bluuebunny/crossref_metadata_2025_split huggingface dataset:
7077 A Rare Case Of Hypophosphatasia Presenting With Osteoporosis In A Young Female Patient- Diagnostic Delay In Hypophosphatasia
Authors: Abdelmasih Randa , Ali Israa 
Published: October 2024

Abstract
Disclosure: R. Abdelmasih: None. I. Ali: None.
Introduction: Hypophosphatasia is a rare hereditary cause of secondary osteoporosis that affects 1/100.000 individuals. The rate of osteoporosis due to hypophosphatasia is probably underestimated as it likely goes undiagnosed in heterogeneous or milder cases. We present a case of Hypophosphatasia that presented initially with osteoporosis and went misdiagnosed for years with intermittent treatment of Bisphosphonate, luckily with no atypical fractures that prompted different course of management for osteoporosis. Case Presentation: A 44-year-old female with a history of rheumatoid arthritis and osteoporosis diagnosed 7 years prior and treated with intermittent bisphosphonate which was discontinued due to side effects including muscle aches and bone pains, presented to our endocrinology clinic to establish care for osteoporosis. Patient denied prior fractures. She reported jaw pain that is being evaluated by otolaryngology and a dentist. Family history is negative. DEXA scan showed Z scores of -1.1, -1.8, and -2.2 of the lumbar spine, femoral neck, and total femur respectively. Laboratory workup showed consistently low alkaline phosphatase (ALP) 25, 20, &lt;20 U/L (ref range 34-123), elevated Vitamin B6 of 167 nmol/L (ref range 20-125), normal parathormone, calcium, phosphate, Vit D, magnesium, and liver enzymes. Genetic testing was sent for Tissue non-specific alkaline phosphatase (TNALP). Hypophosphatasia was diagnosed based on clinical and laboratory findings, patient was started on Asfotase alfa. Clinical course is to be followed. Discussion: Hypophosphatasia is a rare hereditary disorder due to mutation of (TNALP). In normal induvial, TNALP breaks down pyrophosphate to phosphate. It also plays a role in transferring Vit B6 into the tissues. Hence, clinical presentation due to impaired calcium-phosphate hemostasis is broad including musculoskeletal pain, pseudofractues, dental abscess, and neurological symptoms (due to accumulation of Vit B6). The clinical picture varies depending on the heterogenicity of ALPL mutation. Genetic testing is not mandated to establish diagnosis, clinical presentation and laboratory testing including low ALP and elevated Vit B6 are sufficient. However, genetic testing and counseling are recommended for the patient’s sake and their family members. Antiresorptive bone therapy is contraindicated due to a further decrease of bone turnover with reported cases of increased risk of atypical femur fracture, Bone density is reported to improve with enzyme replacement therapy with bone-targeting recombinant alkaline phosphatase (Asfotase Alpha), if further treatment is needed, anabolic treatment is preferred. We present this case to shed light on such a rare disease to decrease rates of underdiagnosis or delayed diagnosis in young patients presenting with osteoporosis for prompt treatment and improved quality of life of these patients.
Presentation: 6/2/2024
7330 Acute Hypercalcemic Renal Failure As A Presenting Manifestation Of Primary Hyperparathyroidism Due To Atypical Adenoma
Authors: Gomes Kellyann M , Davydov Emily , Wu Lahiri Sharon 
Published: October 2024

Abstract
Disclosure: K.M. Gomes: None. E. Davydov: None. S.W. Lahiri: None.
