Risk factors for fractures and avascular osteonecrosis in type 1 Gaucher disease: A study from the International Collaborative Gaucher Group (ICGG) Gaucher Registry

Abstract

We hypothesized that overall disease activity or the severity of involvement of individual disease compartments, as measured by clinical and surrogate markers, predict the risk of avascular osteonecrosis (AVN) or fractures in type 1 Gaucher disease (GD1). We applied our risk‐set matched case‐control method to identify four patient groups within the International Collaborative Gaucher Group (ICGG) Gaucher Registry based on the presence and absence of AVN and fractures. Characteristics of GD1 were examined by comparing the distributions of each risk factor in cases versus matched controls using conditional logistic regression to calculate adjusted odds ratios (OR). Potential risk factors included hematological and visceral parameters, GD1 biomarkers, white blood cells, GBA1 genotype, and spine and femur dual‐energy X‐ray absorptiometry (DXA) Z‐scores. In the total population of 5894 ICGG Gaucher Registry patients, 544 experienced at least one episode of AVN; 2008 reported no history of AVN. Clinical and surrogate markers of disease activity were similar in patients with and without AVN; patients with AVN were 1.6 times more likely to be anemic compared to matched controls (OR = 1.59; 95% confidence interval [CI], 1.06–2.38, p < 0.05). For fractures, 319 patients suffered fractures and 1233 had no prior history of fractures. Clinical and surrogate markers of disease in patients with and without fractures were similar, except for mean lumbar spine DXA Z‐scores. Among patients with fractures, 49.3% had DXA Z‐scores ≤ −1 compared to 31.0% in the control group. Compared to controls with Z‐scores > −1.0, GD1 patients exhibiting Z‐scores ≤ −1 had an OR of 5.55 (95% CI, 1.81–17.02, p < 0.01) for fracture. In GD1, after controlling for gender, year of birth, treatment status, and splenectomy status, we identified new risk factors for AVN and fractures. Concurrent anemia was associated with an increased risk for AVN. Low bone mineral density of the lumbar spine was a strong risk factor for fractures of the spine and femur in GD1. © 2012 American Society for Bone and Mineral Research.

Improvement in Bone Mineral Density and Architecture in a Patient with Gaucher Disease Using Teriparatide

“…Low bone mineral density of the lumbar spine has been shown to be a risk factor for fractures in patients with Gaucher disease (Khan et al 2012). Wenstrup and colleagues showed that treatment with imiglucerase is associated with an increase in BMD T-scores in a dosedependent manner, but the changes could take years to materialize (Wenstrup et al 2007).…”

“…Osteopenia is the most common feature and along with bone pain together is more prevalent in patients that have had a splenectomy (Charrow et al 2000). Osteopenia in patients with a lumbar spine dual X-ray absorptiometry (DXA) z-score less than or equal to -1.0 can increase the risk of fracture at any skeletal site (Khan et al 2012). Infiltrative disease, from Gaucher cells, can damage bone architecture, most commonly affects the spine and one of the reasons why disease control should be achieved as soon as possible (Wenstrup et al 2007;Charrow et al 2007).…”

“…Infiltrative disease, from Gaucher cells, can damage bone architecture, most commonly affects the spine and one of the reasons why disease control should be achieved as soon as possible (Wenstrup et al 2007;Charrow et al 2007). Ischemic disease, for which avascular necrosis is the most debilitating disease, is poorly understood but has been related to anemia (Khan et al 2012).…”

Unexpected macrophage-independent dyserythropoiesis in Gaucher disease

“…11 Importantly, a study of a large cohort revealed that anemia was the only risk factor for avascular osteonecrosis, the most debilitating skeletal complication for GD type 1 patients. 12 Anemia affects 36% of GD patients. 13 The underlying mechanism has not been fully described, although it has been generally attributed to hypersplenism and splenic sequestration.…”

Multinational Registries: Challenges and Opportunities

“…Since its launch in 1991, the registry has collected data from over 6,500 patients in more than 60 countries, resulting in numerous publications and increased knowledge of the natural history of the disease, phenotypic and genotypic variation among patients, diagnosis and treatment patterns, and long-term outcomes. [8][9][10] Multi-national registries can also provide valuable information for more prevalent conditions. Consider GARFIELD-AF (Global Anticoagulant Registry in the FIELD-Atrial Fibrillation), which was designed to evaluate the management and outcomes of patients with newly diagnosed non-valvular atrial fibrillation (AF) and at least one additional risk factor for stroke.…”