Faculty Bibliography

INTRODUCTION/BACKGROUND:Aromatase-inhibitors (AIs) are commonly used for treatment of patients with hormone-receptor positive breast carcinoma, and are known to induce bone density loss and increase the risk of fractures. The current standard-of-care screening tool for fracture risk is bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). The fracture risk assessment tool (FRAX®) may be used in conjunction with BMD to identify additional osteopenic patients at risk of fracture who may benefit from a bone-modifying agent (BMA). The trabecular bone score (TBS), a novel method of measuring bone microarchitecture by DXA, has been shown to be an independent indicator of increased fracture risk. We report how the addition of TBS and FRAX®, respectively, to BMD contribute to identification of elevated fracture risk (EFR) in postmenopausal breast cancer patients treated with AIs. METHODS:100 patients with early stage hormone-positive breast cancer treated with AIs, no prior BMAs, and with serial DXAs were identified. BMD and TBS were measured from DXA images before and following initiation of AIs, and FRAX® scores were calculated from review of clinical records. EFR was defined as either: BMD ≤-2.5 or BMD between -2.5 and -1 plus either increased risk by FRAX® or degraded microstructure by TBS. RESULTS:At baseline, BMD alone identified 4% of patients with EFR. The addition of FRAX® increased detection to 13%, whereas the combination of BMD, FRAX® and TBS identified 20% of patients with EFR. Following AIs, changes in TBS were independent of changes in BMD. On follow-up DXA, BMD alone detected an additional 1 patient at EFR (1%), whereas BMD+ FRAX® identified 3 additional patients (3%), and BMD+FRAX®+TBS identified 7 additional patients (7%). CONCLUSIONS:The combination of FRAX®, TBS, and BMD maximized the identification of patients with EFR. TBS is a novel assessment that enhances the detection of patients who may benefit from BMAs.

Cushing's disease with prolonged exposure to high circulating levels of glucocorticoids is associated with deterioration of the structural integrity of bone, resulting in increased skeletal fragility and fractures. The mechanism of bone repair following successful surgical treatment is poorly understood. A 34-year-old man presented with a tibial fracture and severely low BMD, elevated AM serum cortisol, ACTH, and 24 h urinary free cortisol, which did not suppress with 2 days of high dose dexamethasone. Following transphenoidal resection of a pituitary microadenoma, serum cortisol and ACTH normalized. A repeat DXA at 8 months post-resection showed no change in BMD, however the Trabecular Bone Score (TBS), which reported severe deterioration of trabecular bone architecture at diagnosis, improved to normal. At that time, teriparatide (TPTD) was given for 2 years, which resulted in a 53.9% increase in BMD with only a small improvement in TBS. In this patient, spontaneous recovery of trabecular bone architecture was reflected by the early correction in TBS. Subsequent TPTD treatment was associated with marked improvement in BMD, presumably due to enhanced mineralization. Complete skeletal repair was achieved by this two-step mechanism in a very short time following successful surgical treatment for Cushing's disease.

OBJECTIVE: Insulin resistance has been described in type 1 diabetes mellitus, is related to risk of vascular complications, and may be more common in certain ethnic groups. Estimated glucose disposal rate (eGDR) is a validated clinical tool for estimating insulin sensitivity in type 1 diabetes. Because previous reports of eGDR in adults with type 1 diabetes have included few ethnic minorities, this study explored interethnic differences in eGDR and the relationship of eGDR with diabetic vascular complications. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional study using a sample that included 207 white, black, or Hispanic adults with prior clinical diagnosis of type 1 diabetes who were receiving care at an urban academic medical center. eGDR (milligrams per kilogram per minute) was calculated using HbA1c, waist circumference, and hypertensive status. Race/ethnicity was self-reported. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% CIs of association of eGDR with diabetes complications (cardiovascular disease, retinopathy, albuminuria, and chronic kidney disease above stage 3). RESULTS: Forty-two percent of the participants were women, and mean age was 45 +/- 15 years; 34% were white, 32% were Hispanic, and 34% were black. Ethnicity was significantly associated with eGDR; blacks had significantly lower eGDR (5.66 +/- 2.34) than Hispanics (6.70 +/- 2.29) and whites (7.20 +/- 2.03) (P < 0.001). Patients with the lowest eGDR compared with the highest had a significantly greater risk of any diabetes complication (OR 3.1 [95% CI 1.2-8.1]) compared with the least insulin-resistant patients. CONCLUSIONS: In an urban clinic population of patients with type 1 diabetes, blacks were significantly less insulin sensitive than whites or Hispanics, and lower eGDR was associated with diabetes complications. Further study is needed to determine whether using eGDR to target interventions can improve outcomes.