Bisphosphonates and the kidney

  • Jonathan Green

Bone remodelling is a continuous and dynamic process that normally involves the coordinated interplay among 3 types of cells: the bone resorptive osteoclasts, the bone-forming osteoblasts, and osteocytes, which are thought to act as mechano-transducers in bone [1]. The process becomes unbalanced in the elderly, in patients with benign bone disease [2], and in patients with primary bone lesions from multiple myeloma or bone metastases from solid tumours [3, 4]. Bisphosphonates are synthetic analogues of pyrophosphate–a naturally occurring modulator of mineralisation found in plasma, urine, and bone. They inhibit osteoclast-mediated bone resorption through several mechanisms, including inhibition of osteoclastogenesis, disruption of intracellular vesicular trafficking, and induction of osteoclast apoptosis, as well as indirectly via effects on osteoblasts [5]. Bisphosphonates are transported through the bloodstream and are deposited at sites of active bone remodelling, where they bind avidly to the mineralised bone matrix via the bisphosphonate moiety [5]. During bone resorption, bisphosphonates are internalised by osteoclasts, wherein they mediate their antiresorptive effects [5]. Therefore, bisphosphonates have provided increasing clinical utility in the management of patients with pathologies associated with perturbations in bone metabolism [3, 4, 6].


Multiple Myeloma Zoledronic Acid Acute Tubular Necrosis Metastatic Bone Disease Skeletal Complication 
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© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Jonathan Green
    • 1
  1. 1.Musculoskeletal DiseasesNovartis Institutes for BioMedical ResearchBaselSwitzerland

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