bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic Accuracy of Different Screening Tools for Identifying Osteoporosis Risk Among Post-Menopausal Filipino Women Aged 45–65 Years
Authors: Alcantara Danga Justiene Mia Klarisse , Lim Steven Johnson , Sulit Jacquelyn , Pacheco Elizabeth P 
Published: May 2021

Abstract
Early screening of osteoporosis decreases fracture risk. Several identified clinical risk factors led to the development of screening tools to estimate osteoporosis risk. Bone Mineral Densitometry (BMD) as a diagnostic tool for screening is not practical because of high cost and poor availability. The extensively studied osteoporosis screening tools are: Simple Calculated Osteoporosis Risk Estimation (SCORE), the Osteoporosis Risk Assessment Instrument (ORAI), the Age Bulk One or Never Estrogen (ABONE), body weight (WEIGHT), and the Osteoporosis Risk Index (OSIRIS). These tools were developed and validated in Caucasians. Validation of these tools for specific populations is necessary because of the observed variations in BMD across geographic and ethnic groups. To date, the utility of these screening tools in the Philippines is unknown. We conducted a cross-sectional analysis of all patients who underwent BMD screening for osteoporosis in a tertiary hospital from January 2015 to September 2020. The study participants were postmenopausal Filipino women aged 45 to 65 years. The subjects had no history of osteopenia, osteoporosis, hip or spine fractures, use of osteoporosis medications, renal insufficiency, bilateral oophorectomy, hysterectomy, or early menopause. We identified demographic and clinical risk factors. These risk factors were used to calculate the risk score of five osteoporosis risk assessment tools: ORAI, ABONE, WEIGHT, OSTA, and ORISIS. Using the DEXA T-score as an external criterion, the sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and diagnostic accuracy for each tool were calculated. Included were 1869 subjects with a mean age of 57.9 + 4.3 years old. Osteoporosis, with a T-score of &lt;-2.5 at the lumbar or femoral neck area, was seen in 665 (35.58%). Risk factors such as weight, height, BMI, menopausal years, history of previous fractures, and intake of oral calcium supplements correlated significantly with a higher risk (OR=1.025, 95%CI: 0.974–1.079; OR=1.059, 95%CI: 0.84–1.338; OR=1.063, 95%CI: 0.817–1.383; OR=1.74, 95%CI: 1.198–2.528; and OR=1.088, 95%CI: 0.869–1.319), of having osteoporosis in the said population. ORAI and WEIGHT have the highest probability of identifying patients with a sensitivity of 88.42% and 91.28%, and accuracy of 85.71% and 87.98%. Both performed equally in screening for osteoporosis in this setting. However, ABONE, OSTA, and ORISIS underestimated the number of high-risk osteoporosis patients, because of their low sensitivity and diagnostic accuracy. Both ORAI and WEIGHT are simple and easy to calculate and can serve as an initial screening tool to identify Filipino postmenopausal women who are at high risk for osteoporosis. A prospective study with a correlation of fracture occurrences may provide evidence for the value of these tools as a screening test.
Factors Associated With Inadequate Response to Bisphosphonate Therapy in Patients With Osteoporosis in Real-Life Clinical Practice: a Single-Center Retrospective Analysis of 300 Patients
Authors: Valadares Luciana Pinto , de Araujo Ferreira Bruno Silva , Cunha Bernardo Matos , Moreira Larissa Aniceto , Albinati Batista Frederico Gideoni , Hottz Cristiane Fonseca , Rafael Magalhaes Gabriel Galvao , Rodolpho Ramalho Sergio Henrique 
Published: May 2021

Abstract
