bluuebunny/crossref_metadata_2025_split huggingface dataset:
THU406 24-hydroxylase Deficiency, A Rare Cause Of Hypercalcemia
Authors: Hodge Jordesha , Gortakowski Michele , Barua Nabonita , Jamal Issra , Daniel Shaji , Crosio Stefano 
Published: October 2023

Abstract
Disclosure: J. Hodge: None. M. Gortakowski: None. N. Barua: None.
Background: 24-hydroxylase is encoded by CYP24A1 and functions to convert 1,25 dihydroxyvitamin D and 25-hydroxyvitamin D to their inactive metabolites[1]. 24-hydroxylase deficiency due to CYP24A1 variants is rare and clinical presentation is characterized by hypercalcemia, nephrolithiasis and nephrocalcinosis. Treatment may include thiazide diuretics, sodium cellulose phosphate and ketoconazole.[1] We present a case of hypercalcemia due to 24-hydroxylase deficiency. Clinical Case: A 56-year-old male with chronic kidney disease initially presented with hypercalcemia at age 48 to another institution. He was initially diagnosed with primary hyperparathyroidism in the setting of an inappropriately normal parathyroid hormone (PTH) with hypercalcemia. He subsequently had one parathyroid gland removed a year after diagnosis, then another two years later due to continued hypercalcemia. However, he continued to have persistent hypercalcemia, 10.9-12.7 mg/dL but now in the setting of low PTH. In addition, his 1,25 dihydroxyvitamin D was high normal and 25-hydroxyvitamin D was high off exogenous vitamin D supplementation, which raised the suspicion for 24-hydroxylase deficiency. He presented to our institution eight years later. Initial evaluation revealed, calcium 12.4 (8.6-10.5 mg/dL), phosphorous 2.9 (2.5-4.5 mg/dL), normal albumin, PTH 13 (15-65 pg/mL), 1,25 dihydroxyvitamin D 87.2 (19-79.3 pg/mL) and 25-hydroxyvitamin D 38.3 (20-50 ng/mL), 24hr urine calcium 0.23 (0.05-0.30 g/24hr), fractional excretion calcium 0.02. His 25-hydroxyvitamin D:24,25 dihydroxy vitamin D ratio was unable to be calculated, since 24,25 dihydroxy vitamin D was below the limit of quantification. He also had evidence of nephrocalcinosis on renal ultrasound. Evaluation of other causes of non-PTH mediated hypercalcemia included normal angio converting enzyme, PTHrP level, vitamin A level, SPEP and UPEP. Chest X-ray did not demonstrate any evidence of granulomatous disease. He has been managed conservatively for suspected 24-hydroxylase deficiency. He has been advised to limit calcium and vitamin D intake, as well as sun exposure, with close monitoring of his calcium levels. His calcium levels have ranged from 10.7-12.4 mg/dL and he has had one hospitalization in the setting of heart failure where his calcium levels improved with furosemide to 8.7-9.9 mg/dL. Conclusion: In patients with persistent non-PTH dependent hypercalcemia, 24-hydroxylase deficiency should be a differential diagnosis when other common causes are excluded.
References: 1. Nesterova G, Malicdan MC, Yasuda K, et al. 1,25-(OH)2D-24 hydroxylase (CYP24A1) deficiency as a cause of nephrolithiasis. Clinical Journal of the American Society of Nephrology. 2013;8(4):649-657. doi:10.2215/cjn.05360512
Presentation: Thursday, June 15, 2023
THU410 Retrospective Review Of Adults Patients With Suspected Or Confirmed Hypophosphatasia At The Penn Bone Center
Authors: Tran Richie , Hvisdas Christopher , Riordan Marianne , Novotny Lindsay , Kallish Staci , Patel Kruti , Al Mukaddam Mona 
Published: October 2023

Abstract
Disclosure: R. Tran: None. C. Hvisdas: None. M. Riordan: None. L. Novotny: None. S. Kallish: None. K. Patel: None. M. Al Mukaddam: None.
