From the Guidelines
Paget's disease of bone is a chronic disorder that requires prompt treatment with bisphosphonates to prevent long-term complications and improve quality of life. The disease is characterized by abnormal bone remodeling, resulting in enlarged, weakened bones that may cause pain, deformities, and complications. It typically affects older adults, with most patients being over 50 years of age. The disease often involves the pelvis, skull, spine, and long bones.
Treatment Options
- For asymptomatic patients with normal alkaline phosphatase levels, monitoring without medication is appropriate.
- For symptomatic patients or those with elevated alkaline phosphatase, bisphosphonates are the first-line treatment.
- Zoledronic acid (5mg IV once) is most effective, providing remission for years, as supported by recent studies 1.
- Alternative options include oral alendronate (40mg daily for 6 months) or risedronate (30mg daily for 2 months).
Management and Prevention
- Calcium (1000-1500mg daily) and vitamin D (800-1000 IU daily) supplements should accompany bisphosphonate therapy to prevent hypocalcemia.
- Pain management may include acetaminophen or NSAIDs.
- Patients should be monitored with alkaline phosphatase levels every 6-12 months after treatment.
- Surgery may be necessary for fractures, severe arthritis, or nerve compression.
Disease Pathophysiology
- The disease results from excessive osteoclast activity followed by disorganized bone formation, likely triggered by viral infection in genetically susceptible individuals with SQSTM1 gene mutations, as noted in recent research 2.
- Paget's disease can also increase the risk of developing other conditions, such as osteosarcoma, as mentioned in a recent study 3.
From the Research
Diagnosis of Paget's Disease
- Paget's disease of bone is a benign focal disorder of accelerated skeletal remodeling, which can affect either a single bone (monostotic) or multiple bones (polyostotic) 4.
- Diagnosis is made on the basis of typical radiological features on plain films, while a radionuclide bone scan may be used to assess the extent of disease 5.
- The initial biochemical evaluation of a patient should be done using serum total ALP (alkaline phosphatase) or with the use of a more specific marker of bone formation: PINP (intact N-terminal type 1 procollagen propeptide) or CTX (cross-linked C-telopeptide) 4.
Treatment of Paget's Disease
- The mainstay of treatment for Paget's disease is bisphosphonate therapy, with zoledronic acid being the most effective agent 5, 6.
- A single infusion of zoledronic acid leads to a sustained reduction in bone pain and markers of bone turnover 5, 7.
- Treatment with a bisphosphonate is recommended for most patients with active Paget's disease who are at risk for further skeletal and extraskeletal complications 4.
- Oral bisphosphonates are less potent when compared to zoledronate, but can still be effective in achieving remission in a large proportion of patients 8.
Follow-up and Monitoring
- Measurement of total ALP or other baseline disease activity markers (e.g. CTX) at 6 to 12 weeks, when bone turnover will have shown a substantial decline, is an acceptable and cost-effective option 4.
- Biochemical follow-up is recommended to be used as a more objective indicator of relapse rather than symptoms 4.
- The prolonged response after zoledronate treatment should be assessed every 1-2 years after normal bone turnover, while with less potent drugs, every 6 to 12 months is appropriate 4.