Efficacy and safety of candidate biosimilar CT-P41 versus reference denosumab: a double-blind, randomized, active-controlled, Phase 3 trial in postmenopausal women with osteoporosis.

This 78-week (18-month) study conducted in 479 postmenopausal women with osteoporosis evaluated the efficacy, pharmacodynamics, pharmacokinetics, safety, and immunogenicity of candidate biosimilar CT-P41 relative to US reference denosumab. CT-P41 had equivalent efficacy and pharmacodynamics to US-denosumab, with similar pharmacokinetics and comparable safety and immunogenicity profiles. PURPOSE: To demonstrate equivalence of candidate biosimilar CT-P41 and US reference denosumab (US-denosumab) in postmenopausal women with osteoporosis. METHODS: This 78-week (18-month), double-blind, randomized, active-controlled Phase 3 study (NCT04757376) comprised two treatment periods (TPs). In TPI, patients (N = 479) were randomized 1:1 to 60 mg subcutaneous CT-P41 or US-denosumab. At Week 52, those who had received CT-P41 in TPI continued to do so. Those who had received US-denosumab were randomized (1:1) to continue treatment or switch to CT-P41 in TPII. The primary efficacy endpoint was percent change from baseline in lumbar spine bone mineral density at Week 52. Efficacy equivalence was concluded if associated 95% confidence intervals (CI) for least squares (LS) mean group differences fell within ± 1.503%. The primary pharmacodynamic (PD) endpoint was area under the effect curve for serum carboxy-terminal cross-linking telopeptide of type I collagen through the first 26 weeks, with an equivalence margin of 80-125% (for 95% CIs associated with geometric LS mean ratios). RESULTS: Equivalence was demonstrated for CT-P41 and US-denosumab with respect to primary efficacy (LS mean difference [95% CI]: - 0.139 [- 0.826, 0.548] in the full analysis set and - 0.280 [- 0.973, 0.414] in the per-protocol set) and PD (geometric LS mean ratio [95% CI]: 94.94 [90.75, 99.32]) endpoints. Secondary efficacy, PD, pharmacokinetics, and safety results were comparable among all groups up to Week 78, including after transitioning to CT-P41 from US-denosumab. CONCLUSIONS: CT-P41 was equivalent to US-denosumab in women with postmenopausal osteoporosis, with respect to primary efficacy and PD endpoints.

Race-specific FRAX models are evidence-based and support equitable care: a response to the ASBMR Task Force report on Clinical Algorithms for Fracture Risk.

Task Force on 'Clinical Algorithms for Fracture Risk' commissioned by the American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee has recommended that FRAX® models in the US do not include adjustment for race and ethnicity. This position paper finds that an agnostic model would unfairly discriminate against the Black, Asian and Hispanic communities and recommends the retention of ethnic and race-specific FRAX models for the US, preferably with updated data on fracture and death hazards. In contrast, the use of intervention thresholds based on a fixed bone mineral density unfairly discriminates against the Black, Asian and Hispanic communities in the US. This position of the Working Group on Epidemiology and Quality of Life of the International Osteoporosis Foundation (IOF) is endorsed both by the IOF and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

Performance of VI-RADS in predicting muscle-invasive bladder cancer after transurethral resection: a single center retrospective analysis.

PURPOSE: To assess VIRADS performance and inter-reader agreement for detecting muscle-invasive bladder cancer (MIBC) following transurethral resection of bladder tumor (TURBT). METHODS: An IRB-approved, HIPAA-compliant, retrospective study from 2016 to 2020 included patients with bladder urothelial carcinoma who underwent MRI after TURBT, and cystectomy within 3 months without post-MRI treatments. Three radiologists blinded to pathology results independently reviewed MR images and assigned a VI-RADS score. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of VI-RADS were assessed for diagnosing MIBC using VI-RADS scores ≥ 3 and ≥ 4. Inter-reader agreement was assessed using Gwet's agreement coefficient (AC) and percent agreement. RESULTS: The cohort consisted of 70 patients (mean age, 68 years ± 11 [SD]; range 39-85; 58 men) and included 32/70 (46%) with MIBC at cystectomy. ROC analysis revealed an AUC ranging from 0.67 to 0.77 and no pairwise statistical difference between readers (p-values, 0.06, 0.08, 0.97). Percent sensitivity, specificity, PPV, NPV and accuracy for diagnosing MIBC for the three readers ranged from 81.3-93.8, 36.8-55.3, 55.6-60.5, 77.3-87.5, and 62.9-67.1 respectively for VI-RADS score ≥ 3, and 78.1-81.3, 47.4-68.4, 55.6-67.6, 72.0-78.8 and 61.4-72.9 respectively for VI-RADS score ≥ 4. Gwet's AC was 0.63 [95% confidence interval (CI): 0.49,0.78] for VI-RADS score ≥ 3 with 79% agreement [95% CI 72,87] and 0.54 [95%CI 0.38,0.70] for VI-RADS score ≥ 4 with 76% agreement [95% CI 69,84]. VIRADS performance was not statistically different among 31/70 (44%) patients who received treatments prior to MRI (p ≥ 0.16). CONCLUSION: VI-RADS had moderate sensitivity and accuracy but low specificity for detection of MIBC following TURBT, with moderate inter-reader agreement.

