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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- DXA diagnosis: T-score <= -2.5 at femoral neck, total hip, or lumbar spine
- Fragility hip or vertebral fracture is osteoporosis regardless of T-score
- Screen women >=65 and younger postmenopausal women at increased fracture risk; consider men at risk
- First-line pharmacotherapy for most: oral bisphosphonate such as alendronate
- Evaluate secondary causes: vitamin D deficiency, hyperparathyroidism, hyperthyroidism, Cushing syndrome, CKD, malabsorption, medications
Overview
Osteoporosis is defined by reduced bone strength and increased fracture risk. It may be primary, related to aging and estrogen deficiency, or secondary to endocrine disease, medications, malabsorption, inflammatory disorders, kidney disease, or immobility. Hip and vertebral fractures cause substantial morbidity, mortality, and loss of independence. Step 2 CK frequently tests screening indications, DXA interpretation, secondary cause evaluation, and medication adverse effects.
Epidemiology
Osteoporosis is common in postmenopausal women and older adults. Risk factors include age, female sex, low body weight, prior fragility fracture, parental hip fracture, smoking, excess alcohol, glucocorticoids, rheumatoid arthritis, hypogonadism, hyperthyroidism, hyperparathyroidism, Cushing syndrome, chronic liver or kidney disease, celiac disease, and aromatase inhibitor or androgen deprivation therapy.
Clinical Features
Symptoms
Usually asymptomatic until fracture occurs
Acute back pain after minimal trauma suggesting vertebral compression fracture
Hip, wrist, humerus, or pelvic fragility fracture after low-energy fall
Height loss or kyphosis from vertebral compression fractures
Bone pain should prompt evaluation for fracture, malignancy, osteomalacia, or other pathology
Signs
Kyphosis, loss of height, reduced rib-pelvis distance
Point spinal tenderness with compression fracture
Gait instability and fall risk factors
Features of secondary cause: Cushingoid appearance, hyperthyroidism, hypogonadism, malabsorption
Normal examination is common before fracture
Investigations
First-line
DXA scanMeasures BMD at lumbar spine, total hip, and femoral neck. Osteoporosis T-score <= -2.5; osteopenia -1.0 to -2.5
FRAXEstimates 10-year hip and major osteoporotic fracture risk; used especially in osteopenia
Basic secondary workupCalcium, creatinine, alkaline phosphatase, 25-OH vitamin D, CBC, TSH; add PTH if calcium abnormal
Second-line
Vertebral fracture assessment or spine X-rayIf height loss, back pain, kyphosis, or high risk for silent vertebral fracture
24-hour urine calciumIf hypercalciuria, malabsorption, or recurrent stones suspected
Celiac testing, testosterone, SPEPTargeted testing for secondary causes when clinical clues exist
Specialist
Bone turnover markersMay help monitor adherence/response but not required for diagnosis
Endocrinology referralVery low BMD, recurrent fractures, young patients, complex secondary osteoporosis, or anabolic therapy consideration
1
Lifestyle and fall prevention
- Weight-bearing and resistance exercise; balance training
- Adequate calcium intake through diet/supplement if needed and vitamin D repletion
- Smoking cessation, limit alcohol, vision correction, medication review, home safety interventions
2
When to treat
- Hip or vertebral fragility fracture
- T-score <= -2.5
- Osteopenia with elevated FRAX fracture probability
- High-risk glucocorticoid exposure or other high-risk secondary causes
3
First-line medication
- Oral bisphosphonates: alendronate or risedronate for most patients
- Administration: empty stomach with water, remain upright for at least 30 minutes to reduce esophagitis risk
- IV zoledronic acid if adherence, absorption, or esophageal disease limits oral therapy
4
High and very high risk options
- Denosumab for high fracture risk or renal limitations, but do not stop abruptly without another antiresorptive because rebound vertebral fractures can occur
- Anabolic therapy: teriparatide, abaloparatide, or romosozumab for very high risk, multiple fractures, or very low BMD
- Follow anabolic therapy with antiresorptive therapy to maintain gains
5
Monitoring
- Repeat DXA typically every 1-2 years until stable, then less often
- Reassess bisphosphonate duration and consider drug holiday in lower-risk patients after several years; continue in high-risk patients
Complications
- Hip fracture: Associated with major mortality and loss of independence
- Vertebral compression fracture: Pain, kyphosis, height loss, restrictive lung disease in severe cases
- Medication adverse effects: Bisphosphonate esophagitis, osteonecrosis of jaw, atypical femur fracture; denosumab rebound fractures if stopped
- Chronic pain and disability: From vertebral and nonvertebral fractures
- Secondary osteoporosis progression: Fracture risk remains high if underlying endocrine cause is untreated
USMLE Step 2 CK Exam Tips
- 1T-score <= -2.5 = osteoporosis; Z-score compares to age-matched peers and is used more in younger patients
- 2Low-trauma hip or vertebral fracture = treat as osteoporosis regardless of DXA
- 3Alendronate must be taken upright with water on an empty stomach — esophagitis is a classic adverse effect
- 4Denosumab discontinuation without follow-on therapy can cause rebound vertebral fractures
- 5Long-term bisphosphonates: atypical femur fracture and osteonecrosis of the jaw are rare but tested
- 6Hyperthyroidism, Cushing syndrome, hyperparathyroidism, and glucocorticoids are endocrine secondary causes
- 7Vertebral compression fracture after minimal trauma is a sentinel osteoporosis event
practicetest your knowledge on osteoporosisApply what you've learnt with USMLE Step 2 CK-style questions from the iatroX Q-Bank — endocrine and beyond.
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