Paget's disease of bone: Pathogenesis & Symptoms
Pathogenesis
Paget's disease of bone is characterized by increased bone remodeling and disorganization in the focal area of the bone. One or more bones are involved, especially the axial skeletons pelvis (70%), femur (55%), lumbar spine (53%) and skull (42%). Paget's disease is rare in people under 55 years of age, but prevalence increases after age 55. In some countries it has been reported that 5% of women and 8% of men are lifelong. Especially in European people and rare in Africa and asian. This difference makes us suspect that this disease is not on a genetic basis. It is speculated that infections such as Paramyxovirus may act as triggers for the onset of Paget's disease. Paget's disease has a positive family history in 15% of patients, and the disease is inherited as an autosomal dominant, with incomplete penetrance. The SQSTM1 mutation is found in 40-50% of familial patients and 5-10% of sporadic disease patients. This gene codes for a protein that regulates osteoclast function.
Symptoms
Patients with Paget's disease of bone are most often diagnosed with elevated serum alkaline phosphatase and abnormal radiograph findings. Although clinically symptomatic patients are thought to be fairly low at 5-10% of the total, there are actually 30-40% of symptomatic patients at the time of diagnosis. The most common symptom is bone pain and deafness may occur with skull involvement. Osteosarcoma is a very rare complication (less than 0.5%), but should be suspected if sudden bone pain becomes severe or swelling occurs. Bone deformity and warmth of the skin overlying affected bone can be observed. Diagnosis is usually based on radiograph findings. Typical features seen on the radiograph are focal osteolysis with coarsening of the trabecular pattern, bone expansion, and cortical thickening. The extent of the disease is best seen with a radionuclide bone scan. MRI and CT are not routinely used. In laboratory tests, renal function, calcium albumin, alkaline phosphatase, 25-hydroxyvitamin D, and liver function should be identified to identify other diseases. A typical patient with Paget's disease has elevated serum ALP alone and is not unusual in other labs. However, this disease should not be excluded because ALP level is normal. Bone turnover markers such as bone-specific alkaline phosphatase or procollagen type I N-terminal propeptide are useful in patients with liver disease and are used in conjunction with total serum ALP when assessing diagnostic or therapeutic response. Diffuse diagnosis includes hyperostosis frontalis interna, fibrous dysplasia, pustulotic arthrosteitis, and osteosclerotic metastases.
A principal indication for antiresorptive therapy is bone pain thought to be caused by increased bone metabolic activity. There is no evidence that asymptomatic patients benefit from antiresorptive therapy. Amniobisphosphonate is the treatment of choice, and ALP levels begin to decline 10 days after treatment and reach the lowest level 3-6 months after treatment. As ALP decreases, the symptoms gradually improve.
Paget's disease of bone is characterized by increased bone remodeling and disorganization in the focal area of the bone. One or more bones are involved, especially the axial skeletons pelvis (70%), femur (55%), lumbar spine (53%) and skull (42%). Paget's disease is rare in people under 55 years of age, but prevalence increases after age 55. In some countries it has been reported that 5% of women and 8% of men are lifelong. Especially in European people and rare in Africa and asian. This difference makes us suspect that this disease is not on a genetic basis. It is speculated that infections such as Paramyxovirus may act as triggers for the onset of Paget's disease. Paget's disease has a positive family history in 15% of patients, and the disease is inherited as an autosomal dominant, with incomplete penetrance. The SQSTM1 mutation is found in 40-50% of familial patients and 5-10% of sporadic disease patients. This gene codes for a protein that regulates osteoclast function.
Symptoms
Patients with Paget's disease of bone are most often diagnosed with elevated serum alkaline phosphatase and abnormal radiograph findings. Although clinically symptomatic patients are thought to be fairly low at 5-10% of the total, there are actually 30-40% of symptomatic patients at the time of diagnosis. The most common symptom is bone pain and deafness may occur with skull involvement. Osteosarcoma is a very rare complication (less than 0.5%), but should be suspected if sudden bone pain becomes severe or swelling occurs. Bone deformity and warmth of the skin overlying affected bone can be observed. Diagnosis is usually based on radiograph findings. Typical features seen on the radiograph are focal osteolysis with coarsening of the trabecular pattern, bone expansion, and cortical thickening. The extent of the disease is best seen with a radionuclide bone scan. MRI and CT are not routinely used. In laboratory tests, renal function, calcium albumin, alkaline phosphatase, 25-hydroxyvitamin D, and liver function should be identified to identify other diseases. A typical patient with Paget's disease has elevated serum ALP alone and is not unusual in other labs. However, this disease should not be excluded because ALP level is normal. Bone turnover markers such as bone-specific alkaline phosphatase or procollagen type I N-terminal propeptide are useful in patients with liver disease and are used in conjunction with total serum ALP when assessing diagnostic or therapeutic response. Diffuse diagnosis includes hyperostosis frontalis interna, fibrous dysplasia, pustulotic arthrosteitis, and osteosclerotic metastases.
A principal indication for antiresorptive therapy is bone pain thought to be caused by increased bone metabolic activity. There is no evidence that asymptomatic patients benefit from antiresorptive therapy. Amniobisphosphonate is the treatment of choice, and ALP levels begin to decline 10 days after treatment and reach the lowest level 3-6 months after treatment. As ALP decreases, the symptoms gradually improve.
