First described by Paget in 1870, it is also known as Paget's disease. The onset age is mostly over 50, with a positive family history accounting for 14%, and the male-to-female ratio is 3:2. The incidence rates are high in South Africa and the United States, but reports in China are very few.

bubble_chart Etiology

The cause of Paget's disease of bone remains unclear to this day. Many authors believe it may be a chronic sexually transmitted viral infection. Cell cultures from bone tissue biopsy specimens have revealed the presence of viruses in osteoclasts, while no viruses were found in osteoblasts or normal bone tissue.

bubble_chart Pathological Changes

Mirra proposed that the cause of this disease is due to increased osteoclast activity, leading to severe localized bone resorption that gradually spreads within the affected bone. Therefore, he suggested naming the disease "osteoclastitis." In the early stages, the bone resorption by osteoclasts results in sparse trabeculae and thinning of the cortical bone. Subsequently, the number of osteoclasts decreases, while osteoblasts increase correspondingly, and both the cortical bone and trabeculae are replaced by cancellous bone. Ultimately, whether cortical or cancellous bone, both exhibit a disorderly mosaic structure. The stages of this pathological process are not sharply demarcated, and even in the same patient at the same site, manifestations of bone resorption and bone formation can coexist simultaneously.

The lesions of Paget's disease of bone can occur at one or multiple sites and may be accompanied by tumors, with osteosarcoma being the most common. Some believe that these tumors are actually the result of malignant transformation of Paget's disease of bone.

Symptoms and signs Approximately 10-20% of patients have no clinical symptoms and are often incidentally discovered during X-ray examinations for other diseases.

Back pain Back pain is the most common clinical symptom of Paget's disease. The pain worsens when vertebral pathological fractures occur, and if accompanied by osteosarcoma, the disease progresses rapidly, quickly leading to nerve compression symptoms or even lower limb paralysis.

Bone pain Mainly occurs in weight-bearing bones. Besides the lumbosacral spine, common sites include the femur and pelvis. The pain is usually severe and deep, with severe cases causing bedridden conditions and difficulty turning over. Blood flow in the affected area significantly increases, often resulting in a burning sensation of the skin and reluctance to touch it. Deformities may occur in the long bones of the lower limbs, and severe cases can lead to fractures. Those with skull involvement may experience headaches, tinnitus, and other symptoms. Thickening of the skull increases head circumference, often requiring patients to switch to larger hats.

Arthritis Commonly seen in the hip and knee joints, presenting as pain and functional impairment. It should be differentiated from degenerative arthritis secondary to pelvic and lower limb deformities.

Neck pain Discomfort and pain may occur in the neck and shoulder areas.

bubble_chart Auxiliary Examination

Most patients have elevated serum alkaline phosphatase levels and increased urinary hydroxyproline content, but serum calcium, phosphorus, vitamin D3, and thyroid hormone levels usually remain normal. In recent years, it has been reported that elevated serum calcitonin levels may aid in diagnosis.

helps clarify the diagnosis and determine whether a tumor is present. It may be considered when clinical and X-ray examinations cannot confirm the diagnosis.

Imaging studies

X-ray plain films: In the early stages, absorption is predominant, with typical manifestations including localized osteoporosis. In the skull, the outer table is destroyed first while the inner table remains intact. In long tubular bones, besides reduced trabeculae, thinning of the cortical bone can also be observed. A "V"-shaped demarcation line with clear and sharp edges can be seen at the junction between the lesion and normal cortical bone. In vertebral bodies, pathological fractures may occur. In the advanced stage of the disease, bones show sclerosis and enlargement. While the outer table of the skull still exhibits osteolytic changes, the inner table begins to sclerose. As the lesion progresses, the outer table gradually thickens, eventually leading to the complete disappearance of the boundary between the inner and outer tables, often resulting in the skull thickening several times. In long tubular bones, thickening of the cortical bone and coarse, disordered trabeculae can be observed, along with bending deformities, incomplete transverse fractures, and pathological fractures. The pelvis becomes narrow, and the hip joint space decreases. In severe cases, the femoral head may protrude into the pelvic cavity. In the spine, vertebral bodies significantly enlarge, and the posterior structures also undergo hyperplasia and sclerosis, thickening to 2–3 times the normal size, while the intervertebral spaces generally remain normal.

Other imaging modalities: Radionuclide scanning, CT, and MRI can help differentiate Paget's disease from tumors.

Most asymptomatic or mildly symptomatic individuals often do not require treatment, while a minority with significant symptoms may undergo non-surgical or surgical treatment, with surgical treatment also requiring concurrent medication.

Non-surgical treatment

The main indications include: (1) pain; (2) deformity; (3) serum alkaline phosphatase or urinary hydroxyproline levels increasing to twice the normal value; (4) symptoms of nerve compression; (5) high-output congestive heart failure; (6) pathological fracture; (7) pre-surgical treatment. For Paget's disease, non-surgical treatment primarily involves medication, in addition to protecting the affected bone and preventing pathological fractures.

Calcitonin can inhibit the bone resorption function of osteoclasts. After administration, serum alkaline phosphatase and urinary hydroxyproline levels may decrease accordingly, but in severe cases, abnormal levels may persist long-term. Most patients experience rapid pain relief, reduced limb blood flow, decreased body temperature, and alleviation or disappearance of neurological symptoms.

Bisphosphonates inhibit both bone resorption and formation, leading to bone softening. Relapse is common after discontinuation. Some recommend calcitonin as the first choice when the lesion is in weight-bearing bones, while others advocate combined use of calcitonin and bisphosphonates. Additionally, drugs such as mithramycin may be considered.

Surgical treatment

The main indications for surgical treatment are: (1) certain pathological fractures; (2) severe arthritis; (3) severe deformity in weight-bearing bones. For those with nerve compression symptoms unresponsive to medication, decompression surgery may be performed. However, the incidence of nonunion is higher in pathological fractures treated with internal fixation.