Regional Bone Research Articles

5120 Contribution Of Proximal Femur Geometry And Bone Density Distribution To Hip Fragility In Adults ≥ 50yrs With Longstanding Type 1 Diabetes

Abstract Disclosure: F. Johannesdottir: None. C. D’Mello: None. A.B. Murthy: None. B. Zahedi: None. K. Engelke: None. M.L. Bouxsein: None. E.W. Yu: Grant Recipient; Self; Amgen Inc. Introduction: Adults with type 1 diabetes (T1D) have a 6-fold increased risk of hip fracture, which is explained only in part by lower areal bone mineral density (aBMD) by DXA. We hypothesize that femoral geometry and regional bone deficits at the proximal femur contribute to higher hip fracture risk in older adults with T1D. Further, we determine the influence of age at T1D diagnosis on femoral bone density and structure. Methods: We enrolled 97 individuals with T1D and 53 non-diabetic controls (CON) as part of the T1D Bone Health Connection (BEACON) Study, an ongoing prospective study of adults aged ≥50 years. We obtained computed tomography (CT) scans of the proximal femur (in-plane pixel size 0.98x0.98 mm, 1.25 mm slice thickness) to measure total (Tt), trabecular (Tb) and cortical (Ct) volumetric BMD (vBMD); and volume (Vol) and Ct thickness (Th) in several regions, including total hip, femoral neck (FN), trochanter (TR) and intertrochanter (IT) (Medical Image Analysis Framework, University of Erlangen, Germany). We also assessed total hip and FN aBMD by DXA. We employed ANCOVA models to compare bone outcomes between T1D and controls with adjustment for age, height, and weight, stratified by sex. When comparing bone outcomes within T1D, we adjusted for age, height, weight, and sex. Differences are reported as % difference between the least-square means for the groups. Results: The average age of participants was 64±7 yrs, and similar between T1D and CON (p=0.21). Male T1D were shorter than male CON (173 cm vs 176 cm, p=0.05), but with similar weight (p=0.73). Female T1D were heavier than female CON (71 kg vs 64 kg, p=0.03). The T1D cohort included 50 men and 47 women with mean diabetes duration of 46±10 yrs, mean A1c 7.1±1.0%, and median age at onset 17 yrs (IQR:10-25). Among T1D, 31 (52% female) were diagnosed ≤ age 12. Among men, total hip and FN aBMD did not differ by group, but T1D had smaller FN Tt.Vol (9%) and FN width (8%) (p<0.05 for all). In contrast, there were no differences between T1D and CON in the female cohort, neither by DXA nor CT (p≥0.13). Of note, T1D men appeared to have more poorly controlled diabetes than women (29% of men vs 11% women had A1c ≥8%, p=0.03). Within T1D, those who were diagnosed ≤ age 12 had lower Tb.vBMD (16-18%) at the total hip, TR and IT regions (p<0.05) and tended to have lower Tb.vBMD (16%, p=0.06) at the neck compared to those diagnosed at a later age, but no differences in DXA aBMD (p>0.31). Conclusion: In sum, older men, but not women, with T1D showed some deficits in bone structure at the proximal femur. Adults with T1D who were diagnosed ≤ age 12 had trabecular bone deficits within the proximal femur. Additional studies are needed to identify mechanisms underlying the high hip fracture risk in T1D. Presentation: 6/1/2024

Potential Effects of Lifelong Team Handball and Football Training and Nutritional Habits on Bone Health and Body Composition in Elderly Women.

The aim of this study was to evaluate the effects of lifelong team handball/football training on regional bone health and body composition in elderly women. Seventeen elderly women team handball/football players (65.9 ± 5.7 years) and twenty-one untrained age-matched women (controls) (67.7 ± 5.1 years) participated. Whole-body and regional dual-energy X-ray absorptiometry scans of arms, legs, and lower spine (L1-L4) were performed. We observed 8% and 9% higher bone mineral density (BMD) and bone mineral content (BMC), respectively, at the whole-body level and in the legs and 11.5% higher BMC in the legs in team handball/football players compared to untrained age-matched controls (p < 0.05). Higher total and leg lean body mass (p < 0.05), along with lower total body fat percentage (p < 0.05) and higher T- and Z-scores, markers of fragility risk fracture (0.294 ± 1.461 vs. -0.538 ± 1.031; 1.447 ± 1.278 vs. 0.724 ± 0.823, respectively), were also found in team handball/football players compared to controls (p < 0.05). No significant differences in nutritional habits were observed between groups. Our study suggest that the beneficial effects of lifetime handball/football practice on bone preservation in elderly women occur independently from nutritional intake, which emphasize the potential role of team sports in osteoporosis prevention. Future studies should focus on the cofounding factors and causative mechanisms mediated by team sport practice in osteoporosis prevention.

