Diffuse Bone Pain Research Articles

8031 Pelvic Fracture Related to Brown Tumor in Severe Secondary Hyperparathyroidism

Abstract Disclosure: M. Bodenstab: None. M. Lieberman-Ulm: None. V.S. Lagari-Libhaber: None. Background: Severe hyperparathyroidism can result in end-organ damage to the skeleton, known as osteitis fibrosa cystica (OFC). Histologically, OFC manifests as “Brown tumors”, which are so named due to the hemosiderin deposition that occurs from recurring microtraumas with subsequent hemorrhage. Typical sites of presentation include the mandible, clavicle, ribs, or pelvis, but can occur anywhere in the body. Patients can present with diffuse bone pain, pathological fracture, or bone deformities, though some may be asymptomatic and diagnosed incidentally. While these tumors do not have malignant potential, they can become debilitating in their burden and mimic malignant disease. Treatment focuses on treating the underlying cause of the hyperparathyroidism. Clinical Case: A 52-year-old female with ESRD on thrice weekly hemodialysis secondary to T2DM and HTN presented with right thigh pain and difficulty bearing weight, which began one week after a mechanical fall from standing. X-ray on admission revealed acute nondisplaced pathologic fracture of the right superior pubic ramus related to an underlying 4.7 x 2.2 cm expansile osteolytic lesion. Calcium level corrected for albumin on admission was 9.3 mg/dL, phosphorous 5.6 mg/dL, and PTH 563 pg/mL. Review of our institution’s electronic medical record revealed a maximum PTH level of 1,808 pg/mL three months prior. On CT pelvis, the patient was found to have multiple osteolytic lesions also involving the sacrum, multiple vertebral bodies, and the left pubic ramus, concerning for metastatic disease. Patient underwent pelvic rami bone biopsy resulting as osteoclast type giant cells, hemosiderin deposition and fibrosis in keeping with "brown tumor" of hyperparathyroidism. The patient was started on Cinacalcet 30 mg daily, with plans to titrate as outpatient to target PTH levels. She was also instructed to continue calcium, vitamin D and calcitriol to treat the underlying condition of metabolic bone disease from CKD. Referrals were given for both orthopedic spine and orthopedic oncology for surgical evaluation of her lesions. Discussion: Osteitis fibrosa cystica has become exceedingly rare in the United States and occurs in about 2% of patients with hyperparathyroidism. Due to their low prevalence and radiologic similarity to neoplasm, “Brown tumors” may be mistaken for metastatic disease and can lead to delay in diagnosis. Histology reveals collections of osteoclasts due to excess activity intermixed with fibrous tissue and poorly mineralized woven bone, which will differentiate brown tumor from malignancy. However, further correlation with hypercalcemia and hyperparathyroidism is imperative as brown tumors and other giant cell-containing lesions may be difficult to differentiate histologically. We present this case due to its rarity in clinical practice. Presentation: 6/2/2024

12472 Clinical Features Of Adult Hypophosphatasia And Correlation Between Laboratory Findings And Patient’s Symptomatology: A Retrospective Review At The Penn Bone Center

Abstract Disclosure: J. Ocampo Mascaro: None. R. Tran: None. S. Kallish: Consulting Fee; Self; Sanofi, Amicus. Research Investigator; Self; Ipsen, Sanofi, Incyte, Idorsia. Speaker; Self; Sanofi, Amicus. J. Berman: None. M. Al Mukaddam: Grant Recipient; Self; Ipsen, Incyte Research Funding. Hypophosphatasia (HPP) is an inborn error of metabolism resulting in low activity of the enzyme tissue non-specific alkaline phosphatase (ALP). It primarily involves bone and teeth mineralization. HPP has a wide clinical spectrum. It may present with rickets, fractures, failure to thrive, weakness, respiratory complications, and seizures in its more severe perinatal/infantile forms. Childhood forms tend to be milder but may have substantial musculoskeletal complications and early teeth loss. The clinical picture in adults is extremely variable too. It is usually mild with stress fractures and/or teeth loss in most individuals but can be debilitating in others due to musculoskeletal pain and recurrent fractures. This retrospective study describes the characteristics of 35 adult patients (ages 22-74 years) with HPP based on clinical presentation +/- molecular testing at the Penn Bone Center, located at a US-based large academic hospital. Out of 35 patients, 26 had an ALPL variant in genetic testing (12 pathogenic, 5 likely pathogenic, and 9 of uncertain significance), 3 were negative, and 6 did not undergo testing yet. ALP values ranged from 11 to 39 U/L (N: 38-126). Serum fasting vitamin B6 levels (off supplements) ranged from normal range to 18 times the upper limit of normal. Main symptoms reported were fractures (74%), arthralgias/myalgias (51%), diffuse bone pain (29%), atraumatic teeth loss (20%), muscle weakness (14%), and nephrolithiasis (9%). We found no significant negative correlation between ALP levels and number of symptoms (rs -0.026) or age of first symptom occurrence (rs 0.205). We also found no significant positive correlation between B6 elevation and number of symptoms (rs 0.236) or age of first symptom occurrence (rs -0.175). Six patients within our cohort had previous or current treatment with asfotase alfa. This is an FDA-approved therapy for the treatment of perinatal, infantile, and childhood HPP and has been used in adult patients if one of the presenting symptoms was before age 18 years. Response to therapy in our patient cohort was mixed. Three out of six patients discontinued treatment due to lack of clinical benefit. Continued research of the clinical characteristics of adult HPP is needed to better understand its natural history, markers of severity of disease, and how to determine who may potentially benefit from asfostase alfa therapy. Presentation: 6/1/2024

