How to test for Paget's disease (Osteitis Deformans)?

From the Guidelines

Paget's disease should be tested using a combination of blood tests and imaging studies, starting with a blood test measuring alkaline phosphatase (ALP) levels, followed by more specific bone turnover markers, and then confirmed with imaging studies such as X-rays, bone scans, CT scans, or MRI. When testing for Paget's disease, it is essential to consider the differential diagnosis, which includes osteoporosis, degenerative disease, and Paget’s disease of bone, as noted in the ESMO clinical practice guidelines 1. The initial screening typically involves blood tests to measure ALP levels, which are often elevated in Paget's disease due to increased bone turnover. If ALP is elevated, more specific bone turnover markers like P1NP or NTX may be ordered to further investigate the condition. Imaging studies are crucial for diagnosis, with X-rays of affected areas being the first step, which may show characteristic changes like bone enlargement, deformities, or a mixed pattern of dense and less dense bone. A bone scan using technetium-99m, as mentioned in the context of detecting skeletal pathology 1, can reveal areas of increased bone activity throughout the skeleton, even in asymptomatic regions. CT scans or MRI may be used for more detailed evaluation, especially if complications like fractures or nerve compression are suspected, providing structural information on skeletal damage, similar to their use in metastatic bone disease 1. In some cases, a bone biopsy may be necessary to confirm the diagnosis or rule out other conditions like bone cancer. This comprehensive approach helps clinicians accurately diagnose Paget's disease and determine its extent, which is crucial for developing an appropriate treatment plan, prioritizing morbidity, mortality, and quality of life as the primary outcomes. Key points to consider when testing for Paget's disease include:

• Initial screening with blood tests measuring ALP levels
• Use of more specific bone turnover markers if ALP is elevated
• Imaging studies, including X-rays, bone scans, CT scans, or MRI, to confirm diagnosis and evaluate extent of disease
• Consideration of differential diagnosis, including osteoporosis and degenerative disease
• Potential use of bone biopsy to confirm diagnosis or rule out other conditions.

From the FDA Drug Label

Paget’s disease of bone (osteitis deformans) is an idiopathic disease characterized by chronic, focal areas of bone destruction complicated by concurrent excessive bone repair, affecting one or more bones. These changes result in thickened but weakened bones that may fracture or bend under stress Signs and symptoms may be bone pain, deformity, fractures, neurological disorders resulting from cranial and spinal nerve entrapment and from spinal cord and brain stem compression, increased cardiac output to the involved bone, increased serum alkaline phosphatase levels (reflecting increased bone formation) and/or urine hydroxyproline excretion (reflecting increased bone resorption)

The diagnosis of Paget's disease can be supported by:

• Increased serum alkaline phosphatase levels
• Increased urine hydroxyproline excretion
• Bone pain
• Deformity
• Fractures
• Neurological disorders Testing for Paget's disease may involve measuring:
• Serum alkaline phosphatase (SAP) levels
• Urine hydroxyproline/creatinine ratios (UOHP/C) 2

From the Research

Diagnosis of Paget's Disease

To diagnose Paget's disease, the following methods can be used:

• Plain radiographs of the suspicious regions of the skeleton are recommended for patients with suspected Paget's disease 3, 4, 5
• Radionuclide bone scans are recommended for assessing the extent of Paget's disease 6, 4, 7
• Serum total alkaline phosphatase (ALP) is recommended as a first-line biochemical screening test in combination with liver function tests in screening for the presence of metabolically active PDB 6, 5
• More specific markers of bone formation or bone resorption, such as PINP (intact N-terminal type 1 procollagen propeptide) or CTX (cross-linked C-telopeptide), can be used for initial biochemical evaluation 5

Biochemical Evaluation

After diagnosis, the following biochemical evaluations can be used to assess the response to treatment or evolution of the disease:

• Measurement of serum total alkaline phosphatase or more specific markers of bone formation or bone resorption 4, 5
• Serial radionuclide bone scans may determine the response to treatment if the markers are normal 4
• Biochemical follow-up is recommended to be used as a more objective indicator of relapse rather than symptoms 5

Treatment

The mainstay of treatment for Paget's disease is bisphosphonate therapy, with zoledronic acid being the most effective agent:

• A single 5-mg dose of intravenous zoledronic acid is the current standard therapy for Paget's disease 6, 4, 7, 5
• Bisphosphonates are recommended for the treatment of bone pain associated with Paget's disease 6, 4, 7, 5
• Treatment with a bisphosphonate is recommended for most patients with active Paget's disease who are at risk for further skeletal and extraskeletal complications 4, 5