CHICAGO — Fracture risk increases in arthritis patients within about 3 months of starting corticosteroids and remains high, according to Dr. Nelson Watts.
“How much of this is steroids and how much of this is the underlying disease is unanswered,” said Dr. Watts, director of the bone health and osteoporosis center at the University of Cincinnati.
Glucocorticoid-induced osteoporosis results from a variety of systemic effects of corticosteroids, but it's the combination of reduced bone formation and increased bone resorption that causes a “double whammy” for patients—a troubling aspect for rheumatologists, who regularly dispense corticosteroids for their patients, Dr. Watts said at a symposium sponsored by the American College of Rheumatology.
The exact dose at which corticosteroids increase fracture risk is also difficult to tease out because of the underlying disease. One study observed that fracture risk was dose dependent and significantly higher with 2.5 mg/day or more of oral prednisone, with increases of 61% in hip and 160% in vertebral fractures (J. Bone Miner. Res. 2000;15:993-1000).
“It may well be that people who need 2.5 [mg]/day of prednisone are at increased risk for fracture not because of prednisone, but because of their rheumatoid arthritis; … clearly, as the dose goes up, the risk increases,” he said.
The American College of Rheumatology just began the process of revising its 2001 guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis. The current guidelines highlight lifestyle modifications, such as calcium and vitamin D supplementation, weight-bearing exercise, and minimization of alcohol intake.
There is at least one supportive trial for virtually all therapies, but several intervention trials have produced conflicting results for some agents, according to a recent review of glucocorticoids and the risk of osteoporosis (Expert Opin. Drug Saf. 2009;8:33-47).
The value of calcium and vitamin D supplementation is unclear, Dr. Watts said. In a relatively small trial in 96 RA patients on prednisone, daily supplementation with 500 IU of vitamin D and 1,000 mg of calcium carbonate per day significantly improved bone mineral density, at a rate of 0.72% in the lumbar spine and 0.85% in the trochanter per year, compared with losses of 2% and 0.9%, respectively, among patients on placebo (Ann. Intern. Med. 1996;125:961-8).
In four prospective studies in 173 patients who recently started corticosteroid therapy, however, bone loss occurred at a rate of 3%-5% per year, despite daily supplementation with 500-800 mg of calcium.
Two other studies that Dr. Watts highlighted reported no bone loss in patients who were given up to 1,000 mg per day of calcium and up to 500 IU per day of vitamin D, although he noted that these patients had been on corticosteroid therapy for at least 1 year and in most cases almost 5 years.
“It's not clear to me how much of a role vitamin D and calcium will play in preventing bone loss,” he said.
Studies show that the risk for spinal fracture falls within a year or two of stopping therapy, although hip fracture risk remains increased over baseline.
Dr. Watts disclosed that he has relationships with Amgen Inc., Eli Lilly & Co., Procter & Gamble Co., Sanofi-Aventis, Novo Nordisk Inc., and Novartis Pharmaceuticals Corp., which manufactures Reclast.
http://www.rheumatologynews.com/article/S1541-9800(09)70110-3/fulltext