Osteoporosis

Clinical Background

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
Gender - F>M

Risk Factors

Primary osteoporosis (result of bone loss as a function of normal aging)
- Caucasian or Asian race (relative risk increases by 1.5-3 for each T score decrease -1 on BMD)
- Female sex
- Older age (relative risk increases by 2-3 per decade over 50 years)
- Low body weight (<127 lbs. or BMI less than or equasl to21, relative risk increases by 1.2-2)
- Family history of osteoporosis
- Personal history of fracture (relative risk increases up to 8)
- Tobacco history (relative risk increases by 1.2-2)
- History of hip fracture in first degree relative (relative risk increases by 1.2-2)
Secondary osteoporosis (disease or medication-induced bone loss)
- Long-term glucocorticoid or immunosuppressive therapy
- Cushing disease
- Chronic renal disease
- Hyperthyroidism
- Vitamin D deficiency
- Cancer treatment
- Malabsorptive disorders (eg, Crohn disease, celiac disease)
- Hypogonadism
- Anticonvulsant therapy (eg, phenytoin)

Pathophysiology

Usually a result of age-related bone loss due to abnormal bone remodelling
May occur because patient did not reach optimal bone mass as an adolescent
Regulated by vitamin D, calcium, estrogens, androgens, parathyroid hormone

Clinical Presentation

Asymptomatic, found by screening
Sentinel fractures
- Also called fragility fractures
- Often the first sign of osteoporosis in an asymptomatic patient
- Defined as wrist, hip or vertebral fracture
Most common presentation in symptomatic patients
- Height loss
- Kyphosis
- Bone pain
- History of previous fractures

Treatment (National Osteoporosis Foundation)

Indications for treatment
- BMD T scores below -2.0 by hip/spine DEXA with no risk factors
- BMD T scores below -1.5 by hip/spine DEXA with 1 or more risk factors
- Prior vertebral or hip fracture
Recommend
- DEXA every two years
Rare complication of osteoporosis therapy is jaw osteonecrosis
- Majority of patients are on high dose IV therapy with nitrogen containing therapy
- Almost exclusively in oncology patients with dental problems
- No known monitoring tests to predict this complication

Prevention

Discontinue tobacco
Avoid excess alcohol intake
Engage in weight bearing activities (lifelong)
Adequate calcium, vitamin D intake in childhood and adolescence
Continued adequate intake of calcium and vitamin D as an adult
Preventative measures for falls in the elderly

See Also

Adrenal Hyperfunction - Cushing Disease

Diagnosis

Indications for testing
- Diagnosis is initiated through population screening or when someone presents with a suspicious fracture. Imaging studies are the preferred method for both screening and differential diagnosis. Laboratory tests are useful in working up possible secondary diseases such as metabolic disorders. Imaging studies and laboratory tests may be useful in monitoring therapy
- Refer to Osteoporosis topic at www.arupconsult.com for the fracture risk assessment tool
- Refer to Osteoporosis topic at www.arupconsult.com for National Osteoporosis Foundation's chart of Clinical Assessment of Osteoporosis in Postmenopausal Women and Men Age 50 and Older
Laboratory testing
- May be useful to rule out secondary causes of osteoporosis
- Laboratory testing to consider:
  - Serum calcium - hypercalcemia
  - Might be suggestive of hyperparathyroidism, multiple myeloma, cancer
  - Complete blood count demonstrating anemia
    - Might be suggestive of multiple myeloma, cancer
  - Alkaline phosphatase - Paget disease
  - Serum albumin - malnutrition
  - Vitamin D 25(OH)D - malabsorption, celiac disease in patients older than 50
  - TSH - hyperthyroidism
Imaging studies
- DEXA - dual energy X-ray absorptiometry
  - Measures BMD of lumbar spine, total hip or femoral neck
  - Compares BMD to normal populations to generate T scores
  - T score less than or equasl to -2.5 confirms osteoporosis (WHO definition)
  - T score between -1.0 and -2.4 confirms osteopenia
  - Indications for measuring BMD by DEXA
    - Estrogen-deficient female
    - All females greater than or equal to 65 years old
    - Vertebral abnormalities suggestive of osteoporosis
    - Chronic glucocorticoid therapy
    - Primary hyperparathyroidism, other diseases with known risk for development of osteoporosis
    - Prior history of fragility fracture
    - Therapy
      - Monitor while taking a FDA approved drug
      - DEXA measurements at 23 month intervals are sufficient for monitoring therapy response
- Peripheral densitometry (portable machines for mass screening of populations)
  - Measures BMD of hand, heel or radius
  - If abnormal, need confirmatory DEXA
  - Cannot be used for monitoring therapy
- VFA (vertebral fracture analysis)
  - Component of the DEXA
  - Need to confirm fracture with X-ray
  - Helps to identify possible vertebral fractures
  - Indications
    - Documented height loss >2 cm
    - Fracture after age 50 years
    - Long-term glucocorticoid treatment
    - Other findings suggestive of fracture
- Other testing
  - CT or ultrasound are not the testing of choice at this time