Introduction: Bone mineral density (BMD) measurement by dual X-ray absorptiometry (DXA) is a useful tool to monitor response to osteoporosis treatment in clinical practice. Despite bisphosphonates therapy, some patients may exhibit bone loss during treatment for different reasons. These patients may have greater fracture risk than responders and may have unrecognized secondary causes that require further attention and treatment. Objectives: To identify factors associated with inadequate response (IR) to bisphosphonates therapy in patients with osteoporosis in real-life clinical practice. Methods: This is a single-center case-control study of patients with osteoporosis treated with bisphosphonates as recommended. Baseline and follow-up (12–24 months/apart) DXA scans were performed on same device (GE-Lunar Prodigy). IR was defined as loss of BMD greater than the least significant change (LSC) on the follow-up DXA. Clinical, biochemical and densitometric parameters of patients with IR were compared to responders using t-test or Mann-Whitney test (continuous), or chi-square test (categorical variables), as appropriated. We used logistic regression to assess the association magnitude between exposures and IR. Results: From 300 patients included from 2014 to 2018 (13% males, mean age 68 ±10 years), 198(66%) were treated with oral bisphosphonates and 102(34%) with zoledronic acid (ZA). IR was observed in 44(15%) patients. All parameters were similar at baseline, except for greater prevalence of oral bisphosphonates (82% vs 63%, p=0.016) and anticonvulsants use (18% vs 7%, p=0.015) in patients with IR compared to responders. Additionally, patients with IR exhibited a lower % change in CTX following therapy in comparison to responders (median -37% [IQR -68; -16%] vs -57% [-74; -32], p=0.029, respectively), and higher serum CTX levels after treatment (median 236pg/mL [IQR 162; 344] vs 165pg/mL [119; 254], p=0.004). The likelihood of IR was greater with oral bisphosphonates then with ZA (OR 2.61, IC95% 1.16–5.81, p=0.002), and with anticonvulsants use (OR 2.94. IC95% 1.19–7.25, p=0.019). The association with IR persisted for both variables (p≤0.01), when accounted simultaneously in the same model, along with age and gender. Conclusion: Inadequate bisphosphonate response was present in 15% of individuals, which was independently associated with anticonvulsant use and particularly among those on oral bisphosphonate therapy rather than ZA. This knowledge may help to clinically identify potential modifiable factors related to unresponsiveness and to optimize treatment accordingly.
Impact of Measuring Bone Mineral Density at Bilateral Hip
Authors: Singh Abhilasha , Sharma Anu 
Published: May 2021

Abstract
Osteoporosis is a systemic disease characterized by low bone mineral density (BMD) leading to an increased risk of fracture. The current guidelines vary regarding the measurement of BMD at unilateral versus bilateral hip. We hypothesized that a discordance exists between bone densities measured at both hips and that patients undergoing unilateral hip imaging are at risk for under diagnosis. A retrospective chart review was performed to include all patients age 18 years and older, who underwent bone density measurement in 2019 at a single center using Hologic densitometer. Data gathering included BMD and T- scores at bilateral hip for all postmenopausal women and men above the age of 50 yrs. The continuous variables were expressed as means with standard deviation for normal distribution and analyzed with a two-sample t-test. Multiple regression analysis was used to test the effect of underlying medical conditions on T-score at bilateral hips. For all analyses, a p-value of &lt;0.05 was considered significant. 150 patients were included in the study (127 females and 23 males) with a mean age at imaging of 65.2 + 9.7 years and body mass index (BMI) of 27.2 + 6.1 kg/m2. 9% (n=14) of patients were observed to have discordance between T scores at both hips, out of which 13 individuals would have been underdiagnosed if one side was measured alone. There was a significant difference between mean BMD at total hip (left hip 0.84 + 0.14 g/cm2 vs right hip 0.82 + 0.14 g/cm2; p&lt;0.05). Among individuals with discordant T scores, a positive correlation was observed with BMI at the left femoral neck (r= 0.54, p= 0.04). Results: of multiple regression analysis showed that 67% of variation in the T score at right femoral neck could be accounted for by underlying medical conditions. Appointment duration and cost were unchanged when scanning unilateral or bilateral hip, 30 minutes, and $250 respectively. In summary, scanning bilateral hips provides treatment opportunities for patients who would otherwise be underdiagnosed without an additional increase in cost.
