Following are features of Paget's disease except -
Paget's disease of bone (PDB) is a common condition characterised by focal areas of increased and disorgan ised bone remodelling. It mostly affects the axial skele ton, and bones that are commonly involved include the pelvis, femur, tibia, lumbar spine, skull and scapula. PATHOPHYSIOLOGY-Diseases of bone The primary abnormality is increased osteoclastic bone resorption, accompanied by marrow fibrosis, increased vascularity of bone and increased osteoblast activity. Bone in PDB is architecturally abnormal and has reduced mechanical strength. Osteoclasts in PDB are increased in number, are unusually large and contain characteristic nuclear inclusion bodies. Genetic factors are impoant and mutations in the SQSTM1 gene are a common cause of classical PDB. The presence of nuclear inclusion bodies in osteoclasts has fuelled speculation that PDB might be caused by a slow virus infection with measles or distemper but the evidence is conflicting. Biomechani cal factors may help determine the pattern of involve ment, since PDB often stas at sites of muscle inseions into bone and, in some cases, localises to bones or limbs that have been subjected to repetitive trauma or overuse. Involvement of subchondral bone can compromise the joint and predispose to OA ('Pagetic ahropathy'). CLINICAL FEATURES -The classic presentation is with bone pain, deformity, deafness and pathological fractures, but many patients are asymptomatic and diagnosed from an abnormal Xray or blood test performed for another reason. Cli nical signs include bone deformity and expansion, increased warmth over affected bones, and pathological fracture. Bone deformity is most evident in weight bearing bones such as the femur and tibia, but when the skull is affected the patient may complain that hats no longer fit due to cranial enlargement. Neurological problems, such as deafness, cranial nerve defects, nerve root pain, spinal cord compression and spinal stenosis, are recognised complications due to enlargement of affected bones and encroachment upon the spinal cord and nerve foraminae. Surprisingly, deafness seldom results from compression of the auditory nerve, but is conductive due to osteosclerosis of the temporal bone. The increased vascularity of Pagetic bone makes opera tive procedures difficult and, in extreme cases, can precipitate highoutput cardiac failure in elderly patients with limited cardiac reserve. Osteosarcoma is a rare but serious complication that presents with subacute onset of increasing pain and swelling of an affected site. INVESTIGATIONS -The characteristic features are an elevated serum ALP and bone expansion on Xray, with alternating areas of radiolucency and osteosclerosis (Fig. 25.57B). ALP is normal in about 5% of cases, usually because of mono stotic involvement. Radionuclide bone scanning is useful to define the presence and extent of disease (Fig. 25.57A). If the bone scan is positive, Xrays should be taken of an affected bone to confirm the diagnosis. Bone biopsy is not usually required but may help to exclude osteo sclerotic metastases in cases of diagnostic unceainty. MANAGEMENT-The main indication for treatment with inhibitors of bone resorption is bone pain thought to be due to increased metabolic activity (Box 25.82). It is often difficult to dif ferentiate this from pain due to complications such as bone deformity, nerve compression symptoms and OA. If there is doubt, it can be wohwhile giving a therapeu tic trial of antiresorptive therapy to determine whether the symptoms improve. A positive response indicates that the pain was due to increased metabolic activity. The aminobisphosphonates pamidronate, zoledronate and risedronate are more effective than simple bisphos phonates such as etidronate and tiludronate at suppress ing bone turnover in PDB, but their effects on pain are similar. Although bisphosphonates suppress bone turn over in PDB, there is no evidence to show that they alter the natural history or prevent complications. Calcitonin can be used as an alternative but is less convenient to administer and more expensive. Repeated courses of bisphosphonates or calcitonin can be given if symptoms recur. If symptoms do not respond to antiresorptive therapy, it is likely that the pain is due to a complication of the disease and this should be managed according to the principles described on page 1085. DAVIDSONS PRINCIPLES AND PRACTICE OF MEDICINE 22ND EDITION PAGE NO-1128,112
Deformity of bones
Secondary osteosarcoma
Lowered serum alkaline phosphatase
Increased Urinary excretion of hydroxyproline
Endocrinology