Paget’s disease (pagetdisease, PD), also known as deformational osteitis or deforming osteitis, is a common metabolic bone disease and dystrophic bone disease of unknown cause. Paget first described the clinical features of the disease in 1877, characterized by increased bone reconstruction, bone hypertrophy, abnormal bone structure, and resulting in bone pain, deformity, and local skin fever.
The whole body can be involved, but the ribs, skull and pelvis are the most vulnerable, and in severe cases, disability can result from compression of nerves and blood vessels by the deformed bones. The disease is mostly detected incidentally on imaging or because of increased serum alkaline phosphatase (AKP) activity; the lesions are highly restrictive and new Paget’s disease injuries rarely develop in unaffected areas after a definitive diagnosis.
1, Epidemiological features.
There are significant geographical differences. It is most common in the United Kingdom, followed by Australia, New Zealand, and North America, and is rare in Africa and Asia. It mainly invades the elderly, uncommon under 50 years of age, and the incidence increases with age; more men than women ((1.8:1). The incidence of Paget’s disease has decreased in recent years, probably due to environmental factors or ethnic changes in the population.
2. Etiology.
Extensive research has been conducted in recent years on the etiology of Paget’s disease of bone, and new breakthroughs have been made in genetics and virology. In terms of genetic etiology, one study found that about 1/3 of patients have genetic variants in the kinship clade and in patients without a family history of the disease. Thus the possible etiology seems to be a variation in the gene, but it is not clear how the variation leads to the restriction of the bone lesion. the study by Friedrichs et al. supported the viral theory by finding an inclusion body-like virus in the osteoblasts of patients with this disease under electron microscopy. No studies on the etiology of PD have been reported in China.
3. Pathological changes.
The basic pathological changes are osteolytic and abnormal proliferative bone lesions. Microscopically, osteoclasts and osteoblasts are actively proliferating, bone trabeculae are irregularly thickened, and the bone marrow cavity is replaced by fibrous connective tissue and blood vessels. The characteristic change is a large number of well-defined blue-stained bone adhesion lines in the widened trabeculae, which is due to the sudden interruption and change of lamellar bone and woven bone direction caused by bone resorption and degeneration during the disease development.
4.Clinical features.
It is diverse. The lesion can be confined to one bone tissue or invade multiple bones throughout the body, most often invading the pelvis, lumbosacral, spine, skull, femur and tibia. The most common symptoms are: Paget’s disease bone pain, which is more limited in some patients and is evident in weight-bearing areas; in advanced stages, it can produce deformities such as bowing prominence of the femur and tibia, which may have no clinical symptoms, or may manifest as mechanical pain in the affected limb or contralateral side. Abnormal mechanical stress effects at the site of bone loss can lead to cortical fracture of the fissure, which can then progress to a complete fracture.
The most common complication is deafness due to cranial involvement, followed by spinal cord compression, cranial nerve palsy, hydrocephalus, and other nerve root compression syndromes. patients with Paget’s disease of bone are at significantly increased risk of developing osteoarthritis, which may present with typical arthritic manifestations. All patients with osteosarcoma over the age of 60 years are at risk for complications of Paget’s disease of bone. They may also present with theft syndrome, which is due to increased blood flow to the bone and may be complicated by paraplegia if it occurs in the thoracic spine.
5. Imaging features.
The early stage can be detected by radiological examination. x-ray examination: the bone ends are obviously involved, the cortical and cancellous boundaries disappear, the bone volume increases, but the bone trabeculae are coarse and sparse, the arrangement is disorganized in the form of striated high-density shadow, intertwined in a grid-like change, resembling cotton wool-like change, the osteolytic activity is dominant, causing focal osteolytic lesions; subsequently, osteosclerosis occurs and develops, and mixed signs of osteolysis and osteosclerosis appear.
The sensitivity of X-ray examination is lower than that of isotope bone imaging, and the rat face sign of bone imaging has diagnostic value. isotope bone scan can determine the distribution of the disease, especially the potential complications of lesions at the skull base, spine, and long bones, as part of the early diagnostic evaluation. CT and MRI scans can detect small lesions early and facilitate early diagnosis; they are useful for evaluating skull base invasion, spinal stenosis, and other neurological complications. X-ray performance is atypical and often requires biopsy to confirm the diagnosis; CT-guided coarse needle aspiration can obtain satisfactory lesion tissue.
