UTRECHT, The Netherlands, Aug. 17 — Fosamax (alendronate) proved more effective than a vitamin D3 analogue in preventing glucocorticoid-induced bone loss in patients treated for rheumatic diseases, according to researchers here.
An 18-month study found a 4% difference in bone-mineral density of the lumbar spine favoring Fosamax (alendronate) over alfacalcidol, a vitamin D3 analogue, Ron de Nijs of University Medical Center Utrecht, and colleagues, reported in the Aug. 17 issue of the New England Journal of Medicine.
Active vitamin D3 analogues, such as alfacalcidol, stimulate the formation and action of osteoblasts, whereas bisphosphonates, such as Fosamax, induce apoptosis of osteoclasts and inhibit bone resorption, the researchers wrote.
In the randomized double-placebo, double-blind trial, 201 patients with rheumatic diseases started glucocorticoid therapy at a daily dose equivalent to at least 7.5 mg of prednisone. The mean cumulative glucocorticoid doses during the study were 5,790 mg ?± 3,663 mg in the Fosamax group and 5,704 mg ?± 3375 mg in the alfacalcidol group, a difference of 86 mg.
One third of the patients had rheumatoid arthritis, one third had polymyalgia, while the rest had another rheumatic disease, the researchers said.
Patients from 23 outpatient clinics in the Netherlands were randomized to 10 mg of Fosamax and a placebo capsule of alfacalcidol daily or alfacalcidol (1??g) and a placebo tablet of Fosamax daily.
At 18 months, the bone-mineral density of the lumbar spine increased by 2.1% in the Fosamax group (95% confidence interval, 1.1% to 3.1%) but decreased by 1.9% in the alfacalcidol group (CI, -3.1% to -0.7 %). The mean difference of change in bone mineral density between the two groups was 4.0% (CI, 2.4% to 5.5%), the researchers reported.
Changes in bone mineral density at other sites — femoral neck, total hip — were similar. For example, density at the femoral neck increased 1.4% in the Fosamax group and decreased 2.0% in the alfacalcidol group, for an absolute difference of 3.4% (CI, 1.3% to 5.5%), the researchers reported.
Although there were more new vertebral deformities in the alfacalcidol group compared with the Fosamax patients, the difference was not significant, the researcher said.
Three Fosamax patients had a new vertebral deformity, compared with eight alfacalcidol patients with 13 new deformities, of which five were symptomatic in three patients (hazard ratio, 0.4; CI, 0.1 to 1.4).
Further, two Fosamax patients had actual fractures, one in the midfoot and another of the forearm. In the alfacalcidol group, the three fractures included one of the femoral neck, one of the pubic bone, and one of a rib, the researchers reported.
There were few side effects for either treatment, the researchers wrote. Adverse event for the Fosamax group included hypercalcemia in three patients versus seven in the alfacalcidol group. In one Fosamax patient, calcium supplementation was stopped because of hypercalcemia, but no reduction in the dose of alfacalcidol was necessary because serum calcium became normal. There was no report of thyroid or renal dysfunction during the study.
Because of logistic difficulties, the researcher said they were not able to measure 24-hour urinary calcium, although hypercalciuria is often found in patients receiving active vitamin D3 metabolites. Therefore, they suggested, that in addition to measuring serum calcium levels, urinary calcium monitoring may be necessary for safety reasons in patients receiving vitamin D3.
According to the investigators, Merck provided matched Fosamax and placebo tablets. Teva Pharmaceuticals provided matched alfacalcidol and placebo capsules. Dr. de Nijs reported having received grant support from the Dutch Health Care Insurance Board, while other investigators reported consulting or lecture fees from Eli Lilly, Merck, Procter & Gamble; Chiron Vaccines, Baxter, Organon, Janssen-Cilag, Wyeth, Abbott, Novartis, Roche, Sanofi-Aventis, and Schering-Plough.
Primary source: New England Journal of Medicine
de Nijs, RNJ, et al “Alendronate or Alfacalcidol in Glucocorticoid-Induced Osteoporosis” N Engl J Med 2006; 355:675-684.