What is the recommended work‑up for suspected osteoporosis?

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Work-up for Osteoporosis

Dual-energy X-ray absorptiometry (DXA) of the lumbar spine and hip is the primary diagnostic test for osteoporosis, supplemented by targeted laboratory testing to identify secondary causes of bone loss. 1, 2

Primary Imaging Assessment

DXA scanning of the lumbar spine (L1-L4) and both hips (femoral neck and total hip) is the gold standard for diagnosing osteoporosis and predicting fracture risk. 1, 2 This imaging modality has been clinically validated to accurately predict fracture risk and correlates directly with the amount of force necessary to fracture bone. 1

Indications for DXA Testing

Obtain DXA screening in the following populations:

  • All women ≥65 years and all men ≥70 years (asymptomatic screening) 1
  • Women <65 years or men <70 years with risk factors including:
    • Current smoking 1
    • Low body weight (<127 lb or 57.6 kg) 1
    • Maternal hip fracture after age 50 1
    • History of amenorrhea >1 year before age 42 1
    • Height loss or thoracic kyphosis 1
    • Glucocorticoid use ≥5 mg prednisone equivalent daily for ≥3 months 1
  • Any individual ≥50 years with a fragility fracture (wrist, hip, spine, or proximal humerus with minimal trauma) 1
  • Any individual with insufficiency fractures at any age 1

Alternative Imaging When DXA is Limited

For patients with advanced degenerative spine changes, scoliosis, or conditions that spuriously elevate BMD measurements, consider:

  • DXA of the distal one-third radius (nondominant forearm) 1, 2
  • Quantitative CT (QCT) of the lumbar spine and hip 1, 2

These alternatives avoid the falsely elevated readings caused by facet joint osteoarthritis, vertebral fractures, or spondylosis. 1

Vertebral Fracture Assessment

Add vertebral fracture assessment (VFA) via DXA for patients with T-scores <-1.0 and any of the following:

  • Women ≥70 years or men ≥80 years 1
  • Historical height loss >4 cm (>1.5 inches) 1
  • Self-reported but undocumented prior vertebral fracture 1
  • Glucocorticoid therapy ≥5 mg prednisone equivalent daily for ≥3 months 1

VFA is performed concomitantly with DXA at the same visit, providing point-of-care assessment for vertebral compression fractures. 1

Laboratory Evaluation for Secondary Causes

A focused laboratory panel is essential to detect secondary causes of osteoporosis, which can be identified in the majority of cases with appropriate testing. 1 The following tests have 92% sensitivity for detecting secondary causes when no obvious etiology is apparent from history and physical examination: 1

Essential Laboratory Tests

  • Complete blood count (CBC) to assess for hematologic disorders 1, 2
  • Comprehensive metabolic panel including:
    • Serum calcium (to assess for hypercalcemia or hypocalcemia) 1, 2, 3
    • Creatinine and BUN (kidney function) 2
    • Liver function tests (ALT, AST, alkaline phosphatase) 2, 3
  • 25-hydroxyvitamin D [25(OH)D] level 1, 3
    • Levels <20 ng/mL predict increased risk of osteoporosis-related adverse events 1
    • Severe deficiency can cause osteomalacia with bone pain and muscle weakness 1
  • Parathyroid hormone (PTH) if hyperparathyroidism is suspected 1, 2
  • Serum phosphorus to detect phosphate wasting or osteomalacia 1
  • Lactate dehydrogenase (LDH) and alkaline phosphatase as markers of bone turnover 1, 3

Additional Testing When Indicated

Consider these tests based on clinical suspicion:

  • Thyroid-stimulating hormone (TSH) if hyperthyroidism suspected 4
  • Serum protein electrophoresis if multiple myeloma is a concern 1
  • Testosterone level in men with suspected hypogonadism 4, 5
  • 24-hour urine calcium if hypercalciuria suspected 1

Diagnostic Interpretation

Osteoporosis is diagnosed when DXA shows a T-score ≤-2.5 at the lumbar spine, femoral neck, or total hip. 2, 3, 6 The T-score compares the patient's BMD to young-adult reference populations. 2

A fragility fracture (particularly vertebral or hip) establishes the diagnosis of osteoporosis regardless of T-score. 2, 3 Most fragility fractures actually occur in individuals with T-scores higher than -2.5, confirming that the fracture itself demonstrates skeletal fragility. 2

Risk Stratification Beyond BMD

For patients with osteopenia (T-score between -1.0 and -2.5), calculate 10-year fracture risk using the WHO Fracture Risk Assessment Tool (FRAX). 1 Treatment should be considered if:

  • 10-year risk of major osteoporotic fracture ≥20% 1
  • 10-year risk of hip fracture ≥3% 1

Note that FRAX has not been validated in certain populations (e.g., HIV-infected patients) and may underestimate fracture risk in these groups. 1

Special Populations

Premenopausal Women and Men <50 Years

Use Z-scores (comparison to age-matched controls) rather than T-scores to detect secondary causes of osteoporosis in these populations. 2 DXA is still appropriate for initial imaging when risk factors are present. 1

Patients on Chronic Glucocorticoids

Obtain DXA with VFA or dedicated spine X-rays as soon as possible for adults initiating or continuing glucocorticoids ≥2.5 mg/day for >3 months. 7 These patients have dramatically elevated vertebral fracture risk (>50% prevalence in those over 70 years). 8

For acute back pain in glucocorticoid users, obtain standard 2-view X-rays of the symptomatic spine region first, not MRI. 7

Spine Surgery Candidates

Preoperative testing with DXA (T-score <-2.5), CT (Hounsfield units <97.9), or serum vitamin D3 (<20 ng/mL) predicts increased risk of postoperative adverse events in patients undergoing spinal instrumentation. 1 One of these tests should be performed preoperatively in patients with suspected osteoporosis. 1

Common Pitfalls to Avoid

  • Do not rely on plain radiographs for osteoporosis diagnosis—radiographic evidence of bone loss is not apparent until 30-40% of bone mass has been lost. 2 Plain films are appropriate only for evaluating suspected acute fractures. 2

  • Do not skip evaluation for secondary causes, particularly in premenopausal women, men under 50, and patients with very low Z-scores. 1, 2 Secondary osteoporosis accounts for a substantial proportion of cases and requires specific treatment. 1

  • Do not ignore degenerative changes that can falsely elevate lumbar spine BMD measurements—use alternative sites (forearm or QCT) when significant spondylosis, facet arthropathy, or scoliosis is present. 1, 2

  • Do not overlook asymptomatic vertebral fractures—more than 65% of vertebral fractures are clinically silent, and their presence changes risk stratification to very high risk requiring immediate treatment. 2, 7

  • Do not forget vitamin D assessment—vitamin D deficiency is highly prevalent and treatable, with levels <20 ng/mL associated with increased fracture risk. 1 Adequate repletion (800-1000 IU daily for maintenance) is essential for bone health. 1, 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Initial Laboratory Workup for Osteoporosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Osteoporosis: A Review.

JAMA, 2025

Research

Osteoporosis in men: an Endocrine Society clinical practice guideline.

The Journal of clinical endocrinology and metabolism, 2012

Research

Osteoporosis - risk factors, pharmaceutical and non-pharmaceutical treatment.

European review for medical and pharmacological sciences, 2021

Guideline

Imaging Guidelines for Glucocorticoid-Induced Osteoporosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Imaging Guidelines for Chronic Steroid Use with High-Energy Fall

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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