (ESR) Total White Blood Cell count and RBC count. DiscussionIn majority cases this study showed Erythroid Hyperplasia. It is sharp contrast with other study where myeloid hyperplasia was evident. This study also differs from other study where high number of bone marrow granuloma was reported. In this study only 1.92% cases showed bone marrow granuloma. This study also documented higher number of anaemic cases mostly because of the institute serves poor and tribal population. ConclusionIn our study the cases showing granuloma and hyperplasia of myeloid series were limited. With introduction of Directly Observed Treatment and house to house active case search helped to sharply decrease bone marrow granuloma by limiting multi-organ spread. This study showed, ESR level may be considered as prognostic parameters of tuberculosis.

Imaging of the degenerative spine using a sagittal T2-weighted DIXON turbo spin-echo sequence

PurposeTo evaluate the diagnostic performance of a sagittal T2-weighted DIXON turbo spin-echo (TSE) sequence and to assess whether fat-only images could replace dedicated sagittal T1-weighted sequences for magnetic resonance imaging (MRI) of the degenerative spine. Method35 patients (56.5 ± 19.8 years, 62.9 % males) with lumbar back pain (LBP) who underwent MRI of the lumbar spine including a sagittal T2-weighted DIXON sequence (acquisition time: 3:25 min) and T1-weighted sequence (acquisition time: 3:03 min) were included. Two image layouts (layout 1: fat-only AND water-only AND in-phase images of the DIXON sequence; layout 2: water-only AND in-phase images of the DIXON sequence AND T1-weighted images) were evaluated by two readers (R1 and R2) concerning degenerative changes including diagnostic confidence (1 – low, 2 – intermediate, and 3 – high) and signal changes of vertebral bone marrow (BM). Results were compared between readers and layouts. ResultsNo differences were observed in the number of detected pathologies on a segment-wise level, nor in the number of segments affected by degenerative changes when comparing evaluations of layout 1 and layout 2 for each reader. Diagnostic confidence was high without a statistically significant difference between the readings of both layouts (R1: layout 1: 2.79 ± 0.41, layout 2: 2.81 ± 0.39, p = 0.53; R2: layout 1: 2.99 ± 0.07, layout 2: 2.99 ± 0.07, p = 0.99). ConclusionsIn patients with LBP, MRI using a sagittal T2-weighted DIXON sequence and no separate T1-weighted sequence might be sufficient to accurately detect common degenerative changes with high diagnostic confidence. Sparing dedicated T1-weighted sequences can considerably reduce overall scan time.

Human Aging Alters the Spatial Organization between CD34+ Hematopoietic Cells and Adipocytes in Bone Marrow.

SummaryAge-related clonal hematopoiesis is a major risk factor for myeloid malignancy and myeloid skewing is a hallmark of aging. However, while it is known that non-cell-autonomous components of the microenvironment can also influence this risk, there have been few studies of how the spatial architecture of human bone marrow (BM) changes with aging. Here, we show that BM adiposity increases with age, which correlates with increased density of maturing myeloid cells and CD34+ hematopoietic stem/progenitor cells (HSPCs) and an increased proportion of HSPCs adjacent to adipocytes. However, NGFR+ bone marrow stromal cell (NGFR+ BMSC) density and distance to HSPCs and vessels remained stable. Interestingly, we found that, upon aging, maturing myeloid cell density increases in hematopoietic areas surrounding adipocytes. We propose that increased adjacency to adipocytes in the BM microenvironment may influence myeloid skewing of aging HSPCs, contributing to age-related risk of myeloid malignancies.

Megakaryocytes promote osteoclastogenesis in aging.

Megakaryocytes (MKs) support bone formation by stimulating osteoblasts (OBs) and inhibiting osteoclasts (OCs). Aging results in higher bone resorption, leading to bone loss. Whereas previous studies showed the effects of aging on MK-mediated bone formation, the effects of aging on MK-mediated OC formation is poorly understood. Here we examined the effect of thrombopoietin (TPO) and MK-derived conditioned media (CM) from young (3-4 months) and aged (22-25 months) mice on OC precursors. Our findings showed that aging significantly increased OC formation in vitro. Moreover, the expression of the TPO receptor, Mpl, and circulating TPO levels were elevated in the bone marrow cavity. We previously showed that MKs from young mice secrete factors that inhibit OC differentiation. However, rather than inhibiting OC development, we found that MKs from aged mice promote OC formation. Interestingly, these age-related changes in MK functionality were only observed using female MKs, potentially implicating the sex steroid, estrogen, in signaling. Further, RANKL expression was highly elevated in aged MKs suggesting MK-derived RANKL signaling may promote osteoclastogenesis in aging. Taken together, these data suggest that modulation in TPO-Mpl expression in bone marrow and age-related changes in the MK secretome promote osteoclastogenesis to impact skeletal aging.

