Faculty Bibliography

Anorexia nervosa is complicated by low bone mineral density (BMD) and increased fracture risk associated with low bone formation and high bone resorption. The lumbar spine is most severely affected. Low bone formation is associated with relative insulin-like growth factor 1 (IGF-1) deficiency. Our objective was to determine whether bone anabolic therapy with recombinant human (rh) IGF-1 used off-label followed by antiresorptive therapy with risedronate would increase BMD more than risedronate or placebo in women with anorexia nervosa. We conducted a 12-month, randomized, placebo-controlled study of 90 ambulatory women with anorexia nervosa and low areal BMD (aBMD). Participants were randomized to three groups: 6 months of rhIGF-1 followed by 6 months of risedronate ("rhIGF-1/Risedronate") (n = 33), 12 months of risedronate ("Risedronate") (n = 33), or double placebo ("Placebo") (n = 16). Outcome measures were lumbar spine (1° endpoint: postero-anterior [PA] spine), hip, and radius aBMD by dual-energy X-ray absorptiometry (DXA), and vertebral, tibial, and radial volumetric BMD (vBMD) and estimated strength by high-resolution peripheral quantitative computed tomography (HR-pCT) (for extremity measurements) and multi-detector computed tomography (for vertebral measurements). At baseline, mean age, body mass index (BMI), aBMD, and vBMD were similar among groups. At 12 months, mean PA lumbar spine aBMD was higher in the rhIGF-1/Risedronate (p = 0.03) group and trended toward being higher in the Risedronate group than Placebo. Mean lateral lumbar spine aBMD was higher, in the rhIGF-1/Risedronate than the Risedronate or Placebo groups (p < 0.05). Vertebral vBMD was higher, and estimated strength trended toward being higher, in the rhIGF-1/Risedronate than Placebo group (p < 0.05). Neither hip or radial aBMD or vBMD, nor radial or tibial estimated strength, differed among groups. rhIGF-1 was well tolerated. Therefore, sequential therapy with rhIGF-1 followed by risedronate increased lateral lumbar spine aBMD more than risedronate or placebo. Strategies that are anabolic and antiresorptive to bone may be effective at increasing BMD in women with anorexia nervosa. © 2021 American Society for Bone and Mineral Research (ASBMR).

There is a global increase in the prevalence of severe obesity in females during adolescence, which is a critical period for neurocognitive development. An increasing number of adolescents and young adults are now undergoing weight loss surgery as a treatment strategy for obesity. In addition to metabolic complications, obesity has been linked to neurocognitive comorbidity, and studies exploring cognitive performance in adolescents with severe obesity and the impact of bariatric surgery on cognitive abilities are limited. Verbal memory and executive function were assessed cross-sectionally in 69 females with moderate to severe obesity and 24 females without obesity, 13-24 years old. In an exploratory analysis, cognitive changes were also assessed longitudinally over 12 months in a subset of 35 females with moderate to severe obesity following weight loss surgery (n = 21) or following usual care without surgery (n = 14). In cross-sectional analysis, females with moderate to severe obesity showed lower scores for short-term and long-term recall (verbal memory) and response inhibition and cognitive flexibility (executive function) than the comparison group, when adjusted for age and baseline intelligence. Females with moderate to severe obesity who underwent surgery showed significant weight loss but no improvement in verbal memory and executive function scores over 12 months compared with those who did not have surgery. Females with moderate to severe obesity demonstrate worse performance in tests of verbal memory and executive function than the comparison group without obesity. In addition, exploratory analyses provide no indication that weight loss surgery improves these observed cognitive decrements over a period of 12 months. Further studies are necessary to comprehensively evaluate changes in cognitive function following bariatric surgery.

