Paget’s Disease Treatment

What is Paget’s Disease?

Paget’s disease of bone is a disorder characterized by accelerated bone turnover and abnormal remodeling, which results in bone overgrowth, pain, and deformities. These features occur due to abnormalities in the osteoclast –cells responsible for bone resorption. Most patients with the disease are asymptomatic. Genetic and environmental factors likely play a role in the pathogenesis of disease. The condition typically affects individuals age >55 and is more common in men than women.

Patients with chronic skeletal disease are at increased risk of developing osteosarcoma, a typically fatal bone cancer. Individuals may experience swelling, pathologic fracture, or pain that is inadequately treated with analgesics.

What Causes Paget’s Disease of bone?

Paget’s disease is caused by osteoclast abnormalities. This cell is normally responsible for bone resorption. In Paget’s disease, there is increased bone turnover and abnormal remodeling related to osteoclast dysfunction. This leads to overgrowth of bone at sites such as skull, spine, and pelvis. The most likely etiology of Paget’s disease is a complex interaction between genetic and environmental factors. Most cases are acquired by autosomal dominant inheritance.

How Common is Paget’s Disease?

Paget’s disease of bone is a relatively common disorder that is often initially evaluated in the primary care clinic. Most individuals require referral to an endocrinology specialist. Paget’s disease has a prevalence of approximately 2%-9% in older adults. One study found a prevalence of about 3%-3.7% in people over age 40. England, Scotland, and Central Europe have the highest disease prevalence Worldwide. The prevalence of disease appears to have been diminishing for the past 25 years. Individuals are normally diagnosed after age 55. Paget’s disease of bone is more common in men compared to women.

Signs and Symptoms

Most individuals with Paget’s disease of bone are asymptomatic. Patients may develop symptoms due to bone overgrowth and deformity, which can directly result in pain. Individuals can also experience pain due to coexisting osteoarthritis, fracture, nerve compression, or tumor. The most frequent sites of bone involvement include the:

• Skull
• Thoracolumbar spine
• Pelvis
• Long bones of the lower limbs

Bone growth resulting in nerve compression normally leads to radiculopathy and chronic back pain. Patients with skull involvement often experience hearing loss (due to damage of the cochlea). Osteosarcoma, is a rare but dreadful complication that usually affects individuals with long-standing disease. It is often characterized by pain that is unresponsive to mediations, swelling, and pathologic fracture.

Diagnosis

The diagnosis of Paget’s disease is suggested based on symptoms and physical examination, but typically confirmed with laboratory and imaging studies. Your doctor will typically order basic laboratory studies such as a comprehensive metabolic panel (CMP), vitamin D, phosphate, and complete blood cell count (CBC). The comprehensive metabolic panel contains information such as kidney function, liver function (AST, ALT, alkaline phosphatase, bilirubin), electrolytes, and glucose. Paget’s disease will often show an increased serum alkaline phosphatase. Your doctor may confirm that this is bone related by requesting a bone-specific alkaline phosphatase. Laboratory values generally correlate with disease severity - high levels suggest severe disease. Serum calcium and phosphorus are typically normal.

Your doctor will often obtain x-rays of the bone, which may show dense bone with thickening and enlargement. These are also helpful in identify fractures, tumors, and osteoarthritis. Your doctor may also order radionuclide bone scanning or bone scintigraphy to evaluate for the extent of disease.

Paget's Disease Treatment

Patients with Paget’s disease often require the use of hearing aids, physical therapy, analgesics for joint pain, and ambulatory aids (e.g., walkers). In addition, many benefit from medical therapy with bisphosphonates. Bisphosphonate therapy can improve bone pain, nerve compression, and x-rays findings of bone lesions. The most commonly prescribed agents include:

• Fosamax (alendronate)
• Reclast (zoledronate)
• Actonel (risedronate)
• Boniva (ibandronate)
• Aredia (pamidronate)

In elderly patients or those with severe disease, the preferred bisphosphonate is Reclast (zolendronic acid). Rarely, patients are treated with a medication called Miacalcin (calcitonin). Potential side-effects of bisphosphonates include gastroesophageal reflux disease, flu-like symptoms, musculoskeletal pain, and osteonecrosis of the jaw. Individuals should avoid starting bisphosphonates within 3-6 months of dental surgery.

Individuals with Paget’s disease also typically receive supplemental vitamin D and calcium to avoid low calcium levels (hypocalcemia). The recommended daily intake of calcium is about 1000mg. Most experts recommend that patients also receive about 800-1000 U of vitamin D daily. Vitamin D is usually supplemented in the form of ergocalciferol (vitamin D3).