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
Sex – M<F

Risk Factors

Primary osteoporosis (bone loss as a result of normal aging)
- Caucasian or Asian race – relative risk increases by 1.5-3.0 for each T score decrease of 1 on bone mineral density (BMD)
- Female sex
- Older age – relative risk increases by 2-3 each decade >50 years
- Low body weight (<127 lbs. or BMI ≤21) – relative risk increases by 1.2-2.0
- Family history of osteoporosis
- Personal history of fracture – relative risk increases up to 8
- Tobacco history – relative risk increases by 1.2-2.0
- History of hip fracture in first-degree relative – relative risk increases by 1.2-2.0
Secondary osteoporosis (bone loss as a result of disease or medication)
- Long-term glucocorticoid or immunosuppressive therapy
- Cushing syndrome
- 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 remodeling
May occur because patient did not reach optimal bone mass as an adolescent
Bone metabolism regulated by vitamin D, calcium, estrogens, androgens, parathyroid hormone

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
Most common presentation in symptomatic patients
- Height loss
- Kyphosis
- Bone pain
- History of previous fractures

Treatment

Indications for treatment (National Osteoporosis Foundation)
- BMD T scores < -2.0 by hip/spine dual energy x-ray absorptiometry (DEXA) with no risk factors
- BMD T scores < -1.5 by hip/spine DEXA with 1 or more risk factors
- Prior vertebral or hip fracture
Once treatment is initiated, recommend DEXA every 2 years
Rare complication of osteoporosis therapy is jaw osteonecrosis
- Majority of patients are on high-dose IV therapy with nitrogen-containing drug (bisphosphonates)
- Occurs almost exclusively in oncology patients with dental problems
- No known monitoring tests available to predict this complication

Prevention

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

Screening

Assessments, recommendations and scoring criteria

WHO FRAX™ (Fracture Risk Assessment) tool – provides 10-year fracture probability based on patient’s risk (eg, clinical risk factors, BMI)
- Benefits
  - Useful in estimating fracture risk over 10-year period
- Limitations
  - Not validated in treated patients or in men, women, or children outside the age range
  - Can be used for only 4 ethnic groups (Caucasian, African American, Hispanic, Asian)
  - Other important risk factors not included (falls, high-bone tumor, rate of bone loss)

National Osteoporosis Foundation (NOF) clinical assessment criteria

NOF clinical assessment criteria for osteoporosis in postmenopausal women and men >50 years
Obtain a detailed patient history pertaining to clinical risk factors for osteoporosis-related fracture Modify diet/supplements and other clinical risk factors for fracture Estimate patient’s 10-year probability of hip and any major osteoporosis-related fracture using the U.S.-adapted WHO algorithm Decisions on whom to treat and how to treat should be based on clinical judgment using this guide and all available clinical information Consider FDA-approved medical therapies based on the following: Vertebral or hip fracture (clinical or morphometric) DEXA hip (femoral neck or total site) or spine T score ≤-2.5 Low bone mass (T score between –1 and –2.5 based on FRAX) and U.S.-adapted WHO 10-year probability of a hip fracture (≥3%) or probability of any major osteoporosis-related fracture (≥20%) Patient preferences may indicate treatment for people with 10-year fracture probabilities below these levels Consider non-medical therapeutic interventions Modify risk factors related to falling Consider physical and occupational therapy, including walking aids and hip-pad protectors Perform weight-bearing activities daily Patients not requiring medical therapies at time of initial evaluation should be clinically reevaluated when medically appropriate Patients taking FDA-approved medications should have laboratory and bone density reevaluation >2 years or when medically appropriate

NOF clinical assessment criteria for osteoporosis in postmenopausal women and men >50 years

Obtain a detailed patient history pertaining to clinical risk factors for osteoporosis-related fracture
Modify diet/supplements and other clinical risk factors for fracture
Estimate patient’s 10-year probability of hip and any major osteoporosis-related fracture using the U.S.-adapted WHO algorithm
- Decisions on whom to treat and how to treat should be based on clinical judgment using this guide and all available clinical information
Consider FDA-approved medical therapies based on the following:
- Vertebral or hip fracture (clinical or morphometric)
- DEXA hip (femoral neck or total site) or spine T score ≤-2.5
- Low bone mass (T score between –1 and –2.5 based on FRAX) and U.S.-adapted WHO 10-year probability of a hip fracture (≥3%) or probability of any major osteoporosis-related fracture (≥20%)
- Patient preferences may indicate treatment for people with 10-year fracture probabilities below these levels
Consider non-medical therapeutic interventions
- Modify risk factors related to falling
- Consider physical and occupational therapy, including walking aids and hip-pad protectors
- Perform weight-bearing activities daily
Patients not requiring medical therapies at time of initial evaluation should be clinically reevaluated when medically appropriate
Patients taking FDA-approved medications should have laboratory and bone density reevaluation >2 years or when medically appropriate