The potential effect of romosozumab on perioperative management for instrumentation surgery.

Age-related changes in bone health increase the risk for complications in elderly patients undergoing orthopedic surgery. Osteoporosis is a key therapeutic target that needs to be addressed to ensure successful instrumentation surgery. The effectiveness of pharmacological interventions in orthopedic surgery, particularly the new drug romosozumab, is still unknown. We aim to evaluate the effect of 3-month romosozumab treatment on biomechanical parameters related to spinal instrumentation surgery, using the Quantitative Computed Tomography (QCT)-based Finite Element Method (FEM). This open-labeled, prospective study included 81 patients aged 60 to 90 years, who met the osteoporosis criteria and were scheduled for either romosozumab or eldecalcitol treatment. Patients were assessed using blood samples, dual-energy absorptiometry (DXA), and QCT. Biomechanical parameters were evaluated using FEM at baseline and 3 months post-treatment. The primary endpoints were biomechanical parameters at 3 months, while secondary endpoints included changes in regional volumetric bone mineral density around the pedicle (P-vBMD) and vertebral body (V-vBMD). Romosozumab treatment led to significant gains in P-vBMD, and V-vBMD compared to eldecalcitol at 3 months. Notably, the romosozumab group showed greater improvements in all biomechanical parameters estimated by FEM at 3 months compared to the eldecalcitol group. Romosozumab significantly increased the regional vBMD as well as biomechanical parameters, potentially offering clinical benefits in reducing post-operative complications in patients with osteoporosis undergoing orthopedic instrumentation surgery. This study highlights the novel advantages of romosozumab treatment and advocates further research on its effectiveness in perioperative management.

The Pediatric Ankle: Normal Variations and Maturation-Dependent Pathology.

The pediatric ankle can present a broad range of normal variation and pathology unique to certain stages of development. Understanding the expected age ranges of ossification and fusion about the ankle is essential to provide accurate diagnoses regarding skeletal integrity. This conclusion has been well characterized radiographically and is supported by cadaveric research.The range of appearances on magnetic resonance imaging has also been well described. Knowledge about the structure of the periosteum and perichondrium aids in image interpretation as well as explaining typical injury patterns. The expected appearance of the physis and regional bone marrow signal is also of utmost importance.Ultrasonography is a valuable tool in pediatric musculoskeletal imaging but is limited when there is concern for intra-articular pathology. Computed tomography tends to be reserved for preoperative evaluation. We describe normal variation and maturation-dependent pathology of the pediatric ankle with an emphasis on imaging considerations.

Bodyweight influences the relationship between serum testosterone and bone mineral density in men with spinal cord injury.

Cross-sectional study. To examine the association between serum testosterone levels (T levels) and bone mineral density after spinal cord injury (SCI). Medical research center. Body composition assessments were measured in 53 men with chronic SCI. Serum T levels were measured after an overnight fast. Total and regional bone mineral density (BMD) and bone mineral content (BMC) were measured using dual-energy X-ray absorptiometry. Participants were classified into three groups based on their body weight [<65 kg, 65-80 kg, >80 kg] or serum T levels into low (400 ng/dl), mid-normal (401-544 ng/dl) and normal (>545 ng/dl) ranges. Serum T level was negatively related to body weight (r = -0.33, P = 0.016), fat mass (r = -0.46, P < 0.001) and percentage fat mass (r = -0.48, P < 0.001). There were no significant relationships between serum T levels and any of the bone health measurements. Body weight was related to total, regional (P < 0.01 for both) and knee BMD (P < 0.05). T level was only related to total and regional BMD in the group with body weight of 65-80 kg. Testosterone has no direct relationship with BMD except within a specific weight group. However, body weight or fat mass negatively influences circulating T levels in men with SCI. The relationship between serum T levels and BMD is mediated by body weight in men with SCI.

Muscle-to-Bone Ratio in NCAA Division I Collegiate Football Players by Position.