Use Machine Learning Methods to Explore the Associated Risk Factors of Osteoporosis or Bone Loss in Chinese People With Type 2 Diabetes: A Clinical Prediction Model
Authors: Mao Yaqian , Liang Jixing , Lin Wei , Wen Junping , Chen Gang 
Published: May 2021

Abstract
Objective: This study aimed to use machine learning (ML) methods to explore the risk factors associated with OP and bone loss in the Chinese T2DM population, so as to construct useful clinical prediction models. Methods: This was a two-center, retrospective study. The data came from a chronic disease epidemiological investigation database conducted in Ningde City and Wuyishan City, Fujian Province, China from March 2011 to December 2014. Finally, 798 T2DM patients who met the enrollment criteria were included in the final analysis. In order to control gender as a confounding factor that affects the results, we constructed two clinical prediction models based on different genders. We used the least absolute shrinkage and selection operator (LASSO) algorithm to filter relevant feature variables. The selected characteristic variables were modeled by logistic regression (LR), and clinical nomograms were used for more intuitive expression. The stability, clinical applicability and recognition of the model were evaluated by C-index, receiver operating characteristic (ROC) curve, calibration chart and decision curve analysis (DCA). Internal verification was achieved through bootstrapping validation. Results: In exploring the related risk factors of OP or bone loss in female T2DM patients. There were a total of 9 related predictors, namely age, marital status, glutamyl transpeptidase, fracture, coronary heart disease, fruit-flavored drinks, moderate-intensity exercise, menopause and nap time were determined by LASSO analysis from a total of 69 variables. The model we constructed using these 9 related predictors showed medium prediction ability (C-index value: 0.738, 95%CI[0.692, 0.784]), the C-index in bootstrapping validation was 0.714, and the area under the ROC curve (AUC) was 0.738. The DCA showed that if the risk threshold was between 4% and 100%, the nomogram could be used clinically. In exploring the related risk factors of OP and bone loss in male T2DM patients. A total of 12 related predictors were identified from 65 variables through LASSO analysis, including age, marital status, fasting serum insulin, alanine aminotransferase, coronary heart disease, respiratory diseases, diabetic retinopathy, seafood, desserts, fruit-flavored beverages, coffee, high-intensity exercise. The model we constructed using these 12 related predictors showed medium prediction ability (C-index value: 0.751, 95%CI[0.694–0.808]), the C-index in bootstrapping validation was 0.704, and the AUC value was 0.751. The DCA showed that if the risk threshold was between 3% and 68%, the nomogram could be used clinically. Conclusion: We explored the associated risk factors of osteoporosis or bone Loss in Chinese people with type 2 diabetes, and developed a risk nomogram with moderate predictive power. The nomogram can help clinicians and patients make joint decisions before treatment.
Assessment of Hypercalcemia Management at an Academic Institution
Authors: Nagelberg Jodi , Hakim Robert , Kimura Brad , McCowen Karen C , Block Shanna 
Published: May 2021

Abstract
Background: Currently, there is no widely accepted clinical practice guideline for the management of severe hypercalcemia in hospitalized patients.
Objective: The purpose of this project was to analyze management of hypercalcemia in hospitalized patients at an academic medical center, then establish and implement a clinical practice guideline for hypercalcemia treatment.
Design: Retrospective chart review of all patients admitted for management of hypercalcemia over 37 consecutive months.
Setting: Urban academic tertiary referral center
Measurements: We examined which calcium- lowering medications were used, how often 2 medications were needed, average time to normocalcemia, incidence of hypocalcemia post treatment, serum phosphorus nadir and serum creatinine peak. We also assessed medication appropriateness (dose and frequency).
Results: Seventy-two patients were included; 58 patients with hypercalcemia of malignancy and 14 patients with hypercalcemia of other diagnoses. In the malignancy group the most common treatment was a combination of calcitonin + bisphosphonate (43%), followed by bisphosphonate alone (29%) and calcitonin alone (24%). In the non-malignancy group, calcitonin alone was used in 50%, calcitonin + bisphosphonate in 21% and a bisphosphonate alone in 14%. Denosumab was rarely used in both groups. The median time to normocalcemia was 3.0 days irrespective of diagnostic group. Seventy two percent of the patients with malignancy and 86% of the non-malignancy group achieved normocalcemia. The incidence of hypocalcemia was 21% (12/58) in the malignancy subgroup and 29% (4/14) in the others after treatment. Serum creatinine did not change from baseline to post-treatment in either population. Median serum phosphorus dropped from 2.9 mg/dL to 1.8 mg/dL in the malignancy group and 4.2 mg/dL to 2.1 mg/dL in the non-malignancy group. Only 41% of patients that received calcitonin, were given recommended dose, route, and frequency.
Conclusion: Based on the results of this study, a hypercalcemia treatment guideline was developed, highlighting appropriate medication dose and frequency. This guideline recommends zoledronic acid alone for asymptomatic malignancy patients, and in combination with calcitonin for symptomatic patients. In contrast, calcitonin alone is considered first line for non-malignant conditions.
