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The Physician's Guide to Laboratory Test Selection and InterpretationOsteoporosis
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 ≤21, 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
Diagnosis
- Indications for Ordering
- Laboratory testing
- Not used as part of screening
- When osteoporosis confirmed, use to rule out secondary causes
- 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 ≤ -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 ≥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
- DEXA – dual energy X-ray absorptiometry
Preventative Measures
- 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
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
Disease Monitoring
- Monitor patients currently receiving treatment
- Ideal marker(s) not available currently
- Recommended testing – collagen crosslinked telopeptides (NTx or CTx), serum propeptide of type I collagen (PINP) and perhaps osteocalcin, bone specific alkaline phosphatase
- 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
- Serum propeptide of type 1 procollagen (PINP) is a by-product of collagen synthesis
- 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 out-dated
- Best marker available currently
- Recommended testing: collagen crosslinked telopeptides (NTx or CTx) and serum propeptide of type I collagen (PINP)
Click here for a chart of Clinical Assessment of Osteoporosis in Postmenopausal Women and Men Age 50 and Older
