Research Paper on Paget’s Disease Of Bone

Paget’s Disease Of Bone

James Paget, 1877

Paget’s disease of bone

general information about disease

Etiology:

genetic causes

viral causes

Effects of disease

skeletal

spinal

neurological

Diagnosis of Disease

radiographic examinations

laboratory tests

Treatment and Prognosis for patient

bisphosphonates

calcitonin

disease can be treated but not cured.

Paget’s Disease of Bone

In 1877, Sir James Paget first described a disease that he had identified in a small number of patients who had been described as “having overly large heads and enlarged or deformed extremities with a higher likelihood of fracture.” (Chaffins) While Paget believed that this disease was a relatively new one, archaeological studies have since found evidence of it in skeletons from the first century A.D., as well as from the Medieval period. “Paget’s disease of bone (PDB), also called osteitis deformans, “is a nonmalignant disease of bone that causes accelerated and abnormal bone remodeling.” (Chaffins) In other words, as a bone in the human body naturally decays, old bone would normally be recycled into the components to construct new bone tissue. But with Paget’s disease of bone, the rate of bone rebuilding and that of the bone decaying is out of sync, resulting in “production of bone that is denser than normal, but which is structurally disorganized and mechanically weak.” (Daroszewska, 270) In humans, the only other major bone disorder that is more common than Paget disease of the bone is osteoporosis. Paget’s disease is typically a localized condition, meaning it is usually limited, but not exclusively, to a single bone located in the axial skeletal region. And while the exact cause of Paget’s disease of bone is not known, it is likely that genetic factors are involved. There is also new evidence that certain viral agents associated with the measles virus, the canine distemper virus, and the respiratory syncytial virus may also be involved in the development of Paget’s disease of bone. In the United States, approximately 1% of the population may get this disease, but those susceptible can usually trace their lineage to Western Europe. The disorder is rare in lieages from China, India, Japan, and other parts of Asia, as well as, strangely, Scandinavia.

It has been recognized for more than 50 years that Paget’s disease of bone has a genetic component to it, and between 15% and 40% of patients have family history of the disease. While “epidemiological studies indicate that the risk for developing PDB in relatives of patients with the disease is increased between 7 and 10 times.” (Daroszewska, 271) It is believe that Paget’s disease of the bone demonstrates Autosomal Dominant Inheritance as well as familial clustering of genes associated with the disease. And patients who have family members with Paget’s disease generally will develop more pronounced effects of the disease at an earlier age. There has also been a familial link to a predisposition for the disease to attack a particular bone in the body, but this is not a widely spread feature of the disease. The evidence for genetic factors in the development of Paget’s disease can also be found in the fact that certain ethnic groups are more likely to develop the disease, even after leaving their homeland and emigrating to other parts of the world. The fact that the disease continues to be prevalent in certain ethnic groups, despite the fact that they have emigrated, increases the likelihood that the disease is caused by genetic factors within the group rather than environmental factors within the environment where they reside. Recent molecular genetic research has also identified a number of genes that are likely involved in the development and mechanisms of Paget’s disease. (Daroszewska, 272)

In most patients, pain is often the symptom that causes a person to seek treatment, or at least discovery of what is causing the pain. In the case of Paget’s disease of bone, the individual consequences of the disease will depend upon which bone is the sight of the infection, how long the disease has been present, and the number of bones affected. When Paget’s disease affects the skull, the affects can be a deformity of the skull, hearing loss, and other neurological consequences due to the bone interacting with the brain tissue. In the spine, Paget’s disease can lead to “nerve root compression, spinal stenosis, the cauda equina syndrome and fractures.” (Seton) Complications of Paget’s disease can be high output failure, renal stones or hypercalcaemia, and sometimes, when a patient is bedridden, profound shifts in calcium. Rarely, a cancer called osteosarcoma may arise in older people affected by Paget’s, these cancers form a major proportion of osteosarcoma in senior citizens. (Seton)

Studies have determined that since the pattern of this disease follows the same pattern as degenerative joint disease in the elderly, Paget’s disease is normally located in the axial skeleton, skull, and long bones of the legs (tibia and femur), as well as in the lumbar and cervical regions, hips, and knees. “In patients with skull involvement, hearing loss is the most common complication, but tinnitus might also occur. Dental complications in patients with maxillary or mandibular disease include malocclusion and loss of teeth.” (Singer 484) But the most common site of Paget’s disease is the spine, with the sacrum and lumbar region being affected most often. When the disease affects the lower extremities, fractures are the most common symptom of the disease and generally are across the bone. Paget’s disease has also been known to have effects on the cardiovascular system and metabolism. (Singer 484)

Paget’s disease can often be diagnosed through radiological technology, such as X-rays, CT scans, and MRI’s; and there are a number of signs of Paget’s disease among which are “osteoporosis circumscripta, lesions, osteosclerosis, increased thickness and circumference of bone, compression from softening of bone, separation and displacement of teeth, picture-frame vertebrae, enlarged cranium with increase in the marrow space, and intense uptake of radioactive tracers by involved bone.” (Flowers, S34) In the early stages of the disease, a condition called osteolysis can usually be detected on radiographs as lesions on the bones. As the disease progresses, radiographs can show an increase in the density of the bone, abnormal structures, thickening of the bones, as well as discrete fractures. (Chaffins) In the sclerotic phase of the disease, bones can be uniformly thickened without natural striations; giving the bones an “ivory” appearance. But since radiological markers can often be confused with other diseases, laboratory testing should also be undertaken for a confident diagnosis. “Total serum alkaline phosphatase and urinary pyridinoline are 2 of the most important lab tests for diagnosis of Paget disease.”(Chaffins) Studies have demonstrated that there is a direct association between progression of the disease and the level of certain biochemical markers.

