Building Bones on Prednisone

ABSTRACT & COMMENTARY

Synopsis: Among patients on prednisone therapy for rheumatoid arthritis, those receiving a daily regimen of calcium carbonate plus vitamin D3 gained bone mineral density in the lumbar spine and trochanter, while those receiving a placebo lost bone mineral density.

Source: Buckley LM, et al. Ann Intern Med 1996;125: 961-968.

Buckley et al randomized 130 patients with rheumatoid arthritis, three-fourths of whom were women, in a double-blind trial to receive either placebo or calcium carbonate (1000 mg/d) plus vitamin D3 (500 IU/d), in the form of Os-Cal 250 D (2 tablets twice a day). During the two years of follow-up, about two-thirds of the patients were on chronic prednisone therapy. At baseline and annually thereafter, study subjects were asked about smoking history, use of alcohol, menstrual history, parity, fracture history, medication use (including thyroid medication and estrogen replacement therapy), calcium intake (assessed using the Food Frequency Questionnaire and 3-day dietary history), activity level (measured by the Framingham Activity Index), and disease severity (determined by the Health Assessment questionnaire). They were also given a severity score, based on radiologic findings. Bone mineral densities of the femur (femoral neck, Ward triangle, and trochanter) and lumbar spine were measured at baseline and each year using dual-energy x-ray absorptiometry.

During the two-year follow-up period, 29 (22%) of the original 130 subjects dropped out of the study (15 in the treatment group and 14 in the placebo group)—14 for personal reasons, one because of death, three due to serious illness (inflammatory bowel disease, cancer, and amyotrophic lateral sclerosis), and 11 because of gastrointestinal toxicity. Of the seven patients in the treated group who dropped out because of gastrointestinal toxicity, six had indigestion and one had constipation. Pill counts performed every six months indicated that more than 90% of the patients took at least 80% of the medication. Those in the treatment group showed an average increase in bone mineral density in the lumbar spine of 0.63% per year, and those in the placebo group showed an average annual decrease of 1.31%, for a difference of 2.65% per year. Similarly, those in the related group had an average increase in bone mineral density in the trochanter of 0.85%, and those in the placebo group lost 0.9% annually, for a difference of 2.08% per year. These differences were not seen among the patients who were not on prednisone and who served in control groups, receiving either calcium plus vitamin D3 or placebo.

COMMENT BY RICHARD G ROBERTS, MD, JD

Chronic low-dose steroid therapy is associated with a loss of bone mineral density and a higher rate of fracture in lumbar vertebrae. A variety of approaches have been tried to prevent osteoporosis due to steroids. Calcitonin, estrogen, biphosphonates, and potent vitamin D analogues appear to be effective, but cost and side effects limit their utility. Calcium carbonate and vitamin D3 supplementation has the advantage of being nonprescription, relatively inexpensive, and well tolerated. This study found that such supplementation did increase lumbar and trochanter bone mineral density for patients on chronic steroids, while those on placebo lost bone density.

The authors point out several limitations in their study. The durability of the benefits of supplementation beyond two years is uncertain. The beneficial effects of supplementation are unknown for those taking more than 10 mg/d of prednisone. Because the imaging technique was changed partway through the study, half of the baseline values of bone mineral density of the anteroposterior spine were imputed from the baseline measurements of bone mineral density of the lateral spine, thus raising the possibility of measurement error. Most importantly, the outcomes that were measured (i.e., bone mineral density) were only intermediate outcomes; the effect of supplementation on outcomes of greatest importance to patients (e.g., fracture rates) is not answered by this study. Exercise, smoking cessation, adequate calcium and vitamin D intake, and, where appropriate, estrogen replacement therapy remain the mainstays of osteoporosis prevention. Whether additional calcium and vitamin D supplementation will decrease fracture rates on high-risk patients, such as those on chronic prednisone therapy, remains to be determined.