Dengel, DR, Studee, HR, Juckett, WT, Bosch, TA, Carbuhn, AF, Stanforth, PR, and Evanoff, NG. Muscle-to-bone ratio in NCAA Division I collegiate football players by position. J Strength Cond Res 38(9): 1607-1612, 2024-The purpose of this study was to compare the muscle-to-bone ratio (MBR) in National Collegiate Athletic Association Division I football players (collegiate football players [CFP]) to healthy, age-matched controls. In addition, we examined MBR in CFP by position. A total of 553 CFP and 261 controls had their total and regional lean mass (LM), fat mass (FM), and bone mineral content (BMC) determined by dual x-ray absorptiometry (DXA). College football players were categorized by positions defined as offensive linemen (OL), defensive linemen (DL), tight end, linebacker (LB), running back (RB), punter or kicker, quarterback (QB), defensive back (DB), and wide receiver (WR). There were significant differences between CFP and controls for total LM (80.1 ± 10.0 vs. 56.9 ± 7.8 kg), FM (22.2 ± 12.5 vs. 15.2 ± 7.1 kg), and BMC (4.3 ± 0.5 vs. 3.1 ± 0.5 kg). Although there were significant differences in body composition between CFP and controls, there was no significant differences in total MBR between CFP and controls (18.6 ± 1.4 vs. 18.8 ± 1.7). Regionally, CFP had significantly lower trunk MBR than controls (26.7 ± 2.7 vs. 28.7 ± 4.2), but no difference was seen in leg or arm MBR. Positional differences in CFP were noted as total MBR being significantly higher in DL (19.0 ± 1.4) than in DB (18.1 ± 1.3), WR (18.1 ± 1.3), and LB (18.2 ± 1.3). OL had a significantly higher total MBR (19.2 ± 1.3) than DB (18.1 ± 1.3), LB (18.2 ± 1.3), QB (18.1 ± 1.0), and WR (18.1 ± 1.3). In addition, RB had significantly higher total MBR (18.8 ± 1.3) than DB (18.1 ± 1.3) and WR (18.1 ± 1.3). This study may provide athletes and training staff with normative values when evaluating total and regional MBR with DXA.

Rectal metastasis arising from breast cancer: a case report.

Breast cancer is the most common cancer among women worldwide. Breast cancer often metastasizes to the regional lymph nodes, bone, brain, liver, and lungs, whereas gastrointestinal tract metastases are rare. Herein, we present a rare case of rectal metastasis from breast cancer that occurred during palliative chemotherapy. A 69-year-old female with a history of invasive ductal carcinoma, negative for hormonal receptors and positive for human epidermal growth factor receptor 2 (HER2) receptor, underwent various treatments, including neoadjuvant chemotherapy, breast-conserving surgery, and adjuvant therapy. Eight months postoperatively, the patient experienced axillary lymph node recurrence, requiring palliative chemotherapy. Despite ongoing treatment, metastatic lesions were confirmed in the lungs and pleura. During palliative chemotherapy, the patient developed anal pain, and subsequent examination revealed an infiltrating rectal lesion. Despite histological confirmation of metastatic breast carcinoma and tubular adenoma, a multidisciplinary decision was made regarding palliative chemotherapy over surgical intervention. Eribulin was administered, but due to the patient's inability to tolerate the treatment, she passed away 3 months after rectal lesion diagnosis. Although breast cancer metastasis to the rectum is rare, clinicians should consider the possibility of rectal involvement and perform a digital rectal examination if anal symptoms are present.

Postoperative decrease in Hounsfield unit values at adjacent vertebrae after thoraco-pelvic fusion as a risk factor of proximal junctional kyphosis.

Proximal junctional kyphosis and failure is a common complication of adult spinal deformity surgery, with osteoporosis as a risk factor. This retrospective study investigated the influence of long thoracolumbar fusion with pelvic fixation on regional bone density of adjacent vertebrae (Hounsfield units on computed tomography) and evaluated the association between bone loss and the incidence of proximal junctional kyphosis and failure. Patients who underwent long thoracolumbar fusion (pelvis to T10 or above) or single-level posterior lumbar interbody fusion (control group) between 2016 and 2022 were recruited. Routine computed tomography preoperatively and within 1-2 weeks postoperatively was performed. Postoperative changes in Hounsfield unit values in the vertebrae at one and two levels above the uppermost instrumented vertebrae (UIV + 1 and UIV + 2) were evaluated. Overall, 127 patients were recruited: 45 long fusion (age, 73.9 ± 5.6 years) and 82 proximal junctional kyphosis and failure (age, 72.5 ± 9.3 years). Postoperative computed tomography was performed at a median [interquartile range] of 3.0 [1.0-7.0] and 4.0 [1.0-7.0] days, respectively. In both groups, Hounsfield unit values at UIV + 2 were significantly decreased postoperatively. In the long-fusion group, Hounsfield unit values at UIV + 1 and UIV + 2 were significantly lower in patients with proximal junctional kyphosis and failure (within 18 months postoperatively) than in those without proximal junctional kyphosis and failure. Proximal junctional kyphosis and failure and long thoraco-pelvic fusion negatively affect regional Hounsfield unit values at adjacent levels immediately after surgery. Patients with subsequent proximal junctional kyphosis and failure show greater postoperative bone loss at adjacent levels than those without.

