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


Primary Osteoporosis

  • Postmenopausal = estrogen deficiency resulting to increased bone loss
  • Age-related = occurs in both men and women
  • Idiopathic = rare

Secondary Osteoporosis

  • Endocrine diseases [eg Cushing’s syndrome, hypogonadism (mostly in men), hyperthyroidism, hyperparathyroidism, type 1 or 2 diabetes, premature menopause, acromegaly, porphyria, growth hormone deficiency, etc]
  • Medications (eg corticosteroids, Heparin, anticonvulsants, immunosuppressants, aromatase inhibitors, gonadotropin-releasing hormone agents, proton pump inhibitors, Medroxyprogesterone, etc)
  • Chronic diseases [eg renal impairment, liver cirrhosis, malabsorption, rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), AIDS/HIV, ankylosing spondylitis, hemophilia, major depression, organ transplantation, Marfan syndrome, osteogenesis imperfecta, etc]
  • Others (eg malnutrition, malignancy, excessive alcohol, prolonged immobility, pregnancy, total parenteral nutrition, etc)

Glucocorticoid-induced Osteoporosis (GIOP)

  • When on oral glucocorticoid therapy, bone loss occurs in the 1st 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


Indications for Bone Mineral Density (BMD) Measurements in Women

  • All women ≥65 years or postmenopausal women <65 years with ≥1 risk factor for fracture/osteoporosis [recommended by the U.S. National Osteoporosis Foundation (NOF) and the US Preventive Services Task Force (USPSTF)] or using Osteoporosis Self-Assessment Tool for Asians [(OSTA), low weight for age] to assess risk and the need for bone mineral density measurement
    • Based on the OSTA, consider a DXA scan if patient is high risk (>20) while a DXA scan is deferred if patient is low risk (<0); for patients with medium risk (0-20), consider a DXA scan if other osteoporosis risk factors are present
  • All postmenopausal women with:
    • Prior low-trauma fractures of hip, wrist, and/or spine
    • Any type of fracture as an adult after age of 50 years
    • Radiological evidence of osteopenia or vertebral deformity 
    • Corticosteroid therapy equivalent to ≥5 mg/day of prednisone for ≥3 months or other medications associated with bone loss
  • Peri- or postmenopausal women with osteoporosis risk factors willing to receive medical therapy: 
    • Low body mass index (BMI), loss of height, thoracic kyphosis
    • Systemic corticosteroid therapy of ≥3 months or other medications associated with bone loss
    • Family history of osteoporotic fracture
    • Presence of estrogen deficiency (eg prolonged secondary amenorrhea, hypogonadism, premature natural or surgical menopause <45 years, early menopause <40 years)
    • Current smoking or excessive alcohol intake
  • Presence of conditions related to osteoporosis (eg hyperparathyroidism, hyperthyroidism, anorexia nervosa, malabsorption, Cushing’s syndrome, prolonged immobilization, rheumatoid arthritis)
  • Women considering treatment for osteoporosis and if bone mineral density facilitates decision
  • Monitor effect of osteoporosis treatment

Some authorities recommend that patients >65 years with multiple risk factors be started on treatment for osteoporosis without bone mineral density measurements

World Health Organization (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 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 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

Laboratory Tests

  • Complete blood count (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 procollagen (P1NP), tissue transglutaminase antibodies [immunoglobulin A and immunoglobulin G (IgA and IgG)], serum protein electrophoresis (SPEP)
  • Others (eg thyroid function as indicated, parathyroid hormone)



  • Scintigraphic bone studies, X-ray of lateral thoracolumbar 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 with bone mineral density T-score <-1.0 at the spine, total hip, or femoral neck
    • Women 65-69 years with bone mineral density T-score <-1.5 at the spine, total hip, or femoral neck
    • Postmenopausal women with low-trauma fracture during adulthood, historical height loss (current height - peak height at 20 years) 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 measurements are unavailable


Bone Mineral Density (BMD) Measurements

  • Bone mineral density measurements give an accurate reflection of bone mass and confirm diagnosis of osteoporosis
  • An excellent predictor of future fracture risk
    • For each standard deviation (SD) reduction in bone mineral density, there is approximately a two-fold increased risk of 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 BMD Measurement

  • Dual energy X-ray absorptiometry (DXA) of hip and spine
    • Gold standard
    • Diagnose osteoporosis based on BMD of the hips (conventionally)
    • Monitor therapeutic response based on BMD of the spine
    • Fracture risk assessment based on DXA measurement at the hip in patients with GIOP

    Bone Mineral Density T-SCORE

  • World Health Organization (WHO) Recommended Values* for Diagnosis of Osteoporosis
    Bone Mineral Density T-score (SD) Definition
    T ≥ -1 Normal
    -2.5 < T < -1 Osteopenia (low bone mass)
    T ≤ -2.5 Osteoporosis
    T ≤ -2.5 + fracture Severe/established osteoporosis

*Values are based on DXA
T-score: A comparison with young normal adult mean of the same sex

  • Quantitative Computed Tomography scan (QCT)
    • Used as an alternative technique when 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 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)
  • Computed tomography (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

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 

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