Abstract: Hypophosphatasia (HPP) is a rare inherited genetic disorder that affects the mineralization of bones and teeth. HPP is the result of a pathogenic variant involving the tissue nonspecific alkaline phosphatase (ALPL) gene. The clinical presentations of HPP greatly vary from serious perinatal manifestations (respiratory failure, seizures, and death) to mild manifestations in adulthood. In adults, hallmark signs and symptoms include early loss of primary or secondary teeth, osteoporosis, osteomalacia, recurring metatarsal stress fractures, and abnormal laboratory values, such as low alkaline phosphatase (ALP), elevated phosphoethanolamine, and elevated vitamin B6.The treatment and follow up of adults with HPP are not clearly described. This retrospective study characterizes 43 patients referred to the Penn Bone Center for suspected HPP. Twelve of the 43 patients had a confirmed HPP diagnosis based on both clinical presentations and evidence of variant in the ALPL gene. The twelve patients consisted of both female and male adults between the ages of 24 to 74. In addition, the patients had abnormal ALP levels, ranging between less than 5 to 38 units per liter (normal range: 38 to 126 U/L). Six of these patients had previous or current use of asfotase alfa with variable treatment response. Two patients decided to stop treatment due to lack of clinical benefit or worsening of symptoms while on asfotase alfa therapy. Biochemical and bone mineral density follow-up while on therapy has not been shown to be helpful in monitoring treatment response. Asfotase alfa is a subcutaneously administered synthetic human alkaline phosphatase that was approved by the Federal Drug Administration (FDA) in 2015 for treatment of perinatal/infantile- and juvenile-onset hypophosphatasia. However, the efficacy of treatment in adults remain unclear at this time. Further research is required to better define the natural progression of mild or adult-onset hypophosphatasia and the patients who would benefit from enzyme therapy.
Presentation: Thursday, June 15, 2023
THU411 Fracture And Osteoporosis In Hereditary Connective Tissue Disorders: A Systematic Review And Meta-analysis
Authors: Charoenngam Nipith , Rittiphairoj Thanitsara , Jaroenlapnopparat Aunchalee , Ponvilawan Ben , Waitayangkoon Palapun , Supakitjanusant Pichatorn , Prasitsumrit Vitchapong , Pongchaiyakul Chatlert , Holick Michael F 
Published: October 2023

Abstract
Disclosure: N. Charoenngam: None. T. Rittiphairoj: None. A. Jaroenlapnopparat: None. B. Ponvilawan: None. P. Waitayangkoon: None. P. Supakitjanusant: None. V. Prasitsumrit: None. C. Pongchaiyakul: None. M.F. Holick: None.
Introduction: Hereditary connective tissue disorders (HCTDs) refer to a constellation of conditions caused by defects in the structure and synthesis of extracellular matrix. It is well-known that bone fragility is the hallmark feature of osteogenesis imperfecta. Interestingly, other HCTDs, including Ehlers-Danlos syndrome (EDS), Marfan’s syndrome (MFS) and Loeys-Dietz syndrome (LDS) are shown to be associated with bone fragility. However, most of the existing studies were small in sample sizes, thereby limiting validity and generalizability. Therefore, we aimed to identify all available data, using systematic review and meta-analysis, to determine the risks of fracture and osteoporosis in patients with HCTDs, including EDS, MFS and LDS. Methods: From inception to June 2022, potentially eligible studies were identified in the Medline and EMBASE databases using search strategy that included terms for “HCTD”, “Fracture” and “Osteoporosis”. Eligible studies must consist of a group of patients with HCTD and report prevalence/incidence of fracture/osteoporosis in their participants, with or without comparison with healthy individuals. Point estimates with standard errors were obtained from each study and combined using the generic inverse variance method. Results: Among the 4,206 articles that were identified, 19 studies fulfilled the eligibility criteria. The pooled prevalence of fracture in patients with EDS, MFS and LDS were 44% (95%CI, 25 - 65%, I2 88%), 17% (95%CI, 11 - 26%, I2 68%), 69% (95%CI, 47 - 85%, I2 83%), respectively. The pooled prevalence of osteoporosis among patients with EDS was 17% (95%CI, 8 - 34%, I2 96%). EDS was associated with fracture [pooled odds ratio 4.90 (95%CI, 1.49 - 16.08, I2 86%)], but not osteoporosis [pooled odds ratio 1.34 (95%CI, 0.28 - 6.36, I2 87%). One study reported a 5% (95%CI, 3 - 8%) prevalence of osteoporosis in MFS, and MFS was associated with fracture [incidence rate ratio 1.35 (95%CI, 1.18 - 1.55)] and osteoporosis [subhazard ratio 3.97 (95%CI, 2.53 - 6.25)]. Conclusion: EDS was associated with fracture, which could be independent of osteoporosis status. MFS had a milder degree of increased risk of fracture and osteoporosis. Despite the lack of data from cohort studies, there was a significantly higher rate of fracture in LDS.