Challenging diagnosis of a rare disease: hypophosphatemic osteomalacia – case report and literature review

Hypophosphatemic osteomalacia is a rare condition caused by different causes, all resulting in disturbances of calcium-phosphate management. One of the most common causes among adults is tumor-induced osteomalacia, which is characterized by increased secretion of fibroblast growth factor-23. Its symptoms are vague, tests necessary for diagnosis are not commonly used by clinicians and some of them are only available in highly specialized centers. Due to these reasons, patients often are misdiagnosed for more common conditions and are left without proper treatment for many years. We present a case of a patient suffering from multiple fractures, diffuse bone pain, and muscle weakness, who was previously misdiagnosed for osteoporosis, primary and secondary hyperparathyroidism. We discuss the pathophysiology of tumor-induced osteomalacia, diagnostic path, differential diagnosis, available forms of treatment and possible complications.

Brown tumors: Retrospective analysis of 26 cases.

Brown tumors are reactive osteolytic lesions caused by hyperparathyroidism. These rare lesions are non-neoplastic processes that result from bone resorption. The purpose of this study was to retrospectively review a 34-year experience with brown tumors in our institution. We retrospectively analyzed the records of 26 consecutive patients with brown tumor who were treated in our institution between May 1988 and October 2020, with a mean follow-up of 36,1 months. 17 male (65,4%) and 9 female (34,6%) patients with a mean age of 41,6 were included in the study. Localized bone pain was present in 13 cases (50,0%) as the first presenting symptom. 3 patients (11,5%) presented with diffuse bone pain. 7 patients (26,9%) were diagnosed with brown tumor while being investigated for pathological fractures. The other 3 patients (11,5%) were diagnosed while being evaluated for hypercalcemia symptoms. 7 patients (26,9%) had solitary lesions, while 19 patients (73,1%) had multiple lesions. Pelvis, femur, ribs, tibia, proximal humerus and mandible were the most common sites of localization. 23 patients (88,5%) were diagnosed with primary hyperparathyroidism, while the other 3 patients (11,5%) had secondary hyperparathyroidism. A total of the 65 lesions, 23 (35.4%) underwent orthopedic surgery, and 42 (64.6%) were followed up conservatively after parathyroidectomy. Orthopedic surgery was performed in 21 of 26 patients, the other 5 cases were followed up conservatively. Intralesional curettage was performed in 19 cases (82,6%). The resulting cavity was filled with bone cement in 11 cases (47,8%). Bone grafting was applied in 8 cases (34,8%). No recurrence was observed in any of the patients. The diagnosis of brown tumor begins with clinical suspicion. Endocrinology and general surgery consultation is important before surgery. Treatment of brown tumors requires a multidisciplinary approach.

#108 Mineral and bone disorders during chronic kidney disease

Abstract Background and Aims The objectives of our work were to describe mineral and bone disorders in patients with chronic kidney disease (CKD) not yet at the dialysis stage and to assess the compliance of phosphocalcic balance indicators with international KDIGO recommendations Method It was a retrospective study conducted over a 10-month period (01 November 2018 to 31 August 2019) in the nephrology and haemodialysis department of the Renaissance University Hospital in Ndjamena. We have included all patients followed up in the unit for non-dialysis CKD, aged over 18 years and consenting to participate to this study. Results A total of 387 patients files were collected, 82 of which have been taken on. The average age of the patients was 52.7 (± 15.8) years, with a male predominance (67.1%). The comorbidities were arterial hypertension (71.9%) and diabetes (24.4%). CKD has predominated in stage V (55%), followed by stage III (23%). Clinical signs were mainly diffuse bone pain (37.8%), pruritus (8.5%), muscle pain (7.3%) and insomnia (8.5%). Disorders in phosphocalcic metabolism have been noticed in stage IV (11.9% and 10.7%) and stage V (40.5% and 34.5%) for hypocalcaemia and hyperphosphataemia. Secondary hyperparathyroidism and 25 OH vitamin D deficiency were respectively 28.8% and 40.5% in stage V CKD. Compliance with international KDIGO recommendations was 59.7%, 53.7% and 37% respectively for serum calcium, serum phosphorus and parathyroid hormone. Radiological fractures were observed in 4.9% of patients. The management of these disorders has focused on calcium carbonate (52.4%), native vitamin D (64.6%) and Cinacalcet (6.1%) administration. Hypocalcaemia (p = 0.005) and hyperphosphataemia (p = 0.0001) were higher in stage V patients, with a significant difference. Conclusion The treatment of mineral and bone disorders has way to go for the majority of patients, due to lack of resources and the exorbitant cost of treatment. Prevention of mineral and bone disorders is a fundamental pillar of CKD treatment for our patients.

