Patients who receive intravenous (IV) pulsed doses of methylprednisolone have significant bone loss after 6 months of treatment, according to a study in the September issue of Annals of Rheumatic Diseases.

The findings challenge conventional wisdom, which holds that the short exposure time associated with pulsed IV methylprednisolone would not lead to significant bone loss. "Our study…demonstrated that intravenous pulse treatment…as currently used in the treatment of patients with various rheumatological disorders, leads to a high rate of bone loss," wrote researchers at the Leeds Teaching Hospital Trust in Leeds, United Kingdom. "However…this bone loss…is arrested by the concomitant use of antiresorptive osteoporosis treatment with [hormone replacement therapy] or bisphosphonates."

Senior Investigator Paul Emery, MD, an ARC Professor of Rheumatology at the Leeds Teaching Hospital Trust, told CIAOMed that physicians need to know that patients requiring corticosteroid treatment should be informed that "significant bone loss occurs with IV pulse steroids and that active intervention is required. We will continue to investigate all patients with secondary osteoporosis."

In a study of 38 patients, 30 of them women, the Leeds researchers found that femoral neck and total hip bone mineral density (BMD) had decreased by an average of 2.2% and 1.1%, respectively, after the six-month treatment period with the IV pulsed methylprednisolone. In addition, the spine BMD was reduced by approximately 1% at disks L2-4.

Interestingly, Dr. Emery and colleagues noted that among patients treated with either bisphosphonates or estrogen, the femoral neck BMD increased by an average of 1.6%; the total hip BMD rose by slightly more than 3%; and the targeted disks of the spine showed a BMD increase averaging 4.5%. In patients who did not receive antiresorptive therapy and who were given oral prednisolone, the femoral neck BMD decreased an average of 4.4%; the total hip BMD declined by about 2.4%; and the targeted spine disks decreased by about 2%. For those who did not receive either antiresorptive therapy or concomitant oral corticosteroids, BMD losses averaged 1.7% at the femoral neck, 1.9% at the total hip, and 2.6% at the targeted vertebral disks.

To determine whether IV pulsed methylprednisolone affected bone mass, the investigators recruited 38 patients who required this treatment for various rheumatic disorders. They assessed the patients at baseline and after 6 months of treatment. At those assessment periods, the patients underwent dual energy x-ray absorptiometry (DXA) measurement of BMD at the hip and lumbar spine.

The patients averaged 48.4 years of age, with an average body mass index of 24.9. Their median disease duration was 3.2 years, with a range of 0.1 to 40 years. During the study period, the patients received an average cumulative methylprednisolone dose of 3 g, which was given as an average of 5.7 pulses over a median period of 5.7 months, with the treatment period ranging from 2.3 to 33.7 months. In addition, 34 of the patients (89%) also received pulses of cyclophosphamide. Among these patients, 20 (53%) were taking oral corticosteroids, and 8 (21%) received either a bisphosphonate or estrogen.

These study findings show that corticosteroid treatment with IV pulses of methylprednisolone "leads to a high rate of bone loss that cannot be ignored," the authors wrote. Optimistically, though, preventive treatment with either bisphosphonates or estrogen is effective. "Prevention of bone loss in [such] patients…should be considered," they wrote, adding that "this is especially important in patients with low BMD, high disease activity, and other risk factors for osteoporosis."

Reference

Haugeberg G, Griffiths B, Sokoll KB, Emery P. Bone loss in patients treated with pulses of methylprednisolone is not negligible: a short term prospective observational study. Ann Rheum Dis. 2004;63:940-944.