bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Unusual Suspect: Hypocalcemia in Preeclampsia After Magnesium Infusion
Authors: Abdulhadi Basma , Agarwal Monica 
Published: May 2021

Abstract
Background: Magnesium plays a vital role in calcium homeostasis. Magnesium sulfate is used in obstetric populations for the management of preeclampsia and eclampsia. Hypocalcemia secondary to iatrogenic hypermagnesemia is an uncommon complication. We report a case of symptomatic hypocalcemia due to hypermagnesemia. Clinical Case: A 26-year-old female with type 1 diabetes at 33 weeks gestation was admitted for preeclampsia. She had severe hypertension and proteinuria, and the decision to induce labor was made. She was started on a magnesium sulfate drip and remained on the drip for 33 hours. Magnesium levels peaked at 7.5 mg/dL (1.7–2.5 mg/dL). The magnesium drip was suspended after delivery. She complained of mild tingling and numbness in her hands, feet, and perioral area. Shortly after delivery, she had a pre-syncopal event. The laboratory evaluation revealed a calcium of 5.9 mg/dL (8.4–10.4) with an albumin of 2.2 g/dL (3.7–5.5), magnesium of 4.2 mg/dL, phosphorus 2.2 mg/dL (2.3–4.6) and GFR above 60 mL/min/1.73m2 . Spot urine calcium to creatinine ratio was 0.17 mg/dL. The 25-hydroxy vitamin D level was low at 12 ng/mL (20–100). The parathyroid hormone (PTH) level was inappropriately normal at 21.7 pg/mL (12–88). She had no history of hypocalcemia, and calcium level obtained six months before the presentation was normal. She received one calcium gluconate infusion, was then started on a continuous calcium gluconate infusion for symptomatic hypocalcemia. She also received oral supplementation of calcium and vitamin D. The calcium levels normalized within 24 hours as the hypermagnesemia resolved from the discontinuation of the magnesium drip. The subsequent PTH level was 38.8 pg/mL. She was discharged on vitamin D supplements. She had no recurrence of hypocalcemia. Conclusion: Our case highlights the effect of magnesium infusion on the parathyroid gland leading to profound symptomatic hypocalcemia. Magnesium plays an essential role in the secretion of PTH. Transient hypoparathyroidism can occur due to hypomagnesemia and hypermagnesemia (tocolytic therapy). In hypomagnesemia, the parathyroid gland secretes insufficient PTH, and the renal and skeletal response to PTH is reduced. In hypermagnesemia, the magnesium activates the extracellular calcium-sensing receptor, subsequently causing inhibition of the parathyroid gland. Amelioration of hypermagnesemia leads to the normalization of parathyroid function. Health care providers should be aware of this phenomenon, especially in the obstetric population receiving magnesium infusion. The monitoring of calcium levels may be necessary for this patient population. The laboratory testing should include magnesium in the evaluation of hypocalcemia. References:
1. Shoback, D. (2008). Hypoparathyroidism. New England Journal of Medicine, 359(4), 391–403.
Unusual Case of Pelvic Osteomyelitis Revealing Osteoporosis
Authors: Farooqi Iqra N , Sharma Anupa 
Published: May 2021

Abstract
Pelvic osteomyelitis is an uncommon and challenging condition to treat. Pressure ulcers, spinal injuries, contiguous sources of tracking infections, pelvic surgical procedures, traumatic injuries and open fractures all serve as nidi for developing pelvic osteomyelitis. We present a case of pelvic osteomyelitis suspected to be caused by insufficiency fractures due to osteoporosis in an anorexic adult.51 year old postmenopausal Caucasian female with undiagnosed anorexia presented to the hospital for severe right-sided pelvic pain and nausea. She denied fevers, vomiting, trauma, surgical procedures, history of pelvic infections, abnormal vaginal discharge, travel, prolonged steroid therapy. She disclosed a strict vegetarian diet, excessive daily exercise, low dairy intake and over 100lb intentional weight loss over the past 30 years. She reported normal menses, used oral contraceptives between ages of 25 to 30, and reached menopause at 49 years. For many years, she denied medical care including age-appropriate cancer screenings. She is employed in academia and denies tobacco, alcohol or drug use. On admission, height 153cm and weight 43kg, BMI 