How to prevent glucocorticoid-induced osteoporosis
ABSTRACTWhen prescribing glucocorticoids for long-term treatment, physicians should take steps to prevent osteoporosis, a common and serious side effect of these drugs.
KEY POINTS
- Glucocorticoids have both direct and indirect effects on bone cells, and they both suppress bone formation and promote resorption.
- Patients who need glucocorticoids should receive the lowest effective dose for the shortest possible time. They should also be advised to undertake general health measures, including stopping smoking, reducing alcohol intake, exercising daily, and taking in adequate amounts of calcium and vitamin D.
- Bisphosphonates and teriparatide (Forteo) are approved for treating glucocorticoid-induced osteoporosis, but adherence to guidelines for managing this condition is far from optimal.
INHALED STEROIDS IN HIGH DOSES MAY ALSO INCREASE RISK
Although inhaled glucocorticoids are generally believed not to affect bone, some evidence suggests that in high doses (> 2,000 μg/day) they may result in significant osteoporosis over several years.14,15
In a retrospective cohort study, van Staa et al15 compared the risk of fracture in 171,000 patients taking the inhaled glucocorticoids fluticasone (Flovent), budesonide (Pulmicort), or beclomethasone (Beconase); 109,000 patients taking inhaled nonglucocorticoid bronchodilators; and 171,000 controls not using inhalers. They found no differences between the inhaled glucocorticoid and nonglucocorticoid bronchodilator groups in the risk of nonvertebral fracture. Users of inhaled glucocorticoids had a higher risk of fracture, particularly of the hip and spine, than did controls, but this may have been related more to the severity of the underlying respiratory disease than to the inhaled glucocorticoids.
Weldon et al16 suggested preventive measures to prevent glucocorticoid-induced effects on bone metabolism when prescribing inhaled glucocorticoids to children. They stated that prophylaxis against osteoporosis requires suspicion, assessment of bone density, supplemental calcium and vitamin D, and, if indicated, bisphosphonates to prevent bone fractures that could compromise the patient’s quality of life.
PREVENTING AND TREATING BONE LOSS DUE TO GLUCOCORTICOIDS
Effective options are available to prevent the deleterious effects of glucocorticoids on bone.
A plethora of guidelines offer direction on how to reduce fracture risk—ie, how to maintain bone mineral density while preventing additional bone loss, alleviating pain associated with existing fractures, maintaining and increasing muscle strength, and initiating lifestyle changes as needed.17,18 Guidelines from the American College of Rheumatology (ACR),17 published in 2001, are being updated. United Kingdom (UK) guidelines,18 published in December 2002, differ slightly from those of the ACR.
Limit exposure to glucocorticoids
Oral glucocorticoids should be given in the lowest effective dose for the shortest possible time. However, there is no safe oral glucocorticoid dose with respect to bone. Alternate-day dosing suppresses the adrenal axis less but has the same effect as daily dosing with regard to bone.
Recommend lifestyle measures from day 1
All guidelines recommend that as soon as a patient is prescribed a glucocorticoid, the clinician should prescribe certain preventive measures, including:
- Smoking cessation
- Weight-bearing and strength-building exercises
- Calcium intake of 1,000 to 1,500 mg per day
- Vitamin D 800 to 1,000 IU per day.
Calcium and vitamin D for all
The Cochrane Database of Systematic Reviews19 evaluated the data supporting the recommendation to use calcium and vitamin D as preventive therapy in patients receiving glucocorticoids. Five trials with 274 patients were included in the meta-analysis. At 2 years after starting calcium and vitamin D, there was a significant weighted mean difference of 2.6% (95% confidence interval [CI] 0.7–4.5) between the treatment and control groups in lumbar spine bone mineral density.
The authors concluded that because calcium and vitamin D have low toxicity and are inexpensive, all patients starting glucocorticoids should also take a calcium and a vitamin D supplement prophylactically.
Bisphosphonates are effective and recommended
The ACR17 and UK18 guidelines said that bisphosphonates are effective for preventing and treating bone loss in patients receiving glucocorticoids.
More recently, Stoch et al20 evaluated the efficacy and safety of alendronate (Fosamax) 70 mg weekly for preventing and treating bone loss in patients on glucocorticoid therapy. At 12 months, bone mineral density in the lumbar spine, trochanter, and total hip had increased from baseline in the alendronate group and was significantly higher than in the placebo group. At the same time, levels of biochemical markers of bone remodeling were significantly lower than at baseline in the alendronate group.
For premenopausal women, postmenopausal women on estrogen replacement therapy, and men, the ACR17 recommends risedronate (Actonel) 5 mg per day or alendronate 5 mg per day; for postmenopausal women not on estrogen, risedronate 5 mg per day or alendronate 10 mg per day is recommended.
