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Anorexia nervosa is a psychiatric eating disorder related to malnutrition and consequent altered metabolism. A 48-year-old female with a history of anorexia in the last 2 years referred to our hospital with spinal pain. She underwent spinal X-ray and magnetic resonance imaging (MRI) showing multiple vertebral collapses in dorsal and lumbar spine with inversion of normal bone marrow and soft tissue signal in T1-weighted and STIR images. We describe this case of spinal 'flip-flop' phenomenon, underlining how what seems a technical failure is actually a specific imaging pattern related to the clinical context., (© 2020 The Royal Australian and New Zealand College of Radiologists.)

Bone marrow adiposity (BMA) is an underestimated tissue, with properties that may alter bone strength especially in diseases that fragilize bone such as anorexia nervosa. In the present study, we investigated the regional characteristics of BMA at the hip of 40 underweight and 36 weight-recovered anorexic women, along with 10 healthy women, using magnetic resonance spectroscopy at multiple anatomical subregions (acetabulum, femoral neck, proximal femoral diaphysis and greater trochanter) to measure bone marrow fat fraction (BMFF) and apparent lipid unsaturation levels (aLUL). Correlations between BMFF, aLUL, body fat percentage (BF), and bone mineral density (BMD) at the femoral neck and total hip, both measured using dual-energy X-ray absorptiometry, were assessed in anorexic patients. Whereas BMFF was significantly higher and aLUL significantly lower at the femoral neck of underweight and weight-recovered patients compared to controls (BMFF: 90.1 ± 6.7% and 90.3 ± 7.5% respectively versus 81.3 ± 8.1%; aLUL: 7.6 ± 1.4% and 7.3 ± 1.3% versus 9.2 ± 1.5%), BMFF and aLUL were not significantly different between the 2 subgroups of patients. Besides, three noteworthy features were observed between BMA and the other measured parameters in anorexic patients. First, synergic alterations of BMA were observed at all sites, with an inverse relationship between BMFF and aLUL (ρ = -0.88). Second, bone mineral compartment and BMA were associated, as a negative correlation between total hip BMD and BMFF was observed at all sites except the greater trochanter (ρ = [-0.32;-0.29]), as well as a positive correlation with aLUL at all sites except the proximal femoral diaphysis (ρ = [0.25;0.37]). Finally, we found a positive correlation between BF and BMFF at the femoral neck (ρ = 0.35), and a negative correlation between BF and aLUL at this same subregion (ρ = -0.33), which suggest a complex relationship between BMA and BF. Overall, BMA possesses regional specificities which may impair bone health, even after weight recovering., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Anorexia nervosa (AN) is a psychiatric disorder characterized by inappropriate nutrient intake resulting in low body weight. Multiple hormonal adaptations facilitate decreased energy expenditure in this state of caloric deprivation including non-thyroidal illness syndrome, growth hormone resistance, and hypogonadotropic hypogonadism. Although these hormonal adaptations confer a survival advantage during periods of negative energy balance, they contribute to the long-term medical complications associated with AN, the most common of which is significant bone loss and an increased risk of fracture. In recent years, marrow adipose tissue (MAT) has emerged as an important potential determinant of the low bone mass state characteristic of AN. Unlike subcutaneous and visceral adipose tissue depots which are low in AN, MAT levels are paradoxically elevated and are inversely associated with BMD. In this review, we discuss what is known about MAT in AN and the proposed hormonal determinants of this adipose tissue depot., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Adolescents and women with anorexia nervosa have increased bone marrow fat and decreased bone formation, at least in part due to hormonal changes leading to preferential stem cell differentiation to adipocytes over osteoblasts., Objective: The purpose of this study was to evaluate marrow fat content and correlate with age and disease severity using knee MRI with T1 relaxometry (T1-R) and MR spectroscopy (MRS) in 70 adolescents with anorexia nervosa., Materials and Methods: We enrolled 70 girls with anorexia nervosa who underwent 3-T knee MRI with coronal T1-W images, T1-R and single-voxel proton MRS at 30 and 60 ms TE. Metaphyses were scored visually on the T1-W images for red marrow. Visual T1 score, T1 relaxometry values, MRS lipid indices and fat fractions were analyzed by regression on age, body mass index (BMI) and bone mineral density (BMD) as disease severity markers. MRS measures included unsaturated fat index, T2 water, unsaturated and saturated fat fractions., Results: All red marrow measures declined significantly with age. T1-R values were associated negatively with BMI and BMD for girls ≤16 years (P=0.03 and P=0.002, respectively) and positively for those≥17 years (P=0.05 and P=0.003, respectively). MRS identified a strong inverse association between T2 water and saturated fat fraction from 60 ms TE data (r=-0.85, P<0.0001). There was no association between unsaturated fat index and BMI or BMD., Conclusions: The association between T1 and BMI and BMD among older girls suggests more marrow fat in those with severe anorexia nervosa. In contrast, the physiological association between marrow fat content and age remained dominant in younger patients. The strong association between T2 water and saturated fat may relate to the restricted mobility of water with increasing marrow fat.

