Osteoporosis

Primary Authors: Meikle, A. Wayne, MD. Straseski, Joely A., PhD, MS, MT(ASCP), DABCC.

  • Key Points
  • Diagnosis
  • Screening
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Content

Monitoring Therapeutic Efficacy of Antiresorptive Drugs for Osteoporosis

Patients at high risk for fracture by bone mineral density testing (BMD) are usually placed on antiresorptive drug therapy in an effort to reduce their risk for fracture. To determine the efficacy of the treatment or confirm patient’s compliance with oral therapy, BMD is recommended 12 to 24 months post therapy initiation (National Osteoporosis Foundation [NOF], 2013; Endocrine Society, 2012; International Society for Clinical Densitometry [ISCD], 2008).  The addition of bone turnover markers (BTMs) allows treatment efficacy and patient compliance determinations within 3-6 months post therapy initiation (Lee, 2012).  BTMs should not be used to screen for or diagnose osteoporosis (International Osteoporosis Foundation/International Federation of Clinical Chemistry and Lab Medicine [IOF-IFCC], 2011).

When to Monitor

  • For oral therapy monitoring – recommend baseline and follow-up testing at 3-6 months for both resorptive and formation markers (NOF, 2013)
  • Serum and urine specimen collection
    • Suggest morning collection from fasting patients due to diurnal variation of markers and effect from foods  (Endocrine Society Clinical Practice Guideline, 2012; NOF, 2013)
    • If not possible, collect specimens under the same circumstances (eg, at same time of day)
  • Interpretation
    • Most societies consider ≥30% change from baseline a true change

Which Tests to Use for Monitoring

  • No marker proven better than others (Lee, 2012)
  • IOF-IFCC (2011) goal – to standardize markers used in monitoring in an effort to allow for collaborative data collection

Recommended Markers (IOF-IFCC, 2011)

Recommended Marker

ARUP Tests

Interpretation

Bone Formation

Serum procollagen type 1 N-terminal propeptide

Procollagen Type I Intact N-Terminal Propeptide 0070236

Increase from baseline level indicates therapeutic response

Bone Resorption

Serum collagen type I cross-linked telopeptide (best test for patients on antiresorptive therapy)

C-Telopeptide, Beta-Cross-Linked, Serum 0070416

Decrease from baseline level indicates therapeutic response

Increased level in postmenopausal women associated with increased risk of hip and nonvertebral fracture

Indications for Testing

  • Initiated through population screening or when patient presents with suspicious fracture

Laboratory Testing

  • Most useful tests to rule out secondary causes of osteoporosis (NOF, 2013)
    • Serum calcium, phosphorus, magnesium
    • CBC – if anemia present, rule out underlying conditions, such as multiple myeloma, cancer, malabsorption
    • Renal function testing – rule out renal disease
    • Alkaline phosphatase – rule out Paget disease
    • 24-hour urine calcium – detect hypercalcemia
    • Serum albumin – rule out malnutrition
    • Vitamin D 25(OH)D – rule out vitamin D deficiency; rule out malabsorption and celiac disease in patients >50 years
    • Thyroid stimulating hormone (TSH) – rule out hyperthyroidism
    • Liver function tests – rule out chronic liver disease
    • Testosterone (males) – rule out hypogonadism; use in younger men
    • Parathyroid hormone (PTH) – rule out hyperparathyroidism

Imaging Studies

  • Dual-energy x-ray absorptiometry (DXA)
    • Gold standard testing for diagnosis
    • Measures bone marrow density (BMD) of lumbar spine, total hip or femoral neck
      • Compares BMD to normal populations to generate T score
      • T score ≤-2.5 confirms osteoporosis (WHO definition)
      • T score between -1.0 and -2.5 confirms osteopenia
  • Peripheral dual-energy x-ray absorptiometry (pDXA) – portable machines for mass screening of populations
    • Measures BMD of forearm, finger, or heel
    • If abnormal result, need confirmatory DXA
  • Vertebral fracture analysis (VFA)
    • Component of DXA
    • Assists in identifying possible vertebral fractures
    • Confirm fracture with x-ray