16.7kg/m2. Examination was notable for frail body habitus, moderate RLQ and pelvic tenderness, prominent PSIS and SI joints with decreased RLE range of motion. Laboratory results showed calcium 9.5mg/dL (n 8.6–10.4), phosphorus 4.1mg/dL (2.5–4.5), ALP 181IU/L (45–115), PTH 23pg/dL (n 9–76), Vitamin D 35ng/dL (n 25–80), 24-hour urinary calcium 285mg/24h (n 50–400). Abdominopelvic CT scan showed chronic right pubic ramus and bilateral sacral insufficiency fractures confirmed on MRI with septic arthritis of the pubic symphysis, osteomyelitis of pubic bodies and intramuscular abscess extending to the right adductor muscle. Wound culture was positive for Streptococcus viridans and pelvic bone biopsy showed degenerative changes. The patient completed IV Ceftriaxone therapy and underwent DXA scan confirming osteoporosis (T-scores:-3.8 lumbar spine L1-L4, -3.6 left femoral neck, -3.3 right femoral neck). Alendronate 10mg daily and calcium citrate-vitamin D 1000mg-800IU twice daily was prescribed. Diagnostic workup for secondary causes of severe osteoporosis was unremarkable except for hypercalciuria, for which calcium supplement was held with a plan to repeat in the future. Concern for her cachectic appearance and severity of her illness also elicited a dietician referral. Pelvic osteomyelitis and septic arthritis are seldom found without inciting insults. We report an atypical cause of presumed anorexia induced osteoporosis resulting in pelvic osteomyelitis. Untreated osteoporosis may lead to fracture, resulting in inflammation and predisposing patients to infections. Thus, early recognition and evaluation of osteoporosis in patients at high risk for fracture, such as patients with anorexia, is critical for prevention.
Global Wnt Inhibition With a Porcupine Inhibitor Decreases Established Trabecular Bone in a Mouse Model of Fibrous Dysplasia
Authors: Lung Hsuan , Moody Tania , Wentworth Kelly , Kang Misun , Ho Sunita , Hsiao Edward 
Published: May 2021

Abstract
Background: G protein-coupled receptors (GPCRs) mediate a wide spectrum of physiological functions, including bone development and remodeling. Fibrous dysplasia (FD) is a common skeletal dysplasia caused by increased Gs-GPCR signaling and characterized by fibrotic expansile bone lesions. FD has no effective medical treatments. Our prior studies used the ColI(2.3)+/Rs1+ mouse model where osteoblastic-cell Gs signaling induced a dramatic FD-like phenotype and increased Wnt signaling, which we hypothesized is a major driver of the phenotype. Furthermore, we previously showed that blocking Rs1 expression could reverse the abnormal bone phenotype, providing proof-of-concept for finding therapies for FD.
Methods: Long bone stromal cells from wildtype and ColI(2.3)+/Rs1+ 9-week-old male mice were analyzed by single-cell RNAseq to identify potential cellular sources of Wnt ligands. We compared these findings with global inhibition of Wnt activity by oral administration of the porcupine inhibitor LGK974 to ColI(2.3)+/Rs1+ mice. These mice were analyzed by histology and micro-computed tomography (micro-CT).
Results: Control and ColI(2.3)+/Rs1+ bones showed similar scRNAseq results, except for a large expansion of osteoblastic lineage cells and increased differential expression (DE) genes in this cluster. Expression of Gi-GPCRs was increased, potentially as compensation for the strong Gs-GPCR pathway activation induced by Rs1 expression. We also found increased GH/IGF1 pathway activation in the osteoblastic cluster, and expression of multiple Wnt ligands within multiple cell clusters. We also identified a cell population unique to the ColI(2.3)+/Rs1+ FD-like bone lesions. Broad Wnt production inhibition of porcupine by LGK974 induced dose-dependent resorption of the abnormal FD bone shown by decreased bone volume and trabecular thickness; however, the fibrocellular infiltrate in the ColI(2.3)+/Rs1+ mice was still present.
Conclusions: FD-like bones of ColI(2.3)+/Rs1+ mice showed broad activation of Wnt signaling in multiple cell types, suggesting both cell autonomous and non-cell autonomous activity. Broad Wnt inhibition decreased established FD-like trabecular bone, but the fibrocellular infiltrate did not fully reverse. These results suggest distinct roles of Gs-GPCR and Wnt signaling in FD pathogenesis.
