Paget's Disease

Definition/Description

Also known as Osteitis Deformans, Paget's disease of the bone is a metabolic bone disease caused by increased bone resorption followed by excessive unrestricted bone formation, due to activated osteoclasts. The normal bone marrow is replaced by increased and unorganized collagen and fibrous tissue, which lacks the structural stability of normal bone. This increased bone mass formation leads to complications such as fractures, arthritis, deformities, pain, and to a patient's weakened condition. Paget's disease is the second most common metabolic bone disease to osteoporosis [1][2][3]

                          

Prevalence

  • After Osteoporosis, Paget's disease is the most common skeletal disorder. Paget's disease affects approximately 2% to 5% of the population older than 40, and seen in 10% of the population over the age of 70 years old. [4]
  • Paget's disease affects men more than woman by a 3:2 ratio. [4]
  • Evidence has shown that genetic factors of 40% of the individuals with Paget's disease have first-degree relatives with Paget's disease. [4][5]
  • There is a prevalence in British cities of about 2% and 8.3% in Lancaster, England. The United States, Great Britain, Australia, and New Zealand have high prevalences because of increased populations along with northern European ancestry. This condition is rare in Asian, African, Scandinavian, Indian, and Japanese populations. [6]
  • A recent study shows an estimated prevalence in the United States of 1% to 2% with nearly equal distribution between whites and blacks and between sexes. [7]
  • Recently, the prevalence of Paget's disease has decreased by 50% of the prevalence in 1983.[8]

Characteristics/Clinical Presentation

A patient with Paget's disease will often present as asymptomatic. However, the clinical presentation of a symptomatic patient varies greatly, due to the different levels of severity of this condition.

  • Bone pain presents as constant, deep, and aching. Bones most commonly affected by Paget's disease include: Pelvis, Lumbar spine, Sacrum, Femur, Tibia, Skull, Shoulders, Thoracic spine, Cervical spine, and the ribs. [1]
  • Joint pain including swelling and stiffness may present due to the damage of the cartilage lining the joints near the affected bones. [8]
  • The most common symptom experienced with symptomatic Paget's disease is an aching pain worse at night that decreases with physical activity. [1][2]
  • Muscular pain may present as referred pain from bony structures involved or as a complication due to the mechanical changes from the joint and bone defects. [1][2]
  • Neurological pain due to a compressed nerve root or the spinal cord may cause symptoms such as a sharp pain, numbness, tingling, weakness, hearing loss, and double vision. [4]
  • Patients with Paget's disease usually describe their pain as continuous. Different from osteoarthritis, pagetic bone pain usually increases with rest, on weight bearing, when the limbs are warm, and at night[5]
  • As many as 70% of people with Paget's disease present asymptomatic and is usually detected through radiographs and laboratory tests which are most times ordered for other indications[9][10]

 Other clinical presentations may include [4]:

  • Bone deformities such as bowlegs, and increased skull size
  • Warmth over the affected bone or joint.
  • Facial weakness or numbness.
  • Loss of bowel or bladder control which may indicate spinal cord damage.

Associated Co-morbidities

  • Paget's disease has an insidious onset and the disease progresses slowly. When Paget's disease is present in many bones the overactive osteoclasts have the ability to release enough calcium in the blood stream to cause hypercalcemia, which can cause symptoms such as fatigue, weakness, loss of appetite, abdominal pain, and constipation. [2][1]
  • Neurological complications due to nerve entrapment syndromes or nerve root compression as they exit the foramina which is narrowed by the increased bone mass of Paget's disease. [2]
  • Hearing loss due to increased temporal bone mass and 8th spinal nerve compression. [2]
  • Bone deformities such as increased skull size and bowing of limbs. [2]
  • People with Paget's disease are also more susceptible to fractures because Pagetic bone is weaker than normal bone.[1][2]
  • Cardiovascular problems may arise when 1/3 to 1/2 of the skeleton is involved, heart failure is possible due to an increased cardiac output (this is the most common cause of death in people with advanced Paget's disease).[1]
  • Metabolic complications of Paget's disease may include renal stones, hyperparathyroidism, and hypercalcemia[9][10]
  • A rare complication is sarcoma which is a bone cancer (also known as osteosarcoma or osteogenic sarcoma). This cancer may develop in Pagetic bone, which occurs in less than 1 percent of people with Paget's disease and usually doesn't develop until many years after the onset.[4]

