bluuebunny/crossref_metadata_2025 huggingface dataset:
6578 National Trends in Vitamin D Deficiency and Racial-Ethnic Differences Among US Women With Low Bone Mineral Density
Authors: Atri Avica , Anastasopoulou Catherine
Published: October 2024

Disclosure: A. Atri: None. C. Anastasopoulou: None.

Introduction: Vitamin D (Vit D) plays a critical role in maintaining bone mineralization and its deficiency adversely impacts bone health. Contemporary trends of Vit D deficiency (VDD) and racial-ethnic differences in these trends among US women with low bone mineral density (BMD) are not well elucidated. Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) for the years 2009-10, 2013–14 and 2017–18 to include U.S. women ≥ 50 years with femoral neck T score ≤ -1. Osteoporosis was defined by a T-score ≤ -2.5. BMD assessment in NHANES was not completed in 2011–12 and 2015–16, and therefore not included in the analysis. Femoral neck BMD was measured by dual energy x-ray absorptiometry (DEXA) on Hologic Discovery Model A Densitometers (Hologic, Inc., Bedford, Massachusetts). VDD was defined as serum 25(OH)D <30 nmol/L. Participants with missing data on race-ethnicity, BMD and Vit D data were excluded. Independent samples median test was used for comparing medians. The Cochran-Armitage test was utilized for trend analysis. Results: Overall, in women with low BMD, from 2009-10 to 2017-18, prevalence of osteoporosis increased from 13.7% to 16.9% while VDD decreased significantly from 5.6% to 2.3% (p trend = 0.001). When stratified by race-ethnicity, the prevalence of osteoporosis increased in Whites (14.1% to 17.6%, p trend = 0.001), Hispanics (12.6% to 13.7%, p trend = 0.001) and Other race-ethnicity (Asian/Mixed) (14.1% to 21.4%, p trend = 0.001), but a modest decrease was noted among the Black population (7.3% to 6.8%, p trend = 0.001). VDD was disproportionately high among Blacks (In 2009-10: 28.1% vs 4.2% in Whites, 5.4% in Hispanics and 10.7% among Others). However, significantly improving trends in VDD were observed among all the groups, regardless of race/ethnicity, to 12.5% prevalence among Blacks, 1.3% in Whites, 4.9% in Hispanics and 1.1% in the Other race ethnicity group (p trend = 0.001). Discussion In this contemporary analysis, rates of VDD have decreased from nearly 1 in 20 to 1 in 50 women with low BMD in the US. Highest prevalence of VDD was noted among Blacks, seen in nearly 1 in 3 Black women in 2009-10, with improvement to 1 in 8, in 2017-18. Similar favorable trends of decline in VDD were observed across all other racial-ethnic groups as well. Despite the overall improvement in VDD, prevalence of osteoporosis declined only among Black women, suggesting the potential role of other protective factors against osteoporosis among them. Nevertheless, VDD continues to remain prevalent in this high-risk group, emphasizing the need for public health interventions to bridge this gap.

Presentation: 6/2/2024
7633 Novel CASR Gene Mutation in a patient with Familial Hypocalciuric Hypercalcemia and Papillary Thyroid Cancer
Authors: Parihar A , Nylen E S , Gandhi S M
Published: October 2024

Disclosure: A. Parihar: None. E.S. Nylen: None. S.M. Gandhi: None.

Familial Hypocalciuric Hypercalcemia (FHH) is predominantly caused by loss-of-function mutations in the calcium-sensing receptor (CaSR) characterized by a benign elevation in calcium and PTH which can be mistaken for primary hyperparathyroidism (PHPT). Missense mutations in the CaSR gene causing FHH have been documented but not much is known regarding their clinical significance. We describe a patient with FHH found to have a novel variant mutation. A 37-year-old male with hypogonadism and fatty liver was incidentally found to have hypercalcemia suggestive of PHPT with elevated PTH (102-114 pg/ml), normal vitamin D, and Fractional Excretion of Calcium (FECa) of 0.014. His father also had hypercalcemia and had undergone parathyroid surgery. The patient denied kidney stones and had a normal bone density. Subsequent Sestamibi and 4D CT scan suggested parathyroid adenoma on the left mid-lower pole of the thyroid. Neck ultrasound also showed a left 1.2 x 1 x 1 cm thyroid nodule as well as a left neck mass with calcifications. Fine needle aspiration was positive for metastatic Papillary thyroid cancer(PTC) in the left neck mass and patient underwent total thyroidectomy along with subtotal parathyroidectomy and lateral neck dissection. Thyroid pathology confirmed multifocal PTC with lymph node involvement that were BRAF V600 positive. Parathyroid pathology was benign hyperplasia. The PTH level decreased appropriately intraoperatively (69%), but postoperatively a rise was noted with levels remaining 70-90 pg/ml with normal calcium levels. Repeat FECa was 0.007, supporting the diagnosis of FHH. Given patient’s father also had hypercalcemia, genetic testing was pursued. This revealed CaSR gene missense mutation (c.1382T>C p.Leu461Pro, heterozygous). This variation is not present in population databases and has been classified as a variant of uncertain significance. It can be difficult to distinguish PHPT from FHH based on FECa as in this case. The patient also had PTC which is not known to be associated with FHH. Due to uncertain significance of this novel CaSR missense mutation, long term follow-up and further familial genetic testing will help better understand clinical implications.

Presentation: 6/2/2024
12375 Rhabdomyolysis As A Cause Of PTH-independent Hypocalcemia In A Child With Acute Influenza Infection
Authors: Bhattarai Samhita , Halpin Kelsee
Published: October 2024

Disclosure: S. Bhattarai: None. K. Halpin: None.

