Background/Purpose: Gaucher disease (GD) is a rare lysosomal storage disorder caused by mutations in the glucocerebrosidase gene, leading to defective lysosomal acid β-glucosidase. Its incidence ranges between 0.4 and 5.8 for 100,000 inhabitants. GD patients may present splenomegaly, hepatomegaly, cytopenia, and/or skeletal disease. Bone manifestations (BM) include acute or chronic bone pain, risk of pathologic fractures (PF), epiphyseal avascular necrosis (AVN), bone infarcts and/or decreased bone mineral density. We aimed to describe BM at baseline and during follow-up in a large cohort of GD patients.

Methods: We conducted a monocentric retrospective study of GD patients followed in a French referral center for lysosomal disorders and enrolled in the French Gaucher Disease Registry. Their demographical and clinical characteristics at diagnosis, and their treatments, clinical bone manifestations and imaging during follow-up were collected.

Results: A total of 128 GD patients (123 GD type 1 and 5 GD type 3) were followed up for a median [interquartile range] of 24.7 [12.9–34.3] years. Male/female ratio was 0.9. Genotype was N370S/N370S for 22 (17.1%), N370S/other for 77 (60.2%), and other/unknown for 29 (22.7%) patients. Median age at GD diagnosis was 19.2 [9.1–29.2] years. BM were the first GD symptom for 11 (8.6%) patients. At GD diagnosis, 31 (28.2%) had chronic bone pain, and 16 (12.5%) had acute bone crisis. During follow-up, 98 (76.6%) had clinical BM. Thirty (23.5%) patients had had at least one episode of epiphyseal AVN, including 14 (10.9%) with multiple AVN. Of the 52 AVN episodes, 33 (63.5%) involved femoral head, 6 (11.5%) humeral head, 6 (11.5%) knees, and 8 (15.4%) other joints. Diaphyseal or metaphyseal bone infarcts occurred in 32 (25.0%) patients, including 12 (9.4%) with multiple bone infarcts. Of the 50 episodes of bone infarcts, femoral diaphysis was involved in 18 (36%) cases, tibia in 13 (26%), pelvis in 6 (12%) and humerus in 3 (6%). PF occurred in 38 (29.7%) patients: 25 had a unique PF, whereas 13 had ≥2 PFs. On the 66 PF, 25 (37.9%) were located on upper limbs, 19 (28.8%) on lower limbs, and 15 (22.7%) were vertebral fractures. Of the 77 patients with available bone X-rays, 48 (62.3%) were pathologic, showing Erlenmeyer flask deformity in 28 (36.4%) cases, osteopenia in 18 (23.4%) and/or osteolytic lesions in18 (23.4%). Evidence of bone marrow infiltration was present for at least 62 (52.1%) of the 119 patients with available magnetic resonance imaging. Of the 66 patients with available bone densitometry during follow-up, 29 (43.9%) had osteopenia with T-score between -1 and -2.5, and 11 (16.7%) had osteoporosis with T-score < -2.5. In 2019, 118 (92.2%) were alive. Among them, 106 (89.8%) are currently treated with imiglucerase (n=54), velaglucerase (n=31), or eliglustat (n=21).

Conclusion: This retrospective monocentric study of 128 patients followed up in a GD referal center during a median of 25 years provides useful information on bone involvement in GD, which occurs in a large majority of GD patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/bone-manifestations-in-gaucher-disease-a-monocentric-study-of-128-patients/