Medications

  • Although only 5% of people with Paget's disease experience pain, the type of pain is very important to determine. [2]
  • Pain that is caused by an elevated SAP (Serum Alkaline Phosphatase) and resulting in an increased bone turnover, responds well to osteoclasts inhibitors such as bisphosphonates (ex. Zoledronic acid, Risedronate, Alendronate, Pamidronate, Etidronate Disodium). [1][2]
  • The gold standard for drug therapy for Paget's disease is bisphosphonates, which are aimed at decreasing abnormal bone resorption. The goal is to cause full remission of Paget's disease and establishing normal levels of SAP. These medications are intended to increase bone density and reduce the activity of Paget's disease. [1][2][4]
  • Zoledronate is the preferred intravenous bisphosphonate, but pamidronate is also a well tolerated intravenously administered drug for treatment of Paget's disease[9]
  • Patients who may not tolerate bisphosphonates can use Calcitonin, a natural hormone involved in calcium regulation and bone metabolism. Calcitonin is a drug that is administered by injection.[4]
  • Pain caused by nerve compression (caused by bone deformity or arthritis) should be treated with standard pain relievers such as NSAIDS and analgesics.[2]

Diagnostic Tests/Lab Tests/Lab Values

  • Radiographic Imaging (primary): Plain X-Ray should be performed in at least one skeletal area (usually in a painful area) to help confirm the diagnosis of Paget's disease. X-rays can also diagnose secondary conditions such as a fracture or arthritis. [1][2]
  • Isotopic Bone Scan (Scintigraphy) are more sensitive radiographic images which highlight affected areas of Paget's disease, but the Scintigraphy is only positive if the condition is active. [2]
  • Scintigraphy is recommended for patients with symptomatic and asymptomatic Paget's disease to determine the severity and involvement of the skeletal structures. [2]
  • Scintigraphy can also be used to monitor a patient's therapeutic response to therapy based on the results of a second diagnostic test. [1][2]
  • A Bone Biopsy may also be performed (especially if the X-ray and CT scan are negative) to make a differential diagnosis which would rule out hyperparathyroidism, bone metastasis, multiple myeloma, and fibrous dysplasia. [2]
  • Biochemical Tests: Serum Alkaline Phosphatase (SAP) is an enzyme that is produced by bone cells and are excessively produced in bone containing Paget's disease. [1][2]
  • In 85% of patients with Paget's disease, SAP levels are elevated. A solid relationship exists between the severity of the disease measured by the scintigraphy, and the increased levels of SAP in untreated Paget's disease. [2]
  • Many other biochemical tests are available which assess bone matrix resorption such Urinary and Serum Deoxypyridinoline, N-telopeptide, and Alpha and Beta C telopeptides, but none of these tests are as readily available as the SAP diagnostic lab test. [2]
  • Diagnosis of Paget's disease may be suspected based on symptoms, but radiographs are the most specific diagnosis test[5]

                  Image:Pelvis_Paget's_disease.jpg                                          Bowing Tibia of Patient with Paget's disease                                                         

  Radiograph of Pelvis of Patient with Paget's Disease   Radiograph of Bowing Tibia in Patient with Paget's Disease

Causes

  • The exact cause of Paget's disease is unknown, though it is thought to be a slow, viral bone infection due to risk factors that include a gene-environment interaction. [1][2][4]
  • The prevalence and causes of Paget's disease has been associated with genetic and geographical factors. A positive family history is reported in as many as 40% of patients with Paget's disease [1][2][4][5]
  • Paget's disease is mostly seen in an autosomal dominant distribution, and there have been three identifiable chromosomal regions associated with Paget's disease. [1]
  • Geographically, populations in European, British, and Australian origin, and a migratory influence also play an important role especially in countries which of the early population migrated from Britain (United States, Australia, New Zealand, Canada).[1]
                          

