Faculty Bibliography

Osteoporosis is a disease of weak bone and increased fracture risk caused by low bone mass and microarchitectural deterioration of bone tissue. The standard-of-care test used to diagnose osteoporosis, dual-energy x-ray absorptiometry (DXA) estimation of areal bone mineral density (BMD), has limitations as a tool to identify patients at risk for fracture and as a tool to monitor therapy response. Magnetic resonance imaging (MRI) assessment of bone structure and microarchitecture has been proposed as another method to assess bone quality and fracture risk in vivo. MRI is advantageous because it is noninvasive, does not require ionizing radiation, and can evaluate both cortical and trabecular bone. In this review article, we summarize and discuss research progress on MRI of bone structure and microarchitecture over the last decade, focusing on in vivo translational studies. Single-center, in vivo studies have provided some evidence for the added value of MRI as a biomarker of fracture risk or treatment response. Larger, prospective, multicenter studies are needed in the future to validate the results of these initial translational studies. LEVEL OF EVIDENCE: 5 J. Magn. Reson. Imaging 2016.

Purpose To describe a nonlinear finite element analysis method by using magnetic resonance (MR) images for the assessment of the mechanical competence of the hip and to demonstrate the reproducibility of the tool. Materials and Methods This prospective study received institutional review board approval and fully complied with HIPAA regulations for patient data. Written informed consent was obtained from all subjects. A nonlinear finite element analysis method was developed to estimate mechanical parameters that relate to hip fracture resistance by using MR images. Twenty-three women (mean age +/- standard deviation, 61.7 years +/- 13.8) were recruited from a single osteoporosis center. To thoroughly assess the reproducibility of the finite element method, three separate analyses were performed: a test-retest reproducibility analysis, where each of the first 13 subjects underwent MR imaging on three separate occasions to determine longitudinal variability, and an intra- and interoperator reproducibility analysis, where a single examination was performed in each of the next 10 subjects and four operators independently performed the analysis two times in each of the subjects. Reproducibility of parameters that reflect fracture resistance was assessed by using the intraclass correlation coefficient and the coefficient of variation. Results For test-retest reproducibility analysis and inter- and intraoperator analyses for proximal femur stiffness, yield strain, yield load, ultimate strain, ultimate load, resilience, and toughness in both stance and sideways-fall loading configurations each had an individual median coefficient of variation of less than 10%. Additionally, all measures had an intraclass correlation coefficient higher than 0.99. Conclusion This experiment demonstrates that the finite element analysis model can consistently and reliably provide fracture risk information on correctly segmented bone images. (c) RSNA, 2016 Online supplemental material is available for this article.

PURPOSE: To use 7T magnetic resonance imaging (MRI) to determine how trabecular bone microarchitecture varies at the epiphysis, metaphysis, and diaphysis of the distal radius. MATERIALS AND METHODS: The distal radius of 24 females (mean age = 56 years, range = 24-78 years) was scanned on a 7T MRI using a 3D fast low-angle shot sequence (0.169 x 0.169 x 1 mm). Digital topological analysis was applied at the epiphysis, metaphysis, and diaphysis to compute: total trabecular bone volume; trabecular thickness, number, connectivity, and erosion index (a measure of network resorption). Differences and correlations were assessed using standard statistical methods. RESULTS: The metaphysis and epiphysis had 83-123% greater total bone volume and 14-16% greater trabecular number than the diaphysis (both P < 0.0001). The erosion index was significantly higher at the diaphysis than the metaphysis and epiphysis (both P < 0.01). The most elderly volunteers had lower trabecular number (<66 years mean 0.29 +/- 0.01; >/=66 years, 0.27 +/- 0.02, P < 0.05) and higher erosion index (<66 years mean 1.18 +/- 0.17; age >/=66 years, mean 1.42 +/- 0.46, P < 0.05) at the epiphysis; differences not detected by total trabecular bone volume. CONCLUSION: 7T MRI reveals trabecular bone microarchitecture varies depending on scan location at the end-of-bone, being of overall higher quality distally (epiphysis) than proximally (diaphysis). Age-related differences in trabecular microarchitecture can be detected by 7T MRI. The results highlight the potential sensitivity of 7T MRI to microarchitectural differences and the potential importance of standardizing scan location for future clinical studies of fracture risk or treatment response. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:872-878.