Other Testing

  • Calcaneal quantitative ultrasound – sensitivity (21-45%) and specificity (88-96%) too low to recommend use
  • Quantitative computed tomography – not enough research to recommend at this time

Differential Diagnosis

Assessments, recommendations and scoring criteria

  • WHO FRAX (Fracture Risk Assessment) tool – provides fracture probability based on patient’s risk (eg, clinical risk factors, BMI)
    • Benefits
      • Useful in estimating fracture risk over 10-year period
      • Country-specific
    • Limitations
      • Not validated in treated patients or in individuals outside the age range (≤40 years or ≥90 years)
      • Not validated for use of lumbar spine BMD
      • Calculations available for only four ethnic groups (Caucasian, African American, Hispanic, Asian)
      • Other important risk factors not included (eg, falls, high rate of bone loss)
  • QFracture scoring calculator – newest scoring system (non-validated)
  • Laboratory testing – may be useful for monitoring therapy; refer to Key Points section
  • Imaging studies
    • DXA – for monitoring while taking an FDA-approved drug
      • 1–2 years after initiation of therapy
      • Follow-up in 23-month intervals is sufficient for monitoring therapy response
    • Peripheral densitometry (portable machines for mass screening of general populations) cannot be used for monitoring therapy

Osteoporosis is a skeletal disorder characterized by decreased bone strength and density.

Epidemiology

  • Prevalence – 74% of females >80 years have osteoporosis
  • Age – onset usually >50 years
  • Sex – M<F
  • Ethnicity – lower incidence in African Americans

Risk Factors

  • Relative risk factors for primary osteoporosis (bone loss as a result of normal aging)
    • Caucasian or Asian race – increases by 1.5-3.0 for each T score decrease of 1.0 on bone mineral density (BMD)
    • Female sex
    • Older age – increases by 2-3 each decade >50 years
    • Low body weight (<127 lbs. or BMI ≤21) – increases by 1.2-2.0
    • Family history of osteoporosis
    • Personal history of fracture – increases up to 8
    • Tobacco history – increases by 1.2-2.0
    • History of hip fracture in first-degree relative – increases by 1.2-2.0
  • Risk factors for secondary osteoporosis (bone loss as a result of disease or medication)

Pathophysiology

  • Bone metabolism regulated by vitamin D, calcium, estrogens, androgens, parathyroid hormones
  • Usually a result of age-related bone loss due to abnormal bone remodeling
  • May occur because patient did not reach optimal bone mass as an adolescent

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

Indications for Laboratory Testing

Tests generally appear in the order most useful for common clinical situations.
Click on number for test-specific information in the ARUP Laboratory Test Directory

C-Telopeptide, Beta-Cross-Linked, Serum 0070416
Method: Quantitative Electrochemiluminescent Immunoassay

Limitations

Baseline concentration of CTX must be established before treatment begins

Intraindividual variability of CTX must be considered when interpreting test results (eg, diet, exercise, time of day)

May be significant overlap in CTX between individuals with and without osteoporosis

Test result cannot be used to predict fractures

CTX concentration may be higher than expected in individuals with reduced kidney function (reduced excretion of CTX)

Procollagen Type I Intact N-Terminal Propeptide 0070236
Method: Quantitative Radioimmunoassay

Limitations

Less biological variation than s-CTX

Test cannot replace BMD screening to diagnose osteoporosis

Intraindividual variability of test due to diet, exercise, time of day, etc., must be taken into account when interpreting test results

Additional Tests Available

CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Comments

Screening test for osteoporosis

Thyroid Stimulating Hormone with reflex to Free Thyroxine 2006108
Method: Quantitative Electrochemiluminescent Immunoassay

Comments

Rule out thyroid disease as etiology of osteoporosis

Vitamin D, 25-Hydroxy 0080379
Method: Quantitative Chemiluminescent Immunoassay

Comments

Assess for Vitamin D deficiency; rule out malabsorption and celiac disease in patients >50 years

Calcium, Serum or Plasma 0020027
Method: Quantitative Spectrophotometry

Comments

Detect hypercalcemia

Calcium, Urine 0020472
Method: Quantitative Spectrophotometry

Comments

Detect hypercalcemia

Phosphorus, Inorganic, Plasma or Serum 0020028
Method: Quantitative Spectrophotometry