Purpose: Women with anorexia nervosa (AN) have increased marrow fat despite severe depletion of body fat. Recent studies have suggested that marrow fat composition may serve as a biomarker for bone quality. The purpose of our study was to investigate marrow fat composition of the femur using proton MR spectroscopy ((1)H MRS), and the relationship between measures of marrow fat composition and BMD and body composition in women with AN and normal-weight controls., Materials and Methods: 14 women with AN (29.5±1.9years) and 12 age-matched normal-weight controls underwent (1)H MRS to determine total marrow fat content and marrow fat composition of the femoral diaphysis and soleus intramyocellular lipids und unsaturated muscle lipids. MRI was performed to quantify abdominal fat, thigh fat and muscle areas. Lumbar spine BMD, fat and lean mass were assessed by DXA., Results: Subjects with AN had higher marrow fat content (p<0.05), but similar marrow fat composition (p>0.05) compared to normal-weight controls. There was an inverse association between marrow methylene protons, an estimate of fatty acid (FA) saturated bonds, and lumbar spine BMD (r=-0.52, p=0.008) independent of %ideal body weight (%IBW). Olefinic protons at 5.3ppm, an estimate of FA unsaturated bonds, were inversely associated with body fat depots, independent of %IBW, and positively associated with soleus unsaturation (p≤0.05)., Conclusion: Women with AN have higher total femoral marrow fat but similar composition compared to normal-weight controls. The degree of marrow FA saturation correlates inversely with BMD, suggesting that saturated lipids may have negative effects on BMD. The degree of marrow FA unsaturation correlates positively with soleus unsaturation, suggesting that marrow fat composition may be influenced by the same factors as ectopic lipid composition in muscle., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Women with anorexia nervosa (AN) have elevated marrow fat mass despite low visceral and subcutaneous fat depots, which is inversely associated with bone mineral density (BMD). Whether marrow fat mass remains persistently elevated or decreases with recovery from AN is currently unknown. In this study, we investigated changes in marrow fat in women who have recovered from AN (AN-R). We also studied the relationship between preadipocyte factor (Pref)-1-a member of the EGF-like family of proteins and regulator of adipocyte and osteoblast differentiation-and fat depots and BMD in AN-R compared with women with AN and healthy controls (HC). We studied 29 women: 14 with active or recovered AN (30.7 + 2.2 years [mean ± SEM]) and 15 normal-weight controls (27.8 ± 1.2 years). We measured marrow adipose tissue (MAT) of the L4 vertebra and femur by (1) H-magnetic resonance spectroscopy; BMD of the spine, hip, and total body by DXA; and serum Pref-1 and leptin levels. We found that MAT of the L4 vertebra was significantly lower in AN-R compared with AN (p = 0.03) and was comparable to levels in HC. Pref-1 levels were also significantly lower in AN-R compared with AN (p = 0.02) and comparable to levels in healthy controls. Although Pref-1 was positively associated with MAT of the L4 vertebra in AN (R = 0.94; p = 0.002), we found that it was inversely associated with MAT of the L4 vertebra in HC (R = -0.71; p = 0.004). Therefore, we have shown that MAT and Pref-1 levels decrease with recovery from AN. Our data suggest that Pref-1 may have differential effects in states of nutritional deprivation compared with nutritional sufficiency., (Copyright © 2012 American Society for Bone and Mineral Research.)