Transitioning from interventional radiology: ideas for the inevitable.

BACKGROUND: Interventional Radiology (IR) is a highly rewarding specialty, both for its salutary effects for patients, as will as the satisfaction it provides for the operating radiologists. Nonetheless, arduous work and long hours have led to numerous reports of burnout amongst interventional radiologists (IRs). MATERIALS AND METHODS: Six long-term academic radiologists in leadership positions briefly chronicle their becoming IRs, their type of transitioning from IR, and the pros and cons of those respective transitions. RESULTS: The specific transitions include reduced time in IR, switching to diagnostic radiology, becoming involved in medical school education, ceasing IR leadership, and retirement. Pros and cons of the various transition strategies are highlighted. CONCLUSION: As the taxing work and long hours are so ubiquitous for IRs, and as burnout is so common, transitioning from IR is highly likely eventually for IRs. The varied transition experiences highlighted in this report hopefully will be helpful for current and aspiring IRs.

Clinical indications, safety, and effectiveness of percutaneous image-guided adrenal mass biopsy: an 8-year retrospective analysis in 160 patients.

PURPOSE: To assess indications, safety, and effectiveness of percutaneous adrenal mass biopsy in contemporary practice. METHODS: This institutional review board-approved, retrospective study included all patients undergoing percutaneous image-guided adrenal mass biopsies at an academic health system from January 6, 2015, to January 6, 2023. Patient demographics, biopsy indications, mass size, laboratory data, pathology results, and complications were recorded. Final diagnoses were based on pathology or ≥ 1 year of imaging follow-up when biopsy specimens did not yield malignant tissue. Test performance calculations excluded repeat biopsies. Continuous variables were compared with Student's t test, dichotomous variables with chi-squared test. RESULTS: A total of 160 patients underwent 186 biopsies. Biopsies were indicated to diagnose metastatic disease (139/186; 74.7%), for oncologic research only (27/186; 14.5%), diagnose metastatic disease and oncologic research (15/186; 8%), and diagnose an incidental adrenal mass (5/186; 2.7%). Biopsy specimens were diagnostic in 154 patients (96.3%) and non-diagnostic in 6 (3.8%). Diagnostic biopsies yielded malignant tissue (n = 136), benign adrenal tissue (n = 12), and benign adrenal neoplasms (n = 6) with sensitivity = 98.6% (136/138), specificity = 100% (16/16), positive predictive value = 100% (136/136), and negative predictive value = 88.9% (16/18). Adverse events followed 11/186 procedures (5.9%) and most minor (7/11, 63.6%). The adverse event rate was similar whether tissue was obtained for clinical or research purposes (10/144; 6.9% vs. 1/42; 2.4%, p = 0.27), despite more specimens obtained for research (5.8 vs. 3.7, p < 0.001). CONCLUSION: Percutaneous adrenal mass biopsy is safe, accurate, and utilized almost exclusively to diagnose metastatic disease or for oncologic research. The negative predictive value is high when diagnostic tissue samples are obtained. Obtaining specimens for research does not increase adverse event risk.

Evidence-Based Guideline for the management of osteoporosis in men.

Historically, osteoporosis has been viewed as a disease of women, with research, trials of interventions and guidelines predominantly focused as such. It is apparent, however, that this condition causes a substantial health burden in men also, and that its assessment and management must ultimately be addressed across both sexes. In this article, an international multidisciplinary working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases presents GRADE-assessed recommendations for the diagnosis, monitoring and treatment of osteoporosis in men. The recommendations are based on a comprehensive review of the latest research related to diagnostic and screening approaches for osteoporosis and its associated high fracture risk in men, covering disease burden, appropriate interpretation of bone densitometry (including the use of a female reference database for densitometric diagnosis in men) and absolute fracture risk, thresholds for treatment, and interventions that can be used therapeutically and their health economic evaluation. Future work should specifically address the efficacy of anti-osteoporosis medications, including denosumab and bone-forming therapies.

