Bisphosphonates in the treatment of Paget's disease

• bisphosphonates are the mainstay of treatment of Paget's disease due to their influence on bone remodelling
• lead to inhibition of bone resorption
  • bind to calcium hydroxyapatite - leads to prevention of bone turnover
  • cellular effects - inhibition of osteoclast function, induction of apoptosis, reduction of production and activity of bone-remodelling units
• routes and dosages vary with respect to different bisphosphonates
  • usually they are poorly absorbed from the gastrointestinal tract
  • oral drugs should be taken on an empty stomach at least half an hour before the intake of food or drink
• disodium etidronate was the first bisphosphonate to be used in the management of Paget's disease. However this drug may be associated with bone demineralisation and is relatively ineffective and second- and third- generation bisphosphonates have been developed
• all of the second- and third- generation bisphosphonates lead to:
  • a reduction in indices of bone turnover in 80%
  • result in a biochemical remission in 50-75% of patients after a single course of treatment
  • result in new bone formation with a lamellar pattern
  • these bisphosphonates rarely result in bone mineralisation abnormalities
  • these drugs should be prescribed only following consultation of their respective summary of drug characteristics
• in general, treatment should be with an oral second- or third- generation bisphosphonate in the initial management of Paget's disease requiring treatment; the use of intravenous therapy may be indicated if there oral therapy is ineffective; neurological complications are also an indication for intravenous therapy
• newer drugs such as zoledronate has been shown to be the most potent drug in the bisphosphonate family with profound suppression of disease activity

Reference

1. Singer FR. The evaluation and treatment of Paget's disease of bone. Best Pract Res Clin Rheumatol. 2020 Jun;34(3):101506.