Presentation: Thursday, June 15, 2023
THU412 Role of Glucocorticoid On Bone Metabolism Through AKAP13
Authors: Igarashi Katsushi , Ishida Akiko , Koide Hisashi , Yokote Koutaro 
Published: October 2023

Abstract
Disclosure: K. Igarashi: None. A. Ishida: None. H. Koide: None. K. Yokote: None.
It is not completely clear to what extent glucocorticoids are involved in which stages and sites of bone differentiation, development, and maintenance. we investigated the mechanism of glucocorticoid regulation through the regulation of Rho activation using a regulatory system for the expression of the RhoA activator AKAP13. To examine the effect of glucocorticoids on preosteoblasts, immortalized bone marrow mesenchymal stem cells (imBMSCs) were sown in 6-well plates at a concentration of 2x105/well and treated with various concentrations (0-1000 nM) of dexamethasone (Dex) 24 hr later, and The expression of GILZ, osteoblast and adipocyte-associated markers were evaluated using qRT-PCR. AKAP13 expression vector and AKAP13 siRNA were used to examine the response to Dex. GILZ was induced in a Dex-dependent manner on both day1 and day4. In the differentiation phase, PPARG2 expression was not changed by Dex, but GILZ was induced in a similar Dex-dependent manner. In proliferating imBMSCs, Dex treatment tended to enhance PPARG2 expression in a dose-dependent manner by introducing AKAP13 expression vectors. On the other hand, AKAP13 gene expression was significantly down-regulated in imBMSCs treated with AKAP13 siRNA, and Alp2 mRNA was up-regulated in imBMSCs treated with Dex compared to those not treated with Dex. It has a nuclear receptor binding domain and is known to be involved in osteogenesis. On the other hand, AKAP13 expression was decreased by osteoblast differentiation in an in vitro system, suggesting that AKAP13 may influence the regulation of GC action between the proliferative and differentiation phases of BMSCs.
Presentation: Thursday, June 15, 2023
THU442 A Case Of Early Medication Related Osteonecrosis Of The Jaw In Patient Receiving Intravenous Zoledronate For Treatment Of Osteoporosis
Authors: Ekpe Victor , Au Xiu Ying , Golson Maria , McGuire Lisa E , Aguirre Lina E 
Published: October 2023

Abstract
Disclosure: V. Ekpe: None. X. Au: None. M. Golson: None. L.E. McGuire: None. L.E. Aguirre: None.
Introduction: Medication related Osteonecrosis of the jaw (MRONJ) is a rare side effect in patients receiving nitrogen-containing bisphosphonates intravenously and other anti-bone resorptive agents such as denosumab . The incidence is 0.1% in patients with metabolic bone disease1. Annual infusions of zoledronic acid have been recommended in order to improve patient compliance, optimize therapeutic effects and to minimize side effects in selected patients. Risk factors include history of malignancy, smoking, poor dental health, prior oral surgery, high dose exposure to zoledronic acid and longer duration of treatment with anti-resorptive therapy. Increasing usage of bisphosphonates and other antiresorptive drugs, have led to an increased incidence of MRONJ. Clinical Case: We report the case of a 63-year-old Caucasian female suffering from osteoporosis who developed early stage MRONJ. She has a history of several years of oral bisphosphonate treatment and three annual administrations of zoledronic acid. Patient presented with a new complaint of gum pain and a sore above her tooth. Prior routine dental exams have all been unremarkable. She was promptly referred and evaluated by a dental provider. Dental photographs showed a resorptive defect at the gumline. Patient was diagnosed with medication related osteonecrosis of the jaw (MRONJ) in the gum area above tooth number 9. Our patient was treated with oral amoxicillin 500mg twice daily and chlorhexidine gluconate mouth rinse twice daily. The intravenous zoledronic acid was discontinued. Her gum infection resolved. Discussion: Early detection of MRONJ is possible in patients potentially at risk for this rare complication. Providers should be aware of MRONJ and refer those patients on antiresorptive drugs to the dentist for frequent evaluation and assessment for any drug-related jaw changes.
References: 1. Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR, Felsenberg D, Gagel RF, Gilsanz V, Guise T, Koka S, McCauley LK, McGowan J, McKee MD, Mohla S, Pendrys DG, Raisz LG, Ruggiero SL, Shafer DM, Shum L, Silverman SL, Van Poznak CH, Watts N, Woo SB, Shane E; American Society for Bone and Mineral Research. Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2007 Oct;22(10):1479-91. doi: 10.1359/jbmr.0707onj. PMID: 17663640. 2. Shoback D, Rosen CJ, Black DM, Cheung AM, Murad MH, Eastell R. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Guideline Update. J Clin Endocrinol Metab. 2020 Mar 1;105(3):dgaa048. doi: 10.1210/clinem/dgaa048. PMID: 32068863.
