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Indications for Bisphosphonate Treatment


Paget Disease: When to Treat and When Not to Treat

  • Authors: Frederick R. Singer, MD
  • CME Released: 8/4/2009
  • Valid for credit through: 8/4/2010
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Target Audience and Goal Statement

This activity is intended for primary care physicians, orthopaedists, endocrinologists, rheumatologists, and other physicians who care for patients with Paget's disease.

The goal of this activity is to diagnose and treat Paget's disease effectively.

Upon completion of this activity, participants will be able to:

  • Identify elements of the clinical presentation of Paget's disease
  • Describe complications of Paget's disease
  • Specify the most potent bisphosphonate in the treatment of Paget's disease
  • Classify who should receive immediate treatment for Paget's disease


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  • Frederick R. Singer, MD

    Director, Endocrine/Bone Disease Program, John Wayne Cancer Institute, Saint John's Health Center, Santa Monica, California; Clinical Professor of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California


    Disclosure: Frederick R. Singer, MD, has disclosed that he has acted as a consultant for Amgen Inc. Dr. Singer has also disclosed that he has acted as a consultant to, been involved in speaker's bureaus for (honoraria), and has received grant/research support (including for clinical trials) from Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; and Procter & Gamble.

CME Author(s)

  • Charles P. Vega, MD, FAAFP

    Associate Professor; Residency Director, Department of Family Medicine, University of California, Irvine


    Disclosure: Charles P. Vega, MD, FAAFP, has disclosed no relevant financial relationships.


  • Jenny Buckland

    Editor, Nature Reviews Rheumatology


    Disclosure: Jenny Buckland has disclosed no relevant financial relationships.

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Paget Disease: When to Treat and When Not to Treat: Clinical Presentation


Clinical Presentation

The clinical manifestations of Paget disease range from no symptoms in patients who are diagnosed accidentally to painful deformities of one or more bones in symptomatic patients. Symptoms and signs are more likely to occur in patients with polyostotic involvement than in those with monostotic involvement of the skeleton. In the latest large study of patients referred for evaluation of Paget disease, 34% had a monostotic lesion, with an overall average of 5.5 lesions per patient in the whole group.[3]

An accidental discovery of Paget disease often occurs through the finding of elevated serum alkaline phosphatase activity on a screening chemistry panel followed by radiologic documentation of the disorder. Elevations of alkaline phosphatase activity reflect an increased number of osteoblasts in the sclerotic lesions of a patient with Paget disease. The activity of this enzyme reflects the rate of bone formation and the level of activity correlates directly with the extent of skeletal involvement.[4] Normal levels are found in patients with small foci of active disease. Other indices of bone formation might also be increased, including levels of bonespecific alkaline phosphatase, procollagen type 1 N-propeptide or osteocalcin,[5] but levels of these markers are not often tested for in clinical evaluations of patients who are not suspected of having bone disease. Biochemical markers of bone resorption are also increased in the serum or urine, or both, of most patients with Paget disease. Serum and urine levels of N-telopeptide and C-telopeptide, and urine pyridinoline levels might be increased,[5] but in clinical practice serum alkaline phosphatase activity remains the most common metabolic parameter to reveal ‘silent Paget disease’. Paget disease is most likely to be noted in radiologic examinations intended to evaluate abdominal symptoms, back pain, pelvic pain or hip pain. In most of these cases, Paget disease is likely to be asymptomatic.

Bone pain in Paget disease is generally mild to moderate, is usually persistent, and might be slightly more severe in the weightbearing lower extremities. Pain in the lower extremity should be readily distinguished from arthritic pain, which is often much more severe during weight bearing and usually is absent or reduced in severity when the individual is sitting or lying. Skeletal deformities of Paget disease are most easily recognized in the skull and facial bones, and in the extremities. The skull enlarges asymmetrically over many years and would most readily be appreciated in an individual whose hat size has increased over time. Lateral or anterior bowing (or both) of the lower extremities can be seen in patients whose femur or tibia is completely or nearly completely affected by Paget disease.