Diagnostic challenges in hypophosphatasia in adult patients / Desafios do diagnóstico da hipofosfatasia em adultos

Introdução: Hipofosfatasia é um distúrbio metabólico que afeta a mineralização óssea e dentária, causada por mutações no gene ALPL, levando à deficiência enzimática da fosfatase alcalina tecido não-específica. A forma adulta caracteriza-se por fraturas atípicas do fêmur, osteomalácia, osteoporose, grave osteoartropatia, condrocalcinose e artralgia. Objetivo: Demonstrar desafios diagnósticos relacionados à hipofosfatasia através do relato de dois casos. Paciente 1: feminino, 59 anos, encaminhada para avaliação clínica devido às fraturas patológicas de difícil consolidação e osteoporose generalizada de causa genética. Relata perda dentária precoce da arcada superior, fraturas na coluna, em ombro esquerdo e no fêmur. Atualmente, queixa-se de dor crônica intensa, com uso de múltiplos medicamentos. Achados clínicos, laboratoriais e radiológicos foram compatíveis com o diagnóstico de hipofosfatasia. Paciente 2: masculino, 31 anos, filho da paciente 1, encaminhado para avaliação clínica por fratura patológica precoce em fêmur esquerdo e osteoporose não esclarecida. Atualmente relata dor e claudicação importante em membro inferior esquerdo, associado à lombalgia crônica. Confirmação do diagnóstico de hipofosfatasia por exames laboratoriais e radiológicos e sequenciamento do gene ALPL, aliados ao diagnóstico da sua genitora. Discussão: Hipofosfatasia é uma doença rara de herança autossômica dominante e recessiva. Pacientes acometidos apresentam fraturas constantes, densidade mineral óssea baixa, cicatrização óssea deficitária. É comum a hipofosfatasia ser diagnosticada erroneamente como osteopenia e/ou osteoporose primária, acarretando prejuízos ao paciente. Ressalta-se a importância da história clínica completa e dos antecedentes familiares a fim de se obter um diagnóstico precoce, garantindo, por sua vez, o adequado acompanhamento e manejo terapêutico (AU)

Introduction: hypophosphatasia is a metabolic disorder affecting bone and tooth mineralization, caused by mutations in the ALPL gene leading to enzymatic deficiency of tissue non-specific alkaline phosphatase. The adult form is characterized by atypical femur fractures, osteomalacia, osteoporosis, severe osteoarthropathy, chondrocalcinosis, and arthralgia. Objective: to demonstrate diagnostic challenges related to hypophosphatasia through the report of two cases. Patient 1: female, 59 years old, referred for clinical evaluation due to pathological fractures of difficult consolidation and generalized osteoporosis of genetic cause. She reports early tooth loss in the upper arch, fractures in the spine, left shoulder and femur. Currently, he complains of severe chronic pain, with use of multiple medications. Clinical, laboratory, and radiological findings were compatible with the diagnosis of hypophosphatasia. Patient 2:male, 31 years old, son of patient 1, referred for clinical evaluation due to an early pathological fracture in the left femur and unclear osteoporosis. He currently reports pain and significant claudication in the left lower limb, associated with chronic low back pain. Confirmation of the diagnosis of hypophasatasia by laboratory and radiological tests and sequencing of the ALPL gene combined with the diagnosis of his mother. Discussion: hypophosphatasia is a rare disease of autosomal dominant and recessive inheritance. Affected patients have constant fractures, low bone mineral density, and impaired bone healing. It is common for hypophosphatasia to be misdiagnosed as osteopenia and/or primary osteoporosis, which can be harmful to the patient. The importance of a complete clinical history and family history is emphasized in order to obtain an early diagnosis, ensuring adequate follow-up and therapeutic management (AU)

Desafios do diagnóstico da hipofosfatasia em adultos / Diagnostic challenges in hypophosphatasia in adult patients

RESUMO:Introdução: Hipofosfatasia é um distúrbio metabólico que afeta a mineralização óssea e dentária, causada por mutações no gene ALPL, levando à deficiência enzimática da fosfatase alcalina tecido não-específica. A forma adulta caracteriza-se por fraturas atípicas do fêmur, osteomalácia, osteoporose, grave osteoartropatia, condrocalcinose e artralgia. Objetivo: Demonstrar desafios diagnósticos relacionados à hipofosfatasia através do relato de dois casos. Paciente 1: feminino, 59 anos, encaminhada para avaliação clínica devido às fraturas patológicas de difícil consolidação e osteoporose generalizada de causa genética. Relata perda dentária precoce da arcada superior, fraturas na coluna, em ombro esquerdo e no fêmur. Atualmente, queixa-se de dor crônica intensa, com uso de múltiplos medicamentos. Achados clínicos, laboratoriais e radiológicos foram compatíveis com o diagnóstico de hipofosfatasia. Paciente 2: masculino, 31 anos, filho da paciente 1, encaminhado para avaliação clínica por fratura patológica precoce em fêmur esquerdo e osteoporose não esclarecida. Atualmente relata dor e claudicação importante em membro inferior esquerdo, associado à lombalgia crônica. Confirmação do diagnóstico de hipofosfatasia por exames laboratoriais e radiológicos e sequenciamento do gene ALPL, aliados ao diagnóstico da sua genitora. Discussão: Hipofosfatasia é uma doença rara de herança autossômica dominante e recessiva. Pacientes acometidos apresentam fraturas constantes, densidade mineral óssea baixa, cicatrização óssea deficitária. É comum a hipofosfatasia ser diagnosticada erroneamente como osteopenia e/ou osteoporose primária, acarretando prejuízos ao paciente. Ressalta-se a importância da história clínica completa e dos antecedentes familiares a fim de se obter um diagnóstico precoce, garantindo, por sua vez, o adequado acompanhamento e manejo terapêutico. (AU)