Malignant Leydig Cell Tumor of Testis: Case Report

Testicular tumors accounts for % of the tumors in men. 5% of which are the sex cord stromal tumors and the remaining are of germ cell origin. Leydig cell are the common subtype of Sex cord stromal tumors and accounts for 1%-2% of all the testicular tumors. Tumor arises from the leydig cells that normally reside in the interstitium of testicles and secrete testosterone in the presence of leutenizing hormone. They show a bimodal distribution with peaks in the prepubertal age group and between 30-60yrs of age. Leydig cell tumor being a hormonally active tumor often presents with precocious puberty, breast tenderness and gynaecomastia. Histopathology reveals a well circumscribed mass .Cut surface shows golden brown homogenous appearance. Microscopically, tumor cells are large to polygonal with round to oval nucleus with deeply granular cytoplasm. Cytoplasm shows characteristics rod sghaped crystals referred to as “ crystalloids of Reinke”. Leydig cell tumors are mostly follow a benign course but approximately 5-10% of these have malignant potential. Regional lymph nodes, lungs , liver and bones are the commonest sites of metastsis. Due to aggressive difficult to treat nature of metastatic disease it is essential to differentiate benign leydig cell tumor from its malignant counterpart in order to guide its initial surgical and radiological management. Assessment of the clinicopathological features of Leydig cell tumor allows for its optimal management.

Primary thymic adenoid cystic carcinoma with high-grade transformation: A clinicopathological and immunohistochemical analysis of 4 cases

Four cases of a distinct carcinoma of the thymic gland are presented. The patients were 4 adult males with an age range from 40 to 47 years (mean, 43.5 years). Clinically, all patients presented with non-specific respiratory symptoms. None of the patients had any prior history of head and neck neoplasm or surgery in that anatomic area. Large anterior mediastinal masses were found on diagnostic imaging with concurrent metastatic disease to pleura, lungs, regional lymph nodes and bones. Microscopically, all tumors were composed of a solid proliferation of hyperchromatic, monomorphic small cells with focal cytoplasmic clearing embedded in a fibromyxoid stroma. In one case, occasional duct-like structures were identified. Immunohistochemically, the tumors were positive for pancytokeratin, CD117 and MYB and negative for myoepithelial markers. Systemic chemotherapy was initiated in all patients. Despite therapy, clinical follow-up revealed that all 4 patients died of their disease 11–23 months after their initial diagnosis. The cases in this series highlight a tumor that is different from conventional thymic carcinoma and that has the morphological and immunohistochemical features commonly seen in adenoid cystic carcinomas with high-grade transformation. Correct diagnosis is essential for patient management.

Endophenotypes of Primary Osteoarthritis of the Hip Joint in the Bulgarian Population over 60 Years Old.