Context: Although women with anorexia nervosa (AN) have severe depletion of body fat, a paradoxical increase in bone marrow fat has been described. Recent data suggest that marrow fat measured by 1H-magnetic resonance spectroscopy (MRS) in combination with bone mineral density (BMD) may be more valuable than either parameter alone in detecting bone weakness., Objective: The objective of the study was to investigate the effect of AN on accumulation of marrow fat in spine and femur using 1H-MRS and the relationship between marrow fat, BMD, and body composition in subjects with AN and normal-weight controls., Design: This was a cross-sectional study., Setting: The study was conducted at a referral center., Patients: Patients included 10 women with AN (29.8 +/- 7.6 yr) and 10 normal-weight age-matched women (29.2 +/- 5.2 yr)., Interventions: There were no interventions., Main Outcomes Measure: Marrow fat content of the fourth lumbar vertebra and femur measured by 1H-MRS. BMD of spine and hip measured by dual-energy x-ray absorptiometry., Results: Subjects with AN had higher marrow fat at the fourth lumbar vertebra and femur compared with controls (P = 0.004-0.01). There was an inverse correlation between marrow fat of L4 and femur and BMD of the spine and hip (r = -0.56 to -0.71, P = 0.01-0.0002) and body mass index and sc adipose tissue of the thigh (r = -0.49 to -0.71, P = 0.03-0.0007). There was an inverse correlation between femur marrow fat and sc and total abdominal adipose tissue (r = -0.53 to -0.67, P = 0.003-0.03)., Conclusion: Women with AN have greater lumbar and femoral marrow fat than controls, and marrow fat correlates inversely with BMD. This paradoxical increase in marrow fat at a time when sc and visceral fat are markedly reduced raises important questions about functional consequences of this process.

Objective: Changes of the peripheral blood cell count in patients with anorexia nervosa (AN) are frequent. Anemia and leukopenia are observed in one-third of these patients. Examination of the bone marrow reveals in almost 50% of the patients with AN signs of bone marrow atrophy and can additionally suffer from a gelatinous bone marrow transformation., Method: Published studies and investigations concerning hematological changes in patients with AN were reviewed., Results: Anemia and mild neutropenia are detectable in almost one-third of these patients, whereas thrombocytopenia is rather uncommon. The exact mechanism for these findings is still unclear, but 50% of AN-patients with hematological changes display morphological signs of partial bone marrow atrophy., Discussion: Changes of the peripheral blood cell count in patients with AN is a frequent observation but the peripheral blood cell count cannot predict the severity of bone marrow atrophy. All hematological and morphological alterations disappear completely and rapidly after sufficient refeeding.

History and Admission Findings: A 26-year-old woman was admitted because of excessive weight loss: her body mass index was 11.3 kg/m (2). She reported an adequate food intake and denied fear of gaining weight., Investigations: The leukocyte count on admission was 2.0/nl. Bone marrow biopsy showed gelatinous bone marrow transformation with hypocellularity. Psychiatric examination and observation of the patient's eating behavior revealed symptoms typical of anorexia nervosa., Diagnosis, Treatment and Course: Because of the diagnosis of anorexia nervosa behaviour therapy was started. During the following months the patient continually gained weight. But it took nine months for leukocyte count to be normal, by which time her body mass index had risen to 17.8 kg/m (2)., Conclusion: Severe weight loss in anorexia nervosa may lead to leukopenia and gelatinous bone marrow transformation. The abnormal leukocyte count can become normal by maintaining body weight within the normal range.

Patients with anorexia nervosa (AN) usually have abnormal bone and bone marrow metabolism resulting in osteopenia and serous bone marrow change. There is an increased risk of stress/insufficiency fractures and these can be the first presentation of AN. This case report describes a patient with previously undiagnosed AN who presented with foot pain. The serous bone marrow changes of AN were found to mask the MR imaging features of stress fractures, as both had low T1w and high T2w and STIR signal intensities. Contrast enhancement was not helpful but actually masked fractures. Scintigraphy was helpful. The radiologist might be the first clinician to raise the possibility of AN and should be aware of the difficulties in diagnosing stress fractures in bones with underlying serous bone marrow change. In this severe case of AN even the heel fat pad and the fat pad in Kager's triangle had undergone serous change.

