What are the differential diagnoses for low bone density in a 58-year-old man with chronic obstructive pulmonary disease on systemic glucocorticoids and a T-score of –2?

Differential Diagnoses for Low Bone Density (T-score -2.0) in a 58-Year-Old Male with COPD on Steroids

This patient has osteopenia (T-score -2.0) with a clear primary etiology—glucocorticoid-induced osteoporosis (GIOP)—but you must systematically evaluate for additional contributing secondary causes that commonly coexist in COPD patients on chronic steroids. 1

Primary Diagnosis

Glucocorticoid-Induced Osteoporosis (GIOP)

• This is the most likely primary diagnosis given chronic systemic steroid use for COPD 1
• GIOP causes rapid bone loss, particularly in the first 3-6 months of treatment, with continued decline during persistent use 1
• The T-score of -2.0 represents osteopenia (between -1.0 and -2.5), which is common in steroid-treated patients 1
• Even inhaled corticosteroids at high doses can contribute to bone loss, though less than oral steroids 2, 3

Secondary Contributing Factors to Evaluate

COPD-Specific Risk Factors

Chronic Obstructive Pulmonary Disease Itself

• COPD independently increases osteoporosis risk 4-fold even without glucocorticoid therapy 4
• Vertebral fractures occur in 48.7% of COPD patients never exposed to steroids 5
• Systemic inflammation from COPD directly impairs bone metabolism 6

Low Body Mass Index (BMI)

• Weak but significant correlation exists between low BMI and decreased bone mass in COPD patients 4
• Malnutrition and muscle wasting common in advanced COPD contribute to bone loss 6

Endocrine Disorders

Hypogonadism

• Serum estradiol-17β (not testosterone) correlates with bone mass in men with chronic lung disease 4
• Hypogonadism is common in chronic illness and should be screened 1

Vitamin D Deficiency

• Extremely common in COPD patients due to reduced sun exposure and chronic illness 6
• Vitamin D deficiency is a COPD-specific risk factor for osteoporosis 6

Hyperparathyroidism

• Must be excluded as a secondary cause of osteoporosis 1

Hyperthyroidism

• Known to adversely affect BMD and should be screened 1

Cushing Syndrome

• Consider if patient has clinical features beyond expected from exogenous steroid use 1

Nutritional and Malabsorption Disorders

Gastrointestinal Malabsorption

• Conditions associated with secondary osteoporosis include sprue, malnutrition, and vitamin D deficiency 1

Chronic Alcoholism

• Common in COPD patients and independently causes bone loss 1

Other Medical Conditions

Chronic Renal Failure

• Alters bone mineral density through multiple mechanisms 1

Rheumatoid Arthritis or Other Inflammatory Arthritides

• May coexist with COPD and independently cause bone loss 1

Multiple Myeloma

• Must be excluded in older males with low bone density 1

Prolonged Immobilization

• Common in severe COPD and accelerates bone loss 1

Recommended Diagnostic Workup

Laboratory Evaluation

• Serum calcium, phosphate, alkaline phosphatase, and 25-hydroxyvitamin D levels 1
• Renal function (creatinine, eGFR) 1
• Thyroid function tests (TSH) 1
• Serum estradiol-17β (more predictive than testosterone in men) 4
• Parathyroid hormone (PTH) if calcium abnormal 1
• Complete blood count and serum protein electrophoresis to exclude myeloma 1

Imaging Considerations

• Vertebral fracture assessment (VFA) should be performed, as vertebral fractures are extremely common (63.3%) in COPD patients on systemic steroids and often asymptomatic 5
• Repeat DXA in 1-2 years to monitor response if treatment initiated 7, 8

Critical Clinical Pearls

Common Pitfalls to Avoid:

• Do not assume steroids are the only cause—COPD itself quadruples osteoporosis risk 4
• Do not overlook vitamin D deficiency, which is nearly universal in this population 6
• Do not forget to check estradiol-17β rather than just testosterone in men 4
• Do not miss asymptomatic vertebral fractures, which occur in >60% of steroid-treated COPD patients 5

Treatment Threshold:

• While this patient has osteopenia (T-score -2.0), treatment with bisphosphonates is strongly recommended for adults ≥40 years receiving chronic glucocorticoids, even without osteoporosis diagnosis 1
• Calcium 1000-1200 mg/day and vitamin D 800-1000 IU/day supplementation are mandatory before initiating pharmacologic treatment 7, 8