Disease Monitoring

Monitor patients currently receiving treatment
- Monitoring of therapy has no clear markers that are proven to be better than others (Simon, 2007)
- Recommendations for markers
  - Synthesis markers - bone specific alkaline phosphatase, osteocalcin, serum propeptide of type 1 procollagen (PINP_
Resorptive markers - urinary C and T pyridinium and crosslinks (NTx or CTx)
Bone markers
- Cannot be used to make decisions regarding treatment initiation
- Need initial testing prior to therapy initiation and repeat testing 4-6 months later
- Bone formation markers
  - Serum propeptide of type 1 procollagen (PINP) is a by-product of collagen synthesis
    - Best monitoring marker for patients on PTH therapy
  - Serum bone specific alkaline phosphatase - osteoblast related protein
  - Serum osteocalcin - osteoblast related protein
- Bone resorption markers
  - Urine and serum cross-linked N-telopeptides - collagen breakdown products
  - Serum cross-linked C-telopeptides - collagen breakdown products
  - Pyridinium crosslinks - collagen breakdown product
  - Serum hydroxyproline - collagen breakdown product, test is outdated

Tests

Tests generally appear in the order most useful for common clinical situations

Test name: C-Telopeptide, Beta-Cross-Linked, Serum

ARUP #: 0070416

Methodology: Electrochemiluminescent Immunoassay

Use:

CTx aids in monitoring antiresorptive therapies (e.g., bisphosphonates and hormone replacement therapy) in postmenopausal women and individuals diagnosed with osteopenia

Limitations:

Test cannot replace Bone Mineral Density to diagnose osteoporosis

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

Test name: Procollagen Type I Intact N-Terminal Propeptide

ARUP #: 0070236

Methodology: Radioimmunoassay

Use:

PINP is the most effective marker of bone formation and is particularly useful for monitoring bone formation therapies and antiresorptive therapies

Limitations:

Less biological variation

Follow-up:

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

Test name: N-Telopeptide, Cross-Linked, Urine

ARUP #: 0070062

Methodology: Chemiluminescent Immunoassay

Use:

Use NTx (urine) to measure bone resorption

Limitations:

Follow-up:

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

Test name: N-Telopeptide, Cross-Linked, Serum

ARUP #: 0070500

Methodology: Enzyme-Linked Immunosorbent Assay

Use:

Use NTx (serum) to measure bone resorption

Limitations:

Urine test preferred over serum

Follow-up:

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

Test name: Bone Specific Alkaline Phosphatase

ARUP #: 0070053

Methodology: Chemiluminescent Immunoassay

Use:

Measures the rate of bone formation

Limitations:

Liver alkaline phosphatase can affect the measurement of bone-specific alkaline phosphatase in this assay

Follow-up:

When using test to monitor osteoporosis therapy, recommend initial testing prior to beginning therapy and reevaluate 3-4 months after starting therapy

Test name: Osteocalcin by Electrochemiluminescent Immunoassay

ARUP #: 0020728

Methodology: Electrochemiluminescent Immunoassay

Use:

Reflects and predicts the rate of bone loss in postmenopausal women
Indicates rate of bone turnover
May assist in choosing the most effective treatment for osteoporosis
Measures bone formation

Limitations:

Follow-up:

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

Test name: Pyridinium Crosslinks (Total)

ARUP #: 0070213

Methodology: Enzyme Immunoassay

Use:

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

Limitations:

Follow-up:

Test name: Vitamin D, 25-Hydroxy

ARUP #: 0080379

Methodology: Chemiluminescent Immunoassay

Use:

Measure vitamin D levels in serum or plasma to rule out deficiency in patients taking calcium supplementation

Limitations:

Follow-up:

Test name: Calcium, Serum or Plasma

ARUP #: 0020027

Methodology: Spectrophotometry

Use:

Measure level of calcium in serum or plasma

Limitations:

Follow-up:

Additional Tests Available

Test name: Deoxypyridinoline Crosslinks

ARUP #: 0070212

Methodology: Enzyme Immunoassay

Comments:

Test name: Hydroxyproline, Total Urine

ARUP #: 0080328

Methodology: Ion Exchange Chromatography

Comments:

Test name: Pyridinoline & Deoxypyridinoline by HPLC

ARUP #: 0080342

Methodology: High Performance Liquid Chromatography

Comments:

