Marked Osteopenia and Iincreased Bone Resorption in Gaucher Disease Patients in Spite of Enzyme Replacement Therapy

OLIVERI B,; GOLDSTEIN G; RIVERO M; PARISI MS; AGUILAR G; MAUTALEN C

Minneapolis

Congreso; 25th Anual Meeting ASBMR; 2003

American Society for Bone and Mineral Research

Gaucher disease results from mutations that confer a deficit in activity of b glucocerebrosidase, which inturn leads to accumulation of the lipid glucocebrosidase in the macrophages of various organ systems. Theorgans affected include spleen, liver, lung, kidney, bone and bone marrow. 80 % of patients with Gauchertype I have skeletal involvement ( bone pain , bone marrow infiltration, osteopenia, pathologic fractures,impairment of remodelling, and osteonecrosis) which is disabling and has a negative impact on the patient´squality of life. A cross-sectional study was peformed to evaluate bone mass and mineral metabolism in youngpatients with Gaucher Disease receiving enzyme replacement therapy (ERT). The study populationcomprised 8 patients ( 4 women , 4 men) aged (X± SE) 25 ± 3.0 years (range (r): 18-43 ) with a bodymass index of 19.1 ± 2 . Five patients were splenectomized ( total: 4; partial: 1) , 4 had hepatomegaly , 7referred bone pain, 3 reported “bone crisis” and 4 suffered osteoporotic fractures. All patients had beenreceiving ERT (imiglucerase) in a dose of 30 ± 1.8 IU/kg/ 2 weeks) during 4.7± 1.6 years ( r:1.0-12).Bone Mineral Density (BMD) of lumbar spine (LS) and Total Skeleton (TS) was measured by DEXA.Serum calcium( sCa), phosphate (sP), 25(OH)D, bone alkaline phosphatase (BAP), osteocalcin (BGP), andcrosslaps (CTX) were measured ( see table below). BMD was found to be significantly diminished: Z scorewas -1.96 ( p<0.001) for TS and Z score was – 1.5 ( p<0.01) for LS. Biochemical determinations werewithin normal range except for bone markers : BAP 117 ± 32 IU/L (normal values (NV) : 31-95) ( 1/8 abovenormal level); BGP : 40 ± 21 ng/ml ( NV: 11-46 ) (1/8 above normal level) and CTX 842 ± 224 ng/ml (NV:40-450) ( 6/8 above normal level).Although the patients had been receiving ERT they presented frequent bone symptoms and a significantdiminution in BMD associated with high bone resorption. Higher doses of ERT and biphosphonate therapyshould be evaluated to improve bone status.