Causes, Symptoms, Diagnosis
Paget's disease is a chronic disease characterized by an alteration of the bone remodeling cycle, due to which some bone areas become metabolically hyperactive and richly vascularized.
The initial event is probably represented by a marked increase in bone resorption, due to the excessive activity of osteoclasts. Osteolysis is followed by a compensatory increase in bone formation induced by locally recruited osteoblasts. The accelerated osteoblastic activity produces a disorganized bone tissue, where the normal architecture is replaced by the coarse arrangement of lamellas and trabeculae ("mosaic" model). As a consequence, the newly formed bone can gradually increase in volume, decrease its biomechanical efficiency and load resistance, with effects also on contiguous joints. The bone matrix is replaced with an inadequately mineralized, softer and weaker structure. The patient suffering from Paget's disease is therefore susceptible to pain, fractures, skeletal deformations, secondary osteoarthritis or compression of nerve structures. Depending on the part of the body involved, various neurological, cardiac, metabolic or rheumatologic complications may progressively arise. Paget's disease typically begins in elderly subjects and can affect any skeletal bone, although more commonly it occurs in the spine, pelvis, long limb bones or skull.
Paget's bone disease is often asymptomatic, or clinical signs are confused with other skeletal anomalies associated with aging. Typically, the diagnosis is defined following a radiological examination or a routine biochemical evaluation. Blood tests often indicate an increase in alkaline phosphatase, a parameter that reflects rapid bone turnover. Bone scintigraphy determines the degree of bone involvement, while bone biopsy is only necessary if an osteosarcoma is suspected. The course of Paget's bone disease is very variable: periods of stability can be alternated with periods of rapid progression.
To remember
- Symptoms of Paget's disease can result from:
- High bone turnover: deep and continuous pain affecting the affected bone segment;
- Deformity (widening or bending of bones, disabilities etc.);
- Degenerative articulation (arthrosis secondary);
- Compression of nervous structures;
- Fractures.
- Although it is a chronic condition, the disease does not spread to new bones, but tends to localize in one or some areas of the body.
- During the diagnostic tests the doctor must carefully evaluate the clinical picture to make sure that there are no medical conditions associated with Paget's disease (heart failure, neurological deficits, osteoarthritis, etc.).
Currently, a definitive cure for Paget's bone disease is not available, but some drugs can help keep the disease under control, alleviate the symptoms and slow down (or block) the onset of complications. From this point of view, early diagnosis is very important because, if treatment is administered before serious disorders occur, the prognosis for affected patients is generally good.
The choice of therapeutic strategy to be undertaken in patients suffering from Paget's disease can be complex because:
- there are no two subjects affected identically by the disease;
- sometimes it is difficult to predict whether a patient, who does not show signs of the disorder, may develop symptoms or complications later on.
In most cases, Paget's disease does not compromise quality of life and therapy may not be necessary, especially if the disease is asymptomatic and there is no evidence of cellular hyperactivity. The goal of drug therapy is to alleviate bone pain and help prevent disease progression. Currently, the most commonly used drugs are bisphosphonates, powerful inhibitors of bone resorption, which help control the disease and reduce pain and other symptoms. Possible complications often make use of a specific treatment, such as: therapy for painful, anti-inflammatory manifestations to decompress nerve roots, surgical interventions (nervous decompression, osteotomy to correct deformity or arthroplasty).
drugs
Pharmacological treatment is recommended:
- When the pain is clearly related to Paget's disease (and not to another bone disease);
- To prevent or delay the progression of complications.
Bisphosphonates and calcitonin are the drugs approved for the treatment of Paget's disease: they allow to control the exaggerated rate of bone turnover, suppressing the hyperactivity of bone cells and influencing the flow of mineral ions.
Bisosfonates are generally the first choice treatment for Paget's disease . These drugs reduce the speed of bone turnover, relieve bone pain, promote the healing of osteolytic lesions and restore normal bone histology. Treatment with bisphosphonates involves rapid remission of symptoms related to increased bone turnover, but has little effect on other symptoms.
Bisphosphonates are indicated for treating a variety of bone diseases. For example, they are also included in the therapeutic protocol of osteoporosis, where they help to increase bone density. In the treatment of Paget's disease, some bisphosphonates are taken orally, while others are given intravenously. The oral form is generally well tolerated, but long-term therapy may involve several side effects, such as: heartburn, osteonecrosis of the jaw and sometimes increased bone pain for a short period of time. Any deficiency of calcium and vitamin D must be corrected before starting therapy with a bisphosphonate, to avoid hypocalcemia. Furthermore, none of these drugs should be used by patients with severe kidney disease. Serum alkaline phosphatase monitoring allows to monitor the effects of treatment with bisphosphonates and disease activity.
