# Gaucher Disease in Internal Medicine and Dentistry
## 3 GD in Internal Medicine
Currently, only two cases of NS, associated with GD and infiltration of kidneys by GCs without AL, are described [39]. \begin{table}
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* _Bone tissue involvement_ GCs seem to influence the hematopoiesis and the balance of the number and the activity of the osteoblasts and osteoclasts, inducing an impaired shaping of trabecular and cortical bone [40]. An element that may confuse the GD diagnosis is the presence of atypical variants of GCs, found in untreated patients [41]. Their effect on the bone tissue is a progressive and centrifugal displacement of normal adipocytes [42], initially into the axial skeleton and then into the extremities [43]. This infiltrative process sets early in the GD and it usually develops before the bone symptoms [44]. The pathogenesis is not entirely clear. However, in several studies, it was found that the glucocerebrosidase inhibition alters the processes of erythropoiesis, the myeloid proliferation and the differentiation/development of mesenchymal stem cells [45]. In addition, the expression profiles of cytokines and prostaglandandins of bone marrow mesenchymal stromal cells are altered. These changes, due to the osteoclasts and plasma cells proliferation, not only reduce the bone mineral density (BMD), but also induce the onset of polyclonal and monoclonal gammopathies [46]. The manifestations of bone involvement in GD include bone pain or bone crisis, bone marrow infiltration, avascular osteheocrosis (AVN), infarction, pathological fractures, typical deformities, and an early osteopenia and osteoporosis. Bone pain and kyphosis are GD pathogenomic signs [47]. According to the literature, 80-95% of patients with GD1 have a bone involvement [48], and in the 25-32% of cases, it represents the only or the main manifestation of GD [49; 50; 51; 52; 53]. The detectable clinical signs of GD1 are Erlenmeyer's femur deformity resulting from meta-physeal enlargement of the bone, osteolytic lesions and bone crisis. They are characterized by severe bone pain, resulting from limited or localized bone infarcts. The latter sign may be a precursor of future osteheocrosis and fractures. [54; 55]. Histologically, there is a very heterogeneous picture of infiltrated bone marrow by GCs, characterized by areas of the femoral head with viable bone adjacent to other areas infiltrated by GCs [56]. However, it is still unclear whether the severity of bone involvement is related to the extent of the infiltration by GCs or to other pathological mechanisms [57; 58]. Radiologically, there is the characteristic appearance of 'worm-eaten' bone tissue [55]. For diagnostic purposes, BMD by dual-energy X-ray absorptiometry (DXA), bone marrow biopsy, axial skeleton X-rays and the search for potential malignant tumors, should be assessed. In adults, it is recommended a DXA of the lumbar spine and left and right hip. Magnetic resonance imaging (MRI) is the radiological gold standard for the skeletal involvement monitoring [59]. Under the age of 19, the radiological evaluation of the tibae is recommended. However, under the age of 9, it is very difficult to assess the bone marrow infiltration. In addition, children should be examined radiologically every year [60]. The pattern of infiltration provides information on the GD severity. At this regard, there are two typical pictures: type A (homogeneous) and type B (inhomogeneous); the latter is less reversible and with a poor outcome [61]. Another analysis to assess the extent of BM infiltration is a quantitative chemical shift imaging (QCSI) technique [62]. It measures the fat fraction of BM in vertebrae. Values below 0.23 are predictive of bone complications [61]. Moreover, certain indices such as the Dusseldorf score (performed in the MRI examination), especially in adults, together with bone marrow burden (BMB) and with verteb disc ratio (VDR), could be useful to monitor the disease gravity and the response to pharmacological treatment [63].