DENVER — People on long-term glucocorticoids have a significant risk for fracture at relatively high bone mineral density T scores. As a result, physicians need to rethink their management of this population.
“In glucocorticoid osteoporosis, the fracture risk seems to take off quite dramatically somewhere around T scores of −1.5,” Dr. Philip Sambrook said during a clinical roundtable session on glucocorticoid-induced osteoporosis at the annual meeting of the American Society for Bone and Mineral Research. “Most of the guidelines around the world are now suggesting that the intervention threshold [for those on glucocorticoids] should be [a T score of] about −1.5.”
Patients on glucocorticoids typically have midline fractures of the vertebrae, where the bone just collapses in the middle of the vertebra.
“This is different from the anterior wedge fracture that occurs most commonly in postmenopausal women with osteoporosis,” noted Dr. Nancy Lane, who also participated in the roundtable session. This is because there are some differences in how bones become fragile in the presence of glucocorticoids. “A number of studies have shown that patients on glucocorticoids, for the most part, tend to fracture at bone densities that are greater than [those of] postmenopausal women with osteoporosis.”
Dr. Lane and her colleagues have followed bone density in mice that were exposed to moderate doses of glucocorticoids. They found that most of the bone loss occurred very quickly. At roughly a month (28 days), there was a 20% loss in trabecular vertebral bone mineral density (BMD) as measured by quantitative CT, a 3-D means of assessing bone volume. However, during days 28–56 there was little additional loss of bone mass. “Upon giving the mice glucocorticoids, we found that bone resorption went up very quickly,” said Dr. Lane, who is the director of the center for healthy aging at the University of California, Davis. By day 7, there was nearly a doubling in bone turnover as measured by CTx, a C-terminal telopeptide of type I collagen, which is a serum marker of bone resorption.
In addition, they found very little change in serum levels of osteocalcin (a biomarker of bone formation) for the first 7 days. Osteocalcin levels then began to decline. “It looks like glucocorticoids also change osteocyte gene expression,” she said.
Thus, with glucocorticoids, bone formation goes down and bone resorption goes up. “I always say that bone doesn't have a chance in the presence of glucocorticoids,” said Dr. Lane.
Dr. Sambrook, who heads the bone and joint group at the Kolling Institute of Medical Research of Royal North Shore Hospital in Sydney, presented cases that “really illustrate the type of patients that we often struggle with.”
Patient No. 1
A 66-year-old woman was recently diagnosed with polymyalgia rheumatica. She had been started on 25 mg/day prednisone and the disease activity lessened in response. Her history included chronic atopic dermatitis and hypothyroidism. She had no other medical problems. There was no family history of hip fracture. She did not smoke or drink. She had a slightly early menopause but had not used hormone therapy. She reported consuming one or two servings of dairy products daily. She also considered herself to be physically active, although she had no formal exercise program.
As part of her work-up, she had a spine x-ray, which showed a vertebral deformity (compression). BMD measurements showed modest osteopenia (T scores of −1.5 at the spine and −1.6 at the hip). She had normal levels of calcium and parathyroid hormone (PTH). Her vitamin D level was equivocal, however. Her thyroid function was normal.
This patient had modest osteopenia at the time of her diagnosis. Once she was started on glucocorticoids, her T scores could have fallen rapidly and then stabilized over time, without treatment for bone loss, said Dr. Sambrook. “As she becomes established on glucocorticoids, she will perhaps not lose that much bone,” but she's at risk of fracture.
So, when clinical trial data are interpreted, it's important to keep two clinical scenarios in mind: prevention (when initial rapid loss of bone is to be avoided) and treatment (when the patient is on chronic glucocorticoids and may not be losing a lot of bone but is still at risk for fracture).
“Most of us would believe that vitamin D [plus] calcium is an adjunctive therapy,” said Dr. Sambrook. The data appear to back that up. In a 1996 trial, patients with glucocorticoid osteoporosis were randomized to 50,000 U/week of vitamin D plus 1,000 mg/day of calcium, or placebo. Both groups lost bone at the spine quite rapidly, although there was a trend for patients on vitamin D and calcium to do slightly better (J. Rheumatol. 1996;23:995–1000).