ABSTRACT: Introduction: hypophosphatasia is a metabolic disorder affecting bone and tooth mineralization, caused by mutations in the ALPL gene leading to enzymatic deficiency of tissue non-specific alkaline phosphatase. The adult form is characterized by atypical femur fractures, osteomalacia, osteoporosis, severe osteoarthropathy, chondrocalcinosis, and arthralgia. Objective: to demonstrate diagnostic challenges related to hypophosphatasia through the report of two cases. Patient 1: female, 59 years old, referred for clinical evaluation due to pathological fractures of difficult consolidation and generalized osteoporosis of genetic cause. She reports early tooth loss in the upper arch, fractures in the spine, left shoulder and femur. Currently, he complains of severe chronic pain, with use of multiple medications. Clinical, laboratory, and radiological findings were compatible with the diagnosis of hypophosphatasia. Patient 2:male, 31 years old, son of patient 1, referred for clinical evaluation due to an early pathological fracture in the left femur and unclear osteoporosis. He currently reports pain and significant claudication in the left lower limb, associated with chronic low back pain. Confirmation of the diagnosis of hypophasatasia by laboratory and radiological tests and sequencing of the ALPL gene combined with the diagnosis of his mother. Discussion: hypophosphatasia is a rare disease of autosomal dominant and recessive inheritance. Affected patients have constant fractures, low bone mineral density, and impaired bone healing. It is common for hypophosphatasia to be misdiagnosed as osteopenia and/or primary osteoporosis, which can be harmful to the patient. The importance of a complete clinical history and family history is emphasized in order to obtain an early diagnosis, ensuring adequate follow-up and therapeutic management. (AU)

Modified Unipolar Hemiarthroplasty for the Treatment of Metastatic Lesions of Proximal Femur with Pathological Fractures: Case Series of Six Patients

@#Introduction: Proximal femur resection and endoprosthetic reconstruction is the preferred treatment for extensive bony destruction and pathological fractures. Due to the relatively high cost of endoprosthesis, we adopted the modified unipolar hemiarthroplasty (MUH) for reconstruction when the mode of treatment was for palliation. Materials and Methods:This is a retrospective case study of six patients, who had bone and multi-organs metastases with extensive proximal femur involvement with pathologic fractures who underwent resection and MUH reconstruction during the period 2013 to 2017. All patients were classified as Group B / C based on Scandinavian Sarcoma Group survival scoring, with estimated survival of maximum six months. The basic MUH construct consisted of AustinMoore prosthesis which was secured to a Küntscher nail using cerclage wire and cemented into the femoral canal. Subsequently, the whole length of the prosthesis which remained outside the canal was coated with cement. Results:The mean age was 61.8 years. The mean survival was 3.9 months, post-operation. There was no implant failure during patients’ life span; however, a third of the patients developed infection. Wheel chair ambulation was started immediately post-operation for all patients, and two patients progressed to walking frame ambulation. The total cost of each construct was below US$490 in comparison to long-stem hemiarthroplasty (roughly US$ 1700). Conclusion: Our aim was to alleviate pain, facilitate rehabilitation, ease nursing care and improve quality of life for metastatic bone disease patients until end of life. MUH for the treatment of pathological fracture in proximal femoral metastases is a feasible palliative surgical modality in resource-limited settings.

Bilateral Proximal Femur Fractures in a Patient with Renal Tubular Acidosis: A Case Report

@#The diagnosis of pathological fractures is on the rise. Themorbidity involved does not only burden the patient and theirfamilies but it has a great toll on the healthcare system aswell. Early identification of the patient at risk is aninvaluable tool to cut cost and improve the patient’s qualityof life. Multiple renal pathologies have been highlighted inrelation to the risk of pathological fractures; however,complications in renal tubular acidosis have been rarelydocumented. Nevertheless, prompt action with adequate andrelevant patient education ultimately can reduce theassociated morbidity. We present a case of poor control ofthe disease and its debilitating pathological fracturecomplications.