Introduction: Hypocalcemia is characterized by low blood calcium level. Normal range for calcium for ages 12- 19-year is 8.5-10.6 mg/dli . Severe hypocalcemia is considered as serum calcium level of <7 mg/dl. Hypoparathyroidism, pseudohypoparathyroidism and Vitamin D deficiency are some of the most common causes encountered by pediatrician endocrinologists. Rhabdomyolysis with hypocalcemia and elevated PTH is a rare presentation that should be considered, particularly for children presenting with acute viral illness. We present a rare case of rhabdomyolysis associated with hypocalcemia not related to hypoparathyroidism. Case: A 12-year-old female presented to the ED with body ache, poor oral intake and vomiting. She was found to be influenza positive. Labs showed hypocalcemia (4.8 mg/dl). She had an undetectable 25-OH vitamin D level (<5 ng/ml) and elevated iPTH level (609 pg/ml). We discussed the possibility of her etiology of hypocalcemia as Vitamin D deficiency although her presentation was atypical at an older age with negative imaging for rickets, hyperphosphatemia (6.0 mg/dl), and normal ALP (334 unit/L). She did not have any phenotypic features of Albright’s hereditary osteodystrophy with normal renal function. She had elevated CK (4829 U/L) supporting rhabdomyolysis secondary to acute influenza as a cause of her hypocalcemia. Rhabdomyolysis, a known complication of influenza infection, causes cell membrane destruction which impairs the normal function of Na-K-ATPase channel leading to increase in intracellular sodium activating Na/Ca exchanger. This in turn causes influx of calcium intracellularly causing hypocalcemia. Additionally, any injury leads to high phosphorus release from cells due to its lysis. High phosphorus is also caused by reduced oxidative metabolism in muscles impairing phosphate use. This excess of phosphate then combines with calcium and causes calcium-phosphate complex in soft tissues. Hyperphosphatemia additionally inhibits 1 alpha hydroxylase limiting formation of calcitriol leading to hypocalcemia. iiConclusion: Our patient had severe hypocalcemia due to influenza-related rhabdomyolysis. Rhabdomyolysis is an important cause of hypocalcemia in children, especially with acute viral illness. Accordingly, it is also important to obtain serum electrolytes in patients presenting with rhabdomyolysis as hypocalcemia may lead to complications like seizures and cardiac arrhythmia. Endnotes:i Roizen, Jeffrey & Shah, Vipul & Levine, Michael & Carlow, Dean. (2013). Determination of Reference Intervals for Serum Total Calcium in the Vitamin D-Replete Pediatric Population. The Journal of clinical endocrinology and metabolism. 98. 10.1210/jc.2013-3105.ii Ding LN, Wang Y, Tian J, Ye LF, Chen S, Wu SM, Shang WB. Primary hypoparathyroidism accompanied by rhabdomyolysis induced by infection: A case report. World J Clin Cases. 2019 Oct 6;7(19)

Presentation: 6/2/2024
6858 Robot-Assisted Surgery of Mediastinal Intrathymic Parathyroid Adenoma: A Case Report
Authors: Jovanovic Filip , Jovanovic Visnja , Attaullah Khan Mohammed , Fletcher Stephen
Published: October 2024

Disclosure: F. Jovanovic: None. V. Jovanovic: None. M. Khan: None. S. Fletcher: None.

Background: Ectopic foci of parathyroid tissue pose a diagnostic challenge and lead to a delay in patient care. We present a case report of intrathymic parathyroid adenoma with successful removal using robot-assisted surgery. Case Report: A 33-year-old female with past medical history of gastroesophageal reflux disease, depression, and chronic anemia was found to have hypertension during her third trimester prenatal visit. The patient was complaining of fatigue, abdominal discomfort, and constipation. Laboratory results showed elevated serum calcium 11.3 mg/dL (7.9–10.6), albumin 2.7 gm/dL (3.4–5.0), corrected calcium 12.3 mg/dL (7.6–10.6), and parathyroid hormone (PTH) 122 pg/mL (14–72). A year after childbirth, she continued to experience these symptoms with persistent hypercalcemia and no etiology identified. As part of diagnostic workup, the patient underwent computed tomography (CT) with and without (WWO) contrast of the neck and sestamibi parathyroid scan, both of which were unremarkable. The patient was then referred to a tertiary hospital for a technetium 99m sestamibi followed by single-photon emission computed tomography (SPECT) imaging of neck and chest, which showed scintigraphic findings suspicious of ectopic parathyroid adenoma in the upper mediastinum. Over the next few months, the patient underwent SPECT imaging and 4D helical CT WWO contrast of the neck and thorax that showed 1cm ectopic parathyroid adenoma within the left thymic lobe, at the level of the top of the pulmonary artery arch and upper ascending aorta proximal to the arch. Upon patient’s admission to a quaternary medical center, her lab work showed serum calcium 11 mg/dL and PTH 237 pg/dL. The decision was made to proceed with surgical resection of intrathoracic parathyroid adenoma using robot-assisted (da Vinci® Surgical System) thymectomy. Histopathology analyses of surgery specimens were consistent with parathyroid adenoma and benign thymic tissue. The patient’s lab work on the following day showed significant improvement with serum calcium 8.5 mg/dL and PTH 30.9 pg/mL. While literature review acknowledges intrathymic location of ectopic thyroid[1], research on minimally invasive surgical approach involving this pathology is scarce. Upon surgery, the patient reported full resolution of her symptoms. Conclusion: Persistent hypercalcemia in the setting of unrevealing parathyroid adenoma should prompt suspicion for ectopic parathyroid location. Robot-assisted thymectomy poses a minimally invasive surgical approach in diagnosing and treating mediastinal intrathymic parathyroid adenoma. References:1.Abraham BM Jr, Sharkey E, Kwatampora L, Ranzinger M, von Holzen U. Mediastinal Intrathymic Parathyroid Adenoma: A Case Report and Review of the Literature. Cureus. 2023 Jul 22;15(7):e42306.

Presentation: 6/2/2024
6795 Romosozumab improves bone mineral density and markers of bone resorption in a patient with osteogenesis imperfecta
Authors: Shakir Mohamed K M , Godar Cassandra M , Piech Ricard , Duc Hoang Thanh
Published: October 2024

Disclosure: M.K. Shakir: None. C.M. Godar: None. R. Piech: None. T.D. Hoang: None.

