Pagets Disease What is Paget's disease?

Paget's disease is a chronic bone condition characterized by disorder of the normal bone remodeling process. Normal bone has a synchronized relationship of mechanisms that act to lay down new bone and take up old bone. This relationship (referred to as remodeling) is essential for maintaining the normal calcium levels in our blood. In bone affected by Paget's disease, the bone remodeling is disturbed and not synchronized. As a result, the bone that is formed is abnormal, enlarged, not as dense, brittle, and prone to breakage (fracture). Paget's disease affects older bone of adults. It's estimated that 1% of adults in the U.S. have Paget's disease. There is an extremely rare form of Paget's disease in children, referred to as juvenile Paget's disease. Paget's disease is also known as osteitis deformans. What causes Paget's disease? It is not known what causes Paget's disease. Recently, certain genes have been associated with Paget's disease, including the Sequestrosome 1 gene on chromosome 5. Virus infection may be necessary to trigger Paget's disease in people who have inherited the genetic tendency to develop the condition. Functions of Bones Bone is often stereotyped as simply a protective and supportive framework for the body. Though it does perform these functions, bone is actually a very dynamic organ that is constantly remodeling and changing shape to adapt to the daily forces placed upon it. Moreover, bone stores crucial nutrients, minerals, and lipids and produces blood cells that nourish the body and play a vital role in protecting the body against infection. All these functions make approximately 206 bones of the human body an organ that is essential to your daily existence. The skeletal system consists of bones, cartilage, and the membranes that line the bones. Each bone is an organ that includes connective tissue (bone, blood, cartilage, adipose tissue, and fibrous connective tissue), nervous tissue, and muscle and epithelial tissues (within the blood vessels). Bones have many functions, including Support. Bones provide a framework for the attachment of muscles and other tissues.

Protection. Bones such as the skull and rib cage protect internal organs from injury.

Movement. Bones enable body movements by acting as levers and points of attachment for muscles. Mineral storage. Bones serve as a reservoir for calcium and phosphorus, essential minerals for various cellular activities throughout the body. Blood cell production. The production of blood cells, or hematopoiesis, occurs in the red marrow found within the cavities of certain bones. Energy storage. Lipids (fats) stored in adipose cells of the yellow marrow serve as an energy reservoir. Bone Structure There are two kinds of bone tissue

Compact bone is the hard material that makes up the shaft of long

bones and the outside surfaces of other bones. Compact bone consists of cylindrical units called osteons (Haversian systems). Each osteon contains concentric lamellae (layers) of hard, calcified matrix with osteocytes (bone cells) lodged in lacunae (spaces) between the lamellae. Smaller canals, or canaliculi, radiate outward from a central canal (Haversian canal), which contains blood vessels and nerve fibers. Osteocytes within an osteon are connected to each other and to the central canal by fine cellular extensions. Through these cellular extensions, nutrients and wastes are exchanged between the osteocytes and the blood vessels. Perforating canals (Volkmann's canals) provide channels that allow the blood vessels that run through the central canals to connect to the blood vessels in the periosteum that surrounds the bone.

Spongy bone consists of thin, irregularly shaped plates called trabeculae, arranged in a latticework network. Trabeculae are similar to osteons in that both have osteocytes in lacunae that lie between calcified lamellae. As in osteons, canaliculi present in trabeculae provide connections between osteocytes. However, since each trabecula is only a few cell layers think, each osteocyte is able to exchange nutrients with nearby blood vessels. Thus, no central canal is necessary. Here are the main features of a long bone The diaphysis, or shaft, is the long tubular portion of long bones. It is composed of compact bone tissue.

The epiphysis (plural, epiphyses) is the expanded end of a long bone.

The metaphysis is the area where the diaphysis meets the epiphysis. It includes the epiphyseal line, a remnant of cartilage from growing bones. The medullary cavity, or marrow cavity, is the open area within the diaphysis. The adipose tissue inside the cavity stores lipids and forms the yellow marrow.

Articular cartilage covers the epiphysis where joints occur.

The periosteum is the membrane covering the outside of the diaphysis (and epiphyses where articular cartilage is absent). It contains osteoblasts (bone-forming cells), osteoclasts (bone-destroying cells), nerve fibers, and blood and lymphatic vessels. Ligaments and tendons attach to the periosteum.

The endosteum is the membrane that lines the marrow cavity.

