Summary

Paget's Disease of Bone (Osteitis Deformans) is a chronic metabolic bone disorder characterized by excessive and disorganized bone turnover. [1] It begins with a phase of intense osteoclastic resorption (lytic phase), followed by aberrant and chaotic osteoblastic bone formation (sclerotic phase). This results in bone that is expanded, hypervascular, and structurally weak (woven bone), predisposing to deformity, fracture, and pain. It typically affects older adults (>55 years) and has a predilection for the pelvis, spine, skull, and femur. Management focuses on symptom control and normalizing bone turnover using potent bisphosphonates, specifically Zoledronic Acid. While often asymptomatic, the most feared complication is osteosarcomatous transformation (<1%), heralded by new, severe pain. [2,3]

Key Facts

• Pathology: Primary disorder of the osteoclast (giant, multinucleated, overactive) resulting in "mosaic" woven bone.
• Prevalence: Second most common metabolic bone disease after osteoporosis; ~2-3% of >55s in UK [1].
• Key Diagnostic: Isolated elevated Alkaline Phosphatase (ALP) with normal calcium and phosphate (usually).
• Classic Signs: Sabre tibia (anterior bowing), skull enlargement ("hat doesn't fit"), local warmth, dilated scalp veins.
• Treatment of Choice: IV Zoledronic Acid (5mg single dose) - provides remission for >5 years.
• Malignancy Risk: Osteosarcoma in <1% (but 30-fold increased risk compared to gen pop).
• Genetics: Strong familial link; SQSTM1 mutation in 40-50% of familial cases.
• Complications: Deafness, Spinal Stenosis, High Output Cardiac Failure, Osteoarthritis.

Clinical Pearls

Diagnostic Pearl: "The Isolated ALP" - An elderly patient with markedly elevated ALP but normal GGT/Liver enzymes and normal Calcium/Phosphate has Paget's disease until proven otherwise.

Clinical Sign: "My Hat Don't Fit" - Expansion of the calvarium (skull) is a classic sign. Patients may report increasing hat size.

Exam Finding: "Tibial Warmth" - The affected limb often feels hot to the touch compared to the unaffected side due to extreme hypervascularity of the Pagetic bone. This can act as a vascular shunt causing high-output cardiac failure.

Red Flag: "Change in Pain Character" - Pagetic bone pain is typically a dull, boring ache. If a patient reports a sudden change to severe, sharp pain or a new localized swelling, you MUST exclude osteosarcoma.

Pitfall Warning: Do not mistake the radiological appearance of active lytic Paget's (e.g., osteoporosis circumscripta) for metastatic disease. A bone scan showing expansile, intense uptake throughout the whole bone helps differentiate.

Why This Matters Clinically

Paget's disease is frequently encountered incidentally on blood tests (high ALP) or X-rays. Differentiating active, symptomatic disease requiring treatment from inactive disease is crucial to prevent complications like deafness (skull involvement), spinal stenosis, and secondary osteoarthritis. The advent of single-dose zoledronic acid has transformed management, effectively "curing" the metabolic activity for years. Missing the diagnosis can lead to preventable deformity and disability. Conversely, treating asymptomatic patients with low-risk disease is controversial (PRISM trial). [4]

Structured Approach

Look:

• Gait Analysis:
  • Antalgic: Shortened stance phase on painful side.
  • Waddling (Trendelenburg): If pelvic/hip involvement causes abductor weakness.
  • Short Leg: If tibial/femoral bowing causes effective leg length discrepancy.
  • Stiffness: Reduced hip flexion/extension due to secondary OA.
• Posture: Kyphosis, loss of lumbar lordosis.
• Deformity: Inspect for tibial bowing, skull enlargement ("hat sign").
• Inspect for surgical scars (previous fixation).

Feel:

• Temperature: Palpate over tibia/femur for increased warmth.
• Tenderness: Direct bone tenderness suggests active disease or microfractures.
• Deformity: Palpate irregularity of cortical bone.

Move:

• Assess adjacent joints (hip/knee) for secondary OA.
• Assess spine range of motion (often restricted).

Neurology:

• Cranial Nerves:
  • CN VIII (Vestibulocochlear): Most common. Test hearing (Whisper/Rinne/Weber). Otosclerosis causes conductive loss; nerve compression causes sensorineural loss.
  • CN II/V/VII: Assess vision, facial sensation, facial power (rarely affected by skull base foraminal narrowing).
• Spinal Cord:
  • Long Tract Signs: Check for hyper-reflexia, clonus, or Babinski sign (suggesting cervical/thoracic myelopathy from vertebral expansion).
  • Peripheral Nerve: Assess for LMN signs (wasting/weakness) at the level of spinal stenosis (e.g., L4/5).

Natural History

Paget's is progressive if untreated, but progression is slow. Activity tends to persist in affected sites but rarely spreads to new bones. Clinical severity varies widely; many patients remain asymptomatic for life. With modern bisphosphonate therapy, metabolic activity can be suppressed for prolonged periods, effectively altering the natural history.

