bluuebunny/crossref_metadata_2025_split huggingface dataset:
8476 Case of Zoledronic Acid Induced Acute Anterior Uveitis In A 63-Year-Old Woman
Authors: Halstrom R , Perez J Sanchez , Lobo-Chan A M , Reutrakul S 
Published: October 2024

Abstract
Disclosure: R. Halstrom: None. J. Sanchez Perez: None. A. Lobo-Chan: None. S. Reutrakul: None.
Background: Bisphosphonates used for osteoporosis treatment are commonly known for their adverse gastrointestinal side effects and jaw osteonecrosis. Here, we document a case of anterior uveitis and scleritis post intravenous zoledronic acid infusion. Clinical case: A 63-year-old woman with osteoporosis, Graves disease complicated by thyroid eye disease s/p thyroidectomy, gastroesophageal reflux disease, positive antinuclear antibody and cataracts presented for a follow up of osteoporosis. She previously took alendronate 70 mg weekly for four years given a multi-bone arm fracture after a fall from standing height. On follow up 2 years after treatment, bone mineral density (BMD) by dual-energy absorptiometry had improved in the right femoral neck (T score from -3.3 to -1.8). A repeat BMD while on drug holiday showed T-score at left femoral neck of -2.4, with a calculated fracture risk assessment tool (FRAX) score of 18% and 4.8% for major and hip osteoporotic fractures, respectively. A zoledronic acid infusion was given due to elevated FRAX score, fracture history, and severe acid reflux. Nine days post-infusion, she presented to the emergency room with 2 days of right eye pain with blurry vision, eyelid swelling, photophobia, and tearing. Physical examination showed conjunctival and scleral injection, punctate epithelial erosions on corneal staining, and anterior chamber with anterior chamber cell. Labs were notable for weak positive RNP 29 (&lt;19u). The following autoantibodies and levels were within normal limits: TSH 2.08 (0.35-4.0 mciu/ml), freeT4 1.0 (0.6-1.7 ng/dl), C3 152 (90-180 mg/dl), C4 33 (12-47 mg/dl), ESR 9 (&lt;20 mm/hr), CRP 7 (&lt;19u), SSA 0 (&lt;29AU/ml), SSB 0 (&lt;29AU/ml), dsDNA 4 (&lt;24IU), Rh Factor (&lt;10IU/ml), CCP 7 (&lt;19U), and ANA. The patient was started on prednisolone acetate 1% 4 times daily, cyclopentolate twice daily with naproxen added 3 days later for additional anti-inflammatory treatment for the mild scleritis component. Therapy led to significant improvement on follow up 3 weeks later and topical corticosteroids and oral NSAIDs were tapered and discontinued. Conclusion: The onset of ocular symptoms and negative inflammatory workup raised concern for bisphosphonate induced anterior uveitis and scleritis. This case displays a rare side effect of bisphosphonate induced ocular inflammation with an approximate incidence of 0.046%-1% (1). We present this case in a patient with autoimmune disease and prior tolerance to oral bisphosphonate to shed light on a lesser-known side effect of bisphosphonates to promote prompt recognition and treatment. Reference: (1) Chartrand, Nicholas A., et al. “Ocular Side Effects of Bisphosphonates: A Review of Literature.” Journal of Ocular Pharmacology and Therapeutics, 39;1;2023, 3-16.
Presentation: 6/3/2024
7192 Description Of Patients With Post-surgical Hypoparathyroidism In Clinical Follow-up In Brazil
Authors: Dos Santos Lívia Marcela , Oliveira Martins Graziela , Costa Figueiredo Luis Felipe , de Lemos Manuela Nascimento , Viana Lima Jose , Azevedo Alvares Leonardo , Naomi Sakane Eliane , Maria Scalissi Nilza 
Published: October 2024

Abstract
Disclosure: L.D. Santos: None. G. Oliveira Martins: None. L. Costa Figueiredo: None. M. Nascimento de Lemos: None. J.V. Lima: None. L.A. Alvares: None. E.N. Sakane: None. N. Scalissi: None.
