Faculty Bibliography

Osteopenia is a complication of anorexia nervosa (AN) associated with a two- to three-fold increase in fractures. Nutritional deficits and hormonal abnormalities are thought to mediate AN-induced bone loss. Alterations in bone microarchitecture may explain fracture risk independent of bone mineral density (BMD). Advances in CT imaging now allow for noninvasive evaluation of trabecular microstructure at peripheral sites in vivo. Few data are available regarding bone microarchitecture in AN. We therefore performed a cross-sectional study of 23 women (12 with AN and 11 healthy controls) to determine hormonal predictors of trabecular bone microarchitecture. Outcome measures included bone microarchitectural parameters at the ultradistal radius by flat-panel volume CT (fpVCT); BMD at the PA and lateral spine, total hip, femoral neck, and ultradistal radius by dual energy X-ray absorptiometry (DXA); and IGF-I, leptin, estradiol, testosterone, and free testosterone levels. Bone microarchitectural measures, including apparent (app.) bone volume fraction, app. trabecular thickness, and app. trabecular number, were reduced (p<0.03) and app. trabecular spacing was increased (p=0.02) in AN versus controls. Decreased structural integrity at the ultradistal radius was associated with decreased BMD at all sites (p<or=0.05) except for total hip. IGF-I, leptin, testosterone, and free testosterone levels predicted bone microarchitecture. All associations between both IGF-I and leptin levels and bone microarchitectural parameters and most associations between androgen levels and microarchitecture remained significant after controlling for body mass index. We concluded that bone microarchitecture is abnormal in women with AN. Endogenous IGF-I, leptin, and androgen levels predict bone microarchitecture independent of BMI.

CONTEXT/BACKGROUND:Despite having low visceral and sc fat depots, women with anorexia nervosa (AN) have elevated marrow fat mass, which is inversely associated with bone mineral density (BMD). Adipocytes and osteoblasts differentiate from a common progenitor cell, the human mesenchymal stem cell. Therefore, understanding factors that regulate this differentiation process may provide insight into bone loss in AN. OBJECTIVE:The objective of the study was to investigate the relationship between preadipocyte factor-1 (Pref-1), a member of the epidermal growth factor-like family of proteins and regulator of adipocyte and osteoblast differentiation, and fat depots and BMD in AN. DESIGN/METHODS:This was a cross-sectional study. SETTING/METHODS:The study was conducted at a clinical research center. PATIENTS/METHODS:Patients included 20 women with AN (26.8 +/- 1.5 yr) and 10 normal-weight controls (29.2 +/- 1.7 yr). INTERVENTIONS/METHODS:There were no interventions. MAIN OUTCOMES MEASURE/METHODS:Pref-1, leptin, IGF-I, IGF binding protein (IGF-BP)-2 and estradiol levels were measured. BMD of the spine and hip was measured by dual-energy x-ray absorptiometry. Marrow fat content of the L4 vertebra and femur was measured by (1)H-magnetic resonance spectroscopy. RESULTS:Pref-1 levels were significantly higher in AN compared with controls (P = 0.01). There was a positive correlation between Pref-1 and marrow fat of the proximal femoral metaphysis (R = 0.50, P = 0.01) and an inverse association between leptin and L4 marrow fat (R = -0.45, P < 0.05). There was an inverse association between Pref-1 and BMD of both the anteroposterior spine and lateral spine (R = -0.54, P = 0.003; R = -0.44, P = 0.02, respectively). CONCLUSIONS:Pref-1 is elevated in AN. Pref-1, IGF-I, IGF-BP2 and leptin are associated with marrow adiposity and BMD.

OBJECTIVE:To compare breath-hold 1H-magnetic resonance spectroscopy (1H-MRS) with respiratory-gated 1H-MRS and computed tomography (CT) for quantification of hepatic lipid content. METHODS:Twenty-three premenopausal women underwent breath-hold point-resolved single-voxel 1H-MRS of the liver followed by respiratory-gated 1H-MRS at 3 Tesla and CT slice through the liver. Interscan variability for 1H-MRS was assessed in 6 volunteers. Pearson correlation coefficients, Bland-Altman 95% limit of agreement, and concordance correlation coefficients were calculated. RESULTS:There was a strong correlation between breath-hold and respiratory-gated 1H-MRS (r = 0.94, P < 0.0001; concordance correlation coefficient, 0.75). Using Bland-Altman analysis, all but 2 data points were within the limits of agreement. Both 1H-MRS techniques had low interscan variability. There was an inverse correlation of both 1H-MRS techniques with CT attenuation values of the liver. CONCLUSIONS:Breath-hold 1H-MRS is a reliable method to measure hepatic lipid content at 3 Tesla. Breath-hold 1H-MRS of the liver provides data that closely correlates with that obtained from longer-duration respiratory-gated technique.

