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)
- T-score of -2.5 or less in lumbar spine, femoral neck, total hip, and/or one-third radius, even without marked fracture
- 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
- 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
- Serum calcium, phosphorus, magnesium
- 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 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
- 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
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 Rheumatology; 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)
- 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
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
Quantitative Electrochemiluminescent Immunoassay
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
Quantitative Radioimmunoassay
Quantitative Chemiluminescent Immunoassay
Quantitative Chemiluminescent Immunoassay
Quantitative Enzyme-Linked Immunosorbent Assay
Quantitative Electrochemiluminescent Immunoassay
Quantitative Enzyme Immunoassay
Quantitative Enzyme Immunoassay
Preferred test for screening and monitoring of thyroid function
Quantitative Chemiluminescent Immunoassay
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
High Performance Liquid Chromatography (HPLC)
Quantitative Spectrophotometry
Quantitative Spectrophotometry
Quantitative Spectrophotometry
Quantitative Spectrophotometry
Evaluate for kidney dysfunction in patients with known risk factors (eg, hypertension, diabetes, obesity, family history of kidney disease)
Quantitative Chemiluminescent Immunoassay/Quantitative Enzyme-Linked Immunosorbent Assay
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
Quantitative Chemiluminescent Immunoassay
Aid in the investigation of hepatobiliary and bone disease
Quantitative Enzymatic
May assist in assessing nutritional status or in indicating a possible chronic process
Quantitative Spectrophotometry
Preferred test to diagnose vitamin D insufficiency and monitor response to therapy
Testing is recommended only for patients at risk for vitamin D insufficiency
Quantitative Chemiluminescent Immunoassay
Identify risk in patients with palpable thyroid nodules
Quantitative Electrochemiluminescent Immunoassay
Reflex: if TSH is outside the reference interval, then free thyroxine (T4) testing will be added
Initial screening for hepatobiliary inflammation
Quantitative Enzymatic/Quantitative Spectrophotometry
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
Quantitative Electrochemiluminescent Immunoassay
Medical Experts
Straseski

References
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Buckley L, Guyatt G, Fink HA, et al. 2017 American College of Rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res (Hoboken). 2017;69(8):1095-1110.
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Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologists and American College of Endocrinology Clinical Practice Guidelines for the diagnosis and treatment of postmenopausal osteoporosis - 2016. Endocr Pract. 2016;22(Suppl 4):1-42.
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Cosman F, de Beur SJ, LeBoff MS, et al. Clinician's guide to prevention and treatment of osteoporosis. Osteoporos Int. 2014;25(10):2359-2381.
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Hans DB, Kanis JA, Baim S, et al. Joint official positions of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX(Ž). Executive summary of the 2010 Position Development Conference on Interpretation and Use of FRAXŽ in Clinical Practice. J Clin Densitom. 2011;14(3):171-180.
ISCD - Osteoporosis
International Society for Clinical Densitometry. ISCD. Middletown, CT [Accessed: May 2018]
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McCloskey E, Johansson H, Oden A, et al. Fracture risk assessment. Clin Biochem. 2012;45(12):887-893.
Practice Bulletin 129: Osteoporosis-ACOG
Practice Bulletin 129: Osteoporosis (September 2012, Reaffirmed 2016) (Replaces Practice Bulletin Number 50, January 2004). Washington, DC: American College of Obstetricians and Gynecologists (ACOG). [Reaffirmed: 2016; Accessed: Jan 2018]
USPSTF - Final Recommendation Statement: Osteoporosis to Prevent Fractures: Screening
U.S. Preventive Services Task Force. Final recommendation statement: osteoporosis to prevent fractures: screening. Rockville, MD: [Published: Jun 2018; Accessed: Aug 2018]