These recommendations are based on the Royal College of Physicians guideline, Glucocorticoid-induced osteoporosis [RCP, 2002].

Corticosteroids and bone mineral density

• Prior and current exposure to oral corticosteroids is associated with an increased risk of fracture. The magnitude of risk is of substantial importance, and is beyond that explained by low bone mineral density (BMD). This is based on evidence from a meta-analysis of seven cohort studies (n = 42,000) which included men and women followed up for 176,000 patient-years [Kanis et al, 2004].

People 65 years of age or more, or less than 65 years of age with a previous fragility fracture

• Increasing age and a previous fragility fracture are both associated with an increased risk of fracture, which is independent of low BMD. Therefore, all older people and those younger people with a history of fragility fracture should be considered to be at high risk of fracture (regardless of their T-score), and should be started on treatment to prevent corticosteroid-induced osteoporosis. For more information on the risk of fracture with increasing age or a history of previous fragility fracture, see the CKS topic on Osteoporosis - treatment.

People less than 65 years of age without a previous fragility fracture

• People less than 65 years of age without a fragility fracture are at a lower risk of fracture, and require a DXA scan to assess BMD before starting drug treatment to prevent corticosteroid-induced osteoporosis.

These recommendations are based on the Royal College of Physicians guideline, Glucocorticoid-induced osteoporosis [RCP, 2002].

Lifestyle advice

• These recommendations are pragmatic and have been extrapolated from trials showing that immobility, smoking, and alcohol consumption (more than 2 units per day) are associated with an increased risk of fracture in postmenopausal women with osteoporosis.

Stopping or reducing the dose, duration, and frequency of corticosteroids

• There is some trial evidence that the effects of corticosteroids on bone mineral density (BMD) are at least partially reversible on stopping treatment.
• There is a dose-dependent relationship between corticosteroid use and fracture risk. However, the increased risk of vertebral fractures, even for doses of prednisolone between 2.5 mg and 7.5 mg per day, indicates that there is no 'safe dose' of oral corticosteroids.
• Treatment with corticosteroids for periods as short as 3 months may result in increased fracture risk. Studies conducted in people taking corticosteroids for at least 6 months have shown bone loss to be greatest in the first few months after starting treatment (for example, as high as 30% in the first 6 months).
• Evidence that bone loss is related to the cumulative dose of corticosteroids provides a strong rationale for considering preventive measures in individuals receiving intermittent courses of oral prednisolone over longer periods of time.
• More than three or four courses of corticosteroids taken in the previous 12 months is considered to be equivalent to more than 3 months of continuous treatment. If the intermittent courses are spread over a much longer term, then this is not regarded as such an important risk factor [Francis, Personal Communication, 2006].

BMD and risk of fracture

• Osteoporosis prophylaxis is recommended if the T-score is –1.5 or less, based on the evidence that fractures occur at a higher BMD in corticosteroid-induced osteoporosis than in postmenopausal osteoporosis.

Referring men and premenopausal women

• All men and premenopausal women should be investigated for secondary causes of osteoporosis (for example hypogonadism) if they are found to have osteoporosis; this is usually done by a specialist.
• See the CKS topic on Osteoporosis - treatment for more information on secondary causes of osteoporosis.

These recommendations are based on the Royal College of Physicians guideline, Glucocorticoid-induced osteoporosis [RCP, 2002].

Bisphosphonates

• The evidence on bisphosphonates for the prevention and treatment of corticosteroid-induced osteoporosis is less robust than for postmenopausal osteoporosis. The RCP summarized the evidence on treatments for corticosteroid-induced osteoporosis and concluded that the efficacy of bisphosphonates varies, but beneficial effects on bone mineral density (BMD) in the spine and hip have been demonstrated. Fracture was not a primary endpoint of any study, but a reduction in vertebral fracture was observed in post-hoc or safety analyses of trials of etidronate, alendronate, and risedronate.

Calcium and vitamin D

• The RCP summarized the evidence on calcium and vitamin D supplements in corticosteroid-induced osteoporosis and concluded that calcium plus vitamin D supplementation improves spine and proximal femur BMD, but the evidence is inconsistent. The effect on vertebral fracture risk has not been adequately assessed.

Vitamin D analogues (alfacalcidol and calcitriol)

• If a bisphosphonate is contraindicated or is not tolerated, the person may be started on alfacalcidol or calcitriol. CKS considers that since these drugs are rarely prescribed in primary care, advice should be sought from a specialist.
• The RCP summarized the evidence on vitamin D analogues and concluded that it is inconsistent regarding effects on BMD and fracture. A later meta-analysis of 54 trials indicated that vitamin D₃ analogues are more effective than no treatment, placebo, plain vitamin D₃, and/or calcium at decreasing the risk of vertebral fractures [de Nijs et al, 2004]. Bisphosphonates, however, are more effective than vitamin D₃ analogues at preserving bone density and decreasing the risk of vertebral fractures.

Zoledronic acid

• Zoledronic acid has recently been licensed for the treatment of steroid-induced osteoporosis [ABPI Medicines Compendium, 2009]. Since it is a once-yearly infusion, it could be considered in people with problems with delayed oesophageal emptying, people who are unable to sit or stand upright for 30 minutes after taking a bisphosphonate, or those with active or recent gastrointestinal problems. However, since it is an infusion, it can only be given in secondary care.

Monitoring calcium levels

• The advice to check serum calcium levels if hypocalcaemia or hypercalcaemia is suspected before or during treatment reflects advice in the summaries of product characteristics for bisphosphonates and preparations containing calcium and vitamin D [ABPI Medicines Compendium, 2005; ABPI Medicines Compendium, 2008].