Atypical parathyroid adenomas have uncertain malignant potential and are a rare cause of primary hyperparathyroidism. Compared to typical parathyroid adenomas, patients with atypical parathyroid adenomas have higher preoperative serum calcium and parathyroid hormone (PTH) levels. However pre-operative distinction between atypical parathyroid adenomas, typical adenomas and parathyroid carcinoma is challenging, and histological evaluation is needed for definitive diagnosis. A 59-year-old female with history of nephrolithiasis presented with syncope. Laboratory evaluation revealed a serum calcium of 21.3 mg/dL (8.2-10.2), creatinine of 2.35 mg/dL with GFR of 36 mL/min/1.723 m2, PTH of 3711 pg/mL (15-65), 25-hydroxy vitamin D of 12 ng/mL, phosphorus of 5.6 mg/dL (2.5-4.5). She incidentally tested positive for COVID-19. CT abdomen/pelvis demonstrated bilateral obstructive renal calculi requiring stent placement. Despite treatment with intravenous normal saline, 4 mg of zoledronic acid, two doses of 300 units of calcitonin, and cinacalcet 30 mg twice daily, repeat calcium and creatinine were 17.9 mg/dL and 3.64 mg/dL, respectively, and hemodialysis was initiated. CT neck and chest identified a 2.0 x 2.3 x 3.8 cm hypodense nodule inferior to the left thyroid lobe. A parathyroid planar scan with SPECT/CT showed uptake within the hypodense nodule. Bone scan did not reveal any disease. The enlarged left parathyroid gland was removed. Intra-operatively, PTH decreased to 302 pg/mL. Pathological evaluation of the left inferior parathyroid gland revealed a 4.2 cm partially encapsulated hypercellular neoplasm weighing 7.3 grams with increased mitotic activity and focally thickened fibrotic capsule and no extracapsular or vascular invasion consistent with atypical parathyroid adenoma. On postop day 4, her calcium declined to 7.1 mg/dL and PTH was 383 pg/mL. Calcium supplementation was initiated due to concern for hungry bone syndrome. On postop day 14, calcium increased to 10.3 mg/dL and supplementation was discontinued. Her calcium levels have remained normal without supplementation three months after surgery. Severe hypercalcemia causing renal failure is an uncommon manifestation of primary hyperparathyroidism. Preoperative differentiation of parathyroid carcinomas and parathyroid adenomas is difficult, but important since surgical management of these two distinct entities differs. Higher preoperative calcium and PTH levels and concomitant renal failure suggest parathyroid carcinoma. This case highlights the challenge of differentiating atypical parathyroid adenomas from parathyroid carcinoma since both conditions can present with severe hypercalcemia and renal failure. Further research on the risk of carcinoma and recurrence of hypercalcemia in atypical parathyroid adenoma is needed.
Presentation: 6/2/2024
8305 Assessing The Relationship Between Oral Health And Bone Disease Among Post-menopausal Women
Authors: Tahir Nataliyah , Ahmad Sophie , Batra Kavita , Gupta Ashok , Izuora Kenneth E 
Published: October 2024

Abstract
Disclosure: N. Tahir: None. S. Ahmad: None. K. Batra: None. A. Gupta: None. K.E. Izuora: Research Investigator; Self; Novo Nordisk.
Background: Menopause is associated with significant bone loss and worsening oral health, especially periodontal disease (PD). The purpose of this study was to understand the relationship between oral health and bone loss and the factors that influence this relationship. This will help better understand their pathophysiology and provide guidance for more appropriate care. Methods: ​​This cross-sectional study included post-menopausal women undergoing routine bone density evaluation at a diagnostic radiology center. After participants signed informed consent, histories were collected via an investigator-administered questionnaire, the oral cavity was inspected for teeth loss and PD, and a bone density assessment, interpreted by a radiologist, was obtained. The significance level was set at 5% and data were analyzed using chi-square and logistic regression tests. Results: In a sample of 100 eligible participants, the mean age and body mass index (BMI) were 68.17 ± 8.33 years and 29.59 ± 6.13 kg/m2 respectively. Twenty-three participants (23.0%) had T2DM, 29 (29.0%) had &lt; 20 natural teeth and 17 (17.0%) had normal bone mineral density. In an unadjusted simple logistic regression, age, BMI, race/ethnicity, number of natural teeth, history of PD, and history of osteoporotic fracture were associated with bone loss. However, in the binary logistic regression, the only significant predictors of bone loss included age (aOR 1.171, p&lt;0.001), BMI (aOR 0.763, p&lt;0.001), and the history of osteoporotic fractures (aOR 21.273, p=0.021). Conclusion: Clinical variables associated with bone loss in our study included older age, lower BMI, and history of osteoporotic fracture. These are established risk factors for bone loss. Although unadjusted results suggest a relationship between oral health measures and bone loss, these relationships were not present when other factors were included in a multivariate model. These findings suggest PD by itself may not be a risk factor for bone loss but may reflect the similarity in the risk factors for both conditions.