PURPOSE/OBJECTIVE:To compare the pathology results of CT-guided and blind bone marrow aspirations and biopsies. METHODS:Ninety-eight consecutive CT-guided biopsies and 98 age- and gender-matched blind (non-CT-guided) posterior iliac crest bone marrow aspirations and biopsies performed in 2017 were reviewed for adequacy of core biopsies and aspirate smears. CT procedure images and CT abdomen/pelvis images were reviewed to evaluate anatomic features of the posterior ilium and soft tissues. Statistical analysis was performed using a T test, Fisher exact test, and Kruskal-Wallis test. RESULTS:There was no significant difference in the age and gender of the two groups (p > 0.05). However, the CT-guided group had a higher BMI (p = 0.0049) and posterior soft tissue thickness (p = 0.0016). More CT-guided biopsy samples (CT 93 (95%); blind 77 (79%); p = 0.0006) and aspirate smears (CT 90 (92%); blind 78 (80%); p = 0.042) were categorized as adequate. The CT-guided group had longer core lengths (CT 1.4 ± 0.6 (range 0.3-3.5) cm; blind 1.0 ± 0.60 (range 0-2.6) cm; p = 0.0001). Overall, 131/164 (80%) of the cases had at least one of the described features (slanted posterior ilium (angle > 30°), 30%; rounded posterior ilium, 20%; thick posterior ilium cortex, 13%; focal lesion in posterior ilium, 12%; prior procedure in posterior ilium, 5%; posterior soft tissue thickness > 3 cm, 40%). CONCLUSION/CONCLUSIONS:CT-guided bone marrow procedures were more likely to result in both adequate aspirate smears and biopsy samples and longer core lengths when compared with blind procedures.

PURPOSE/OBJECTIVE:To determine the effect of intra-articular corticosteroid injections on lumbar spine trabecular density. MATERIALS AND METHODS/METHODS:This retrospective study was IRB-approved and HIPAA-compliant. We identified 50 patients (26 F, 24 M, mean age 69 ± 14 years) who had undergone at least three medium or large joint corticosteroid injections using insoluble corticosteroids and a subsequent non-contrast abdominal CT within 5 years of the first injection. About 126 age- and sex-matched controls without history of prior corticosteroid use who had undergone non-contrast abdominal CT were identified. Cumulative corticosteroid dose was calculated. Density measurements (HU) of trabecular bone of L1 to L4 were performed, and measurements of L1 were compared to established normative data. Groups were compared using a two-sided paired t-test or a chi-squared test. Linear regression analysis between cumulative corticosteroid dose and trabecular density was performed. RESULTS:Patients underwent a mean of 4 corticosteroid injections (range 3 to 11) with a mean cumulative corticosteroid dose of 232 ± 100 mg triamcinolone equivalent (range 120 mg to 480 mg). There was no significant difference in trabecular density of L1 to L4 between cases and controls, and there was no significant difference in trabecular density at L1 compared to normative data (p > 0.2). There was no association between cumulative intra-articular corticosteroid dose and mean lumbar trabecular density (p > 0.3). CONCLUSION/CONCLUSIONS:Patients who underwent repetitive intra-articular insoluble corticosteroid injections showed no increased risk of bone loss compared to controls. Cumulative intra-articular corticosteroid dose was not associated with lumbar trabecular density.

PURPOSE/OBJECTIVE:To determine (i) whether intra-articular gadolinium from MR arthrography (MRA) results in gadolinium deposition in the brain and (ii) whether there is a correlation between intra-articular gadolinium dose and intracranial gadolinium deposition. MATERIALS AND METHODS/METHODS:This retrospective study was institutional review board (IRB) approved and HIPAA compliant. The study group included consecutive adult patients who had undergone MRA of the hip or shoulder and subsequent MRI of the brain. None of the patients had a history of intravenous gadolinium exposure. A control group of patients of similar age and sex who were never exposed to gadolinium and had brain MRIs available was included. Signal intensities (SI) of four brain regions: pons, dentate nuclei (DN), globus pallidi (GP), and thalamus (Thal) normalized to cerebrospinal fluid (CSF) and expressed in SI ratios were measured on T1-weighted non-contrast MR images. Groups were compared using the student's t test. Linear correlation analysis of gadolinium dose and brain SI ratios was performed, and Pearson correlation coefficients (r) are reported. RESULTS:We identified 109 patients (mean age 44 ± 14 years, 54% men) who had undergone MRA and 149 controls of similar age and sex distribution. There was no significant difference in mean SI ratios of the brain regions between patients and controls: pons/CSF (p = 0.7), DN/CSF (p = 0.4), GP/CSF (p > 0.99), Thal/CSF (p = 0.3). Within the MRA group, gadolinium dose was not associated with SI ratios (p > 0.2). CONCLUSION/CONCLUSIONS:Our study found no MR evidence of intracranial gadolinium deposition following MRA. In addition, there was no association between intra-articular gadolinium dose and SI ratios in commonly affected regions of the brain.

