Faculty Bibliography

Context/UNASSIGNED:Thyroid hormone plays a critical role in cardiovascular function. Severe hypothyroidism can be associated with "myxedema heart" characterized by relative bradycardia and pericardial effusion. Effusions associated with severe hypothyroidism can be large. Despite the large volume of effusions, tamponade is not a common consequence. However, with the incorporation of echocardiography into routine practice for evaluation of effusion, echocardiographic findings suggestive of clinical tamponade occur frequently. Case Description/UNASSIGNED:We report a series of 3 patients with large pericardial effusions secondary to severe hypothyroidism. These cases serve to demonstrate the discordance between echocardiographic signs consistent with tamponade with a patient's stable clinical hemodynamics. We also report the development of bronchial obstruction, a rare complication of a large effusion due to severe hypothyroidism. Conclusions/UNASSIGNED:While pericardial effusion associated with severe hypothyroidism has been described for decades, the echocardiographic findings may be less well known and may lead to unnecessary downstream testing or invasive management. We use our case series to facilitate a summary of what is known about the epidemiology, mechanism and physiology, and expected outcomes of myxedema associated pericardial effusion. Finally, in the setting of current paucity of clinical guidelines, we aim to familiarize clinicians with the phenomenon of pseudotamponade and suggest management strategies for myxedema associated pericardial effusion to guide clinicians to use conservative medical management in majority of cases.

The 2019 International Society for Clinical Densitometry (ISCD) Position Development Conference Task Force for monitoring with dual-energy X-ray absorptiometry (DXA) identified detection of atypical femur fractures (AFFs) as an important topic and established this working group to answer key questions in this area. The authors conducted a systematic review of the literature and deliberated on proposed ISCD positions, which were then reviewed by an external expert panel and vetted at the 2019 ISCD Position Development Conference in Kuala Lumpur on March 23, 2019. This paper summarizes the final ISCD positions and the rationale for supporting these positions. Default-length femur imaging or extended-length femur imaging as well as full-length femur imaging (FFI), both single-energy and dual-energy scans, by DXA can detect abnormalities in the spectrum of AFF. It is important to visually inspect all DXA scans of the hip and femur, and report on findings of focal periosteal and endosteal thickening at the lateral cortex (grade: Good, A, W). FFI is the preferred DXA scan mode for detecting abnormalities in the spectrum of AFF. The FFI report should state the absence or presence of abnormalities in the spectrum of AFF. If focal thickening is present on the lateral cortex, the report should state whether a lucent line is seen (grade: Fair, C, W). The ISCD recommends considering the use of bilateral FFI in patients who are currently or have been in the past year on potent antiresorptive therapy (ie, oral or intravenous bisphosphonate or subcutaneous denosumab therapy) for a cumulative period of 3 or more years, especially those on long-term glucocorticoid therapy (grade: Fair, B, W). More research is needed to determine the role of repeat testing and the optimal time interval for follow-up DXA scans, whether an automated measuring tool would perform better than visual inspection, whether FFI would change patient management and outcomes, and the cost-effectiveness of FFI.

The incidence of pericardial effusion in hypothyroidism is 3% in the earlymild stage and up to 80%in patients with myxedema.We present three cases of severe hypothyroidism causing cardiac tamponade. CASE 1. 61-year-old woman with Hashimoto's thyroiditis who initially presented with generalized muscle weakness, found to have a large pericardial effusion with tamponade physiology. Initial labs revealed TSH 198.74 and FT4 < 0.10. Pericardiocentesis was done draining 1.5 L of fluid. CASE 2. 63 year-old woman with no past medical history presented after a mechanical fall, found to have an acute basal ganglion ischemia. TTE was obtained to complete CVA work-up revealing a large pericardial effusion with with tamponade physiology. labs were notable for a TSH 47. CASE 3. 66 year-old woman with hypothyroidism presented with lethargy and dyspnea. TTE revealed large pericardial effusion with tamponade physiology. CT chest revealed a large pericardial effusion that was narrowing the distal left mainstem and left lower lobe bronchi. Pericardiocentesis was done draining 1.1 L of fluid. Pericardial effusion in hypothyroidism is due to increased capillary permeability and impaired lymphatic drainage with subsequent leakage of fluid rich proteins and glycosaminoglycans into the interstitial space. Factors affecting capillary permeability include absence of FGF signaling and decrease in adrenomedullin, resulting in destabilization of the VE-cadherin/b-catenin complex at the cell-cell junctions. There has been no correlation with TSH levels and the existence of effusion. Clinical symptoms of tamponade are uncommon due to slow accumulation of fluid and pericardial distensibility. It is hypothesized that heart rate is within normal range or bradycardic due to decrease sympathetic activity. The color of the fluid is most commonly straw-colored or gold. And the cells are predominantly lymphocytes. The treatment should be individualized. The effusion can be reversed only with levothyroxine because the slow rate of accumulation. Pericardiocentesis is only done when there is hemodynamically instability. Cardiac tamponade presenting with normal or low heart rate with high TSH is highly suggestive of hypothyroidism as the culprit

