Glucocorticoid-Induced Osteoporosis

Glucocorticoid induced osteoporosis is bone loss and fragility fracture caused by glucocorticoid therapy. It is the most common cause of secondary osteoporosis.

Oral prednisolone 5 mg daily or more (or equivalent) for 3 months or longer carries the main risk. Fracture risk rises within 3 months, correlates with dose, and falls after stopping. About 30 to 50% of long term users have a fracture, and vertebral fractures occur at higher bone density than in other forms.

High dose inhaled, intravenous pulse, injected and topical steroids contribute. The underlying disease (rheumatoid arthritis, inflammatory bowel disease, asthma) also increases risk.

Pathophysiology.

Glucocorticoids rapidly increase osteoclast activity, then suppress osteoblast number and function and promote osteocyte apoptosis, with reduced bone formation. They also reduce intestinal calcium absorption, increase urinary calcium loss, suppress sex steroids and cause muscle loss, and increase falls.

• Often silent until fracture. Vertebral fractures (back pain, height loss), hip and rib fractures.
• Cushingoid features, myopathy and fall tendency.

Red flags.

• Acute severe back pain on glucocorticoid therapy.
• Rapid height loss or multiple fractures.

• Fracture risk assessment in all adults starting glucocorticoid for 3 months or longer, with the dose taken into account (risk is higher at over 7.5 mg prednisolone daily).
• DXA of lumbar spine and hip, and lateral spine imaging or vertebral fracture assessment (about 30% of vertebral fractures are silent).
• Calcium, vitamin D, creatinine, phosphate, parathyroid hormone, testosterone or oestradiol, and tests for other secondary causes.

Differential diagnosis.

• Osteoporosis from the underlying disease (inflammation, malabsorption, immobility), hypogonadism and vitamin D deficiency.
• Osteonecrosis of the femoral head (hip pain with normal DXA), myeloma and metastases.

• Use the lowest effective glucocorticoid dose and the shortest duration; prefer inhaled, topical or steroid sparing drugs where possible.
• Calcium 1000 to 1200 mg daily from diet and supplements, vitamin D 800 units daily, weight bearing activity, falls prevention, stopping smoking and limiting alcohol.
• Treat when there is a prior fragility fracture, age 70 years or older, a T-score of -1.5 or lower (or -2.5 or lower in younger adults), or high fracture risk. Oral alendronate 70 mg weekly or risedronate 35 mg weekly is first line. Zoledronic acid 5 mg intravenously yearly, or denosumab 60 mg subcutaneously every 6 months, if oral therapy is unsuitable.
• Teriparatide 20 micrograms subcutaneously daily for up to 24 months for very high risk (vertebral fractures or fractures on a bisphosphonate).
• Continue treatment while glucocorticoid is continued, and consider stopping bisphosphonate after glucocorticoid cessation in low risk patients.
• Premenopausal women and women who may become pregnant: bisphosphonates persist in bone and may affect the foetus, so use only for fracture or very high risk, with effective contraception.

Special groups. Children and adolescents: manage in a specialist team, and use bisphosphonate (pamidronate or zoledronic acid) only after fragility fracture. Older adults: assess falls risk and vitamin D status.

Monitoring. DXA every 1 to 2 years while on therapy, calcium and creatinine yearly, and adherence reviews.

Referral and escalation. Rheumatology or endocrinology for children, premenopausal women, vertebral fractures or very high risk.