Low-grade oncocytic tumor: a review of radiologic and clinical features.

PURPOSE: The 2022 World Health Organization classification of renal neoplasia expanded the spectrum of oncocytic neoplasms to encompass newly established and emerging entities; one of the latter is the low-grade oncocytic tumor (LOT). This study reports the radiologic appearance and clinical behavior of LOT. METHODS: In this IRB-approved, HIPPA-compliant retrospective study, our institution's pathology database was searched for low-grade oncocytic tumors or neoplasms. Patient age, gender, and comorbidities were obtained from a review of electronic medical records, and imaging characteristics of the tumors were assessed through an imaging platform. RESULTS: The pathology database search yielded 14 tumors in 14 patients. Four patients were excluded, as radiologic images were not available in three, and one did not fulfill diagnostic criteria after pathology re-review. The resulting cohort consisted of 10 tumors (median diameter 2.3 cm, range 0.7-5.1) in 10 patients (median age 68 years, range 53-91, six women). All tumors presented as a solitary, well-circumscribed, mass with solid components. All enhanced as much or almost as much as adjacent renal parenchyma; all but one enhanced heterogeneously. None had lymphadenopathy, venous invasion, or metastatic disease at presentation or at clinical follow-up (median, 22.2 months, range 3.4-71.6). Among five tumors undergoing active surveillance, mean increase in size was 0.4 cm/year at imaging follow-up (median 16.7 months, range 8.9-25.4). CONCLUSION: LOT, a recently described pathologic entity in the kidney, can be considered in the differential diagnosis of an avidly and typically heterogeneously enhancing solid renal mass in an adult patient.

A randomized, double-blind, single-dose, phase 1 study comparing the pharmacokinetics, pharmacodynamics, safety, and immunogenicity of denosumab biosimilar CT­P41 and reference denosumab in healthy males.

BACKGROUND: This study's objective was to demonstrate pharmacokinetic (PK) similarity and safety of denosumab biosimilar, CT­P41, and United States-licensed reference denosumab (US-denosumab) in healthy male Asian adults, considering also pharmacodynamic (PD) outcomes. RESEARCH DESIGN AND METHODS: This double-blind, two-arm, parallel-group, Phase 1 study randomized (1:1) healthy males to a single (60-mg) subcutaneous dose of CT­P41 or US-denosumab. Primary endpoints were area under the concentration - time curve (AUC) from time zero to infinity (AUC0-inf), AUC from time zero to the last quantifiable concentration (AUC0-last), and maximum serum concentration (Cmax). PK equivalence was determined if 90% confidence intervals (CIs) for ratios of geometric least-squares means (gLSMs) were within the predefined 80-125% equivalence margin. Secondary PK, PD, safety, and immunogenicity outcomes were also evaluated. RESULTS: Of 154 participants randomized (76 CT­P41; 78 US-denosumab), 151 received study drug (74 CT­P41; 77 US-denosumab). Primary and secondary PK results, PD results, safety, and immunogenicity were comparable between groups. Ninety percent CIs for ratios of gLSMs were within the predefined equivalence margin for AUC0-inf (100.4-114.7), AUC0-last (99.9-114.3), and Cmax (95.2-107.3). CONCLUSIONS: Following a single dose in healthy males, CT­P41 demonstrated PK equivalence with US-denosumab. TRIAL REGISTRATION: ClinicalTrials.gov: NCT06037395.

Comparison of the cost-effectiveness of sequential treatment with abaloparatide in US men and women at very high risk of fractures.

