Secondary Causes of Osteoporosis and Diagnostic Tests
Secondary osteoporosis is caused or exacerbated by specific disease processes or medications, and comprehensive testing can identify these causes with 92% sensitivity. 1
Common Secondary Causes of Osteoporosis
Endocrine Disorders
- Hypogonadism (accounts for 40-60% of cases in men) 1
- Estrogen deficiency (accounts for 35-40% of cases in premenopausal women) 1
- Cushing's syndrome 1
- Hyperparathyroidism 1, 2
- Hyperthyroidism 1, 2
- Diabetes mellitus (types 1 and 2) 1
- Acromegaly 1
- Adrenal insufficiency 1
Gastrointestinal Disorders
- Malabsorption syndromes 1
- Celiac disease 1
- Inflammatory bowel disease 1
- Gastrectomy 1
- Primary biliary cirrhosis 1
- Bariatric surgery 1
Hematologic Disorders
- Multiple myeloma 1, 2
- Leukemias and lymphomas 1
- Hemophilia 1
- Sickle cell disease 1
- Thalassemia 1
- Systemic mastocytosis 1
Lifestyle and Substance-Related Factors
- Alcoholism (accounts for 40-60% of cases in men) 1
- Tobacco use 1
- Opioid use 1
- Physical inactivity 1
- Dietary calcium deficiency 1
Inflammatory and Infectious Conditions
Other Conditions
- Chronic kidney disease 1
- Vitamin D deficiency 1
- Chronic metabolic acidosis 1
- Immobilization 1
- Organ transplantation 1
- Congestive heart failure 1
- Multiple sclerosis 1
- Depression 1
Medication-Induced Osteoporosis
- Glucocorticoids (accounts for 40-60% of cases in men and 35-40% in women) 1
- Anticonvulsants 1
- Anticoagulants 1
- Antiretrovirals 1
- Glitazones 1
- Antipsychotics 1
- Cyclosporine and tacrolimus 1
- Gonadotropin-releasing hormone agonists 1
- Excess thyroxine 1
- Methotrexate 1
- Proton pump inhibitors 1
Diagnostic Tests for Secondary Osteoporosis
First-Line Laboratory Tests (92% sensitivity when combined) 1
- Complete blood count 1
- Comprehensive metabolic panel including:
- Serum 25-hydroxyvitamin D level 1, 2
- Parathyroid hormone (PTH) 1
- Thyroid-stimulating hormone (TSH) 1
- 24-hour urine calcium and creatinine 1
Gender-Specific Tests
- For men: Total and free testosterone 1
- For young amenorrheic women: Estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin levels 1
Additional Tests Based on Clinical Suspicion
- For patients on tenofovir: Simultaneous serum phosphate and creatinine, spot urine phosphate, and creatinine to calculate fractional excretion of phosphate 1
- For suspected osteomalacia: Evaluate for low calcium, low phosphorus, low 25(OH)D, elevated alkaline phosphatase, and elevated PTH 1
- For suspected multiple myeloma: Serum and urine protein electrophoresis 2
- For suspected Cushing's syndrome: Overnight dexamethasone suppression test or 24-hour urinary free cortisol 2
- For suspected celiac disease: Tissue transglutaminase antibodies 2
Clinical Approach to Diagnosis
- Begin with thorough history focusing on risk factors, medications, and symptoms of secondary causes 1
- Perform physical examination looking for signs of underlying conditions 1
- Order first-line laboratory tests for all patients with osteoporosis or recent fragility fracture 2
- Order additional targeted tests based on clinical suspicion 2
- Consider bone mineral density testing with DXA for patients with risk factors 1
- For patients with osteopenia, calculate 10-year fracture risk using FRAX 1
Important Clinical Considerations
- Secondary causes of osteoporosis are present in 44-90% of patients with low bone mineral density 1
- Multiple secondary causes can coexist in the same patient 2
- Older women and men with metabolic disorders associated with secondary osteoporosis have a 2-3 fold higher risk of hip and vertebral fractures 1
- Treatment of the underlying secondary cause can significantly improve bone health in many cases 3, 2
- When secondary osteoporosis is drug-induced, management requires both treatment of osteoporosis and prevention of further drug effects on bone 3