The efficacy of romosozumab for improving osteoporosis and preventing skeletal fractures is uncertain in patients with osteogenesis imperfecta (OI). In this case report we describe the beneficial effect of romosozumab on markers of bone turnover and bone density in a patient with OI. A 64-year-old man with OI was referred to endocrinology for evaluation of repeated fractures. The patient had a few fractures as a child (2 collar bones and wrist, oldest at age 14); and he recovered well. He reports that he has had a short stature and blue sclera but was otherwise asymptomatic. His son was also diagnosed with OI based on bone biopsy showing abnormalities suggestive of OI type II or IV. This son has had multiple fractures, 10 shoulder dislocations, and 2 hip replacements. He has another son with a history of multiple fractures but no formal diagnosis of OI. His third son has no findings. The patient’s brother has been diagnosed clinically with OI type 4, and had genetic testing showing a COL1A1 pathogenic variant (c. 976G>C, p.Gly326Arg) . Genetic testing in our patient revealed a COL1A1 pathogenic variant (c. 976G>C, p.Gly326Arg) confirming the diagnosis of OI type 4. 8 years ago, he was treated with alendronate for 12 months, which did not prevent recurrent fractures, and all therapies were discontinued. However, recently, the frequency of fractures involving multiple sites had increased. At presentation, his lumbar and bilateral total hip bone mineral density (BMD) values were severely decreased to 0.725 and 0.566 g/cm2, (T scores -3.3 and -3.1) respectively. Because of severe osteoporosis, he was treated with romosozumab 210 mg every month. After 12 months of treatment, his lumbar and total hip BMD increased by 28.3% and 7.2 % respectively. Additionally, bone formation markers increased, and bone resorption markers decreased at 12 months of therapy. He did not develop any fractures after treatment with romosumab. No severe adverse drug effects were observed. At the end of 12 months he received 5 mg zoledronic acid IV. This case revealed good responses of BMD and bone turnover markers to romosozumab treatment, which can be considered as an effective treatment option for osteoporotic OI patients. Studies involving large number of patients are required.

Presentation: 6/2/2024
5122 Severe Hypercalcemia as a Manifestation of Immune Reconstitution Inflammatory Syndrome in a Patient with AIDS and Disseminated MAC Infection
Authors: Vahidi Rad Mona , Ahmed Samir , Kumar Aditi
Published: October 2024

Disclosure: M. Vahidi Rad: None. S. Ahmed: None. A. Kumar: None.

Introduction: Granulomatous disease can cause hypercalcemia due to increased production of 1,25 dihydroxyvitamin-D. Mycobacterium avium complex (MAC) infection is an AIDS (acquired immunodeficiency syndrome)-defining illness and a granulomatous disease that can lead to hypercalcemia. We report a case of severe hypercalcemia from Immune Reconstitution Inflammatory Syndrome (IRIS) in a patient with AIDS and disseminated MAC which developed several months after initiation of appropriate antibiotic and antiviral therapy. Clinical Case: A 30-year-old female with HIV on anti-retroviral therapy and disseminated MAC infection on antibiotics developed PTH independent mild hypercalcemia in the 10.9-11.5 mg/dL range about 4 months after initiation of antiviral and antibiotic therapy. 1,25 dihydroxyvitamin D level was normal at 50 pg/mL (reference range 18-78 pg/mL). The hypercalcemia worsened and about 8 months after initiation of antimicrobial therapy, she had a hospitalization for severe hypercalcemia with corrected calcium of 15.2 mg/dL and acute kidney injury. PTH was suppressed at 6.9 pg/mL and repeat 1,25 dihydroxyvitamin D level was elevated at 129 pg/mL (reference range 18-78 pg/mL). Other testing for PTH independent hypercalcemia including PTH- Related Peptide, serum protein electrophoresis (SPEP) and TSH were normal. She was diagnosed with hypercalcemia from increased calcitriol production in the setting of IRIS secondary to disseminated MAC. Hypercalcemia secondary to increased production of calcitriol in patients with MAC and HIV infection might happen or worsen months after starting the antimicrobial treatments and has been reported as a potential manifestation of immune reconstitution. MAC-associated IRIS has been reported to be associated with a T-helper cell response with increased number of interferon-gamma-producing T-cells and Th1-cytokines that can potentially cause a granulomatous reaction. These granulomas will have increased macrophage 1-alpha-hydroxylase activity that can further result in more production of 1,25 dihydroxyvitamin D3 and cause more hypercalcemia. Prednisone was started with resultant improvement in hypercalcemia. Conclusion: Severe hypercalcemia due to worsening of subclinical granulomatous infections such as MAC can be a manifestation of IRIS in patients with HIV infection or AIDS who are on antiretroviral treatments. This responds to glucocorticoids.

Presentation: 6/2/2024
7635 Severe Osteoporosis in a Patient with Heterotopic Calcification: A Case Report
Authors: Bacha D Salih , Khan L Z
Published: October 2024

Disclosure: D. Salih Bacha: None. L.Z. Khan: None.