BACKGROUND: Osteoporotic-related fractures represent an increasing burden to patients, health care systems and society. AIMS: This study estimated cost-effectiveness of sequential treatment with abaloparatide (ABL) followed by alendronate (ALN) compared to relevant alternative strategies in US men and women aged 50 to 80 years at very high fracture risk (bone mineral density T-score ≤ - 2.5 and a recent fracture). METHODS: A lifetime Markov-based microsimulation model was used to estimate healthcare costs and quality-adjusted life years (QALYs). Comparators were sequential treatment with unbranded teriparatide (TPTD)/ALN, generic ALN monotherapy, and no treatment. Analyses were conducted based on initial fracture site (hip, vertebral, or any fracture) and treatment efficacy data (derived from clinical trials or a recent network meta-analysis). RESULTS: From all analyses completed, sequential ABL/ALN demonstrated more QALYs for lower healthcare costs versus unbranded TPTD/ALN. No treatment was dominated (higher costs for less QALYs) versus ALN monotherapy. Sequential ABL/ALN resulted in favorable cost-effectiveness (at US threshold of $150,000/QALY) versus generic ALN monotherapy in men aged ≥ 50 years with any fracture type, women aged ≥ 65 years with any fracture type, and women aged ≥ 55 years having a hip or vertebral fracture. DISCUSSION: Similar cost-effectiveness of sequential ABL/ALN versus unbranded TPTD/ALN, ALN monotherapy, and no treatment was observed in both US men and women at very high fracture risk, with a moderate improvement in cost-effectiveness in men versus women and in patients with a hip or vertebral fracture. CONCLUSIONS: Sequential therapy with ABL/ALN was cost-effective in US men and women at very high risk of fractures.

Patients' preferences for fracture risk communication: the Risk Communication in Osteoporosis (RICO) study.

The RICO study indicated that most patients would like to receive information regarding their fracture risk but that only a small majority have actually received it. Patients globally preferred a visual presentation of fracture risk and were interested in an online tool showing the risk. PURPOSE: The aim of the Risk Communication in Osteoporosis (RICO) study was to assess patients' preferences regarding fracture risk communication. METHODS: To assess patients' preferences for fracture risk communication, structured interviews with women with osteoporosis or who were at risk for fracture were conducted in 11 sites around the world, namely in Argentina, Belgium, Canada at Hamilton and with participants from the Osteoporosis Canada Canadian Osteoporosis Patient Network (COPN), Japan, Mexico, Spain, the Netherlands, the UK, and the USA in California and Washington state. The interviews used to collect data were designed on the basis of a systematic review and a qualitative pilot study involving 26 participants at risk of fracture. RESULTS: A total of 332 women (mean age 67.5 ± 8.0 years, 48% with a history of fracture) were included in the study. Although the participants considered it important to receive information about their fracture risk (mean importance of 6.2 ± 1.4 on a 7-point Likert scale), only 56% (i.e. 185/332) had already received such information. Globally, participants preferred a visual presentation with a traffic-light type of coloured graph of their FRAX® fracture risk probability, compared to a verbal or written presentation. Almost all participants considered it important to discuss their fracture risk and the consequences of fractures with their healthcare professionals in addition to receiving information in a printed format or access to an online website showing their fracture risk. CONCLUSIONS: There is a significant communication gap between healthcare professionals and patients when discussing osteoporosis fracture risk. The RICO study provides insight into preferred approaches to rectify this communication gap.

Feasibility and safety of bipolar radiofrequency track cautery during percutaneous image-guided abdominal biopsy procedures.

PURPOSE: The purpose of this study was to assess the feasibility and safety of using a bipolar radiofrequency track cautery device during percutaneous image-guided abdominal biopsy procedures in at-risk patients. METHODS: Forty-two patients (26-79 years old; female 44%) with at least one bleeding risk factor who underwent an abdominal image-guided (CT or US) biopsy and intended bipolar radiofrequency track cautery (BRTC) were retrospectively studied. An 18G radiofrequency electrode was inserted through a 17G biopsy introducer needle immediately following coaxial 18G core biopsy, to cauterize the biopsy track using temperature control. Bleeding risk factors, technical success, and adverse events were recorded. RESULTS: BRTC was technically successful in 41/42 (98%) of procedures; in one patient, the introducer needle retracted from the liver due to respiratory motion prior to BRTC. BRTC following percutaneous biopsy was applied during 41 abdominal biopsy procedures (renal mass = 12, renal parenchyma = 10, liver mass = 9, liver parenchyma = 5, splenic mass or parenchyma = 4, gastrohepatic mass = 1). All patients had one or more of the following risk factors: high-risk organ (spleen or renal parenchyma), hypervascular mass, elevated prothrombin time, renal insufficiency, thrombocytopenia, recent anticoagulation or anticoagulation not withheld for recommended interval, cirrhosis, intraprocedural hypertension, brisk back bleeding observed from the introducer needle, or subcapsular tumor location. No severe adverse events (grade 3 or higher) occurred. Two (2/41, 5%) mild (grade 1) bleeding events did not cause symptoms or require intervention. CONCLUSION: Bipolar radiofrequency track cautery was feasible and safe during percutaneous image-guided abdominal biopsy procedures. IRB approval: MBG 2022P002277.