BACKGROUND: Bisphosphonate therapy for osteoporosis has been associated with atypical femoral fractures. To date, there have been few reports in the literature regarding the preoperative and postoperative courses of patients who have sustained bisphosphonate-associated complete atypical femur fractures. OBJECTIVES/PURPOSES: The purposes of this study were to (1) characterize the preoperative course of patients who eventually presented with bisphosphonate-associated complete atypical femur fractures (duration of bisphosphonate treatment, pain history, risk of converting a nondisplaced fracture to a complete fracture); (2) evaluate the percentage of patients who achieved radiographic union of those fractures after treatment; and (3) determine the patients' recovery of function using the Short Musculoskeletal Functional Assessment. METHODS: Thirty-three patients with 41 atypical, low-energy femur fractures associated with >/= 5 years of bisphosphonate use were treated with intramedullary nailing between 2004 and 2011 at one center. The main outcome measurements were Short Musculoskeletal Functional Assessment for function and radiographic evaluation for fracture healing. Patients had been treated with bisphosphonates for an average of 8.8 years (range, 5-20 years) before presentation. RESULTS: Patients reported a mean of 6 months of pain before presentation (range, 1-8 months). Sixty-six percent of patients with surgically treated complete fractures became pain-free and 98% were radiographically healed by 12 months. Sixty-four percent of patients who underwent intramedullary nailing reported a functional return to baseline within 1 year. Patients who reported major functional limitations at latest followup listed pain and apprehension as the major causes of their limitation. CONCLUSIONS: Patients with surgically treated bisphosphonate-associated complete femur fractures achieved generally reliable although delayed fracture healing if malaligned, and nearly two-thirds of patients returned to self-reported baseline function within 1 year. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

BACKGROUND: Prior studies have suggested that Asian patients and women may be more likely to sustain atypical femoral fractures in association with bisphosphonate use. However, they do not account for confounders such as asymptomatic patients who are long-term bisphosphonate users or patients sustaining osteoporotic fractures. QUESTIONS/PURPOSES: The purpose of this study was to determine the differences in sex and racial association with atypical femoral fractures by comparing demographic characteristics of patients who sustained an atypical bisphosphonate-associated fracture with patients on long-term bisphosphonates without fractures and with patients who sustained osteoporotic fractures. METHODS: Three groups from prospective registries were identified: (1) patients with atypical femur fractures associated with long-term bisphosphonate use (BFF) (n = 54); (2) patients on long-term bisphosphonates but with no associated fractures (BNF) (n = 119); and (3) patients with osteoporotic proximal femur fractures not associated with bisphosphonates (PFF) (n = 216). Age, sex, and self-reported race/ethnicity were documented and compared. Multivariate and univariate analyses were done as well as age- and sex-stratified analyses. RESULTS: Age and sex distributions of the BFF and BNF patients were similar. There was a higher percentage of Asian patients in the BFF group (17%) than in the BNF group (3%; p = 0.004) as well as Hispanics (13% versus 3% in BNF; p = 0.011). Patients in the BFF group were younger than those in the PFF group (67.5 versus 78.4 years; p < 0.001) and had fewer males (7% versus 14%; p < 0.001). CONCLUSIONS: These data suggest that Asians are at higher risk for atypical bisphosphonate-associated fractures. We recommend closer followup in Asian patients who are taking bisphosphonates. LEVEL OF EVIDENCE: Level III, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

