Skeletal involvement in Gaucher disease: An observational multicenter study of prognostic factors in the Argentine Gaucher disease patients

Abstract

Patients with Gaucher type 1 (GD1) throughout Argentina were enrolled in the Argentine bone project to evaluate bone disease and its determinants. We focused on presence and predictors of bone lesions (BL) and their relationship to therapeutic goals (TG) with timing and dose of enzyme replacement therapy (ERT). A total of 124 patients on ERT were enrolled in a multi-center study. All six TG were achieved by 82% of patients: 70.1% for bone pain and 91.1% for bone crisis. However, despite the fact that bone TGs were achieved, residual bone disease was present in 108 patients on ERT (87%) at time 0. 16% of patients showed new irreversible BL (bone infarcts and avascular osteonecrosis) despite ERT, suggesting that they appeared during ERT or were not detected at the moment of diagnosis. We observed 5 prognostic factors that predicted a higher probability of being free of bone disease: optimal ERT compliance; early diagnosis; timely initiation of therapy; ERT initiation dose ≥45 UI/kg/EOW; and the absence of history of splenectomy. Skeletal involvement was classified into 4 major phenotypic groups according to BL: group 1 (12.9%) without BL; group 2 (28.2%) with reversible BL; group 3 (41.9%) with reversible BL and irreversible chronic BL; and group 4 (16.9%) with acute irreversible BL. Our study identifies prognostic factors for achieving best therapeutic outcomes, introduces new risk stratification for patients and suggests the need for a redefinition of bone TG. Am. J. Hematol. 91:E448-E453, 2016. © 2016 Wiley Periodicals, Inc.

Transformation in pretreatment manifestations of Gaucher disease type 1 during two decades of alglucerase/imiglucerase enzyme replacement therapy in the International Collaborative Gaucher Group (ICGG) Gaucher Registry

“…With widely available, non‐invasive, reliable testing for GD, diagnostic splenectomy is strongly contraindicated and palliative total splenectomy is not recommended except under life‐threatening circumstances such as uncontrollable bleeding or splenic rupture . The concept that treatment instituted after splenectomy may avert postsplenectomy complications is questionable in light of studies showing that postsplenectomy patients treated with ERT continue nevertheless to suffer new ischemic bone events . It is therefore gratifying to confirm that with the advent of ERT, the number of splenectomized GD1 patients initiating treatment has decreased dramatically.…”

Recent advances in the diagnosis and management of Gaucher disease

“…Even in asymptomatic patients with normal bone marrow density, there may be underlying disruption of the bone’s trabecular architecture, causing a decrease in bone stability [27]. While the basis of the bone pathology observed in GD is still only partially understood, it is estimated that up to 75–90% of patients diagnosed with GD will experience some bone findings throughout the course of their disease [26,28]. Treatment during adolescence, when needed, may ameliorate some of these affects, increasing bone health and stability later in life [26].…”

Assessment of Bone Health in Patients With Type 1 Gaucher Disease Using Impact Microindentation

“…Patients show an improvement of symptoms, with a significant reduction in pain and in the number of bone crises, although improvement in bone mineral density (BMD), measured by DXA, or bone marrow infiltration, measured by magnetic resonance imaging (MRI) can take up to several years . Nonetheless, lesions such as bone infarcts and avascular necrosis are irreversible, and it remains to be shown if early ERT can prevent them …”

“…(14) Nonetheless, lesions such as bone infarcts and avascular necrosis are irreversible, and it remains to be shown if early ERT can prevent them. (15) Several mechanisms have been identified as responsible for bone disease in these patients. First, focal osteopenia and vascular occlusion have been described as a result of direct infiltration by Gaucher cells.…”