Define Paget’s Disease of Bone. Describe its clinical features and investigations.

Definition

Paget’s disease of bone (osteitis deformans) is a chronic disorder of disordered, excessive bone remodelling: intense osteoclastic resorption is followed by disorganised osteoblastic new-bone formation, producing bone that is enlarged, structurally weak and deformed. It affects older adults and may involve one bone (monostotic) or many (polyostotic), commonly the pelvis, femur, tibia, skull and spine.

Clinical Features

Many cases are asymptomatic and found incidentally (a raised alkaline phosphatase or an abnormal radiograph). When symptomatic, features include bone pain, deformity (bowing of the tibia/femur — ‘sabre tibia’, an enlarging skull with increased hat size), warmth over the affected bone (from hypervascularity), and complications. Skull involvement can cause deafness (compression of the eighth nerve).

Investigations

Biochemistry: markedly raised alkaline phosphatase (reflecting bone turnover) with normal calcium and phosphate. Radiographs show characteristic bone enlargement, coarsened trabeculae, mixed lytic and sclerotic areas, cortical thickening and bowing deformity (e.g. ‘flame-shaped’ lytic front in a long bone, ‘cotton-wool’ skull). A bone scan shows the distribution of active disease.

Complications & Management

Complications:

• bone pain, deformity, pathological fracture (often transverse ‘chalk-stick’ fractures), secondary osteoarthritis of adjacent joints, high-output cardiac failure (from hypervascular bone in extensive disease), nerve compression (deafness, spinal stenosis) and, rarely, sarcoma.
• Management: asymptomatic disease may just be observed
• symptomatic disease is treated with bisphosphonates (which powerfully suppress the excessive turnover and relieve pain) plus analgesia, and surgery for fractures, severe deformity (osteotomy) or arthritis (joint replacement).

Pathological Phases

Paget’s disease evolves through recognised phases that explain its mixed radiographic appearance: an early osteolytic phase dominated by intense osteoclastic resorption (a well-defined advancing lytic front, e.g. ‘osteoporosis circumscripta’ in the skull or a flame-shaped front in a long bone); a mixed phase of simultaneous resorption and disorganised formation; and a late sclerotic (burnt-out) phase of dense, coarse, structurally weak bone. This disordered turnover is why the bone enlarges yet fractures and deforms so readily.

Epidemiology & Aetiology

Paget’s disease is predominantly a condition of the middle-aged and elderly, rare before 40, and shows a striking geographical and familial variation in prevalence that points to both genetic susceptibility (a family history is common; SQSTM1 mutations are implicated) and possible environmental triggers. The disordered remodelling begins with abnormally large, overactive osteoclasts, and it is this osteoclastic overactivity that bisphosphonates target so effectively, switching off the accelerated turnover, relieving pain and allowing more normal bone to be laid down.

Assessment of Disease Activity

Because alkaline phosphatase reflects the intensity of bone turnover, it is used both to gauge disease activity and to monitor the response to treatment — a fall towards normal after bisphosphonate therapy indicates suppression of the overactive remodelling. A radionuclide bone scan maps the extent and distribution of active lesions, and plain radiographs characterise individual bones, together guiding which lesions need treatment or surgical attention.

Markedly raised alkaline phosphatase with normal calcium.

• Disordered excessive remodelling → enlarged, weak, deformed bone; older adults.
• Often asymptomatic; bone pain, deformity (sabre tibia), warmth, skull enlargement/deafness.
• ↑↑ alkaline phosphatase with normal calcium & phosphate; mixed lytic/sclerotic X-ray.
• Complications: fracture, OA, high-output cardiac failure, nerve compression, rare osteosarcoma.
• Bisphosphonates suppress turnover and relieve pain; surgery for fracture/deformity/arthritis.