The purpose of the current study was to investigate the association between bone mineral density (BMD) scores and the prevalence of peripheral artery disease (PAD) in a large cohort of subjects who underwent arterial Doppler assessments and calcaneal bone densitometry. The study was performed using data obtained from Life Line Screening Inc. Subjects were self-selected and paid for screening tests. The prevalence of PAD was significantly higher in men with osteopenia (4.5%) and osteoporosis (10.9%) compared to men with normal BMD (3.0%) (p<0.001). Osteopenia (odds ratio (OR) 1.3) and osteoporosis (OR 2.3) were found to be independent risk factors for the presence of PAD in men. The prevalence of PAD was significantly higher in women with osteopenia (4.8%) and osteoporosis (11.8%) compared to women with normal BMD (3.3%) (p<0.001). Osteopenia (OR 1.15) and osteoporosis (OR 1.8) were found to be independent risk factors for the presence of PAD in women. The current study reports a strong association of abnormal BMD analysis with the prevalence of PAD, which persists even when controlling for age and associated atherosclerotic risk factors. Although the mechanism by which these two disease processes is related is not completely elucidated, the presence of osteoporosis should make clinicians aware of the possibility of occult PAD or associated atherosclerotic disease in appropriate patients.

Transient osteoporosis (TO) is a clinical syndrome characterized by joint pain and the presence of bone marrow edema on magnetic resonance imaging (MRI), both of which spontaneously resolve over time. Transient osteoporosis most commonly affects the hip, but also may involve other lower extremity sites. TO likely represents a disorder that may be monoarticular or "migratory" with involvement of two or more lower extremity sites sequentially affected over a number of months. We report on two cases of transient osteoporosis, one involving the knee and one involving the hip, demonstrating the utility of serial bone mineral density measurements at both sites. Additionally, we are able to report on the microarchitectural changes seen at the distal femur on ultra-high resolution (7 T) MRI. Case #1 describes a recurrence of transient osteoporosis of the hip three years after a similar presentation at the contralateral hip and highlights the findings of rapidly changing bone mineral density in this clinical syndrome. In contrast to the spine, hip and forearm, peripheral bone density measurements at the knee are rarely reported and to our knowledge Case #2 represents the first report of transient osteoporosis of the knee demonstrating bone density findings similar to that seen in the hip. We postulate that transient osteoporosis of the knee is part of a clinical spectrum most commonly seen in the hip and one that is marked by lower extremity joint pain, bone marrow edema on MRI and transient decreases in bone mineral density all of which spontaneously resolve without sequelae.

INTRODUCTION: Participants who sustain a fragility fracture are at increased risk for subsequent fractures. Despite the consequences of recurrent fractures, bone mineral density (BMD) testing and treatment rates for osteoporosis after a fracture remain low. The New York University (NYU) Langone Osteoporosis Model of Care was developed to identify women at increased risk for recurrent fractures and to reduce the rates of subsequent fracture through patient and physician education. METHODS: Women aged 50 years and older who had a fracture and received their care at NYU affiliated hospitals were contacted via mail after discharge. Participants were provided educational materials explaining decreased bone strength and its possible relationship to their fracture and were asked to complete a questionnaire. One year postfracture, participants were sent follow-up questionnaires requesting their most recent fracture treatment and BMD information. Educational material was also provided to the treating orthopedic surgeons. RESULTS: Overall, 524 patients were contacted and 210 (40%) enrolled. By the end of 24 months, 92 participants completed their 1-year questionnaire (44% of the enrollees). Forty-two (46%) participants had undergone new BMD testing and 37 (40%) were receiving antiresorptive medications, including 6 (6%) who had not been prescribed these medications before enrolling in the program. CONCLUSIONS: The Osteoporosis Model of Care is a simple and cost-effective educational program, which improved comprehensive fracture care in an actual clinical setting. Patient enrollment remains a challenge in implementing the program. Our program highlights difficulties in providing community-dwelling participants with appropriate postfracture care. With increasing concern among the public regarding the use of bone strengthening medications and continued low postfracture treatment rates, educating patients with high fracture risk is critical to reducing the rate of subsequent fracture. Our Model of Care Program demonstrates both the success and limitations of a postfracture educational approach using discharge diagnosis data to identify patients with fracture.

