Bisphosphonates in the treatment of Paget's disease

• bisphosphonates are the mainstay of treatment of Paget's disease
• 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 (1)
• 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 bisphosponates lead to (1):
  • 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 (2)
  • 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 (3)
• newer drugs such as zoledronate has been shown to be the most potent drug in the bisphophnate family with profound suppression of disease activity (2)

Reference:

• (1) Langston AL, Ralston SH. Management of Paget's disease of bone. Rheumatology (Oxford). 2004;43(8):955-9.
• (2) Singer FR. Paget disease: when to treat and when not to treat. Nat Rev Rheumatol. 2009 Sep;5(9):483-9.