Osteoporosis

Osteoporosis is a skeletal disorder characterized by decreased bone strength and density. Dual-energy x-ray absorptiometry (DXA) is the gold standard test for diagnosis. Laboratory testing is useful in ruling out secondary causes of osteoporosis. Bone turnover marker testing is available but is not the primary method for diagnosing or monitoring 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)

Laboratory Testing

  • Testing for causes of secondary osteoporosis should be considered
    • Serum calcium, phosphorus, magnesium
    • 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
Bone Turnover Markers
Bone Formation Markers ARUP Tests Comments
Serum procollagen type 1 N-terminal propeptide

Serum procollagen type 1 C-terminal propeptide

Procollagen Type I Intact N-Terminal Propeptide 0070236 Most frequently used marker of bone formation

Expect reduced levels when on antiresorptive therapy

Serum osteocalcin Osteocalcin by Electrochemiluminescent Immunoassay 0020728 Limited use in clinical practice due to variability
Serum bone-specific alkaline phosphatase Bone Specific Alkaline Phosphatase 0070053 Expect increased levels with antiresorptive therapies
Bone Resorption Markers
Serum collagen type I cross-linked telopeptide C-Telopeptide, Beta-Cross-Linked, Serum 0070416 Most frequently used resorptive marker
Urine or serum N-telopeptide N-Telopeptide, Cross-Linked, Urine 0070062

N-Telopeptide, Cross-Linked, Serum 0070500

Fasting AM urine spot is optimal
Urine pyridinoline Pyridinium Crosslinks (Total), Urine 0070213

Pyridinoline and Deoxypyridinoline by HPLC 0080342

Expect reduced levels with antiresorptive therapies

Early AM spot urine sample is preferred

Urine deoxypyridinoline Deoxypyridinoline Crosslinks, Urine 0070212

Pyridinoline and Deoxypyridinoline by HPLC 0080342

Expect reduced levels with antiresorptive therapies

Early AM spot urine sample is preferred

Urine hydroxyproline n/a Nonspecific marker; also reflects bone formation
HPLC, high-performance liquid chromatography

Imaging Studies

DXA – gold standard for diagnosis

Differential Diagnosis

Screening

Recommended Populations to Screen for Osteoporosis
  Women Women (postmenopausal) Men
USPSTF, 2018 Women ≥65 years Postmenopausal women <65 years considered at risk for osteoporosis based on formal risk assessment tool Men – evidence is insufficient for a recommendation for or against screening in men
NOF, 2014 Women >65 years Postmenopausal women >50 years with either risk factors or fracture (new or historical adult age fracture) Men >70 years, or >50 years with risk factors or fracture (new or historical adult age fracture)
ACR, 2017 Women or men on glucocorticoids for 6 months, who are <40 years with risk factors or osteoporotic fracture, or ≥40 years
ACR, American College of Radiology; USPSTF, U.S. Preventive Services Task Force

Sources: Cosman, NOF, 2014; Buckley, ACR, 2017; USPSTF, 2018

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)

Pathophysiology

  • 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

ARUP Laboratory Tests

Preferred test to measure bone resorption and monitor response to antiresorptive therapy (eg, bisphosphonates, hormone replacement therapy) in postmenopausal women and individuals with osteoporosis

Does not replace BMD screening to diagnose osteoporosis

Measure bone formation and monitor antiresorptive therapies

When using test to monitor osteoporosis therapy, recommend initial testing should occur prior to beginning therapy; evaluate response 3-6 months after starting therapy

Related Tests

Preferred test for screening and monitoring of thyroid function

Diagnostic evaluation of patients suspected to have collagen lysyl hydroxylase deficiency (Ehlers-Danlos Syndrome type VIA)

May be useful when evaluating bone resorption (eg, osteoporosis)

Preferred test for monitoring bone resorption and response to antiresorptive therapy is c-telopeptide, beta-cross-linked, serum

Screening test for osteoporosis

Evaluate for kidney dysfunction in patients with known risk factors (eg, hypertension, diabetes, obesity, family history of kidney disease)

Panel includes albumin, calcium, carbon dioxide, creatinine, chloride, glucose, phosphorous, potassium, sodium, and blood urea nitrogen (BUN)

May be useful for evaluating calcium metabolism in individuals with hypercalcemia or renal failure in addition to vitamin D, 25-hydroxy testing

Test is not appropriate for diagnosing vitamin D deficiency or insufficiency

Aid in the investigation of hepatobiliary and bone disease

May assist in assessing nutritional status or in indicating a possible chronic process

Preferred test to diagnose vitamin D insufficiency and monitor response to therapy

Testing is recommended only for patients at risk for vitamin D insufficiency

Identify risk in patients with palpable thyroid nodules

Reflex: if TSH is outside the reference interval, then free thyroxine (T4) testing will be added

Initial screening for hepatobiliary inflammation

Panel includes albumin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, bilirubin (direct and total), and protein (total)

Aid in the evaluation of suspected hypogonadism in men

Use to monitor testosterone replacement therapy

Not recommended for use in women and children

Medical Experts

Contributor

References

Additional Resources
Resources from the ARUP Institute for Clinical and Experimental Pathology®