Presentation: Thursday, June 15, 2023
THU468 Finding An Effective Treatment For Osteoporosis In Gaucher Disease
Authors: Lesniak Christopher , Akula Monika Soujanya 
Published: October 2023

Abstract
Disclosure: C. Lesniak: None. M.S. Akula: None.
Background: Gaucher disease is a rare autosomal recessive disorder, leading to a deficiency of the enzyme glucocerebrosidase and accumulation of lipid-laden macrophages and dysfunction of multiple organs. The skeletal system is commonly affected resulting in reduced bone mineral density (BMD), marrow infiltration and bone infarction. Enzyme replacement therapy (ERT) has been a mainstay of treatment, and bisphosphonate therapy has been used to help treat osteoporosis, but newer agents are not well studied in this population. Case Description: The patient is a 62 year old female with a history of Gaucher disease Type 1 (GD1) and osteoporosis, treated with alendronate. She was diagnosed with GD1 in childhood and treated with glucocerebrosidase as ERT. She was diagnosed with osteoporosis in 2018 and started on bisphosphonates after a DXA scan showed a T-score at the lumbar spine of −3.2 and -1.4 at the left hip. She denied bone or back pain and has no history of any osteolytic lesions or osteonecrosis. Workup for secondary causes of osteoporosis was negative. She was taking alendronate 70 mg weekly, calcium 1800 mg daily, and vitamin D 4000 IU daily. Labs showed calcium 9.1 mg/dL, TSH 1.530 uIU/mL, PTH 34 pg/mL, and 25-hydroxy vitamin D 38.7 ng/mL. Repeat DXA scan showed worsening osteoporosis with a T-score at the lumbar spine of −3.4 and left hip of −2.5. As her BMD worsened while on alendronate for 3 years, teriparatide was offered as an alternative treatment. Discussion: Gaucher disease is a rare lysosomal storage disorder affecting multiple organs. Up to 90% of patients with GD1 have bone involvement of some kind. DXA scan should be done soon after diagnosis. Reduced BMD in GD1 is common and is associated with increased fracture risk. ERT has been the main management option to treat bone manifestations with improvement in BMD shown after 3-5 years. After 8 years of treatment with ERT, patients have been shown to reach the BMD of the age and sex matched population. In addition to ERT, calcium and vitamin D3 are recommended to increase BMD. There is no standard of treatment for osteoporosis in Gaucher patients, although bisphosphonates have been shown to improve BMD. Had our patient had early DXA scans, treatment may have been initiated sooner. A single case report showed improvement in BMD with the use of teriparatide after bisphosphonate failure. The efficacy of alternative agents, such as teriparatide and romosumab, in treating osteoporosis in patients with Gaucher disease needs to be further investigated.
Presentation: Thursday, June 15, 2023
FRI691 Intrathyroidal Parathyroid Adenoma With Congenitally Absent Contralateral Thyroid Lobe Treated With Thermal Ablation
Authors: Bilandzic Luka , Bilandzic Luka , Korkusuz Hudayi 
Published: October 2023

Abstract
Disclosure: L. Bilandzic: None. L. Bilandzic: None. H. Korkusuz: None.