Background: While osteoporosis and heterotopic ossification (HO) are distinct conditions affecting bone health, their coexistence poses intriguing clinical challenges. Osteoporosis, characterized by increased bone fragility, typically results from various factors such as aging, steroid use, or malabsorption. HO is a condition where bone forms abnormally in soft tissues. Risk factors that predispose to HO include male sex, spinal cord injury, trauma, surgery, and genetic factors. Treatment of HO is typically surgical resection and NSAIDs. Initial evidence supported the use of bisphosphonates for preventing ectopic bone formation post-trauma, but recent data failed to show significant benefit in HO prevention. This case presents a patient with unique challenges of both HO and bone fragility with multiple severe vertebral fractures. Case: A 44-year-old male patient had a major motor vehicle accident necessitating multiple recurrent abdominal surgeries. During one exploratory laparotomy, diffuse mesenteric calcifications were noted, indicative of HO. A baseline Dual X-ray Absorptiometry (DXA) scan revealed bone density of 1.003 g/cm2 and 0.788 g/cm2 at the spine and femoral neck, respectively, concerning for osteopenia. He was started on zoledronic acid in preparation for upcoming intestinal transplant. Few months after the transplant, he was started on daily tacrolimus and hydrocortisone for immunosuppression. Within months, he experienced sudden back pain while riding an elevator, and was found to have acute fractures in T8 and T9 vertebrae. A repeat DXA scan showed a further decline in bone density to 0.909 g/cm2 and 0.748 g/cm2 at the spine and femoral neck, respectively. Within a year, additional fractures occurred in the thoracic and lumbar spine (T10, T11, T12, L1, L2, L3, and L4), requiring multiple kyphoplasty interventions. Over time, worsening kyphosis, back pain, and height loss occurred, significantly affecting the patient's quality of life. He continued receiving yearly zoledronic acid infusions and underwent regular DXA scans, which revealed mild improvement in his bone density. Currently, there are no established guidelines specifying the optimal duration for bisphosphonate treatment in such cases. Therefore, our individualized treatment plan involves a tentative 10-year course of bisphosphonate treatment with yearly assessment of bone mineral density. Conclusion: Although the patient had some risk factors for osteoporosis, including daily steroid and tacrolimus use, the severity and frequency of his fractures suggested a potential synergy between osteoporosis and HO, where the formation of heterotopic calcifications may have been exacerbating his bone loss. The coexistence of osteoporosis and HO in this patient underscores the need for individualized care and establishment of treatment guidelines in patients with multiple bone disorders.

Presentation: 6/3/2024
6970 Severe Symptomatic Hypophosphatemia After Intravenous Iron Therapy: An Under-recognized Adverse Reaction
Authors: Morvant A , Olajide O
Published: October 2024

Disclosure: A. Morvant: None. O. Olajide: None.

Introduction: Iron deficiency is a common condition that is often treated with intravenous preparations of iron supplementation. It has been documented in the literature that ferric carboxymaltose is the form of intravenous iron supplementation that is associated with the highest incidence of hypophosphatemia, when compared to other formulations of intravenous iron therapy. This case highlights a severe case of hypophosphatemia after ferric carboxymaltose therapy that led to multiple hospitalizations and required several months of oral and intravenous phosphorus repletion. Clinical Case A 36-year-old woman presented to the ED with severe diffuse arthralgias, generalized muscle weakness, and fatigue. Laboratory analysis revealed the following: phosphorus 1.2 mg/dL (2.3-4.7 mg/dL), 25-hydroxyvitamin D 13 ng/mL (25-80 ng/mL), parathyroid hormone 220 pg/mL (16-77 pg/mL), and calcium 8.5 mg/dL (8.4-10.5 mg/dL). She was admitted and started on intravenous and oral phosphorus repletion as well as oral ergocalciferol. She was subsequently discharged home on oral phosphorus and ergocalciferol supplementation, with a phosphorus level of 1.8 mg/dL. She was readmitted one day later with persistent arthralgias, myalgias, and severe fatigue, and found to have a phosphorus level of 1.1 mg/dL. Additional laboratory studies revealed the following: FGF23 41 pg/mL (<59 pg/mL) and 24-hour urine phosphorus 2191 mg/24hr (400-1300 mg/24hr). The patient notably had a history of chronic severe iron deficiency anemia due to menorrhagia and had been treated with intravenous iron sucrose infusions 7 months prior to her presentation. Due to adverse reactions to iron sucrose, this was switched to ferric carboxymaltose, and she had received two doses; one month and two weeks prior to her initial presentation. She was treated again with intravenous and oral phosphorus repletion and ergocalciferol and discharged after two weeks on oral phosphorus and ergocalciferol as well as thrice-weekly intravenous phosphorus infusions in the outpatient setting. She continued intravenous phosphorus infusions for about three months, and this was subsequently discontinued without recurrent hypophosphatemia. She is currently on low doses of oral phosphorus with normophosphatemia. Conclusion: Intravenous ferric carboxymaltose therapy can lead to severe and long-lasting, treatment-resistant hypophosphatemia due to increased urinary phosphate excretion. An increased awareness about this is needed by clinicians in treating patients who receive ferric carboxymaltose and monitoring phosphorous levels is crucial. References: (1) Schaefer, Benedikt et al. “Hypophosphatemia after intravenous iron therapy: Comprehensive review of clinical findings and recommendations for management.” Bone vol. 154 (2022): 116202. doi:10.1016/j.bone.2021.116202

Presentation: 6/1/2024
6721 Short-Term Responses of Serum 25-Hydroxyvitamin D to Weekly Calcifediol or Cholecalciferol in Healthy Subjects
Authors: Caldeira R B , Nunes A S , Cazzetta F Z , Medeiros M S , Oliveira L B , Bandeira M P , Bandeira F F
Published: October 2024

Disclosure: R.B. Caldeira: None. A.S. Nunes: None. F.Z. Cazzetta: None. M.S. Medeiros: None. L.B. Oliveira: None. M.P. Bandeira: None. F.F. Bandeira: None.

