Biomarkers for osteonecrosis in Gaucher disease

Pavlova, Elena; Deegan, Patrick; Cox, Timothy M.

doi:10.1517/17530059.2012.626402

Cited by 5 publications

(3 citation statements)

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“…Levels of plasma chitotriosidase and CCL18 both decreased over time, reflecting an ongoing fall in the total burden of Gaucher cells in the body [ 11 , 33 ]. These biomarkers are being investigated for their potential to predict long-term clinical complications, such as osteonecrosis [ 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

Velaglucerase alfa (VPRIV) enzyme replacement therapy in patients with Gaucher disease: Long‐term data from phase III clinical trials

et al. 2015

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Type 1 Gaucher disease is an inherited lysosomal enzyme deficiency with variable age of symptom onset. Common presenting signs include thrombocytopenia, anemia, hepatosplenomegaly, bone abnormalities, and, additionally in children, growth failure. Fifty-seven patients aged 3–62 years at the baseline of two phase III trials for velaglucerase alfa treatment were enrolled in the single extension study. In the extension, they received every-other-week velaglucerase alfa intravenous infusions for 1.2–4.8 years at 60 U/kg, although 10 patients experienced dose reduction. No patient experienced a drug-related serious adverse event or withdrew due to an adverse event. One patient died following a convulsion that was reported as unrelated to the study drug. Only one patient tested positive for anti-velaglucerase alfa antibodies. Combining the experience of the initial phase III trials and the extension study, significant improvements were observed in the first 24 months from baseline in hematology variables, organ volumes, plasma biomarkers, and, in adults, the lumbar spine bone mineral density Z-score. Improvements were maintained over longer-term treatment. Velaglucerase alfa had a good long-term safety and tolerability profile, and patients continued to respond clinically, which is consistent with the results of the extension study to the phase I/II trial of velaglucerase alfa. EudraCT number 2008-001965-27; http://www.clinicaltrials.gov identifier NCT00635427. Am. J. Hematol. 90:584–591, 2015. © 2015 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

Velaglucerase alfa (VPRIV) enzyme replacement therapy in patients with Gaucher disease: Long‐term data from phase III clinical trials

et al. 2015

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“…Osteonecrosis and osteolytic lesions arise from impaired blood supply to the bone resulting from disturbances in microcirculation related to the underlying marrow. 48 In addition, bone fracture, osteonecrosis, and inflammation are all characterized by excessive osteocyte death. Two mechanistic papers have characterized the relationships among the pattern recognition receptor macrophage-inducible C-type lectin (Mincle), osteocyte death, osteoclast activity, endogenous glycolipids, and osteonecrosis.…”

Section: Discussionmentioning

confidence: 99%

“…46 However, the unitary steps that link pathological glycosphingolipids to impaired microcirculation in the bone and marrow tissues responsible for osteonecrosis, are unclear. 48,50 One possibility is that by enhancing osteoclast migration, activation of Mincle β-glucosylceramides may distract the cells from their coupled physiological role in remodeling bone, thereby leading to obstruction of the capillaries supply in the growth plate region. This phenomenon might explain the apparent paradox between osteoporosis related to imbalanced osteoclast/osteoblast activity and the frequent Erlenmeyer modelling deformity with undertubulated long bones due to impaired endochondral resorption in the metaphyseal regions of long bones.…”

Section: Discussionmentioning

confidence: 99%