Background

Paget’s disease is a chronic disorder characterized by abnormal bone remodeling. This condition typically results in enlarged and weakened bones, leading to various complications such as bone pain, deformities, fractures, and other skeletal abnormalities. 

Paget’s disease primarily affects the way bones grow and repair themselves. It involves the excessive breakdown of bone tissue by specific cells called osteoclasts, followed by an abnormal increase in the formation of new bone tissue by osteoblasts. This process leads to the affected bones becoming more extensive, more brittle, and structurally weaker than normal bone tissue. 

Epidemiology

Prevalence: According to reports, the disease’s prevalence has declined over the previous 20 years and is currently believed to be between 1.5%-8.3%. The prevalence varies among different populations, with a higher incidence reported in individuals of European descent. 

Age of Onset: The disease usually manifests in individuals over the age of 50, with the average age of diagnosis around 55-60 years. However, it can occur at any age, including in younger individuals, although this is relatively uncommon. 

Geographic Distribution: There are geographic variations in the prevalence of Paget’s disease, suggesting a possible genetic and environmental influence. Regions with higher prevalence rates include parts of the United Kingdom, western Europe, and certain areas in the United States, especially those with a higher proportion of individuals of European ancestry. 

Familial Aggregation: There’s evidence of a genetic predisposition to Paget’s disease, as it often clusters in families. The likelihood of developing Paget’s disease is higher in those with a family history of this disease. 

Anatomy

Pathophysiology

Initial Phase 

Excessive Bone Resorption: The process begins with an initial phase of increased bone resorption, where osteoclasts become hyperactive. These overactive osteoclasts excessively break down bone, leading to the release of calcium and other minerals into the bloodstream. This phase causes weakened and structurally abnormal bone. 

Compensatory Bone Formation: In response to the increased bone resorption, the body triggers a compensatory mechanism to form new bone tissue. Osteoblasts are activated to generate new bone to repair the areas undergoing excessive breakdown. However, this new bone formed during this phase tends to be disorganized and structurally weaker than normal bone. 

Mixed Phase: As the disease progresses, there is a mixed phase characterized by both increased bone resorption and abnormal bone formation. This leads to a chaotic pattern of bone remodeling, resulting in enlarged, deformed, and weakened bones. 

End Stage: Eventually, the excessive bone remodeling process leads to the formation of abnormal, enlarged bones that are prone to deformities, fractures, and complications such as arthritis, nerve compression due to enlarged bones pressing on nearby structures, and in rare cases, increased risk of bone cancer (osteosarcoma). 

Etiology

Genetic Factors: Paget’s disease tends to run in families, there may be a hereditary component to the condition. The development of Paget’s condition has been linked to mutations in the SQSTM1 gene. Only a small percentage of those carrying these genetic abnormalities will experience the illness, though. 

Environmental Factors: Paget’s disease may occur because of environmental variables, including exposure to specific viruses or other infectious agents, as well as geographic considerations. However, specific environmental triggers haven’t been conclusively identified. 

Abnormal Bone Remodeling: The disease involves excessive and abnormal bone remodeling, where there’s an imbalance between bone resorption and bone formation. This results in the affected bones becoming larger, weaker, and more prone to deformities. 

Genetics

Prognostic Factors

Extent of Bone Involvement: The severity and extent of bone involvement can affect the prognosis. If Paget’s disease affects a larger area or multiple bones, it may lead to more complications and symptoms. 

Location of the Disease: Paget’s disease can occur in various bones but tends to favor the pelvis, skull, spine & long bones of the legs. The location may influence the risk of complications, such as fractures or nerve compression. 

Age at Diagnosis: Age at the time of diagnosis can impact the prognosis. Those diagnosed at a younger age might have a longer duration of disease and potentially more severe complications. 

Presence of Symptoms: The presence and severity of symptoms such as bone pain, deformity, fractures, and neurological complications can affect the prognosis. Early detection and management of symptoms can lead to better outcomes. 

Complications: Complications associated with Paget’s disease, such as fractures, osteoarthritis, bone deformities, and neurological complications due to nerve compression, can influence the prognosis. 

Clinical History

• Age group 

Paget’s disease of bone typically affects older adults, usually occurring in people over the age of 50 or 55. The average age at which symptoms develop is around 55 to 60 years old. It’s relatively rare in individuals younger than 40. However, while it primarily affects older adults, it can occur at any age. 

Physical Examination

Observation: 

Visual inspection may reveal bone deformities, enlarged or misshapen bones, or changes in posture. Look for signs of increased skull size, deformities in long bones (like bowing of the legs), or spinal curvature. 

Skin changes: Sometimes, overlying skin may show warmth, redness, or local swelling in affected areas. 

Palpation: 

check the bones for tenderness, warmth, or bony enlargement. 

Palpating affected bones may reveal warmth, tenderness, or bony overgrowth. 

Range of Motion Assessment: 

Assessing joint flexibility and mobility, especially if the Paget’s disease has affected nearby joints. 