Introduction: Recent studies have shown that oral calcifediol (CAL) induces faster serum 25-hydroxyvitamin D (25OHD) increases than cholecalciferol (CHO) as demonstrated in some studies on SARS-Cov2 infection. It is hypothesized that this rapid elevation is due to the unique mode of intestinal absorption of CAL to the portal vein system in comparison with CHO which is absorbed mainly by the lymphatic route. Data on weekly administration of calcifediol are still scarce. The aim of the present study was to compare serum 25OHD responses in the short term (30 days) to weekly doses of CAL or CHO in healthy subjects. Methods and Results: We studied 35 subjects (34% men, mean age 24.6 ± 4.6 years, BMI 22.9 ± 2.9 kg/m², waist circumference 74.7 ± 6.5 cm, SBP 111.1 ± 12.7 mmHg, and DBP 73.1 ± 9.1 mmHg) who were randomized to receive weekly oral CAL 70 mcg (18 subjects) or CHO 350 mcg (14,000 IU, 17 subjects). Doses were chosen based on the 2000 IU/day potency equivalence. Patients were matched for age, gender, BMI, and BP. They were contacted weekly to confirm medication adherence. Serum 25OHD concentrations were measured before administration of both agents and 24 hours after the last dose, using an immunochemiluminescent assay (Abbott Diagnostics, Lake Forest, IL, USA) with a detection range from 4.9 to 151.3 ng/ml. At baseline serum 25OHD was 32.1 ±8.8 vs 33.1 ± 6.6 in CAL and CHO groups respectively (p=0.691). In CAL group 8 subjects had serum 25 OHD < 30 ng/mL (1 subject had 14.7 ng/mL) and in the CHO none had serum 25OHD below 20 ng/mL and 5 subjects had levels between 20 and 30 ng/mL. After 1 month, serum 25OHD levels rose significantly 3.3 times more with CAL than with CHO (+29.61 ± 7.39 ng/mL vs. 9.00 ± 3.50 ng/mL; p < 0.001). In CHO group one subject remained with 25OHD below 30 ng/mL after the intervention. Conclusion: We found a rapid and robust elevation of serum 25OHD levels with CAL compared to CHO at similar potency doses. This may have clinical implications for conditions in which there is a need for immediate availability of 25OHD to peripheral tissues.

Presentation: 6/2/2024
12555 Stress Fractures In A Military Population Across Different Career Stages
Authors: Joseph Spiro Andrew , Shakir Mohamed K M , Duc Hoang Thanh
Published: October 2024

Disclosure: A.J. Spiro: None. M.K. Shakir: None. T.D. Hoang: None.

Stress fractures are overuse injuries that occur in people with normal bones in the absence of an acute injury. They tend to occur in individuals who are beginning new or more intense physical activity and affect military personnel at higher rates than the general population. These injuries negatively impact force readiness and may lead to serious injury or discharge from military service. Much of the existing literature has focused on basic training recruits, as this population is known to be susceptible to stress fractures. Few studies have examined military populations with many years of service to evaluate how fracture trends may change after the initial basic-training period. We aimed to characterize stress fracture patterns in military personnel over the full spectrum of career stages, from new recruit through late career, and identify whether stress fracture locations varied by career length. We performed a retrospective chart of review covering a 3-year period (from Jan 1, 2017 to Dec 31, 2019) of military patients in the National Capital Region who were diagnosed with a new stress fracture. Career length was defined at the time of diagnosis as: new recruit (<12 months’ time-in-service), early-career (1 to <5 years’ time-in-service), mid-career (5 to <14 years’ time-in-service), and late-career (≥14 years’ time-in-service). Stress fracture locations were defined as: tibia, fibula, foot, femoral neck, femoral shaft, and pelvis. Frequencies of fracture types and presence of multiple fractures were described and compared by career length group using Chi-square tests. Femoral neck (11.1% vs 3.6%), femoral shaft (8.1% vs 1.8%), and pelvis fractures (3.8% vs 0.7%) were more frequent in new recruits vs other career length groups (p≤0.03 for each). Foot fractures were less frequent (19.2% vs 34.3%) in new recruits vs other career length groups (p<0.001). The presence of multiple fractures (23.7% vs 10.1%) was more frequent in new recruits vs others (p=0.01). Frequencies of each fracture type and of presence of multiple fractures were qualitatively similar among early-career, mid-career, and late-career groups. In our military population, new recruits had higher frequency of femoral neck, femoral shaft, and pelvic fractures, but lower frequency of foot fractures when compared to other patient groups. New recruits also had multiple fractures more often than other patients groups at the time of presentation.

Presentation: 6/1/2024
12366 The Association Between Obstructive Sleep Apnea And Bone Health: A Systematic Review And Meta-analysis
Authors: Boon Teo Chong , Hoe Chan Yong , Tay Joshua K , SJ Cheong Crystal
Published: October 2024

Disclosure: C. Teo: None. Y. Chan: None. J. Tay: None. C. Cheong: None.

Importance: Obstructive sleep apnea (OSA) is a globally prevalent yet underdiagnosed sleep disorder with well-known metabolic consequences. However, the relationship between OSA and bone health, especially osteoporosis, remains poorly understood. Given that both OSA and osteoporosis are highly prevalent chronic conditions with significant public health indications, elucidating the relationship between these conditions is important. Objective: To investigate the association of OSA with bone health, specifically if individuals with OSA had a higher risk of developing osteoporosis, and discuss its clinical implications. Data Sources: A systematic search of MEDLINE (via PubMed), Embase and Cochrane Library from inception to 22 November 2023. Keywords related to obstructive sleep apnea, osteoporosis and bone density were included. Study Selection: Studies that reported on the association between OSA and osteoporosis in adults aged 18 years and above were included. Outcomes of interest included any markers of osteoporosis or bone mineral density. Data Extraction and Synthesis: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and data extracted independently by two observers. Meta-analysis across studies was pooled using a random-effects model. Main Outcome(s) and Measure(s): Correlation of OSA with bone mineral density, as well as the mean difference in bone density scores and the risk of developing osteoporosis among between individuals with OSA and without OSA. Results: We identified 15 studies comprising 158,273 individuals. All studies had low or moderate risk of bias. The presence of OSA was negatively correlated with bone mineral density on meta-analysis (pooled correlation = -0.30; 95% CI -0.42 – -0.17; N = 8). Individuals with OSA also had poorer bone mineral density scores (mean difference = -0.58, 95% CI, -1.15 – 0.01; N = 8), and had significantly higher risk of developing osteoporosis (adjusted odds ratio = 2.18; 95% CI, 1.14–4.136; N = 4). Notably, both body mass index (BMI) and age were not significant effect modulators in the correlation of OSA and bone density. Conclusions and Relevance: OSA is associated with diminished bone health and a significant risk in developing osteoporosis. Further studies are required to determine if treatment of OSA may have the potential to mitigate these risks.

