Faculty Bibliography

BACKGROUND:Despite their higher areal bone mineral density (aBMD), adolescents with obesity (OB) have an increase in fracture risk, particularly of the extremities, compared with normal-weight controls. Whereas bone parameters that increase fracture risk are well characterized in anorexia nervosa (AN), the other end of nutritional spectrum, these data are lacking in adolescents with obesity. OBJECTIVE:Our objective was to compare bone parameters in adolescent girls across the nutritional spectrum, to determine whether suboptimal bone adaptation to increased body weight may explain the increased fracture risk in OB. METHODS:We assessed bone endpoints in 153 adolescent girls 14-21 years old: 50 OB, 48 controls and 55 AN. We used (i) DXA to assess aBMD at the lumbar spine, proximal femur and whole body, and body composition, (ii) high resolution peripheral quantitative CT (HRpQCT) to assess bone geometry, microarchitecture and volumetric BMD (vBMD), and (iii) finite element analysis to assess failure load (a strength estimate) at the distal radius and tibia. All aBMD, microarchitecture and FEA analyses were controlled for age and race. RESULTS:Groups did not differ for age or height. Areal BMD Z-scores at all sites were highest in OB, intermediate in controls and lowest in AN (p < 0.0001). At the radius, cortical area and thickness were higher in OB compared to AN and control groups (p = 0.001) while trabecular area did not differ across groups. Compared to controls, OB had higher cortical porosity (p = 0.003), higher trabecular thickness (p = 0.024), and higher total, cortical and trabecular vBMD and rod BV/TV (p < 0.04). Plate BV/TV did not differ in OB vs. controls, but was higher than in AN (p = 0.001). At the tibia, total, cortical, and trabecular area and cortical thickness were higher in OB vs. controls and AN (p < 0.005). OB also had higher cortical porosity (p < 0.007) and lower trabecular thickness (p < 0.02) than the other two groups. Trabecular number, total and trabecular vBMD, and rod BV/TV were higher in OB vs. controls and AN (p < 0.02), while cortical vBMD and plate BV/TV did not differ in OB vs. the other two groups. Finally, failure load (a strength estimate) was higher in OB at the radius and tibia compared to controls and AN (p < 0.004 for all). However, after adjusting for body weight, failure load was lower in OB vs. controls at both sites (p < 0.05), and lower than in AN at the distal tibia. CONCLUSION:Not all bone parameters demonstrate appropriate adaptation to higher body weight. Cortical porosity and plate BV/TV at the radius and tibia, and cortical vBMD and trabecular thickness at the tibia are particularly at risk. These effects may contribute to the higher risk for fracture reported in OB vs. controls.

OBJECTIVE:To determine the value of low-dose whole-body CT (WBCT) in the management of patients with multiple myeloma (MM) and precursor states. MATERIALS AND METHODS/METHODS:The study group comprised 116 patients (mean age: 68 ± 11 years, 48% women) who underwent WBCT for the work-up or surveillance of MM or MM precursor disease. WBCTs were reviewed for the presence of MM-related bone disease and incidental findings requiring therapy. The medical records, results from bone marrow aspirations and biopsies and follow-up imaging studies were reviewed to assess the influence of WBCT on patient management. RESULTS:Whole-body CT led to a change in management in 32 patients (28%). Of those, 17 patients with MM precursor disease were found to have MM-related bone disease, 13 patients had progression of MM, requiring a change in treatment, in one patient hepatocellular carcinoma was diagnosed, requiring a change in therapy, and one patient had a rib lesion requiring intervention. In 65 patients (56%), WBCT was performed for surveillance of MM precursor disease or stable treated MM, and did not detect new lesions, thereby providing reassurance to the hematologist on disease status and management. In 15 patients (13%) WBCT was performed as a new baseline before a change or new therapy. In 4 patients (3%), WBCT was performed for a change in symptoms, but did not detect lesions that would lead to a change in management. CONCLUSION/CONCLUSIONS:Whole-body CT provides important information for disease monitoring and detection of incidental findings, thereby improving the management of patients with MM.

OBJECTIVE:To describe an ultrasound guided injection technique for diagnosing and treating posteromedial knee friction syndrome, which occurs between the sartorius/gracilis tendons and medial femoral condyle (MFC). MATERIALS AND METHODS/METHODS:Our study was IRB-approved and HIPAA-compliant. We identified patients via a retrospective review of medical records and MRI with posteromedial knee pain and isolated edema between MFC and sartorius/gracilis tendons and no evidence for meniscal tear, ruptured Baker's cyst or degenerative joint disease. Patients were referred for an ultrasound-guided procedure to inject anesthetic and corticosteroid at the site of edema. Procedures were evaluated for technical success, which was defined as satisfactory identification of the injection site and adequate delivery of medication. Follow-up was available up to 8 weeks after the procedure to determine the response and any potential complications. RESULTS:Fourteen subjects with MRI and symptoms of posteromedial knee friction syndrome underwent 14 injections. Technical success was achieved in all procedures, with no complications. At 8 weeks' follow-up, 92% of patients had symptom improvement. VAS before and 8 weeks after the procedure changed from 5.2 ± 2.7 to 0.9 ± 2.1 (p = 0.0002), respectively. CONCLUSION/CONCLUSIONS:Ultrasound-guided injection of edema between the MFC and sartorius/gracilis tendons supports the diagnosis of a posteromedial knee friction syndrome and successfully treats its associated symptoms.

