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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: Complications



Skull, Jaw and Spine

In patients with skull involvement, hearing loss is the most common complication,[8] but tinnitus might also occur.[9] Rarely do patients exhibit symptoms of hydrocephalus even when there has been marked enlargement of the cranium. Dental complications in patients with maxillary or mandibular disease include malocclusion and loss of teeth.[10] The spine is a common site of Paget disease, with the lumbar region and sacrum most commonly involved.[11] Vertebral compression might produce kyphosis, although it is more common to find enlarged sclerotic vertebrae. Pain from associated degenerative arthritis and, less commonly, nerve root or spinal cord impingement might produce considerable morbidity.


Fractures of the lower extremities are a major complication of Paget disease; these breaks are typically transverse in nature, with the bone resembling a piece of chalk that has snapped. Fractures occur more often in the femur than in the tibia. Femoral fractures are also more likely to be associated with nonunion.[12] Incomplete fissure fractures are more common than complete fractures and are usually found along the periosteal edge of the convex surface of a curved bone;[13] they generally do not progress to complete fractures and usually are not painful. When surgery is performed on a predominantly osteolytic lesion, accelerated progression of the lesion in the absence of antiosteolytic drug therapy has been documented.[14]


Paget disease in the pelvis is associated with what is probably the most common severe complication, degenerative arthritis of the hips,[4] a common finding in elderly individuals without Paget disease. Pain resulting from arthritis in the hip can considerably impair mobility over time and is probably the most frequent cause of a surgical procedure in patients with Paget disease—hip replacement.


Sarcomas, most frequently osteosarcomas,[15] can arise in bones affected by Paget disease. These occur in <1% of patients, and the incidence is possibly lower than in the past.[16] The presenting symptom is bone pain, which might be recent in onset or might be a worsening of existing pain. Giant cell tumors, usually benign, are less common than sarcomas and are often painful.[17] Carcinomas can meta stasize to pagetic lesions, perhaps because of increased blood supply to affected bone, and bone marrow malignancies can occur in patients with Paget disease.

Cardiovascular Abnormalities

Cardiovascular complications are not unusual in the aging population of patients with Paget disease. Increased cardiac output correlates with the extent of skeletal involvement, presumably owing to the increased vascularity of most lesions.[18] Despite this, congestive heart failure is not particularly common. Arterial calcification in the aorta, iliac, femoral, gluteal and pelvic arteries seems to be more common than in agematched control indivi duals;[19] the cause of this is unknown. Calcification of the aortic valve[20] and the interventricular septum[21] has also been reported.

Metabolic Abnormalities

Hypercalcemia, particularly in polyostotic patients, can be a consequence of immobilization, although this is not a common event.[22] Bed rest produces a rapid increase in bone resorption and reduced bone formation. Hypercalcemia is more likely to occur in patients with Paget disease as a consequence of primary hyper parathyroidism,[23] probably as a chance occurrence. Hypercalciuria occurs in a subset of patients, but the incidence of renal stones does not seem to be increased.[24] Hyperuricemia, mainly in males,[4] might occur as a conse quence of high turnover of nucleic acids in pagetic lesions. Gout can develop, but studies have reported a variable incidence.