Osteoporosis

= reduced bone mass of normal composition secondary to

1. osteoclastic resorption (85%): trabecular, endosteal, intracortical, subperiosteal
2. osteocytic resorption (15%)

• Prevalence: 7% of all women aged 35–40 years; 12% for males + females aged 50–79 years; ◊ Most common of all metabolic bone disorders; 14 million worldwide by 2020

Classification:

1. Primary / involutional osteoporosis ← cumulative bone loss as people age and undergo sex hormone changes
   1. Type I (postmenopausal) osteoporosis
      = accelerated trabecular bone resorption ← estrogen deficiency
      Fracture pattern: spine and wrist
   2. Type II (senile) osteoporosis
      = proportionate loss of cortical and trabecular bone
      Fracture pattern: hip, proximal humerus, tibia, pelvis
2. Secondary osteoporosis (in 20–30%) = consequence of various medical conditions / use of certain medications

Etiology:

1. CONGENITAL DISORDERS
   1. Osteogenesis imperfecta
      • The only osteoporosis with bending of bones!
   2. Homocystinuria
2. IDIOPATHIC (bone loss begins earlier + proceeds more rapidly in women)
   

   1. Juvenile osteoporosis: <20 years 2. Adult osteoporosis: 20–40 years 3. Postmenopausal osteoporosis: (40–50% lower trabecular bone mineral density in elderly than in young women) >50 years 4. Senile osteoporosis: progressively decreasing bone density at a rate of 8% (3%) in females (males) per year >60 years

3. NUTRITIONAL DISTURBANCES
   scurvy; calcium deficiency; protein deficiency (nephrosis, chronic liver disease, alcoholism, anorexia nervosa, kwashiorkor, starvation, malnutrition, malabsorption)
4. ENDOCRINOPATHY
   Cushing disease, hypogonadism (Turner syndrome, eunuchoidism), hyperthyroidism, hyperparathyroidism, acromegaly, Addison disease, diabetes mellitus, pregnancy, paraneoplastic phenomenon in liver tumors
5. RENAL OSTEODYSTROPHY
   decrease / same / increase in spinal trabecular bone; rapid loss in appendicular skeleton
6. IMMOBILIZATION = disuse osteoporosis
7. COLLAGEN DISEASE, RHEUMATOID ARTHRITIS
8. BONE MARROW REPLACEMENT
   infiltration by lymphoma / leukemia (ALL), multiple myeloma, diffuse metastases, marrow hyperplasia ← hemolytic anemia
9. DRUG THERAPY
   corticosteroids, heparin (15,000–30,000 U for >6 months), methotrexate, excessive alcohol consumption, smoking, Dilantin, aromatase inhibitors, gonadotropin-releasing hormone antagonist
10. RADIATION THERAPY
11. LOCALIZED OSTEOPOROSIS
    immobilization / disuse, Sudeck dystrophy, transient osteoporosis of large joints, regional migratory osteoporosis of lower extremities

• serum calcium, phosphorus, alkaline phosphatase frequently normal
• hydroxyproline may be elevated during acute stage

Significant predictors of osteoporotic fractures:

1. Age
2. History of fracture
3. Failed chair test (= inability to rise from a chair in 3 successions without using arms)
4. Fall within past 12 months

Clinical manifestation:

1. Vertebral compression fracture (HALLMARK)
2. Femoral fracture: neck + intertrochanteric region
3. Fracture of distal radius (Colles) and tibia

Technique of Bone Densitometry:

1. Single-Photon Absorptiometry
   measures primarily cortical bone of appendicular bones, single-energy ¹²⁵I radioisotope source
   Site: distal radius (= wrist bone density), os calcis
   Dose: 2–3 mrem
   Precision: 1–3%
2. Dual-Photon Absorptiometry
   radioactive energy source with 2 photon peaks; should be reserved for patients <65 years of age because of interference from osteophytosis + vascular calcifications
   Site: vertebrae, femoral neck
   Dose: 5–10 mrem
   Precision: 2–4%
3. Single X-ray Absorptiometry
   = area projectional technique for quantitative bone density measurement
   Site: distal radius, calcaneus
   Dose: low
   Precision: 0.5–2%
4. Dual Energy X-ray Absorptiometry (DXA / DEXA)
   = quantitative digital radiography
   • Most widely used & most precise technique!
   • Standard of reference for diagnosis of osteoporosis in conjunction with Fracture Risk Assessment Tool at http://www.shef.ac.uk/FRAX/ for results of a 10-year probability of a major osteoporotic fracture in hip, spine, proximal humerus, distal forearm
   
   Technique:
   • mobile x-ray source composed of 2 different photon energy levels (constant + pulsed) moves together with detection system
   • rectilinear / fan-beam scanners
   • attenuation values of soft tissues are subtracted, leaving only the attenuation values of bone
   • lateral scanning of spine increases accuracy without superimposition of posterior elements + marginal osteophytes + vascular calcifications
   
   Advantage:
   1. low radiation dose with higher radiation flux than radioisotope source of dual-photon absorptiometry
   2. uses sites where osteoporotic fractures occur
   3. low cost; ease of use; rapidity of measurement
   
   Limitation of 2-dimensional (areal) technique:
   1. no distinction between cortical + trabecular bone
   2. no discrimination between changes secondary to bone geometry + increased bone density
   3. regulatory oversight for ionizing radiation
   