Development, Implementation, and Assessment of a Quality, Research, Education, and Wellness (QREW) Professional Development Lecture Series for Radiology Faculty.

RATIONALE AND OBJECTIVES: Professional development is important to academic radiologists. We developed, implemented, and assessed an internal professional development lecture series focusing on the non-interpretative themes of Quality, Research, Education, and Wellness (QREW). MATERIALS AND METHODS: The faculty of a 29-member abdominal radiology division at an academic hospital were invited to deliver 1-hour virtual lectures on noninterpretative topics to division colleagues. Topics were curated by division leadership based on the perceived needs of faculty. Anonymous feedback was collected from attendees for quality improvement purposes and analyzed using descriptive statistics and Fisher's exact test. RESULTS: Over 17 months, 13 QREW lectures were delivered. In total, 91 feedback forms were completed by faculty (mean 7 forms, range 2-12 per session). Of these, 57 responses (63%) were by those <7 years post training ("junior faculty"), 34 responses (37%) by those ≥ 7 years from training ("senior faculty"). Most respondents reported low levels of prior instruction (80/90, 89%) and personal knowledge (49/91, 54%) on topics. Compared to senior faculty, a greater proportion of junior faculty reported less prior instruction (73% vs 98%, P < 0.001) and less personal knowledge (32% vs 65%, P < 0.01). Most respondents agreed or strongly agreed that the topics were important to their clinical practice (87/90, 97%), professional development (86/90, 96%), and personal well-being (82/91, 90%). Faculty identified the QREW program as a major contributor to their professional development. CONCLUSION: A noninterpretative professional development lecture series delivered by radiology faculty in a virtual, interactive format is feasible and effective, particularly for junior faculty.

Racial variation in healthcare resource utilization and expenditures in knee/hip osteoarthritis patients: a retrospective analysis of a Medicaid population.

BACKGROUND: Osteoarthritis (OA) is a leading cause of chronic pain and disability. Prior studies have documented racial disparities in the clinical management of OA. The objective of this study was to assess the racial variations in the economic burden of osteoarthritis within the Medicaid population. METHODS: We conducted a retrospective observational study using the MarketScan Multi-State Medicaid database (2012-2019). Newly diagnosed, adult, knee and/or hip OA patients were identified and followed for 24 months. Demographic and clinical characteristics were collected at baseline; outcomes, including OA treatments and healthcare resource use (HCRU) and expenditures, were assessed during the 24-month follow-up. We compared baseline patient characteristics, use of OA treatments, and HCRU and costs in OA patients by race (White vs. Black; White vs. Other) and evaluated racial differences in healthcare costs while controlling for underlying differences. The multivariable models controlled for age, sex, population density, health plan type, presence of non-knee/hip OA, cardiovascular disease, low back pain, musculoskeletal pain, presence of moderate to severe OA, and any pre-diagnosis costs. RESULTS: The cohort was 56.7% White, 39.9% Black and 3.4% of Other race (American Indian/Alaska Native, Hispanic, Asian, Native Hawaiian/Other Pacific Islander, two or more races and other). Most patients (93.8%) had pharmacologic treatment for OA. Inpatient admission during the 24-month follow-up period was lowest among Black patients (25.8%, p < .001 White vs. Black). In multivariable-adjusted models, mean all-cause expenditures were significantly higher in Black patients ($25,974) compared to White patients ($22,913, p < .001). There were no significant differences between White patients and patients of Other race ($22,352). CONCLUSIONS: The higher expenditures among Black patients were despite a lower rate of inpatient admission in Black patients and comparable length and number of hospitalizations in Black and White patients, suggesting that other unmeasured factors may be driving the increased costs among Black OA patients.

Higher healthcare costs were observed in Black Medicaid patients with knee/hip osteoarthritis despite lower rates of inpatient admission. We observed these differences in this Medicaid population, where socioeconomic status is more homogeneous.Black patients had significantly higher healthcare costs compared to White patients and the difference persisted even after accounting for underlying differences in Black and White patients.Higher healthcare costs among Black patients were found in both the baseline and follow-up periods overall for all types of healthcare (hospitalizations, ER, office visit, other services).Higher hospitalization costs in Black patients were observed despite lower rates of hospitalizations in Black patients. These increased costs cannot be attributed to either longer or more frequent hospitalizations; no significant difference in either the length of stay or the number of hospitalizations was observed when comparing Black patients to White patients.

