Faculty Bibliography

BACKGROUND:Altered bone microarchitecture and higher marrow adipose tissue (MAT) may reduce bone strength. High resolution pQCT (HRpQCT) allows assessment of volumetric BMD (vBMD), and size and microarchitecture parameters of bone, while 1H-magnetic resonance spectroscopy (1H-MRS) allows MAT evaluation. We have reported impaired microarchitecture at the non-weight bearing radius in adolescents with anorexia nervosa (AN) and that these changes may precede aBMD deficits. Data are lacking regarding effects of AN on microarchitecture and strength at the weight-bearing tibia in adolescents and young adults, and the impact of changes in microarchitecture and MAT on strength estimates. OBJECTIVE:To compare strength estimates at the distal tibia in adolescents/young adults with AN and controls in relation to vBMD, bone size and microarchitecture, and spine MAT. DESIGN AND METHODS/METHODS:This was a cross-sectional study of 47 adolescents/young adults with AN and 55 controls 14-24years old that assessed aBMD and body composition using DXA, and distal tibia vBMD, size, microarchitecture and strength estimates using HRpQCT, extended cortical analysis, individual trabecular segmentation, and finite element analysis. Lumbar spine MAT (1H-MRS) was assessed in a subset of 19 AN and 22 controls. RESULTS:Areal BMD Z-scores were lower in AN than controls. At the tibia, AN had greater cortical porosity, lower total and cortical vBMD, cortical area and thickness, trabecular number, and strength estimates than controls. Within AN, strength estimates were positively associated with lean mass, aBMD, vBMD, bone size and microarchitectural parameters. MAT was higher in AN, and associated inversely with strength estimates. CONCLUSIONS:Adolescents/young adults with AN have impaired microarchitecture at the weight-bearing tibia and higher spine MAT, associated with reduced bone strength.

Bone marrow-derived myeloid cells can accumulate within tumors and foster cancer outgrowth. Local immune-neoplastic interactions have been intensively investigated, but the contribution of the systemic host environment to tumor growth remains poorly understood. Here, we show in mice and cancer patients (n = 70) that lung adenocarcinomas increase bone stromal activity in the absence of bone metastasis. Animal studies reveal that the cancer-induced bone phenotype involves bone-resident osteocalcin-expressing (Ocn⁺) osteoblastic cells. These cells promote cancer by remotely supplying a distinct subset of tumor-infiltrating SiglecF^high neutrophils, which exhibit cancer-promoting properties. Experimentally reducing Ocn⁺ cell numbers suppresses the neutrophil response and lung tumor outgrowth. These observations posit osteoblasts as remote regulators of lung cancer and identify SiglecF^high neutrophils as myeloid cell effectors of the osteoblast-driven protumoral response.

CONTEXT:Acromegaly is characterized by growth hormone (GH) and insulinlike growth factor-1 (IGF-1) hypersecretion, and GH and IGF-1 play important roles in regulating body composition and glucose homeostasis. OBJECTIVE:The purpose of our study was to investigate body composition including ectopic lipids, measures of glucose homeostasis, and gonadal steroids in patients with active acromegaly compared with age-, body mass index (BMI)-, and sex-matched controls and to determine changes in these parameters after biochemical control of acromegaly. DESIGN:Cross-sectional study of 20 patients with active acromegaly and 20 healthy matched controls. Prospective study of 16 patients before and after biochemical control of acromegaly. MAIN OUTCOME MEASURES:Body composition including ectopic lipids by magnetic resonance imaging/proton magnetic resonance spectroscopy; measures of glucose homeostasis by an oral glucose tolerance test; gonadal steroids. RESULTS:Patients with active acromegaly had lower mean intrahepatic lipid (IHL) and higher mean fasting insulin and insulin area under the curve (AUC) values than controls. Men with acromegaly had lower mean total testosterone, sex hormone-binding globulin, and estradiol values than male controls. After therapy, homeostasis model assessment of insulin resistance, fasting insulin level, and insulin AUC decreased despite an increase in IHL and abdominal and thigh adipose tissues and a decrease in muscle mass. CONCLUSIONS:Patients with acromegaly were characterized by insulin resistance and hyperinsulinemia but lower IHL compared with age-, BMI-, and sex-matched healthy controls. Biochemical control of acromegaly improved insulin resistance but led to a less favorable anthropometric phenotype with increased IHL and abdominal adiposity and decreased muscle mass.

