Paget's disease of bone: causes, symptoms, and treatment

Paget's disease of bone is one of those conditions that most patients have never heard of until they're diagnosed with it, often incidentally, when an X-ray or blood test done for something else shows unexpected findings. It's the second most common bone disorder after osteoporosis, yet it remains underdiagnosed, particularly in India where awareness is limited.

In my practice, I encounter Paget's disease occasionally, typically in patients over 50 who come in with persistent bone pain that doesn't quite fit the pattern of arthritis or osteoporosis. The condition can be mild enough to need no treatment, or serious enough to cause fractures, deformities, and neurological complications. Understanding it early makes all the difference.

What happens in Paget's disease?

Normal bone is constantly remodeling itself — old bone tissue is removed by cells called osteoclasts, and new bone is laid down by osteoblasts. This turnover is carefully balanced, producing bone that is strong, dense, and properly structured.

In Paget's disease, this balance goes haywire. Osteoclasts become overactive, breaking down bone too quickly. The osteoblasts try to keep up by producing new bone rapidly, but the bone they create is disorganized, structurally chaotic, with a mosaic pattern of woven and lamellar bone that lacks the ordered architecture of normal bone.

The result: bones that are larger than normal, but weaker. They bend more easily, fracture more readily, and can become deformed over time.

Which bones Are affected?

Paget's disease can affect any bone, but it has a predilection for certain areas:

• Pelvis, the most commonly affected bone (found in about 70% of cases)
• Femur (thigh bone) — can cause bowing of the leg
• Tibia (shin bone), visible anterior bowing ("saber shin")
• Skull, can cause headaches, hearing loss, and increased hat size
• Spine — particularly the lumbar vertebrae. Can lead to spinal stenosis and nerve compression
• Clavicle and humerus, less common

The disease can be monostotic (affecting one bone) or polyostotic (multiple bones). It almost never affects the entire skeleton.

Causes and risk factors

The exact cause of Paget's disease isn't fully understood. Two main theories exist:

Genetic factors: There's a strong familial component. About 15-30% of patients have a first-degree relative with the disease. Several gene mutations have been linked to it, including the SQSTM1/p62 gene. If a parent has Paget's, you have a significantly higher risk.

Viral theory: Some researchers believe a slow-acting viral infection (possibly paramyxovirus family) in osteoclasts may trigger the abnormal bone remodeling. This theory is debated but not disproven.

Demographics:

• More common in people of European descent
• Affects men slightly more than women
• Rare before age 40; prevalence increases with age
• Less common in Asian populations, though underdiagnosis may be a factor in India

Symptoms: what to watch For

Here's the tricky part, most people with Paget's disease have no symptoms at all. The condition is often discovered accidentally through:

• An elevated alkaline phosphatase (ALP) on a routine blood test
• An incidental X-ray finding showing characteristic bone changes

When symptoms do occur, they include:

Bone pain: Deep, aching pain in the affected bone. Unlike arthritic pain, it's often constant and may worsen at night. About 40% of symptomatic patients report bone pain.

Bone deformity: Visible bowing of the legs (tibial or femoral bowing). The skull may enlarge gradually — a patient noticing their hats don't fit anymore is a classic presentation.

Fractures: Pagetic bone fractures more easily than normal bone. These can be full fractures or stress fractures (incomplete cracks) that cause persistent pain.

Joint pain: When Paget's affects bone near a joint (especially the hip or knee), it can alter joint mechanics and accelerate arthritis in that joint.

Neurological symptoms: Pagetic bone in the skull can compress cranial nerves, causing hearing loss (affects up to 30-50% of patients with skull involvement). Spinal involvement can cause nerve compression leading to leg weakness, numbness, or sciatica.

Warmth over affected bone: Increased blood flow to pagetic bone can make the overlying skin feel warm to touch.

Diagnosis

Blood tests

Serum alkaline phosphatase (ALP): Elevated in active Paget's disease. This is the primary marker used for diagnosis and monitoring treatment response. A significantly elevated ALP in a patient over 50 with bone pain should raise suspicion.