Association of Modic change types and their short tau inversion recovery signals with clinical characteristics- a cross sectional study of chronic low back pain patients in the AIM-study

BackgroundModic Changes (MCs, magnetic resonance imaging (MRI) signal changes in the vertebral bone marrow extending from the vertebral endplate) may represent a subgroup of nonspecific chronic low back pain that could benefit from a specific management. The primary aim was to compare clinical characteristics between patients with type 1 versus type 2 MCs. The secondary aim was to explore associations between clinical characteristics and MC related short tau inversion recovery (STIR) signals.MethodsThis cross-sectional study used baseline data prospectively collected between 2015 and 2017 on the 180 patients included in the AIM-study (Antibiotics In Modic changes), a randomized controlled trial in a Norwegian hospital out-patient setting of patients with chronic low back pain, a lumbar disc herniation within the last 2 years, low back pain intensity score ≥ 5 (on a 0–10 scale) and current type 1 or type 2 MCs at the previously herniated lumbar disc level. We used prespecified clinical characteristics including self-report measures, physiologic measures and functional measures from clinical history and examination. The diagnostic accuracy of various clinical characteristics to discriminate between patients with type 1 MCs (with or without additional type 2 MCs) and patents with type 2 MCs only (not type 1) were assessed by calculating the area under the receiver-operating curve. We assessed the correlations of clinical characteristics with details of MC related STIR signal increase.ResultsNo clinical characteristic differed between patients with type 1 (n = 118) versus type 2 (but not type 1) (n = 62) MCs. The clinical characteristics showed no/minor differences or no/weak correlations with MC related STIR signal increase. Patients with a positive Springing test (at any lumbar level) had slightly less volume of STIR signal increase than those with a negative test (mean difference 1.3 on a 0–48 scale, 95% CI 0.3 to 2.3).ConclusionClinical characteristics were similar for patients with type 1 MCs and patients with type 2 MCs, and showed no clinically relevant correlations with MC related STIR signal increase.Trial registrationClinicalTrials.gov NCT02323412, First registered 23 December 2014

Laboratory and clinical findings and their association with viral and proviral loads in cats naturally infected with feline leukemia virus

This study was conducted to correlate clinical, laboratory, and bone marrow (BM) changes in cats naturally infected with feline leukemia virus and their association with viral loads in blood and BM and proviral loads in BM. Cats were classified into five groups based on antigenemia, clinical and/or laboratory findings and viral/proviral loads, according to a prospective study: symptomatic progressive (GI); asymptomatic progressive (GII); regressive (GIII); unclassified (GIV); or healthy (GV). |Correlations between these five groups and viral/proviral loads were evaluated. High viral and proviral loads were detected in GI and GII and viral loads were significantly associated with laboratory signs. Proviral loads detected in BM were significantly lower in GIII and GIV. GI cats were more likely to develop hematopoietic disorders than those from the other groups. Hematological and clinical disorders and disease severity are related to higher viral blood and proviral BM loads.

MON-337 Peripheral Neurological Complications in Pregnancy- Is Idiopathic Transient Osteoporosis of Pregnancy Concerning?

Idiopathic transient osteoporosis of pregnancy (ITOP) is a rare and under-reported condition that has affected healthy pregnancies. ITOP usually presents in the final trimester of a normal pregnancy. Radiographic studies detect drastic loss of bone mass, elevated rates of turnover in the bone, and edema in the affected portion.We present a 26-year-old previously healthy woman, who was admitted at 39 weeks of gestation with severe left hip pain and inability to walk for one month.The pain was constant, progressive, involving left lower limb, and associated with numbness and weakness. Neurological exam revealed diminished power in the left hip (motor power was 2/5), and inability to stand and walk due to pain in the left hip. She was unable to stand by herself. Investigations revealed anemia, low vitamin B12, low vitamin D and magnesium. Bilateral hip MRI showed increased T2WI signal in the left femoral head consistent with idiopathic transient osteoporosis of the left hip (ITOP). DXA scan showed bone mass density (BMD) below expected for age.The patient had induced vaginal labor without complication. The left hip pain improved after delivery. She was treated conservatively with Calcium, Magnesium and vitamin D. The patient symptoms completely resolved in 3 months post-delivery. DXA scan and Hip MRI at 1 year interval showed normal BMD and complete resolution of previous bone marrow edema and changes seen in MRI hip.This case report serves to highlight the effect of pregnancy on bone mass during third trimester which may result in transient osteoporosis of pregnancy leading to weakness and gait disturbance. Clinical symptoms can be misdiagnosed as a peripheral neurological complications instead of bone metabolism changes of pregnancy.