Presentation: 6/3/2024
8250 The Impact of Inflammatory bowel disease on Outcomes for Osteoporotic fractures (OF) hospitalization Using the National Inpatient Sample Database
Authors: Khan Shahryar , Zia Laila , Alam Khan Mashal , Kashif Amin Muhammad , Atif Khan Muhammad , Sattar Farhan
Published: October 2024

Disclosure: S. Khan: None. L. Zia: None. M. Khan: None. M. Amin: None. M. Khan: None. F. Sattar: None.

Background: Osteoporosis has a significant implication on healthcare system with increasing hospitalizations for fractures, disabilities, and causing individual financial burden. Patients with Inflammatory bowel disease (IBD) are at higher risk of developing osteopenia and osteoporosis than the general population. We aimed to investigate the effects of sociodemographic of patients and outcomes for OF admissions with or without IBD. Methods: Data were obtained from the National Inpatient Sample, 2020, provided by the Healthcare Cost and Utilization project. This data represents 20% of admissions in the USA, weighted to represent the entire country. Our primary outcome was inpatient mortality, while the secondary outcomes were hospital length of stay (LOS), and total hospitalization charges (THC). We conducted the analysis using STATA software version 18.0, multivariate regression analysis was used to adjust for potential confounders. Results: Among 32 million hospitalizations, we found 60,890 admissions with a principal diagnosis of OF, 730 (1.2%) had concomitant IBD. Our study indicated that patients admitted with IBD were younger (72.63 Vs 78.35 P ≤ 0.05), more likely to be white (91.7% Vs 85.6%) and had higher Chronic steroid use (8.8% Vs 4.3, P = 0.02). The number of patients died during hospitalization for OF were 1455, 2.3% in non-IBD and 4% with IBD. There was no significant difference in inpatient mortality of patients admitted for OF with or without IBD, Crude Odds ratio of Mortality 1.75 (95% CI 0.77-3.98) and adjusted odds ratio of Mortality 2.03 (95% CI 0.86-4.82). Multivariable analysis revealed that Age (OR= 1.02; 95% CI 1.009-1.03), female (OR= 0.58; 95% CI 0.45-0.75), Charlson Comorbidity Index (OR= 1.22; 95% CI 1.18-1.1.27) were predictors of Mortality. Among secondary outcomes, there was no significant difference in LOS (Adjusted Mean difference 0.69, P= 0.27), THC (Adjusted Mean difference 5331, P=0.430). Mean LOS in hospital for OF was 6.16 days and Mean THC was 77652 USD. Conclusion: National admissions data indicates that hospitalizations for Osteoporotic fractures with or without IBD showed no significant difference in inpatient mortality, Length of stay in the hospital and total hospitalization charges. Despite lack of statistical difference, clinical relevance is important given greater mortality in OF with IBD. As physicians, it is important to screen the appropriate population for osteoporosis which can help with earlier diagnosis, guiding for preventive and treatment strategies.

Presentation: 6/3/2024
7090 The Largest Study on Asymptomatic Primary Hyperparathyroidism (APHPT) Conducted at the Tertiary Care Riga East Clinical University Hospital (RECUH)— Three Years of Data
Authors: Stūrīte Diāna , Rasa Ingvars
Published: October 2024

Disclosure: D. Stūrīte: None. I. Rasa: None.

Background: Primary hyperparathyroidism (PHPT) is the third most common endocrine disorder and a leading cause of hypercalcemia in the outpatient setting. The study aimed to assess the characteristics, management and outcomes of pts with APHPT. Methods: A retrospective analysis of data from 168 pts with APHPT, evaluated at RECUH from January 2021 to November 2023 was conducted. Information obtained included medical records, laboratory data, imaging results, surgical protocols, histopathology data. Statistical analysis was performed using IBM SPSS 29.0. Results: From the 168 pts (mean age: 63.7±11.8 years), 86.3% (n=145) were females. Predominantly, 67.3% (n=113) exhibited mild hypercalcemia (2.6-3.0mmol/L), while 22.6% (n=38) had moderate hypercalcemia (3.0-3.49mmol/L), and 4.8% (n=8) -severe hypercalcemia (≥3.5mmol/L). 5.3% (n=9) had normocalcaemic PHPT. The mean preoperative maximal calcium level was 2.9±0.3mmol/L, iPTH level - 247.6±224.9pg/mL, minimal phosphorus - 1.3±6.7mmol/L and 25-OH vitamin D level - 28.3±14.7ng/mL. The mean preoperative eGFR was 90.6±28.2 ml/min/1.73m2, creatinine - 72.5±23.9μmol/L. Parathyroid adenoma sizes ranged from 0.3x0.4cm to 5.3x3.7cm. Calcium levels positively correlated with adenoma cross-sectional area (ρ=0.187, p=0.029) and maximal adenoma dimension (ρ=0.215, p=0.011). Ultrasonography convincingly detected parathyroid adenomas in 63.9% (107/168), SPECT/CT - 68.4% (52/76), 99mTc-sestamibi scintigraphy - 65.6% (61/93), 3D-CT - 70.6% (24/34), contrast-enhanced ultrasonography - 84% (21/25) and MRI in - 40% (2/5) cases. 12.5% (n=21) pts had unlocated parathyroid adenoma. 34.5% (n=58) of pts had osteoporosis, 47.6% (n=80) osteopenia, 12.5% (n=21) had a history of osteoporotic fracture, 17.3% (n=29) had gallstones and 22.0% (n=37) - kidney stones. 80.4% (n=135) of pts had thyroid nodules, 48.2% (n=81) - nontoxic goitre, 24.4% (n=31) - autoimmune thyroiditis, 41.7% (n=70) - hypertension, 10.5% (n=18) - type 2 diabetes. 18.5% (n=31) pts were found to have a diagnosis of malignancy. 61.9% (n=104) of pts underwent parathyroidectomy. Histopathology and radiologic imaging revealed single parathyroid adenoma in 95.2% (n=99), double parathyroid adenomas in 1.9% (n=2), parathyroid hyperplasia in 2.9% (n=3) and parathyroid carcinoma in 1.9% (n=2) pts. The mean maximal postoperative calcium level (n=103) was 2.4±0.1mmol/L, iPTH (n=101) - 63.5±27.7pg/mL, 25-OH vitamin D - 41.5±13.3ng/mL, and the mean minimal phosphorus (n=56) - 1.1±0.2mmol/L. Conclusions: APHPT remains frequently encountered and often showcases bone manifestations. It's crucial to consider the diverse clinical manifestations and associated conditions in patients with APHPT.