Rare Case of Severe Hypercalcemia Secondary to Atypical Sestamibi Negative Parathyroid Cystic Adenoma
Authors: Gusov Timur , Liu John Chen , Naha Sowjanya , Marium F N U , Parimi Joseph Theressa Nehu , Gundluru Rajani , Syed Hasan 
Published: May 2021

Abstract
Primary hyperparathyroidism (PHPT) is defined as excessive secretion of parathyroid hormone (PTH) originating from the parathyroid gland. The most common cause is a single parathyroid adenoma which is typically solid. Cystic parathyroid adenomas (CPA) are the cause of about 1–2% of cases of primary hyperparathyroidism. It is known that cystic parathyroid adenomas are a result of degeneration of an existing parathyroid adenoma. SestaMIBI is an imaging study based on uptake of radioactive technetium99 and used to localize parathyroid adenomas. We describe an unusual case of severe hypercalcemia secondary to 99mTc sestaMIBI negative atypical parathyroid cystic adenoma. A 56-year-old male presented to our facility with nausea and vomiting. His past medical history included hypertension and hepatitis C with no history of fractures or kidney disease. Physical examination was normal. Upon admission the patient was afebrile with blood pressure of 170/120 mmHg and heart rate of 62 bpm. Chemistry showed Calcium of 14.5 mg/dL (8.6–10.2mg/dL), phosphorus 2.2 (2.7–4.5) mh/dL, magnesium 1.8 (1.7–2.6)mg/dL, intact PTH of 375 (15–65) pg/mL, PTH-related peptide &lt;2.0 pmol/L(&lt;2 pmol/L), 25-OH vitamin D of 19 ng/ml (30–80), Creatinine 1.22 (0.7–1.2)mg/dL, alkaline phosphatase 95 (40–129) units/L. He was started on aggressive hydration, calcitonin 4 units/kg, 4 mg of IV Zolendroninc acid. Neck sonogram revealed a large, complex, predominantly anechoic lesion with solid vascular components and thick internal septations in the inferior and medial aspect of the right thyroid lobe measuring 3 x 2 x 5.5 cm. Findings were confirmed with CT of the neck. Since Sestamibi scan (planar and SPECT/CT) did not show uptake in parathyroid glands, the cyst was thought to be of thyroid origin. Fine needle aspiration was not able to detect cellular material, but PTH was &gt;100 pg/ml on the FNA sample. Otolaryngology service was consulted for parathyroidectomy. During the surgical treatment, the right upper parathyroid gland was removed with no changes in serum PTH. Next, the cystic lesion was removed with normalization of serum PTH (from 218 pg/ml to 35.2 pg/ml respectively). Intraoperative frozen section analysis was read as a cystic parathyroid adenoma. The final pathology report revealed cystic parathyroid tissue favoring parathyroid adenoma with focal atypia. Hypercalcemia resolved. Conclusions: Atypical cystic parathyroid adenomas are a rare cause of PHPT. 90% of parathyroid cysts are nonfunctional. Above mention is a case of a patient presenting with hypercalcemic crisis secondary to cystic parathyroid adenoma, which posed a diagnostic challenge as both neck ultrasound and 99mTc sestaMIBI scan were inconclusive. These findings should trigger suspicion for functional parathyroid lesions. Cystic components should be evaluated for PTH levels and if significantly elevated should be treated as a parathyroid adenoma.