BACKGROUND: Glucocorticoid-induced osteoporosis (GIO) is the most common secondary form of osteoporosis, and glucocorticoid users are at increased risk for fracture compared with nonusers. There is no established relationship between bone mineral density (BMD) and fracture risk in GIO. We used 3 Tesla (T) MRI to investigate how proximal femur microarchitecture is altered in subjects with GIO. METHODS: This study had institutional review board approval. We recruited 6 subjects with long-term (> 1 year) glucocorticoid use (median age = 52.5 (39.2-58.7) years) and 6 controls (median age = 65.5 [62-75.5] years). For the nondominant hip, all subjects underwent dual-energy x-ray absorptiometry (DXA) to assess BMD and 3T magnetic resonance imaging (MRI, 3D FLASH) to assess metrics of bone microarchitecture and strength. RESULTS: Compared with controls, glucocorticoid users demonstrated lower femoral neck trabecular number (-50.3%, 1.12 [0.84-1.54] mm(-1) versus 2.27 [1.88-2.73] mm(-1) , P = 0.02), plate-to-rod ratio (-20.1%, 1.48 [1.39-1.71] versus 1.86 [1.76-2.20], P = 0.03), and elastic modulus (-64.8% to -74.8%, 1.54 [1.22-3.19] GPa to 2.31 [1.87-4.44] GPa versus 6.15 [5.00-7.09] GPa to 6.59 [5.58-7.31] GPa, P < 0.05), and higher femoral neck trabecular separation (+192%, 0.705 [0.462-1.00] mm versus 0.241 [0.194-0.327] mm, P = 0.02). There were no differences in femoral neck trabecular thickness (-2.7%, 0.193 [0.184-0.217] mm versus 0.199 [0.179-0.210] mm, P = 0.94) or femoral neck BMD T-scores (+20.7%, -2.1 [-2.8 to -1.4] versus -2.6 [-3.3 to -2.5], P = 0.24) between groups. CONCLUSION: The 3T MRI can potentially detect detrimental changes in proximal femur microarchitecture and strength in long-term glucocorticoid users. J. MAGN. RESON. IMAGING 2015;42:1489-1496.

PURPOSE: To evaluate the within-day and between-day measurement reproducibility of in vivo 3D MRI assessment of trabecular bone microarchitecture of the proximal femur. MATERIALS AND METHODS: This Health Insurance Portability and Accountability Act (HIPPA)-compliant, Institutional Review Board (IRB)-approved study was conducted on 11 healthy subjects (mean age = 57.4 +/- 14.1 years) with written informed consent. All subjects underwent a 3T MRI hip scan in vivo (0.234 x 0.234 x 1.5 mm) at three timepoints: baseline, second scan same day (intrascan), and third scan 1 week later (interscan). We applied digital topological analysis and volumetric topological analysis to compute the following microarchitectural parameters within the femoral neck: total bone volume, bone volume fraction, markers of trabecular number (skeleton density), connectivity (junctions), plate-like structure (surfaces), plate width, and trabecular thickness. Reproducibility was assessed using root-mean-square coefficient of variation (RMS-CV) and intraclass correlation coefficient (ICC). RESULTS: The within-day RMS-CVs ranged from 2.3% to 7.8%, and the between-day RMS-CVs ranged from 4.0% to 7.3% across all parameters. The within-day ICCs ranged from 0.931 to 0.989, and the between-day ICCs ranged from 0.934 to 0.971 across all parameters. CONCLUSION: These results demonstrate high reproducibility for trabecular bone microarchitecture measures derived from 3T MR images of the proximal femur. The measurement reproducibility is within a range suitable for clinical cross-sectional and longitudinal studies in osteoporosis. J. Magn. Reson. Imaging 2015;42:1339-1345.