Systemic Involvement

There are many different systems that may be affected by Paget's disease and many associated conditions[1]:

Pain

Skeletal

  • Kyphoscoliosis
  • Bone Bowing (outward bowed femur or forward bowed femur)
  • Coxa Varus (waddling gait) _Coxa_Valga
  • Acetabular protrusion
  • Osteoarthritis
  • Fractures
  • Bone enlargement
  • Vertebral compression

Muscular

  • Myalgia
  • Stiffness
  • Weakness

Neurological

  • Nerve compression conditions including cranial, spinal, and peripheral nerves
  • Hearing loss
  • Mental confusion due to deteriorated cognitive function

Cardiovascular

  • Heart failure
  • Increased vascularity (causing increased skin temperature around affected area)
  • Increased cardiac output

Other

  • Overall fatigue
  • Vertigo
  • Dizziness
  • Tinnitus

Medical Management (current best evidence)

Medical Management of Paget's disease depends on the symptoms the patient is experiencing. Pain that arises due to elevated SAP (Serum Alkaline Phosphatase) levels responds well to osteoclast inhibitor medications, while pain that arises from nerve irritation (due to bone deformity) should be treated with NSAIDS or analgesics. Many patients have seen good results from combining analgesics and physical therapy, electrical nerve stimulation, hydrotherapy, and acupuncture. [1][2]

 First Line of Treatment

Due to abnormal osteoclast activity, inhibition of bone resorption with bisphosphonates is the gold standard and first treatment initiated to decrease osteoclastic activity, improve bone density, and increase the strength of the bone itself. Bisphosphonates many times provide long-lasting remissions and treatment response is monitored through assessing the reduction of biomechanical markers such as the SAP levels. Patients should intake 1000-1500 mg of calcium and at least 400 U of vitamin D daily. This recommendation is especially important while utilizing bisphosphonate treatments. The goal of this treatment is to cause a full remission (normal SAP levels) and prevent complications of this condition.

Second Line of Treatment

Depending on the severity of pagetic changes and degree of pain, NSAIDS and other anti-inflammatories are used to control the pain. Some patients benefit from a combination of medications such as an analgesic and antidepressant. Modalities such transcutaneous electrical nerve stimulation (TENS), hydrotherapy, acupuncture, and physical therapy may also provide pain relief. Orthopedic assistive devices such as canes and shoe lifts may help some patients.

Third Line of Treatment

Surgical intervention may be indicated if a patient is resistant to pharmacological or orthopedic interventions. A Joint replacement is indicated if severe degenerative joint breakdown is present. If a nerve compression syndrome is present and the patient is nonresponsive to conservative treatment, surgery is required. Other common surgeries for Paget's disease include occipital craniectomy to relieve basilar and nerve compression, and tibial osteotomy if the varus deformity is severe.

Physical Therapy Management (current best evidence)

  • Pain caused by increased skeletal abnormalities leads to loss of muscle strength, decreased range of motion, and cardiovascular endurance resulting in functional limitations. Physical Therapy and exercise can assist in maintaining muscle strength, flexibility and joint range of motion, increased endurance, and decrease the chances of deconditioning [1][6]
  • Strengthening muscles around the joints affected and its adjacent joints can help minimize skeletal complications of Paget's disease [1]
  •  Improvements in cardiovascular function and cardiac output also can result from physical therapy improving functional activities such as walking endurance and longer distances [1]
  • A physical therapist may also provide orthotics and other assistive devices to help in management of extremity deformities. The physical therapist can aid in correcting this problem by providing inserts or making appropriate shoe modifications. Bracing may also be beneficial with an open reduction and internal fixation limb surgeries. Assistive devices fo ambulation, such as a cane or walker, can help reduce weight-bearing and pain following these surgeries[1][6]
  • A physical therapist can also assist a patient with Paget's disease in home modifications to make the patient safer with mobility around the home[6]
  • Modalities can also be beneficial such as superficial heat, transcutaneous electrical nerve stimulation (TENS), and massage, may be helpful for muscle pain, tenderness, and tightness [6]
  • May need to avoid impact activities such as jogging, running, jumping, and aggressive forward bending and twisting exercises, if the spine is affected by Paget's disease [1]

