Osteoporosis

Diagnosis

Indications for Testing

Bone mineral density (BMD) testing (DXA) is recommended for women ≥65 years, postmenopausal women with risk factors, and men ≥70 years or younger men with risk factors (see Screening for details).

Criteria for Diagnosis

• Postmenopausal women (Camacho, American Association of Clinical Endocrinologists [AACE], 2016)
  • T-score of -2.5 or less in lumbar spine, femoral neck, total hip, and/or one-third radius, even without marked fracture
    • T-score is defined as standard deviation of individual’s BMD from the mean value for healthy young Caucasian women
  • Low-trauma fracture in spine or hip, irrespective of BMD
  • Low bone mass or osteopenia (T-score from -1 to -2.5) with fragility fracture of the proximal humerus, pelvis, or distal forearm
  • Low bone mass or osteopenia and high fracture probability based on fracture risk assessment tool (FRAX)
• Other populations
  • T-score of -2.5 or less at the femoral neck (WHO standard for osteoporosis diagnosis; International Society for Clinical Densitometry [ISCD], 2015)
  • Z-scores for BMD, rather than T-scores, are preferred in premenopausal women/girls and in boys/men <50 years (ISCD, 2015)

• Testing for causes of secondary osteoporosis should be considered
  • Serum calcium, phosphorus, magnesium
    • If hypercalcemia present – evaluate for hyperparathyroidism, multiple myeloma, cancer
    • Hypophosphatemia – suggests osteomalacia
  • CBC – if anemia present, evaluate for underlying conditions, such as multiple myeloma, cancer, malabsorption
  • Renal function testing – for renal disease assessment
  • Alkaline phosphatase – evaluate for Paget disease
  • 24-hour urine calcium – to detect hypercalciuria
  • Serum albumin – malnutrition, malabsorption assessment
  • Vitamin D 25(OH)D – for vitamin D deficiency; evaluate patients >50 years for malnutrition, malabsorption, and celiac disease
  • Thyroid stimulating hormone (TSH) – evaluate for hyperthyroidism
  • Liver function tests –  evaluate for chronic liver disease
  • Testosterone (males) – evaluate younger men for hypogonadism
  • Parathyroid hormone (PTH) (intact or PTH-related protein [PTHrP]) – evaluate for hyperparathyroidism
• Testing for bone turnover
  • Consider testing at initial diagnosis and at follow-up (Camacho, AACE, 2016; Cosman, National Osteoporosis Foundation [NOF], 2014)
  • Higher rates of bone turnover are associated with higher fracture risk

Imaging Studies

DXA – gold standard for diagnosis

Differential Diagnosis

• Fracture
  • Metastatic cancer
  • Primary cancer
  • Paget disease
  • Gaucher disease
  • Osteomalacia
  • Fibrous dysplasia
• Decreased bone density
  • Drugs
  • Cushing syndrome
  • Chronic renal disease
  • Chronic liver disease
  • Thyroid disease
  • Vitamin D deficiency
  • Cancer therapy
  • Hypogonadism
  • Amenorrhea
  • Malabsorption
  • Crohn disease
  • Celiac disease
  • Primary hyperparathyroidism
  • Renal calcium leak

Screening

Monitoring

• Laboratory testing
  • Bone turnover markers may be useful for monitoring therapy response (Camacho, AACE, 2016; Cosman, NOF, 2014)
  • Vitamin D 25(OH)D – consider reevaluating for adequate concentrations after supplementation
• Imaging studies
  • DXA – for monitoring during treatment
  • Reevaluate at 1-2 years until stable, then repeat every 1-2 years, or less frequently if clinically indicated (Cosman, NOF, 2014)

Background

Epidemiology

• Prevalence – ~10 million people in the U.S. have osteoporosis (NOF, 2014)
• Age – onset usually >50 years
• Sex – M<F
• Ethnicity – lower incidence in African Americans

Risk Factors

• Risk factors for primary osteoporosis (bone loss as a result of normal aging)
  • Caucasian or Asian race
  • Female sex
  • Older age – up to 50% of women and 25% of men >50 years will have osteoporosis-related fracture (NOF, 2018)
  • Low body weight (<127 lbs or body mass index [BMI] ≤21), weight loss, or malnutrition
  • Family history of hip fracture
  • Personal history of fracture
  • Tobacco use or history of use
  • History of alcohol intake >3 units daily
• Risk factors for secondary osteoporosis (bone loss as a result of disease or medication)
  • Medications – glucocorticoids, immunosuppressive therapy, thyroxine, aromatase inhibitors, thiazolidine, anticonvulsant therapy (eg, phenytoin)
  • Cushing syndrome
  • Secondary hyperparathyroidism
  • Hyperthyroidism
  • Vitamin D deficiency
  • Cancer therapy
  • Malabsorptive disorders (eg, Crohn disease, celiac disease)
  • Hypogonadism
  • Amenorrhea

• Bone metabolism regulated by vitamin D, calcium, estrogens, androgens, PTH
• Age-related bone loss due to abnormal bone remodeling results in decreasing bone density
• Osteoporosis may be worse if optimal bone mass was not achieved

Clinical Presentation

• Often asymptomatic, discovered during screening
• Sentinel fractures
  • Also called fragility fractures
  • Often the first sign of osteoporosis in an asymptomatic patient
  • Defined as wrist, hip, or vertebral fracture (even in the presence of trauma)
• Most common presentation in symptomatic patients
  • Height loss
  • Kyphosis
  • Bone pain
  • History of previous fractures