Pamidronate and Zoledronic Acid in the Treatment of Paget's Disease of Bone

Abstract

Paget's disease of bone (PDB) is a condition characterized by excessive and abnormal bone remodelling. Due to a high rate of bone remodelling, bisphosphonates, and especially pamidronate and the newer zolendronate, are indicated in the treatment of PDB. The presence of asymptomatic, but active PDB represents an indication for treatment aimed at preventing later complications. An additional indication for treatment is the involvement of skeletal segments that may give rise to severe complications. Pamidronate has a long history in the treatment of PDB. The more utilised regimen is 3 to 6 i.v. infusion of 60 mg of pamidronate at an infusion rate of 1 mg/min within 3-21 days. Zolendronate (5 mg once yearly) is the most powerful amino-bisphosphonate currently used. This primacy recognizes both the ability to inhibit the farnesyl-pyrophosphate synthetase and the higher affinity to hydroxyapatite crystals as a cause. Both pamidronate and zolendronate are effective in PDB, with an evidence-based superiority of the latter.

Chemical approaches to inhibitors of isoprenoid biosynthesis: targeting farnesyl and geranylgeranyl pyrophosphate synthases

“…25 FPPS has been identied as a target for a series of drugs acting as anticancer, antimicrobial and antiparasitic agents. 26 In particular, human FPPS is a drug target for cancer, 27,28 osteoporosis and related diseases, [29][30][31] Paget's disease, 32,33 metastatic diseases, 34 and cardiovascular disorders. 35 Inhibition of human GGPPS has been reported as a new route to bone antiresorption 36 and the same enzyme from Plasmodium has been identied as a target against malaria.…”