Osteoporosis

From IDWiki

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