Presentation: 6/3/2024
8317 Biochemical Adequacy And Renal Complications In Long-Term Management Of Patients With Postsurgical Hypoparathyroidism
Authors: Hong A Ram , Yong Park Ji , Choi Wonsuk , Yoon Jee Hee , Kim Hee Kyung , Kang Ho-Cheol 
Published: October 2024

Abstract
Disclosure: A. Hong: None. J. Park: None. W. Choi: None. J. Yoon: None. H. Kim: None. H. Kang: None.
Background: Hypoparathyroidism (HypoPT) most commonly develops after neck surgery, particularly thyroid surgery. Permanent postsurgical HypoPT necessitates calcium and active vitamin D supplementation for 12 months or more due to irreversible parathyroid damage following surgery. This study investigated the biochemical adequacy of conventional therapy (i.e., active vitamin D and/or calcium) in patients with permanent postsurgical HypoPT based on recent guidelines and assessed the incidence of renal complications. Materials and Methods: The study included 62 adult patients with permanent postsurgical HypoPT who underwent total thyroidectomy for papillary thyroid cancer at Chonnam National University Hwasun Hospital. Biochemical parameters, including albumin-adjusted serum total calcium, ionized calcium, phosphate, creatinine, parathyroid hormone, magnesium, 25-hydroxyvitamin D (25[OH]D), and 24-h urine calcium, were measured. Renal ultrasound and KUB X-ray were performed for all patients. Results: The mean age of the patients was 55.5 ± 12.4 years, with 48 (77.4%) being female. The median follow-up duration after surgery was 10.6 years (interquartile range 9.0-15.5 years). At the time of evaluation, all patients were treated with calcitriol. Additional treatment, including calcium carbonate or cholecalciferol, was received by 43 (69.4%), and 28 (45.2%) were given thiazide diuretics. Thirty-seven (59.7%) patients had values below the recommended serum calcium (albumin-adjusted or ionized) concentration, while three (4.8%) had values above the upper normal limit of serum phosphate level. Serum 25(OH)D levels were maintained within the normal range (30-50 ng/mL) in 27 (43.5%) patients, and 47 (75.8%) patients met normal serum magnesium levels. Hypercalciuria, defined as &gt;7.5 mmol/day in men and &gt;6.25 mmol/day in women, was observed in 12 (19.4%) patients. Nephrolithiasis and nephrocalcinosis were present in 2 (3.2%) patients each. No patient had chronic kidney disease (CKD), defined as an estimated glomerular filtration rate &lt;60 mL/min/1.73 m2. Conclusion: Conventional management for permanent postsurgical HypoPT appears suboptimal for certain patients. However, the incidence of renal complications, such as hypercalciuria, nephrolithiasis/nephrocalcinosis, and CKD, was not commonly observed in a real-world setting during the 10 years of follow-up. This observation may be associated with a higher prescription rate of thiazide diuretics.
Presentation: 6/2/2024
12538 Blocking Oxidized Phospholipids Improves Bone Mass In Mice By Transcriptional Reprogramming Of Osteoblastic Cells: Analysis At The Single Cell Level
Authors: Palmieri Michela , Nookaew Intawat , Almeida Maria , Joseph Teenamol E , O’Brien Charles A , Ambrogini Elena 
Published: October 2024

Abstract
Disclosure: M. Palmieri: None. I. Nookaew: None. M. Almeida: None. T.E. Joseph: None. C. O'Brien: None. E. Ambrogini: None.