Long-term Prognostic Factors

Outcomes with Treatment

Key Guidelines

1. Paget's Association / Bone Research Society Guidelines (2019): Recommend Zoledronic Acid as first-line therapy for symptomatic disease. Link
2. Endocrine Society Clinical Practice Guideline (2014): Diagnose with plain films; monitor with ALP; Treat risk of complications not just symptoms. PMID: 25406298

Landmark Trials

PRISM Trial (2010) — Paget's Disease: Randomized Trial of Intensive versus Symptomatic Management

• Comparison: Intensive bisphosphonate (aiming for normal ALP) vs Symptomatic treatment.
• Outcome: No difference in fracture risk, hearing loss, or need for surgery. Quality of life similar.
• Clinical Impact: Suggests we should treat symptoms, not just the ALP number. Treating asymptomatic patients is controversial. PMID: 20035311

Reid et al. (NEJM 2005) — Zoledronic Acid vs Risedronate

• Comparison: Single 5mg IV Zoledronic acid vs 30mg Risedronate daily x 60d.
• Outcome: 96% response rate for Zol vs 74% Risedronate. Remission maintained far longer in Zol group.
• Clinical Impact: Established Zoledronic acid as the Gold Standard treatment. PMID: 16135834

Zoledronate in Prevention of Paget’s (ZiPP) Study (Ongoing)

• Investigating if treating genetically susceptible individuals (SQSTM1) prevents disease development.

Controversies in Management

Treating Asymptomatic Disease

• Pro: Prevention of complications (deformity, deafness, sarcoma) is theoretically possible if turnover is suppressed early.
• Con: The PRISM trial showed no benefit in clinical endpoints. Zoledronate has risks (ONJ, AFF).
• Consensus: Most specialists treat if the disease is in a "critical site" (weight-bearing bone, skull base, spine) even if asymptomatic, especially in younger patients with active disease (high ALP). In older patients with non-critical disease (e.g., pelvic), observation is preferred.

Targeting ALP vs Symptoms

• Traditional goal was normalization of ALP. PRISM suggested symptom control is adequate. However, many clinicians still strive for biochemical remission as a marker of biological control.

Bisphosphonate Safety Profile

Given the long duration of action, safety is paramount:

• Atypical Femoral Fractures (AFF): Rare subtrochanteric fractures associated with long-term bisphosphonate use. Risk is very low with single-dose Zoledronate compared to continuous oral dosing.
• Osteonecrosis of the Jaw (ONJ): Exposed bone in the jaw that fails to heal. Incidence is 1/10,000 to 1/100,000 in osteoporosis, slightly higher in Paget's due to higher doses. Risk factors include invasive dental surgery.
• Hypocalcaemia: Zoledronate causes a transient drop in calcium. Mandatory Vitamin D replacement (e.g., 50,000 IU loading dose) is required before infusion.

What is Paget's Disease?

Bone is a living tissue that constantly renews itself—old bone is removed and new bone is built. In Paget's disease, this process goes out of control. The "demolition" cells work too fast, and the "building" cells rush to keep up. The result is new bone that is grown too quickly—it is larger and deformed, but actually weaker and more brittle than normal bone.

Is it cancer?

No. Paget's disease is a benign (non-cancerous) metabolic condition. There is a very small risk (less than 1%) that it can develop into bone cancer, but for the vast majority, this never happens.

Why does my leg feel warm?

Because the bone is rebuilding so furiously, it needs a lot of blood supply. The extra blood vessels make the skin over the bone feel warm to the touch.

How is it treated?

We have very effective treatments called bisphosphonates. The most common is a drip called Zoledronic Acid. It acts like a "brake" on the overactive bone cells. A single 15-minute infusion can control the disease for 5 years or more. It often stops the pain effectively.

Can I pass it on?

There is a genetic link. If you have a close relative (parent or sibling) with Paget's, your risk is higher (about 7 times the general population). However, many people who carry the gene modifications never actually develop the disease.

Can I exercise?

Yes. Exercise is vital for maintaining joint mobility and muscle strength, which supports the bones. However, if you have significant bowing of your leg bones, high-impact activities (like running on hard surfaces) should be avoided to reduce the risk of stress fractures. Swimming and cycling are excellent alternatives.

Will I go deaf?

Hearing loss is a common complication if the skull is involved, but it is not inevitable. It happens because the growing bone narrows the channel for the hearing nerve or stiffens the tiny ear bones. If you notice changes in your hearing, tell your doctor—treating the Paget's disease can often stop the hearing loss from getting worse.

Does diet help?

A sensible diet rich in Calcium (dairy, leafy greens) and Vitamin D (oily fish, fortified cereals) is important for all bone health. We will check your Vitamin D levels before starting treatment, as the medication works best when your levels are normal.

What if I need dental work?

If you are taking bisphosphonates (the bone medication), you must tell your dentist. There is a very small risk of a condition called "osteonecrosis of the jaw" after invasive dental surgery (like extractions), so it is best to get any major dental work done before starting the infusion if possible.