Restricted range of motion or joint stiffness might be present. 

Neurological Examination (if applicable): 

If Paget’s disease has affected the spine, a neurological examination may be necessary to check for signs of nerve compression or spinal cord involvement, like sensory changes, muscle weakness, or abnormal reflexes. 

Assessment of Associated Symptoms: 

Paget’s disease can lead to complications like bone pain, fractures, joint pain, hearing loss, and in rare cases, increased risk of bone cancer (osteosarcoma). Evaluate and inquire about these symptoms during the examination. 

Age group

Associated comorbidity

Osteoarthritis: Paget’s disease can lead to the development of osteoarthritis in affected joints due to the abnormal bone remodeling process, leading to joint pain and stiffness. 

Hearing Loss: In cases where Paget’s disease affects the bones of the skull, particularly the bones around the ears, it can lead to hearing loss. 

Neurological complications: Compression of nerves due to enlarged bones can result in neurological complications such as tingling, numbness, or weakness in certain areas of the body. 

Cardiac issues: Rarely, Paget’s disease may affect the heart, leading to heart complications in severe cases. 

Associated Activities: 

Pain Management: Paget’s disease can cause bone pain, which may require pain management strategies such as over-the-counter pain relievers or, in severe cases, prescription medications. 

Physical Therapy: Physiotherapy and exercises can help maintain joint mobility and function, especially in cases where Paget’s disease affects weight-bearing joints. 

Monitoring and Follow-up: Regular monitoring by a healthcare professional is essential to track the progression of the disease and address any complications that may arise. 

Surgical Intervention: In severe cases where bone deformities or complications like fractures occur, surgical intervention may be necessary to stabilize or correct the affected bones. 

Associated activity

Acuity of presentation

Bone Pain: Paget’s disease can cause bone pain, which may be localized and worsen at night or during activity. 

Bone Deformities: Affected bones might become enlarged,or develop deformities due to the excessive bone remodeling. 

Fractures: Weakened bones may be more susceptible to fractures. 

Joint Stiffness: Paget’s disease can affect adjacent joints to the affected bones, leading to stiffness and reduced range of motion. 

Neurological Symptoms: In rare cases where the disease affects the skull, it can lead to compression of nerves, resulting in symptoms like headaches, hearing loss, and vision changes. 

Elevated Alkaline Phosphatase Levels: Blood tests might reveal elevated alkaline phosphatase, which is a marker of increased bone turnover. 

Complications: Rarely, complications like osteoarthritis, heart failure and bone sarcomas may arise.

Differential Diagnoses

Osteoporosis: This condition involves a reduction in bone density, leading to weakened bones and an increased risk of fractures. While it can cause bone pain and deformities, the characteristic bone changes in osteoporosis differ from those seen in Paget’s disease. 

Osteoarthritis: The condition affects the joints. Osteoarthritis causes cartilage to break down and may cause stiffness, joint pain & reduced range of motion. Although it affects joints, it doesn’t cause the same bone changes as Paget’s disease. 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Monitoring and Assessment: 

Regular monitoring through clinical examinations, blood tests (serum alkaline phosphatase), and imaging studies (MRI, X-rays) to assess disease activity, bone changes, and complications. 

Lifestyle Modifications: 

Encouraging a healthy lifestyle that includes adequate calcium and vitamin D intake to support bone health. 

Weight-bearing exercises and physical therapy may help maintain bone strength and function. 

Medications: 

Bisphosphonates: These are the primary medications used to manage Paget’s disease. They help to regulate bone remodelling and reduce excessive bone breakdown. Examples include alendronate, risedronate, and zoledronic acid. 

Calcitonin: It is another option that can help in reducing bone turnover and pain relief. 

Pain Management: Nonsteroidal anti-inflammatory drugs (NSAIDs) or analgesics may be used to treat Paget’s disease-related pain and discomfort. 

Surgical Intervention (if needed): 

Surgery might be considered in certain cases where complications arise, such as severe bone deformities, fractures, neurological complications due to nerve compression, or when medication fails to control symptoms. 

Complications Management: 

Addressing complications that may arise from Paget’s disease, such as osteoarthritis, fractures, hearing loss (if affecting the skull), or neurological symptoms due to compression of nerves. 

Patient Education and Support: 

Providing information and support to patients about their condition, treatment options, and lifestyle modifications to manage the disease effectively. 

Teaching patients the value of consistent treatment programmes and routine follow-ups. 

Consultation and Multidisciplinary Approach: 

In complex cases or when complications arise, involving specialists like physical therapists, neurologists & orthopedic surgeons ensure comprehensive care. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

lifestyle-modifications-in-treating-pagets-disease

Diet and Nutrition: Bone health requires a well-balanced diet high in calcium and vitamin D. Adequate intake of these nutrients helps in supporting bone mineral density and overall bone strength. A dietitian’s guidance may be helpful in planning a suitable diet. 

Lifestyle Modifications: Regular weight-bearing exercise, such as walking, can enhance general health and aid in maintaining bone strength. However, high-impact activities might increase the risk of fractures and should be avoided or modified based on individual circumstances. Physical therapy may also be beneficial in managing mobility and function. 