Bone Mineral Density Assessment Following Radiotherapy Related Insufficiency Fractures (RRIFs) of the Pelvis
Authors: Grigoriadou Victoria Chatzimavridou , Higham Claire Emily 
Published: May 2021

Abstract
Background: Pelvic radiotherapy causes symptomatic Radiotherapy Related Insufficiency Fractures (RRIFs) in around 20% of patients. Pathophysiology and predisposing factors for RRIFs are not well understood. Some studies have determined low BMD/osteoporosis to be a risk factor but only a few utilised DXA assessment of BMD at baseline prior to radiotherapy or at the time of RRIF development. Primary or secondary interventions to prevent/treat RRIFs have not been assessed. Methods: Retrospective analysis of patients (n=44; 42F; median age 65.5yrs [IQR 55, 73]) who underwent a DXA (Hologic) scan (Lumbar Spine (LS) (L1-4), Total Hip (TH), Femoral neck (FN) and Trabecular Bone Score (TBS)) following a diagnosis of pelvic RRIF between 2010–2019 at a tertiary referral cancer centre in the UK. Patient characteristics and treatment history were assessed. Osteoporosis (T-score &lt;-2.5), osteopenia (T-score &lt;-1 &gt;-2.5) and normal BMD (T-score &gt;-1) were defined as per WHO classification. Results: Cancer diagnoses; cervical (n=17), endometrial (n=9), vaginal (n=6), anal (n=6), other (n=6). Cancer treatments; chemotherapy (n=36), surgery (n=22), brachytherapy (n=26). Conventional risk factors for osteoporosis; previous fragility fracture (n=9, one on bisphosphonate prior to RRIF), smoking (n=7), glucocorticoid use (n=4), parental hip fracture (n=3), alcohol excess (n=3) and hypogonadism (n=2 and 8 on HRT). Median BMI = 25.4 [22.8, 28.5] kg/m2. Median interval between initiation of radiotherapy and RRIF was 9.8 [7.1, 19.3] months and between RRIF and DXA 3.5 [2, 8] months. At the time of the RRIF, 5 had normal BMD, 20 had osteopenia and 16 osteoporosis. Three patients were &lt;40yrs at time of DXA (lowest Z-score -2 at LS in n=1). Median T-scores in LS, FN and TH were -1.8 [-2.8, -0.98], -1.65 [-2.4, -1.18] and -1.25 [-1.68, -0.5] respectively; N=24 had all Z-scores ≥-1. Median TBS T-score was -2.65 [-3.48, -2]. Median 10-yr hip fracture risk (FRAX HF) was 1.8% [0.7–4.1], major osteoporotic fracture risk (FRAX MO) was 8.9% [5.2- 13] (if RRIF included as FRAX risk factor: 2.9% [1–5] and 15% [8.7- 20] respectively). FRAX HF was ≥ 3% in n=14 and FRAX MO ≥ 20% in n=6 (accounting for RRIF: n= 20 and 12 respectively). Most patients therefore fell below the intervention threshold. Pelvic radiotherapy dose was negatively associated with LS BMD (p=0.0228). Body mass index was positively correlated with LS BMD (p=0.002). Discussion: Most patients did not have osteoporosis at the time of RRIF and overall had low fragility fracture risk as defined by FRAX. RRIFs can also occur with normal hip and spine BMD. Low BMD at the spine was however associated with higher pelvic radiotherapy dose. The mechanism of RRIFs is likely different to osteoporotic fragility fractures and whilst low BMD is a probable risk factor, further studies are required to fully understand their pathophysiology and how fracture risk should be best assessed in these patients.
Temporal Trends in Prescribing of Bone-Directed Therapies in the United States, 2009–2020
Authors: Cromer Sara , D’Silva Kristin M , Yu Elaine Wei-Yin , Landon Joan , Desai Rishi , Kim Seoyoung C 
Published: May 2021

Abstract
Multiple new osteoporosis therapies, including some with novel mechanisms of action, have been introduced in the past decade. However, little is known about temporal trends in prescribing these new medications. Using claims data from the Clinformatics Data Mart (Optum, Inc.), we determined the number of enrolled individuals over age 50 who were prescribed any osteoporosis medication during each quarter between January 1, 2009 and March 31, 2020. Of all individuals receiving therapy, we then calculated the percent receiving each medication. In subgroup analyses, we limited the population to (1) only those with ICD codes for osteoporosis in the current or previous three quarters and without codes for active malignancy during the current or previous quarter, and (2) only those with ICD codes from an oncology provider for active malignancy likely to metastasize to bone during the current or previous quarter. In the all-user cohort, a total of 15.48 million unique prescription or medication administration claims from 1.46 million unique individuals during the study period were analyzed. Of these, 89% were women and 71% over the age of 65, with a mean age of 69. Alendronate was the most common medication used, representing &gt;50% of all treated individuals, and its use increased over time. Percent of users receiving zoledronic acid doubled during this period but remained &lt;5%. Use of other bisphosphonates declined steadily. By comparison, after its approval in 2010, denosumab use increased rapidly, reaching 10% of users in 2015 and 15% of users in 2018. Percent of individuals treated with raloxifene declined after 2013. Use of teriparatide, abaloparatide, and romosozumab remained less than 2% throughout the study period. Trends in the osteoporosis cohort paralleled those in the all-user cohort. In the malignancy cohort, alendronate and zoledronic acid were each used in approximately 30% of individuals at the onset of the study, and both declined over the decade. By contrast, denosumab use rapidly increased after introduction and surpassed use of either bisphosphonate by 2013. Denosumab use continued to increase over time and reached approximately 50% of all bone-directed medication use in the malignancy cohort. Use of other medications, mainly alternate bisphosphonates, was low and declined throughout the study period. In a privately insured cohort between 2009–2020, denosumab use increased significantly in both osteoporosis and malignancy populations, outpacing gains in use of other agents, despite guidelines suggesting that either bisphosphonates or denosumab could be considered first-line therapy for osteoporosis.