Here are the main features of short, flat, and irregular bones: In short and irregular bones, spongy bone tissue is encircled by a thin layer of compact bone tissue. In flat bones, the spongy bone tissue is sandwiched between two layers of compact bone tissue. The spongy bone tissue is called the diploe. Periosteum covers the outside layer of compact bone tissue. Endosteum covers the trabeculae that fill the inside of the bone.

In certain bones (ribs, vertebrae, hip bones, sternum), the spaces between the trabeculae contain red marrow, which is active in hematopoiesis. Etiology Although the etiology of Paget's disease is unknown, studies have provided some support for both viral and hereditary causes. Viral antigens have been detected in affected osteoclasts by numerous methods and research teams. In the United States, the measles virus antigen is most commonly detected in patients with Paget's disease. A positive family history is reported in as many as 40 percent of patients with Paget's disease. Much attention has been focused on a pagetic susceptibility locus at human chromosome 18q

Several genetic abnormalities, many affecting osteoclast generation and activity, have been identified. Mutations of the Sequestrum 1 gene from chromosome 6 are commonly related to Paget's disease. Appearance of involved bone on electron microscopy suggests a viral infection, but a viral cause has not been established. Symptoms of Paget's Disease Bone pain from microfractures or osteoarthritis; if the jaw is involved, teeth may become

loose Headaches and loss of hearing or vision from pressure on nerves, brain, or spinal cord and reduced blood flow Pain or neuropathy from pressure on nerves Increased head size, bowing of a limb, or curvature of the spine Hip pain Damage to cartilage of joints, which may lead to osteoarthritis Heart failure (only in severe cases, especially in patients with heart disease) Kidney stones (more common in patients with Paget's disease) Sarcoma, in less than 1 percent of patients with Paget's disease Patients with bone pain caused by Paget's disease usually describe the pain as continuous. Unlike osteoarthritis, pagetic bone pain usually increases with rest, on weight bearing, when the limbs are warmed, and at night.1,4 Paget's disease can cause osteoarthritis if the affected section of bone is near a joint.1 A variety of deformities may occur, including kyphosis; shortened or bowed limbs9 (Figure 1); leonine facies3; frontal bossing of the forehead3; dental abnormalities; and, in severe cases, an enlarged cranium that may be difficult to hold erect. Neurologic symptoms arise from the compression of nerves, which is caused by osseous growth. Resulting sequelae include cranial nerve, brain stem and cerebellar deficits, and deficits caused by spinal stenosis. Although cardiovascular involvement is uncommon, patients with widespread Paget's disease and extensive hypervascularization of the bone marrow can present with an arteriovenous shunt leading to high output cardiac failure. The incidence of malignant degeneration of pagetic bone ranges from less than 1 percent to 10 percent, depending on disease severity.1 Usually, these tumors are highly malignant osteosarcomas, fibrosarcomas, or undifferentiated spindle cell sarcomas.13,14 Radiologic characteristics suggestive of malignant transformation include cortical breakthrough and soft tissue masses.15 Patients with Paget's disease may also develop several types of pseudomalignancy, including pseudosarcoma and pseudo giant cell tumors that are responsive to corticosteroids. Paget's pseudosarcoma typically presents as a slow-growing, localized, periosteal mass on pagetic bone. It has a predilection for long bones, especially the femur, and differs from a true sarcoma in that it does not destroy cortical bone or invade