Data are conflicting regarding the impact of weight loss on mood and anxiety in adolescent and young adult females with moderate to severe obesity (OB), who are at increased risk for mood dysfunction compared with normal-weight females (NW). We examined depressive and anxiety symptoms in 94 females 13-21 years old: 39 in the NW group (body mass index [BMI]: 5^th -85^th percentiles) and 55 in the OB group (BMI >40 kg/m² or >35 kg/m² with comorbidities). Fifteen participants in the OB group who underwent bariatric surgery (gastric bypass or sleeve gastrectomy) and 15 getting routine care were re-assessed after 6 months. The Beck Depression Inventory-II (BDI-II) and State-Trait Anxiety Inventory (STAI) assessed depressive and anxiety symptoms, respectively. The OB group had higher BDI-II and STAI T-scores (P < .0001), a higher prevalence of clinical depression and anxiety (P < .001), and reported greater suicidal ideation (P = .02) vs the NW group. The bariatric surgery and non-surgical groups did not differ for changes in BDI-II and STAI T-Scores and suicidality over 6-month follow-up, despite greater weight loss in the former. Depressive and anxiety symptoms and suicidality were more frequently observed in the OB vs NW group. These symptoms did not improve following bariatric surgery despite significant weight loss, underscoring the need to investigate determinants of emergence and resolution of these symptoms in the OB group.

PURPOSE/OBJECTIVE:Given the paucity of reliable predictors of tumor recurrence, progression, or response to somatostatin receptor ligand (SRL) therapy in acromegaly, we attempted to determine whether preoperative MR image texture was predictive of these clinical outcomes. We also determined whether image texture could differentiate somatotroph adenomas from non-functioning pituitary adenomas (NFPAs). METHODS:We performed a retrospective study of patients with acromegaly due to a macroadenoma who underwent transsphenoidal surgery at our institution between 2007 and 2015. Clinical data were extracted from electronic medical records. MRI texture analysis was performed on preoperative non-enhanced T1-weighted images using ImageJ (NIH). Logistic and Cox models were used to determine if image texture parameters predicted outcomes. RESULTS:Eighty-nine patients had texture parameters measured, which were compared to that of NFPAs, while 64 of these patients had follow-up and were included in the remainder of analyses. Minimum pixel intensity, skewness, and kurtosis were significantly different in somatotroph adenomas versus NFPAs (area under the receiver operating characteristic curve, 0.7771, for kurtosis). Furthermore, those with a maximum pixel intensity above the median had an increased odds of IGF-I normalization on SRL therapy (OR 5.96, 95% CI 1.33-26.66), which persisted after adjusting for several potential predictors of response. Image texture did not predict tumor recurrence or progression. CONCLUSION/CONCLUSIONS:Our data suggest that MRI texture analysis can distinguish NFPAs from somatotroph macroadenomas with good diagnostic accuracy and can predict normalization of IGF-I with SRL therapy.

BACKGROUND:African Americans (AA) have more favorable bone density and microarchitecture compared to Whites (W), which may explain their observed lower fracture rates. Obesity has deleterious effects on bone microarchitecture and strength estimates and is associated with an increase in fracture risk. Adolescence and young adulthood are periods of active bone accrual and also periods characterized by an increasing prevalence of obesity. The effect of obesity on the relationship between race and bone parameters remains unclear, particularly in youth. OBJECTIVE:To assess differences in BMD, bone microarchitecture and strength estimates in AA and W adolescents and young adults with moderate to severe obesity. We hypothesized that racial differences in bone endpoints in lean youth would also be noted in youth with moderate to severe obesity. METHODS:who underwent dual energy X-ray absorptiometry (DXA), high resolution peripheral quantitative computed tomography (HRpQCT), extended cortical analysis (ECA) and micro-finite element analysis (FEA) to obtain measures of volumetric bone mineral density (vBMD), bone geometry, microarchitecture, and strength estimates at the distal radius and tibia. RESULTS:We found no differences between AA and W for total fat and lean mass, and areal BMD Z-scores (p > 0.05 for all). At the distal radius, no significant differences were detected in vBMD, bone geometry or microarchitecture (p > 0.05 for all); however, stiffness and failure load were higher in the AA group (p = 0.031 and 0.047 respectively). At the distal tibia, cortical vBMD was higher in AA vs. W (p = 0.012), while trabecular number was higher and trabecular separation lower in W vs. AA (p ≤ 0.028). Stiffness and failure load trended higher in AA vs. W (p = 0.052 and p = 0.048, respectively). Groups did not differ for any other bone parameter (p > 0.05). CONCLUSION:Racial differences in bone endpoints appear to be less marked in those with moderate to severe obesity, suggesting that effects of obesity may blunt the effect of race on bone endpoints.