CONTEXT/BACKGROUND:Visceral adiposity is a strong determinant of GH secretion, and low endogenous GH secretion is associated with increased insulin resistance, a key component of the metabolic syndrome. Increased fat accumulation in skeletal muscle and liver may play an etiological role in the development of insulin resistance and other complications of the metabolic syndrome. Little is known about the role of decreased endogenous GH secretion in the pathogenesis of insulin resistance in obesity. OBJECTIVE:To investigate the relationship between intramyocellular lipids (IMCL), intrahepatic lipids, and peak-stimulated GH in premenopausal women with obesity. DESIGN AND SETTING/METHODS:We conducted a cross-sectional study at a clinical translational research center. PATIENTS/METHODS:Patients included 21 premenopausal women with obesity (mean body mass index, 34.0 +/- 4.5 kg/m(2)) and 17 normal-weight controls (mean body mass index, 21.9 +/- 2.0 kg/m(2)) of comparable mean age. MAIN OUTCOMES MEASURES/METHODS:IMCL and intrahepatic lipids were measured with proton magnetic resonance spectroscopy ((1)H-MRS). Body composition was measured with magnetic resonance imaging. Peak GH was measured after stimulation with GHRH-arginine. RESULTS:Obese subjects had higher IMCL, intrahepatic lipids, abdominal and thigh fat, and thigh muscle mass compared with normal-weight controls. There were strong inverse associations between peak GH and both IMCL and intrahepatic lipids independent of age and visceral adiposity. There were positive associations between IMCL and intrahepatic lipids with measures of insulin resistance and serum triglycerides. CONCLUSION/CONCLUSIONS:In premenopausal women with obesity, peak GH is inversely associated with IMCL and intrahepatic lipids independent of age and visceral adiposity. This suggests that low GH may contribute to insulin resistance in obesity through effects on muscle and intrahepatic lipids.

PURPOSE/OBJECTIVE:To determine inter-scan, inter-reader and intra-reader variability of trabecular structure analysis using flat-panel volume computed tomography (fp-VCT) in cadaver knee specimens. METHODS:Five explanted knee specimens were imaged at three different time points using fp-VCT. Four parameters that quantify trabecular bone structure of the proximal tibia were measured by two observers at two different time points. Bland-Altman analysis was used to compute the inter-scan, inter-observer and intra-observer variability. RESULTS:Inter-scan variability was low, with a mean difference of 0% and a standard deviation less than 8.4% for each of the four parameters. The inter-observer and intra-observer variability was less than 2.8% +/- 8.5%. CONCLUSION/CONCLUSIONS:Fp-VCT is a method for assessing trabecular structure parameters with low inter-scan, inter-reader and intra-reader variability.

OBJECTIVE:The purposes of this study were to describe the imaging appearance of transverse thickening along the articular surface of the supraspinatus and infraspinatus tendons presumed to represent the rotator cable on MR arthrographic images obtained with the shoulder in abduction and external rotation (ABER) and in the non-ABER position and to assess the role of the rotator cable in the diagnosis of rotator cuff tears. MATERIALS AND METHODS/METHODS:The study group comprised 54 patients who underwent arthroscopy of the shoulder and preoperative MR arthrography in which ABER images were obtained. Two blinded reviewers independently examined the ABER and non-ABER images for the presence of the rotator cable and rotator cuff tears. RESULTS:In intact rotator cuffs, the presumed rotator cable was not well visualized on non-ABER images. In one case of prominent rotator cable, MR arthrography showed no tear on non-ABER images, but at arthroscopy, a partial-thickness undersurface tear was found. On non-ABER images, both readers readily visualized the rotator cable in eight and 10 of 18 cases (44% and 56%) of partial-thickness undersurface tear and four of five cases (80%) of full-thickness tear. On ABER images, both readers readily visualized the rotator cable in 15 and 17 of 31 cases (48% and 55%) of intact cuff, 14 and 15 of 18 cases (78% and 83%) of undersurface tear, and four and five cases (80% and 100%) of full-thickness tear. Interobserver agreement on cable visualization was almost perfect (kappa = 0.86). CONCLUSION/CONCLUSIONS:On non-ABER MR arthrographic images, thickening along the articular side of the supraspinatus and infraspinatus tendons presumed to represent the rotator cable suggests the presence of a partial-thickness rotator cuff tear. On ABER images, the cable is well defined in intact and torn rotator cuffs.