Aim. To identify subgroups of patients with primary osteoarthritis of the hip joint (pHOA) with similar imaging and laboratory findings, disease evolution, and response to conventional therapies. Methods. We performed further statistical analyses on patient data from two published, double-blind, randomized, and placebo-controlled studies (DB-RCTs), which examined the effects of intra-articular corticosteroids (ia-CSs), hyaluronic acid (ia-HA)-KИ-109-3-0008/14.01.2014, and intravenous bisphosphonates (iv-BPs) -KИ- 109-3-0009/14.01.2014 compared to the country's standard pHOA therapy. The data span an 8-year follow-up of 700 patients with pHOA, including: 1. Clinical parameters (WOMAC-A, B, C, and T; PtGA). 2. Laboratory markers (serum calcium and phosphate levels; 25-OH-D and PTH, markers for bone sCTX-I and cartilage uCTX-II turnover). 3. Radiological indicators: X-ray stage (Kellgren-Lawrence (K/L) and model (Bombelli/OOARSI), width (mJSW), speed (JSN mm/year), and zone of maximum narrowing of the joint space (max-JSN)-determining the type of femoral head migration (FHM). 4. DXA indicators: bone geometry (HAL; NSA; and MNW); changes in regional and total bone mineral density (TH-BMD, LS-BMD, and TB-BMD). 5. Therapeutic responses (OARSI/MCII; mJSW; JSNmm/yearly) to different drug regimens (iv-BP -zoledronic acid (ZA/-5 mg/yearly for 3 years)); ia-CS 40 mg methylprednisolone acetate, twice every 6 months; and ia-HA with intermediate molecular weight (20 mg/2 mL × 3 weekly applications, two courses every 6 months) were compared to standard of care therapy (Standard of Care/SC/), namely D3-supplementation according to serum levels (20-120 ng/mL; target level of 60 ng/mL), simple analgesics (paracetamol, up to 2.0 g/24 h), and physical exercises. The abovementioned data were integrated into a non-supervised hierarchical agglomerative clustering analysis (NHACA) using Ward's linkage method and the squared Euclidean distance to identify different endophenotypes (EFs). Univariate and multivariate multinomial logistic regression analyses were performed to determine the impact of sex and FHM on clinical and radiographic regression of pHOA. Results. A baseline cluster analysis using incoming (M0) patient data identified three EFs: hypertrophic H-HOA, atrophic A-HOA, and intermediate I-HOA. These EFs had characteristics that were similar to those of patients grouped by radiographic stage and pattern ('H'-RPs, 'I'-RPs, and 'A'-RPs), p < 0.05). The repeated cluster analysis of M36 data identified four EF pHOAs: 1. Hypertrophic (slow progressors, the influence of the type of femoral head migration (FHM) outweighing the influence of sex on progression), progressing to planned total hip replacement (THR) within 5 (K/LIII) to 10 (K/LII) years. 2. Intermediate (sex is more important than the FHM type for progression) with two subgroups: 2#: male-associated (slow progressors), THR within 4 (K/LIII) to 8 years. (K/LII). 2* Female-associated (rapid progressors), THR within 3 (K/LIII) to 5 (K/LII) years. 3. Atrophic (rapid progressors; the influence of FHM type outweighs that of sex), THR within 2 (K/LIII) to 4 (K/LII) years. Each EF, in addition to the patient's individual progression rate, was also associated with a different response to the aforementioned therapies. Conclusions. Clinical endophenotyping provides guidance for a personalized approach in patients with pHOA, simultaneously assisting the creation of homogeneous patient groups necessary for conducting modern genetic and therapeutic scientific studies.

Assessment of regional and total skeletal metabolism using 18F-NaF PET/CT in patients with chronic kidney disease.

The study aims to assess regional and total bone metabolic activity in patients with chronic kidney disease using Na[18F]F PET and correlation between semi-quantitative indices and blood parameters. Seventy-two subjects (mean age 61.8 ± 13.8years) were included. Of these 24/72 patients had end-stage renal disease (ESRD) (GFR < 15mL/min/1.73 m2), 38/72 had chronic kidney disease (CKD) (GFR between 60 and 15mL/min/1.73 m2), and 10/72 were controls with normal renal function. All subjects underwent Na[18F]F PET-CT with a dose activity of 0.06mCi/Kg. Regional and total skeletal metabolism were assessed with mean SUVs in a skeletal volume of interest (VOI), bone to soft tissue index (B/S), global SUV mean (GSUV mean) of the whole bone, and uptake in the femoral neck. Statistically significant differences were observed in a number of 18F-NaF metrics like femoral neck metabolism in CKD and ERSD groups in comparison to control in right (P = 0.003) and left femur (P = 0.006), bone to soft tissue index in the femur (P = 0.016) and GSUV5 (P = 0.006). There is also a significant difference in SUV mean in lumbar vertebrae (L1-L4) among CKD, ESRD, and controls. There was a moderate correlation between 18F-NaF PET scan uptake and blood parameters such as ALP and PTH. Na[18F]F uptake parameters were significantly different in low versus high bone turnover state. The assessment of total skeleton and regional metabolism and bone turnover in CKD patients is feasible with Na[18F]F PET. Na[18F]F can help to detect early changes in bone metabolism and assess the progression of bone disease in this complex condition. Quantification with Na[18F]F PET might provide better assessment of the bone turnover. The difference in Na[18F]F uptake in CKD compared to controls is likely related to a change in bone turnover which, however, requires further validation.

Relationship between Femur Mineral Content and Local Muscle Strength and Mass.