Moderate hematologic abnormalities, like anemia or leukopenia, are frequently seen in anorexia nervosa, whereas pancytopenia and bone marrow abnormalities are uncommon. We report a case of tricytopenia with gelatinous bone marrow transformation in anorexia nervosa. Marrow gelatinous transformation (also called serous fat atrophy or starvation marrow) is characterized by the association of marrow hypoplasia and interstitial infiltration of a ground gelatinous substance (acidic mucopolysaccharides). Changes in peripheral blood cell counts are various and moderate, and do not always reflect the severity of bone marrow damage. The pathogenesis is not yet well elucidated but is certainly related to the nutritional status because gelatinous bone marrow transformation is found in anorexia nervosa and in other clinical situations with cachexia. Gelatinous transformation of the marrow is reversible with feeding.

Anorexia nervosa is a chronic psychiatric process characterized by a restrictive disorder in alimentary habits. Hematologic alterations in the peripheral blood include cytopenias involving one or more hematopoietic lineages. Morphologic changes in the bone marrow and stereologic alterations in bone marrow adiopocytes may also be observed in anorexia nervosa. We present a 12-year-old girl who had chronic anorexia and one third of body weight loss during an 8-month period. She was apathetic and had missed several menstrual cycles. The sex maturity rating was Tanner stage IV. There was no lymphadenopathy, no hepatosplenomegaly, and no identifiable tumor mass. She was not anemic, but was found to have leukopenia, neutropenia and a low level of triiodothyronine. Sections of the bone marrow biopsy showed almost complete serous atrophy (gelatinous degeneration) of the bone marrow. In this patient, the bone marrow alteration is related to nutritional deprivation of anorexia nervosa.

The clinical history and biochemical and hematologic variables for 44 consecutive patients diagnosed with anorexia nervosa were recorded. Bone marrow aspirates and biopsy specimens were analyzed by standard morphologic procedures, and bone marrow adipocytes were studied morphometrically. The bone marrow of the 44 patients was classified as normal (5 cases [11%]), hypoplastic or aplastic (17 [39%]), with partial or focal gelatinous degeneration (13 [30%]), or with complete gelatinous degeneration of the bone marrow (GDBM; 9 [20%]). These patterns correlated with amount of weight loss (P = .005) but not other clinical findings. WBC counts were lower in patients with GDBM (P = .0189), but this and other peripheral blood variables did not always reflect the severity of bone marrow damage. Hypoplastic or aplastic bone marrow showed an increase in bone marrow fat fraction due to an increase in adipocyte diameters, while in GDBM, fat fraction and adipocyte diameters decreased. Morphologic changes in bone marrow and stereologic alterations in bone marrow adipocytes may be observed in anorexia nervosa. The extent of damage is related to the amount of weight loss, not to other factors. Peripheral blood cell counts may not reflect the extent of damage. In some patients, this process may be reversible with reestablishment of adequate nutritional intake.

Objective: The objective of this study was to assess and quantify bone marrow changes in patients with anorexia nervosa using 1H magnetic resonance spectroscopy and relaxometry., Methods: The bone marrow fat fraction and the longitudinal and transverse relaxation times (T1 and T2, respectively) of water were measured in the lumbar and femoral marrow of 20 patients with anorexia nervosa and 19 healthy control subjects., Results: Patients with anorexia nervosa showed significant hyperhydration and reduction of the fat fraction in their bone marrow, predominantly in the proximal femur. These changes were associated with hematological abnormalities. In a retest of seven patients after psychotherapy and gain of weight, the pathological changes in marrow proved to be largely reversible in correlation with the increase in body mass index., Conclusions: Fat depletion and excess of tissue water in the bone marrow in anorexia nervosa can be quantified by 1H magnetic resonance spectroscopy and relaxometry. The distribution of the pathological changes in the lumbar and femoral marrow follows the pattern of normal bone marrow conversion from hematopoietic to cellular during childhood.