B-Lymphoblastic Leukemia Presenting with Eosinophilia: A Case Report and Review

B-lymphoblastic leukemia (B-ALL) presenting with eosinophilia represents a rare entity. In particular, the unique clinical manifestations as well as the genetic and molecular pathogenesis of the associated eosinophilia have been topics of debate and investigation. Herein, we present a case of B-ALL presenting with concomitant eosinophilia and a review of the published cases, including 120 additional cases. The patient, at presentation, was a 20-year-old female who presented with cardiac, neurologic, and cutaneous signs of eosinophilia and with leukocytosis (WBC 51, 40% eosinophils, 0% blasts), anemia, and thrombocytopenia. Imaging revealed multi-focal brain infarcts, pulmonary infiltrates, and myocarditis. Empiric steroids, colchicine, and intravenous immunoglobulin were initiated. One week after presentation, bone marrow biopsy revealed a hypercellular (>95%) marrow with 50% blasts and marked eosinophilia, which on later review revealed an immunophenotype most consistent with B-ALL (positive for Pax5, CD10, CD19, CD20, cCD22, CD34, CD45, CD79a, HLA-DR, and TdT and negative for MPO and CD117). Conventional cytogenetic analysis of the bone marrow was unable to be performed. Fluorescence in situ hybridization (FISH) revealed an IGH rearrangement in 10.5% of nuclei analyzed. After three weeks of treatment with steroids and resolution of symptomatic organ involvement, a repeat bone marrow biopsy did not show any evidence of malignancy or genetic abnormalities. The patient was continued on a steroid taper, did not initiate further antileukemic therapy, and was lost to follow up. Ten weeks after initial presentation and after completing a steroid taper, the patient presented with diffuse bone pain. Repeat bone marrow biopsy showed B-ALL with 64% blasts and increased eosinophils, normal conventional cytogenetics and hematologic malignancy sequencing panel, and FISH with gain of Xp in 20.5% of nuclei analyzed; a lumbar puncture did not detect blasts in the cerebrospinal fluid. The patient began induction therapy with aBFM, rituximab, PEG-asparaginase, and intrathecal cytarabine. A bone marrow biopsy performed four months after her initial presentation revealed a mildly hypocellular marrow with 3% B-lymphoblasts and no eosinophilia, suggesting residual disease, with no evidence of cytogenetic or molecular genetic abnormalities. As a result, therapy with blinatumomab was initiated. A follow up bone marrow biopsy performed six months after her initial presentation revealed a hypocellular marrow with multilineage maturation and no excess blasts with normal cytogenetic and molecular genetic studies. A literature review identified 120 additional cases of ALL with eosinophilia. In summary, it tends to present in adolescent males, often with mild anemia and thrombocytopenia and no peripheral blasts, which can lead to a delay in diagnosis of ALL. The eosinophilia is often symptomatic, with cardiopulmonary involvement being the most common, and can lead to rapid mortality in a substantial number of cases. A significant proportion of cases of ALL with eosinophilia involve t(5;14)(q31;q32), leading to overexpression of IL-3, which was not definitively found in this patient; however, there are numerous other recurrent abnormalities that may be contributing to the pathogenesis, both concurrently with and in the absence of this translocation, including other rearrangements of IGH as well as IKZF1 and CDKN2A abnormalities. Prompt diagnosis, now commonly using sensitive molecular diagnostic assays, and initiation of glucocorticoids for symptom control and subsequent antileukemic therapy, are essential to avoiding complications of eosinophilia in such patients.

Abstract #1399545: Calcification of Left Atrial Appendage in Autosomal Recessive Hypophosphatemic Rickets Type 2 (ENPP1 Mutation)

Autosomal Recessive Hypophosphatemic Rickets type 2 (ARHR2) is a rare genetic condition secondary to a loss-of-function mutation in ENPP1 gene. ARHR2 is associated with renal phosphate wasting and suppressed 1,25-dihydroxyvitamin D due to increased FGF-23 levels and causing abnormal bone mineralization. Furthermore, as ENPP1 is implicated in the generation of PPi (inorganic pyrophosphate) which inhibits hydroxyapatite deposition, some ARHR2 patients present with life-treating generalized arterial calcification of infancy (GACI). We reported the case of a 32-year-old woman with a known diagnosis of ARHR2 since the age of seven. At that time, she presented a growth failure, bowed legs but no GACI history. She was treated from the age of 7 to 18 with phosphate supplements and calcitriol. She had ten surgeries for her leg deformities and had a subtotal parathyroidectomy at age 13 for primary hyperparathyroidism. She was referred to a tertiary centre for management of hypophosphatemia and diffuse bone pain. The alkaline phosphatase was at the upper limit of normal but imagings, including computed tomography scans and bone scintigraphy, did not show pseudofractures. Her chronic pain was associated with osteoarthritis and periarticular calcifications. She was treated for hypertension, and had a history of preeclampsia at 33 weeks of pregnancy. At the physical exam, a 30 mm Hg systolic blood pressure differential was noted between the right and left arms, suspect of severe subclavian artery stenosis. Additional investigations demonstrated a normal cardiac ultrasound (US), an Agatson score of 0 (coronary calcium scan) but extensive calcifications of the left atrial appendage, dense calcifications of the mitral valve and numerous calcifications in the ascending aortic wall. The spectrum of clinical manifestations associated with ENPP1-related conditions (GACI and ARHR2) is still unclear. In some patients who survive GACI, resolution of vascular calcifications has been reported. Furthermore, this case raises the possibility of undetected vascular calcifications in the infancy uncovered only after the diagnosis of ARHR2. Previous cases reported pulmonary stenosis, thickening of the aortic valve, and increased carotid intima-media thickness in patients with ARHR2 phenotype. Left atrial calcifications have been described in mechanical valve replacement, mitral stenosis, post-radiotherapy and in chronic kidney disease. Recommendations of cardiac US and kidney US have been proposed at the diagnosis of AHRH2. We further suggest vascular screening with cardiac scans to examine large vessels, and calcium score in these patients.

