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

Abstract

Gaucher disease (GD), one of the most common lysosomal disorders (a global population incidence of 1:50,000), is characterized by beta-glucocerebrosidase deficiency. Some studies have demonstrated bone infiltration in up to 80% of patients, even if asymptomatic. Bone disorder remains the main cause of morbidity in these patients, along with osteoporosis, avascular necrosis, and bone infarcts. Enzyme replacement therapy (ERT) has been shown to improve these symptoms. This cross-sectional study included patients with type 1 Gaucher disease (GD1) selected from the Catalan Study Group on GD. Clinical data were collected and a general laboratory workup was performed. Bone mineral density (BMD) was measured at the lumbar spine and hip using dual-energy X-ray absorptiometry (DXA). Patients with bone infarcts or any other focal lesion in the area of indentation visible on imaging were excluded. Bone Material Strength index (BMSi) was measured by bone impact microindentation using an Osteoprobe instrument. Analysis of covariance (ANCOVA) models were fitted to adjust for age, sex, weight, and height. Sixteen patients with GD1 and 29 age- and sex-matched controls were included. GD1 was associated with significantly lower BMSi (adjusted beta -9.30; 95% CI, -15.18 to -3.42; p = 0.004) and reduced lumbar BMD (adjusted beta -0.14; 95% CI, -0.22 to -0.06; p = 0.002) and total hip BMD (adjusted beta -0.09; 95% CI, -0.15 to -0.03; p = 0.006), compared to GD1-free controls. Chitotriosidase levels were negatively correlated with BMSi (linear R = 51.6%, p = 0.004). Bone tissue mechanical characteristics were deteriorated in patients with GD1. BMSi was correlated with chitotriosidase, the marker of GD activity. Bone disorder requires special consideration in this group of patients, and microindentation could be an appropriate tool for assessing and managing their bone health. © 2017 American Society for Bone and Mineral Research.

Bone Material Strength Index as Measured by Impact Microindentation in Postmenopausal Women With Distal Radius and Hip Fractures

“…(18) Our results are also consistent with studies that have shown BMSi to be lower in select patient populations with known skeletal fragility, including those with a history of bone stress injury, (25) type 2 diabetes, (9)(10)(11) HIV, (12) acromegaly, (13) and Gaucher's disease. (14) Our study is the first to examine BMSi in patients with DRFs and is the first to suggest a relationship between occurrence of DRF and BMSi that is independent of femoral neck aBMD. This observation is meaningful, because hip aBMD is commonly used in clinical practice to estimate fracture risk.…”

“…(6)(7)(8) Although the precise mechanical properties reflected by impact microindentation remain to be established, recent studies using the technique have shown cortical bone properties measured in vivo at the tibial diaphysis to be worse in select patient populations with known skeletal fragility, including those with type 2 diabetes, (9)(10)(11) human immunodeficiency virus (HIV), (12) acromegaly, (13) and Gaucher's disease. (14) Notably, cross-sectional studies have shown that impact microindentation at the tibia diaphysis discriminates individuals with a history of fragility fracture in some, (15)(16)(17) but not all, studies. (18) These studies enrolled subjects with different types of fractures, which may have contributed to the discrepant findings.…”

Added Value of Impact Microindentation in the Evaluation of Bone Fragility: A Systematic Review of the Literature

“…The majority of these studies included patients with endocrine disorders such as diabetes mellitus and acromegaly (n = 8) (36,41,48,49,(62)(63)(64)(65). Six studies focused on patients having sustained fragility or stress fractures (33-35, 38, 50, 55), three studies evaluated BMSi outcomes in patients receiving osteoporosis treatment (37,44,68) and another three studies reported on patients with a rare metabolic bone disorder: Type 1 Gaucher Disease, Paget's and Camurati-Engelmann disease (57,60,67). Seven studies, two of which included patients with diabetes mellitus (41,63), were performed in two population-based cohorts from Sweden and Australia, both designed to assess epidemiological data in osteoporosis (39,43,51,54,69).…”

Clinical Measurements of Bone Tissue Mechanical Behavior Using Reference Point Indentation

“…Though the mechanisms driving reduced BMSi in diabetics are unclear, the changes BMSi has been associated with the accumulation of advanced glycation end products (AGEs) in human bone 33 and may be the putative mechanism for the fragility observed in T2D. BMSi has also been reported in other clinical morbidities, including chronic kidney disease and transplantation 45 , acromegaly 46 , Paget’s disease 47 , Camurati-Engelmann disease, Type 1 Gaucher disease 48 , and obesity 49 , with BMSi observed to be lower in the respective pathological cohorts.…”