bluuebunny/crossref_metadata_2025_split huggingface dataset:
THU466 XLH During Pregnancy: A Closer Look Based On Real-World Experience
Authors: Ali Dalal S , Khan Aliya Aziz 
Published: October 2023

Abstract
Disclosure: D.S. Ali: None. A.A. Khan: Advisory Board Member; Self; Amgen Inc, Takeda. Grant Recipient; Self; Alexion Pharmaceuticals, Inc., Amgen Inc, Radius Health, Inc, Takeda, Ultragenyx.
Background: X-linked hypophosphatemia (XLH) is a genetic disorder caused by mutation in the PHEX gene leading to excess serum levels of the phosphate-regulating hormone fibroblast growth factor 23 (FGF23). High FGF23 causes renal phosphate wasting, decreased production of serum 1,25-dihydroxy vitamin D, and increased metabolism of 1,25-dihydroxy vitamin D, leading to hypophosphatemia. Maintaining normal serum phosphorus levels in pregnant women with XLH is critically important to ensure mineralization of the fetal skeleton. Multiple factors may influence phosphorus homeostasis in pregnancy, including an increase in PTHrP production and a tripling of calcitriol beginning in the first trimester. Case study: 30 years old Gravida 1 Para 0 with XLH, diagnosed at the age of 18 months. She has a pathogenic heterozygous mutation of the PHEX gene (c.1645+1G&gt;A). Treated with phosphate and calcitriol since diagnosis. Had no history of neonatal seizure or respiratory distress, and no dental or renal manifestations. No prior fractures or corrective surgeries and has a normal BMD. No history of enthesopathy, however, has chronic joint pain &gt; 1 year. The pregnancy progressed well with no issues; the patient chose not to undergo amniocentesis for fetal diagnosis. She was monitored closely every 3 weeks, aiming to maintain the serum phosphorus within the normal range to ensure adequate mineralization of the fetal skeleton. The requirements for phosphate increased by 50% in the 2nd trimester and by 125% in the 3rd trimester compared to baseline. While the calcitriol dose increased by 25% in the 3 trimesters compared to baseline. Because further increases in the calcitriol dose were associated with hypercalciuria, the dose was carefully titrated. The mean serum phosphorus level was maintained in the low normal reference range at 0.79 - 0.8 mmol/L (NR: 0.8-1.45), mean TmP/GFR 0.611 (NR: 0.96-1.44). She was induced at 37 weeks due to cholestasis, and delivered with a vaginal delivery. The baby boy weighed 2.690 kg and had slightly low serum phosphorus and calcium levels at birth, which corrected spontaneously. DNA analysis confirmed that the baby also has a pathogenic mutation of the PHEX gene. Conclusion: There was a noticeable variation in the serum phosphorus levels during the 1st and 2nd trimesters and less so in the 3rd trimester and during lactation. The dose of phosphate and active vitamin D required careful upward titration to maintain a normal serum phosphorus level. Therefore, close monitoring is essential. Although the rate of c-sections is higher (76%) amongst the XLH patient population compared to the normal population 27.1%, our patient delivered vaginally with no adverse skeletal outcomes in the mother or neonate.
Presentation: Thursday, June 15, 2023
FRI670 Osteoblast Rna Sequencing In T1d Mice Reveals Genetic Signature Of Maladaptation To Hypoxia And Compromised Collagen Synthesis
Authors: Kim Se Min , Hong Juhyeon , Sultana Farhath , Shelly Eleanor , Korkmaz Funda , Gimenez Judit , Yuen Tony , Daehn Ilse , Choi Jungmin , Zaidi Mone 
Published: October 2023

Abstract
Disclosure: S. Kim: None. J. Hong: None. F. Sultana: None. E. Shelly: None. F. Korkmaz: None. J. Gimenez: None. T. Yuen: None. I. Daehn: None. J. Choi: None. M. Zaidi: None.