Клинический случай дебюта гистиоцитоза из клеток Лагерганса под маской ревматологического заболевания

A pediatrician faces with the differential diagnosis of oncological, oncohematological diseases which could have rheumatological "masks". According to medical literature, the most important symptoms are the joint pain at night, diffuse bone pain and organomegaly. Among the laboratory markers of oncological/oncohematological diseases the most important are bi-/trilineage cytopenia, high level of ESR, LDH, uric acid; including in the differential diagnosis of the neoplastic process in the detection of unilateral sacroiliitis without damage of other joints is necessary. The clinical case of a patient with Lagerhans cell histiocytosis is presented for differential diagnosis with the debut of spondyloarthritis for increasing the alertness of pediatricians and rheumatologists in children with musculoskeletal pain. Key words: Lagerhans cell histiocytosis, juvenile idiopathic arthritis, juvenile ankylosing spondylitis

From Lysis to Hemolysis

Introduction: Sickle cell disease (SCD) is the most common genetic disease in the world. Vitamin D deficiency has been described in several patients with this disease. We report the case of a patient in whom osteomalacia revealed the disease. Observation: The patient was 35 years old, not an alcoholic, not exposed to toxic products, with a family history of sickle cell disease in her 4 brothers and sisters. She reports the appearance of diffuse bone pain but which predominates in the axial skeleton, the ribs and the rhizomelic zones having motivated several hospitalizations. These pains are recurrent with new attacks on the lumbar spine, and sacroiliac joints with intense pain. Paraclinical examinations revealed: normal long bone radiographs without bone lysis, a CT scan of the sacroiliac joints without any aspect of sacroiliitis, but revealing multiple vertebral condensing bone lesions in streaks, diffuse at the level of the iliac wings with osteolysis surrounded by non aggressive osteocondensation. Densitometry was normal, vitamin D deficiency was noted at 29 ng/mL with elevated alkaline phosphatase, normal concentrations of Calcemia and Phosphoremia respectively at 96 mg/L and 36 mg/L, contrasting with hyperparathyroidism with a blood level of parathyroid hormone elevated to twice the normal level at 104.4 pg/mL It should be noted that the patient had received per os vitamin D supplementation before coming to us. The diagnosis of osteomalacia secondary to vitamin D deficiency complicated by secondary hyperparathyroidism was retained. Given the family history, we looked for the existence of sickle cell disease which was finally confirmed on hemoglobin electrophoresis with an AS profile. Conclusion: The association between vitamin D deficiency and sickle cell disease is not uncommon, and is explained by the ethnic origin, race, skin color, genetics and physiological features of patients with this disease rather than the disease itself.

PSAT193 Skeletal Fluorosis due to Inhalant Abuse

Abstract Introduction Skeletal fluorosis (SF) is a rare toxic osteopathy characterized by massive bone fixation of fluoride. It is prevalent in India, China, and Africa due to fluoride water contamination, high consumption of brick tea, or even fluoride air pollution in industrialized areas. In the United States, it does not constitute a public health issue; however, it has been found recently in individuals who inhale high amounts of recreational fluoride. The mechanism of fluoride toxicity on the bone is attributed to its anabolic effect, and patients usually present with diffuse and chronic bone pain, non-vertebral fractures, and hyperparathyroidism. Case We present the case of a 39-year-old woman, who presented with bone pain and joint stiffness leading to impaired gait. She was previously seen by neurology, rheumatology, and oncology due to concern for neuropathy, rheumatoid arthritis, or possible occult malignancy but was referred after an inconclusive workup. Her past medical history was significant for a motor vehicle accident resulting in chronic back pain. She began using painkillers, but eventually, she turned to inhalants to help with pain management and depressive symptoms. Her inhalant of choice was keyboard cleaner. Slowly, she began noticing diffuse bone pain, muscle weakness, and difficulty walking that required her to use crutches. She continued to abuse inhalants 2-4 cans per day for about 5 years until March 2021. Physical exam was relevant for multiple bony prominences bilaterally on the elbows and thoracic spine. She also had a diminished range of motion of her 4 limbs, being unable to fully extend arms or legs. Lab evaluation showed elevated alkaline phosphatase 971, normal AST/ALT, vitamin-D 52, normal serum calcium and PTH, elevated random urine fluoride 23 mg/L (<3.2), elevated osteocalcin 292ng/ml (<32), and elevated N-telopeptide 2283 BCE/mmol cr (<64). Upper extremity x-rays showed evidence of diffuse mature periosteal reaction involving the proximal humerus, radius, ulna, and metacarpals and prominent medial and lateral epicondylar enthesopathy consistent with fluorosis. Discussion Skeletal fluorosis should be suspected in patients at risk for fluoride inhalation. Occupational exposure including huffing was key in this case. Diagnosis was confirmed by the detection of excess fluoride in the blood and urine. Currently, the only accepted treatment is to stop further ingestion or inhalation of fluoride. The half-life of retained fluoride in the bone is about 7 years. Unfortunately, there is no antidote for SF. One theoretical therapy is teriparatide, which might accelerate bone turnover and release skeletal fluoride. Further research is needed to identify more treatment options for patients diagnosed with this condition as the substance abuse crisis worsens in many developed countries. This case also emphasizes the importance of a thorough history prior to undertaking costly, time-consuming medical workups. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Erdheim-Chester Disease: A Case of a Cardiac Involvement