If the patient is unable to tolerate bisphosphonates, the doctor may prescribe calcitonin, a natural hormone (produced by the thyroid gland) involved in the regulation of calcium and bone metabolism. Calcitonin-based therapy reduces pain, normalizes calcium levels and improves the radiological appearance of pagetic bone. Calcitonin is a drug that is given by injection or nasal spray. Side effects may include nausea, facial flushing and irritation at the injection site. Furthermore, it is to be remembered that the long-term use of calcitonin-containing drugs is associated with an increased risk of cancer. The drug may be appropriate for some patients, but is considered less effective than bisphosphonates, therefore rarely used. For pain associated with Paget's disease, medications such as: ibuprofen, naproxen, aspirin, acetaminophen or several other non-steroidal anti-inflammatory drugs (NSAIDs) may also be indicated by the doctor. In association with pharmacological therapy, measures such as orthoses, sticks and other orthopedic devices can also be envisaged, useful if the disease causes walking problems.
To learn more: Drugs to cure Paget's disease »
Surgery
When symptoms cannot be managed with conventional drug therapy, surgery can be used. This treatment is rarely necessary and should be considered only in certain circumstances, for example to correct severe deformities of pagetic bone, arthrosis, pathological fractures and reduce nerve compression.
blood vessels in the affected bones (hypervascularization). For this reason, in anticipation of an orthopedic surgery, it is possible to adopt a pharmacological pre-treatment that reduces the activity of the disease, in order to prevent or reduce serious intraoperative bleeding.
Surgery may be recommended for three major complications of Paget's disease:
- Fractures . Surgical therapy can help bones heal in a better position;
- Severe degenerative arthritis . People with severe arthritis related to Paget's disease are generally treated with medication and physical therapy. If these are no longer effective, hip or knee replacement can be considered to avoid severe disability;
- Bone deformity . The cutting and realignment of the pagetic bone (a procedure called osteotomy) can be indicated to reduce stress and pain in "load bearing" joints, as in the case of the knee or hip.
Bones affected by Paget's disease can take longer to heal than normal bones, so a long period of rehabilitation may be necessary after surgery. Complications resulting from enlargement of the skull or spine can damage the nervous system. However, most neurological symptoms, even moderately severe ones, can be treated with a drug and do not require neurosurgery. Decompressive laminectomy can be performed if medical therapy fails to help patients with neurological problems resulting from spinal cord compression.
Prognosis
The success of the treatment depends on the extent and degree of activity of the disease. The outlook for people diagnosed with Paget's disease is generally good, especially if the therapy is adopted before major changes occur in the affected bones. Drug therapy can reduce symptoms, but it is not a definitive cure. Treatment should aim to achieve and maintain normalization of bone turnover for as long as possible. Therapy monitoring is based on the determination of total or bone alkaline phosphatase, taking into consideration that the parameter falls within the norm after approximately 6 months from the beginning of the therapeutic cycle. Patients must frequently undergo medical supervision, partly because of the risk of osteosarcoma, an extremely rare complication, but correlated with a poor prognosis (most patients die within three years). Osteosarcoma typically presents with an increase in bone pain and other signs poorly sensitive to medical care. Radiographic investigations and bone biopsy can help confirm the diagnosis.
Lifestyle
There are no useful measures to prevent the onset of Paget's disease. Adopting a healthy diet and performing regular physical activity are important measures to preserve skeletal health and maintain joint mobility.
To reduce the risk of complications associated with Paget's bone disease, it may be useful to follow these steps:
- Prevent falls. Paget's bone disease exposes the patient to a high risk of bone fractures. For this reason, it is advisable to prevent accidents by taking precautionary measures, such as using non-slip mats in the bathtub or in the shower, securing exposed cables and installing a handrail on the stairs. In some cases, the use of a walking stick or walker may be recommended.
- Eat well. There is no special diet to prevent or help treat Paget's disease, but the diet should include an adequate supply of calcium and vitamin D, which facilitates calcium absorption and is particularly important during bisphosphonate therapy. On the doctor's advice, it is important to obtain an adequate intake of vitamins and calcium even with the possible intake of supplements, to be carefully evaluated in patients who have had kidney stones.
- Regular exercise. Regular physical activity takes on a very important value, as it helps to avoid weight gain (and the pressure of the added pounds on the weakened bone), to keep the bones resistant and the joints mobile. Before starting, it is advisable to seek advice from your doctor to choose the exercise program that best suits your needs. Some activities may damage or stress pagetic bones excessively.