Clinical Burden and Practice Patterns in Patients With Chronic Hypoparathyroidism in the United States (US): A Claims Data Analysis Using Diagnosis-Based Criteria
Authors: Sharma Dolly , Deering Kathleen L , Loustau Patrick , Culler Michael D , Allas Soraya , Weiss Blandine , Mitchell Deborah M , Astolfi Danette , Mannstadt Michael 
Published: May 2021

Abstract
Objectives: Significant knowledge gaps exist regarding the comorbidities, treatment and lab testing patterns of patients with chronic hypoparathyroidism (cHP). This study describes a large cohort of patients with cHP identified using a diagnosis-based criteria from a claims database.
Methods: This retrospective cohort study was conducted using a large (130 million individuals) claims database (HealthVerity Closed Payer Claim Medical and Pharmacy databases: Private Source 20) from Oct 2014 to Dec 2019. Eligible patients had ≥2 diagnosis claims of HP (ICD9/10 codes: E20.0, E20.8, E20.9, 252.1) that were 6–15 months apart, a prescription claim for either active vitamin D, calcium, PTH or thyroid replacement therapy between the first qualifying HP claim and within 30 days of the second HP claim, and continuous enrollment for one year before the index date (the date of the first of two qualifying HP diagnosis claims) and ≥16 months after. Patients were followed up to two years after the index date. Patient characteristics, comorbidities, lab testing and treatment patterns were descriptively analyzed.
Results: Out of 43,640 patients with a diagnosis claim for HP, 4,118 patients met the eligibility criteria. The mean age of the cohort was 56.5 years + 18.6 (SD), and 76.4% were females, similar to data from other large cohort studies. The most common comorbidities during the 1-year follow-up were hypertension (56.0%), hypocalcemia (38.7%), cancer (30.5%, of which 24% were thyroid cancers), diabetes (29.4%), chronic pulmonary disease (24.1%), cardiac arrhythmias (17.4%), CKD stage 3–5 (17.0%), osteoporosis (9.6%) and neuropsychiatric disorders, including depressive disorders (22.0%), anxiety (21.6%), and sleep-wake disorders (18.4%). During the 1-year follow up, commonly monitored lab tests included serum calcium (89.9%), eGFR/creatinine (85.7%), 25-hydroxy vitamin D (61.1%), and intact PTH (43.9%). Remarkably, serum phosphorous (36.3%), serum magnesium (35.4%), and 24h-urine calcium (10.5%) were much less often monitored. In addition, BMD was measured in 10.9% patients. Also during the 1-year follow-up, 67.1% of patients had a prescription claim for thyroid replacement therapy, 60.5% for calcitriol, 15.7% for ergocalciferol, and 3.4 % for PTH.
Conclusion: Findings from this study highlight the high comorbidity burden in cHP patients which aligns with the monitoring patterns. Kidney function appears to be a key concern and may be important when considering therapeutic intervention. The comorbidities and practice patterns observed in this study are consistent with the results obtained using a surgery-based approach to identify cHP patients in the same claims database. Future studies will also examine the economic burden of cHP.