The main feature of skeletal abnormality in type 1 diabetes (T1D) is low bone turnover with decreased osteoblastic bone formation [1, 2]. However, the mechanism of osteoblast dysfunction remains unclear. We generated T1D mice using low dose streptozotocin (STZ). T1D mice showed lower bone mass (g/cm2) at the femur (0.07 vs. 0.09*) and trends at lumbar spine (0.05 vs. 0.06, p=0.08) compared with control group at 8 weeks after inducing T1D. Osteoblasts were differentiated using bone marrow mesenchymal stem cells, and RNAseq was performed to analyze the transcriptome of osteoblasts. In gene set enrichment analysis, several pathways including immune, hypoxia, and glycolytic pathway were enriched. The osteogenic genes panel showed decreased Bglap and Col1a1 expression, together with lower expression of Bmp2 and Wnt5a, suggesting decreased bone formation might be related to the suppression of BMP and WNT signaling. Particularly, P4ha2, encoding prolyl 4-hydroxylase subunit alpha–2, which are responsible for posttranslational modification of collagen were downregulated in T1D osteoblasts (log2FC = – 1.7**). Among genes in hypoxia pathway, Egln3 encoding prolyl hydroxylase domain-containing protein 2 and Vhl encoding von Hippel-Lindau tumor suppressor, both of which stabilize HIF–α were downregulated (log2FC = – 2.8** and – 0.31*, respectively) likely for promoting HIF–α dependent gene expression in hypoxia. However, genes of the growth signaling pathway namely Pgf, Vegfa, and Igf1r were downregulated (log2FC = – 3.1**, – 0.4* and – 0.5**, respectively). Altogether, our findings suggest that maladaptation to hypoxic condition in T1D with compromised growth signaling pathway and impaired collagen synthesis might be related to osteoblasts dysfunction in T1D bone. (* p &lt; 0.05 and ** p &lt; 0.001)
[1] Shanbhogue VV et al, JBMR. 2015[2] Rubin MR et al, JCEM. 2022
Presentation: Friday, June 16, 2023
FRI678 Baseline Characteristics Of Fracture Liaison Service In Ajou University Hospital
Authors: Chung Yoon-Sok , Kim Jung-Hyun , Lee Soo-Ryeon , Choi Yong Jun 
Published: October 2023

Abstract
Disclosure: Y. Chung: None. J. Kim: None. S. Lee: None. Y. Choi: None.
Introduction: Fracture Liaison Service (FLS) had been set-up in many countries and regions. The Ajou University Hospital (tertiary care academic medical center in South Korea) has launched FLS program mainly composed of femoral fragility fractures. Methods: The baseline characteristics of study subjects were recorded on their initial admission. Data were derived from Ajou University Hospital from April 2019 to August 2022 for hip fracture patients aged 50 or older. Results: The average age was 78.4 years old (range 55 ∼ 98), with 68 male patients and 203 female patients (total 271 subjects). Area of fractures are intertrochanter 120, neck 102, subtrochanter 16, diaphysis 16, and unknown 13 subjects. Fracture type are fragility (osteoporosis) 209, atypical (antiresoprtive drug associated) 15, periprosthetic 17, cancer-related 10, osteomalacia 1, high-energy trauma 6, and unknown 13 subjects. Location of fall were 153 indoor, 73 outdoor, and 45 unknown. Bathrooms and bedrooms accounted for the largest portion of indoor falls. The bone mineral density (BMD) were tested in 215 subjects before discharge. Among them 132 were osteoporosis, 77 were osteopenia or normal, and 6 were undetermined in BMD. Of the 245 subjects who measured the serum 25-OH-Vitamin D, 206 were lower than the normal reference range. Among 244 subjects who measured serum PTH, 64 were higher than the normal reference range. The serum CTX and P1NP were also measured in 240 and 234 subjects, respectively. Among them, 52 subjects and 68 subjects revealed higher than the normal reference range of CTX and P1NP, respectively. Conclusion: Baseline characteristics of study subjects were evaluated in the Ajou University Hospital FLS Program. A significant number of patients included in the FLS were confirmed to have osteopenia or normal BMD. The majority of fracture patients had vitamin D deficiency, and a significant number of fracture patients had elevated serum CTX and P1NP levels.
Presentation: Friday, June 16, 2023
FRI690 Should Treatment For Osteoporosis Be Started In Patients With Primary Hyperparathyroidism Within The First Year After Parathyroidectomy?