Post-surgical hypoparathyroidism is an event that may occur, especially after extensive procedures in the cervical region. There are few long-term follow-up studies on individuals who develop permanent post-surgical hypoparathyroidism and its long-term complications. Objective: This study aims to assess the clinical and laboratory characteristics of patients diagnosed with permanent hypoparathyroidism at a tertiary care center in Brazil. Methods: We conducted a retrospective analysis of medical records. Results: We evaluated 27 patients with permanent hypoparathyroidism, with an average age of 53 years (SD=10), where 15% were alcohol and tobacco consumers, and 88% were female. The average time of permanent hypoparathyroidism diagnosis was 9 years and 3 months. Regarding the surgical indication, 35% were due to Graves' disease, 25% for thyroid goiter, 25% for thyroid cancer, and 15% for glottic cancer. Only 15% had a description of the parathyroid glands in the pathology report. As for medications, all patients were using calcium carbonate, with an average dose of 1700 mg daily per individual. 90% of the patients were using calcitriol, with an average dose of 0.64 mcg daily, and 55% were using cholecalciferol, with an average weekly dose of 9700 IU. Hydrochlorothiazide was used by 35% of the patients, with an average daily dose of 34 mg. Regarding postoperative exams 24 hours after surgery, only half had the parathyroid hormone (PTH) test requested or available, with only one patient having PTH &gt;10 pg/mL. Regarding chronic complications, 15% presented with nephrolithiasis, 5% with subcapsular cataract, 5% with prophylaxis for seizures, 15% with a diagnosis of depression, and 10% with arrhythmias. Conclusion: Individuals with permanent hypoparathyroidism require attention due to chronic complications, and proper treatment aims to reduce the chance of developing other diseases associated with permanent post-surgical hypoparathyroidism.
Presentation: 6/2/2024
9198 Dimeric [Cys25]PTH(1-34) Induces Differential Transcriptional Responses Versus Monomeric PTH(1-34)
Authors: Noh Minsoo , Jieun Kim Hani , Kim Jinseok , Kang Mikyung , Young Lee Soo , Lee Hunsang , Lee Sihoon 
Published: October 2024

Abstract
Disclosure: M. Noh: None. H.J. Kim: None. J. Kim: None. M. Kang: None. S. Lee: None. H. Lee: None. S. Lee: None.
Introduction: Patients with hypoparathyroidism caused by the homozygous mutation that changes arginine to cysteine at position 25 in parathyroid hormone (PTH) exhibit high bone densities, which suggests a potential influence of the mutant hormone on bone formation. We also have found that [Cys25]PTH forms homodimers, and that the dimeric peptide exhibits altered functionality versus monomeric PTH. Dimeric [Cys25]PTH(1-34) (Dimer) thus displays selective binding to the G protein-coupled PTH1R conformation (RG) in vitro and markedly diminished cAMP-inducing capability in vivo. Despite these alterations, Dimer induced bone anabolic effects in both calvarial injection assays and after injection in ovariectomized osteoporotic mice, closely mimicking the effects of PTH(1-34) (wtPTH). Our current objective is to explore the downstream signaling pathways activated by Dimer vs wtPTH to help elucidate the bone anabolic effects of the Dimeric analog and its therapeutic potential. Methods: A phospho-protein antibody array assay developed for G protein-coupled receptor (GPCR) downstream target proteins was employed in HEK293/hPTH1R (GP-2.3) cells following treatment with chemically synthesized wtPTH or Dimer. We further conducted RNA-seq analysis of transcriptome changes in primary cells collected from calvarial bones of mice treated with wtPTH or Dimer at 6, 12, and 24-hours post-injection. Finally, we used quantitative reverse transcription PCR (qRT-PCR) to analyze changes in specific marker genes in tibiae and kidney isolated from mice after treatment with Dimer vs. wtPTH. Results: The number of phosphorylated proteins significantly regulated by PTH1R upon exposure to Dimer was remarkably enhanced, relative to the number regulated upon exposure to wtPTH. RNA-seq analysis revealed that the early effects of wtPTH and Dimer on transcriptional regulation were similar, whereas marked differences in expression levels became apparent over time. qRT-PCR analyses of RNA expression levels in kidneys versus tibiae from mice treated with wtPTH or Dimer revealed in bone that the expression of genes associated with bone catabolism, particularly RANKL, was significantly lower in response to Dimer as compared to wtPTH treatment, while in kidney there was an overall reduced response to Dimer as compared to wtPTH. Conclusions: Our study supports the hypothesis that as compared to PTH(1-34), dimeric [Cys25]PTH (1-34) induces altered signaling responses in vivo and has a lower effect on bone catabolism. Dimeric [Cys25]PTH(1-34) thus holds interest as a potential bone anabolic agent that utilizes a distinct mechanism of action.