Among the stimuli able to prevent early decreases in bone mineralization, exercise has a noticeable role per se as the source of mechanical stimulus or through lean tissue enlargement by its increasing of tensional stimulus. However, prevention strategies, including exercise, generally do not establish the moment in life when attention should begin to be paid to bone integrity, according to age group- and sex-related differences. Thus, this study analyzed the relationship between variables from the diagnosis of total and regional body composition, muscle strength, and bone mineral content (BMC) of femurs in young adult males. Thirty-four young Caucasian men (24.9 ± 8.6 years) had their body composition and bone density assessed by dual X-ray absorptiometry. The subjects performed a one-repetition maximum test (1-RM) in a bench press, front pulley, seated-row, push press, arm curl, triceps pulley, leg flexion, leg extension, and 45° leg press for the assessment of muscle strength in upper and lower limbs in single- and multi-joint exercises. Lean tissue mass in the trunk and upper and lower limbs were related to femoral BMC (Pearson coefficient ranging from 0.55 to 0.72, p < 0.01), and 1-RM values for different exercises involving both upper and lower limbs also correlated with femoral BMC (Pearson coefficients ranging from 0.34 to 0.46, p < 0.05). Taken together, these correlations suggest that muscle mass and strength are positively linked with the magnitude of femoral mass in men, even in early adulthood. Hence, the importance of an enhanced muscle mass and strength to the health of femoral bones in young adults was highlighted.

Abstract 4492: Deferiprone optimization for the treatment of triple-negative breast cancer

Abstract Triple-negative breast cancer (TNBC) is the leading cause of new cancer cases and the second leading cause of cancer deaths in American women disproportionately affecting Black and Hispanic women under 40. Currently, there is no targeted therapy for TNBC and treatment options to manage this lethal disease include surgery, adjuvant chemotherapy and radiotherapy. Among the chemotherapy agents, combination of the PARP inhibitors with DNA-damaging results in a more promising anti-tumor effect. A better understanding of TNBC etiology has aided in unraveling the roles of two additional cellular targets - androgen receptor (AR) and histone lysine demethylase (KDM) - in the viability and survival of TNBC. Interestingly, AR overexpression is the most important driver of prostate cancer (PCa). A class of current medications used to treat PCa act as androgen receptor (AR) antagonists (or antiandrogens). Antiandrogens are under investigation in the clinic as potential therapies for luminal AR (LAR) subtypes of TNBC, a particularly worrisome subtype that frequently metastasizes to regional lymph nodes and bones. Although LAR TNBC constitutes 15-20% of TNBCs, it is characterized by minimal response to chemotherapy and aggressiveness. It is therefore plausible to repurpose and optimize antiandrogens, in the context of designed multiple ligands; to obtain a TNBC-targeting therapy effective against several subtypes of this heterogenous disease, including the basal subtype that is responsible for ~80% of TNBC incidence. The proposed therapeutics are dual-acting antiandrogen-KDM inhibitors. The antiandrogen moiety of these agents will enable TNBC cell-targeting and translocation of the drug into the nucleus where inhibition of KDM will prevent transcription of KDMs that promote tumor growth. The three pharmacophores of these agents are (i) an AR binding group, (ii) a linker, and (iii) an iron-binding group. Two functional classes of these compounds, alkyl- and aryl-derivatives, vary in the design of the AR binding moiety. To optimize these agents, the methylene linker length is varied in each class for in vitro determination of the optimal length for increased drug efficacy. The compounds are tested on TNBC cell lines (MDA-MB-231, low AR+; and MDA-MB-453, high AR+), and ER+ BCa (MCF-7) while PCa cell lines (LNCaP PCa, AR+; and DU 145, PCa, AR-) serve as controls for AR dependency of the compounds. Longer linker length compounds exhibited low micromolar cytotoxicity and selectivity for AR+ TNBC and PCa cell lines. Further analysis of lead compounds in TNBC cells aided in understanding the effects on targets, transcriptomic effects via RNA sequencing analysis and the mechanism of action. Thus far, the designed dual-acting therapeutics have potential to revolutionize the design of anticancer drugs and improve treatment outcome for TNBC patients. Citation Format: Alexis Johnston, Adegboyega K. Oyelere. Deferiprone optimization for the treatment of triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4492.