Do I need special shoes?

If your legs have become bowed, one leg might effectively become shorter than the other. This can cause back pain. A simple shoe lift (orthotic) inserted into your shoe can correct this leg length discrepancy and improve your walking comfort.

Common Exam Questions

OSCE Station: History Taking

Candidate Instructions: "A 68-year-old man presents with aching leg pain. Take a focused history."

Key Questions to Ask:

1. Pain Analysis:
   • "Is the pain deep and boring?" (Bone pain)
   • "Is it worse at night?" (Pagetic pain is often nocturnal)
   • "Does resting help?" (If yes -> OA. If no -> Paget's)
2. Deformity:
   • "Have you noticed your leg changing shape?" (Bowing)
   • "Has your hat size changed?" (Skull expansion)
3. Complications:
   • "Have you noticed any hearing loss?" (CN VIII)
   • "Any numbness or weakness in limbs?" (Spinal stenosis)
4. Family History:
   • "Does anyone in your family have bone probems?" (Strong genetic link)
5. Systems Review:
   • "Any kidney stones?"
   • "Any heart trouble?"

Questions that frequently appear in examinations:

1. Medical Finals (Data Interpretation): "A 70-year-old man has an isolated raised Alkaline Phosphatase (ALP = 900) on routine bloods. Calcium, Phosphate, and LFTs are normal. What is the most likely diagnosis?"

2. MRCS/Surgical Finals: "Describe the radiological features of Paget's disease of bone." (Expected answer: Osteoporosis circumscripta, cortical thickening, coarsened trabeculae, bone expansion, bowing).

3. PLAB: "A patient with known Paget's disease presents with new, severe, worsening pain and swelling in his femur. What is the most important complication to exclude?" (Answer: Osteosarcoma).

4. Pharmacology: "What is the mechanism of action of Zoledronic acid in Paget's disease?" (Answer: Inhibits osteoclast-mediated bone resorption by inhibiting farnesyl pyrophosphate_synthase).

5. Ent/Neurology: "A 65-year-old man presents with progressive hearing loss and increasing hat size. Diagnosis?"

Viva Points

Opening Statement (How to start your viva answer):

"Paget's disease of bone is a chronic disorder of bone remodelling characterised by focal areas of excessive osteoclastic resorption followed by disordered, excessive osteoblastic formation. This results in bone that is expanded, vascular, and structurally weak. It is common in the elderly (>55), particularly in the UK. The diagnosis is often suggested by an isolated elevated ALP and confirmed by characteristic X-ray changes. Management involves bisphosphonates (Zoledronic acid) for symptomatic disease."

Key Facts to Mention:

• Disorder of the OSTEOCLAST (giant, multinucleated)
• "Mosaic pattern" of woven bone
• Isolated High ALP
• Zoledronic acid 5mg IV is Gold Standard treatment (Reid 2005)
• Osteosarcoma is the rare (<1%) but feared complication

Evidence to Cite:

• "Reid et al. (NEJM 2005) demonstrated that a single dose of Zoledronic acid is superior to Risedronate, with response rates of 96% vs 74%, and remission lasting years."
• "The PRISM Study (2010) suggests that intensive treatment of asymptomatic patients to normalize ALP does not improve clinical outcomes (fractures/hearing/pain) compared to symptomatic treatment."

Structured Answer Framework:

1. Definition: Uncoupled remodelling, weak woven bone
2. Clinical Features: Pain, deformity (sabre shin), deafness, high output failure
3. Investigations: Isolated High ALP, X-ray findings (lytic/mixed/sclerotic)
4. Management: Zoledronic acid (efficacy)
5. Complications: #, OA, Nerve compression, Sarcoma

Common Mistakes

What fails candidates:

• ❌ Confusing Paget's with Metastases (both can be lytic/sclerotic, but Paget's expands the bone, Mets usually destroy/replace)
• ❌ Thinking Calcium is high (It is usually NORMAL in Paget's)
• ❌ Suggesting surgery as first line (Biophsophonates are first line)
• ❌ Forgetting Osteosarcoma as a red flag

Examiner Follow-Up Questions

Expect these follow-up questions:

1. "Why can Paget's cause heart failure?"

   • Answer: The highly vascular Pagetic bone has multiple arterio-venous shunts, significantly decreasing peripheral vascular resistance and demanding a high cardiac output. This only occurs when >15-20% of the skeleton is affected.

2. "Which cranial nerve is most commonly affected and why?"

   • Answer: The vestibulocochlear nerve (CN VIII). It is compressed within the auditory canal by the expanding petrous temporal bone, or due to otosclerosis/ossicle fusion.

3. "How would you monitor a patient after treatment?"

   • Answer: Monitor symptoms and serum ALP annually. A rise in ALP suggests relapse. Retreatment is only indicated for symptomatic relapse with biochemical progression.

Last Reviewed: 2025-12-26 | MedVellum Editorial Team

Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists and current guidelines.