Osteoporosis

Definition

• Disorder of bone mineral density (quantity) and bone quality leading to decreased bone strength and increased fracture risk
• T-score < -2.5 and elevated FRAX/CAROC risk

Fragility Fracture

• A fracture occurring spontaneously or following minor trauma such as a fall from standing height or less, excluding craniofacial, hand, ankle, and foot fractures

Pathophysiology

• Resorption by osteoclasts
• Affects trabecular bone first
• Osteoblasts release RANK-ligand, which signals osteoclasts RANK receptor

Differential Diagnosis

• Normal age-related bone loss
• Metabolic
  • Vitamin D deficiency
  • Primary hyperparathyroidism
  • Hypercortisolism
  • Hyperthyroidism
  • Growth hormone deficiency
  • Diabetes mellitus
• Gastrointestinal
  • Malabsorption: celiac disease, postoperative
  • Inflammatory bowel disease
  • Cirrhosis
• Hematologic
  • Multiple myeloma
  • Chronic hemolytic anemia
  • Systemic mastocytosis
• Rheumatologic
  • Rheumatoid arthritis
  • Osteogenesis imperfecta
  • Ehlers-Danlos syndrome
  • Marfan syndrome
  • Homocystinuria
• Drug-induced
  • Alcohol
  • Heparin
  • Glucocorticoids
  • Thyroxine suppressive therapy
  • Anticonvulsant drugs
  • Antidepressants (SSRIs and TCAs)
  • Gonadotropic-releasing hormone analogs
  • Cyclosporine
  • Chemotherapy
  • HIV meds: tenofovir disoprostol fumarate
• Renal
  • Hypercalciuria
  • Renal disease
• Miscellaneous
  • Eating disorders
  • Immobilization
  • Hepatic disease
  • Smoking

Screening

• Older adults ≥50 years
• Anyone ≥65 years
• Menopausal women or Men 50-64 with risk factors
  • Fragility fracture after age 40 years
  • Prolonged glucocorticoids (≥7.5mg/d for 3+ months)
  • Use of high-risk medications, such as aromatase inhibitors or androgen-deprivation therapy
  • Parental hip fracture
  • Vertebral fracture or osteopenia identified on radiography
  • Current smoking
  • High alcohol intake
  • Low body weight < 60kg or major weight loss >10% of body weight at age 25 yrears
  • Rheumatoid arthritis
  • Other disorders strongly associated with osteoporosis
• Age < 50 years
  • Fragility fracture
  • Prolonged use of glucocorticoids (≥7.5mg/d for 3+ months)
  • Use of high-risk medications, such as aromatase inhibitors or androgen-deprivation therapy
  • Hypogonadism or premature menopause
  • Malabsorption syndrome
  • Primary hyperparathyroidism
  • Other disorders strongly associated with rapid bone loss or fracture with high FRAX (preferred over CAROC)

Risk Factors

• Race: Latino > white > black
• Increasing age (70% over 80 years)
• Early menopause or oopherectomy
• Prednisone use >7.5mg daily for 3+ weeks

Clinical Assessment

• Inquire about falls in the last 12 months
• Prior fragility fractures
• Parental hip fracture
• Steroid use
• Current smoking
• High alcohol intake ≥3 units daily

Clinical Manifestations

• Fragility fracture
• Risk factors, including poor dietary intake, early menopause, steroid use
• Screening for spinal compression fractures with 2s and 6s
  • Height loss >2cm measured or 6cm historical
  • Pelvis-rib space <2 fingers
  • Occiput-to-wall >6cm

JAMA RCE

• Weight <51kg (LR+ 7.3)
• Occiput-to-wall distance (LR+ 4.6, LR- 0.5)
• Rib-to-pelvis distance < 2 fingers (LR+ 3.8, LR- 0.6)
• Tooth count less than 20
• Height loss
• Humped back (self-reported) (LR+ 3)

Falls Risk

• Gait
• Balance
• Timed get-up-and-go ≥12 sec (3m/10ft)
• Medications including antihypertensives
• Home environment, including clutter and footwear

Investigations

• Screen with bone-mineral density > 65yrs
  • DEXA T-score -1 to -2.5 is osteopenia
  • DEXA T-score less than -2.5 is osteoporosi
  • CAROC or FRAX tool for risk stratification
• Bloodwork
  • Calcium, albumin
  • CBC
  • Creatinine
  • ALP (r/o Paget's)
  • TSH
  • SPEP if vertebral fractures (r/o myeloma)
  • 25-OH-vitamin D, repeated 3-4 months after adequate replacement if low

Management

Indications for treatment

• Any fragility fracture
• Calculate FRAX score
• Moderate-risk patients
  • Vertebral fracture or wrist fracture
  • Rapid bone loss or low lumbar T_score
  • Falls ≥2/yr
  • Concurrent high-risk medications, including glucocorticoids, hypogonadism, primary hyperparathyroidism, rheumatoid arthritis, or aromatase inhibitor therapy

Non-pharmacologic

• Environment modification
• Weight-bearing exercise
• Tai Chi
• Increased dietary vitamin D and calcium
  • Calculator available on Osteoporosis Canada website
• Local falls-prevention programs may be available

Pharmacologic

• Vit D supplementation
  • 400-1000 IU for <50 years
  • 800-2000 IU for ≥50 years
  • every additional 1000 IU raises Vit D levels by 15 over 3 months
• Calcium 1200mg po daily if dietary intake inadequate

Bisphosphonates

• Kills osteoclasts
• Prevents vertebral, hip, and non-vertebral fractures
• Plan for 5 years then reassess
  • Continue if still high risk
• Give sitting up, no food 30min before or 1-2h after, stay upright for 1-2h after
• Alendronate
• Risderonate
• Side effects
  • Pill esophagitis
  • Osteonecrosis of the jaw (rare)
  • Atypical femoral fractures
    • Subtrochanteric fracture
    • More in Asians and diabetes

Denosumab

• RANK-L inhibitor
• Prevents vertebral, hip, and non-vertebral fractures

Teriparatide (PTH analogue)

• Prevents vertebral and non-vertebral fractures, but not hip fractures

SERMs

• Decreases release of RANK-L from osteoblasts
• Protect against vertebral fractures, but not hip or non-vertebral fractures

Estrogen

• Decreases release of RANK-L from osteoblasts
• Prevents vertebral, hip, and non-vertebral fractures

Prognosis

• Hip fracture in women: 23% die within 1 year

Further Reading

• Papaioannou et al. 2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. CMAJ 2010;182(17):1864-1873.
• Osteoporosis Canada Quick Reference Guide 2010