Authors: Swe Khine Mon , Chiu Alexander , Pelley Elaine 
Published: October 2023

Abstract
Disclosure: K. Swe: None. A. Chiu: None. E. Pelley: None.
Osteoporosis is one of the indications for parathyroidectomy in patients with primary hyperparathyroidism. Studies show the improvement of bone mineral density (BMD) in the lumbar spine and hip within the first year after parathyroidectomy. Therefore, the decision to treat osteoporosis has usually been delayed until a follow-up bone densitometry scan (DXA) at least one year after parathyroidectomy. To study the BMD changes with or without osteoporosis treatment till first follow-up DXA after parathyroidectomy, we retrospectively reviewed a prospective database of patients undergoing parathyroidectomy for primary hyperparathyroidism between 2010 to 2017 at our institution. We included both male and female patients between the ages 50 to 80, with a history of fragility fracture and/ or T score less than -2.4, and normal renal function. We excluded patients with persistent hyperparathyroidism post-surgery, osteoporosis medication within 3 years before surgery, and DXA performed outside of our facility. Patients who received osteoporosis medication between surgery and the first follow-up DXA were compared to those who underwent surgery alone. We compared the changes in BMD at the total hip and lumbar spine (L1-L4) between baseline and the first follow-up DXA for the two groups. Data was evaluated using a student’s t-test. A total of 386 patients underwent parathyroidectomy during the study period of which 92 patients met the inclusion criteria. Among them, 28 patients were treated after surgery and 64 patients had parathyroidectomy alone. The mean duration to treatment initiation after surgery was approximately 4 months (SD +/- 3 months), and the mean duration until the first follow-up DXA after the surgery was 17 months (SD +/- 8 months). There was no difference in the change of BMD at the total hip between two groups. Both increased by 0.01 g/cm2 (p=0.74). However, there was a greater increase in BMD at the lumber spine for those treated (0.047 g/cm2 increase) compared to surgery alone (0.019 g/cm2 increase) (p=0.02). We concluded that initiation of osteoporosis treatment within the first year after parathyroidectomy led to similar BMD outcomes at the total hip, but the treatment group experienced greater gains in BMD at the lumbar spine compared to parathyroidectomy alone, in patients with primary hyperparathyroidism and osteoporosis.
Presentation: Friday, June 16, 2023
FRI694 Hypercalcemia And Renal Failure As Initial Presentation Of A Rare Case Of Primary Splenic Large B Cell Lymphoma
Authors: Ding Ning , Majumdar Sachin K 
Published: October 2023

Abstract
Disclosure: N. Ding: None. S.K. Majumdar: None.
Background: Hypercalcemia can be seen in patients with malignancy. However, primary splenic large B cell lymphoma presenting with hypercalcemia and renal failure is rare. Clinical Case: A 75-year-old male with PMH of migraine headaches and hearing loss was sent to the hospital by his primary care doctor due to lab abnormalities, including hypercalcemia and renal failure. He also had abdominal pain, weakness, polyuria, and weight loss for several weeks. He took calcium 1000 mg and vitamin D 5000 units daily. Laboratory tests showed creatinine 2.8 (0.4-1.3) mg/dL, calcium 13.8 (8.8-10.2) mg/dL, ionized calcium 6.75 (4.6-5.08) mg/dL, phosphorus 3.6 (2.2-4.5) mg/dL, PTH 12.6 (15-65) pg/mL, PTHrP 23 (14-27) pg/mL, 25-hydroxy vitamin D 53 (30-100) ng/mL, 1,25-dihydroxy vitamin D 171 (18-72) ng/L, CTX collagen C-telopeptide 1137 pg/ml, SPEP without significant abnormality, UPEP with Bence-Jones proteinuria. Skeletal series showed no suspicious lesions, but MRI abdomen revealed an 11 cm splenic mass. Patient underwent splenectomy and pathology revealed diffuse large B-cell lymphoma. Following surgery, his hypercalcemia resolved without additional interventions. 1,25-dihydroxy vitamin D reduced to 25 ng/l and CTX reduced to 451 pg/ml. Further workup, including bone marrow biopsy and imaging, were negative. Patient was subsequently diagnosed with primary splenic large B cell lymphoma. He completed R-CHOP therapy and had no hypercalcemia in follow-up labs. Conclusion: Calcitriol-mediated hypercalcemia occurs in less than 1% of lymphomas, and primary splenic lymphoma constitutes less than 1% of non-Hodgkin lymphomas. The case represents an extremely rare etiology for hypercalcemia. Interestingly, elevated 1,25-dihydroxy vitamin D and hypercalcemia resolved after splenectomy. Clinicians should consider lymphoma as a potential cause of hypercalcemia and renal failure in elderly patients.