CONTEXT/BACKGROUND:Obesity in adolescents is increasingly prevalent and its impact on cardiovascular risk important to determine. Hormonal predictors of cardiovascular risk markers in obese adolescents are not known. OBJECTIVE:Our objective was to examine whether relative GH deficiency and cortisol excess are determinants of increased cardiovascular risk markers in obese teenage girls. DESIGN AND SETTING/METHODS:A cross-sectional study was conducted at a clinical research center. STUDY PARTICIPANTS/METHODS:Thirty girls (15 obese girls and 15 normal-weight controls) 12-18 years old matched for maturity and race. MAIN OUTCOME MEASURES/METHODS:Inflammatory markers of cardiovascular risk including high-sensitivity C-reactive protein (hsCRP), TNF-alpha receptors 1 and 2, E-selectin, soluble intercellular adhesion molecule-1, and IL-6 were analyzed. Leptin, adiponectin, and 24-h urine free cortisol (UFC) were also measured. A GHRH-arginine stimulation test was performed. RESULTS:The hsCRP levels were higher in obese girls than controls (4.63 +/- 4.81 vs. 0.67 +/- 0.72 mg/liter; P = 0.002 after log conversion), as were other markers of cardiovascular risk. Eight of the 15 obese girls but no normal-weight girl had hsCRP higher than 3 mg/liter (P = 0.002). Body mass index sd score was higher than 4.0 in 87.5% of girls with hsCRP higher than 3 mg/liter and no girls with hsCRP less than 3 mg/liter. Girls with hsCRP higher than 3 mg/liter had higher UFC and lower peak GH compared with those with hsCRP less than 3 mg/liter. Peak GH was an important negative predictor of most markers of increased cardiovascular risk. In addition to peak GH, UFC and adiponectin independently predicted hsCRP. CONCLUSION/CONCLUSIONS:Relative GH deficiency and cortisol excess are significant contributors to increased levels of markers of cardiovascular risk in obese adolescent girls.

OBJECTIVE:To describe the correlation between medial patellar ossification and prior patella subluxation and/or dislocation. MATERIALS AND METHODS/METHODS:A retrospective billing database search identified 544 patients who had been diagnosed with patellar instability over a 13-year period. One hundred twenty-eight patients met the inclusion criteria. After review by a staff orthopedic surgeon and two musculoskeletal radiologists, 28 patients were found to have medial patellar ossification. The size and location of medial patellar ossification was recorded. RESULTS:Of the 28 patients (20 males, eight females, age 13-66 years, mean 28 years) who were found to have medial patellar ossification, 22 had radiographs, 16 had magnetic resonance imaging, and ten had both. The medial patellar ossification ranged in size from 2 to 18 mm with an average of 6.8 mm. Twelve were located in the medial patellofemoral ligament (MPFL), 14 in the medial joint capsule, and two in both the MPFL and joint capsule. Twenty-seven of 28 patients had a single ossification, and one patient had two ossifications. The timing from injury to first imaging of the lesion ranged from 10 days to a chronic history (> or = 35 years) of patellar instability. CONCLUSION/CONCLUSIONS:Medial patellar ossification correlates with a history of prior patella subluxation and/or dislocation. The medial ossification can be seen within the MPFL or the medial joint capsule, suggesting remote injury to these structures. The presence of this lesion will prompt physicians to evaluate for patellar instability.

OBJECTIVE:The purpose of this study was to describe the MRI findings of an entity in which patients present with hip pain, abnormal MR signal intensity of the quadratus femoris muscle, and narrowing of the ischiofemoral space. MATERIALS AND METHODS/METHODS:We reviewed MR images of 12 hips in nine patients with hip pain and abnormal MR signal intensity of the quadratus femoris muscle. Using axial MR images, two musculoskeletal radiologists measured the ischiofemoral and quadratus femoris spaces. We also examined changes to muscles and tendons for the presence of edema and tears. Data were compared with 11 hips in 10 control subjects. Statistical analyses determined interobserver variability and differences between groups. RESULTS:Subjects with an abnormal quadratus femoris muscle were all women 30-71 years old (mean age, 53 years) and had significantly narrower ischiofemoral spaces when compared with control subjects (13 +/- 5 vs 23 +/- 8 mm, respectively; p = 0.002). The quadratus femoris space was significantly narrower in affected subjects (7 +/- 3 vs 12 +/- 4 mm; p = 0.002). Abnormalities of the quadratus femoris muscle included edema (100%), partial tear (33%), and fatty infiltration (8%). The hamstring tendons of affected subjects showed evidence of edema (50%) and partial tears (25%). CONCLUSION/CONCLUSIONS:Ischiofemoral impingement may represent a cause of hip pain and should be considered in cases with MR signal abnormality of quadratus femoris muscle.