Erdheim-Chester disease (ECD) is a rare non-Langerhans histiocytic multisystem disorder due to xanthogranulomatous infiltration of tissues by spumous histiocytes, It typically presents with diffuse bone pain however the cardiac manifestation are common and occur to 75% of the patients. It is frequently asymptomatic and detected incidentally on radiological imaging and it most commonly manifests as pericardium and myocardium infiltration We report the case of a 66-year-old woman patient, admitted for diffuse bone pain, asthenia and a left arm weakness who presented and infiltration of the aorta with a coated aspect, a thickened right atrium and a small pericardial effusion.

Osteitis Fibrosa Cystica; A Forgotten Manifestation of Secondary Hyperparathyroidism Due to End-Stage Renal Disease: A Case Report

IntroductionOsteitis fibrosa cystica is a rare complication of secondary hyperparathyroidism. Even though it is thought to be a disease of the past, it still continues to be seen in this modern era in the setting of undiagnosed or untreated chronic kidney disease.Case PresentationA 26-year-old married Ethiopian women presented with 4 year history of progressive proximal weakness of extremities and diffuse bone pain. Physical examination revealed diffuse bone tenderness and features consistent with myopathy. Blood work up showed raised creatinine, markedly elevated PTH, borderline low calcium, and vitamin D in severe deficiency range. X-Ray findings were consistent with classical skeletal lesion of severe secondary hyperparathyroidism.ConclusionOsteitis fibrosa cystica is a rare but still frequent complication of secondary hyperparathyroidism, which may be the initial presentation of chronic kidney disease. This case report emphasizes the importance of considering secondary hyperparathyroidism in patients presenting with weakness and bone pain to allow for early diagnosis, treatment, and improvement of overall prognosis.

Fluoride toxicity: A tale of two sources

The aim of this study was to identify the cause and source of two patients’ clinical manifestations. Case#1 was a 47-year-old male with diffuse bone pain and weakness aggravated by exertion. Past medical history revealed two surgeries for a left fibular fracture with eventual resection of installed hardware. Current medications included: oxycodone, montelukast, and vitamin D3. Magnetic resonance imaging and x-ray showed L5–6 fusion and diffuse trabecular thickening. A pelvic bone biopsy showed features consistent with severe skeletal fluorosis. Case#2 was a 61-year-old male post-heart transplant patient. His medications included: cyclosporine A, prednisone, rosuvastatin, amlodipine, and voriconazole. He complained of joint pain, his alkaline phosphatase was 222 U/L (reference range 40–129 U/L), and his bone density scan showed periostitis. Fluoride was measured in heparinized-plasma in both patients using a fluoride ion-selective-electrode on an Orion™ Dual Star pH/ISE meter (Thermo Scientific). The analytical measurement range is 4.0–21.0 μmol/L with an upper reporting limit of 105 μmol/L. Case#1 and case#2 had plasma fluoride concentrations of 11.3 and 17.5 μmol/L, respectively (reference-range < 4 μmol/L). Fluoride is often added to drinking water, toothpastes, and mouth rinses to prevent dental cavities. While food generally contains low levels of fluoride, tea and seafood have been found to have higher levels. Several medications containing fluorine are used for treating skin diseases and cancer. Following ingestion, plasma concentrations peak within an hour and up to 50% is stored in bones/teeth while the rest is primarily eliminated in the urine. The average person ingests ∼2–3 mg fluoride per day with a recommended daily intake of 3–4 mg/day by the United States Department of Agriculture. Chronic ingestion exceeding 20 mg/day can pose a risk to bone health leading to denser brittle bones, joint pain, and limited joint movement. In case#1, the source of fluoride was identified as excessive consumption of strong black tea (> 10 servings per day). In case#2, voriconazole (trifluorinated antifungal) was associated with the development of excess fluoride and periostitis. Plasma fluoride testing can be useful for diagnosing acute environmental toxicity, as well as, monitoring those taking fluorine-containing drugs. Detailed patient histories are required to identify common (voriconazole) or less-common (tea) sources. Patient#1 limited his tea consumption to one cup/day and his fluoride levels returned to normal on follow-up three months later. Patient#2 was switched from voriconazole to itraconazole (nonfluorinated triazole) and fluoride levels returned to normal. Pain resolution or improvement was also noted in both cases.