Guidelines for osteoporosis screening

Organization	All women ≥65 years	Women <65 years	Others
U.S. Preventive Services Task Force (2002)	Yes	≥60 years who are at increased risk
American Association of Clinical Endocrinologists (2003)	Yes	<65 years who have 1 or more risk factors History of fracture not caused by severe trauma
American College of Obstetricians and Gynecologists (2004)	Yes	<65 years who have 1 or more risk factors Postmenopausal with history of fracture Do not screen more frequently than every 2 years
National Osteoporosis Foundation (2008)	Yes	50-70 years who have 1 or more risk factors	Men ≥70 years All adults >50 years with family history All adults considered for osteoporosis therapy Monitor anyone on therapy
American College of Physicians (2008)	No recommendation		Assess for risk in older men If male at risk for osteoporosis, obtain DEXA
International Society for Clinical Densitometry (2008)	Yes	Fragility fracture	Men ≥70 years Men 50-69 years with risk factors All with risk-factor history All adults considered for osteoporosis therapy Monitor anyone on therapy

QFracture™ scoring calculator – newest non-validated scoring system

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

Test Name and Number	Recommended Use	Limitations
CBC with Platelet Count & Automated Differential 0040003 Method: Automated Cell Count with Flow Cell Differential	Results showing anemia suggestive of multiple myeloma, cancer
Thyroid Stimulating Hormone 0070145 Method: Electrochemiluminescent Immunoassay	Rule out hyperthyroidism
Vitamin D, 25-Hydroxy 0080379 Method: Chemiluminescent Immunoassay	Appropriate for assessment of Vitamin D status, including general population screening for deficiency; can also be used for assessment of hypocalcemia
Calcium, Serum or Plasma 0020027 Method: Spectrophotometry	Measure level of calcium in serum or plasma
Alkaline Phosphatase, Serum or Plasma 0020005 Method: Enzymatic	Rule out Paget disease
Albumin, Serum by Nephelometry 0050671 Method: Nephelometry	Rule out malnutrition
C-Telopeptide, Beta-Cross-Linked, Serum 0070416 Method: Electrochemiluminescent Immunoassay	CTx aids in monitoring antiresorptive therapies (eg, bisphosphonates and hormone replacement therapy) in postmenopausal women and individuals diagnosed with osteopenia	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
Procollagen Type I Intact N-Terminal Propeptide 0070236 Method: Radioimmunoassay	Most effective marker of bone formation and is particularly useful for monitoring bone formation therapies and antiresorptive therapies When using test to monitor osteoporosis therapy, recommend initial testing prior to beginning therapy and reevaluate 3-6 months after starting therapy	Less biological variation
N-Telopeptide, Cross-Linked, Urine 0070062 Method: Chemiluminescent Immunoassay	Use NTx to measure bone resorption 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: Enzyme-Linked Immunosorbent Assay	Use NTx to measure bone resorption 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
Bone Specific Alkaline Phosphatase 0070053 Method: Chemiluminescent Immunoassay	Measures rate of bone formation When using test to monitor osteoporosis therapy, recommend initial testing prior to beginning therapy and reevaluate 3-6 months after starting therapy	Liver alkaline phosphatase can affect the measurement of bone-specific alkaline phosphatase in this assay
Osteocalcin by Electrochemiluminescent Immunoassay 0020728 Method: Electrochemiluminescent Immunoassay	Reflects and predicts the rate of bone loss in postmenopausal women Indicates rate of bone turnover May assist in choosing most effective treatment for osteoporosis Measures bone formation When using test to monitor osteoporosis therapy, recommend initial testing prior to beginning therapy and reevaluate 3-6 months after starting therapy
Pyridinium Crosslinks (Total) 0070213 Method: Enzyme Immunoassay	Monitor therapy response especially in a short amount of time (2-3 months)

Additional Tests Available

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Deoxypyridinoline Crosslinks 0070212 Method: Enzyme Immunoassay
Hydroxyproline, Total Urine 0080328 Method: Ion Exchange Chromatography
Pyridinoline & Deoxypyridinoline by HPLC 0080342 Method: High Performance Liquid Chromatography
Vitamin D, 1, 25-Dihydroxy 0080385 Method: Radioimmunoassay
Parathyroid Hormone, Intact 0070346 Method: Electrochemiluminescent Immunoassay