June 7, 2000 -- People with asthma are frequently prescribed oral steroids, but a new study suggests that even three months of relatively low dose treatment can increase the risk of fracture by 70% -- a much faster rate of "bone-wasting" than experts previously predicted.
The good news, however, is that the study also suggests that when the drugs are stopped, the risk decreases with similar speed. This quickness is very surprising, C. Conrad Johnston, MD, an expert on osteoporosis, tells WebMD. Johnston, who is a professor of medicine at Indiana University School of Medicine in Indianapolis, was not associated with the study.
The drugs associated with this increased risk -- oral corticosteroids -- are prescribed for a number of inflammatory conditions, such as asthma, joint disorders, and inflammatory bowel disorder. Johnston says that the link between steroid use and fracture has been known for many years, but most experts believed that the adverse effect was not evident until after prolonged use. This new finding questions that belief, he says.
The researchers analyzed medical records from nearly 250,000 people who were taking oral steroids to the same number of healthy non-users who were the same age and sex. The team of researchers from England, Canada, and the Netherlands followed the users of oral steroids for the entire time they were taking the drugs and for about three months after they received their last prescriptions.
In the study, which was published in the Journal of Bone and Mineral Research, the researchers report that the steroid users had 20 fractures for every 1,000 people per year, compared to 13 fractures for every 1,000 people for the control group.
There are other factors that can increase fracture risk, such as illness or other drugs, but the researchers write that even after accounting for those other risks, the rate of fractures "was significantly higher among oral corticosteroid users." They also found that when the dose of the oral steroid was increased, the fracture rate also increased.
The results of this study suggest that when a physician prescribes an oral steroid he or she should also prescribe a bisphosphonate such as Fosamax , which is used for treatment of osteoporosis, says Stavros C. Manolagas, MD, PhD, professor of medicine and director of the center for osteoporosis and metabolic bone disease at the University of Arkansas. Bisphosphonates have been shown to help counteract the loss of bone mineral density that is associated with steroids, he says. "It makes perfect sense to start [bisphosphonates] immediately; there is no reason to wait for months," Manolagas says.
However, Johnston says the jury is still out on the need to prescribe bisphosphonates for everyone taking steroids because "everybody doesn't get fractures."
The authors of the study, as well as Johnston and Manolagas, say the most puzzling aspect of the new finding is the speed at which the fracture risk increases. Manolagas tells WebMD that three months is too short a time for bone mineral density to significantly decrease. In his editorial, he suggests that the steroids may kill osteocytes, the most common type of bone cells. This cell death, called apoptosis, may increase the fracture risk, he says.
Johnston says that Manolagas may be on the right track but he says he doubts that the cell death theory can explain "the finding that fracture risk can change so quickly." He says the answer may lie not in total bone mineral density loss but "in where you lose it and the site at which it is replaced."
- Just three month's worth of oral steroids, which are commonly prescribed to patients with asthma and disorders of the joints and bowels, increased chances of sustaining fractures by 70%. The large European study shows these fractures can happen much faster than experts have expected.
- When the oral steroids are stopped, the risk decreases at a similarly rapid rate.
- Observers note treatment for osteoporosis should be included with oral steroid therapy, but they don't agree when bone protection should begin, since not everyone gets fractures. Doctors also are unsure of why the risk of fracture increases so quickly.