Comments

Detect hypophosphatemia

Alkaline Phosphatase, Serum or Plasma 0020005
Method: Quantitative Enzymatic

Comments

Rule out Paget disease

Albumin by Nephelometry 0050671
Method: Quantitative Nephelometry

Comments

Rule out malnutrition

Hepatic Function Panel 0020416
Method: Quantitative Enzymatic/Quantitative Spectrophotometry

Comments

Rule out chronic liver disease

Panel includes albumin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, bilirubin, and protein

Renal Function Panel 0020144
Method: Quantitative Chemiluminescent Immunoassay/Quantitative Enzyme-Linked Immunosorbent Assay

Comments

Rule out renal disease

Panel includes albumin, calcium, carbon dioxide, creatinine, chloride, glucose, phosphorous, potassium, sodium, and BUN

Testosterone, Adult Male 0070130
Method: Quantitative Electrochemiluminescent Immunoassay

Comments

Rule out hypogonadism

Bone Specific Alkaline Phosphatase 0070053
Method: Quantitative Chemiluminescent Immunoassay

Comments

Measure bone formation and monitor antiresorptive therapies

When using test to monitor osteoporosis therapy, recommend initial testing prior to beginning therapy and reevaluate 3-6 months after starting therapy

N-Telopeptide, Cross-Linked, Urine 0070062
Method: Quantitative Chemiluminescent Immunoassay

Comments

Measure bone resorption and monitor antiresorptive therapy (eg, bisphosphonates and hormone replacement therapy)

When using test to monitor osteoporosis therapy, recommend initial testing prior to beginning therapy and reevaluate 3-6 months after starting therapy

N-Telopeptide, Cross-Linked, Serum 0070500
Method: Quantitative Enzyme-Linked Immunosorbent Assay

Comments

Measure bone resorption and monitor antiresorptive therapy (eg, bisphosphonates and hormone replacement therapy)

When using test to monitor osteoporosis therapy, recommend initial testing prior to beginning therapy and reevaluate 3-6 months after starting therapy

Urine test preferred over serum

Osteocalcin by Electrochemiluminescent Immunoassay 0020728
Method: Quantitative Electrochemiluminescent Immunoassay

Comments

Measure bone formation and  monitor antiresorptive therapies

When using test to monitor osteoporosis therapy, recommend initial testing prior to beginning therapy and reevaluate 3-6 months after starting therapy

Thyroid Stimulating Hormone 0070145
Method: Quantitative Chemiluminescent Immunoassay

Comments

Rule out thyroid disease

Pyridinium Crosslinks (Total), Urine 0070213
Method: Quantitative Enzyme Immunoassay

Comments

Monitor therapeutic response, especially in a short amount of time (2-3 months)

Deoxypyridinoline Crosslinks, Urine 0070212
Method: Quantitative Enzyme Immunoassay

Comments

Alternate test for monitoring osteoporosis therapy

Pyridinoline and Deoxypyridinoline by HPLC 0080342
Method: High Performance Liquid Chromatography

Comments

Alternate test for monitoring osteoporosis therapy

Vitamin D, 1, 25-Dihydroxy 0080385
Method: Quantitative Chemiluminescent Immunoassay

Comments

Primarily indicated during patient evaluations for hypercalcemia and renal failure

Should not be used to diagnose vitamin D deficiency; however, normal result does not rule out vitamin D deficiency

Recommended test for diagnosing vitamin D deficiency is Vitamin D 25-hydroxy

Parathyroid Hormone, Intact 0070346
Method: Quantitative Electrochemiluminescent Immunoassay

Comments

Rule out hyperparathyroidism

Guidelines

BoneSource. New Healthy Bones for Life Clinician's and Patient Guides. National Osteoporosis Foundation. Arlington, VA [Accessed: Nov 2015]

Chopin F, Biver E, Funck-Brentano T, Bouvard B, Coiffier G, Garnero P, Thomas T. Prognostic interest of bone turnover markers in the management of postmenopausal osteoporosis. Joint Bone Spine. 2012; 79(1): 26-31. PubMed