Presentation: Friday, June 16, 2023
FRI699 Hyperphosphatemia In The Setting Of Sodium Hypochlorite Use
Authors: Champagne Kareen , Mooradian Arshag D , Gupta Nidhi , Haas Michael J , Gandhi Gunjan Y , Jurado-Flores Marilu M 
Published: October 2023

Abstract
Disclosure: K. Champagne: None. A.D. Mooradian: None. N. Gupta: None. M.J. Haas: None. G.Y. Gandhi: None. M.M. Jurado-Flores: None.
Introduction: Acute elevation of serum phosphorous occurs for various reasons, including cellular injury (hemolysis, rhabdomyolysis, tumor lysis syndrome), decreased excretion (acute renal injury), or increased absorption/intake. Case Description: A 20-year-old woman presented as a pedestrian struck by a car after a motor vehicle accident. She sustained significant injury to the left leg, including degloving injury, femur, and tibia fracture requiring intramedullary nailing, skin graft, and multiple debridements. A review of systems was positive for chronic constipation. Physical exam was remarkable for several large, deep wounds on the left leg with a wound vac. Her wound was treated with sodium hypochlorite 0.25% solution. Laboratory results revealed that serum CK was 2,903 U/L on admission, and serum phosphorous level was normal and only started to rise one month after admission. She was transfused for blood loss and received IV fluids intermittently. Serum ionized calcium was low on admission at 0.90 mmol/L, calcium supplement was started, and hypocalcemia resolved. GFR dropped twice (at 46 and 62 mL/min/1.73M2) during admission but recovered to normal within a day. Serum phosphorous was elevated and ranged from 4.7-8.0 mg/dL, magnesium level fluctuated between 1.5-2.5 mg/dL, the parathyroid hormone was low at 7.0 pg/ml, 25-hydroxy vitamin D was low at &lt;5.0 ng/ml, 1,25-dihydroxy vitamin D was low at &lt;5.0pg/ml, FGF-23 was high at 616 RU/ml. Sevelamer was given for 9 days and discontinued. Sodium hypochlorite 0.25% solution and calcium supplement were discontinued, and vitamin D supplementation was initiated. The fractional excretion of phosphorous calculated from spot urine phosphorous and creatinine was low at 3.03%. Seven days later, plasma phosphorous levels normalized. Discussion: Sodium hypochlorite is a strong alkali (pH ∼11) and is the active ingredient of bleach. When exposed to water, it forms hypochlorous acid that generates superoxide radicals, leading to oxidative injury and cell death. This solution is bactericidal and may cause some tissue injury as well. It is used in healthcare settings to disinfect dialysis machines and tunneled catheters, surgical equipment, wound cleaning, hand hygiene, and root canal sterilization. It may increase the risk of hyperphosphatemia when used in a patient with immobilization, bone fractures, hypoparathyroidism, low vitamin D, multiple blood transfusions, and wound debridements. There have been rare reports of acute kidney injury with an intravenous bleach injection.
Presentation: Friday, June 16, 2023
SAT190 The Effect Of Mechanical Loading On Bone Growth Ex Vivo
Authors: Aeppli Tim , Zhang Zhengpei , Zaman Farasat , Savendahl Lars S 
Published: October 2023

Abstract
Disclosure: T. Aeppli: None. Z. Zhang: None. F. Zaman: None. L.S. Savendahl: None.