PURPOSE/OBJECTIVE:To determine the value of anesthetic injection during hip MR arthrography (anesthetic MRA) to differentiate between intra- and extra-articular pathology in patients with hip pain. MATERIALS AND METHODS/METHODS:This retrospective study was IRB-approved and HIPAA-compliant. We included 75 consecutive adult patients (46 women, mean age 38 ± 13 years) who were referred for MRA. All patients underwent a focused hip examination including active flexion, passive flexion, and passive flexion with internal and external rotation, immediately prior to injection. Anesthetic MRA was performed following fluoroscopically guided intra-articular injection of contrast mixed with anesthetic. Following the injection, the hip examination was repeated, and the pain response was recorded. Clinical records, including response to corticosteroid injections, physical therapy notes, and operative reports were reviewed for verification of intra- and extra-articular pathology as the source of hip pain (gold standard). The positive (PPV) and negative predictive values (NPP) of anesthetic MRA to differentiate between intra- and extra-articular pathology were calculated. RESULTS:On MRI, 41 patients had only intra-articular and 5 patients only extra-articular pathology, while 29 patients had both, intra- and extra-articular pathology. Forty-three patients had pain relief and 32 patients had no pain relief after anesthetic injection. PPV of anesthetic MRA to detect intra-articular pathology was 91% and NPV was 67%. CONCLUSION/CONCLUSIONS:Anesthetic MRA can be used as an adjunct to define the origin of hip pain. A positive response suggests intra-articular pathology which can be helpful to localize the source of pain in equivocal cases where both intra- and extra-articular pathology are evident on MRI.

Dedifferentiated chordoma is a rare chordoma subtype characterized by a high-grade sarcoma juxtaposed to conventional chordoma. We identified a series of dedifferentiated chordomas, reviewed clinicopathologic features, performed next-generation sequencing in select cases, and analyzed all related English-language publications. Our series included 7 men and 3 women (age 15 to 80 y [median: 54 y]; <1% of >1000 chordomas surveyed). The tumor (2.8 to 24.5 cm [median: 5.8 cm] in size) presented de novo or as recurrence (including postradiotherapy) in sacrum (n=5), skull base (n=2), lumbar spine (n=1), thoracic/mediastinum (n=1), and lung (n=1; as metastasis). Histologically, the dedifferentiated component (3% to 95% [median: 60%]) was pleomorphic-to-fibrosarcomatous, juxtaposed to conventional (n=8) or chondroid (n=2) component. By immunohistochemistry, the conventional/chondroid component consistently expressed cytokeratin and brachyury, whereas the dedifferentiated component showed loss of both. We identified a sacral conventional chordoma with INI1 loss, with one of the lung metastases showing biphasic histology with loss of cytokeratin and brachyury in the dedifferentiated component. Sequencing identified tumor suppressor mutations in 4 tumors, including TP53 mutations in the dedifferentiated component in 3 tumors. Of 7 patients with follow-up, 6 developed metastases; 4 died at 15 to 99 months (median: 24 mo) after dedifferentiated chordoma diagnosis. Collectively, of 87 dedifferentiated chordoma patients described in 1913-2020 (including 10 herein), the median overall survival was 20 months. In summary, dedifferentiated chordoma involves diverse sites and presents de novo, postradiotherapy, or as recurrence/metastasis months-to-years after initial diagnosis. The dedifferentiated component shows loss of brachyury and cytokeratin staining and harbors recurrent TP53 mutations, implicating tumor suppressor dysregulation in chordoma dedifferentiation.