osteoporosis
OSTEOPOROSIS
Osteoporosis is the progressive, systemic skeletal disease characterized by decreased bone mass and micro-architectural deterioration of bone tissue leading to increased bone fragility and susceptibility to fractures.
The more risk factors (eg history, of fracture, advanced age, comorbidities, impaired vision) that are present, the greater the risk of fracture.

Diagnosis

Bone Mineral Density Measurements
  • Bone mineral density (BMD) measurements give an accurate reflection of bone mass and confirm diagnosis of osteoporosis
  • An excellent predictor of future fracture risk
    • For each SD reduction in BMD, there is approximately a 2-fold increased risk fracture
  • Recommended when results would affect management
  • Identifies patients for possible pharmacologic therapy
  • Used for therapeutic monitoring in patients with glucocorticoid-induced osteoporosis (GIOP)
Methods of Bone Mineral Density Measurement
  • Dual energy X-ray absorptiometry (DXA) of hip and spine
    • Gold standard
    • Diagnose osteoporosis based on bone mineral density (BMD) mesasurement of the hips (conventionally)
    • Monitor therapeutic response based on bone mineral density (BMD) of the spine
    • Fracture risk assessment based on DXA measurement at the hip in patients with GIOP

Bone Mineral Density T-score

WHO Recommended Values* for Diagnosis of Osteoporosis
Bone Mineral Density T-score (SD) Definition
T ≥ -1 Normal
T < -1 to < -2.5 Osteopenia (low bone mass)
T ≤ -2.5 Osteoporosis
T ≤ -2.5 + fracture Severe/established osteoporosis
*Values are based on dual energy X-ray absorptiometry (DXA)
T-score: A comparison with young normal adult mean of the same sex
  • Quantitative CT scan (QCT)
    • Used as an alternative technique when dual energy X-ray absorptiometry (DXA) is not available
    • Measures bone strength in the axial skeleton and volumetric bone density of the vertebra and hip
    • Has higher radiation dose compared to dual energy X-ray absorptiometry (DXA)
  • Trabecular Bone Score (TBS)
    • Evaluates microarchitectural texture of the bone
    • Highly sensitive in predicting fracture risk
Screening Methods (Not for Diagnosis or Monitoring)
  • Peripheral dual-energy X-ray absorptiometry (pDXA)
  • CT-based assessments: Peripheral QCT
  • Quantitative ultrasound densitometry (QUS) of heel, tibia, patella and other peripheral skeletal sites
If fracture is present: Physical exam, lab tests and radiologic tests should also be conducted to exclude underlying diseases that mimic, aggravate or cause osteoporosis eg secondary osteoporosis

Laboratory Tests

  • CBC, erythrocyte sedimentation rate (ESR)
  • Renal function tests (eg BUN, creatinine)
  • Electrolytes (eg ionized calcium [Ca], phosphate, magnesium [Mg])
  • Serum 25-hydroxyvitamin D, total protein, albumin, aspartate aminotransferase (AST), alkaline phosphatase
  • Urinalysis
  • Bone turnover markers
    • May be considered in the primary evaluation and follow-up of patients with osteoporosis
    • Identifies patients at high risk for fractures
    • Used to evaluate efficacy and compliance to current treatment
    • Eg serum C-telopeptide (CTX), osteocalcin, N-terminal propeptide of type 1 procollage (P1NP), tissue transglutaminase antibodies (IgA and IgG), serum protein electrophoresis (SPEP)
  • Others (eg thyroid function as indicated, parathyroid hormone)