Differential Diagnosis

 After obtaining a clinical history and several radiographs and laboratory tests the differential diagnosis can narrowed down to a select few including [6][4]:

  • Osteoarthritis
  • Osteoporosis
  • Rheumatoid arthritis
  • Psoriatic arthritis
  • Ankylosing spondylitis
  • Diffuse idiopathic skeletal hyperostosis
  • Pseudogout
  • Peyronie disease
  • Bone Metastases
  • Fibrous Dysplasia
  • Blastic Metastases
  • Myelofibrosis
  • Renal Osteodystrophy
  • Fluorosis
  • Mastocytosis
  • Tuberous Sclerosis
  • Calvarial Hyperostosis

 Many of these conditions may co-exist with Paget's disease.

Case Reports

http://www.ejbjs.org/cgi/reprint/58/7/994

http://proquest.umi.com.libproxy.bellarmine.edu/pqdweb?index=7&did=1953783091&SrchMode=2&sid=1&Fmt=6&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1271026385&clientId=1870

add links to case studies here (case studies should be added on new pages using the case study template)

[1]

Resources

Foundation for Paget's Disease: http://www.paget.org/

Medline Plus: http://www.nlm.nih.gov/medlineplus/pagetsdiseaseofbone.html

American Academy of Orthopedic Surgeons: http://orthoinfo.aaos.org/topic.cfm?topic=A00076

Online Medical Library: http://www.merck.com/mmpe/sec04/ch037/ch037a.html

Arthritis Foundation: http://www.arthritis.org/

Medicine Net: http://www.medicinenet.com/pagets_disease/article.htm

National Institute of Arthritis Musculoskeletal and Skin Diseases:  http://www.niams.nih.gov/Health_Info/Bone/Pagets/pagets_disease_ff.asp

Recent Related Research (from Pubmed)

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References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 Goodman C, Fuller K. Pathology: Implications for the Physical Therapist. St. Louis, Missouri: Saunders Elsevier;2009.
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20 2.21 2.22 Josse R, Hanley D, Kendler D, Marie LG, Adachi J, Brown J. "Diagnosis and Treatment of Paget's Disease of the Bone".Clin Invest Med August 2007: E210-E223.
  3. Seitz, Sebastian, Priemel, Matthias. “The Second Most Common Bone Disease: A Review on Paget’s Disease of Bone”. European Journal of Trauma and Emergency Surgery. November 2008.
  4. 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 Goodman C, Snyder T. Differential Diagnosis for Physical Therapists: Screening for Referral. St. Louis, Missouri: Saunders Elsevier, 2007.
  5. 5.0 5.1 5.2 5.3 Schneider, Doron, Hofmann, Mary T. “Diagnosis and Treatment of Paget’s Disease of Bone”. American Family Physician. May 2002: 65. No.10.
  6. 6.0 6.1 6.2 6.3 6.4 6.5 Chow, David. Emedicine. Med Web:Paget Disease. http://emedicine.medscape.com/article/311688-overview. Updated December 18,2008. Accessed April 2, 2010.
  7. Hadjipavlou, Alexander G, Gaitanis, Ioannis N. “Paget’s Disease of Bone and its Management”. The Journal of Bone and Joint Surgery. March 2002: 84B. No.2.
  8. 8.0 8.1 Medical Foundation for Medical Education and Research. Mayo Clinic: Paget’s disease of bone.http://www.mayoclinic.com/health/pagets-disease-of-bone/DS00485. Updated August 15, 2008. Accessed March 3, 2010.
  9. 9.0 9.1 9.2 Seton, Margaret. “Diagnosis, Complications and Treatment of Paget’s disease of bone”. Aging Health.
  10. 10.0 10.1 Roux, Christian, Dougados, Maxime. “Treatment of Patients with Paget’s Disease of Bone”. Disease Management. November 1999: 58 (5):823-830.