Presentation: 6/3/2024
12466 Dual Bone Defect In Patients With Charge Syndrome
Authors: Reyes N , Santen R J , Jan De Beur S M , Balasubramanian R 
Published: October 2024

Abstract
Disclosure: N. Reyes: None. R.J. Santen: None. S.M. Jan De Beur: None. R. Balasubramanian: None.
Chromodomain Helicase DNA-binding protein 7 (Chd7) is an ATP-dependent chromatin modifier that mediates nucleosome remodeling. Chd7 mutations result in CHARGE syndrome characterized by coloboma, heart defects, choanal atresia, growth/developmental delay, ear abnormalities, and hypogonadotropic hypogonadism/Kallmann syndrome (IHH/KS). Testosterone has direct and indirect effects (through estrogen), to increase bone formation and decrease bone resorption. Untreated hypogonadism is associated with decreased bone density and fractures. Reports of fractures and low bone density in CHARGE syndrome patients have been attributed to sex hormone deficiency associated with hypogonadism. However, recent data from a Chd7 mouse knockout model suggests an intrinsic Chd7-related bone defect. In wild-type mice, Chd7 promotes osteogenic differentiation of mesenchymal stem cells. Chd7 deficient mice show markedly reduced osteoblasts. Thus, we propose, a dual bone defect in CHARGE syndrome resulting from impaired osteogenesis from CHD7 and sex steroid deficiency; and increased bone resorption due to lack of sex steroids. Here we present two individuals with CHARGE syndrome with markedly low bone density and literature review supporting the dual bone defect concept. Case 1 is a 30 yo male with a pathogenic CHD7 mutation, multiple congenital anomalies of CHARGE syndrome and hypogonadotropic hypogonadism. He had multiple fractures in his teen age years and a bone density Z score of -5.2 at the lumbar spine and -3.3 at the left femoral neck. Because he did not tolerate androgen therapy, a single infusion of zoledronic acid was administered with no further fractures for eight years following infusion. Case 2 is a male evaluated for IHH/KS and ultimately diagnosed with CHARGE Syndrome based on a pathogenic CHD7 mutation. Despite 7 years of testosterone therapy with full virilization, his bone density remained low at Z-score of -1.9 at the spine and -2.6 at the total hip. Results: Both patients had low bone density, one while untreated and the other after full virilization with exogenous androgens. This raises the question whether the bone defects were related to the CHD7 mutation, to androgen deficiency or both. To answer this question, a literature search examined bone density data in untreated patients with CHARGE syndrome versus IHH/KS. We found substantially lower bone density in untreated CHARGE patients Z score -3.46±0.36 (SEM) (n=13) versus IHH/KS -2.16 ±1.0 (n=4). Furthermore, the bone density was also lower in treated CHARGE patients -2.46±0.28 (n=6) versus IHH/KS -0.94±0.26 (n=140). Conclusion: These data, taken together, provide direct human evidence to support the concept that the CHD7-related CHARGE syndrome patients have a defect in both osteogenesis as well as an effect of sex steroid deficiency on bone.
Presentation: 6/3/2024
6986 Efficacy and Safety of Weekly Liquid Alendronate Sodium Trihydrate in Korean Postmenopausal Women with Osteoporosis: A 12-Month, Multi-Center, Randomized Trial
Authors: Rhee Y , Ahn S , Hong N , Seo D , Hong S 
Published: October 2024

Abstract
Disclosure: Y. Rhee: None. S. Ahn: None. N. Hong: None. D. Seo: None. S. Hong: None.