Gelatinous bone marrow transformation (GMT) is a rare disorder of unknown pathogenesis, characterized by fat cell atrophy, focal loss of hematopoietic cells, and deposition of extracellular gelatinous substances, which histochemically are mucopolysaccharides, rich in hyaluronic acid. To elucidate the conditions in which GMT develops, 155 cases of GMT that had been found in our archives among 80,000 marrow biopsies were revised. GMT occurred exclusively in adults, more often in males (n = 101) than in females (n = 54). Incidence and severity of GMT lesions were maximal in young adults. The spectrum of underlying diseases was heterogeneous and age-dependent. Anorexia nervosa, acute febrile states, and AIDS in younger ages (<40 years), alcoholism and lymphomas in middle ages, and carcinomas, lymphomas, and chronic heart failure in older ages (>60 years) were most commonly associated with GMT. Seventy-eight percent of patients with GMT showed weight loss; 81% were anemic. GMT in some cases may be a reversible lesion if the underlying disorder can be eliminated. In conclusion, GMT represents an indicator of severe illness in a patient but is not specific for a particular disease. Because GMT develops in different pathologic conditions, we suggest that basic bioregulatory processes play a role in its pathogenesis.

Objective: To assess the distribution of marrow changes in the bones of the lower limbs of patients with anorexia nervosa (AN) and to correlate the importance of the extent of marrow changes with clinical and hematologic data., Materials and Methods: The frequency of serouslike marrow (low signal intensity on T1-weighted images and very high signal intensity on T2-weighted images) was determined with MR imaging in the bones of the feet, distal tibias, and proximal femurs in 19 patients with AN., Results: Serouslike marrow was found with an increasing frequency from proximal to distal in the lower-limb bones (femur, 31%; distal phalanx of the first toe, 79%). The patients with abnormal femoral marrow (n = 6) were more severely emaciated and had lower leukocyte and neutrophil counts than the patients with normal femoral marrow (n = 13). Among these patients, the six patients with at least two involved bones in the feet had lower blood cell counts than the seven patients with fewer than two involved bones., Conclusion: In the lower limbs of patients with AN, marrow changes predominate in the distal aspects. This distribution pattern is the reverse of that seen in most bone marrow disorders but is similar to the normal conversion of hematopoietic to fatty marrow. The importance of the blood cell count changes is correlated with the extent of marrow changes in the limbs.

Purpose: To identify bone marrow abnormalities on magnetic resonance (MR) images of patients with anorexia nervosa (AN) and to correlate the findings with body mass index (BMI) and blood cell count., Materials and Methods: The signal intensity patterns in the lumbar, pelvic, and femoral marrow spaces were evaluated on MR images obtained in 14 patients with AN and 14 control subjects., Results: Six patients with AN had a waterlike signal intensity pattern either throughout the three marrow spaces (five patients) or only in the marrow cavity of the proximal femur (one patient). Results of biopsy performed in one of the six patients showed that the marrow had findings typical of serous atrophy. The BMI values and blood cell counts in the six patients were lower than those of the eight other patients with AN and the 14 control subjects., Conclusion: Bone marrow has an unusual signal intensity and distribution at MR imaging in patients with AN who have a low BMI value and biologic signs of bone marrow dysfunction.

Two patients with anorexia nervosa and gelatinous bone marrow justify a review of the cases in the literature. This gelatinous substance is related to an increase in mucopolysaccharides present in the marrow which replace the medullary fat mobilised by the maintenance of energy reserves; this increase would be unfavorable for hematopoiesis.

Marrow specimens from six patients with anorexia nervosa and three with involuntary starvation were examined for the presence of gelatinous transformation and marrow cell necrosis. Five of the patients had pancytopenia. Acanthocytes were present in the circulation of all nine. In only two patients was marrow cellularity adequate. Gelatinous transformation was present in every marrow specimen and was of a marked degree in eight. Marrow cell necrosis was identified in all nine marrow specimens. The necrosis was extensive in one specimen, focal in the others and limited to the areas of gelatinous transformation. Severe malnutrition was the single element common to all the patients.