P067 Bone manifestations of Haematological Malignancies

Abstract Background Bone manifestations complicate many haematological malignancies and usually reflect a progression of the disease, affecting the prognosis (1). Because of the diversity of imaging appearances and clinical behavior of this spectrum of disease, diagnosis can be challenging. The Objectives is to describe the characteristics of bone manifestations in hematologic malignancies. Methods A retrospective descriptive study reviewing the medical records of all patients with hematologic malignancies, hospitalized in an internal medicine department. Results Among 70 patients, 39 men and 31 women were enrolled. The mean age was 55 years (15–83 years). Bone manifestations were related to multiple myeloma (28 cases), Hodgkin's disease (16 cases), non-Hodgkin's lymphoma (13 cases), chronic leukaemia (6 cases), acute leukaemia (5 cases) and Waldenström's disease (2 cases). The clinical presentation was dominated by: an alteration of the general condition (45 cases), peripheral lymphadenopathy (28 cases), hepato-splenomegaly (22 cases), diffuse bone pain (21 cases), back pain (16 cases) and night sweats (13 cases). The complete blood count found cytopenia in 47 cases. Patients presented a biologic inflammatory syndrome (58 cases), kidney failure (23 cases) and hypercalcemia (13 cases). Osteolytic lesions were objectified in 13 cases and vertebral collapse in 4 cases. A myelogram was performed in 40 cases, a lymph node biopsy in 25 cases, a bone marrow biopsy (6 cases) and a bone biopsy in 4 patients. The treatment was based on chemotherapy +/- radiotherapy. Therapeutic abstention was indicated in some patients. Conclusion Multiple myeloma and Hodgkin’s disease have shown the most bone manifestations. Knowledge of the different characteristics of hematological malignancies is essential to enable early diagnosis and appropriate treatment.

Microarchitectural parameters and bone mineral density in patients with tumour-induced osteomalacia by HR-pQCT and DXA.

Tumour-induced osteomalacia (TIO) is a rare paraneoplastic condition characterised by decreased tubular phosphate reabsorption. The purpose of this study is to evaluate bone mineral density (BMD) and microarchitecture in six TIO patients, compared with 18 healthy controls. Volumetric BMD and microarchitecture were evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT), and areal BMD by dual-energy X-ray absorptiometry (DXA). Differences between groups were significant for p < .05. All TIO subjects were healthy until the development of diffuse bone pain and multiple skeletal fractures and deformities. At baseline, sPi and TmPi/GFR were low and patients were on vitamin D and phosphate replacement at the study. Compared with controls, TIO patients had lower aBMD at lumbar spine and hip, and lower vBMD at trabecular, cortical and entire bone, at distal radius (R) and distal tibia (T): trabecular vBMD (R = 118.3 × 177.1; T = 72.3 × 161.3 gHA/cm3 ); cortical vBMD (R = 782.3 × 866.5; T = 789.1 × 900.9 gHA/cm3 ); total region vBMD (R = 234.5 × 317; T = 167.1 × 295.8 gHA/cm3 ). Bone microarchitecture was very heterogeneous among patients and significantly different from controls: lower cortical thickness (R = 0.59 × 0.80; T = 0.90 × 1.31 mm), bone volume-to-total volume ratio (R = 0.09 × 0.14; T = 0.06 × 0.13) and Tb.N (R = 1.46 × 2.10; T = 0.93 × 1.96 mm-1 ) and also higher Tb.Sp (R = 0.70 × 0.41; T = 1.28 × 0.45 mm) and Tb.1/N.SD(R = 0.42 × 0.18; T = 0.87 × 0.20 mm). In this original study of TIO patients, DXA and HR-pQCT evaluation identified lower areal and volumetric BMD and severely impaired microarchitecture at cortical and trabecular bones, which probably contribute to bone fragility and fractures.

Persistent phosphaturic mesenchymal tumor causing tumor-induced osteomalacia treated with image-guided ablation

