Manage Patients on Glucocorticoids Differently

Bisphosphonates do appear to improve bone density in these patients. In another study, researchers demonstrated that daily alendronate increases bone density in patients who receive glucocorticoid therapy, compared with those on placebo (N. Engl. J. Med. 1998;339:292–9). Similar results have been demonstrated with etidronate, risedronate, and zoledronic acid.

Dr. Sambrook recommended that the patient receive calcium and vitamin D supplementation. Also, “we would primarily give her bisphosphonates until prednisone is discontinued” and possibly beyond, depending on her overall fracture risk after prednisone treatment. It's also important to think about trying to minimize the dose of prednisone.

The woman returned for x-ray of the spine 2 years later. Her bone density was stable, although she had developed mild esophageal symptoms. On endoscopy, these were attributed to esophagitis. She was still taking low-dose prednisone, so she was switched to a different bisphosphonate.

Patient No. 2

A 24-year-old woman has had systemic lupus erythematosus for 3 years, and the disease has become severe over that time. Her SLE complications have included encephalitis, vasculitis, renal involvement, and deep vein thrombosis. She had no family history of osteoporosis. She did not consume much dietary calcium, although she claimed to get adequate sun exposure. She had been on an oral contraceptive since the age of 17. Her appetite and weight were average and stable.

At the time of her presentation, she had been on prednisone for 6 months, with dosages averaging 25–50 mg daily. However, the recent onset of renal complications required increasing the dose to 75 mg daily. She was also taking an antimalaria drug. Her vitamin D level was equivocal and needed to be addressed. She had normal calcium and PTH levels and normal thyroid function. However, her spine T score was −1.4 and her hip T score was −1.0.

The concern to Dr. Sambrook was the effect of bisphosphonates on the fetal development. Although the patient was not pregnant at the start of therapy, she might have become so intentionally or unintentionally. Bisphosphonates are classified as pregnancy category C drugs by the U.S. Food and Drug Administration, meaning that they are contraindicated in pregnancy.

“The reports that have been published so far have generally not identified any developmental or bone density abnormalities,” in association with prenatal exposure to bisphosphonates, Dr. Sambrook noted. Some reports have identified lower birth weight, lower gestational age at birth, and higher rates of spontaneous abortion with exposure to bisphosphonates.

“These have to be interpreted in context. These women are already ill—otherwise they wouldn't be on steroids—and that's going to affect those types of outcomes,” he cautioned.

In animal studies, in which pregnant animals have been subjected to 10 times the recommended human bisphosphonate dose, maternal toxicity, growth retardation, and fetal loss have been reported. “But these are very high doses. What do we see in real life?” Dr. Sambrook asked.

In a study from Canada published this year, researchers followed 21 women who were exposed to bisphosphonates either during or less than 3 months before pregnancy, and then compared them with matched control women. Outcomes were similar between the two groups, suggesting that preconceptional and first-trimester use of bisphosphonates may not pose substantial fetal risks (Bone 2009;44:428–30).

“These data are fairly reassuring in terms of the safety in patients treated prior to becoming pregnant or … if they become pregnant while on bisphosphonates,” he said. However, bisphosphonates should be stopped as soon as it's known that a patient is pregnant, if not prior to her becoming pregnant.

One approach to managing this patient is to simply watch her and measure BMD in 12 months. Another is to use a bisphosphonate in conjunction with vitamin D and calcium supplementation. Risedronate might be the better choice, given its quicker onset and offset of action, he said.

“As long as she stayed on prednisone, I might not be as aggressive as with postmenopausal women,” Dr. Sambrook noted. If the prednisone dose was decreased, he said that he might consider stopping bisphosphonate treatment.

Dr. Lane and Dr. Sambrook both reported significant financial relationships with several pharmaceutical companies.

Dual-energy x-ray absorptiometry provides “areal” BMD (g/cm

Source ©Elsevier