Resistance training effects on pubertal children with a risk of developing pediatric dynapenia

PurposeMany modern-day children are at risk of pediatric dynapenia (muscle weakness). We examined the effects of a 12-week resistance training (RT) program on neuromuscular function and body composition parameters in pubertal children with a risk of dynapenia.MethodsTwelve children (13.4 ± 0.9 y) with dynapenia performed a progressive RT program consisting of knee extension and flexion, bench press, abdominal crunch, back extension, lateral pull-down, elbow flexion, and upright row (1–2 sets of 10–15 repetitions/exercise) twice/week for 12 weeks. Outcome measures included one-repetition maximum (1-RM) strength, maximal voluntary isometric contraction (MVIC) torque, rate of torque development (RTD), electromyographic (EMG) activity, muscle thickness (MT), muscle quality (MQ) assessed by echo intensity (MQEI) of the knee extensors and specific tension of MVIC torque to thigh fat-free mass (MQST), and total and regional body and bone composition assessed by dual-energy X-ray absorptiometry. Changes in the measures before and after the 12-week RT and associations among the measures were analyzed by linear mixed models.ResultsSignificant (p < 0.05) increases in 1-RM (63.9 ± 4.5%), MVIC torque (16.3 ± 17.8%), MT (18.8 ± 5.5%) and MQ (MQEI: -25.9 ± 15.2%; MQST: 15.1 ± 18.8%;) were evident from pre- to post-training. Total fat-free mass (FFM) increased by 2.3 ± 3.2% from baseline (p = 0.01), but no changes (p > 0.05) in the other measures were observed. Significant (p < 0.05) associations between the changes in 1-RM and/or MVIC torque and the changes in quadriceps MT, MQEI, MQST and total body FFM were evident.ConclusionsThe 12-week RT was effective for improving neuromuscular and body composition parameters, and thereby reversed the risk of pediatric dynapenia.

Enlarged Cervical Lymph Nodes as a First Presentation of Metastatic CA Prostate

Prostate cancer is one of the common cancers in the world. It often metastasizes to the regional lymph nodes, bones, lungs, pleura, liver, and adrenal glands but metastasis to supraclavicular lymph nodes is very uncommon. Cervical lymph node metastasis as the first clinical manifestation of the prostate carcinoma has been reported only a few times till date. We present an unusual case of a 70- year old male who presented with enlarged swellings on the left side of his neck and was diagnosed with carcinoma prostate.

Is Regional Bone Mineral Density the Differentiating Factor Between Femoral Neck and Femoral Trochanteric Fractures?

Background Osteoporosis is globally recognized as a prevalent bone disease, and proximal femoral fractures constitute a serious complication associated with it. In recent years, the frequency of hip fractures has increased rapidly, with ramifications that extend into the social and economic aspects of both patients' lives and healthcare systems. The primary goal of this study is to discover whether bone mineral density (BMD) in specific regions of the hip could be related to femoral neck or trochanteric fractures. Methodology This prospective cohort study employed dual-energy X-ray absorptiometry (DEXA) measurements on 70 individuals with proximal femoral fractures. The participants sought treatment at the emergency department of our unit for hip fractures and adhered to our predefined eligibility criteria. These criteria primarily included (i) age exceeding 60 years and (ii) a diagnosis of either femoral neck or trochanteric fracture attributed to (iii) a low-energy lateral fall and (iv) a previously established state of complete ambulation before the occurrence of the fracture. In this context, we recorded the BMD of the hip, as well as the BMD values of the upper and lower halves of the neck, trochanteric region, and diaphysis. For the comparison of the categorical variables, Pearson's χ2 criterion was used, whereas Student's t-test was applied for the comparison of means of quantitative variables across fracture types. Results No statistical differences were identified when comparing regional BMDs and T-scores with the fracture type. This conclusion was also reconfirmed concerning age, gender, and Tonnis classification. Only a moderate correlation was observed, demonstrating lower values of regional BMDs in women compared to men. Conclusions The inability of our study to establish a direct correlation between BMD measurements across diverse areas of the proximal femur underlines the imperative need for subsequent investigations. These studies should not only integrate more precise techniques for measuring and mapping the BMD of different hip regions but should also encompass a comprehensive examination that would consider both intrinsic and extrinsic characteristics of the proximal femur.

Reference centiles of bone mineral density, and body composition of lower limbs in children and adolescents for Hologic DXA Discovery model A.