BACKGROUND:Dietary restriction (DR), defined as reduced nutrient intake without malnutrition, is associated with longevity extension, improved glucose metabolism, and increased stress resistance, but also poor wound healing. Short-term preoperative DR followed by a return to normal feeding after surgery results in improved surgical outcomes in preclinical models. However, the effect of preoperative DR on wound healing and perioperative glucose homeostasis is currently unknown. Here, we tested the effects of two different preoperative DR regimens-protein restriction (PR) and methionine restriction (MR)-on wound healing and perioperative glucose homeostasis using an established murine model of wound healing in both nondiabetic and diabetic mice. MATERIALS AND METHODS:Surgical outcomes were tested using the McFarlane flap in nondiabetic and streptozotocin-induced diabetic mice. Short-term dietary preconditioning included 1 wk of PR or MR diet (1-2 wk) versus an isocaloric complete diet before surgery; all mice were returned to a complete diet postoperatively. Outcome measures of flap wound recovery included skin viability and laser Doppler imaging of flap perfusion and assessment of CD45+ cell infiltration. Glucose homeostasis was assessed by glucose tolerance testing and by perioperative glucose levels in the diabetic cohort. RESULTS:No significant differences were observed in percentage of viable skin, perfusion, or immune cell infiltration at 7-10 d after surgery in PR or MR mice compared with controls in healthy or diabetic mice. Preoperative glucose tolerance and postoperative glucose levels were however significantly improved by both PR and MR in diabetic mice. CONCLUSIONS:Short-term dietary preconditioning with PR or MR did not impair wound healing in nondiabetic or diabetic mice. However, both regimens reduced preoperative hyperglycemia in diabetic mice. Thus, brief preoperative dietary manipulations stand as strategies to potentially improve perioperative hyperglycemia with no deleterious effects on wound healing in mice.

OBJECTIVE:To determine the role of brown adipose tissue (BAT) in cancer activity. MATERIALS AND METHODS/METHODS:The study group comprised 142 patients (121 female, 21 male; mean age, 49 ± 16 years) who underwent F18-FDG PET/CT (PET/CT) for staging or surveillance of cancer and who were BAT-positive on PET/CT. BAT volume by PET/CT, abdominal (visceral and subcutaneous) fat and paraspinous muscle cross-sectional areas (CSA) were assessed. Groups with and without active cancer on PET/CT were compared using a two-sided paired t test. Linear regression analyses between BAT and body composition parameters were performed. RESULTS:There were 62 patients (54 female, eight male) who had active cancer on PET/CT and 80 patients (67 female, 13 male) without active cancer. Groups were similar in age and BMI (p ≥ 0.4), abdominal fat and muscle CSA, fasting glucose, and outside temperature at time of scan (p ≥ 0.2). Patients who had active cancer on PET/CT had higher BAT volume compared to patients without active cancer (p = 0.009). In patients without active cancer, BAT was positively associated with BMI and abdominal fat depots (r = 0.46 to r = 0.59, p < 0.0001) while there were no such associations in patients with active cancer (p ≥ 0.1). No associations between BAT and age or muscle CSA were found (p ≥ 0.1). CONCLUSIONS:BAT activity is greater in patients with active cancer compared to age-, sex-, and BMI-matched BAT-positive patients without active cancer, suggesting a possible role of BAT in cancer activity.

OBJECTIVE:In anorexia nervosa, a psychiatric disease characterized by self-induced starvation and a model of chronic undernutrition, levels of subcutaneous (SAT) and visceral (VAT) adipose tissue are low, whereas marrow adipose tissue (MAT) levels are elevated compared to normal-weight women. The reason for this paradoxical elevation of an adipose tissue depot in starvation is not known. We sought to understand changes in MAT in response to subacute changes in weight and to compare these changes with those of other fat depots and body composition parameters. DESIGN AND METHODS/METHODS:We conducted a 12-month longitudinal study including 46 premenopausal women (n = 26 with anorexia nervosa and n = 20 normal-weight controls) with a mean (s.e.m.) age of 28.2 ± 0.8 years. We measured MAT, SAT, VAT and bone mineral density (BMD) at baseline and after 12 months. RESULTS:At baseline, SAT (P < 0.0001), VAT (P < 0.02) and BMD of the spine and hip (P ≤ 0.0002) were significantly lower and vertebral and metaphyseal MAT (P ≤ 0.001) significantly higher in anorexia nervosa compared to controls. Weight gain over 12 months was associated with increases not only in SAT and VAT, but also epiphyseal MAT (P < 0.03). Changes in epiphyseal MAT were positively associated with changes in BMD (P < 0.03). CONCLUSIONS:In contrast to the steady state, in which MAT levels are higher in anorexia nervosa and MAT and BMD are inversely associated, short-term weight gain is associated with increases in both MAT and BMD. These longitudinal data demonstrate the dynamic nature of this fat depot and provide further evidence of its possible role in mineral metabolism.

