Gaucher Disease in Bone: From Pathophysiology to Practice

Abstract

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.

Identification of risk features for complication in Gaucher’s disease patients: a machine learning analysis of the Spanish registry of Gaucher disease

“…Two observations, already accepted in Gaucher research, were also confirmed in this machine-learning study: first, the fact that spleen-removal patients have a higher risk of presenting more serious and extensive bone disease; second, our observation that almost all patients with new bone crisis – despite having received long-term ERT – had previous bone lesions, which remind us that the most feared complication in GD1 are not solved merely by starting ERT. These two facts confirm previous reports and provide validity of our analysis [ 42 , 45 – 47 ]. In addition, genotypes different from homozygous NM_000175.…”

“…This study is the first attempt to establish a correlation network among different biochemical and clinical characteristics in a national-base cohort. We have aimed to analyse diagnostic data and to relate them with long-term complications as bone crises, development of neoplasia or PD, which are the most common and disabling complications [ 41 – 45 ].…”

“…It is a priority to identify accurate risk factors of bone crisis to improve treatment dosage and to avoid this complication. The standard biomarkers related to GD (ChT activity, CCL18/PARC and GluSph concentrations) have been discarded as risk factors for bone complication [ 50 , 51 ] even though their concentration will be increased during bone crisis, due to the acute inflammatory event [ 45 , 49 ]. This reminds us of the importance to continue searching for other biomarkers.…”

Identification of risk features for complication in Gaucher’s Disease patients: A Machine Learning analysis of the Spanish Registry of Gaucher Disease.

“…This study is the rst attempt to establish a correlation network among different biochemical and clinical characteristics in a national-base cohort. We have aimed to analyse diagnostic data and to relate them with long-term complications as bone crises, development of neoplasia or PD, which are the most common and disabling complications (41)(42)(43)(44)(45).…”

“…It is a priority to identify accurate risk factors of bone crisis to improve treatment dosage and to avoid this complication. The standard biomarkers related to GD (ChT activity, CCL18/PARC and GluSph concentrations) have been discarded as risk factors for bone complication (50,51) even though their concentration will be increased during bone crisis, due to the acute in ammatory event (45,49). This reminds us of the importance to continue searching for other biomarkers.…”