Prescription opioid utilization patterns, and associated outcomes, among privately insured patients prescribed opioids to manage pain associated with osteoarthritis.

OBJECTIVE: To describe utilization patterns, negative clinical outcomes and economic burden of patients diagnosed with osteoarthritis (OA) of the hip and/or knee who received a prescription for tramadol or non-tramadol opioids vs. non-opioid drugs. METHODS: Optum Healthcare Solutions, Inc. commercial claims data were used (1/2012--3/2017). Adults with ≥2 diagnoses of OA of the hip and/or knee, and ≥30 days supply of pain medications were identified during the three-year period from the date of first prescription (index date) after the first OA diagnosis. Drug utilization statistics in the follow-up period were summarized by initial treatment (i.e. tramadol, non-tramadol opioids, non-opioid drugs). Opioid initiators were matched to those initiated on non-opioid treatments using a propensity score model accounting for baseline characteristics. Matched pairs analysis compared outcomes for these cohorts. RESULTS: Of 62,715 total patients, 15,270 (24.3%) initiated treatment with opioids, including 3,513 (5.6%) on tramadol and 11,757 (18.7%) on non-tramadol opioids. Opioid initiators had more comorbidities, higher baseline healthcare costs, and were more likely to have OA of the hip. Among non-opioid initiators, 27.5% switched to tramadol and 63% switched to non-tramadol opioids. Among tramadol initiators, 71% switched to non-tramadol opioids. Patients initiated on opioids had 20.4% (p < .01) higher all-cause healthcare costs and higher percentages experiencing multiple negative clinical outcomes (all p < .01) compared to matched controls. CONCLUSIONS: Most patients with OA of the hip and/or knee either initiate on or switch to opioids for long-term management of OA-related pain despite known risks. This highlights the need for new treatments that delay or prevent use of opioids.

Efficacy and Safety of Transdermal Abaloparatide in Postmenopausal Women with Osteoporosis: A Randomized Study.

Anabolic therapies, recommended for patients at very high fracture risk, are administered subcutaneously (SC). The objective of this study was to evaluate the efficacy and safety of the abaloparatide microstructured transdermal system (abaloparatide-sMTS) as an alternative to the SC formulation. This phase 3, noninferiority study (NCT04064411) randomly assigned postmenopausal women with osteoporosis (N = 511) 1:1 to open-label abaloparatide administered daily via abaloparatide-sMTS or SC injection for 12 months. The primary comparison between treatment groups was the percentage change in lumbar spine bone mineral density (BMD) at 12 months, with a noninferiority margin of 2.0%. Secondary endpoints included percentage change in total hip and femoral neck BMD, bone turnover markers, dermatologic safety, and new clinical fracture incidence. At 12 months, percentage increase from baseline in lumbar spine BMD was 7.14% (SE: 0.46%) for abaloparatide-sMTS and 10.86% (SE: 0.48%) for abaloparatide-SC (treatment difference: -3.72% [95% confidence interval: -5.01%, -2.43%]). Percentage change in total hip BMD was 1.97% for abaloparatide-sMTS and 3.70% for abaloparatide-SC. Median changes from baseline at 12 months in serum procollagen type I N-terminal propeptide (s-PINP) were 52.6% for abaloparatide-sMTS and 74.5% for abaloparatide-SC. Administration site reactions were the most frequently reported adverse events (abaloparatide-sMTS, 94.4%; abaloparatide-SC, 70.5%). Incidence of serious adverse events was similar between groups. Mild or moderate skin reactions occurred with abaloparatide-sMTS with no identifiable risk factors for sensitization reactions. Few new clinical fractures occurred in either group. Noninferiority of abaloparatide-sMTS to abaloparatide-SC for percentage change in spine BMD at 12 months was not demonstrated; however, clinically meaningful increases from baseline in lumbar spine and total hip BMD were observed in both treatment groups. © 2023 Radius Health, Inc and The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Economic and Humanistic Burden Among Medicare-Aged Women With Fragility Fracture in the United States.