Background: Bone growth is a multi-step process that involves proliferation and differentiation of chondrocytes within the growth plate. Apart from local regulation by various signaling pathways, chondrocytes respond also to external cues such as nutrition, inflammation and mechanical load that may increase or stunt growth. The Hueuter and Volkmann law describes the effect of mechanical loading on bone growth stating that bone growth is inhibited by increased mechanical compression and is promoted by reduced loading. To this date, no data is available investigating the local effects of mechanical loading on bone growth in the absence of systemic growth factors in small embryonic bones. Aim: The aim was to study the effects of mechanical loading on bone growth in an ex vivo bone culture model. Methods: Cultured femur and metatarsal bones from rats (E19.5) were studied and local/direct effects of mechanical loading on bone growth were investigated. A range of different mechanical forces was applied to femur and metatarsal bones every 2-3 days. To monitor bone growth, digital pictures were taken and bone length was measured every 2-3 days. The loaded bones were compared to control bones (sham-loaded). Results: When applying different mechanical load to metatarsal bones, bone growth was suppressed in a dose-dependent manner. On day 5, after applying mechanical loading (0.4 N) twice on day 0 and 2, metatarsal bone growth was significantly suppressed when compared to unloaded control bones (p&lt;0.05). In contrast, when mechanical loading was applied repetitively to femur bones, bone growth was significantly stimulated (p&lt;0.001) when compared to unloaded control bones. Conclusion: In conclusion, depending on the type of bone (embryonic rat metatarsal bone and the larger rat femur bone) mechanical loading exerts opposite effects on bone growth in an ex vivo culture model. The effect of mechanical loading on bone growth requires further in vivo investigations to increase our understanding on the role of mechanical loading in different bones and bone growth disorders.
Presentation: Saturday, June 17, 2023
SAT217 Chronic Asymptomatic Hypoparathyroidism Due To Two Separate Single Nucleotide Heterozygous Mutations In The CaSR Gene
Authors: Anto Antony Mc , Gundlapally Sindhusha , Storm Shelby , Russell Peyton , Verma Vipin , Kant Ravi 
Published: October 2023

Abstract
Disclosure: M. Antony: None. S. Gundlapally: None. S. Storm: None. P. Russell: None. V. Verma: None. R. Kant: None.
Introduction: The most common cause for acquired hypoparathyroidism is either post-surgical or autoimmune destruction of the parathyroid glands. The clinical presentation can range from an asymptomatic state to severe life-threatening symptoms that require intensive therapeutic management with intravenous and/or oral calcium, calcitriol and in some cases, recombinant parathyroid hormone therapy. Hypoparathyroidism secondary to CASR (calcium sensing gene receptor) gene mutation is an uncommon etiology that can also have a varied clinical presentation as above. Clinical Case: A 60-year-old Caucasian male with no significant past medical history was found to have chronic hypocalcemia. He denied experiencing symptoms such as numbness, tingling or cramping sensation around face, lips, or upper extremities. He denied a history of movement disorder or dental problems. He denied a history of neck surgeries or neck radiation exposure. He denied a family history of calcium disorders. He was on calcium carbonate/Vitamin D3 600 mg/400 I.U once daily. The first documented low corrected serum calcium was 6.9 mg/dl (8.6-10.0 mg/dl) in November of 2017. Since then, there have been multiple low corrected serum calcium levels ranging between 7 to 7.6 mg/dl. Patient underwent endocrinology work-up after withholding the above calcium/Vitamin D3 supplementation and it revealed a low corrected serum calcium of 7.6 mg/dl with an inappropriately normal serum PTH level of 37 pg/ml (15-65 pg/ml), normal vitamin D level of 45.1 ng/ml (&gt; 30.0 ng/ml), normal serum phosphorus 3.8 mg/dl (2.5-4.5 mg/dl), and normal serum magnesium 1.8 mg/dl (1.6-2.6 mg/dl). The 24-hour urine calcium was 93 mg/24 hour with a corresponding 24-hour urine creatinine of 1836 mg (1040-2350 mg/24hour) and urine volume of 1625 ml. CASR gene analysis revealed two separate single nucleotide heterozygous mutations. The first mutation was at Exon 4/7, nucleotide position was c.614G&gt;A and Amino Acid position was p.Arg205His. The second mutation was at Exon 7/7, nucleotide position was c.2546T&gt;C and Amino Acid Position is p.lle849Thr. Due to lack of specific symptoms, patient was not initiated on specific therapies such as calcitriol or Natpara (recombinant PTH) and was advised to continue taking the daily calcium/vitamin D3 supplementation. He is being currently monitored every 4 to 6 months to assess for any clinical symptoms along with pertinent laboratory work-up. Conclusion: Hypoparathyroidism due to CASR gene mutation has a varied clinical presentation. One-third of cases do not develop any clinical symptoms, such as our patient and hence do not warrant any specific treatment other than periodic clinical and biochemical assessment.