Novel Method in Performing PTH Washout for Localizing Parathyroid Adenoma: Case Report & an Institute Experience in Qatar
Authors: Mohammad Salameh Obada Khalil , Gul Wajiha , Al-Thani Noora , Alamer Zaina Abdelhalim , Elhadd Tarik A , Bashir Mohammed , Abou-Samra Abdul B , Zirie Mahmoud A , Naem Emad 
Published: May 2021

Abstract
Introduction: Primary hyperparathyroidism (PHPT) is a common cause of hypercalcemia and mostly caused by benign solitary benign adenoma (80 to 85 %). Definite treatment is the surgical removal. The most commonly used diagnostic modalities are Sestamibi scan and neck ultrasound (US) which can be inconclusive in some cases. Parathyroid hormone (PTH) washout obtained with ultrasound guided FNA may be useful to accurately localize the adenoma. In our study we describe a novel method for PTH washout. Methods: First, blood samples are drawn from the patient’s peripheral vein and placed in two yellow top tubes (3 ml of blood in each tube). 1 ml of normal saline (NS) will be add to Tube # 1 (Control tube). The suspected parathyroid lesion aspirate is obtained via US guided FNA. It is washed in 1 ml of NS and added to tube #2 (PTH washout tube). Both tubes are sent to our local laboratory for PTH assay. The ratio of PTH in PTH washout tube to control tube (PTH W/C ratio) is calculated and considered positive if more than 2. Results: Total 16 patients (12 females and 4 males) underwent the PTH washout procedure. All patients had PHPT. Out of 16 patients, 13 had inconclusive Sestamibi scan while 3 patients didn’t have the scan due to pregnancy. PTH W/C ratio was positive in 13 patients (ruled in) and negative (ruled out) in 3 patients. All patients underwent parathyroid surgery. The operative findings and pathology report were consistent with PTH W/C ratio findings. i.e. parathyroid hypercellularity was found in all the 13 patients ruled in by PTH W/C ratio. Post-surgery, biochemical parameters normalized in all. Conclusion: PTH washout is an important tool in localizing parathyroid lesion in PHPT when Sestamibi scan cannot be done or if it is inconclusive. PTH W/C ratio can be performed with our novel method to accurately localize the PTH lesion and improve surgical outcome.
Secondary Hyperparathyroidism Among Bariatric Patients: Unraveling the Prevalence of an Overlooked Foe
Authors: Mendonça Fernando , Neves João Sérgio , Silva Maria Manuel , Canha Marta Borges , Costa Cláudia , Cabral Pedro , Guerreiro Vanessa , Lourenço Rita , Meira Patricia , Ferreira Maria J , Salazar Daniela , Pedro Jorge , Varela Ana , Viana Sara , Belo Sandra , Lau Eva , Souto Selma , Freitas Paula , Carvalho Davide ,   CRIO group
Published: May 2021

Abstract
Introduction: Bariatric surgery (BS) is an effective therapeutic approach for obese patients. It is associated with important gastrointestinal anatomic changes, predisposing these subjects to altered nutrient absorption that impact phosphocalcium metabolism. This study aims to clarify the prevalence of secondary hyperparathyroidism (SHPT) and its predictors in patients submitted to BS. Methods: Retrospective unicentric study of 1431 obese patients who underwent metabolic surgery between January/2010 and June/2017 and who were followed for, at least, a year. In this group, 185 subjects were submitted to laparoscopic adjustable gastric banding (LAGB), 830 underwent Roux-en-Y gastric bypass (RYGB) and 416 sleeve gastrectomy (SG). Data comprising 4 years of follow-up were available for 333 patients. We compared the clinical and analytical characteristics of patients with and without secondary hyperparathyroidism (considering SHPT a PTH˃69pg/mL), taking also into account the type of surgery. A multiple logistic regression was performed to study the predictors of SHPT after BS. Results: The overall prevalence of SHPT before surgery was 24.9%, 11.2% one year after surgery and 21.3% four years after surgery. At 12 months after surgery, LAGB had the highest prevalence of patients with SHPT (19.4%, N=36), RYGB had 12.8% (N=274) and SG 5.3% (N=131). At 48 months after surgery, RYGB had the highest prevalence of SHPT (27.0%, N=222), LAGB had 13.2% (N=53) and SG 6.9% (N=58). Multi-variate logistic analysis showed that increased body mass index and age, decreased levels of vitamin D and RYGB were independent predictors of SHPT one year after surgery. The only independent predictor of SHPT four years after surgery was RYGB. Conclusion: The prevalence of SHPT is considerably higher before and four years after BS than 1 year after surgery. This fact raises some questions about the efficacy of the implemented follow-up plans of vitamin D supplementation on the long term, mainly among patients submitted to RYGB.