Oxidized phospholipids containing phosphatidylcholine (PC-OxPLs), present on oxidized low-density lipoproteins (OxLDL) and apoptotic cells, are pathogenic in many diseases, including osteoporosis. The E06 IgM antibody binds PC-OxPLs and blocks their adverse effects. In our studies, six-month-old female and male mice overexpressing a single chain (scFv) form of the antigen-binding domain of E06 IgM (E06-scFv) have high cancellous and cortical bone mass. In addition, E06-scFv transgenic mice are protected against high fat diet- and age-induced bone loss. E06-scFv increases osteoblast number, bone formation rate and reduces osteoblast apoptosis. To investigate the effect of E06-scFv on osteoblastic cells transcriptional reprogramming, we performed single cell RNA-sequencing (scRNA-seq) of mesenchymal cells from long bones of 6-months old WT and E06-scFv transgenic female and male mice. Based on the total of over 7,500 osteoblastic cells, we focused the analysis on 3 cell clusters, pre-osteoblasts, identified by high levels of osteopontin (Spp1), osteoblasts, identified by high expression of osteocalcin (Bglap) and adipo-CAR expressing the adipogenic marker Adipoq in addition to high expression of the stromal marker Cxcl12. In both males and female transgenic mice, the relative number osteoblasts increased [12.0 % in females and 23.7 % in males; conversely, the relative number of adipo-CAR cells decreased [18.2 % in females and 15.1 % in males] compared to WT. We performed the analysis of functional enrichment-based gene ontology by piano software package and found that, in the three clusters of both male and female transgenic mice, there was an upregulation of gene expression, with a range of 37-125 genes per cluster, related to extracellular matrix organization [p range 0.0003-3.95E-09], bone mineralization [p range 0.04-0.0022] and cell adhesion [p range 0.019-0.00008]. Consistent with these results, bulk RNA sequencing indicated that these ontology terms were downregulated in calvaria-derived osteoblasts treated with OxLDL [extracellular matrix organization p= 1.19E-13; bone mineralization p= 0.0018655; cell adhesion p= 2.73E-12]. Based on these results, we conclude that PC-OxPLs not only affect osteoblast number but also decrease osteoblast activity on a single cell basis.
Presentation: 6/1/2024
5159 Bone Disease Related To PLS3 Gene Mutation
Authors: Saberi Sima , Helen Esfandiari Nazanene 
Published: October 2024

Abstract
Disclosure: S. Saberi: None. N. Esfandiari: None.
Background: A variety of genes play a role in the development of osteoporosis. One of these is PLS3, located on the X chromosome. PLS3 gene mutation leads to defective function of the protein Plastin 3. Plastin 3 functions in the binding and bundling of F-actin, a main component of the actin cytoskeleton. In the skeletal system the actin cytoskeleton regulates adaption to gravity and mechanical stress. Dysregulation of this gene is associated with diseases of the bone, including osteoporosis. Clinical Case: A 60-year-old man with a history of hearing loss since age 52, hypothyroidism diagnosed at age 57 presents to the Genetics Clinic after 2 grandsons were diagnosed with osteogenesis imperfecta. The mothers (his two daughters) of the two grandsons were found to be carriers of the PLS3 gene mutation. Because of their carrier status the patient was screened and a pathogenic partial gene deletion of exons 8 to 16 in the PLS3 gene was detected. The patient has a history of a right wrist fracture at age 16 in a fall from 8 feet height from a ladder, right leg fracture at age 45 when his leg got caught and twisted in a ladder rung, 5 rib fractures and shoulder fracture at age 53 in a fall from 3 feet into a utility hole. A DXA scan showed osteopenia in his left femoral neck (T-score -1.3), normal bone density in his total hip (T score -0.1) and lumbar spine (L1-L4 T-score -0.4). FRAX score for major osteoporotic fracture was 9.4% and hip fracture was 1.2%. Labs for secondary causes of osteoporosis were normal. Due to his gene mutation and fracture history a bisphosphonate was recommended.Clinical Lessons:Obtaining a thorough family history in people with fractures can determine the need for screening for gene mutations associated with osteoporosis. This can identify patients who need more aggressive management.
Presentation: 6/2/2024
7159 Brown Tumor As Primary Presentation Of Parathyroid Carcinoma In A Young Female
Authors: Zachariah S G , Anand R , Wong B Y , Lee H J 
Published: October 2024

Abstract
Disclosure: S.G. Zachariah: None. R. Anand: None. B.Y. Wong: None. H.J. Lee: None.