Background: Regional Dual-energy X-ray absorptiometry (DXA) assessments are useful for patients where whole body measurements are not feasible due to positioning difficulties because of anatomic anomalies (e.g. severe scoliosis) and artifacts due to neuroorthopedic hardware. Until now, there is a lack of reference centiles of bone mineral density and body composition of lower limbs for the DXA device Hologic Discovery model A densitometer. The study aimed to generate age-and sex specific reference centiles of bone mineral content (BMC), bone mineral density (BMD), lean body mass (LBM), and fat mass (FM) of the lower limbs of children and adolescents of Hologic DXA system (Discovery model A). Methodology: Data from children and adolescents aged 8-20 years of the National Health and Nutrition Examination Survey (NHANES) of the years 2015-2018 were used to create age-specific and sex-specific reference centiles. Study population was subdivided into three ethnic groups (non-Hispanic Black, non-Hispanic White and Mexican-American). The LMS method was used to calculate the reference centiles. Study population was adjusted concerning the BMI. Results: A total of DXA scans of 769 non-Hispanic Black children (386 females), 937 non-Hispanic White children (447 females) and 692 Mexican-American children (370 females) were used to calculate age-specific and sex-specific reference curves. 881 DXA scans had to be excluded because of extreme BMI values of the study population, leaving 513 non-Hispanic Black (205 females), 346 Mexican-American children (179 females), 658 Non-Hispanic White (282 females) for statistical analysis and creating age-and sex specific reference centiles after BMI adjustment. Conclusions: We presented pediatric reference centiles for regional bone mineral density, bone mineral content, lean body mass and fat mass of the lower limbs which were age-and sex-specific for three ethnic groups (Mexican-American, non-Hispanic Black and non-Hispanic-White). The reference centiles can be used for the Hologic DXA system Discovery model A with the software version 3.2.

Navigating challenges: a case report on complications in clavicle fracture management with 'K' wire fixation

Orthopaedic metallic pins and wires are commonly used for the fixation of fractures and dislocations, with the shoulder girdle being one of the common areas for their application. Despite recent precautionary measures, complications related to migration of these devices into the pleural cavity continue to be reported. We present a case of a Kirschner wire (K-wire) migration from a left clavicle fracture to the first rib, highlighting the importance of vigilance and immediate intervention in such cases. A 35-year-old female, previously operated for a left clavicle fracture using K-wire and tension band wiring, presented with left shoulder and chest pain eight years later. Radiological investigations revealed a broken K-wire in the pleural cavity, with one portion near the acromio-clavicular region and the other at the posterior aspect of the first rib. Surgical intervention was performed, involving the removal of the K-wire from the chest cavity and clavicle, with subsequent patient recovery. The migration of orthopaedic pins and wires into the chest cavity is a rare but well-documented complication. Previous reports have demonstrated severe consequences, including cardiovascular complications and fatalities. Theories explaining wire migration include muscle action, shoulder mobility, negative intrathoracic pressure during respiration, regional bone resorption, gravitational forces, and even capillary action. To minimize such complications, subcutaneous K-wire ends should be bent, and restraining devices should be used. Close clinical and radiographic follow-up is essential until the pins and wires are removed after achieving the therapeutic goal. In case of migration, prompt removal is necessary to prevent fatal complications. This case report emphasizes the significance of vigilance and proper precautions when using orthopaedic pins and wires for shoulder girdle fractures. Timely intervention is crucial to mitigate severe complications associated with migration. Sharing experiences and lessons learned can contribute to the safer application of these fixation devices in orthopaedic practice.

Age-related variations in trunk composition and patterns of regional bone and soft tissue changes in adult Caucasian women by DXA.

We explored the regional variations in body composition with advancing age in healthy Caucasian females living in the Mediterranean area. The objectives of this study were to establish body composition values for the trunk in healthy women of a Greek origin and to evaluate the effects of aging on the distribution of truncal bone mass, fat mass (FM) and lean mass (LM). Body composition of the trunk and detailed analysis of its anatomical components-the ribs, the thoracic spine, the lumbar spine and the pelvis, and FM and LM ratios--were calculated in 330 women aged 20-85years, using DXA. Peak bone mineral density (BMD) of the trunk was attained between ages 30 and 33. The overall truncal BMD reduction with age was 20.7% (p < 0.001). Peak %LM of the trunk was achieved at age 20. The overall reduction of %LM with age for the trunk was 9.8% (p < 0.001). Peak %FM of the trunk was attained between ages 68 and 73, and the overall %FM reduction with age was 2.8% (p > 0.05). Multiple comparative analyses showed that the 51-60years age group was the landmark age for significant changes of truncal bone mass measures across all age groups (p = 0). For truncal LM and FM metrics, multigroup comparative analysis showed the turning point of significant changes in soft tissue was the 41-50 age bracket (p = 0 and p = 0, respectively). In Greek women, truncal %LM exceeded by far %FM across all ages (p = 0). Our results suggest that aging affects body composition of the trunk in ambulatory healthy women of a Greek origin differently, leading to menopausal loss of bone mass, senior adulthood loss of lean mass, and middle-age storage of fat mass. In adult women, these age-related associations between bone and soft tissue metrics on DXA exams carry implications for the attainment of optimal peak values and shifts in body composition overtime, impacting lifelong skeletal health.