OBJECTIVE: Describe patient characteristics, health care resource utilization, costs, and humanistic burden of women with Medicare insurance with incident fragility fracture who were admitted to post-acute-care (PAC). DESIGN: Retrospective cohort study using 100% Medicare Fee-for-Service (FFS) data. SETTING AND PARTICIPANTS: Community-dwelling female Medicare beneficiaries with incident fragility fracture January 1, 2017, to October 17, 2019, resulting in PAC admission to a skilled nursing facility (SNF), home-health care, inpatient-rehabilitation facility, or long-term acute-care hospital. METHODS: Patient demographic/clinical characteristics were measured during 1-year baseline. Resource utilization and costs were measured during baseline, PAC event, and PAC follow-up. Humanistic burden was measured among SNF patients with linked Minimum Data Set assessments. Multivariable regression examined predictors of PAC costs after discharge and changes in functional status during SNF stay. RESULTS: A total of 388,732 patients were included. Compared with baseline, hospitalization rates were 3.5, 2.4, 2.6, and 3.1 times higher and total costs 2.7, 2.0, 2.5, and 3.6 times higher for SNF, home-health, inpatient-rehabilitation, and long-term acute-care, respectively, following PAC discharge. Utilization of dual-energy X-ray absorptiometry (DXA) and osteoporosis medications remained low: 8.5% to 13.7% received DXA during baseline vs 5.2% to 15.6% following PAC; 10.2% to 12.0% received osteoporosis medication during baseline vs 11.4% to 22.3% following PAC. Dual eligibility for Medicaid (ie, low income) was associated with 12% higher costs; Black patients had 14% higher costs. Activities of daily living scores improved 3.5 points during SNF stay, but Black patients had 1.22-point lower improvement than White patients. Pain intensity scores showed small improvement (-0.8 points). CONCLUSIONS AND IMPLICATIONS: Women admitted to PAC with incident fracture had high humanistic burden with little improvement in pain and functional status and significantly higher economic burden after discharge compared with baseline. Disparities in outcomes related to social risk factors were observed, with consistently low utilization of DXA and osteoporosis medications even after fracture. Results indicate a need for improved early diagnosis and aggressive disease management to prevent and treat fragility fractures.

Perineural Invasion and Spread in Common Abdominopelvic Diseases: Imaging Diagnosis and Clinical Significance.

Malignancies and other diseases may spread by multiple pathways, including direct extension, hematogenous spread, or via lymphatic vessels. A less-well-understood route is the peripheral nervous system, which is known as perineural spread (PNS). In addition to accounting for pain and other neurologic symptoms, PNS affects both disease prognosis and management. Although PNS is commonly discussed in relation to head and neck tumors, there is emerging data regarding PNS in abdominopelvic malignancies and other conditions such as endometriosis. Due to improved contrast and spatial resolution, perineural invasion, a finding heretofore diagnosed only at pathologic examination, can be detected at CT, MRI, and PET/CT. PNS most commonly manifests as abnormal soft-tissue attenuation extending along neural structures, and diagnosis of it is aided by optimizing imaging parameters, understanding pertinent anatomy, and becoming familiar with the typical neural pathways of spread that largely depend on the disease type and location. In the abdomen, the celiac plexus is a central structure that innervates the major abdominal organs and is the principal route of PNS in patients with pancreatic and biliary carcinomas. In the pelvis, the lumbosacral plexus and inferior hypogastric plexus are the central structures and principal routes of PNS in patients with pelvic malignancies. Although the imaging findings of PNS may be subtle, a radiologic diagnosis can have a substantial effect on patient care. Knowledge of anatomy and known routes of PNS and optimizing imaging parameters is of utmost importance in providing key information for prognosis and treatment planning. © RSNA, 2023 Supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article. Quiz questions for this article are available through the Online Learning Center.

Real-world evidence: new opportunities for osteoporosis research. Recommendations from a Working Group from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

This narrative review summarises the recommendations of a Working Group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) for the conduct and reporting of real-world evidence studies with a focus on osteoporosis research. PURPOSE: Vast amounts of data are routinely generated at every healthcare contact and activity, and there is increasing recognition that these real-world data can be analysed to generate scientific evidence. Real-world evidence (RWE) is increasingly used to delineate the natural history of disease, assess real-life drug effectiveness, understand adverse events and in health economic analysis. The aim of this work was to understand the benefits and limitations of this type of data and outline approaches to ensure that transparent and high-quality evidence is generated. METHODS: A ESCEO Working Group was convened in December 2022 to discuss the applicability of RWE to osteoporosis research and approaches to best practice. RESULTS: This narrative review summarises the agreed recommendations for the conduct and reporting of RWE studies with a focus on osteoporosis research. CONCLUSIONS: It is imperative that research using real-world data is conducted to the highest standards with close attention to limitations and biases of these data, and with transparency at all stages of study design, data acquisition and curation, analysis and reporting to increase the trustworthiness of RWE study findings.