6. Laboratory tests.
Blood alkaline phosphatase (AKP) is elevated in 95% of patients, while calcium and phosphorus metabolism are mostly normal. In monoblastic PD, serum AKP is often not elevated, and the patient may not have any clinical symptoms, but is found to have a limited lesion in the bone during physical examination or X-ray or bone imaging due to other diseases. Other bone transformation indicators are often normal. Biochemical evaluation also includes 25-trans-vitamin D testing because osteochondrosis can also manifest bone pain and elevated AKP levels, and vitamin D deficiency must be corrected prior to treatment with dirinitrate compounds.
7. Diagnosis.
Diagnosis relies on the clinical presentation and imaging of the patient, with generalized hyperplasia and pain in the damaged bones. There may be deformities of the head, thinning and compression of the sternum. When the spine is damaged, the patient’s height is reduced. When the spine has a scoliosis deformity, the patient’s motor function is impaired. x-ray typically shows enlarged affected bone with excessive bone resorption and hyperplasia. ct examination allows clear visualization of bone lesions in the bone section and accurate measurement of cranial thickness.
Because of the increased isotope uptake by the affected bone, isotope scans can indicate the extent of bone damage and the effectiveness of treatment. Blood biochemical examination, serum phosphorus may be higher than normal in active patients, and serum ALP is increased in most patients. The diagnosis must be combined with clinical manifestations, imaging manifestations and blood biochemical examinations, and the combination of the three can achieve an early and accurate diagnosis. Based on the increased serum AKP and the typical X-ray features of osteosclerosis, osteolysis and bone swelling. Isotope bone scans are much more sensitive than radiographs in diagnosing Paget’s disease, and more and more clinicians are using bone scans to screen for Paget’s disease, as well as to clarify the distribution of the affected bones.
The disease is usually asymptomatic and is mostly detected incidentally on imaging or as a result of increased serum AKP activity. Diagnostic characteristic imaging and pathological manifestations help in the diagnosis of PD.
8. Clinical typing.
(1) Spongy: Bone trabeculae are thick and normally arranged at the beginning, but later they are disorganized, the bone cortex is gradually thickened and not easily distinguishable from the medullary cavity, the hyaline area coexists with osteosclerosis, and bone bending can be produced due to osteoporosis.
(2) Sclerotic type: bone sclerosis is obvious, its diameter can be increased, less deformity.
(3) Sparing type (mixed type): bone destruction and repair coexist, and there is a cystic translucent area in the sclerotic area.
9. Differential diagnosis.
When the disease is clinically suspected, hyperparathyroidism bone disease, abnormal bone fiber hyperplasia, giant cell tumor of bone, osteosarcoma, multiple myeloma and bone metastasis of prostate cancer should be excluded. It has been reported that this disease can occur in combination with hyperparathyroidism bone disease and giant cell tumor of bone.
10.Treatment.
The aim of treatment is to achieve “three remissions”, i.e. clinical remission (release of bone pain and other symptoms), biochemical remission (return of plasma AKP level to normal reference range), and imaging remission (filling of osteolytic lesions). The current treatment methods are pharmacological and surgical.
11. Treatment indications.
Paget’s disease is treatable, but not all patients require treatment. Only symptomatic Paget’s disease should receive treatment, and bone pain at the site of the Paget’s disease is an indication for treatment. Some patients who are asymptomatic but have lesions of long bones such as the femur, cerebrum, tibia, and vertebral plates should also receive treatment because of the risk of fracture and spinal stenosis; this is especially important after the development of significant osteolytic lesions. Many scholars believe that skull base involvement has the risk of Paget’s osteomalacia deafness, and once it occurs, medication and surgical treatment are generally ineffective, so it should also be an indication for treatment.
12. Pharmacological treatment.
Osteoclasts are the primary cells of Paget’s osteopathy invasion, so treatment is oriented to inhibit osteoclast formation, inhibit destructive bone resorption and induce osteoclast mediation. Calcitonin can inhibit the resorption of destroyed bone and the formation of osteoclasts, but 50% of patients develop antibodies to calcitonin after 6 months of treatment with calcitonin, and some patients develop drug resistance.
Diphosphate compounds such as chlorophosphates, tilaposates, and alanophosphates, which block osteoclast formation and induce osteoclast mediation, are currently the most common and effective drugs used to treat Paget’s disease. Studies have shown that 50% to 60% of patients recovered normal bone conversion after 3-6 months of second-generation diphosphonate treatment; after 2 years of continuous treatment, 1/3 of patients can recover normal bone visualization and even achieve normal bone structure, which can effectively prevent or reduce complications. Most studies have concluded that calcitonin, diphosphonates and other drugs cannot cure Paget’s disease of bone, but only control the pathological process of the disease.