Background: Although alendronate is the most prescribed oral bisphosphonate for osteoporosis treatment, it can lead to gastrointestinal problems, impacting treatment compliance and efficacy. This study aimed to assess the efficacy and safety of once-weekly alendronate sodium trihydrate (ALN-S), an oral solution, compared to once-weekly alendronate sodium (ALN-T), an oral tablet, in Korean postmenopausal women with osteoporosis. Methods: Conducted as a 12-month, multi-center, prospective, randomized, open-labeled, parallel trial at two hospitals in Korea, 170 postmenopausal women were randomized to ALN-S (N=85) or ALN-T (N=85). Bone mineral density (BMD) at the lumbar spine (LS), femoral neck (FN), and total hip (TH) was measured at baseline and after 12 months. Bone turnover markers, including C-telopeptide (CTX) and procollagen type 1 amino-terminal propeptide (P1NP), were assessed at baseline, 6 months, and 12 months. The primary outcome was the percentage change in LS BMD, evaluated for non-inferiority. Results: After 12 months, both ALN-S and ALN-T groups exhibited a significant increase in LS, FN, and TH BMD, with no significant intergroup differences (ALN-S: LS 5.0 ± 0.6%, FN 1.8 ± 0.6%, TH 2.2 ± 0.5%; ALN-T: LS 5.2 ± 0.6%, FN 1.6 ± 0.6%, TH 1.8 ± 0.5%). ALN-S was found to be non-inferior to ALN-T for BMD change at LS (treatment difference: -0.22%, 95% CI: -1.84 to 1.40%), excluding the predefined non-inferiority margin of -2.29%. Changes in both CTX and P1NP over time did not significantly differ between the groups. There was no significant difference in the frequency of adverse events between the groups. Conclusion: Weekly liquid alendronate sodium trihydrate demonstrated non-inferiority to weekly tablet alendronate sodium in increasing LS BMD in Korean postmenopausal women with osteoporosis.
Presentation: 6/2/2024
6424 From Hyperparathyroidism To Neurologic Crisis: A Tale Of Brown Tumor And Spinal Cord Compression
Authors: Kormanis Aryn , Anderson Matthew , McKnight Miya , Darapu Hima 
Published: October 2024

Abstract
Disclosure: A. Kormanis: None. M. Anderson: None. M. McKnight: None. H. Darapu: None.
Background/Objective: In this case, we present a rare and severe consequence of secondary hyperparathyroidism, a Brown tumor leading to spinal cord compression, in a young adult with end-stage renal disease. Case Report: A 26-year-old male with a medical history of polycystic kidney disease and IgA Nephropathy complicated by ESRD, history of brown cell tumors (s/p surgery) was admitted for hospitalization due to hypocalcemia after presenting to the Emergency Department with right lower extremity weakness. Examination revealed right hip flexor weakness and right foot clonus. Lab results showed serum calcium of 10.4 mg/dL . MRI displayed a 2.5cm X 3.7 cm soft tissue mass with circumferential encroachment of the epidural space leading to severe spinal canal stenosis of T4-T5 at the site of prior Brown tumor resection. Ultimately, the patient underwent subtotal parathyroidectomy with left cervical thymectomy, leading to an intra-operative PTH drop from &gt;3500 to 247 pg/mL. Discussion: In the context of treating vertebral brown tumors, the consensus suggests that parathyroidectomy plays a crucial role in achieving both clinical and radiographical amelioration of the tumor. However, in cases like ours where paresis is present, surgical decompression of the tumor becomes imperative. Conclusion: The development of Brown tumors is a severe and rare long-term complication for hyperparathyroidism, and the location of a Brown tumor in the thoracic spine causing symptomatic cord compression is even more rare.
Presentation: 6/2/2024
7655 Genetic Mysteries Unveiled: Unusual Mutation Unraveled In Hypophosphatasia
Authors: Sharma Akanksha , Katikaneni Padma , Tanveer Saira , Selk Karen 
Published: October 2024

Abstract
Disclosure: A. Sharma: None. P. Katikaneni: None. S. Tanveer: None. K. Selk: None.