Title Brown Tumor as Primary Presentation of Parathyroid Carcinoma in a Young Female Introduction/Background: Parathyroid carcinoma (PC) is a rare cause of hyperparathyroidism (HPT) accounting for less than 1% of primary HPT cases. The mean age of PC presentation is 62 years. Long-standing HPT can lead to the formation of osteitis fibrosis cystica (brown tumors). In today’s world of advanced screening, they are an increasingly rare presentation of HPT. We present a case of PC presenting as multiple brown tumors in a young woman. Case: A previously healthy 32-year-old woman presented to the emergency department with right shoulder pain after a mechanical fall. MRI revealed multiple osseous lesions of the proximal humerus, glenoid, and scapula, concerning for possible metastatic malignancy. Notable labs: calcium 13.6 mg/dL [8.5 - 10.5 mg/dL], phosphorus 1.7 mg/dL [2.5 - 4.5 mg/dL], alkaline phosphatase 2,369 U/L [&lt; 130 U/L], 25-OH vitamin D 0.8 ng/mL [30 - 60 ng/mL], and parathyroid hormone greater than 2,500 pg/mL [20-80 pg/mL]. Albumin and renal function were normal. CT chest/abdomen/pelvis showed lytic lesions of the left 7th rib, anterior superior iliac spine (with nondisplaced fracture), pelvis, and sacrum. Subsequent pelvic biopsy showed fragmented bony trabeculae with osteoblastic rimming and rare osteoclasts, fragments of fibrous tissue with few plasma cells and hemosiderin laden macrophages, possibly consistent with brown tumor. On parathyroid ultrasound, a 2.2 cm cystic mass was seen along the left common carotid artery. CT neck confirmed the location and also reported C7-T1 spinal lesions. Calcium levels stabilized with IV fluids and 90 mg IV pamidronate. She underwent a left parathyroidectomy and left hemithyroidectomy with central neck dissection. Pathology was consistent with a low-grade parathyroid carcinoma, with a foci of angioinvasion and capsular invasion without lymph node metastases. The Ki-67 index was less than 1%. Post-operatively, the patient was started on calcium and calcitriol supplementation and did not experience hungry bone syndrome. On further discussion, the patient noted that she had a jaw tumor that was previously biopsied and found to be benign. The patient has since been referred for genetic testing. Conclusion/Clinical Lessons: Both PC and its initial presentation with brown tumors are uncommon. Even more rare is the presentation of both in a young, otherwise healthy female. In this context, it is also important to note that brown tumors can mimic osseous metastases and appropriate biochemical, imaging, and histopathological evaluation is needed. The diagnosis of PC under 40 years of age is uncommon and genetic testing is indicated. Syndromes including multiple endocrine neoplasia type 1, familial isolated hyperparathyroidism, and hyperparathyroidism-jaw tumor syndrome are potential causes of inherited PC.
Presentation: 6/3/2024
5105 Characterization Of Novel PHEX Variants In X-Linked Hypophosphatemic Rickets And Genotype-PHEX Activity Correlation
Authors: Wu Huixiao , Zhao Wanyi , Chen Xinyu , Gao Ling , Xu Chao , Zhao Jiajun 
Published: October 2024

Abstract
Disclosure: H. Wu: None. W. Zhao: None. X. Chen: None. L. Gao: None. C. Xu: None. J. Zhao: None.
X-linked hypophosphatemia (XLHR) is the most common genetic form of hypophosphatemic rickets (HR), which is caused by mutations in the phosphate regulating endopeptidase homolog X-linked (PHEX) gene. Till now, the genotype-phenotype relationship of XLHR and the pathogenic role of PHEX have not been fully determined. Here we summarized clinical features of 49 HR patients and detected 17 novel PHEX variants and 5 novel non-PHEX variants. Then we explored the pathogenesis of new-found variants from protein expression, glycosylation analysis, subcellular localization and endopeptidase activity. The results showed that missense variants (Q189H and X750R) slightly reduced protein expression without obviously altering the length and localization of the protein, while truncating variants significantly impaired the synthesis of PHEX and produced a shorter immature protein retained in cells. No evident correlation was observed between mutation types and clinical phenotypes. However, for the first time ever, we analyzed the relationship between PHEX activity and serum phosphorus level and found that patients with low PHEX activity tended to have severe hypophosphatemia and high rickets severity score (RSS). Then we established two new knock-in XLHR mouse models by introducing into mice two novel Phex variants (c.T1349C and c.C426G) found in patients using CRISPR/Cas9 technology. Both demonstrated the clinical manifestations of XLHR seen in the patients and PhexC426G mice showed more severe phenotype than PhexT[1]349C mice, which further confirmed the rationality of genotype-PHEX enzymatic activity correlation analysis. Therefore, our findings demonstrated that novel PHEX variants could disrupt protein function via affecting protein synthesis, post-translational modification, cellular trafficking and catalytic activity. Our study promoted the understanding of XLHR pathogenic mechanism and PHEX activity-phenotype correlation provided scientific support for precise diagnosis and treatment of XLHR.
Presentation: 6/3/2024