Endocrine · Year 2 · from Endocrine

Case 2: Bone Remodeling - Paget Disease of Bone

Patient Demographics

  • Age: 72 years
  • Sex: Male
  • Occupation: Retired engineer

Chief Complaint

"My leg has been aching and my left leg seems to be bowing."

History of Present Illness

A 72-year-old man presents with progressive left leg pain over 2 years, described as a deep aching sensation that worsens with weight-bearing. He has noticed that his left leg appears to be "bowing" outward. He reports his hat size has increased, and his wedding ring no longer fits. He has some hearing loss in his left ear. He denies any recent fractures or trauma. His family history is notable for his mother having a "bone condition" that required treatment. He is otherwise healthy with well-controlled hypertension.

Physical Examination

  • Vital Signs: BP 136/82 mmHg, HR 70 bpm
  • General: Well-appearing elderly man
  • Head: Frontal bossing, increased skull circumference
  • HEENT: Decreased hearing left ear (conductive)
  • Cardiovascular: Hyperkinetic precordium, soft systolic murmur
  • Extremities:
  • Left tibia: Palpable warmth over anterior surface, bowing deformity
  • Leg length discrepancy (left > right)
  • Skin: Increased warmth over left shin

Workup

  • Laboratory Studies:
  • Calcium: 9.4 mg/dL (normal)
  • Phosphorus: 3.5 mg/dL (normal)
  • PTH: 42 pg/mL (normal)
  • 25-hydroxyvitamin D: 28 ng/mL (borderline low)
  • Alkaline phosphatase (total): 485 U/L (markedly elevated)
  • Bone-specific alkaline phosphatase: Elevated
  • Creatinine: 1.1 mg/dL (normal)
  • C-telopeptide (CTX): Elevated (marker of bone resorption)
  • Imaging:
  • X-ray left tibia: Cortical thickening, mixed lytic and scite lesions, bowing deformity, anterior cortex involvement (classic "saber shin")
  • X-ray skull: Cotton wool appearance, thickened calvarium
  • Bone scan: Markedly increased uptake in left tibia, skull, and pelvis
  • Audiogram: Conductive hearing loss left ear

Diagnosis

Paget disease of bone (polyostotic)

Pathophysiology

  1. Paget disease involves accelerated, disordered bone remodeling
  2. Begins with osteoclast overactivation (lytic phase) - osteoclasts are abnormally large and multinucleated
  3. Followed by compensatory osteoblast activity (mixed/sclerotic phase)
  4. Results in disorganized woven bone that is mechanically weak despite being thickened
  5. Increased bone vascularity causes warmth and can lead to high-output cardiac state in extensive disease
  6. Alkaline phosphatase reflects osteoblast activity and disease extent
  7. Calcium and phosphorus remain normal because resorption and formation are coupled

Treatment

INDICATIONS FOR TREATMENT:

  • Bone pain
  • Involvement of weight-bearing bones (fracture risk)
  • Skull involvement (hearing loss, neurologic complications)
  • Planned orthopedic surgery on affected bone
  • Elevated alkaline phosphatase (>2x normal)
  • Hypercalcemia (rare, with immobilization)

PHARMACOLOGIC:

  1. Bisphosphonates (first-line):
  • Zoledronic acid 5 mg IV single dose (preferred - most potent, long remission)
  • Alternative: Alendronate 40 mg daily x 6 months
  1. Calcium and vitamin D supplementation: 1000 mg calcium, vitamin D 800-1000 IU daily (prevent hypocalcemia with bisphosphonate)
  2. Calcitonin: Rarely used (less effective, reserved for bisphosphonate intolerance)

MONITORING:

  1. Alkaline phosphatase at 3-6 months (should decrease by >75%)
  2. Clinical symptom assessment
  3. Repeat imaging if new symptoms
  4. Consider retreatment if ALP rises and symptoms recur

COMPLICATIONS TO MONITOR:

  1. Pathologic fracture
  2. Hearing loss (cochlear involvement or ossicular Paget)
  3. Spinal stenosis (vertebral involvement)
  4. High-output heart failure (extensive disease)
  5. Osteosarcoma (<1%, suspect if sudden worsening pain)

Clinical Pearl

Paget disease of bone is characterized by focal areas of accelerated and disordered bone remodeling, typically affecting patients over 50 years old. The hallmark laboratory finding is markedly elevated alkaline phosphatase with normal calcium and phosphorus, distinguishing it from primary hyperparathyroidism (elevated calcium) and osteomalacia (low calcium/phosphorus, elevated PTH). The disease proceeds through three phases: lytic (osteoclast predominant), mixed (both cells active), and sclerotic (osteoblast predominant). Clinical features depend on location: skull involvement causes headache, hearing loss, and increased hat size; spine involvement causes pain and spinal stenosis; long bone involvement causes pain, deformity, and fracture risk. Bisphosphonates are highly effective at suppressing disease activity, with zoledronic acid providing the longest remission. Rare transformation to osteosarcoma should be suspected if there is sudden severe pain or rapid radiographic change.

Clinical Image

Diagram demonstrating normal calcium and bone metabolism pathways, with PTH, vitamin D, and their coordinated effects on maintaining calcium homeostasis through actions on bone, kidney, and intestine.

Image Source: Wikimedia Commons - "Calcium regulation and parathyroid hormone" License: CC BY-SA 4.0 URL: https://commons.wikimedia.org/wiki/File:Calcium_regulation_and_the_parathyroid_hormone.svg

All cases for this lecture as Markdown