Assistive Devices: Depending on the extent and location of the affected bone, assistive devices like braces, canes, or orthopedic footwear may help support weakened bones, increase mobility, and lower the chance of fractures or falls. 

Pain Management: Pain associated with Paget’s disease can be managed through various strategies, including over-the-counter or prescription pain medications, physical therapy, heat/cold therapy, and, in some cases, nerve blocks or other interventional pain management techniques. 

Regular Monitoring: Regular visits with medical professionals are necessary to monitor the disease’s development, assess bone health, and adjust treatment plans as needed. Periodic imaging studies, such as X-rays or bone scans, may be performed to evaluate bone changes. 

Effectiveness of Bisphosphonate in treating Paget’s disease

alendronate (Fosamax) 

Alendronate, classified as a strong third-generation bisphosphonate, primarily functions by impeding osteoclastic resorption of bone. Its use is advised in managing Paget’s disease. In cases where patients’ serum alkaline phosphatase levels remain abnormal, retreatment could be contemplated after a six-month assessment following the initial treatment. 

pamidronate (Aredia) 

Pamidronate, classified as a strong third-generation bisphosphonate, primarily functions by impeding osteoclastic resorption of bone 

Studies have demonstrated the efficacy of pamidronate intravenous in treating Paget’s disease and in cases where patients have shown resistance to calcitonin therapy or etidronate. 

risedronate (Actonel, Atelvia) 

Risedronate, classified as strong aminobisphosphonate, primarily functions by impeding osteoclastic resorption of bone. 

Useful in treatment of paget’s disease. 

etidronate (Didronel) 

The first bisphosphonate to be investigated on people and authorised for use in treating Paget disease in the US was etidronate (1978). It is the least effective bisphosphonate medication on the market right now. 

Zoledronate (Reclast, Zometa) 

Bone resorption is inhibited with zoledronate. It causes apoptosis of osteoclasts and suppresses osteoclastic activity. 

Salmon calcitonin (Miacalcin,calcimar injection) 

Salmon calcitonin emerges as a viable treatment for Paget’s disease when bisphosphonates cannot be used. This substance is a peptide hormone that quickly stops bone resorption by attaching to osteoclasts’ calcitonin receptors. Bone cells are not cytotoxically affected by osteoclasts. 

role-of-surgery-in-treating-pagets-disease

Joint Replacement Surgery: Paget’s disease can cause arthritis in affected joints, leading to severe pain and limited mobility. It could be required to have joint replacement surgery, like knee replacement or hip to relieve discomfort and restore joint function. 

Bone Reshaping Surgery: Deformities caused by Paget’s disease like curved spine/bowed legs (scoliosis/ kyphosis) may require corrective surgery to improve function and reduce pain. Osteotomies, which involve cutting and reshaping bones, may be performed in certain cases. 

role-of-management-in-treating-paget-disease

Assessment and Diagnosis: Comprehensive imaging testing, physical examination, and medical history are the first steps in the process. (such as X-rays, MRIs or bone scans) to confirm the diagnosis of Paget’s disease. Blood tests measuring alkaline phosphatase levels are often used to assist in diagnosis. 

Education and Lifestyle Modifications: Educating the patient about Paget’s disease, its progression, and potential complications is crucial. Lifestyle modifications, such as weight-bearing exercises, a well-balanced diet rich in calcium, and avoiding high-impact activities that might exacerbate bone complications, are often recommended. 

Medication: Medications are commonly prescribed to manage symptoms and slow down the progression of Paget’s disease. These may include: 

Bisphosphonates: These drugs help regulate bone remodeling and reduce excessive bone turnover. Examples include alendronate, risedronate, or zoledronic acid. 

Calcitonin: It can be used to reduce bone pain and inhibit bone resorption. 

Pain Relievers: Nonsteroidal anti-inflammatory drugs (NSAIDs) or other pain medications may be prescribed to alleviate discomfort. 

Monitoring and Follow-up: Regular monitoring of the disease progression through clinical evaluations and imaging tests is essential. Follow-up appointments with healthcare providers help assess the response to treatment, manage potential side effects of medications, and adjust the treatment plan accordingly. 

Surgical Intervention (if needed): In some cases, surgical procedures may be considered to manage complications associated with Paget’s disease. This could involve joint replacement surgery for severely affected joints or surgery to stabilize weakened bones at risk of fractures. 

Management of Complications: Complications of Paget’s disease, such as fractures, nerve compression syndromes, and secondary osteoarthritis, may require specific management strategies tailored to each individual case. 

Ongoing Care and Support: Long-term management involves continued support, education, and monitoring to ensure optimal management of symptoms and prevention of complications. Patients may benefit from involvement in support groups or counselling to cope with the emotional and physical challenges of living with Paget’s disease.

Medication

Future Trends

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References

Paget Bone Disease – StatPearls – NCBI Bookshelf (nih.gov)