Presentation: 6/2/2024
8251 The Silent Thief: Neurofibromatosis Type 1 (NF1) Leading to Severe Osteoporosis and Recurrent Bone Fractures
Authors: Hernan Sacoto Daniel , Madani Kulsum , Patel Dhara , De Rosairo Anne , Kiratt Rai Gur , Franco-Akel Alberto A , Belokovskaya Regina
Published: October 2024

Disclosure: D.H. Sacoto: None. K. Madani: None. D. Patel: None. A. De Rosairo: None. G. Rai: None. A.A. Franco-Akel: None. R. Belokovskaya: None.

Introduction: NF1 is an autosomal dominant disorder known to cause a remarkable reduction in bone mineral density (BMD) with almost a fivefold increase in fracture risk. Since fractures are associated with a high disability burden, early identification, prompt treatment, and consideration of prophylactic measures are important. We present a case of NF1 complicated with osteoporosis and recurrent bone fractures. Case presentation: An 85-year-old female with a history of NF1 complicated with a malignant left ankle Peripheral Nerve Sheet Tumor came in after a mechanical fall. Vital signs were stable. Examination demonstrated short stature, widespread cutaneous neurofibromas, and café au lait macules. Complain of generalized bone pain, in addition, to diffuse osseous demineralization on imaging and mild alkaline phosphatase elevation (141 U/L), led to further investigation, which revealed osteomalacia due to severe vitamin D deficiency (9.8 ng/mL) in the setting of malnutrition (albumin:3.4 mg/dL). Otherwise, normal renal function, phosphorus (3.7mg/dL) and calcium corrected for albumin (8.9 mg/dL). Previous records identified a right humerus close proximal fracture three years ago. At that time, a DEXA scan demonstrated severe osteoporosis with a lumbar T-score of -4.8 and dual femur of -3.7. She was started on Vitamin D supplementation, with questionable compliance. Bisphosphonates and denosumab were not prescribed due to the lack of guidelines on NF1 population. During the last two years, she experienced three more fractures, including a left femoral greater trochanteric, right 8th rib, and non-displaced pubic ramus fractures. One month ago, unfortunately, it expired due to septic shock. Discussion: Osteoporosis is found in 20–50% of NF1 patients, and it is associated with reduced serum 25-hydroxyvitamin D primarily due to a reduced expression of Vitamin D Receptor on neurofibromas in addition to reduced sun exposure and poor physical activity. At the molecular level, the loss of neurofibromin function causes a pathological increase in intracellular Ras activity, leading to an induction of osteoclastic activity and inhibition of osteoblastic differentiation. Currently, NF1 patients are resistant to bisphosphonate-induced apoptotic signals, and there are no guidelines for the use of denosumab in NF1 with osteoporosis. However, a recent clinical trial involving 141 NF1 adults identified that weight-bearing exercise, optimizing calcium and 25-hydroxyvitamin D intake and increased sun exposure can minimize BMD loss. However, guidelines for the management of bone abnormalities in NF1, including earlier screening and prophylactic therapy with vitamin D, are needed.

Presentation: 6/3/2024
8446 Thermoneutral Housing has Limited Effects on Social Isolation-Induced Bone Loss in Male C57BL/6J Mice
Authors: Mountain R , Langlais A , Lary C , Motyl K J
Published: October 2024

Disclosure: R. Mountain: None. A. Langlais: None. C. Lary: None. K.J. Motyl: None.

Social isolation stress has numerous known negative health effects, including increased risk for cardiovascular disease, dementia, as well as overall mortality. The impacts of social isolation on skeletal health, however, have not been thoroughly investigated. We previously found that four weeks of social isolation through single housing led to a significant reduction in trabecular and cortical bone in male, but not female, mice. In addition to evidence of reduced bone remodeling, we found a significant elevation of Pdk4 and reduced brown adipocyte and lipid droplet size in the brown fat of isolated male mice, suggesting increased brown fat activation and thermal stress. Single housing at room temperature (∼20-25°C)—below the thermoneutral range of mice (∼26-34°C)—can lead to cold stress, which has known negative effects on bone. Therefore, the aim of this study was to test the hypothesis that housing mice at thermoneutrality, thereby ameliorating cold-stress, will prevent social isolation-induced bone loss in male C57BL/6J mice. 16-week-old mice were randomized into social isolation (1 mouse/cage) or grouped housing (4 mice/cage) at either room temperature (∼23°C) or in a warm temperature incubator (∼28°C) for four weeks (N=16/group). As seen in our previous studies, isolated mice at room temperature had significantly reduced bone parameters, including femoral bone volume fraction (BV/TV), bone mineral density (BMD), and cortical thickness (p < 0.001). Contrary to our hypothesis, these effects were not ameliorated by thermoneutral housing. In fact, 28°C housing tended to reduce BV/TV (p = 0.0711) and BMD (p = 0.0883), and significantly reduced cortical thickness (p = 0.0492) within the grouped mice relative to 23°C housing. There were no differences in serum bone resorption or formation markers between the groups, nor were there any differences in fat or lean mass. Social isolation did significantly increase gene expression of the glucocorticoid receptor Nr3c1 (p = 0.0288) and tended to increase expression of Hsd11b1 (p = 0.0947), an enzyme critical for corticosterone activation, across housing temperatures. Increased glucocorticoid activity can enhance brown fat activation, including increased Pdk4 expression. Overall, our data suggest social isolation-induced bone loss is not a result of thermal stress from single housing. These results provide key insights into the potential mechanisms mediating the effects of social isolation on skeletal health and will inform future studies investigating the role of glucocorticoid signaling.