OBJECTIVE:To assess the radiographic and clinicopathologic features of synovial sarcoma of the nerve that were clinically or radiologically interpreted as benign peripheral nerve sheath tumor. MATERIALS AND METHODS/METHODS:Five patients with synovial sarcoma arising from the peripheral nerve and interpreted clinically and radiologically as peripheral nerve sheath tumors were identified. Clinicopathologic and imaging features were evaluated. RESULTS:There were three females and two males, ranging in age from 28 to 50 (mean 35.8) years. Most patients (4/5) complained of a mass, discomfort or pain. MR images demonstrated a heterogeneous, enhancing, soft tissue mass contiguous with the neurovascular bundle. On histologic examination, most tumors were monophasic synovial sarcoma (4/5). At the time of surgery, all tumors were noted to arise along or within a peripheral nerve. All patients were alive with no evidence of disease with median follow-up of 44 (range 32-237) months. For comparison, approximately 775 benign peripheral nerve sheath tumors of the extremities were identified during the same time period. CONCLUSIONS:Primary synovial sarcoma of the nerve can mimic peripheral nerve sheath tumors clinically and on imaging and should be included in the differential diagnosis for tumors arising from peripheral nerves.

OBJECTIVE:Hemispherical spondylosclerosis (HS) is a rare degenerative entity characterized by dome-shaped sclerosis of a single vertebral body that may pose a diagnostic dilemma. The goal of this study was to describe the MR imaging features of HS. MATERIALS AND METHODS/METHODS:We identified spine radiographs and CT examinations of subjects with HS who also had MR imaging for correlation. Two musculoskeletal radiologists independently assessed sclerosis characteristics, presence of endplate erosions, marrow signal intensity, and disk degeneration (Pfirrmann scale). RESULTS:We identified 11 subjects (six males, five females, mean 48 ± 10 years) with radiographic/CT findings of HS. The most commonly affected vertebral body was L4 (6/11; 55%). On MR imaging, variable signal intensity was noted, being most commonly low on T1 (8/11, 73%) and high on fat-suppressed T2-weighted (8/11, 73%) images. In two subjects, diffuse post-contrast enhancement was seen in the lesion. Moderate disk degeneration and endplate bone erosions adjacent to sclerosis were present in all subjects. Erosions of the opposite endplate were present in two subjects (2/11, 18%). CT data from nine subjects showed the mean attenuation value of HS was 472 ± 96 HU. CONCLUSIONS:HS appearance on MR imaging is variable and may not correlate with the degree of sclerosis seen on radiographs or CT. Disk degenerative changes and asymmetric endplate erosions are consistent markers of HS.

PURPOSE/OBJECTIVE:Osseous metastases often undergo an osteoblastic healing response following chemotherapy. The purpose of our study was to demonstrate the quantitative CT changes in attenuation of osseous metastases before and after chemotherapy. MATERIALS AND METHODS/METHODS:Our study was IRB approved and HIPAA compliant. Our cohort consisted of 86 consecutive cancer patients with contrast-enhanced CTs before and 14 ± 2 (12-25) months after initiation of chemotherapy (60 ± 11 years, 36 males, 50 females). The average and maximum metastasis attenuations were measured in Hounsfield units (HU) by two readers. Treatment effects were assessed using paired t-tests and Fisher exact tests. Intraclass correlation coefficients (ICCs) were calculated. Patient records were reviewed to determine the patient's clinical status (worse, unchanged, or improved) at the time of follow-up CT. RESULTS:The distribution of lesion types was as follows: lytic (30/86, 35%), blastic (43/86, 50%), and mixed lytic-blastic (13/86, 15%). There was a significant increase in average and maximum CT attenuation of metastases following chemotherapy for all patients, which remained statistically significant when stratified by lesion type, clinical status (worsening or improving/stable), cancer type (breast, lung), and radiation therapy (P < 0.05). In a subgroup of patients whose osseous metastases decreased in average attenuation (14/86, 16%), more patients had a worse clinical status (11/14, 79%) (P = 0.02). ICC was almost perfect for average attenuation and substantial for maximum attenuation. CONCLUSION/CONCLUSIONS:Quantitative assessment of osseous metastatic disease using CT attenuation measurements demonstrated a statistically significant increase in attenuation more than 12 months after initiation of chemotherapy.