We present a rare case of primary hyperthyroidism with ectopic adenoma located in the right thyroid lobe with congenitally absent left thyroid lobe which was treated with thermal ablation. A 60-year-old woman was referred to endocrinology clinic for further evaluation of her elevated total serum calcium of 11.4 mg/dL (reference range 8.5-10.5), elevated parathyroid hormone (PTH) level of 106 (10-60 pg/mL). Bone mineral densitometry showed a total T score of -2.9 in L1-L4. Other results were vitamin D 25-OH 30 ng/mL (ref. range 30 - 100), TSH 3.36 µIU/mL (ref range 0.4-5.0), eGFR 83 (normal &gt; 59 mL/min/ 1.73 m²). She was asymptomatic and had no history of kidney stones. Other causes of hypercalcemia were refuted. Given the osteoporosis in her lumbar spine, parathyroid localization and surgery were suggested. Thyroid and parathyroid sonography demonstrated a solid hypoechoic nodule in the right thyroid lobe, 12x10x11mm, with smooth margins, no calcifications, classified as ACR TI-RADS T4. Left thyroid lobe was not appreciated and was considered to be congenitally absent since the patient did not have a history of a previous thyroid resection. Further localization studies (99mTc Sestamibi parathyroid scintigraphy and 4D-CT of the neck) did not reveal any other possible candidates for parathyroid adenomas. Eventually, a fine needle aspiration of the nodule in the right thyroid lobe was performed. PTH needle wash showed a PTH value of 633 pg/mL whereas the PTH value ≥ 100 pg/mL is suggestive of the presence of PTH secreting tissue. Given the thyroid anatomy found with this patient, a right lobe hemithyroidectomy would result with a permanent substitution dependent hypothyroidism. As an alternative, thermal ablation was presented as a treatment option for which the patient opted. She underwent the procedure in local anesthesia. Sonographic imaging of the adenoma was followed by the percutaneous insertion of the coagulation electrode. The utilized high frequency ablator was used with an output of 9 to 40 W and a frequency of 470 ± 10 kHz. There were no complications developed during or after the procedure. Two weeks after the thermal ablation, PTH level was measured at 55 pg/mL, total serum calcium at 9.5 mg/dL, TSH 1.01 µIU/mL. Sonography showed a hyperechoic nodule at the former location of the parathyroid adenoma, which was evaluated as a scar tissue. Three months after the procedure total calcium was at 9.3 mg/dL, PTH at 58 pg/mL, hence no biochemical evidence of pHPT. This is a rare case of ectopic parathyroid adenoma located in the thyroid gland with hemi agenesis of the contralateral lobe. A minimally invasive thermal ablation was performed with the goal of inactivation of the adenoma and preserving the euthyroid function.
Presentation: Friday, June 16, 2023
OR13-06 Romosozumab After Denosumab Improves Lumbar Spine Bone Mineral Density And Microarchitecture Greater Than Denosumab Continuation In Postmenopausal Women
Authors: Hong Namki , Shin Sungjae , Kim Hyunjae , Rhee Yumie 
Published: October 2023

Abstract
Disclosure: N. Hong: None. S. Shin: None. H. Kim: None. Y. Rhee: None.
Transitioning to romosozumab from antiresorptives can be an effective strategy to improve bone strength. A phase 2 trial and a few observational studies showed improvement of lumbar spine bone mineral density (BMD) with maintained hip bone density by romosozumab after denosumab. However, whether transition to romosozumab after denosumab is associated with greater improvement in BMD and microarchitecture compared to denosumab continuation remains unclear. In this propensity score-matched cohort study, we analyzed data from postmenopausal women who initiated denosumab between 2017 and 2020 (at least two injections; n=696). Individuals who were transited to 12 months of romosozumab after denosumab (n=105) were 1:1 matched to those who continued denosumab (n=591) by propensity score using age (69 years), body mass index, BMD, and numbers of denosumab injection at the time of transition, BMD improvement during denosumab treatment, prior fracture and bisphosphonate use (n=93 for each; denosumab-romosozumab [DR] and denosumab-denosumab [DD]). BMD gain by denosumab in DR and DD groups from denosumab initiation to transition time (to romosozumab or denosumab continuation; median 4 times [range 2 to 8] of denosumab injection) was +4.6% and +2.4% in the lumbar spine (LS, T-score −3.4 to −3.1) and total hip (TH, T-score −2.5 to −2.4), without statistical difference. DR group showed greater LSBMD gain compared to the DD (+7.0% vs. +2.5%, P&lt;0.001) during 12 months after the transition time, yielding greater net LSBMD gain in DR (median 2 years of denosumab followed by 1-year romosozumab) compared to DD (median 3 years of denosumab; +11.6% vs. +7.0%, P&lt;0.001). Differences in LSBMD gain between DR and DD groups remained robust (adjusted difference +4.7% point, P&lt;0.001) after adjustment for covariates. Hip BMD changes did not differ between DR and DD (DR vs. DD; FN, +1.3% vs. +2.0%, p=0.409; TH, -0.9% vs. +0.2%, P=0.132). DR group showed significant improvement in the trabecular bone score during romosozumab use (1.288 to 1.311, p=0.005), whereas denosumab continuation in the DD group did not (1.297 to 1.309, p=0.103). During 12 months, one incident morphometric vertebral fracture (grade 1) and one nonvertebral fracture (patella) were observed in DD, whereas one ankle fracture was observed in the DR group. In summary, romosozumab after denosumab improved lumbar spine BMD and microarchitecture greater than denosumab continuation, with the maintenance of hip BMD.
Presentation: Friday, June 16, 2023