While many patients do not require any treatment for Paget’s disease of bone, others do, and therapy consists of chemical agents which are used to suppress the orthoclase activity. These agents are referred to as bisphosphonates and have been proven to be effective in the treatment of patients with Paget’s disease. The U.S. Food and Drug Administration currently has approved 5 bisphosphonates, each with an increased level of potency and effectiveness. “In order of increasing potency, these are etidronate disodium, tiludronate disodium, pamidronate disodium, alendronate sodium and risedronate sodium.” (Chaffins) Besides the use of these agents, Calcitonin is the only other known treatment for Paget’s disease of bone, and is effective in reducing bone turnover. And while there is some evidence that chemical agents can provide some relief for the pain and oseolytic disease often associated with Paget’s disease, “there is no convincing evidence that treatment is effective at preventing chronic complications, such as deafness, deformity and secondary arthritis” (Cundy) However, since chronic complications tend to develop over years, or decades, recent treatments may yet prove themselves effective. There is also the problem of whether or not patients using bisphosphonates can develop a resistance to the drugs. Resistance can be defined as the shortened time to relapse after receiving repeated same-dose treatments, and some patients have demonstrated the ability to develop a resistance to the drugs. Changing the drug, and increasing potency is a viable means of dealing with the problem of resistance, but as the disease progresses toward its final stages, the level of drug needed for treatment can increase exponentially.

How effective treatment can be usually depends upon the individual, their genetic predisposition, but also their lifestyle; including diet and exercise. Since Paget’s disease of bone weakens the bones and often leads to fractures, patients with this disease need to take care to prevent falls. One of the reasons there is a certain level of mortality associated with this disease is the effects on a person’s health due to inactivity caused by fractures. In older patients especially, inactivity can lead to other, more debilitating problems; and therefore patients suffering from Paget’s disease should take care to “fall-proof” their home. This could include using a walker or cane, removing slippery floor coverings, install handrails, or using nonskid mats in showers and baths. By removing the possibility of falling and suffering a major fracture, patients can increase their likelihood of surviving longer with this disease. Diet is also an important part of health and is especially important if a patient is being treated with pharmaceutical agents such as bisphosphonates. Increasing a patient’s intake of Calcium and Vitamin D is another extremely important factor for the uptake of calcium which strengthens bones. And finally, maintaining mobility and bone strength is essential for a patient with Paget’s disease, and nothing can do that better than regular exercise. While some activities could be harmful, consulting a doctor and fitness specialist can help in developing a program of exercise that is optimal.

Paget’s disease of bone is a disease that interferes with the normal biological processes of bone tissue, causing a number of adverse effects which could include things from abnormal bone growth to lesions and fractures. While there are some treatments for Paget’s, these treatments deal mostly with the pain associated with the disease, as well as chemical agents which help regulate bone growth. Despite these treatments, there is really no successful way to deal with the chronic complications associated with the disease. While a patient’s pain can be eased, and the symptoms of the disease delayed, there simply is no cure currently available for patients with Paget’s disease of bone.

Works Cited

Chaffins, Julie A. “Paget disease of bone.” Radiologic Technology 79.1 (2007): 27+.

Academic OneFile. Web. 19 Feb. 2012.

Cundy, Tim, and Brya Matthews. “Paget’s disease of bone.” Expert Review of Endocrinology & Metabolism 4.6 (2009): 651+. Academic OneFile. Web. 21 Feb.

2012.

Daroszewska, Anna, and Stuart H. Ralston. “Mechanisms of Disease: genetics of Paget’s disease of bone and related disorders.” Nature Clinical Practice Rheumatology

2.5 (2006): 270+. Academic OneFile. Web. 19 Feb. 2012.

Flowers, W. Mel, Jr. “Radiological signs of Paget’s disease.” Southern Medical Journal

(Oct. 2004): p. S34. Academic OneFile. Web. 19 Feb. 2012.

Leach, Robin J. And Frederick R. Singer “Do all Paget disease risk genes incriminate the osteoclast?” Nature Reviews Rheumatology. 6.9 (Sept. 2010): p502. Academic

OneFile. Web. 19 Feb. 2012.

Seton, Margaret. “Diagnosis, complications and treatment of Paget’s disease of bone.”

Aging Health 5.4 (2009): 497+. Academic OneFile. Web. 20 Feb. 2012.

Singer, Frederick R. “Paget disease: when to treat and when not to treat.”

Nature Reviews Rheumatology. 5.9 (Sept. 2009): p483. Academic OneFile. Web. 20 Feb. 2012.

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