Metabolic Bone Disease

Question 1

Metabolic Bone Disease

Types

Answer 1

All 3 can lead to bone fragility and fractures.

• Osteoporosis
• Osteomalacia
  
  • Most commonly due to Vitamin D deficiency
• Hyperparathyroidism
  
  • Primary or secondary

Question 2

Osteoporosis

Epidemiology

Answer 2

• Most common metabolic bone disease
  
  • 200 million worldwide
  • 28 million in the U.S.
• Classically associated with post-menopausal women
• Increasing risks found for aging men
  
  • Likely d/t testosterone deficiency

Question 3

Osteoporosis

Overview

Answer 3

• Defined as “porous bone”
• Low bone mass and structural deterioration of bone tissue ⇒ bone fragility and ↑ susceptibility to fractures
• Hip, spine, and wrist are most commonly affected areas
• Usually asymptomatic
• Can produce loss of height, pain, and potential for serious complications

Question 4

Osteoporosis

Pathophysiology

Answer 4

• Due to imbalance between bone resorption and formation
  
  • Osteoclasts ⇒ bone resorption
  • Osteoblasts ⇒ bone formation
• Metabolic ∆ ⇒ ↑ osteoclast number/activity ⇒ uncouples bone turnover
  
  • Estrogen deficiency
  • Immobilization
  • Systemic or local inflammatory diseases

Question 5

Osteoporosis

Indications for Screening

Answer 5

• Previous fracture after age 30
• Family history of hip fracture
• Cigarette smoking
• Weight < 127 lbs
• Low peak bone mineral density
• Low calcium intake
• Eating disorders, physical inactivity, alcohol use
• Low testosterone levels (men), early-onset menopause
• Lack of sunlight exposure

Question 6

Osteoporosis

Associated Medications

Answer 6

• Corticosteroids (most important)
• Anticonvulsants
  
  • Dilantin
  • Phenobarbital
• Heparin
• Cyclophosphamide
• Lupron (GnRH agonist)
• Lithium
• HAART meds for HIV treatment
• Aromatase inhibitors

Question 7

Osteoporosis

Associated Diseases

Answer 7

• Grave’s disease
• Cushing’s syndrome
• Multiple myeloma
• Leukemia
• Primary biliary cholangitis (primary biliary cirrhosis)
• Celiac disease
• Chronic kidney disease
• Rheumatic diseases
  
  • Ankylosing spondylitis
  • Rheumatoid arthritis
  • Systemic lupus erythematosus

Question 8

Bone Mass

Evaluation

Answer 8

• Done using dual-energy x-ray absorptiometry (DEXA)
• Calculates bone mineral density (BMD) (gm/cm²) using attenuation of soft tissue and bone on radiographs
• Compare pt’s BMD to that of young, healthy controls (“T- score”) and with age-matched controls (“Z-score”)
  
  • Normal BMD if T-score > -1
  • Osteopenia (low BMD) if T-score between -1 and -2.5
  • “Osteoporosis” if T-score < -2.5

Question 9

Osteoporosis

Treatment

Answer 9

Treatment goal to prevent fractures:

• Bisphosphonates (most commonly used)
• Teriparatide (recombinant PTH)
• Monoclonal Antibodies

Question 10

Bisphosphonates

Answer 10

• Most commonly used
• Bind to osteoclasts ⇒ ⊗ bone resorption
• Meds:
  
  • PO: alendronate, risedronate, ibandronate
  • IV: ibandronate, zolendronic acid
• Adverse effects:
  
  • GI symptoms
    
    • Esophagitis
  • Myalgias and arthralgias
  • Osteonecrosis of the jaw (rare)

Question 11

Teriparatide

Answer 11

• Recombinant PTH
• ⊕ bone formation (anabolic agent)
• Daily injection
• Duration of therapy: 18-24 months
  
  • Theoretical risk of osteosarcoma beyond 24 months

Question 12

Monoclonal Antibodies

Answer 12

• Denosumab
  
  • mAb against RANKL
    
    • RANKL stimulates pre-osteoclasts to actively resorb bone
  • ⊖ Osteoclast activity ⇒ ⊗ Bone resorption
• Romosozumab
  
  • Recently approved for severe osteoporosis
  • ⊗ Sclerostin (regulatory factor in bone metabolism)
    
    • ↑ Bone formation
    • ↓ Bone resorption

Question 13

Osteomalacia

Overview

Answer 13

• Impaired mineralization of the bone matrix
• D/t ↓ availability of calcium or phosphate for incorporation into hydroxyapatite of bone
• Most common cause in adults is lack of Vitamin D
• In children: “Rickets” refers to the defective mineralization of bone and cartilaginous growth plate
• Characteristic location of spontaneous fractures include pelvis, hip, and ribs
• Pt’s usu. present w/ diffuse pain from microfractures

Question 14

Osteomalacia

Histology

Answer 14

• Widened osteoid seams
• No tetracycline deposits
• Implies defective mineralization of bone

Question 15

Osteomalacia

Diagnosis

Answer 15

Bone biopsy

• Definitive way to distinguish osteomalacia from osteoporosis
• Do after labelling with tetracycline (2 wks)
• From iliac crest
• Need local anesthesia only

Question 16

Vit D

Sources

Answer 16

• Sunlight
• Milk and other dairy products
• Eggs, salmon
• Dietary supplements
• Multi-vitamins

Question 17

Vit D Status

Assessment

Answer 17

• ☑︎ Serum 25-hydroxyvitamin D level
  
  • Relatively accurate reflection of Vit D stores
  • ↓ 25-hydroxyvitamin D ⇒ ↑ PTH
• Vit D repletion ⇒ ↓ PTH
  
  • Useful for monitoring

Question 18

Vit D

Daily Requirements

Answer 18

• People with poor sunlight exposure: at least 400-1,000 IU/day
• Adults older than 70 years: 800-1,000 IU/day
• Patients with malabsorption: 50,000 IU/wk

Question 19

Hyperparathyroidism

Answer 19

• Most common types:
  
  • Primary
    
    • Will see hypercalcemia
  • Secondary d/t renal disease
• Bone biopsy shows osteitis fibrosa cystica
• Characterized by severe bone fragility and bone pain