Diagnostic imaging

The severity of bone pain can vary between patients with Gaucher disease and may be acute or chronic in nature, and may not always correlate with radiological findings.¹⁰ Bone crises are acute episodes of severe skeletal pain associated with fever and oedema, accompanied by leukocytosis and elevated erythrocyte sedimentation rates.^10,11 Bone crises can be immobilising and may require bed rest and opiate analgesia.¹¹ The signs and symptoms of a bone crisis may mimic those of osteomyelitis (localised or generalised inflammation due to infection)¹²; however, toxaemia is not present and blood cultures are negative.¹³ Consequently, bone crises have also been referred to as pseudo-osteomyelitis and aseptic osteomyelitis.^10,13,14 Nevertheless, osteomyelitis has been reported in patients with Gaucher disease and it is important for physicians to distinguish between bone crises and osteomyelitis because the latter is life-threatening.^10,15 In general, MRI and radionuclide bone and bone marrow scintigraphy can provide information to separate bone crises from osteomyelitis 1‒3 days after pain onset.¹¹

Patients with Gaucher disease may experience Erlenmeyer flask deformity (Figure 1); however, this is not necessarily a symptom of the disease and is not specific to Gaucher disease. This deformity is caused by an impairment of remodelling of the metaphyseal and tubular bones and manifests as flaring of the distal lateral aspects of the femur and proximal tibia causing a flask-like appearance.^10,11 Erlenmeyer flask deformity is typically asymptomatic but can be observed in many of the tubular or long bones of the skeleton, and even in the phalanges of some patients with Gaucher disease. However, Erlenmeyer flask deformity does not affect bones of the skull.¹¹

In both children and adults with Gaucher disease, a reduction in bone mass or osteopaenia is common and is associated with an increased risk of bone fractures.^10,16 Patients with severe osteopaenia may develop pathological fractures of the ribs and weight-bearing bones, as well as vertebral compression fractures, which can lead to rounding of the spine and restrictive lung problems and neurological deficits as a result of nerve compression.⁸ The pathophysiology of osteopaenia in Gaucher disease is not clearly understood, as most patients exhibit normal serum concentrations of calcium, phosphorus, γ-carboxy-glutamic acid-protein (bone-GLA protein) and immunoreactive parathyroid hormone; urinary calcium and hydroxyproline excretions are also typically normal.¹⁷ These findings suggest that increased, localised bone resorption, rather than a generalised derangement of bone turnover, may have a greater effect on inducing osteopaenia.⁸ Evidence of osteopaenia is apparent at sites adjacent to bone marrow infiltration by Gaucher cells, but is not limited to these areas as it can also affect trabecular and cortical bone in either a localised or diffuse manner.¹⁰

Avascular necrosis (or osteonecrosis) is believed to be secondary to ischaemia due to chronic infarction (Figure 1). It is bone death, which mainly affects the femoral head, proximal humerus and vertebral bodies. Once the necrotic process of avascular necrosis begins, the process is irreversible and can cause fracture and joint collapse in patients with Gaucher disease.¹⁰

As a result of aberrant remodelling of the bone following bone infarction, deposition of calcium into the bone can occur and cause osteosclerosis. These infarctions are often very painful and can occur in patients with both mild and severe bone disease.^10,17

Histologically, the appearance of infiltrated bone marrow in Gaucher disease is heterogeneous.¹¹ Pathological examination of the femoral head shows areas of vital bone adjacent to bone marrow that has been infiltrated by Gaucher cells. In addition, the femoral head also reveals areas of non-specific chronic inflammation and fibrosis, areas of necrosis in osteocyte-free regions of bone and areas of normal haematopoietic marrow.¹⁹ The extent of bone marrow infiltration by Gaucher cells can be evaluated semi-quantitatively from MRI data of the spine, pelvis and lower limbs by using the BMB score.¹¹

In Gaucher disease, the predominant MRI characteristic of infiltrated bone marrow is low signal intensity on T1-, T2- and T2*-weighted images. T2*-weighted images are determined in relation to signal intensity of subcutaneous fat.²⁰ An increase in signal intensity may be observed on T2-weighted images, which is thought to reflect active bone marrow disease.^20,21For both the lumbar spine and femoral head, higher BMB scores indicate more severe bone involvement.²⁰

In Gaucher disease, low mineral bone mass can be detected by DXA as reduction in BMD.^11,22 In adults, DXA should be performed at the lumbar spine (L1 to L4) and hip (total hip or femoral neck). In children aged ≥5 years, DXA should be performed at the lumbar spine and total body (minus head), considering methodological precision and least significant change detectable by individual equipment. DXA measurements include bone mineral content (g), area (cm²) and BMD (g/cm²). Z-scores should be used to interpret DXA: this is the difference between the individual’s measured value of BMD and the mean general population score in younger individuals. Z-scores below ‒2 indicate reduced BMD. In post-menopausal women and in men aged >50 years, BMD is expressed as T-scores, which are calculated in relation to young adults of the same gender. This is interpreted using the World Health Organization classification of osteopaenia (T-score between ‒1 and ‒2.5) and osteoporosis (T-score less than ‒2.5). A scan of total body (minus head) is mandatory in children with Gaucher disease, although measurement of femoral BMD is unreliable because of the high variability in skeletal maturity, bone size and pubertal stage.¹¹