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Paget’s Disease

Basics

Description

Paget 's disease of bone (osteitis deformans) is a skeletal disorder characterized by a focal increase in bone turnover (i.e., breakdown and formation). In this condition, bone structure and modeling are not normal. Affected bones become enlarged and deformed. пїЅ пїЅ

Epidemiology

  • Prevalence increases with age; affects 3 " пїЅ4% of individuals aged >40 years
  • Men and women equally affected
  • More common in Anglo-Saxons

Etiology

The exact cause is unknown; however, there seems to be a genetic component and a viral association. First-degree relatives of Paget 's patients are 7 " пїЅ10 times more likely to develop the disease. Viruses, such as the canine distemper virus, measles virus, and Paramyxoviridae family of viruses, have been linked to the disease. Current thinking hypothesizes that individuals genetically predisposed to Paget 's disease may develop the disease when they come in contact with a particular virus. пїЅ пїЅ

Diagnosis

  • Paget 's disease is usually asymptomatic. An elevated alkaline phosphatase level on a routine chemistry panel or evidence of Paget 's on x-ray conducted for some other reason usually leads to the diagnosis of this condition.
  • Signs and symptoms of Paget 's disease are related to the disease itself and its complications (i.e., abnormal bone growth and increased blood flow to the affected areas).
  • Any bone can be affected by Paget 's disease; however, pelvis, spine, skull, and long bones of the arms and legs are the most common sites of involvement. These sites are prone to bone deformity (i.e., bow legs, skull enlargement), bone pain (worsens with weight bearing), and fractures.
  • Abnormal bone growth can cause nerve compression. Hearing loss, facial droop, and vision loss are common complications.
  • A pagetic site has increased blood flow and, therefore, the affected area is warm to touch. Increased blood flow can also cause high-output heart failure and other cardiac complications in severe disease.
  • Individuals with Paget 's disease are also at an increased risk of bone tumors (i.e., osteosarcoma, benign giant cell tumors) and arthritis.

Tests

Lab

  • Alkaline phosphatase: An elevated level in an individual without liver problems raises concern for Paget 's disease. It reflects an increase in bone formation.
  • N-telopeptide (NTX): Increased bone resorption associated with Paget 's disease is reflected by elevated levels of Urine NTX.
  • Calcium and phosphate: Normal in most patients, but can increase in the presence of a second disorder such as immobilization. Extremely active Paget 's and bisphosphonate therapy are associated with hypocalcaemia.

Imaging

  • Radionuclide bone scan: Focal areas of increased uptake ( "hot " пїЅ spots) are seen in Paget 's disease.
  • Plain radiographs: X-ray of suspected regions noted on bone scan can confirm the diagnosis and evaluate the extent of the disease. Bone thickening, enlargement, lytic areas, deformity, and fractures can be seen on plain films.

Differential Diagnosis

Unusual for Paget 's to spread to new sites after initial presentation. Therefore, metastatic bone disease needs to be ruled out in individuals with new x-ray findings. Bone biopsy can confirm the diagnosis. пїЅ пїЅ

Treatment

All symptomatic individuals should be treated with an antiresorptive agent. Generally, asymptomatic individuals do not need treatment unless they are at high risk for complications. Suppression of bone remodeling should be considered in the following cases: пїЅ пїЅ

  • Symptoms or complications of Paget 's associated with an elevated alkaline phosphatase or active disease on bone scan (1,2,3)[A]
  • At risk for complications such as nerve compression (skull or spine involvement), fracture (weight bearing bone or joint involvement) or perioperative blood loss (surgery involving an active Paget 's site) (1,2,3)[B]
  • Serum alkaline phosphatase 2 times the upper limit of normal (1,2,3)[C]
  • Hypercalcemia due to immobilization or hyperparathyroidism (4)[B]

Medication

  • Non-narcotic analgesics, such as acetaminophen and NSAIDs, will relieve pain symptoms in most patients.
  • Antiresorptive agents should be considered in high-risk individuals to suppress bone remodeling (1,2,3)[A].Bisphosphonates: Oral and IV preparation can inhibit bone resorption. Zoledronic acid (5 mg IV single infusion), pamidronate (single 60 mg IV infusion over 4 hours for mild disease and 20 " пїЅ60 mg IV every 3 months in more severe disease), alendronate (40 mg/day for 6 months), risedronate (30 mg/day for 2 months), and etidronate (400 mg/day for 6 months) have all been approved by the FDA for treatment of Paget 's disease. Due to greater efficacy, zoledronic acid is generally preferred (5)[B].Side effects: Pill-induced esophagitis has been reported with oral bisphosphonates. Therefore, proper intake (fasting, with 8 oz of water, in the upright position for at least 1/2 hour without other oral intake) is recommended. IV bisphosphonates are associated with low-grade fever and flu-like symptoms for 1 " пїЅ2 days after the infusion. Hypocalcemia can occur with high-dose bisphosphonate therapy. Calcium (1,200 mg/day) and Vitamin D (800 IU/day) supplementation will alleviate this problem. Ocular side effects, such as conjunctivitis, uveitis, and scleritis and osteonecrosis of the jaw, have been described with bisphosphonate therapy.Calcitonin: Subcutaneous injection of calcitonin at bedtime has been approved by the FDA for the treatment of Paget 's disease. Salmon calcitonin 100 units or 0.5 mg of human calcitonin is the usual starting dose followed by 50 " пїЅ100 units every 1 " пїЅ3 days. Symptoms can start to improve after 2 weeks, but remission may require 22 months of therapy. Severe disease may require indefinite treatment or the addition of another agent. Considered as treatment when bisphosphonates are not tolerated.Side effects: Nausea, facial flushing, metallic taste, diarrhea, abdominal pain, and allergic reactions. These symptoms diminish as treatment progresses. Serum anticalcitonin antibodies develop in 20% of individuals treated with salmon calcitonin. These individuals can become resistant to therapy.