Association Between Modic Changes and Low Back Pain in Middle Age: A Northern Finland Birth Cohort Study.

A cross-sectional study of the Northern Finland Birth Cohort 1966 (NFBC1966). The aim of this study was to evaluate the association between the type, size, and location of lumbar Modic changes (MC), and prolonged disabling low back pain (LBP). LBP is the leading cause of disability worldwide and it affects all age- and socioeconomical groups. Only a small proportion of LBP patients are diagnosed with a specific cause: In most cases no single nociceptive cause for the pain can be identified. MC are visualized in magnetic resonance imaging (MRI) as a signal intensity change in vertebral bone marrow and have been proposed to represent a specific degenerative imaging phenotype associated with LBP. MC can be classified into several subtypes, of which inflammatory Type 1 (MC1) is suggested as being more likely to be associated with LBP. We assessed lumbar MRI (n = 1512) for the presence, type, and size of MC. The associations of MC characteristics with prolonged (≥30 days during the past year) and disabling (bothersomeness of LBP at least 6 on a 0-10 Numeric Rating Scale) LBP, evaluated at the time of imaging at 47 years, were analyzed using binary logistic regression, adjusted for sex, BMI, smoking, educational status, lumbar disc degeneration, and disc herniations. Any MC and MC1 were associated with prolonged disabling LBP (odds ratio [OR] after full adjustments 1.50 [95% confidence interval, CI 1.05-2.15] and 1.50 [95% CI 1.10-2.05], respectively). Furthermore, MC covering the whole anterior-posterior direction or the whole endplate, as well as the height of MC, were significantly associated with prolonged disabling LBP (OR after full adjustments 1.59 [95% CI 1.14-2.20], 1.67 [95% CI 1.13-2.46] and 1.26 [95% CI 1.13-1.42], respectively). Our study showed a significant and independent association between MC and clinically relevant LBP. 3.

Daily Ethanol Drinking Followed by an Abstinence Period Impairs Bone Marrow Niche and Mitochondrial Function of Hematopoietic Stem/Progenitor Cells in Rhesus Macaques.

Unhealthy consumption of alcohol is a major public health crisis with strong associations between immunological dysfunctions, high vulnerability to infectious disease, anemia, and an increase in the risk of hematological malignancies. However, there is a lack of studies addressing alcohol-induced changes in bone marrow (BM) and hematopoiesis as fundamental aspects of immune system function. To address the effect of chronic alcohol consumption on hematopoietic stem and progenitor cells (HSPCs) and the BM niche, we used an established rhesus macaque model of voluntary alcohol drinking. A cohort of young adult male rhesus macaques underwent a standard ethanol self-administration protocol that allowed a choice of drinking alcohol or water 22hours/day with periods of forced abstinence that elevated subsequent intakes when alcohol availability resumed. Following the last month of forced abstinence, the monkeys were euthanized. HSPCs and bone samples were collected and analyzed in functional assays and by confocal microscopy. HSPCs from alcohol animals exhibited reduced ability to formgranulocyte-monocyte and erythroidcolonies in vitro. HSPCs also displayed a decrease in mitochondrial oxygen consumption linked to ATP production and basal respiratory capacity. Chronic alcohol use led to vascular remodeling of the BM niche, a reduction in the number of primitive HSPCs, and a shift in localization of HSPCs from an adipose to a perivascular niche. Our study demonstrates, for the first time, that chronic voluntary alcohol drinking in rhesus macaque monkeys leads to the long-term impairment of HSPC function, a reduction in mitochondrial respiratory activity, and alterations in the BM microenvironment. Further studies are needed to determine whether these changes in hematopoiesis are persistent or adaptive during the abstinent period and whether an initial imprinting to alcohol primes BM to become more vulnerable to future exposure to alcohol.

The association between change in bone marrow lesion size and change in tibiofemoral cartilage volume and knee symptoms - results from the ZAP2 trial

Purpose: Subchondral bone marrow lesions (BMLs) are an early sign of knee osteoarthritis (OA) that predicts both cartilage loss and symptomatic progression of OA. Previous studies have suggested targeting BMLs in short-term structure modification trials. A key hypothesis is that shrinkage of BMLs is associated with reduced cartilage loss and improved knee symptoms, but this has been debated. This study used data from a multicentre randomised controlled trial (ZAP2), in which all participants had symptomatic knee OA and BMLs, and the aim was to describe the association between change in BMLs and change in tibiofemoral cartilage volume and knee symptoms.