Presentation: Saturday, June 17, 2023
SAT242 Unusual Case Of Sarcoidosis Presenting With Severe Hypercalcemia: Case Report
Authors: Bhullar Guriqbal , Vora Mehul 
Published: October 2023

Abstract
Disclosure: G. Bhullar: None. M. Vora: None.
Background: This case study discusses an unusual case of hypercalcemia found on routine labs. Clinical Case: A middle-aged Caucasian female with history of MVP, HTN, and anxiety was found to have normal-high calcium of 10.4 mg/dL (nml 8.7-10.4mg/dL) during routine labs offered by her employer. She considered herself relatively asymptomatic and underwent repeat lab testing at her PCP’s office 2 months later which showed calcium of 13.9 mg/dL, ionized calcium of 1.70 mmol/L (nml 1.12-1.32 mmol/L), and intact PTH of 12.4 pg/mL (nml 14.0-72.0 pg/mL). 1 day later, patient presented for an urgent outpatient endocrinology visit. Further questioning revealed polydipsia, polyuria, fatigue, and history of nephrolithiasis more than 10 years ago. Medications included vitamin D, metoprolol, spironolactone, and sertraline. She denied bone pain, weight loss, or GI issues. Physical exam, including heart, chest, and abdomen, was unremarkable. The patient was admitted to a local hospital for hydration and further workup. During her hospital stay, XRAY of chest revealed consolidation in right upper lobe with suspicion of bilateral hilar adenopathy. Contrast CT of chest, abdomen, and pelvis revealed extensive adenopathy, pulmonary nodules, and alveolar consolidation in right upper lobe. Calcified granulomas were found in the spleen. Lab studies showed elevated ACE levels at 87 U/L (nml 14-80 U/L), and elevated activated vitamin D at 108 ng/ml (nml 24.8-81.5 ng/ml). Biopsy results were positive for nonnecrotizing granuloma and negative for malignancy. No suspicious osseous lesions or thyroid gland abnormalities were found. PTHrP and serum protein electrophoresis were found to be in normal range. Hypercalcemia was corrected and patient was treated with glucocorticoids before discharge. Clinical Lesson: Patients with sarcoidosis usually endorse nonspecific symptoms and complaints of pulmonary manifestation may be absent at presentation. 6-13% of sarcoidosis cases involve hypercalcemia (1,2), furthermore, hypercalcemia is more frequently found in white patients (3), who more often present as asymptomatic (4). Thus, clinicians must maintain a high level of suspicion for granulomatous diseases in patients presenting with hypercalcemia regardless of the patient’s symptomology and physical exam findings. References: (1) Baughman RP, Janovcik J, Ray M, Sweiss N, Lower EE. ﻿﻿Calcium and vitamin D metabolism in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2013;30(2):113-120.(2) Studdy PR, Bird R, Neville E, James DG. Biochemical findings in sarcoidosis. J Clin Pathol. 1980;33(6):528-533.(3) Burke RR, Rybicki BA, Rao DS. Calcium and vitamin D in sarcoidosis: how to assess and manage. Semin Respir Crit Care Med. 2010;31(4):474-484.(4) Newman LS, Rose CS, Maier LA. Sarcoidosis [published correction appears in N Engl J Med 1997 Jul 10;337(2):139]. N Engl J Med. 1997;336(17):1224-1234.
Presentation: Saturday, June 17, 2023