Phosphaturic mesenchymal tumors (PMTs) can present with vague symptoms of diffuse bone pain with pathologic fractures that often lead to a delayed diagnosis. We present a 60-year-old patient with a PMT that was persistently hypophosphatemic after resection, who was then successfully treated with cryoablation of the tumor. Tumor-induced osteomalacia (TIO) is a rare cause of hypophosphatemia characterized by vague symptoms of gradual muscle weakness and diffuse bone pain with pathologic fractures that often lead to a delayed diagnosis. This condition is usually caused by benign phosphaturic mesenchymal tumors (PMTs). Here, we present a case of persistent PMT after surgical resection treated with image-guided ablation. We present the patient's clinical examinations and laboratory findings (phosphorus, 1,25 (OH)2D, FGF-23, Intact PTH). Representative histologic images of a PMT are also presented. A 61-year-old male was evaluated for persistent hypophosphatemia and presumed osteomalacia. Six years earlier, he underwent surgical excision of a left ischial mass after presenting with TIO. The pathology was consistent with a PMT; however, hypophosphatemia persisted suggesting incomplete resection. He was treated with calcitriol and phosphate salts. A PET Ga68 dotatate scan of the patient revealed an avid left ischial mixed lytic and sclerotic lesions with marked amount of radiotracer uptake, suggesting persistent tumor. The patient was resistant to re-excision of the tumor due to the extended recovery period from his prior surgery and was treated instead with cryoablation of the tumor. His biochemical findings of hypophosphatemia and elevated FGF23 resolved after the ablation and have remained normal for 5months after surgery. In patients with TIO, wide surgical excision is the treatment of choice. When this is not possible, image-guided ablation is an alternative therapeutic option.

Bone mineral density in patients with thalassemia major, the experience of a single institute

Thalassemia is an inherited disorder causing an imbalance in the development of the globin chain with ineffective erythropoiesis and increased peripheral consumption. Expansion of bone marrow decreases bone mineral density. Bone disease in thalassemia is manifested as diffuse bone pain, scoliosis, spinal deformities, nerve compression, spontaneous fracture. Bone Mineral Density (BMD) is a useful indicator for bone monitoring and assessment and significant predictor of bone disease in thalassemia. The purpose of this study is to evaluate Bone Mineral Density in thalassemia patients and its correlation with other factors. The study was conducted in Hematology Center at Al-Karama Teaching Hospital, Wasit, Iraq, from the first of January to the thirty of April 2019. Fifty-eight thalassemia patients were enrolled in this study. Bone mineral density was assessed using Dual-Energy X-ray Absorptiometry technique (DEXA scan) for the lumber spine (L1-L4) at the Dexa unit in the rehabilitation Center in KUT. The patients were divided according to BMD by Z-Score ≤ 15 years old patients, T score for adults (&gt;15 years old) into three groups: a score ≥ -1 defined as Normal BMD, Osteopenia (between −1 and −2.5 SD), and Osteoporosis (below −2.5 SD). The effect of Gender, Age, frequency of blood transfusion, Hb level, Serum Calcium, and Serum Ferritin on BMD was evaluated. Young patients (with age equal to or younger than 15 years) showed lower bone density than older patients. Also, Patients with Suboptimal blood transfusion had lower bone density than patients than good compliance blood transfusion program, P-value 0.001, 0.012, respectively. The results indicated a direct relationship between the age of the thalassemia patients and bone mass density, P-value = 0.0001, Pearson Correlation = 0.7. Low bone density was reported in young age and suboptimal blood transfusion.

Endocrinopathy Causing Skeletal Decalcification and Ectopic Calcification Highlighted by Imaging Tour

Primary Hyperparathyroidism (PHPT) is an endocrine disorder which is caused by increased production of Parathyroid Hormone (PTH). Hypercalcemia leads to a number of symptoms and may cause patient's morbidity and even mortality if left untreated. In the present case, a 21-year-old female presenting with frequent attacks of urinary tract infection, diffuse bone pain and episodic pain abdomen since 15 months. On clinical, biochemical and radiological evaluation, the case was diagnosed as PHPT due to left superior parathyroid adenoma. Patient underwent uneventful surgical parathyroidectomy following preoperative optimisation. She achieved normocalcaemia without any surgical complications. This case is presented to highlight the impact of hyperparathyroidism on calcium metabolism leading to extensive skeletal decalcification and ectopic deposition of calcium leading to end organ damage. Various images are used to highlight this phenomenon of decalcification and calcification.

Bone involvement in Gaucher disease type 1: a differential diagnosis of multiple fractures in a young patient. Case report