Lesões líticas de alto risco e fraturas patológicas / High-risk lytic lesions and pathologic fractures

Introdução: As neoplasias ósseas, sejam primárias ou metastáticas, representam um grande risco à qualidade de vida do paciente; especialmente quando se tratam de lesões dolorosas e com risco de evoluírem a fraturas ósseas, principalmente as do tipo osteolíticas. Lesões osteolíticas podem ocorrer em diversas patologias ósseas não tumorais, como cisto ósseo simples, cisto aneurismático, hiperparatireoidismo, bem como por neoplasias, entre elas destacando-se Mieloma Múltiplo tumores metastáticos, principalmente, Câncer de Mama, Próstata, Pulmão e Rim, cujas principais complicações são as fraturas ósseas patológicas. Métodos: Foram revisados artigos disponíveis em plataformas indexadas online, bem como revisada a literatura disponível em livros textos, guidelines e base de dados nacionais e internacionais. Resultados: Fraturas patológicas podem acometer até 30% dos pacientes com doença metastática óssea, causando dor importante mesmo no período anterior à fratura propriamente dita (Fratura Iminente) ou quando ela já é inevitável. Visando avaliar de forma objetiva a indicação de intervenções profiláticas, Mirels propôs um escore de pontuação avaliando multifatorialmente as lesões ósseas e seus possíveis prognósticos para fraturas. Conclusão: Embora ainda seja considerada o padrão-ouro e relativamente eficiente, o sistema de pontuação de Mirels deve ser aplicado junto com a avaliação clínica e de exames de imagem do médico, como a melhor forma de antever a fratura e, se possível, tratá-la profilaticamente.

Introduction: Bone neoplasms, whether primary or metastatic, represent a great risk to the patient's quality of life; especially when they deal with painful lesions and risk of developing osteolytic fractures. Osteolytic lesions may occur as a result of several non-tumorous bone pathologies, such as simple bone cyst, aneurysmal cyst, hyperparathyroidism, as well as neoplasias, among them Metastatic Multiple Myeloma, Breast Cancer, Prostate, Lung, and Kidney and its main complications are the bone fractures. Methods: Articles available on online indexed platforms were reviewed, as well as the literature available in national and international text books, guidelines and databases. Results: Pathological fractures can affect up to 30% of patients with metastatic bone disease, causing important pain even in the period before the fracture itself (Imminent Fracture), when it is already inevitable. In order to objectively evaluate the functionality of prophylactic interventions, Mirels proposed a scoring score evaluating multifactorially the bone lesions and their possible prognoses. Conclusion: Although the gold standard is still considered to be relatively efficient, the Mirels scoring system should be applied in conjunction with clinical assessment and imaging of the physician in order to better anticipate the fracture and, if possible, treat prophylactically.

Diagnostic Performance of Diffusion-Weighted Steady-State Free Precession in Differential Diagnosis of Neoplastic and Benign Osteoporotic Vertebral Compression Fractures: Comparison to Diffusion-Weighted Echo-Planar Imaging

PURPOSE: To evaluate the diagnostic performance of diffusion-weighted steady-state free precession (DW-SSFP) in comparison to diffusion-weighted echo-planar imaging (DW-EPI) for differentiating the neoplastic and benign osteoporotic vertebral compression fractures. MATERIALS AND METHODS: The subjects were 40 patients with recent vertebral compression fractures but no history of vertebroplasty, spine operation, or chemotherapy. They had received 3-Tesla (T) spine magnetic resonance imaging (MRI), including both DW-SSFP and DW-EPI sequences. The 40 patients included 20 with neoplastic vertebral fracture and 20 with benign osteoporotic vertebral fracture. In each fracture lesion, we obtained the signal intensity normalized by the signal intensity of normal bone marrow (SI norm) on DW-SSFP and the apparent diffusion coefficient (ADC) on DW-EPI. The correlation between the SI norm and the ADC in each lesion was analyzed using linear regression. The optimal cut-off values for the diagnosis of neoplastic fracture were determined in each sequence using Youden's J statistics and receiver operating characteristic curve analyses. RESULTS: In the neoplastic fracture, the median SI norm on DW-SSFP was higher and the median ADC on DW-EPI was lower than the benign osteoporotic fracture (5.24 vs. 1.30, P = 0.032, and 0.86 vs. 1.48, P = 0.041, respectively). Inverse linear correlations were evident between SI norm and ADC in both neoplastic and benign osteoporotic fractures (r = −0.45 and −0.61, respectively). The optimal cut-off values for diagnosis of neoplastic fracture were SI norm of 3.0 in DW-SSFP with the sensitivity and specificity of 90.4% (95% confidence interval [CI]: 81.0–99.0) and 95.3% (95% CI: 90.0–100.0), respectively, and ADC of 1.3 in DW-EPI with the sensitivity and specificity of 90.5% (95% CI: 80.0–100.0) and 70.4% (95% CI: 60.0–80.0), respectively. CONCLUSION: In 3-T MRI, DW-SSFP has comparable sensitivity and specificity to DW-EPI in differentiating the neoplastic vertebral fracture from the benign osteoporotic vertebral fracture.