Presentation: 6/1/2024
7999 Tumor Induced Osteomalacia Caused By Glomangiopericytoma
Authors: Kabir Nighat , Campbell Elizabeth , Singh Sarvani
Published: October 2024

Disclosure: N. Kabir: None. E. Campbell: None. S. Singh: None.

Introduction: Tumor induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused primarily by FGF-23 secreting tumors. Excessive production of FGF23 causes hypophosphatemia, decreased phosphate resorption in the gut, increased renal phosphate wasting, and decreased activation of Vitamin D. This leads to decreased bone density, bone pain, proximal muscle weakness, impaired gait, and recurrent fractures. Case Presentation: 44 year old male with a history of recurrent insufficiency fractures and weakness. At the time of evaluation, he reported fracture of tibial growth plate, sacral fracture, and metatarsal stress fracture. Other symptoms included bone pain, fatigue, muscle weakness, and intercostal muscle spasms with exertion. His pain was debilitating, requiring crutches to ambulate. Available labs at that time were significant for hypophosphatemia (1.3 mg/dL), elevated ALP (160 U/L), low 25OH-vitamin D (26 ng/mL), and normal calcium (8.7 mg/dL). Urine studies demonstrated phosphaturia (fractional excretion of phosphate, 62.4%). FGF23 level resulted at the upper limit of normal (210 RU/mL). Pending further evaluation, burosumab was started. Further work up included a 68Ga-PET-DOTATATE scan revealing a somatostatin receptor expressing soft tissue mass in the left sphenoid sinus and posterior left ethmoid sinus. The scan also demonstrated impending bilateral femur fractures, prior rib fractures, and sacral insufficiency fractures. Based on these findings, he was admitted to the hospital and underwent prophylactic, intramedullary nail fixation of his bilateral femur fractures. He underwent resection of skull base tumor with the final pathology revealing a sinonasal glomangiopericytoma. Immunohistochemical stain was positive for CD99 and cyclin D1, and focally positive for SMA, consistent with histopathologic diagnosis. Patient required prolonged inpatient rehabilitation to recover independent ambulation. Discussion: Sinonasal glomangiopericytoma (SNGP) is a mesenchymal tumor that accounts for <0.5% of all nasal and sinus tumors. TIO due to SNGP is extremely rare, with only a few cases reported since the 1990s. As seen with our patient, TIO from SNGP rarely presents with sinonasal symptoms, and can often be overlooked. Our patient hadb significant progression of disease and disability due to numerous delays in diagnosis and management. Definitive cure for TIO can be achieved with complete surgical resection of the tumor, but failure to diagnose in a timely manner can result in decline in quality of life. Our takeaway from this case is that providers should obtain FGF23 levels, especially in the setting of hypophosphatemia and phosphaturia, to complete the work up for osteomalacia.

Presentation: 6/1/2024
12597 Undetectable Intact Pth - Can It Still Be Due To Primary Hyperparathyroidism?
Authors: Bantu S S , Rosenthal R S
Published: October 2024

Disclosure: S.S. Bantu: None. R.S. Rosenthal: None.

Introduction: Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia. It is caused by increased levels of parathyroid hormone (PTH) from the parathyroid glands. There is a shift in the clinical presentation of PHPT from symptomatic disease to asymptomatic presentation, due to the inclusion of calcium in basic metabolic panel. We present a patient who had hypercalcemia with undetectable PTH due to PHPT caused by parathyroid adenoma. PTH levels were detectable with resolution of hypercalcemia and improvement in symptoms after the parathyroidectomy. Very few case reports have been reported of PHPT with low or suppressed intact PTH. Case: 66-year-old female with history of hyperlipidemia, hypothyroidism, hypertension, obstructive sleep apnea who was referred for evaluation of hypercalcemia noted on basic metabolic panel. She complained of fatigue, body aches, insomnia and denied any calcium supplements. Calcium 11.1mg/dl, albumin 4.2gm/dl, PTH <1pg/ml, vitamin D 39ng/ml, ionized calcium 1.46 mMol/L, phosphorus 2.6mg/dl, magnesium 2.3mg/dl, PTHrP 0.7pMol/L. After ruling out other causes of hypercalcemia, parathyroid ultrasound showed 1.8 x 1.3 x 1.1cm right inferior parathyroid adenoma. Sestamibi scan showed an approximately 1.5x 1cm lesion in the right inferior parathyroid region confirming the adenoma. A trial of calcitonin was done to make sure it is PHPT to which she responded. Surgery was done with removal of the right inferior parathyroid gland. Intraoperative PTH was done at 5, 10, 15 mins after the removal of the gland which was still undetectable at 1pg/ml. Pathology showed hypercellular parathyroid of 1927mg. Post operatively her symptoms improved with resolution of hypercalcemia and her PTH was detectable at 15.8pg/ml. Discussion: This patient presented as a diagnostic challenge with hypercalcemia, undetectable PTH and parathyroid adenoma. Serial dilutions of the intact PTH were done which didn’t show the hook effect. Undetectable PTH in our case could be explained by the secretion of a mutated form of the intact PTH molecule by the parathyroid adenoma suggesting post-translational change in the molecule that is not measurable by the current assays but still it exerts it effect on the PTH receptor. Our report highlights that PHPT should be considered even in the setting of undetectable serum PTH. More research is needed to study the identification and measurement of the post-translational changes in the intact molecule of the PTH.

Presentation: 6/2/2024