The Calcium-Sensing Receptor (CaSR) Variants at rs1801725 Increase the Risk of Developing Secondary Malignant Cancers
Authors: Beasley Heather K , Actkins Ky’Era , Annika Faucon , Davis Lea , Sakwe Amos M 
Published: May 2021

Abstract
The dysregulation of systemic calcium homeostasis during malignancy is common in most patients with high-grade tumors. The associated comorbidity is known as cancer-induced hypercalcemia (CIH) which affects up to 30% of cases, in the absence of metastasis. In the course of breast cancer progression, the secretion of parathyroid hormone-related protein (PTHrP) by tumor cells and the associated destruction of bone tissues, leads to a progressive increase in systemic calcium or CIH. The increase in circulating Ca2+ is sensed by the calcium-sensing receptor (CaSR), which plays a significant role in maintaining Ca2+ homeostasis. More than 200 mutations and single nucleotide polymorphisms (SNPs) in the CaSR gene have been described, including the A986S CaSR at rs1801725 and Q1011E CaSR at rs1801726 SNPs with reduced sensitivity to Ca2+. Interestingly, high circulating Ca2+ is associated with aggressive breast tumors in premenopausal women and larger tumors in postmenopausal women; however, the contribution of the CaSR in breast cancer progression remains poorly understood. Unlike SNPs at rs1801726, up to 20% of breast cancer patients with SNPs at rs1801725 may be predisposed to higher circulating Ca2+ in the course of their disease. Since breast cancer frequently metastasizes to Ca2+ rich skeletal tissues, we hypothesize that the development of CIH and subsequent desensitization of the CaSR by sustained high Ca2+ is critical for both the adaptation of TNBC cells to CIH in Ca2+ rich microenvironments and TNBC progression. Our preliminary data reveal that the expression level and mutational status of the CaSR is cell type-specific, and that sustained high Ca2+ desensitizes the receptor, but promotes tumor cell growth and motility. Sustained high Ca2+ also triggers the expression of metastasis promoting genes, including the cancer/testis antigen, MAGEC2, and Plasminogen Activator Inhibitor, PAI-2, potentially via the early response genes FOS/FOSB. In addition, our preliminary data show that the A986S SNP is associated with hypercalcemia, secondary malignancy of bone and respiratory organs, and deficiency of humoral immunity. This study provides novel insights into not only the adaptation of TNBC cells to high circulating Ca2+, but also suggests that mutations of the CaSR at rs1801725 are predictive of the likelihood for metastasis to lungs and bone.
Circulating Lipocalin-2 Predicts Changes in Lumbar Spine Bone Mineral Density After Parathyroidectomy in Primary Hyperparathyroidism
Authors: Lee Seunghyun , Hong Namki , Kim Kyoung Jin , Jeong Jong Ju , Rhee Yumie 
Published: May 2021

Abstract
Lipocalin-2(LCN2), known as neutrophil gelatinase-associated lipocalin is known to a regulator of bone homeostasis. Upregulation of LCN2 in mice reduces osteoblast differentiation and stimulates the NF-kB pathway, promoting osteoclastogenesis. High serum LCN2 level was associated with elevated risk of fracture-related hospitalization in elderly women. Bone mineral density(BMD) of primary hyperparathyroidism(PHPT) patients tends to recover after parathyroidectomy, but with different extent. Whether circulating LCN2 can predict the extent of BMD recovery after parathyroidectomy in PHPT remains unclear. Clinical data and preoperative serum samples obtained from 35 PHPT patients (women n=30) who underwent parathyroidectomy at Severance hospital, Seoul, Korea between 2016 and 2019 were analyzed. Among 35 patients, 25 patients underwent BMD before surgery and two years after surgery. LCN2 was measured using enzyme-linked immunosorbent assay kit (DLCN20, R&D Systems, USA). Primary outcome was two-year lumbar spine BMD change (%). Mean age of study subjects was 57±13 years. Calcium and parathyroid hormone (PTH) levels restored to normal range after parathyroidectomy in all subjects (calcium [mean 8.7±0.4mg/dL]; PTH [median 33.3], 25.9 to 47.4 pg/mL). Baseline BMD of lumbar spine(LS), femoral neck(FN), and total hip(TH) were 0.776±0.177 g/cm2, 0.578±0.138 g/cm2, and 0.695±0.150 g/cm2, respectively. At 1 year after parathyroidectomy, BMD increased up to 5.5%, 6.1%, and 4.5% at LS, FN, and TH, respectively. At 2 years after parathyroidectomy, BMD increased up to 8.6%, 7.6%, and 7.2% at LS, FN, and TH, respectively. Log-transformed LCN2 at baseline showed positive correlation with LS BMD changes (%) after 2 years (β Coefficient = 3.46, 95% CI = 0.83 to 6.10, p-value = 0.012). In multiple linear regression model, one log-unit increment in LCN2 was associated with 4.7 percent point increase in LSBMD at two years after parathyroidectomy (adjusted β=4.72, 95% CI = 1.62 to 7.82, p-value = 0.005) after adjustment of PTH, creatinine level, and body mass index. This result remained robust for 3 year change in LSBMD (in subgroup, n=14; adjusted β=4.70, 95% CI = 0.9 to 8.5, p-value = 0.021). In conclusion, preoperative high circulating LCN2 level was associated with more LSBMD gain after parathyroidectomy in patients with PHPT.