surrounding soft tissue.16 Patients may present with metabolic abnormalities, including hypercalcemia, hypercalcuria, and hyperuricemia.1 Diagnosis of Paget's disease may be suspected based on the symptoms, but radiographs are the most specific diagnostic test. Asymptomatic patients with a firstdegree relative with Paget's disease should be screened with a serum alkaline phosphatase test every two to three years. If the serum alkaline phosphatase level is elevated, a bone scan can be performed to determine the extent and activity of Paget's disease. Radiographs should be taken to confirm the diagnosis in a patient with bone scans suggestive of Paget's disease. Pathophysiology Paget's disease of bone is characterized by enhanced resorption of bone by giant, multinucleated osteoclasts, with formation by osteoblasts of disorganized, woven bone. This process evolves through various phases of activity, followed by a quiescent stage. Excessive osteoclastic activity with resorption of normal bone by giant, multinucleated cells begins the cycle. Subsequently, an intense osteoblastic response produces increased disorganized bone formation (in the form of vascular, primitively woven bone) and connective tissue reaction. As the osteoclastic and osteoblastic activities of bone destruction and formation repeat, a high degree of bone turnover occurs. After a variable amount of time, osteoclastic activity may decrease, but abnormal bone formation continues. Some pockets of normal-appearing lamellar bone may replace immature woven bone. Eventually, osteoblastic activity also declines, and the condition becomes quiescent. Sclerotic bone is the hallmark of this stage, and continued bone resorption and formation are minimal or absent. Hence, Paget's disease typically consists of the following 3 phases: (1) lytic, (2) mixed lytic and blastic, and (3) sclerotic or burned out. Note that the above sequence of stages (characterized by increased osteoclastic and then osteoblastic activity, followed by decreased osteoclastic activity and finally by decreased osteoblastic activity) is variable. Each skeletal lesion also has its own pathophysiology and its own unique rate of progression. At any one time, multiple stages of the disease may be demonstrated in different skeletal regions. Medical Management

lab tests Lab tests alone cannot be used to diagnose Paget's disease. Your doctor can use the results of lab tests along with results of your physical and medical exams and bone X-rays.

Alkaline phosphatase test. The most important lab marker for Paget's disease is alkaline phosphatase, which is an enzyme produced by bone. When bonetissue grows quickly, as in Paget's disease, large amounts of alkaline phosphatase are released into the blood. Since other body organs also make this enzyme, your doctor will want to do more tests. The test for alkaline phosphatase can be used to help diagnose people who have symptoms of Paget's disease or to monitor whether the disease is active or inactive. Markers of bone breakdown. Both bone and cartilage contain collagen, which is released when bone tissue breaks down. Pyridinoline, deoxypyridinoline, and N-telopeptide (NTX) are fragments of collagen that may be found in urine. High levels of these substances in the urine may indicate Paget's disease. Tests for these markers may be done to monitor your response to treatment, but they are not generally used to diagnose the disease.

X-rays Several types of X-rays may be used to confirm the diagnosis of Paget's disease and help determine whether there are complications from the disease. X-ray tests may include:

Bone X-rays. X-rays of bones affected by Paget's disease show an uneven pattern of bone growth. The affected bones often look deformed and thickened. Bone scan. This is the best test for diagnosing Paget's disease. You may have a bone scan of your entire body to find out which bones are affected. A bone scan is also useful for finding out whether Paget's disease is active or inactiveand may show small breaks in bones that cannot be seen on a regular X-ray. But a number of diseases can cause an abnormal bone scan. Magnetic resonance imaging (MRI). This test may be most useful if there arenervous system problems, such as hearing loss, vision problems, headaches, weakness or numbness of the face, or dizziness. Bone and nerves in the head affected by Paget's disease can be seen on an MRI. Computerized axial tomography (CAT scan). This test is most often used when bones of the skull or spine are affected by Paget's disease.

If you are diagnosed with Paget's disease, you will need regular checkups by your doctor or nurse to monitor the progress of the disease. Monitoring may include blood and urine tests that measure the amount of chemicals released from bone.

Early Detection Most people are not screened for Paget's disease. But if you have a family history of this disease, you may want to talk with your doctor or nurse about having your blood tested (alkaline phosphatase test) when you reach age 40. Treatment Supportive care for symptoms and complications

Bisphosphonates

Localized, asymptomatic disease requires no treatment. Symptomatic treatment includes analgesics or NSAIDs for pain. Orthotics help correct abnormal gait caused by bowed lower extremities. Some patients require orthopedic surgery (eg, hip or knee replacement, decompression of the spinal cord). Weight bearing should be encouraged, and bed rest should be avoided. Drug therapy: Drug therapy suppresses osteoclast activity. It is indicated for the following:

To prevent or reduce bleeding during orthopedic surgery

To prevent or retard progression of complications (eg, hearing loss, deformity, osteoarthritis, paraparesis or paraplegia related to vertebral Paget's disease, or other neurologic deficits, particularly in a poor surgical candidate) To treat pain clearly related to the pagetic process and not to another source (eg, osteoarthritis)

