Correspondence

More on Pamidronate in Langerhans'-Cell Histiocytosis

N Engl J Med 2001; 345:1502-1503November 15, 2001

Article

To the Editor:

Arzoo et al. (July 19 issue)1 report on a 23-year-old woman with Langerhans'-cell histiocytosis and severe pain due to osteolytic lesions, who had a good response to a 90-mg infusion of pamidronate. Although the literature on the use of pamidronate in patients with Langerhans'-cell histiocytosis is scarce, there have been previous observations.2-4

Elomaa and coworkers reported that the use of pamidronate (1.6 g per day orally for six months) in two adults with multifocal eosinophilic granuloma resulted in pain relief, regression of lesions, and biochemical evidence of decreased bone resorption.2 Recently, my colleagues and I reported our experience in treating a 14-year-old boy who had long-standing multisystem Langerhans'-cell histiocytosis with multifocal bone pain, which was unresponsive to chemotherapy, corticosteroids, antiinflammatory agents, and narcotic analgesics.3 He had a response to two cycles of intravenous pamidronate, each of which consisted of 90 mg per day given on three consecutive days. Two subsequent episodes of deterioration responded to the same treatment. The use of bisphosphonates in the treatment of pulmonary Langerhans'-cell histiocytosis was also recently suggested, on the basis of their relative safety and their documented antimacrophage activity.4

R. Maarten Egeler, M.D., Ph.D.
Leiden University Medical Center, 2300 RC Leiden, the Netherlands
rm.egeler@lumc.nl

4 References

1. 1

   Arzoo K, Sadeghi S, Pullarkat V. Pamidronate for bone pain from osteolytic lesions in Langerhans'-cell histiocytosis. N Engl J Med 2001;345:225-225
   Full Text | Web of Science | Medline

2. 2

   Elomaa I, Blomqvist C, Porkka L, Holmstrom T. Experiences of clodronate treatment of multifocal eosinophilic granuloma of bone. J Intern Med 1989;225:59-61
   CrossRef | Web of Science | Medline

3. 3

   Farran RP, Zaretski E, Egeler RM. Treatment of Langerhans cell histiocytosis with pamidronate. J Pediatr Hematol Oncol 2001;23:54-56
   CrossRef | Web of Science | Medline

4. 4

   Brown RE. Bisphosphonates as antialveolar macrophage therapy in pulmonary Langerhans cell histiocytosis? Med Pediatr Oncol 2001;36:641-643
   CrossRef | Medline

To the Editor:

The observation by Arzoo et al. that pamidronate therapy was effective in relieving bone pain in their patient with osteolytic Langerhans'-cell histiocytosis is consistent with both the pharmacologic action of aminobisphosphonates in this context and the biochemistry of Langerhans'-cell histiocytosis. Nitrogen-containing bisphosphonates inhibit the mevalonate pathway, leading to the reduced formation and function of osteoclasts and to their apoptosis.1,2 Thus, one would expect pamidronate to be effective in relieving bone pain in patients with osteolytic Langerhans'-cell histiocytosis, given the identification of components of the mevalonate pathway in this disease. Specifically, the earlier report of a preponderance of cholesterol esters in histiocytosis X cells3 and my recent detection of the α subunit of both farnesyltransferase and geranylgeranyltransferase in osteolytic lesions from patients with Langerhans'-cell histiocytosis (Figure 1Figure 1Immunohistochemical Detection of the α Subunit Common to Farnesyltransferase and Geranylgeranyltransferase of Human Origin in an Osteolytic Lesion from a Patient with Langerhans'-Cell Histiocytosis (3-3'Diaminobenzidine Tetrahydrochloride Chromogen, ×788).) provide evidence of the mevalonate pathway in osteolytic Langerhans'-cell histiocytosis and support the reported observation by Arzoo et al.

Robert E. Brown, M.D.
Geisinger Medical Center, Danville, PA 17822-0131
rebrown@geisinger.edu

4 References

1. 1

   Fisher JE, Rogers MJ, Halasy JM, et al. Alendronate mechanism of action: geranyl-geraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro. Proc Natl Acad Sci U S A 1999;96:133-138
   CrossRef | Web of Science | Medline

2. 2

   Luckman SP, Hughes DE, Coxon FP, Graham R, Russell G, Rogers MJ. Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res 1998;13:581-589
   CrossRef | Web of Science | Medline

3. 3

   Barbey S, Despres S, Nezelof C. Histiocytose X: étude histochimique des lipides intracytoplasmiques: à propos de 3 observations. Pathol Biol (Paris) 1975;23:639-646
   Web of Science | Medline

4. 4

   Sweetman L. Branched chain organic acidurias. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic basis of inherited disease. 6th ed. Vol. 1. New York: McGraw-Hill, 1989:791-819.
   

Citing Articles (3)

Citing Articles

1. 1

   Athanasios D. Anastasilakis, Gregory A. Kaltsas, Georgios Delimpasis, Ludwig Wilkens, George Kanakis, Polyzois Makras. (2011) Distinctive growth pattern in a patient with a delayed diagnosis of Langerhans’ cell histiocytosis. Pituitary
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2. 2

   Sibel Eyigör, Yeşim Kirazlı, Ayşenur Memis, Gülçin Başdemir. (2005) Erdheim-Chester Disease: The Effect of Bisphosphonate Treatment—A Case Report. Archives of Physical Medicine and Rehabilitation 86:5, 1053-1057
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3. 3

   Daniele Santini, Maria E Fratto, Bruno Vincenzi, Annalisa La Cesa, Caterina Dianzani, Giuseppe Tonini. (2004) Bisphosphonate Effects in Cancer and Inflammatory Diseases. BioDrugs 18:4, 269-278
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