Regression of Bone Lesions in Gaucher's Disease During Treatment With Aminohydroxypropylidene Bisphosphonate

Harinck, HubertusI.J.; Bijvoet, OlavL.M.; Meer, JosW.H. Van Der; Jones, Barrington; Onvlee, G J

doi:10.1016/s0140-6736(84)92579-0

Cited by 29 publications

(8 citation statements)

References 4 publications

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“…M-CSF may enhance the apparent proliferation of macrophages in Gaucher disease (31). The presence of osteopenia (7) and increased bone resorption (36) in Gaucher disease could also be influenced by M-CSF, since it has been observed that rhMCSF promotes bone resorption (37). In our study, M-CSF levels were indeed particularly high in patients with extensive bone disease (data not shown), but since these patients are usually the most severely affected patients, the elevated levels could also be a reflection of more severe disease.…”

Section: Discussionsupporting

confidence: 52%

Elevated Levels of M-CSF, sCD14 and IL8 in Type 1 Gaucher Disease

Hollak

Evers

Aerts

et al. 1997

Blood Cells, Molecules, and Diseases

135

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ABSTRACT:In type 1 Gaucher disease, decreased activity of glucocerebrosidase results in accumulation of glucosylceramide in macrophages. Infiltration of liver, spleen and bone marrow by lipid-laden macrophages leads to hepatosplenomegaly, bone lesions and cytopenia. These abnormal macrophages may produce and release macrophage derived factors and cytokines, which could contribute to the pathophysiology of the disease. Whether these cytokines and factors are elevated in Gaucher disease is currently unknown. In 29 type 1 Gaucher disease patients we measured serum levels of the macrophage derived cytokines IL8, IL6, TNFa , M-CSF and the monocyte/macrophage activation marker sCD14. These factors were studied in relation to disease severity and during treatment with enzyme supplementation therapy. Most patients showed remarkably elevated levels of M-CSF (2-8 fold) and sCD14 (2-5 fold) as compared to normal controls. Levels of IL8 were elevated in all patients (2-20 fold), whereas levels of IL6 and TNFa were normal. There was a significant correlation between severity of the disease as determined by the severity score index (SSI), and M-CSF, sCD14 and IL8 levels. M-CSF and sCD14 levels also correlated with the excess liver and spleen volumes. During treatment with alglucerase, levels of M-CSF and sCD14 declined, but IL8 remained unchanged. The relative reduction in excess liver and spleen volume did not correlate with the relative reduction in M-CSF or sCD14 levels. We conclude that serum levels of M-CSF, sCD14 and IL8 are increased in type 1 Gaucher disease. The biological activities of M-CSF and IL8 may add to the pathophysiology of the disease.

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Section: Discussionsupporting

confidence: 52%

Elevated Levels of M-CSF, sCD14 and IL8 in Type 1 Gaucher Disease

Hollak

Evers

Aerts

et al. 1997

Blood Cells, Molecules, and Diseases

135

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“…12 Interleukin 6 (IL-6) plasma levels, which have been implicated in localized osteolysis in multiple myeloma, are elevated nearly 3-fold in adults with GD. 22 Since anecdotal evidence indicated that bisphosphonates may show some effectiveness in reversing some of the bone manifestations of GD, [23][24][25] a controlled trial of alendronate disodium (ALN) was initiated to test the hypothesis that Gaucher-related bone disease is a high resorption state and to determine whether ALN could improve focal bone lesions and/or BMD to a greater extent than enzyme therapy alone.…”

Section: Introductionmentioning

confidence: 99%

Gaucher disease: alendronate disodium improves bone mineral density in adults receiving enzyme therapy

Wenstrup

Bailey

Grabowski

et al. 2004

Blood

105

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Symptomatic patients with Gaucher disease (GD) (acid ␤-glucosidase [Gcase] deficiency) are treated with injectable human recombinant GCase. Treatment results in significant decreases in lipid storage in liver, spleen, and bone marrow, but the generalized osteopenia and focal bone lesions present in many adult patients are refractory to treatment. A double-blind, 2-arm, placebo-controlled trial of alendronate (40 mg/d) was performed in adults with GD who had been treated with enzyme for at least 24 months. Primary therapeutic endpoints were improvements in (1) bone mineral density (BMD) and content (BMC) at the lumbar spine, and (2) focal lesions in x-rays of long bones assessed by a blinded reviewer. There were 34 patients with GD type 1 (age range, 18-50 years) receiving enzyme therapy who were randomized for this study. After 18 months, ⌬BMD at the lumbar spine was 0.068 ؎ 0.21 and 0.015 ؎ 0.034 for alendronate and placebo groups, respectively (P ‫؍‬ .001). Long-bone x-rays showed no change in focal lesions or bone deformities in any subject in either arm. Alendronate is a useful adjunctive therapy in combination with enzyme replacement therapy (ERT) for the treatment of GD-related osteopenia in adults, but it cannot be expected to improve focal

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“…Among those more widely used in clinical practice, aminohydroxypropylidene bisphosphonate ((3-amino-1-hydroxypropylidene)-1, 1-bisphosphonate; APD) is very potent and has produced excellent results in Paget's disease of bone and malignant hypercalcaemia and in more rare diseases such as juvenile osteoporosis and Gaucher's disease affecting bone. [2][3][4][5][6][7] We have shown that aminohydroxypropylidene bisphosphonate predictably suppresses the activity of Paget's disease and induces long term clinical and biochemical remission. 8 In this report we compare the efficacy of three different therapeutic regimens in 142 patients with active Paget's disease.…”

Section: Introductionmentioning

confidence: 99%

Paget's disease of bone: early and late responses to three different modes of treatment with aminohydroxypropylidene bisphosphonate (APD).

Harinck

Papapoulos

Blanksma

et al. 1987

BMJ

180

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Early and late responses to treatment with either oral (600 mg/day) or intravenous (20 mg/day) (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (aminohydroxypropylidene bisphosphonate; APD) were studied in 142 patients with Paget's disease of bone who had not previously been treated with bisphosphonate. The efficacy of three therapeutic regimens was compared: (a) oral aminohydroxypropylidene bisphosphonate given continuously until six months after the serum alkaline phosphatase activity had returned to normal (long term); (b) oral aminohydroxypropylidene bisphosphonate given until urinary hydroxyproline excretion had returned to normal (short term); (c) intravenous aminohydroxypropylidene bisphosphonate for 10 days. With either oral or intravenous treatment the decrease in urinary hydroxyproline excretion was rapid and always preceded the fall in serum alkaline phosphatase activity. Normal urinary hydroxyproline excretion is essential for return of the serum alkaline phosphatase activity to normal. Complete biochemical remission, defined as return of the serum alkaline phosphatase activity to normal, was obtained in 129 patients (91%). The

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Regression of Bone Lesions in Gaucher's Disease During Treatment With Aminohydroxypropylidene Bisphosphonate

Cited by 29 publications

References 4 publications

Elevated Levels of M-CSF, sCD14 and IL8 in Type 1 Gaucher Disease

Elevated Levels of M-CSF, sCD14 and IL8 in Type 1 Gaucher Disease

Gaucher disease: alendronate disodium improves bone mineral density in adults receiving enzyme therapy

Paget's disease of bone: early and late responses to three different modes of treatment with aminohydroxypropylidene bisphosphonate (APD).

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