INTRODUCTION: Osteoporosis is a disease of weak bone. Our goal was to determine the measurement reproducibility of magnetic resonance assessment of proximal femur strength. METHODS: This study had institutional review board approval, and written informed consent was obtained from all subjects. We obtained images of proximal femur microarchitecture by scanning 12 subjects three times within 1 week at 3T using a high-resolution 3-D FLASH sequence. We applied finite element analysis to compute proximal femur stiffness and femoral neck elastic modulus. RESULTS: Within-day and between-day root-mean-square coefficients of variation and intraclass correlation coefficients ranged from 3.5 to 6.6 % and 0.96 to 0.98, respectively. CONCLUSION: The measurement reproducibility of magnetic resonance assessment of proximal femur strength is suitable for clinical studies of disease progression or treatment response related to osteoporosis bone-strengthening interventions.

Purpose: Elevated bone marrow fat content and elevated intramuscular fat content increase the risk for osteoporotic fracture, but it is unknown if such changes are associated with detrimental changes in bone microarchitecture and bone mass. Our goal was to determine the association between femoral neck bone marrow fat fraction and gluteal muscle fat fraction with: 1) femoral neck bone microarchitecture and 2) femoral neck bone mineral density (BMD). Materials and Methods: This study was HIPAA compliant and institutional review board approved. Written informed consent was obtained. Hips of forty-two consecutive patients referred from the osteoporosis clinic at our institution (mean-age 60.2 +/- 7.5 years) underwent dual-energy X-ray absorptiometry (DXA), high-spatial resolution three-dimensional 3 T MRI with volumetric topological analysis (VTA-MRI), and fat quantification with IDEAL-MRI. Femoral neck BMD T-scores (DXA) and trabecular bone microarchitecture parameters (VTA-MRI) were calculated. Proton density fat fractions (IDEAL-MRI) of the femoral neck bone marrow (FFmarrow) and the gluteus maximus muscle (FFmuscle) were measured by two independent readers. Interreader agreement was calculated using intraclass correlation coefficients (ICC). FFmarrow and FFmuscle were correlated with BMD, bone microarchitecture parameters, age, and body-massindex (BMI). Results: FFmarrow (mean from both readers 70.2 +/- 6.5 %) and FFmuscle (11.3 +/- 3.8 %) measurements showed excellent interreader agreement (ICC = 0.955/0.995; both p < 0.0005). No statistically significant correlation between FFmarrow and BMD was found (r = -0.257, p = 0.155). Age- and BMI-adjusted FFmarrow inversely correlated with trabecular plate-to-rod ratio (r = -0.335; p = 0.049) and trabecular plate-width (r = -0.345; p = 0.042), but not with bone volume fraction (r = 0.155; p = 0.374). FFmarrow correlated with age (r = 0.383; p = 0.021), but not with BMI (r = 0.132; p = 0.445). FFmuscle showed no correlation with BMD or bone microarchitecture. FFmuscle was independently correlated with BMI (r = 0.557; <0.0005) and age (r = 0.438; p = 0.008). Conclusion: Bone marrow fat content inversely correlated with trabecular plate-to-rod ratio and plate-width, but not BMD, suggesting that the increased fracture risk in the setting of elevated bone marrow fat content may in part be mediated via microarchitectural deterioration, rather than via reduced BMD. Gluteal muscle fat content did not correlate with changes in femoral neck microarchitecture or BMD, suggesting that intramuscular fat content may increase fracture risk independent of detrimental changes in bone microarchitecture and BMD. Overall, highresolution 3 T MRI of bone microarchitecture combined with IDEAL-based fat quantification can help provide insight into the relationship between adipose bone marrow, lean muscle mass, and possible mechanisms of osteoporotic fracture risk in vivo