Metabolic Bone Disease

Pathoanatomy

Paget disease is often diagnosed incidentally but can present with generalized bone pain. With proximal femoral and hip involvement, it can be difficult to differentiate generalized bone pain from active disease, stress fracture, or radiculopathy from intraarticular pathology. Intraarticular injection in this situation may aid in differentiating the source of pain. Malignant transformation and Paget sarcoma occur in less than 1% of patients but carry a poor prognosis and should be included in the differential when symptomatic patients with Paget disease of the hip are evaluated. Destructive bone changes and a soft tissue mass superimposed on typical pagetoid bone patterns with recently increased pain may suggest possible sarcomatous change.

Bone pain generally correlates with disease activity. Disease activity can be followed by monitoring of serum alkaline phosphatase and urinary pyridinium cross-links. Increased bone turnover results in increased excretion of type I collagen breakdown products, and the compensatory osteoblastic activity results in increased alkaline phosphatase activity.

The exact cause of Paget disease remains unknown; however, a viral origin was first proposed in 1974, after the discovery of virus-like inclusion bodies in the osteoclasts of affected bone. A viral cause continues to be a focus of current research, with implications for the paramyxovirus family. Multiple molecular markers have also been implicated in the disease process, including interleukin-6, a resorptive cytokine found in the bone marrow of affected patients. Additional work has been undertaken to investigate increased expression of genes that inhibit apoptosis, which leads to a relative increase in the number of osteoclasts. It is more common among relatives of those with Paget disease, with first-degree relatives having a sevenfold increased chance of developing Paget disease. Genetic studies and linkage analysis have implicated the sequestosome 1 gene and multiple other genetic loci as candidate regions for Paget disease. Extensive osteolysis, large numbers of osteoclasts and osteoblasts, and rapid formation of disorganized woven bone remain the histologic hallmarks of pagetoid bone.

A frequent association with disabling hip disease leading to hip arthroplasty has been well established, but it remains unclear whether osteoarthritis (OA) is more common in patients with Paget disease than in age-matched controls. It has been postulated that the pagetic process and deformity predispose patients to develop degenerative arthritis at an accelerated rate secondary to juxtaarticular bony enlargement, resulting in incongruity, altered biomechanics secondary to bowing, and altered subchondral support.

In the region of the hip, characteristic varus bowing of the femur, coxa vara, and protrusio acetabuli are commonly seen in patients with Paget disease. Subcapital fracture, nonunion of the proximal femur, and a distorted and sclerotic canal can complicate treatment. Both medial and concentric wear patterns of the hip joint are common ( Fig. 80.1 ). Hypervascularity characteristic of the active lytic phase of the disease may be associated with increased intraoperative blood loss. Appropriate medical management, including consultation with an endocrinologist, can help mitigate the risk of intraoperative bleeding and postoperative peri-implant bone resorption.

Alternative Treatment

Analgesics and nonsteroidal antiinflammatory drugs (NSAIDs) can be used to reduce bone pain in patients with active disease. However, antiresorptive medications have become the mainstay of modern medical treatment of Paget disease of bone. Antiresorptive medications act by decreasing the osteoclast-mediated bone resorption characteristic of Paget disease both by decreasing active symptoms and reducing future complications. Two main classes of antiresorptive medications are available in the United States: (1) calcitonin and (2) bisphosphonates. Salmon calcitonin is less effective than nitrogen-containing bisphosphonates and requires daily subcutaneous injection. The nitrogen-containing bisphosphonates alendronate, risedronate, and zoledronate acid have all shown varying degrees of effectiveness and potency when serum alkaline phosphatase levels are used as measurement of active disease. Zoledronate has proved particularly effective in arresting active disease and provides the convenience of one-time intravenous dosing over 15 minutes. A summary of commonly used bisphosphonates and dosing regimens is provided in Table 80.1 . Antiresorptive therapy can be used to treat pain caused by Paget disease and to prevent or slow the development of OA and advancing deformity. Antiresorptive therapy is also thought to be effective before surgery for reducing intraoperative bleeding due to hypervascularity in active disease and reducing the potential for postoperative bone resorption. No consensus is seen in the literature regarding the timing of perioperative bisphosphonate therapy. The timing and dosing of antiresorptive therapy should be prescribed in consultation with and monitored by an endocrinologist secondary to potential side effects. Nonsurgical treatment of degenerative arthritis associated with Paget disease is the same as that provided for idiopathic OA and includes antiinflammatory agents, activity modification, and gait aids.