Drug treatment strategies for paget’s disease: relieving pain and preventing progression

ABSTRACT

Introduction

Paget’s disease of bone (PDB) is a focal bone disorder caused by a marked dysregulation of osteoblasts and osteoclasts in basic multicellular units, leading to abnormal and disorganized deposition of collagen fibers (the so-called ‘woven bone’). Therefore, pagetic bones are increased in size, and at increased risk for bone pain, deformities, fractures, osteoarthritis, and, more rarely, neoplastic degeneration.

Areas covered

In this review, we revise the available information concerning the pharmacological treatment of PDB.

Expert opinion

PDB progresses slowly within the affected skeletal sites and, if untreated, often leads to bone overgrowth, with bone pain, deformity, and a likely increased risk of complications. Thus, the primary goal of treatment is the restoration of a normal bone turnover, in order to relieve bone pain or other symptoms and possibly prevent the complications. PDB long remained a poorly treatable disorder until the discovery of antiresorptive agents such as calcitonin first and bisphosphonates (BPs) later. With the recent development of potent intravenous BPs like zoledronate, allowing a better control of disease activity over the long term with a single infusion, has contributed to a marked improvement of the clinical management of this invalidating disorder.

KEYWORDS:

• Paget’s disease of bone
• bisphosphonate
• osteoclast
• bone turnover
• zoledronate
• alendronate
• risedronate
• neridronate

Article highlights

• Paget’s disease of bone (PDB) is a focal disorder of bone and mineral metabolism, mainly characterized by exuberant and abnormal bone turnover leading to overgrowth and deformity of affected skeletal sites.

• In addition to bone pain, the progression of disease often leads to complications like osteoarthritis, hearing loss or other neurological manifestations of nerve compression, and, more rarely, neoplastic degeneration.

• PDB long remained a poorly treatable condition for up to a century, since the discovery of calcitonin, the first antiresorptive agent and then bisphosphonates (BP).

• Nitrogen-BPs (N-BPs) actually represent the treatment of choice for PDB given their high affinity for bone tissue and their greater antiresorptive potency, that allow to relieve symptoms and normalize bone turnover.

• Zoledronate (Zoledronic acid), administered as a single 5 mg intravenous infusion is the most effective N-BP, allowing a long-lasting control of symptoms and of disease activity for up to 7 years or even more.

• In order to arrest the progression of pagetic lesions and prevent the onset of some, if not all, complications resulting from the abnormal turnover and overgrowth of pagetic bone, it would be important to carry out the treatment at an early stage.

Declaration of interest

D Merlotti discloses receiving financial sponsorship from UCB Pharma. L Gennari discloses receiving financial sponsorship from Kiowa Kirin. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.