Gaucher disease: the role of the specialist on metabolic bone diseases

Masi, Laura; Brandi, Maria Luisa

doi:10.11138/ccmbm/2015.12.2.165

Cited by 23 publications

(21 citation statements)

References 38 publications

(39 reference statements)

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“…Skeletal manifestations are prevalent at all ages and are the principal cause of pain, disability, and reduced quality of life . However, there remains a need for uniform recommendations for bone disease evaluation and management . Physicians, including pediatricians, may be unfamiliar with bone pathophysiology and the complexity of the skeletal manifestations arising throughout life.…”

Section: Introductionmentioning

confidence: 99%

Gaucher Disease in Bone: From Pathophysiology to Practice

Hughes

Mikosch²,

Belmatoug

et al. 2019

Journal of Bone and Mineral Research

122

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Gaucher disease (GD) is a rare, genetic lysosomal disorder leading to lipid accumulation and dysfunction in multiple organs. Involvement of the skeleton is one of the most prevalent aspects of GD and a major cause of pain, disability, and reduced quality of life. Uniform recommendations for contemporary evaluation and management are needed. To develop practical clinical recommendations, an international group of experienced physicians conducted a comprehensive review of 20 years’ of the literature, defining terms according to pathophysiological understanding and pointing out best practice and unmet needs related to the skeletal features of this disorder. Abnormalities of bone modeling, reduced bone density, bone infarction, and plasma cell dyscrasias accompany the displacement of healthy adipocytes in adult marrow. Exposure to excess bioactive glycosphingolipids appears to affect hematopoiesis and the balance of osteoblast and osteoclast numbers and activity. Imbalance between bone formation and breakdown induces disordered trabecular and cortical bone modeling, cortical bone thinning, fragility fractures, and osteolytic lesions. Regular assessment of bone mineral density, marrow infiltration, the axial skeleton and searching for potential malignancy are recommended. MRI is valuable for monitoring skeletal involvement: It provides semiquantitative assessment of marrow infiltration and the degree of bone infarction. When MRI is not available, monitoring of painful acute bone crises and osteonecrosis by plain X‐ray has limited value. In adult patients, we recommend DXA of the lumbar spine and left and right hips, with careful protocols designed to exclude focal disease; serial follow‐up should be done using the same standardized instrument. Skeletal health may be improved by common measures, including adequate calcium and vitamin D and management of pain and orthopedic complications. Prompt initiation of specific therapy for GD is crucial to optimizing outcomes and preventing irreversible skeletal complications. Investing in safe, clinically useful, and better predictive methods for determining bone integrity and fracture risk remains a need. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

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Section: Introductionmentioning

confidence: 99%

Gaucher Disease in Bone: From Pathophysiology to Practice

Hughes

Mikosch²,

Belmatoug

et al. 2019

Journal of Bone and Mineral Research

122

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“…En los pacientes con enfermedad de Gaucher no neuronopática, las manifestaciones clínicas muestran una gran variabilidad, aunque la mayoría de ellos tienen compromiso hematológico (anemia y trombocitopenia), visceral (hepatoesplenomegalia) y óseo. Además, pueden aparecer complicaciones neurológicas secundarias como consecuencia de compresión nerviosa de la médula espinal debido al colapso vertebral (28)(29)(30).…”

Section: Hepatopatías Metabólicas Enfermedad De Gaucherunclassified

Guía colombiana para el diagnóstico de la deficiencia de lipasa ácida

Escobar

Montoya

Bermejo

et al. 2017

Rev. Colomb. Gastroenterol.