Imaging

Radiology
  • Scintigraphic bone studies, X-ray of lateral thoraco-lumbar spine or hip (as indicated)
    • Bone loss of >30% is seen as radiological osteopenia in plain X-rays
Vertebral Imaging
  • Recommended for the following:
    • Women ≥70 years and men ≥80 years with bone mineral density (BMD) T-score ≤-1.0 at the spine, total hip, or femoral neck
    • Women 65-69 years and men 70-79 years with bone mineral density (BMD) T-score ≤-1.5 at the spine, total hip, or femoral neck
    • Postmenopausal women and men ≥50 year with low-trauma fracture during adulthood, historical height loss (current height - peak height at 20 year) by >1.5 inches, prospective height loss (current height - recently documented height) by ≥0.8 inches, and/or currently or previously on long-term glucocorticoid treatment
    • Other bone mineral density (BMD) measurements are unavailable
Diagnosis of Postmenopausal Osteoporosis
  • A T-score of ≤ -2.5 in the femoral neck, lumbar spine, total and/or 33% radius
  • Low-trauma fracture of the hip or spine (regardless of BMD)
  • Osteopenia or low bone mass with a fragility fracture of pelvis, proximal humerus or distal forearm
  • Osteopenia or low bone mass and high probability of FRAX™ fracture based on country-specific cutoffs

Assessment

Indications for Bone Mineral Density (BMD) Measurements
  • All women ≥65 years old or women <65 years old with ≥1 risk factor for fracture/osteoporosis [recommended by the U.S. National Osteoporosis Foundation (NOF)] or using Osteoporosis Self-Assessment Tool for Asians (OSTA) low weight for age to assess risk and the need for BMD measurement
  • All men >70 years of age, men >50-69 years old with risk factors, and men >50 years old with history of fracture during adulthood
  • Corticosteroid therapy equivalent to ≥5 mg/day of Prednisone for ≥3 months or other medications associated  with bone loss
  • Low body mass index (BMI) (<127 lb or BMI <20 kg/m2), loss of height, thoracic kyphosis
  • Presence of estrogen deficiency [eg prolonged secondary amenorrhea, hypogonadism, premature natural or surgical menopause <45 years, early menopause (<40 years old)]
  • Presence of conditions related to osteoporosis (eg hyperparathyroidism, hyperthyroidism, anorexia nervosa, malabsorption, Cushing’s syndrome, prolonged immobilization, rheumatoid arthritis)
  • Radiological evidence of osteopenia or vertebral deformity
  • Women considering treatment for osteoporosis and if bone mineral density (BMD) measurement facilitates decision
  • Postmenopausal women who have had any type of fracture as an adult after age of 50 years
Some authorities recommend that patients >65 years old with multiple risk factors or prevalent osteoporotic fracture be started on treatment for osteoporosis without bone mineral density (BMD) measurements

WHO Fracture Risk Assessment Model (FRAX™)
  • Developed to calculate the 10-year risk of osteoporosis fracture, with or without BMD values, based on individual factors (eg sex, age, ethnicity, family history, previous fracture, glucocorticoid treatment, smoking status, alcohol consumption, rheumatoid arthritis, low BMI)
    • Level of fracture probability will vary between countries
  • Useful in identifying among the group of patients with osteopenia those at higher risk of fracture
  • Limitations of FRAX™ include lack of detail on some risk factors (eg smoking, prior fracture, effects of glucocorticoids), non-inclusion of other known risk factors (eg biochemical markers, falls)

Fracture Risk Categories

  • Low risk: BMD T-score at both hip and spine >-1.0, and 10-year hip fracture risk <3%, and 10-year risk of major osteoporotic fractures <20%, with no prior hip or spine fractures
  • Moderate risk: BMD T-score at both hip and spine >-2.5, or 10-year hip fracture risk <3%, or 10-year risk of major osteoporotic fractures <20%, with no prior hip or spine fractures
  • High risk: BMD T-score at hip or spine of ≤-2.5, or 10-year hip fracture risk ≥3%, or 10-year risk of major osteoporotic fracture risk ≥20%, with a prior hip or spine fracture
  • Very high risk: BMD T-score at hip or spine ≤-2.5 with multiple spine fractures

Glucocorticoid-Induced Osteoporosis

  • When on oral glucocorticoid therapy, bone loss occurs in 6-12 months and fracture risk increases within 3-6 months of initiating glucocorticoids
  • Intake of ≥5 mg daily of Prednisolone or its equivalent for ≥3 months is associated with osteoporosis
    • Similar risk is also shown with higher glucocorticoid dose taken for a shorter period of time
    • Strong glucocorticoids inhaled for 7 years are associated with significant bone loss
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