Metabolic Bone Disease Paget ’s Disease

pediagenosis    April 25, 2021    Endocrine , Organ   

Metabolic Bone Disease Paget ’s Disease

Clinical background

Paget’s disease (osteitis deformans) is a chronic bone disorder resulting in bone pain and deformity. It affects up to 10% of the elderly, more commonly men, although it may be asymptomatic and discovered on a routine blood test or X-ray. Most commonly patients present with bone pain or deformity – these are characteristic of the disorder and include bowing of the long bones, skull enlargement with frontal bossing and, less commonly, pathological fractures (Fig. 53a, b and c).

Paget’s disease is characterized by abnormal bone remodelling. Often the disease is picked up by the finding of a high alkaline phosphatase on biochemical screening. Calcium and PTH concentrations are normal but measurements of markers of bone turnover, such as serum bone-specific alkaline phosphatase (BAP) and osteocalcin indicating bone formation and urinary deoxypyridinoline and N-terminal telopeptide indicating bone resorption, may be helpful.

Patients with Paget’s disease are treated with analgesics and bisphosphonates. The latter will reduce bone turnover and improve symptoms. There is an increased risk of malignant change in pagetic bones and any change in symptoms, such as the development of acute pain, heat or fracture in a patient with long-standing disease should be investigated immediately.

Paget’s disease of bone

Aetiology and pathology. Paget’s disease is a relatively rare disorder of bone remodelling that involves greatly accelerated rates of bone turnover, abnormal bone architecture and may lead to gross bone deformity. It is not strictly a metabolic disorder since the disease is focal to bone. The aetiology is poorly understood but may involve a chronic viral infection since inclusion bodies resembling paramyxovirus have been found in pagetic osteoclasts. The disease may be familial and several genetic associations have been identified. Paget’s disease is characterized by features of high metabolic bone activity, including excessive cellularity and vascularity. The osteoclasts, large multinucleate cells which are normally present only when bone is being resorbed, may be huge and highly multinucleate in Paget’s disease, when bone is being haphazardly remodelled. The resultant bone, as with other conditions involving high bone turnover, may be so-called woven bone, which lacks the normal lamellar structure. The spine, sacrum and femur are the most frequency affected bones, followed by the skull and pelvis. Recent advances in the identification of hormones and cytokines involved in the modulation of osteoclastogenesis may throw light on the aetiology of Paget’s disease.

Complications of Paget’s disease reflect the implications of bone deformity on associated soft tissues, and may be neoplastic, rheumatological, neurological and, rarely, cardiac. The spinal cord and brain are at risk of compression, especially the brain stem and cranial nerves, and deafness often results through effects on the skull. Spinal stenosis (narrowing) may occur in vertebral Paget’s disease, and peripheral nerve entrapment may cause, for example, carpal tunnel syndrome. Osteoarthritis is a common complication of Paget’s disease and bone sarcoma may develop. Very occasionally, patients may suffer high-out- put congestive heart failure because of the abnormally high blood flow to bone.