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ResumenIntroducción: la deficiencia de lipasa ácida lisosomal (LAL-D) es una entidad de herencia autosómica recesiva que lleva a la acumulación de esteres de colesterol y triglicéridos en el hígado, bazo y otros órganos. La edad de inicio y la tasa de progresión son muy variables, lo que posiblemente sea explicado por las mutaciones presentes en el gen LIPA. Las manifestaciones clínicas son las mismas que para otras patologías hepáticas, cardiovasculares y metabólicas, lo que hace difícil reconocerla en la práctica clínica. Objetivo: proveer una guía que permita a los clínicos reconocer los principales grupos de riesgo en los cuales se debe sospechar de LAL-D y mejorar su diagnóstico. Metodología: este documento se diseñó como un consenso de expertos en el cual participaron médicos especialistas en gastroenterología, hepatología, endocrinología, genética, patología y pediatría. Se realizó una revisión de la literatura acerca de las manifestaciones clínicas y de las herramientas para el diagnóstico de LAL-D y se siguió la metodología de técnica de grupo nominal. Resultados: se generaron algoritmos diagnósticos por consenso para cada uno de los grupos de riesgo, que facilitaran la sospecha y el diagnóstico de LAL-D. Conclusiones: esta guía propone algoritmos para el diagnóstico de LAL-D con base en el consenso clínico, que buscan optimizar la ruta diagnóstica en los pacientes con dicha patología. Palabras claveDeficiencia de lipasa ácida, enfermedad por depósito de esteres de colesterol, enfermedad de Wolman, dislipidemia, hepatomegalia. AbstractIntroduction: Lysosomal acid lipase deficiency (LAL-D) is an inherited autosomal recessive entity that leads to the accumulation of cholesterol and triglyceride esters in the liver, spleen and other organs. The age of onset and rate of progression vary greatly, possibly explained by mutations of the LIPA gene. Clinical manifestations are the same as those of other hepatic, cardiovascular and metabolic pathologies which makes it difficult to recognize in clinical practice. Objective: The objectives of these guidelines is to help clinicians recognize the major groups at risk for LAL-D and to improve its diagnosis. Methodology: This document was designed as a consensus of experts in gastroenterology, hepatology, endocrinology, genetics, pathology and pediatrics. A review of the literature regarding clinical manifestations and tools for diagnosis of LAL-D was conducted and the nominal group technique was followed. Results: Diagnostic algorithms which facilitate suspicion and diagnosis of LAL-D were generated by consensus for each of the risk groups. Conclusions: This guide proposes algorithms for the diagnosis of LAL-D based on clinical consensus. The algorithms seek to optimize diagnosis for patients with this pathology.

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“…2,3 Bone disease, present in most patients with a variable severity, is due to medular infiltration with glucocerebrosides lowden macrophages, which act directly, by mechanical pressure, and indirectly by cytokine-induced inflammation, influencing osteoblastic and osteoclastic activity. 4 This includes abnormal bone remodeling, osteopenia, osteoporosis, lytic lesions, and avascular necrosis. Clinical manifestations are bone pain, bone crises, and pathological fractures, with disability and a progressive reduction in the quality of life.…”

Section: Introductionmentioning

confidence: 99%

Gene variants of osteoprotegerin, estrogen-, calcitonin- and vitamin D-receptor genes and serum markers of bone metabolism in patients with Gaucher disease type 1

Zimmermann¹,

Popp²,

Rossmann³

et al. 2019

EJEA

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Purpose: Osteopathy/osteoporosis in Gaucher disease type 1 (GD1) shows variable responses to enzyme replacement therapy (ERT); the pathogenesis is incompletely understood. We aimed to investigate the effects of several gene variants on bone mineral density (BMD) and serum markers of bone metabolism in GD1. Patients and methods: Fifty adult Caucasian patients with GD1/117 controls were genotyped for gene variants in the osteoprotegerin (TNFRSF11B; OPG), estrogen receptor alpha, calcitonin receptor (CALCR), and vitamin D receptor (VDR) genes. In patients and 50 matched healthy controls, we assessed clinical data, serum markers of bone metabolism, and subclinical inflammation. BMD was measured for the first time before/during ERT (median 6.7 years). Results: Forty-two percent of patients were splenectomized. ERT led to variable improvements in BMD. Distribution of gene variants was comparable between patients/controls. The AA genotype (c.1024+283G.A gene variant; VDR gene) was associated with lower Z scores before ERT vs GA (P=0.033), was encountered in 82.3% of patients with osteoporosis and was more frequent in patients with pathological fractures. Z score increases during ERT were higher in patients with the CC genotype (c.9C.G variant, TNFRSF11B; OPG gene; P=0.003) compared with GC (P=0.003). The CC genotype (c.1340T.C variant, CALCR gene) was associated with higher Z scores before ERT than the TT genotype (P=0.041) and was absent in osteoporosis. Osteocalcin and OPG were lower in patients vs controls; beta crosslaps, interleukin-6, and ferritin were higher. Conclusions: We suggest for the first time a protective role against osteoporosis in GD1 patients for the CC genotype of the c.9C.G gene variant in the TNFRSFB11 (OPG) gene and for the CC genotype of the c.1340T.C gene variant (CALCR gene), while the AA genotype of the c.1024+283G.A gene variant in the VDR gene appears as a risk factor for lower BMDs. Serum markers suggest decreased osteosynthesis, reduced inhibition of osteoclast activation, increased bone resorption, and subclinical inflammation during ERT.

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Gaucher disease: the role of the specialist on metabolic bone diseases

Cited by 23 publications

References 38 publications

Gaucher Disease in Bone: From Pathophysiology to Practice

Gaucher Disease in Bone: From Pathophysiology to Practice

Guía colombiana para el diagnóstico de la deficiencia de lipasa ácida

Gene variants of osteoprotegerin, estrogen-, calcitonin- and vitamin D-receptor genes and serum markers of bone metabolism in patients with Gaucher disease type 1

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