Hans D, Kanis J, Baim S, Bilezikian J, Binkley N, Cauley J, Compston J, Cooper C, Dawson-Hughes B, Fuleihan G, Leslie W, Lewiecki M, Luckey M, McCloskey E, Papapoulos S, Poiana C, Rizzoli R, FRAX(®) Position Development Conference Members. Joint Official Positions of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX(®). Executive Summary of the 2010 Position Development Conference on Interpretation and use of FRAX® in clinical practice. J Clin Densitom. 2011; 14(3): 171-80. PubMed

International Society for Clinical Densitometry . Middletown, CT [Accessed: Nov 2015]

Liu H, Paige N, Goldzweig C, Wong E, Zhou A, Suttorp M, Munjas B, Orwoll E, Shekelle P. Screening for osteoporosis in men: a systematic review for an American College of Physicians guideline. Ann Intern Med. 2008; 148(9): 685-701. PubMed

McCloskey E, Johansson H, Oden A, Kanis J. Fracture risk assessment. Clin Biochem. 2012; 45(12): 887-93. PubMed

Osteoporosis. American College of Obstetricians and Gynecologists - Medical Specialty Society. 2004 January (Revised 2012 September). NGC: 009321

U.S. Preventive Services Task Force. Screening for osteoporosis: U.S. preventive services task force recommendation statement. Ann Intern Med. 2011; 154(5): 356-64. PubMed

Watts N, Adler R, Bilezikian J, Drake M, Eastell R, Orwoll E, Finkelstein J, Endocrine Society. Osteoporosis in men: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012; 97(6): 1802-22. PubMed

Watts N, Bilezikian J, Camacho P, Greenspan S, Harris S, Hodgson S, Kleerekoper M, Luckey M, McClung M, Pollack R, Petak S, AACE Osteoporosis Task Force. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of postmenopausal osteoporosis. Endocr Pract. 2010; 16 Suppl 3: 1-37. PubMed

General References

Hippisley-Cox J, Coupland C. Predicting risk of osteoporotic fracture in men and women in England and Wales: prospective derivation and validation of QFractureScores. BMJ. 2009; 339: b4229. PubMed

Hlaing T, Compston J. Biochemical markers of bone turnover - uses and limitations. Ann Clin Biochem. 2014; 51(Pt 2): 189-202. PubMed

Lee J, Vasikaran S. Current recommendations for laboratory testing and use of bone turnover markers in management of osteoporosis. Ann Lab Med. 2012; 32(2): 105-12. PubMed

Lewiecki M. In the clinic. Osteoporosis. Ann Intern Med. 2011; 155(1): ITC1-1-15; quiz ITC1-16. PubMed

Rachner T, Khosla S, Hofbauer L. Osteoporosis: now and the future. Lancet. 2011; 377(9773): 1276-87. PubMed

Sweet M, Sweet J, Jeremiah M, Galazka S. Diagnosis and treatment of osteoporosis. Am Fam Physician. 2009; 79(3): 193-200. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Meier C, Nguyen T, Handelsman D, Schindler C, Kushnir M, Rockwood A, Meikle W, Center J, Eisman J, Seibel M. Endogenous sex hormones and incident fracture risk in older men: the Dubbo Osteoporosis Epidemiology Study. Arch Intern Med. 2008; 168(1): 47-54. PubMed

Stevenson D, Schwarz E, Viskochil D, Moyer-Mileur L, Murray M, Firth S, D'Astous J, Carey J, Pasquali M. Evidence of increased bone resorption in neurofibromatosis type 1 using urinary pyridinium crosslink analysis. Pediatr Res. 2008; 63(6): 697-701. PubMed

Terry A, Sandrock T, Meikle W. Measurement of 25-hydroxyvitamin D by the Nichols ADVANTAGE, DiaSorin LIAISON, DiaSorin RIA, and liquid chromatography-tandem mass spectrometry. Clin Chem. 2005; 51(8): 1565-6. PubMed

Medical Reviewers

Last Update: January 2016