UNLABELLED:Prior studies show vertebral strength from computed tomography-based finite element analysis may be associated with vertebral fracture risk. We found vertebral strength had a strong association with new vertebral fractures, suggesting that vertebral strength measures identify those at risk for vertebral fracture and may be a useful clinical tool. INTRODUCTION/BACKGROUND:We aimed to determine the association between vertebral strength by quantitative computed tomography (CT)-based finite element analysis (FEA) and incident vertebral fracture (VF). In addition, we examined sensitivity and specificity of previously proposed diagnostic thresholds for fragile bone strength and low BMD in predicting VF. METHODS:In a case-control study, 26 incident VF cases (13 men, 13 women) and 62 age- and sex-matched controls aged 50 to 85 years were selected from the Framingham multi-detector computed tomography cohort. Vertebral compressive strength, integral vBMD, trabecular vBMD, CT-based BMC, and CT-based aBMD were measured from CT scans of the lumbar spine. RESULTS:Lower vertebral strength at baseline was associated with an increased risk of new or worsening VF after adjusting for age, BMI, and prevalent VF status (odds ratio (OR) = 5.2 per 1 SD decrease, 95% CI 1.3-19.8). Area under receiver operating characteristic (ROC) curve comparisons revealed that vertebral strength better predicted incident VF than CT-based aBMD (AUC = 0.804 vs. 0.715, p = 0.05) but was not better than integral vBMD (AUC = 0.815) or CT-based BMC (AUC = 0.794). Additionally, proposed fragile bone strength thresholds trended toward better sensitivity for identifying VF than that of aBMD-classified osteoporosis (0.46 vs. 0.23, p = 0.09). CONCLUSION/CONCLUSIONS:This study shows an association between vertebral strength measures and incident vertebral fracture in men and women. Though limited by a small sample size, our findings also suggest that bone strength estimates by CT-based FEA provide equivalent or better ability to predict incident vertebral fracture compared to CT-based aBMD. Our study confirms that CT-based estimates of vertebral strength from FEA are useful for identifying patients who are at high risk for vertebral fracture.

Bone strength is affected not only by bone mineral density (BMD) and bone microarchitecture but also its microenvironment. Recent studies have focused on the role of marrow adipose tissue (MAT) in the pathogenesis of bone loss. Osteoblasts and adipocytes arise from a common mesenchymal stem cell within bone marrow and many osteoporotic states, including aging, medication use, immobility, over - and undernutrition are associated with increased marrow adiposity. Advancements in imaging technology allow the non-invasive quantification of MAT. This article will review magnetic resonance imaging (MRI)- and computed tomography (CT)-based imaging technologies to assess the amount and composition of MAT. The techniques that will be discussed are anatomic T1-weighted MRI, water-fat imaging, proton MR spectroscopy, single energy CT and dual energy CT. Clinical applications of MRI and CT techniques to determine the role of MAT in patients with obesity, anorexia nervosa, and type 2 diabetes will be reviewed.

Research into bone marrow adiposity (BMA) has expanded greatly since the late 1990s, leading to development of new methods for the study of bone marrow adipocytes. Simultaneously, research fields interested in BMA have diversified substantially. This increasing interest is revealing fundamental new knowledge of BMA; however, it has also led to a highly variable nomenclature that makes it difficult to interpret and compare results from different studies. A consensus on BMA nomenclature has therefore become indispensable. This article addresses this critical need for standardised terminology and consistent reporting of parameters related to BMA research. The International Bone Marrow Adiposity Society (BMAS) was formed in 2017 to consolidate the growing scientific community interested in BMA. To address the BMA nomenclature challenge, BMAS members from diverse fields established a working group (WG). Based on their broad expertise, the WG first reviewed the existing, unsystematic nomenclature and identified terms, and concepts requiring further discussion. They thereby identified and defined 8 broad concepts and methods central to BMA research. Notably, these had been described using 519 unique combinations of term, abbreviation and unit, many of which were overlapping or redundant. On this foundation a second consensus was reached, with each term classified as "to use" or "not to use." As a result, the WG reached a consensus to craft recommendations for 26 terms related to concepts and methods in BMA research. This was approved by the Scientific Board and Executive Board of BMAS and is the basis for the present recommendations for a formal BMA nomenclature. As an example, several terms or abbreviations have been used to represent "bone marrow adipocytes," including BMAds, BM-As, and BMAs. The WG decided that BMA should refer to "bone marrow adiposity"; that BM-A is too similar to BMA; and noted that "Ad" has previously been recommended to refer to adipocytes. Thus, it was recommended to use BMAds to represent bone marrow adipocytes. In conclusion, the standard nomenclature proposed in this article should be followed for all communications of results related to BMA. This will allow for better interactions both inside and outside of this emerging scientific community.