Bisphosphonates in the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis

Although the relationship of BMD to fracture risk is well documented in postmenopausal osteoporosis, the correlation is not as well established in glucocorticoid-induced bone loss.^2,60 The present data suggest a trend in the reduction of fracture risk observed with the use of bisphosphonates in the treatment of glucocorticoid-induced osteoporosis. This information is promising but requires definitive confirmation in larger trials. Because of the prolonged skeletal retention of bisphosphonates, more extended trials are also needed to clearly establish the safety of long-term therapy in younger patients.

Recommendations for clinical practice

All patients beginning high-dose (Ž7.5 mg/day prednisone) long-term (>6 months) glucocorticoid therapy should be evaluated for pharmacologic prophylaxis against osteoporosis. Because the majority of bone loss occurs within the first 6 months of therapy, clinicians must vigilantly develop a preventative plan in advance, preferably before the glucocorticoid prescription is given to the patient. Current guidelines recommend a baseline BMD measurement of all patients with DEXA to determine the risk of osteoporosis and the monitor the efficacy of the chosen preventative measures throughout the course of therapy. Initial BMD measurements expressed as a T score are essential tools for constructing an individualized strategy. Critical T scores of less than or equal to 1.0 are indicative of high-risk patients.¹⁸ In addition to the risk imposed on patients secondary to their underlying disease state, other patients with strong predictive factors include those who are elderly and at greater risk of falling and those who have a previous history of fractures.

BMD measurements may be repeated in 6 to 12 months, depending on initial bone mass. If BMD has decreased by more than 5% from baseline, the initial choice of therapy should be changed or expanded.^18,61

Both glucocorticoid doses and the length of therapy require continuous reevaluation to decrease the total cumulative dose. If possible, dose maximization of inhaled and topical corticosteroids is recommended before progression to the oral form. More obvious preventive lifestyle modifications include smoking cessation, maintenance of healthy body weight, regular weight-bearing exercise, decreased alcohol consumption, sodium restriction, and increased dietary calcium intake. Most patients will require additional calcium supplementation to meet the ACR recommendation of 1500 mg per day, and patients at risk for vitamin D deficiency may also require supplementation.¹⁸

However, even with appropriate supplementation 1 in 6 corticosteroid-treated patients will experience a radiographically detected vertebral fracture within 12 months.^46,47,54 Therefore, alternative treatment regimens are needed. Bisphosphonate therapy looks promising in the prevention and treatment of CIO with respect to positively affecting BMD. As a result of this encouraging data, alendronate and risedronate have received FDA approval for the indication of CIO. However, it remains to be seen whether the use of these agents can lead to a reduction in fractures, both vertebral and nonvertebral. Subpopulations at highest risk (postmenopausal women and men) may benefit most with regard to fracture risk reduction, but more data are needed before bisphosphonates should be routinely recommended as first-line preventive therapy. Once osteoporosis is established (regardless of the pathogenesis), treatment should be aggressive to prevent further loss of bone density. In this population bisphosphonates are an appropriate therapeutic option, and further data will clarify their impact on the risk of fractures.