Additional Treatment

Issues for Referral

Endocrine referral should be considered for symptomatic individuals with Paget 's disease. ENT, ophthalmology, and orthopedic evaluation should be considered on an individual basis according to symptoms (i.e., hearing loss, vision loss, and fractures). пїЅ пїЅ

Additional Therapies

Other consequences of Paget 's, such as hearing loss, arthritis, and physical deformity, will need to be supported with hearing aids, analgesics, physical therapy, etc. пїЅ пїЅ

Surgery

Surgery to stabilize fractures, nerve decompression, and joint replacement should be considered if complications such as vision loss and arthritis develop. In patients undergoing elective surgery, recommend prophylaxis with a drug that suppresses pagetic activity for 2 " пїЅ3 months. This should reduce hypervascularity and therefore blood loss during the procedure. пїЅ пїЅ

Ongoing Care

Follow-Up Recommendations

Remission is achieved when symptoms improve and a 50% reduction in markers of bone resorption such as NTX and alkaline phosphatase is noted. If relapse, retreatment is as effective. пїЅ пїЅ

Patient Monitoring

Monitor symptoms and serum alkaline phosphatase levels periodically (i.e., every 6 " пїЅ12 months). Consider repeat bone scans and x-rays only if new symptoms develop. Treatment should be considered in symptomatic individuals with elevated alkaline phosphatase. Levels and symptoms should improve with treatment. пїЅ пїЅ

Complications

Patients need to be monitored for osteosarcoma, fractures, nerve compression, and cardiac abnormalities such as high-output failure. пїЅ пїЅ

References

1Ralston пїЅ пїЅSH, Langston пїЅ пїЅAL, Reid пїЅ пїЅIR. Pathogenesis and management of Paget 's disease of the bone. Lancet. 2008;372:155 " пїЅ163. пїЅ пїЅ[View Abstract]2Siris пїЅ пїЅES, Lyles пїЅ пїЅKW, Singer пїЅ пїЅFR. Medical management of Paget 's disease of the bone: Indications for treatment and review of current therapies. J Bone Miner Res. 2006;21(Suppl 2):P94 " пїЅP98. пїЅ пїЅ[View Abstract]3Whyte пїЅ пїЅMP. Clinical practice. Paget 's disease of the bone. N Engl J Med. 2006;355 " пїЅ593. пїЅ пїЅ[View Abstract]4Brandi пїЅ пїЅML, Falchetti пїЅ пїЅA. What is the relationship between Paget 's disease of bone and hyperparathyroidism? J Bone Miner Res. 2006;21(Suppl 2):P69 " пїЅP74. пїЅ пїЅ[View Abstract]5Seaton пїЅ пїЅM, Kranes пїЅ пїЅSM. Use of zolendronic acid in the treatment of Paget 's disease. Ther Clin Risk Manag. 2007;3:913 " пїЅ918.

Codes

ICD9

731.0 Osteitis deformans without mention of bone tumor пїЅ пїЅ

ICD10

  • M88.1 Osteitis deformans of vertebrae
  • M88.88 Osteitis deformans of other bones
  • M88.9 Osteitis deformans of unspecified bone
  • M88.829 Osteitis deformans of unspecified upper arm
  • M88.839 Osteitis deformans of unspecified forearm
  • M88.859 Osteitis deformans of unspecified thigh
  • M88.869 Osteitis deformans of unspecified lower leg

SNOMED

  • 2089002 osteitis deformans (disorder)
  • 203340003 Paget 's disease of pelvis (disorder)
  • 203327008 Paget 's disease-cervical spine (disorder)
  • 203328003 Paget 's disease-thoracic spine (disorder)
  • 203329006 Paget 's disease-lumbar spine (disorder)
  • 203334005 Paget 's disease of humerus (disorder)
  • 203335006 Paget 's disease-radius (disorder)
  • 203336007 Paget 's disease-ulna (disorder)
  • 203342006 Paget 's disease-femur (disorder)
  • 203345008 Paget 's disease-fibula (disorder)
  • 203344007 Paget 's disease-tibia (disorder)

Clinical Pearls

  • Paget 's disease causes bones to become enlarged and deformed.
  • The disease is often asymptomatic. It is often diagnosed after alkaline phosphatase is found to be elevated on routine chemistries or by finding evidence of Paget 's disease on an x-ray.
  • Complications of abnormal bone growth include nerve compression (may lead to hearing loss, facial droop, and vision loss), fractures, high-output heart failure, osteosarcoma, and arthritis.
  • Suppression of the pagetic process with an antiresorptive agent should be considered in all symptomatic individuals and some asymptomatic individuals who are at risk for complications.