Clodronate treatment reduces serum levels of interleukin-6 soluble receptor in Paget's disease of bone.
OBJECTIVE
Interleukin-6 (IL-6) and its soluble receptor (sIL-6R) stimulate osteoclast formation and activity. The primary cell abnormality in Paget's disease of bone (PDB) involves osteoclasts. Pagetic osteoclasts overproduce IL-6 and IL-6 receptor in vitro. In vivo, IL-6 serum levels are very high in the acute phase of PDB. The aim of this study was to evaluate the modification in the serum levels of IL-6, sIL-6R and osteotropic hormones (parathormone, 25OHD3 and 1,25(OH)2D3) as a in long-term response to clodronate treatment in patients with PDB.


METHODS
16 patients (8 females) with polyostotic PDB were studied. IL-6, sIL-6R and osteotropic hormones serum levels were evaluated in active PDB and after clodronate treatment (300 mg injected intravenously for 5 consecutive days). The sequential changes in total alkaline phosphatase (tALP) serum levels were used to assess the maximal pharmacological response to treatment.


RESULTS
In untreated pagetic patients, mean serum levels of IL-6 (3.20+/-1.18 pg/ml) and sIL-6R (35.02+/-8.33 ng/ml) were significantly increased. Serum osteotropic hormone levels fell within the normal range. Eight weeks after treatment, the maximal pharmacological response to clodronate was associated with a significant reduction of sIL-6R serum levels in all patients, without a significant variation in serum IL-6 and osteotropic hormone levels. Moreover, we observed a correlation between lower sIL-6R serum levels before clodronate therapy and complete remission of PBD, defined as a decrease of tALP serum levels within the normal range.


CONCLUSIONS
The decrease in serum sIL-6R levels could be one of the molecular mechanisms that play a role in the clinical response to clodronate treatment in PDB.
Rendina
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Department of Clinical and Experimental Medicine, Federico II University Medical School, Naples, Italy.
Postiglione
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Vuotto
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Di Domenico
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Viceconti
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Mossetti
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Nunziata
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D000328:Adult; D000368:Aged; D000963:Antimetabolites / Q000008:administration & dosage*; D002112:Calcifediol / Q000097:blood; D002117:Calcitriol / Q000097:blood; D004002:Clodronic Acid / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D010001:Osteitis Deformans / Q000097:blood / Q000188:drug therapy*; D010281:Parathyroid Hormone / Q000097:blood; D019947:Receptors, Interleukin-6 / Q000097:blood*; D012995:Solubility
D000963:Antimetabolites; D015850:Interleukin-6; D010281:Parathyroid Hormone; D019947:Receptors, Interleukin-6; D004002:Clodronic Acid; D002117:Calcitriol; D002112:Calcifediol