   Site:
   1. lumbar spine (L1–L4)
   2. proximal femur (total hip, femoral neck, trochanter, Ward area)
   3. calcaneus (95% trabecular bone)
   4. forearm (suboptimal ← mostly cortical bone)
   
   Dose:<3 mrem
   Precision: 1–2%
   Data collected:
   • BMD (bone marrow density) value (g/cm²)
   • T-score = how far is the score from the mean of 50 with a SD of 10 compared with young adults 20–30 years of age (= peak of bone mass)
   • Z-score = location of a score compared to age-matched + gender-matched controls in a distribution with a mean of 0 and a SD of 1.0; particularly important in patients aged >75 years
   
   Interpretation:
   • normal (≥–1.0); osteopenia (<–1.0 but >–2.5); osteoporosis (≤–2.5); severe osteoporosis (≤–2.5 with a fragility fracture)
   
   Pitfalls:
   • weekly phantom calibration to detect scanner drift
     
   • improper patient positioning (decentering of lumbar spine, abduction / external rotation of hip)
   • improper numbering of vertebrae, placement of intervertebral markers, detection of bone edges
   • blurring / irregular contour of bone margins ← patient motion
   • anatomic artifacts from
     1. superimposed disease: degenerative disk disease, compression fracture, postsurgical defect, overlying atherosclerotic calcifications
     2. implanted devices: stent + vena cava filter, GI barium, hardware, vertebroplasty cement
     3. external objects: piercing, bra clips, metallic buttons
   • Results from different scanners not interchangeable ← differences in scanners and software programs
5. Quantitative Computed Tomography
   = determines true volumetric density (mg/cm³) by providing separate estimates of trabecular + cortical bone BMD over 2–4 vertebrae (T12–L4)
   • high-turnover cancellous bone is important for vertebral strength and has high responsiveness
   • trabecular bone + low-turnover compact bone can be measured separately
   
   Advantage:
   • allows separate analysis of trabeculae + cortices
   • selective assessment of metabolically active trabecular bone in center of vertebral body
   • better sensitivity than projectional methods (DXA)
   • exclusion of structures not contributing to spine mechanical resistance
   
   Disadvantage:
   • high radiation dose
   • poor precision limited to longitudinal assessment
   • high costs
   • high degree of operator dependence
   • need for considerable amount of space
   • limited scanner access
   
   Pitfalls affecting measurements:
   • myelofibrosis + hematopoietic disorders + fat
   
   Technique:
   • use of low-dose commercial CT scanner
   • compared to external bone mineral reference phantom that is scanned simultaneously with patient to calibrate CT attenuation measurements
   • 10-mm–thick section with gantry angle correction through center of vertebral body
   • results expressed as absolute values / Z and T scores
   
   Site: vertebrae L1–L3, other sites
   Use: assessment of vertebral fracture risk; measurement of age-related bone loss; follow-up of osteoporosis + metabolic bone disease
   1. single energy: 300–500 mrem; 6–25% precision
   2. dual energy: 750–800 mrem; 5–10% precision
   
   ◊Most sensitive technique!
6. Peripheral Quantitative CT
   = exact 3-dimensional localization of target volumes with multisection data acquisition capability covering a large volume of bone
   Site: distal radius
7. Quantitative Heel Ultrasound
   = determines US stiffness index(SI) using formula
   SI = 0.67 • BUA [dB/MHz] + 0.28 • SOS [m/s] – 420 SOS = speed of sound BUA = broadband ultrasound attenuation for 200–600 kHz
   as a risk assessment independent from DEXA
   ◊Fracture risk increases with decrease in SI
   Precision: 2.2%
   Disadvantage: lack of sensitivity, equipment drift
   Location: axial skeleton (lower dorsal + lumbar spine), proximal humerus, neck of femur, wrist, ribs
   Radiographs:
   • Radiographs: insensitive prior to bone loss of 25–30%
   • Bone scans do NOT show a diffuse increase in activity
   • increased radiolucency = decreased number + thickness of trabeculae = osteopenia (“poverty of bone”):
     • relatively prominent primary trabeculae ← initially selective loss of secondary trabeculae
     • juxtaarticular osteopenia with trabecular bone predominance (eg, distal radius + proximal femur):
       • accentuation of compressive + tensile trabeculae
       • sparsely trabeculated region in inferomedial femoral neck between converging primary and secondary compressive groups = Ward triangle
     • Trabecular bone responds to metabolic changes faster than cortical bone
   • cortical thinning (endosteal + intracortical + periosteal resorption):
     • scalloping of inner cortical margin
     • widening of marrow canal
     • prominent longitudinal cortical striations = tunneling
     • irregular definition of outer bone surface
       • Most specific finding of high bone turnover
   • delayed fracture healing with poor callus formation (DDx: abundant callus formation in osteogenesis imperfecta + Cushing syndrome)
   
   Cx: fracture for 1÷2 women + 1÷4 men >age 50 years
   1. Fractures at sites rich in labile trabecular bone (eg, vertebrae, wrist) in postmenopausal osteoporosis
   2. Fractures at sites containing cortical + trabecular bone (eg, hip) in senile osteoporosis
   
   Rx: calcitonin, sodium fluoride, diphosphonates, parathyroid hormone supplements, estrogen replacement