Investigations used in Paget disease of bone

Bone-turnover markers can be used to diagnose Paget disease, and assess a patient’s response to treatment. These include markers of:

  • bone formation (eg serum total and bone-specific alkaline phosphatase concentrations)
  • bone resorption (eg degradation products of type I collagen such as urinary deoxypyridinoline and N-telopeptides).

Serum total alkaline phosphatase concentration is the main test used to confirm the diagnosis of Paget disease, as well as to indicate disease activity and assess response to treatment; it is sensitive, cheap and convenient. Reference ranges vary among laboratories, but a serum total alkaline phosphatase concentration above 125 units/L in the absence of another cause (eg liver function abnormality, vitamin D deficiency, hyperparathyroidism) suggests active Paget disease. A normal serum total alkaline phosphatase concentration does not exclude the diagnosis; it can mean that a single bone is affected (mono-ostotic disease) or that the disease is relatively inactive. In patients with impaired liver function, serum total alkaline phosphatase can be difficult to interpret; use bone-specific alkaline phosphatase instead.

Because most patients with Paget disease are asymptomatic, a diagnosis is often made after an incidental finding of:

  • raised serum total alkaline phosphatase concentration
  • pagetic lesions on X-rays or bone scans.

X-rays are useful in Paget disease for:

  • monitoring response to therapy (eg deformities in long bones, resolution of lytic lesions)
  • evaluating cases that are resistant to therapy (eg continuing symptoms, persistently elevated serum total alkaline phosphatase concentration)
  • identifying lesions at critical sites (eg skull, vertebrae) in patients with neurological symptoms.

Nuclear bone scanning is a sensitive but nonspecific technique for detecting pagetic bone lesions. It is used to determine the extent and distribution of disease, rather than for diagnosis. Bone biopsy is rarely required to confirm the diagnosis of Paget disease, or to differentiate it from other lytic or sclerotic bone disorders.