Paget disease of bone: neurologic complications

Gregory Gruener MD MBA (Dr. Gruener of Loyola University Chicago Stritch School of Medicine has no relevant financial relationships to disclose.)
Zachary N London MD, editor. (Dr. London of the University of Michigan has no relevant financial relationships to disclose.)
Originally released July 17, 2000; last updated April 14, 2015; expires April 14, 2018

This article includes discussion of Paget disease of bone: neurologic complications and osteitis deformans. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Paget disease of bone is an osteoclastic-mediated disorder of bone where abnormal bone resorption and inadequate remodeling leads to mechanically weakened bone. Demonstrating variable geographic prevalence, it is becoming less frequent, and age of onset is lengthening in areas of high prevalence. A combination of genetic and environmental triggers appears to describe its pathophysiology and is helping to clarify other inherited osteolytic disorders of bone and their related cellular processes. In this article, the author provides the latest recommendations from the PRISM study with respect to symptomatic versus intensive treatment of Paget disease of bone with bisphosphonates. Recent concerns over the safety issues with bisphosphonate therapy are also addressed.

Key points

 

• Paget disease of bone (PDB) is a disorder of bone remodeling where abnormal bone resorption and inadequate remodeling results in mechanically weakened bone.

 

• Paget disease of bone is asymptomatic in over 70% of individuals and often identified incidentally by an elevated serum alkaline phosphatase or screening plain films of the abdomen.

 

• Paget disease of bone demonstrates variable geographic prevalence, highest in Northwestern Europe, but is becoming less frequent in areas of once-high prevalence that predate current treatments.

 

• Neurologic syndromes of Paget disease of bone result from the close relationship between the skeletal and nervous system, and although direct compression explains most observed syndromes, vascular steal phenomena may also play a role.

 

• The primary intervention for Paget disease of bone is bisphosphonate treatment, after calcium and vitamin D deficiencies are corrected; zoledronate may be the treatment of first choice.

Historical note and terminology

Although Wilks described the disorder in 1869 (Wilks 1869) and another condition shared a similar name (Czerny 1873), Sir James Paget's publication of a necropsy report as a form of “chronic inflammation of the bones” (osteitis deformans) provided the first thorough description of the disorder (Paget 1877); by 1889 the disorder was officially associated with Paget when the eponym, Paget disease of bone (PDB), was added to the Oxford English Dictionary. In his original report, Paget described a man who presented with thigh pain and tibial deformity and died 22 years later from a malignant tumor of the radius (Colman 2002). Paget later published additional cases that with his original report identified many of the clinical and pathological features we now recognize (Paget 1882). However, his suggestion of an inflammatory etiology has not been shown to be true.

Paget disease of bone is a focal disorder where the normal relationship between the continuous remodeling of bone by resorption and reformation is disrupted. Increased bone resorption with increased but abnormal bone reformation results in a disorganized mechanical structure and formation of thickened and structurally weakened bone (“mosaic” pattern of lamellar bone). The most common sites of involvement are the pelvis, lumbar spine, and femur, which are involved in more than 75% of cases; polyostotic disease is a more common occurrence than monostotic. The predilection for involvement of the vertebrae and the skull (skull involvement has a lower prevalence in men) is reflected by the potential for neurologic complications involving the spinal cord, cauda equina or spinal nerves, cranial nerves, and brain (Kanis 1998).

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