Osteoporosis

Definition
A skeletal disease characterized by low bone mass, disruption of skeletal microarchitecture, and increased skeletal fragility resulting in fractures occurring with a fall from standing height or less or with no trauma


Epidemiology
Elderly >60 years
F:M=4:1
9 million osteoporotic fractures worldwide in 2000

Risk Factors

Nonmodifiable	Advanced age (>65) Female gender Caucasian or Asian ethnicity Family history of osteoporosis History of atraumatic fracture
Modifiable	Low body weight (<58 kg or BMI <20) Calcium or vitamin D deficiency Inadequate physical activity Cigarette smoking Excessive alcohol intake (>2 drinks/d) Medications: chronic corticosteroids, excessive thyroid hormone replacement, medroxyprogesterone acetate, heparin

Pathophysiology
Bone undergoes continuous resorption and formation
10% of adult skeleton is remodelled each year
Bone loss results from an imbalance between resorption and formation
Human skeleton comprises approximately

• 80% cortical bone
• 20% trabecular bone

Osteoporotic fractures occur at sites with more than 50% trabecular bone

• Vertebral body
• Proximal femur
• Distal forearm

Bone loss leads to thinning of the trabecular plates
This causes a disproportionate loss of bone strength
Peak bone mass is achieved by the age of 30 years
After skeletal maturity bone is lost at about 1% per year

Aetiology
Aging
Hypoestrogenemia

Commonly Associated Conditions

• Malabsorption sydromes: gastrectomy, IBD, celiac disease
• Hypoestrogenism: menopause, hypogonadism, eating disorders, elite athletes
• Chronic liver disease, hemochromatosis
• Endocrinopathies: hyperparathyroidism, hyperthyroidism
• Multiple myeloma, multiple sclerosis, osteomalacia, rheumatoid arthritis
• Medications (see “Medications” under “Risk Factors”)

Presentation
History

• Review risk factors
• Often no clinic findings until fracture occurs

Physical Exam

• Thoracic kyphosis
• Height loss >1.5 cm

Investigation

Initial lab	To elicit common causes of secondary osteoporosis: 25-hydroxyvitamin D CBC Serum calcium, total protein, creatinine, alkaline phosphatase
DEXA	DEXA of the lumbar spine/hip is the gold standard for measuring BMD BMD is expressed in terms of T scores and Z scores. T score T score is the number of standard deviations (SDs) a patient's BMD deviates from the mean for young normal (age 25–40) controls of same sex. WHO defines normal BMD as a T score ≥ –1, osteopenia as a T score between –1 and –2.5, and osteoporosis as a T score ≤ –2.5. WHO thresholds can be used for postmenopausal women and men >50 years of age. Z score Z score is a comparison of the patient's BMD with an age-matched population. Z score <–2.0 should prompt evaluation for causes of secondary osteoporosis. US densitometry is used to measure BMD at the calcaneus (heel). Lower cost and no radiation exposure but not as accurate as DEXA. Plain radiographs lack sensitivity to diagnose osteoporosis, but abnormality (e.g., widened intervertebral spaces, rib fractures, vertebral compression fractures, etc.) should prompt evaluation of BMD.
Bone biopsy	Rarely is needed to rule out neoplasms and other metabolic bone diseases. Pathological Findings Reduced skeletal mass, trabecular bone thinned or lost more so than cortical bone Osteoclast and osteoblast number variable No evidence of other metabolic bone diseases and no increase in unmineralized osteoid Marrow normal or atrophic

Differential Diagnosis

• Multiple myeloma or other neoplasms
• Osteomalacia
• Type I collagen mutations
• Osteogenesis imperfecta

Management
Treat patients with a

• T score ≤ –2.5 with no risk factors
• T score ≤ –2.0 and 1 or more risk factors
• prior history of osteoporotic fracture at the spine or hip.

  Calcium	1,500 mg and vitamin D 700–800 IU daily Options: Bisphosphonates Alendronate 10 mg PO daily or 70 mg PO weekly Risedronate 5 mg PO daily, 35 mg PO weekly, 75 mg PO twice monthly, or 150 mg PO monthly Zoledronic acid 5 mg IV yearly These drugs become incorporated into skeletal tissue, where they inhibit the resorption of bone by osteoclasts. Raloxifene 60 mg PO daily Selective estrogen receptor modulator with positive effects on BMD and fracture risk but no stimulatory action on breasts or uterus Decreases vertebral but not hip fractures. Increases risk of thromboembolism. Teriparatide 20 mg SC daily Recombinant formulation of PTH. When given daily, it promotes new bone formation. Studies have shown a reduction in the incidence of vertebral fractures by 65%. No data exist on its safety and efficacy after >2 years of use. Primarily indicated for those with worsening osteoporosis despite bisphosphonate therapy. Estrogen 0.625 mg PO daily with progesterone if women has a uterus): Effective in prevention and treatment of osteoporosis (35% reduction in hip and vertebral fractures after 5 years of use), but the risks (e.g., increased rates of myocardial infarction, stroke, breast cancer, pulmonary embolus, and deep vein thrombosis) must be weighed against the benefits. Strontium 2 g PO daily: Appears to inhibit bone resorption and increase bone formation Available for use in Europe Calcitonin Acts by reducing the number of osteoclasts, therefore decreasing bone turnover. Has been shown to increase BMD, but no studies have shown conclusively a reduction in the occurrence of fractures. May decrease acute vertebral compression-fracture pain (analgesic).
  Lifestyle modification	Exercise: Any weight-bearing exercise 30 min 3×/wk (1)[B] Smoking cessation Decrease fall risk Evaluate and treat all patients presenting with fracture resulting from minimal trauma.
  General Prevention	The aim in the prevention and treatment of osteoporosis is to prevent fracture. Exercise (weight-bearing, aerobic, and strength training) increases BMD, although unclear if it prevents fractures. Calcium (1200 mg) and vitamin D (700–800 IU) daily Avoid smoking Limit alcohol use (<2 drinks/d) Screen all women ≥65 years and women ≥60 who are at high risk for fracture (2)[B]. Consider screening elderly men at high risk for fracture. Correct treatable medical conditions and other risk factors.
  Surgery	Options for patients with painful vertebral compression fractures failing medical treatment: Vertebroplasty: Orthopedic cement is injected into compressed vertebral body. Kyphoplasty: A balloon is expanded within compressed vertebral body to reconstruct volume of vertebrae. Cement is injected into the space.
  Follow-up	Weight-bearing exercises such as walking, jogging, stair climbing, and tai-chi. These activities have been shown to decrease falls. All successful studies on the treatment of osteoporosis involve weight-bearing exercise. BMD should be tested no earlier than 2 years after starting bisphosphonate. Uncertain if repeat DEXA scanning is of value. Radiographs for acute pain, suspected fractures

  
  
  Complications
  • Severe, disabling pain
  • Dorsal/lumbar neurologic deficits secondary to vertebral fracture (rare)
  
  
  Prognosis
  • With treatment, 80% of patients stabilize skeletal manifestations, increase bone mass, increase mobility, and have reduced pain.
  • 15% of vertebral and 20–40% of hip fractures may lead to chronic care and/or premature death.