Osteoporosis Diagnosis

Indications for Bone Mineral Density (BMD) Measurements 

• 2014 National Osteoporosis Foundation (NOF)
  • Women ≥65 years; postmenopausal women >50 years with risk factors for fracture
  • Men ≥70 years, or >50 years with risk factors for fracture
• 2015 International Society for Clinical Densitometry (ISCD)  
  • Women ≥65 years; postmenopausal women <65 years with a risk factor for low bone mass
  • Women during menopausal transition with risk factors for fracture
  • Men ≥70 years, or <70 years with a risk factor for low bone mass
  • Adults:
    • With a fragility fracture
    • With a condition or who are taking medications associated with low bone mass/bone loss
    • Being considered for pharmacological therapy
    • Receiving treatment to monitor effect
    • Not on treatment in whom evidence of bone loss would require treatment 
• 2018 US Preventive Services Task Force (USPSTF)
  • Women ≥65 years; postmenopausal women <65 years considered at increased risk for osteoporosis based on formal clinical risk assessment tool  
• Some authorities recommend that patients >65 years old with multiple risk factors or prevalent osteoporotic fracture be started on treatment for osteoporosis without BMD measurements

Glucocorticoid-induced Osteoporosis

• BMD testing within 6 months of starting glucocorticoid therapy is performed in:
  • Adults <40 years old with history of osteoporotic fracture OR other significant osteoporosis risk factors
  • Adults ≥40 years old with FRAX with glucocorticoid dose correction
    • The risk generated with FRAX is increased by 1.15 for major osteoporotic fracture and 1.2 for hip fracture if glucocorticoid therapy is >7.5 mg/day

Osteoporosis Self-Assessment Tool for Asians (OSTA)

• Formula combines patient’s age and body weight 
• Useful for identifying young postmenopausal women for BMD testing 
  • Can support detecting a postmenopausal woman’s risk for osteoporosis

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, 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

• Measure patient’s height and weight
  • Decrease in patient's height >4 cm (>1.5 in)
• Evaluate patient’s muscle strength and balance and for the presence of kyphosis 
• Tenderness over the anterior tibia or thoracic vertebrae may indicate focal bone disease or osteomalacia; presence of blue sclerae or joint laxity may indicate osteogenesis imperfecta

• 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
• Identify patients for possible pharmacologic therapy
• Used for therapeutic monitoring in patients with glucocorticoid-induced osteoporosis (GIOP)

• DXA of hip and spine
  • Gold standard
  • Diagnose osteoporosis with a hip and/or spine DXA BMD T-score of ≤-2.5
  • 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 (BMD) T-Score¹

¹Should be used for postmenopausal women and men ≥50 years old
²Values are based on DXA 
T-score: A comparison with young normal adult mean of the same sex

                       BMD Z-Score³

• Quantitative CT 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

• Peripheral DXA (pDXA)
• CT-based assessments: Peripheral QCT
• Quantitative ultrasound densitometry (QUS) of heel, tibia, patella and other peripheral skeletal sites

• Complete blood count (CBC), erythrocyte sedimentation rate (ESR)
• Renal function tests (eg blood urea nitrogen [BUN], creatinine), liver function tests (LFTs) 
• Electrolytes (eg ionized calcium, phosphate, magnesium)
• Serum 25-hydroxyvitamin D, total protein, albumin, aspartate aminotransferase (AST), alkaline phosphatase
• Urinalysis, urinary N-telopeptide (uNTX), 24-hour urinary calcium
• Bone turnover markers
  • May be considered in the primary evaluation and follow-up of patients with osteoporosis
  • Elevated levels indicate rapid bone loss and identify 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 (IgA and IgG), serum protein electrophoresis (SPEP)
• Others (eg thyroid function as indicated, parathyroid hormone, total and free testosterone)

• 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

• 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 BMD T-score ≤-1.5 at the spine, total hip, or femoral neck
  • Postmenopausal women and men ≥50 years with low-trauma fracture during adulthood, historical height loss (current height - peak height at 20 years) by >1.5 in, prospective height loss (current height - recently documented height) by ≥0.8 in, and/or currently or previously on long-term glucocorticoid treatment
  • Other BMD measurements are unavailable

• A T-score of ≤-2.5 in the femoral neck, lumbar spine, total proximal femur 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 or with multiple fractures at other sites
• Osteopenia or low bone mass and high probability of FRAX™ fracture based on country-specific cutoffs