OBJECTIVE:To investigate the effects of short-term GH administration on abdominal subcutaneous adipocyte size and CT attenuation in men with abdominal obesity. DESIGN:, mean IGF-1 SDS: -1.9±0.5) who underwent abdominal subcutaneous adipose tissue (SAT) aspirations to determine adipocyte size, CTs for body composition and measures of glucose tolerance at baseline and 6weeks. GH dosing was titrated to target IGF-1 levels in the upper normal age-appropriate range. RESULTS:GH administration decreased subcutaneous abdominal adipocyte size compared to placebo. Adipocyte size was positively associated with 120-min glucose and HOMA-IR and inversely associated with peak-stimulated GH and CT attenuation. CT attenuation of SAT was inversely associated with 120-min glucose and HOMA-IR and increased following GH administration. CONCLUSION:In men with abdominal obesity, subcutaneous abdominal adipocyte size is positively associated with measures of impaired glucose tolerance and administration of GH at doses that raise IGF-1 levels within the normal range, decreases abdominal subcutaneous adipocyte size, suggesting that GH administration improves the health of adipose tissue. Clinical trials number: NCT00131378.

BACKGROUND:Previous studies have demonstrated that an individual's race and ethnicity are important determinants of their areal bone mineral density (aBMD), assessed by dual-energy X-ray absorptiometry. However, there are few data assessing the impact of race on bone microarchitecture and strength estimates, particularly in older adolescent girls and young adults. We hypothesized that bone microarchitecture and strength estimates would be superior in Blacks compared to White and Asian American adolescent girls and young adults of similar age based on reports of higher aBMD in Blacks. METHODS:We assessed BMD using dual-energy X-ray absoptiometry (DXA), bone microarchitecture at the distal radius and distal tibia using high-resolution peripheral quantitative computed tomography (HRpQCT) and estimated measures of bone strength using micro-finite element analysis (FEA) in 35 White, 15 Asian American, and 10 Black girls 14-21 years. RESULTS:After controlling for height, most DXA measures of aBMD and aBMD Z scores were higher in Black girls compared with Whites and Asian Americans. HRpQCT and FEA showed that at the distal radius, Blacks had greater cortical perimeter, cortical area, trabecular thickness, trabecular BMD, estimated failure load, and stiffness than the other two groups. For the distal tibia, trabecular number and BMD were higher in Blacks than Asian Americans. CONCLUSIONS:Particularly at the distal radius, adolescent and young adult White and Asian American girls have less favorable bone microarchitecture and lower bone strength than Blacks, possibly explaining the lower risk of fracture seen in Blacks. LEVEL OF EVIDENCE:Level II.

OBJECTIVE:To evaluate the diagnostic yield of two acquisitions of single-contrast CT arthrography (CTA) of the shoulder in internal, neutral, or external glenohumeral rotation with arthroscopic correlation. MATERIALS AND METHODS/METHODS:The CT study was obtained using two acquisitions (first the humerus positioned in maximum tolerated external rotation with the arm along the body and the second with the humerus in internal rotation with the palm placed flat on the table). Two independent readers blinded to the arthroscopic results evaluated the CTA images for labral tears, glenoid bone loss/fractures, and cartilage loss. For each CTA acquisition, sensitivity and specificity for detection of the aforementioned pathology were assessed. Inter-reader agreement was quantified by weighted ĸ statistics. RESULTS:Sensitivity and specificity for detecting anteroinferior or posterior labral tears was highest with neutral rotation (sensitivity 91-100%, specificity 61-100%). For glenoid fracture, sensitivity (67%) was highest with external rotation and specificity (100%) was highest with internal rotation. For cartilage loss, sensitivity (64%) and specificity (89%) was highest with external rotation and neutral rotation, respectively. Neutral rotation showed high sensitivity and specificity for glenoid fractures and cartilage loss. Inter-reader agreement ranged from fair to very good. CONCLUSIONS:Neutral glenohumeral position in shoulder CT arthrography was adequately sensitive and specific for the detection of intra-articular pathology, avoiding the use of more than one acquisition.