Test name: Vitamin D, 1, 25-Dihydroxy

ARUP #: 0080385

Methodology: Radioimmunoassay

Comments:

Test name: Parathyroid Hormone, Intact

ARUP #: 0070346

Methodology: Electrochemiluminescent Immunoassay

Comments:

References

Guidelines

Kanis JA, Black D, Cooper C, Dargent P, wson-Hughes B, De Laet C, Delmas P, Eisman J, Johnell O, Jonsson B, Melton L, Oden A, Papapoulos S, Pols H, Rizzoli R, Silman A, Tenenhouse A. A new approach to the development of assessment guidelines for osteoporosis. Osteoporos Int. 2002;13(7):527-536.

Osteoporosis prevention, diagnosis, and therapy. JAMA. 2001;285(6):785-795.

Osteoporosis prevention, diagnosis, and therapy. NIH Consens Statement. 2000;17(1):1-45.

Cited References

Clinician’s Guide to Prevention and Treatment of Osteoporosis, Washington, D.C.: National Osteoporosis Foundation, 2008.

General References

Becker C. Pathophysiology and clinical manifestations of osteoporosis. Clin Cornerstone. 2006;8(1):19-27.

Bonnick SL. Osteoporosis in men and women. Clin Cornerstone. 2006;8(1):28-39.

Dennison E, Mohamed MA, Cooper C. Epidemiology of osteoporosis. Rheum Dis Clin North Am. 2006;32(4):617-629.

Hochberg MC. Recommendations for measurement of bone mineral density and identifying persons to be treated for osteoporosis. Rheum Dis Clin North Am. 2006;32(4):681-689.

Lata PF, Elliott ME. Patient assessment in the diagnosis, prevention, and treatment of osteoporosis. Nutr Clin Pract. 2007;22(3):261-275.

Marx RE, Cillo JE Jr, Ulloa JJ. Oral bisphosphonate-induced osteonecrosis: risk factors, prediction of risk using serum CTX testing, prevention, and treatment. J Oral Maxillofac Surg. 2007;65(12):2397-2410.

McCormick RK. Osteoporosis: integrating biomarkers and other diagnostic correlates into the management of bone fragility. Altern Med Rev. 2007;12(2):113-145.

Olson AF. Osteoporosis detection: is BMD testing the future?. Nurse Pract. 2007;32(6):20-27.

Rosen CJ. Clinical practice. Postmenopausal osteoporosis. N Engl J Med. 2005;353(6):595-603.

Seibel MJ. Biochemical markers of bone turnover: part I: biochemistry and variability. Clin Biochem Rev. 2005;26(4):97-122.

Shoback D. Update in osteoporosis and metabolic bone disorders. J Clin Endocrinol Metab. 2007;92(3):747-753.

Simon LS. Osteoporosis. Rheum Dis Clin North Am. 2007;33(1):149-176.

Singer A. Osteoporosis diagnosis and screening. Clin Cornerstone. 2006;8(1):9-18.

Sorensen MG, Henriksen K, Schaller S, Karsdal MA. Biochemical markers in preclinical models of osteoporosis. Biomarkers. 2007;12(3):266-286.

Worsfold M, Powell DE, Jones TJ, Davie MW. Assessment of urinary bone markers for monitoring treatment of osteoporosis. Clin Chem. 2004;50(12):2263-2270.

References from the ARUP Institute for Clinical and Experimental Pathology Research®

Terry AH, Sandrock T, Meikle AW. Measurement of 25-hydroxyvitamin D by the Nichols ADVANTAGE, DiaSorin LIAISON, DiaSorin RIA, and liquid chromatography-tandem mass spectrometry. Clin Chem. 2005;51(8):1565-1566.

Medical Reviewers

Lehman, Christopher M., M.D. Co-Medical Director, University Hospital Clinical Laboratory; Associate Professor, Clinical Pathology, University of Utah

Longo, Nicola , M.D., Ph.D. Medical Director, Biochemical Genetics at ARUP Laboratories; Adjunct Associate Professor, Pediatrics and Pathology, University of Utah

Meikle, A. Wayne, M.D. Medical Director, RIA and Endocrinology at ARUP Laboratories; Professor of Internal Medicine and Pathology, University of Utah

Pasquali, Marzia , Ph.D., FACMG Medical Director, Biochemical Genetics and Supplemental Newborn Screening at ARUP Laboratories; Associate Professor, Clinical Pathology, University of Utah

Roberts, William L. , M.D., Ph.D. Medical Director, Automated Core Laboratory at ARUP Laboratories; Professor, Pathology, University of Utah

Comprehensive Review: January 2008
Last Update: September 2008