How do steroids induce osteoporosis in older adults, especially those with a history of fractures or other risk factors?

How Steroids Induce Osteoporosis

Glucocorticoids cause osteoporosis through a dual mechanism: they rapidly increase osteoclast-mediated bone resorption while simultaneously suppressing osteoblast-mediated bone formation, with the highest rate of bone loss occurring within the first 3-6 months of treatment. 1

Primary Mechanisms of Bone Loss

Direct Effects on Bone Cells

• Glucocorticoids induce apoptosis (cell death) in osteoblasts and osteocytes, which are the cells responsible for building new bone, thereby directly decreasing bone formation 1, 2

• Steroids prolong the lifespan of osteoclasts, the cells that break down bone, leading to increased bone resorption 2, 3

• This creates an imbalance where bone breakdown exceeds bone formation, resulting in net bone loss 1, 4

Calcium Homeostasis Disruption

• Glucocorticoids suppress intestinal calcium absorption from the gut, reducing the amount of calcium available for bone mineralization 1, 5, 3

• Steroids increase urinary calcium excretion by decreasing renal tubular calcium reabsorption, further depleting the body's calcium stores 1, 5, 3

• These calcium losses trigger secondary hyperparathyroidism, where the parathyroid glands increase PTH secretion in response to low calcium levels, which paradoxically increases bone resorption to maintain serum calcium 1, 3

Temporal Pattern and Dose Relationship

Rapid Onset of Bone Loss

• The highest rate of bone loss occurs within the first 3-6 months of glucocorticoid treatment, due to early osteoclast activation followed by decreased osteoblast proliferation 1

• Fracture risk increases rapidly within 3 months of commencing oral glucocorticoids, making early intervention critical 6

Dose-Dependent Effects

• Doses ≥2.5 mg/day of prednisone increase fracture risk at both spine and hip, while doses <2.5 mg/day still increase spinal fracture risk 1

• Very high doses (≥30 mg/day) and high cumulative doses (≥5 gm/year) further increase fragility fracture risk, with peak incidence at 12 months 1

• Prolonged use (>3 months) is associated with numerous complications including osteoporosis, regardless of the specific dose used 1

Additional Contributing Factors in Older Adults

Age-Related Vulnerabilities

• Advancing age and menopause further increase the rate of bone resorption, magnifying the impact of the remodeling imbalance caused by steroids 1

• Postmenopausal women are at particularly high risk and should be given special consideration before initiating corticosteroid therapy 5

Compounding Risk Factors

• Prior fracture history is the strongest predictor of future fracture in patients receiving glucocorticoids 7

• Additional risk factors include low body weight (<70 kg), family history of hip fractures, smoking, excess alcohol intake, inadequate exercise, and vitamin D deficiency 1

• Malnutrition and lack of weight-bearing exercise further compromise bone health in older adults on steroids 1, 7

Clinical Implications

Fracture Risk Assessment

• All adults beginning or continuing >3 months of glucocorticoid treatment should have initial fracture risk assessment as soon as possible after GC initiation, including bone mineral density testing with vertebral fracture assessment 1

• For adults ≥40 years, use FRAX with glucocorticoid dose correction (increase major osteoporotic fracture risk by 1.15 and hip fracture risk by 1.2 if prednisone dose >7.5 mg/day) 1

Preventive Strategies

• All patients receiving corticosteroids should receive 800-1000 mg/day calcium and 800 IU/day vitamin D supplementation to counteract the calcium malabsorption and urinary losses 1, 7

• Lifestyle modifications are essential: smoking cessation, limiting alcohol, and regular weight-bearing exercise for 30-60 minutes daily 1, 5

• For patients at medium, high, or very high fracture risk, pharmacologic treatment with bisphosphonates, denosumab, or parathyroid hormone analogs is strongly recommended as soon as possible after GC initiation 1

Reversibility

• Fracture risk decreases within 3 months after cessation of glucocorticoid therapy, and bone mineral density may increase when steroids are discontinued, particularly in children and young adults 1, 2

• A 3-month wait period between glucocorticoid exposures may be ideal in patients at high risk for osteoporosis development 2