D. Sudhaker Rao, MD

At right you see a pelvic x-ray film of an 80-year-old African American woman who presented with hip pain. The condition was correctly diagnosed 40 years ago, but it could not be treated effectively at the time because of poor understanding of the disease.[[{"type":"media","view_mode":"media_crop","fid":"26564","attributes":{"alt":"Paget's disease","class":"media-image media-image-right","id":"media_crop_3927116125833","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"2502","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"width: 187px; height: 146px; float: right; margin: 3px;","title":" ","typeof":"foaf:Image"}}]]

We began current treatments with oral etidronate, changed that to intravenous pamidronate, and changed her again to zoledronate after seeing the results of bone markers. With each treatment, bone markers have normalized but then slowly regressed again.

X-ray films of this woman’s pelvis and femurs were consistent with Paget disease of bone, of which she had more than a 40-year history.

We wonder whether Sir James Paget himself ever saw a worse case of the disorder he described.

Her serum alkaline phosphatase at the time of initial diagnosis (40 years ago, in Detroit) was 1350 IU/L.

X-ray films at the time of presentation showed diffuse cortical and trabecular 

thickening with bony expansion involving the pelvis and progressive bowing of both femora (Figure 1). In addition, bilateral coxa vara had developed, with severe right hip joint-space loss and remodeling of the superior aspect of the femoral head and significant inferior osteophyte formation (Figure 2).

She was treated with bisphosphonates, first with oral etidronate and later with intravenous pamidronate. Guided by the markers of bone turnover (bone-specific alkaline phosphatase [BSAP] and urine and serum telopeptides), we switched this to zoledronate. 

Each of these various treatments normalized the values for BSAP and telopeptides, after which they would relapse slowly. These measures remain normal after the last infusion in May 2014.

This woman’s condition is noteworthy for its severity, and instructive for its lesson about the goals of treatment.

Paget disease of bone (osteitis deformans) is a chronic skeletal disorder characterized by abnormal and excessive remodeling of bone. After osteoporosis, it is the second most common bone disorder in the United States, with an estimated prevalence of 3% to 4% in individuals older than 40 years. The prevalence is about 50% higher among men than among women.

About 15% of patients with Paget disease of bone also have a family member with the disease.

Many patients with Paget disease of bone do not know they have the disease, having minimal or no symptoms. About 35% of patients have symptoms related to the disease when it is first diagnosed. The most common symptom is joint pain that may be confused with degenerative arthritis. The first manifestation of the disease, as in this case, is usually an elevated serum alkaline phosphatase.

Viral infections (paramyxoviruses) and genetics are believed to play a role in pathogenesis. 

The goal of treatment is to relieve bone pain; halt progression of the disease; and prevent bone deformities, complications related to neural encroachment syndromes, and osteosarcoma.

 Also, the quality of life is affected in some individuals, especially those with involvement of the skull (Figures 3 and 4).

In an earlier era, large doses of prednisone were used, presuming an inflammatory pathogenesis. However, this was soon abandoned, as the inflammatory hypothesis was abandoned and the aim of treatment evolved to preventing disease progression and fractures and alleviating bone pain. Later, large doses of vitamin D were used, because of lack of success of corticosteroids and their potential complication of hypercalcemia.

Management changed dramatically in the early 1970s, with the introduction of calcitonin as a specific treatment. In recent decades, the availability of bisphosphonates has revolutionized treatment. Currently, the following bisphosphonates are available for its treatment: etidronate, tiludronate, alendronate, risedronate, pamidronate, and zoledronate.

At presentation, this patient had advanced deformities. We have monitored disease activity with bone markers, and accordingly her bone markers are within normal range. While her condition is not curable, we believe that treatment has had an impact on disease progression.

Treatment has also alleviated her hip pain. She has never remarked about pain in her head (Figures 3 and 4).



This unfortunate lady presents with severe Paget disease of bone, not commonly seen in the past few years. Of interest is the uncommon presentation of Paget disease of bone in African Americans, suggesting this lady may have a mixed ancestry. 

Paget disease of bone has decreased in prevalence in the recent past, as documented in studies from England and New Zealand.

 The only population study in the United States, the NHANES (National Health and Nutrition Examination Survey) population in the early 1960s, suggested a prevalence of 0.9%.

Sir James Paget’s original patient developed sarcomatous degeneration of the femoral head, the most common reason for bone sarcomas in adults. In this patient, extensive involvement of the pelvis has resulted in softening of the bone and axial migration of the femoral heads, producing a triangular appearance to the pelvis. There is extensive involvement of the femora and the expanded femoral head no longer fits smoothly in the acetabulae, producing a secondary osteoarthritis. This causes the patient to stand in a bent-forward “simian” posture. 

The etiology of Paget disease is not known, but there has been extensive research into the association of mutations in the ubiquitin (UBA) domain of the sequestrum (

) gene. These mutations have the effect of increasing NF-kB signaling. Also, a “fingerprint” abnormality has been found in Paget osteoclasts that is reminiscent of an RNA virus. Although a specific virus has not been clearly identified, the evidence does suggest that a virus triggers the activation of the mutated gene.

The bisphosphonates are clearly the most effective agents in this disease, and any activity of Paget disease justifies therapy. Intravenous zolendronic acid has proved the most effective of the bisphosphonates,

 as demonstrated in this patient. Resistance to one bisphosphonate does not preclude use of another. 

Dr Altman is Professor in the Department of Rheumatology at Ronald Reagan UCLA Medical Center and a member of the Rheumatology Network Editorial Board. 

Clinical practice. Paget's disease of bone. 

Paget's disease of bone-becoming a rarity?

Altman RD, Bloch DA, Hochberg MC, Murphy WA. 

Prevalence of pelvic Paget's disease of bone in the United States.

A single infusion of zoledronic acid produces sustained remissions in Paget disease: data to 6.5 years.

Republished: Paget's disease of bone: clinical review and update.

Articles

Whatever is causing this woman’s hip pain, her x-ray film looks quite severe. The diagnosis was correct 40 years ago, but it couldn’t be treated effectively then. What’s the problem?

Author | D. Sudhaker Rao, MD

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80-Year-Old Woman With Hip Pain