OBJECTIVES: Progression of an incomplete atypical femoral fracture (IF) to a complete fracture in patients on long term bisphosphonate (BP) therapy can be catastrophic. We aimed to determine the frequency and imaging features of IF in asymptomatic patients on long-term BP therapy and to identify distinguishing clinical and laboratory markers in the subset of patients who develop these fractures. MATERIAL AND METHODS: From August 2009 to March 2011, 220 femoral radiographs in 110 asymptomatic patients (101 women, 9 men, age 47-94) were reviewed by 2 radiologists. All patients were on BP therapy for at least 3years and had no history of hip/thigh pain or recent trauma. MRI was performed when a fracture was suspected on radiographs. Bone mineral density, serum calcium, 25-hydroxy vitamin D, intact parathyroid hormone, serum c-telopeptide and urine n-telopeptide were obtained in all patients. RESULTS: Two of 110 patients (1.82%, confidence interval of 0.6% to 6.3%) had 3 IFs. Both patients, age 50 and 57, were Caucasian, active and on BP for 8years. MRI confirmed radiographic findings in both patients. Both women had T-scores in the osteopenic range at 2 sites and osteoporotic range at 1 site. CONCLUSION: The 1.82% frequency of IF in asymptomatic patients on long term BP therapy is higher than that suggested in the literature. Statistical differences between fracture and non-fracture groups were not presented as the patient population was too small to draw any significant conclusions.

OBJECTIVE: : To describe the outcomes for patients treated at a single institution, who sustained incomplete bisphosphonate-induced femoral fractures. DESIGN: : Retrospective review. SETTING: : University-based academic medical center. PATIENTS: : Thirty-one patients with 43 incomplete fractures met the inclusion criteria. INTERVENTION: : Nonoperative management or surgical intervention for fractures with refractory symptoms or progression of fracture lucency on radiographs. MAIN OUTCOME MEASUREMENTS: : Radiographic assessments and the Short Musculoskeletal Functional Assessment to gauge functional status. RESULTS: : The cohort was all women with an average age of 69.2 (range: 46-92) years and had been treated with bisphosphonate therapy for an average of 9.1 (range: 5-20) years. The average healing time for all incomplete fractures was 9.4 (range: 1.5-36) months. Forty-nine percent of the fractures (21 of 43 fractures) were ultimately treated with surgery for impending complete fracture or failure of nonsurgical management. Of the incomplete fractures treated with surgery, 81% became pain free and 100% were radiographically healed at a mean of 7.1 (range: 1.5-12) months. In contrast, of the nonoperatively treated incomplete fractures, only 64% were pain free at latest follow-up, with only 18% of fractures demonstrating radiographic evidence of healing at an average of 11 (range: 6-24) months. Standardized dysfunction index from the Short Musculoskeletal Functional Assessment was better (19.7) in the surgical group than in the nonsurgical group (19.7 vs. 25.7, P = 0.0017). CONCLUSIONS: : A higher percentage of patients treated surgically became asymptomatic and demonstrated radiographic evidence of healing earlier than those treated nonsurgically. Surgical intervention is effective for relief of symptoms when treating incomplete bisphosphonate-related femur fractures, and patients should be counseled to the potential benefits of prophylactic surgery. LEVEL OF EVIDENCE: : Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Objectives: To elucidate the effects of prolonged bisphosphonate (BP) exposure on the development of atypical fragility fractures and to define risk factors.Methods: Approval was obtained from the IRB. A retrospective chart analysis was performed on 51 patients with complete subtrochanteric or diaphyseal femoral fracture(s) from January 2005 to April 2011 while on BP for at least 3 years; 25 patients (mean age 67.52) had all available data. All fractures included in the study were low or no energy fractures. Relevant clinical and demographic data including age, gender, ethnicity, height, weight, comorbid medical conditions, and medications were collected. Imaging and laboratory data including calcium, alkaline phosphatase, 25-hydroxy vitamin D(25-OHD), intact parathyroid hormone(PTH), serum c-telopeptide(CTX), urine n-telopeptide(NTX), bone mineral density, radiography and MRI were obtained in all patients.Results: The majority of patients were Caucasian, on alendronate, had bilateral findings, and almost half had prodromal symptoms. 45.8% had a 25-OHD level that was suboptimal (less than 30 ng/ml). Mean BP duration was 9.84 years and mean bone densities were in the osteopenic, not osteoporotic, range.Conclusion: Certain characteristics in patients with atypical BP-related fracture include relatively young age, long duration of BP use, suboptimal 25-OHD and bone densities in non-osteoporotic ranges. All of these may be significant risk factors for insufficiency fracture development.