Serum calcium and phosphorus: Usually normal, unless the patient is immobilized (which can cause hypercalcemia).

Bone turnover markers: N-telopeptide (NTx) and C-telopeptide (CTx) may be elevated, reflecting increased bone turnover.

Imaging

X-rays: The gold standard for confirming Paget's. Classic findings include:

• Cortical thickening and coarsened trabecular pattern
• Osteolytic (bone destruction) and osteosclerotic (excess bone formation) areas, sometimes in the same bone
• Bone enlargement and deformity
• The characteristic "cotton wool" appearance of the skull
• "Picture frame" vertebra in the spine

Bone scan (technetium-99m): Shows increased uptake in all pagetic bones, useful for determining the extent of disease and identifying all affected bones, as many won't cause symptoms.

CT/MRI: Ordered when spinal stenosis or nerve compression is suspected.

Bone biopsy

Rarely needed. Only considered when the diagnosis is uncertain or when there's concern about malignant transformation (see complications).

Complications

If left untreated, advanced Paget's disease can cause:

• Pathological fractures, particularly in the femur and tibia
• Severe arthritis — in joints adjacent to affected bones (especially the hip)
• Hearing loss, from skull bone changes compressing the auditory nerve
• Spinal stenosis, pagetic vertebrae encroach on the spinal canal
• Heart failure — in very extensive disease, the increased blood flow through pagetic bone can strain the heart (rare)
• Osteosarcoma, malignant transformation occurs in less than 1% of cases, but this is the most feared complication. Sudden increase in pain, rapid swelling, or a rising ALP in a previously stable patient warrants urgent investigation.

Treatment

Who needs treatment?

Not everyone with Paget's disease requires medication. Treatment is recommended for:

• Patients with bone pain due to active Paget's
• Disease in weight-bearing bones (risk of fracture or deformity)
• Skull involvement (risk of hearing loss)
• Before planned surgery on a pagetic bone (to reduce bleeding)
• Disease near major joints (to prevent arthritis progression)
• Elevated ALP more than twice the upper normal limit

Bisphosphonates, The mainstay

Bisphosphonates suppress the overactive osteoclasts, normalizing bone turnover. The most commonly used options:

• Zoledronic acid (IV): A single infusion often normalizes ALP for 2-5 years. This is my preferred choice for most patients — one dose, long-lasting effect, high remission rates (about 90%).
• Risedronate (oral): Taken daily for 2 months. Effective but less potent than zoledronic acid.
• Alendronate (oral): Another option, taken daily for 6 months.

Treatment response is monitored by tracking ALP levels, a significant drop (>75% from baseline) indicates good response.

Pain management

• NSAIDs for bone pain
• Physiotherapy for maintaining joint mobility and muscle strength
• Assistive devices (cane, walker) if leg deformity affects gait

Surgery

Surgery may be needed for:

• Fractures through pagetic bone (require careful fixation due to altered bone structure)
• Joint replacement when secondary arthritis develops
• Spinal decompression for nerve compression
• Osteotomy to correct severe bowing deformity

Living with Paget's disease

Most patients with Paget's disease live normal, active lives with proper management. The key is:

• Regular monitoring of ALP levels (every 6-12 months)
• Adequate calcium and vitamin D intake (important for bone health generally)
• Regular exercise, weight-bearing activity helps maintain bone strength
• Prompt attention to any new symptoms, especially sudden increases in pain

When to See a doctor

• Persistent, deep bone pain lasting more than 2-3 weeks
• Visible bowing or enlargement of a limb bone
• Hearing changes without obvious ear problems
• An incidentally found elevated ALP on blood work
• Leg pain with numbness or weakness (possible spinal involvement)
• Family history of Paget's disease combined with bone symptoms

Paget's disease is manageable and treatable, but it needs to be identified first. If you're over 50 and have unexplained bone pain or an elevated alkaline phosphatase level, ask your doctor about Paget's — it may be more common than you think.