Risk of malignancy in T1-hyperintense Bosniak version 2019 class II and IIF cystic renal masses.

BACKGROUND: Bosniak classification version 2019 includes cystic masses in class II and IIF based partly on their hyperintense appearance at T1-weighted MRI. The prevalence of malignancy in non-enhancing heterogeneously T1-hyperintense masses is unknown, nor whether the pattern of T1 hyperintensity affects malignancy likelihood. PURPOSE: To determine the malignancy proportion among six patterns of T1 hyperintensity within non-enhancing cystic renal masses. METHODS: This retrospective, single-institution study included 72 Bosniak class II and IIF, non-enhancing, T1-hyperintense cystic renal masses. Diagnosis was confirmed by histopathology or by follow-up imaging demonstrating 5-year size and morphologic stability, decreased in size by ≥ 30%, resolution, or Bosniak down-classification. Six patterns of T1 hyperintensity were pre-defined: homogeneous (pattern A), fluid-fluid level (pattern B), peripherally markedly T1-hyperintense (pattern C), containing a T1-hyperintense non-enhancing nodule (pattern D), peripherally T1-hypointense (pattern E), and heterogeneously T1-hyperintense without a distinct pattern (pattern F). Three readers independently assigned each mass to a pattern. Individual and mean malignancy proportion were determined. Mann-Whitney test and Fischer's exact test compared the likelihood of malignancy between patterns. Inter-reader agreement was analyzed with Gwet's agreement coefficient (AC). RESULTS: Among 72 masses, the mean number of masses assigned was 11 (15%) to pattern A, 21 (29%) to pattern B, 6 (8%) to pattern C, 7 (10%) to pattern D, 5 (7%) to pattern E, and 22 (31%) to pattern F. Five of 72 masses (7%) were malignant; none was assigned pattern A, B, or D. Mean malignancy proportion was 5% (0/9, 1/6, and 0/4) for pattern C, 13% (0/4, 1/3, and 1/7) for pattern E, and 18% (5/20, 3/21, and 4/25) for pattern F. Malignant masses were more likely assigned to pattern E or F (p = 0.003-0.039). Inter-reader agreement was substantial (Gwet's AC: 0.68). CONCLUSION: Bosniak version 2019 class IIF masses that are non-enhancing and heterogeneously T1-hyperintense with a fluid-fluid level are likely benign. Those that are non-enhancing and heterogeneously T1-hyperintense without a distinct pattern have a malignancy proportion up to 25% (5/20).

Differentiating Benign From Malignant Cystic Renal Masses: A Feasibility Study of Computed Tomography Texture-Based Machine Learning Algorithms.

OBJECTIVE: The Bosniak classification attempts to predict the likelihood of renal cell carcinoma (RCC) among cystic renal masses but is subject to interobserver variability and often requires multiphase imaging. Artificial intelligence may provide a more objective assessment. We applied computed tomography texture-based machine learning algorithms to differentiate benign from malignant cystic renal masses. METHODS: This is an institutional review board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study of 147 patients (mean age, 62.4 years; range, 28-89 years; 94 men) with 144 cystic renal masses (93 benign, 51 RCC); 69 were pathology proven (51 RCC, 18 benign), and 75 were considered benign based on more than 4 years of stability at follow-up imaging. Using a single image from a contrast-enhanced abdominal computed tomography scan, mean, SD, mean value of positive pixels, entropy, skewness, and kurtosis radiomics features were extracted. Random forest, multivariate logistic regression, and support vector machine models were used to classify each mass as benign or malignant with 10-fold cross validation. Receiver operating characteristic curves assessed algorithm performance in the aggregated test data. RESULTS: For the detection of malignancy, sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve were 0.61, 0.87, 0.72, 0.80, and 0.79 for the random forest model; 0.59, 0.87, 0.71, 0.79, and 0.80 for the logistic regression model; and 0.55, 0.86, 0.68, 0.78, and 0.76 for the support vector machine model. CONCLUSION: Computed tomography texture-based machine learning algorithms show promise in differentiating benign from malignant cystic renal masses. Once validated, these may serve as an adjunct to radiologists' assessments.