Gaucher disease type 1 (GD1) is a rare inherited disease caused by mutations in the GBA1 gene, which encodes the lysosomal enzyme glucocerebrosidase, leading to decreased enzyme activity and the consequential accumulation of its substrate, glucosylceramide, within macrophages. Bone involvement in GD1 may include avascular necrosis, bone infarcts, fragility fractures, lytic or sclerotic bone lesions and osteomyelitis. Bone pain can manifest as an acute and very painful bone crisis or a chronic pain that might vary in intensity, usually caused by fractures or avascular necrosis with progressive collapse of bone and joints. Hence, this report aims to describe a case of Gaucher disease type 1 and discuss its diagnosis, bone involvement and management, since late diagnosis or inadequate therapy can lead to clinical worsening, irreversible mobility impairment and increased morbidity. AGR, a 32-year-old male patient, was admitted to the Rheumatology Service with a previous history of diffuse bone pain, episodic hyperemia in the lower limbs since the age of 9 and two low-impact fractures. He had an initial non-confirmed diagnostic hypothesis of chronic recurrent multifocal osteomyelitis and was taking dipyrone and tramadol to reduce pain. His physical examination evinced overweight (body mass index: 29.7 kg/m2) and hepatosplenomegaly. Laboratory tests shown thrombocytopenia, with platelet count 103,000/mm3 (reference value [RV]: 140,000-450,000/mm3), serum phosphorus 4.7 mg/dL (RV: 2.7-4.5 mg/dL), C-reactive protein 88.8 mg/dL (RV: &lt; 5 mg/dL) and ferritin 1336 ng/mL (RV: 30-400 ng/mL). Biochemical and bone turnover markers were normal, including serum total calcium and magnesium, parathyroid hormone, 25-OH vitamin D, alkaline phosphatase, procollagen type-I N-terminal propeptide and C-terminal telopeptide of type I collagen. Conventional radiographies and magnetic resonance imaging were performed and confirmed previous fractures in the right humerus and the right acetabulum. They also showed sclerotic lesions in the left femur and Erlenmeyer flask deformities in the distal femurs and the proximal tibias. Bone scintigraphy indicated a bone infarct area in the left tibia. Areal bone mineral density (BMD) evaluated by bone densitometry showed a left total femur Z-score of +4.3 and left femoral neck Z-score of +4.5. Differently, the bone microarchitecture and volumetric BMD, evaluated by a high-resolution peripheral quantitative computed tomography (HR-pQCT) at distal radius and distal tibia, demonstrated an impairment of cortical compartment with lower cortical thickness and lower cortical volumetric BMD, possibly contributing to the low-impact fractures. Considering the compatible radiological findings, associated with hepatosplenomegaly and thrombocytopenia, Gaucher disease type 1 became the major hypothesis. It was confirmed after enzymatic dosage, which showed low residual glucocerebrosidase activity and high serum chitotriosidase. Enzyme replacement therapy was started with taliglucerase alfa, a recombinant enzyme preparation that aims to supply the lacking glucocerebrosidase in lysosomes. After 6 months of treatment, patient reported a significant improvement in bone pain and general quality of life. Therefore, clinicians should be alert to young patients with multiple low-impact fractures and further evaluate other possible bone involvement, as GD1 may be a differential diagnosis. Since it needs specific treatment, early diagnosis can be crucial to avoid permanent bone damage and morbidity.

MON-922 Multiple Endocrine Neoplasia Type 1- A Clarion Call for Clarity

A 35-year-old gentleman presented with epigastric pain and bilious emesis. He also endorsed urinary frequency, non-bloody diarrhea and diffuse bone pain. On physical examination he had epigastric tenderness and multiple hyperpigmented skin lesions.An abdominal computed tomography (CT) scan revealed multiple diverticula with peri-colonic fat stranding in the descending and sigmoid colon, concerning for diverticulitis. He was started on a course of metronidazole and ciprofloxacin. A 3.1 cm mass was incidentally noted in the uncinate process of the pancreas. Bilateral adrenal nodules were also appreciated.An endoscopic ultrasound (EUS) guided trans-gastric fine needle aspiration biopsy was performed, revealing a well differentiated pancreatic neuroendocrine tumor (pNET - pT3N1Mx, intermediate risk). Chromogranin A was elevated to 108 ng/ml (reference range <93 ng/ml). Serum and urine metanephrine, V-peptide, gastrin, glucagon and parathyroid hormone related peptide were all normal; indicating a nonfunctioning neuroendocrine tumor. He underwent a pancreaticoduodenectomy. Octreotide scan was unrevealing for residual uptake. Adrenal biopsy revealed adrenal adenomas.Three years later, he presented with severe abdominal pain and a new pancreatic mass was noted on CT. Chromogranin A was elevated to 227 ng/mL. EUS revealed a 0.35 cm mass in the bed of the pancreatic head, encasing the superior mesenteric artery. Pathology was positive for recurrence of the neuroendocrine tumor.He was hypercalcemic to 11.4 mg/dL and parathyroid hormone was elevated to 319 pg/mL. CT neck revealed a 0.1 cm nodule concerning for parathyroid adenoma. He underwent a subtotal parathyroidectomy.Genetic testing confirmed Multiple Endocrine Neoplasia Type 1 (MEN1) with a heterozygous mutation of the menin1 gene.MEN1 is a rare genetic syndrome with affected individuals at increased risk of developing pancreatic, pituitary, parathyroid gland and cutaneous tumors. With a kaleidoscope of presentations, clinicians must maintain a high index of suspicion for MEN1, particularly for cases with nonfunctioning pNETs which present insidiously and are the foremost cause of mortality in MEN1 patients.1Further clarity is needed on MEN1 associated pNET prognostic risk stratification, surveillance and targeted immunochemotherapy.2 Timely and algorithmic screening for MEN 1 syndrome in patients with pancreatic incidentalomas is essential to improving patient outcomes.1.Kamilaris CDC, Stratakis CA. Multiple Endocrine Neoplasia Type 1 (MEN1): An Update and the Significance of Early Genetic and Clinical Diagnosis. Front Endocrinol. 2019;10:339. doi:10.3389/fendo.2019.003392.Yates CJ, Newey PJ, Thakker RV. Challenges and controversies in management of pancreatic neuroendocrine tumours in patients with MEN1. Lancet Diabetes Endocrinol. 2015;3(11):895-905. doi:10.1016/S2213-8587(15)00043-1