Introduction: Hypophosphatasia (HPP), an inherited dental-osseous metabolic illness, is caused by inactivating mutations in the gene encoding the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP), which leads to a decrease in TNSALP enzymatic activity. Patients with HPP typically experience dental and skeletal mineralization issues as their most common symptoms; musculoskeletal abnormalities, numerous fractures, tiredness, and migraines are less common clinical presentations. Case Report: Our 75-year-old male patient initially presented 1.5 years prior following a spontaneous T12 vertebral fracture. A bone biopsy was performed and did not reveal evidence of malignancy. Testing for SPEP/UPEP was not consistent with myeloma, and thyroid testing was also unrevealing. His alkaline phosphatase level was consistently &lt;40 IU/L since 1999. An evaluation was done for low alkaline phosphatase and secondary reasons for bone loss. This testing did not reveal vitamin D deficiency, parathyroid disease, hypophosphatemia, laboratory evidence of celiac disease, hypogonadism, or hypomagnesemia. A vitamin b6 level was markedly elevated at 119 ng/mL (ref range 2.1-21.7) while not on supplementation. He had noticed multiple fractures as a child, but he had written them off as minor injuries. He could clearly remember breaking his right wrist and clavicle. As an adult, he had rib fractures and a foot fracture. He was unable to recollect losing his primary teeth. Almost all his teeth are crowns or implants despite taking exceptional care of them. He did not have joint hypermobility. Genetic testing revealed the patient was heterozygous for an ALPL gene variant, c.876_882delinsT. It was a variant of undetermined significance at that time. His daughter also was found to have a low alkaline phosphatase and the same genetic test result. She also has experienced dental carries and joint pain. Our patient initiated teriparatide due to the need for more urgent therapy for extensive spinal surgery. He was later transitioned to asfotase alfa therapy and has not had any further fractures at the time of this report. Discussion: Hypophosphatasia is a rare inborn disorder due to mutations in the tissue nonspecific alkaline phosphatase gene ALPL and is characterized by low ALP levels. Affected individuals will also have elevated vitamin b6 levels and urinary phosphoethanolamine (PEA) levels. Early diagnosis of HPP is necessary to prevent bone fracture pain and improve quality of life. Inaccurate assessments can miss diagnoses of parents and other family members and even lead to lost opportunities to treat a patient with a substantial illness burden. This case highlights the mutation c.876_882delinsT as a likely pathologic variant in the ALPL gene. It also supports that patients with HPP can also respond to teriparatide treatment.
Presentation: 6/2/2024
6864 Genetic Profile And Identification Of A Novel Mutation In PHEX In X-Linked Hypophosphatemia (XLH) Patients At A Brazilian Research Center: Insights And Implications
Authors: Rodrigues da silva Maisa Monseff , de Araújo Iana Mizumukai , A de Paula Francisco J 
Published: October 2024

Abstract
Disclosure: M. Monseff Rodrigues da silva: None. I.M. de Araújo: None. F.J. de Paula: None.
Background: X-Linked Hypophosphatemia (XLH) is a rare genetic disorder characterized by low phosphate levels in the blood, primarily caused by mutations in the PHEX gene, leading to bone skeletal deformities and reduced quality of life. XLH genetics is extensively studied with over 500 pathogenic mutations in the PHEXgene having been identified. Common mutations include missense, nonsense, and splicing, accounting for approximately 50% of cases. However, genotype-phenotype correlations remain unclear. Methods: We conducted a cross-sectional study using a convenience sample selected from the osteometabolism an outpatient clinic in Brazil. Genetic analysis was performed using next-generation sequencing (NGS; Ilumina) in collaboration with Mendelics Laboratory. Results: In our study, 9 out of 10 patients showed previously known and reported mutations, with 60% exhibiting common mutation types. The mutations occur in different codons; however, the most prevalent consequence was the substitution of glycine (G) with adenine (A), present in 40% of the patients. One patient, however, showed a unique missense mutation in PHEX gene (arginine to glutamate at codon 266), which leads to a premature stop codon, a mutation absent in over 183,000 X chromosomes from XLH individuals. Even though this mutation was novel, no significant diferences in the phenotype of this patient were seen in comparision with the rest of the cohort. Discussion: The findings of our study underscore the genetic heterogeneity characteristic of XLH, as evidenced by the fact that 90% of our patient cohort exhibited mutations previously identified in the literature, with a significant 60% showing common mutation types. This highlights the recurring genetic patterns in XLH, which can be instrumental for diagnostic and - perhaps in the future - therapeutic strategies. Particularly notable is the predominant mutation involving the substitution of glycine with adenine, found in 40% of our patients, underscoring its potential role as a key mutation in the pathogenesis of XLH. Furthermore, the discovery of a novel missense mutation in one patient, resulting in a premature stop codon, enriches the mutation spectrum of XLH and suggests a deeper complexity in the genetic landscape of the disease. This mutation, not previously documented in the extensive database of over 183,000 X chromosomes from XLH individuals, opens new avenues for research into the disease's molecular mechanisms and potential genotype-phenotype correlations. Conclusion: This study underlines the genetic diversity within XLH, emphasizing the need for comprehensive genetic analysis to understand the full spectrum of the disease. More studies are yet necessary to elucidate if there is a genotype-phenotype correlation.
Presentation: 6/1/2024