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 Topics
  • Videos

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
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

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 DB, Kanis JA, Baim S, Bilezikian JP, Binkley N, Cauley JA, Compston JE, Cooper C, Dawson-Hughes B, Fuleihan GE, Leslie WD, Lewiecki M, Luckey MM, McCloskey EV, Papapoulos SE, 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 NM, Goldzweig CL, Wong E, Zhou A, Suttorp MJ, 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 JA. 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 NB, Adler RA, Bilezikian JP, Drake MT, Eastell R, Orwoll ES, Finkelstein JS, Endocrine Society. Osteoporosis in men: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012; 97(6): 1802-22. PubMed

Watts NB, Bilezikian JP, Camacho PM, Greenspan SL, Harris ST, Hodgson SF, Kleerekoper M, Luckey MM, McClung MR, Pollack RP, Petak SM, 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 TT, Compston JE. 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 TD, Khosla S, Hofbauer LC. Osteoporosis: now and the future. Lancet. 2011; 377(9773): 1276-87. PubMed

Sweet MG, Sweet JM, Jeremiah MP, Galazka SS. Diagnosis and treatment of osteoporosis. Am Fam Physician. 2009; 79(3): 193-200. PubMed

Wyness SP, Straseski JA. Performance characteristics of six automated 25-hydroxyvitamin D assays: Mind your 3s and 2s Clin Biochem. 2015; 48(16-17): 1089-96. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Meier C, Nguyen TV, Handelsman DJ, Schindler C, Kushnir MM, Rockwood AL, Meikle W, Center JR, Eisman JA, Seibel MJ. 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 DA, Schwarz EL, Viskochil DH, Moyer-Mileur LJ, Murray M, Firth SD, D'Astous JL, Carey JC, 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 AH, 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

Tran TS, Center JR, Seibel MJ, Eisman JA, Kushnir MM, Rockwood AL, Nguyen TV. Relationship between Serum Testosterone and Fracture Risk in Men: A Comparison of RIA and LC-MS/MS Clin Chem. 2015; 61(9): 1182-90. PubMed

Medical Reviewers

Last Update: September 2016