When serum alkaline phosphatase (of bony origin) is > 2 times the normal level, even in the absence of symptoms Although disease progression can be retarded, existing deficits (eg, deformity, osteoarthritis, hearing loss, neural impingement) are not reversed. Not all patients need treatment. For example, patients who have abnormal blood tests only may not need treatment. People with Paget's disease who are commonly treated include: Patients with deformities Patients with no symptoms when certain bones (such as weight-bearing bones) are involved, especially if the bony changes are progressing quickly, to reduce the risk of fractures Patients with symptoms

Drug therapy helps prevent further bone breakdown. Currently, there are several classes of medications used to treat Paget's disease. These include: Bisphosphonates -- These drugs are the first-line treatment, and they help increase bone density. Types of bisphosphonates include: o Alendronate (Fosamax) o Etidronate (Didronel) o Pamidronate (Aredia) o Risedronate (Actonel) o Tiludronate (Skelid) o Zoledronic acid (Zometa)

Calcitonin -- This hormone is involved in bone metabolism. Types include: o Intranasal (Miacalcin) o Subcutaneous (Calcimar) Plicamycin (Mithracin)

Analgesics or nonsteroidal anti-inflammatory medications (NSAIDs) may also be given for pain. Localized Paget's disease needs no treatment, if there are no symptoms and no evidence of active disease. Orthopedic surgery may be needed to correct a deformity in severe cases. Surgery Medical therapy prior to surgery helps to decrease bleeding and other complications. Patients who are having surgery should discuss treatment with their physician. There are generally three major complications of Paget's disease for which surgery may be recommended.

Fractures Surgery may allow fractures to heal in better position.

Severe degenerative arthritis If disability is severe and medication and physical therapy are no longer helpful, joint replacement of the hips and knees may be considered. Bone deformity Cutting and realignment of pagetic bone (osteotomy) may help painful weight bearing joints, especially the knees.

Complications resulting from enlargement of the skull or spine may injure the nervous system. However, most neurologic symptoms, even those that are moderately severe, can be treated with medication and do not require neurosurgery. Management Patients report using a wide range of options including acupuncture, tens, aromatherapy and massage. some of these appear beneficial but they have not been systematically researched. specific problems such as limb shortening and deformity may be helped by shoe raises and walking aids. Following surgery, patients may also need to consider adaptations in the home, such as a raised toilet seat and handrails. Emotional Support While Pagets disease is rarely lifethreatening, it can show some of the classic hallmarks of long-term conditions. it is inveterate, caused by non-reversible pathology, may leave residual disability and can need a long period of supervision and observation. some patients may be confused about the nature of the condition and concerned about the possibility of future complications including fracture and deformity. some are frightened by perceived or actual sideeffects of medication or may have unrealistic expectations of the outcome of therapy. Pain is a common feature of Pagets disease and, if this becomes chronic, it may lead to anxiety, social isolation and failure of coping mechanisms as part of a wider healthcare team, nurses may assume the key role of counsellor to patients who are uncertain or concerned about aspects of care. to fulfil this role, it is essential to focus on the individuals needs, offer accurate information and advice and liaise with other health and social care Nursing Diagnosis Pain related to bone deformity and possible joint involvement Impaired mobility realted to bone deformity, fracture, or pain Risk of injury related to limitations of mobility and altered bone metabolism Altered body image related to bone deformities and disturbance in function Activity intolerance related to immobility

Prognosis

Paget's disease itself is not fatal, however, it is associated with an increased risk of a cancerous bone tumor, called osteosarcoma. Paget's disease is a long-lasting (chronic) condition. The outlook is generally good, especially if the condition is diagnosed and treated before major changes in bones have occurred and when there is no osteosarcoma. The 'prognosis' of Paget's Disease usually refers to the likely outcome of Paget's Disease. The prognosis of Paget's Disease may include the duration of Paget's Disease, chances of complications of Paget's Disease, probable outcomes, prospects for recovery, recovery period for Paget's Disease, survival rates, death rates, and other outcome possibilities in the overall prognosis of Paget's Disease. Naturally, such forecast issues are by their nature unpredictable.

Pathophysiology: PAGETS DISEASE

- in Paget's disease, primary defect is in the remodeling system of isolated areas of skeleton; - it is characterized by massive turnover of bone in the affected areas w/ marked increase in both bone resorption & bone formation; - owing to rapid turnover, the bone formed is immature bone; - in the bones affected, there may be either little change in the shape of the bone or very marked change in the bone contour resulting from both lack of appropriate remodeling & change in quality of bone- small increased risk of osteosarcoma;