Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tiludronate ([[(4-chlorophenyl)thio]-methylene]-bis-phosphonate, ClPsMBP, Skelid, Sanofi) is a powerful inhibitor of bone resorption which has been shown to be a highly effective and safe agent for the treatment of Paget's disease of bone. Preclinical studies in vitro and in vivo have demonstrated a dose-dependent inhibitory effect on bone resorption. Unlike other bisphosphonates, tiludronate does not seem to interfere with the differentiation of osteoclasts or with their access to bone mineral. Bone tolerance studies indicate that tiludronate has an excellent therapeutic window. Thus, at the doses which induce a substantial inhibition of bone resorption it neither causes an appreciable effect on mineralisation, nor impairs biomechanical bone resistance. New formulations of tiludronate (tablets) have a bioavailability of 6% (2-11%) when ingested under optimal conditions. The pharmacokinetic profile of tiludronate is linear. Approximately 50% of the absorbed dose is bound to bone and the rate of release from this site is limited by bone turnover. Several open uncontrolled, open randomised, and double-blind, placebo-controlled studies carried out in patients with active Paget's disease have demonstrated that tiludronate reduces bone pain and produces an intense and sustained biochemical response. 3-6 months after starting tiludronate therapy, serum alkaline phosphatase levels fall far more than 50% from baseline values, reaching normal values in a percentage of the cases ranging from 35-70%. At present, tiludronate, together with pamidronate and alendronate, appear to be the drugs of choice for first-line use in the management of relatively young patients at risk of having long-term complications, when long-lasting control of disease activity is required.
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PMID:Tiludronate. A new treatment for an old ailment: Paget's disease of bone. 1124 59

Bone pain and bone deformities are the most common manifestations of Paget's disease of bone, even if the diagnosis is nowadays most often made by chance following a routine measurement of serum alkaline phosphatase. Woven bone is formed following a marked increase in bone resorption due to a stimulation of osteoclast activity. Biphosphonates constitute the modern treatment of Paget's disease of bone. Tiludronate (Skelid), or better risedronate (Actonel), are administered orally every day during at least 2 months. Zoledronic acid (Aclasta), as a single 15-min 5 mg infusion, has been recently compared to risedronate, 30 mg/d orally for 2 months, in two randomized studies including 357 patients. Zoledronic acid had a superior therapeutic efficacy, as judged by its rapidity of action, the duration of the biochemical response and the percentage of responders. Thus, at 6 months, alkaline phosphatase levels were normalized in 89% of the patients in the zoledronic acid group as compared to 58% in the risedronate group. The most frequent side effect was a flu-like syndrome, observed in 10% of the patients. An adequate intake of calcium and vitamin D is recommended to avoid posttreatment hypocalcemia. The introduction of Aclasta should simplify and improve the therapeutic management of Paget's disease of bone.
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PMID:[Treatment of Paget's disease of bone with zoledronic acid]. 1645 55