Reported fracture rates in ankylosing spondylitis have more than doubled since 2000
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Key takeaways:
- Reported fracture rates have increased in both the general population and in patients with ankylosing spondylitis since 2000, despite the introduction of TNF inhibitors.
- The increased fractures could be a result of enhanced detection, or more accurate documentation.
The introduction of TNF inhibitors in 2003 has failed to stop fracture rates in patients with ankylosing spondylitis from more than doubling from 2000 to 2020, according to data published in Arthritis Care & Research.
“Despite some studies suggesting improved bone density with TNF inhibitor use among patients with AS, no large-scale studies have assessed the effect of TNF inhibitors on fracture risk in this population,” Sali Merjanah, MD, of Boston University, lead author of the study, told Healio. “We therefore studied the trends in the incidence rates of fractures among those with AS in time periods before and after the introduction of TNF inhibitors for the treatment of AS, using an interrupted time series analysis.”
To investigate the prevalence of fractures in patients with AS, compared with those without AS, both prior to and after the introduction of TNF inhibitors, Merjanah and colleagues analyzed data from the national U.S. Department of Veterans Affairs database. Patients were included in the analysis if they were aged 18 years or older and had at least one ICD-9 or -10 diagnostic code for AS, as well as at least one prescription for a disease-modifying antirheumatic drug. Meanwhile, an age-matched comparator group was drawn from a random sample of adults without AS.
The main outcome was the occurrence of any fracture in the patients’ femur, radius or vertebra. For patients with AS, follow-up began with disease diagnosis, while comparator follow-up began when individuals met age and VA health care requirements. All participants were followed until they experienced a fracture, reached the age of 90 years, died or left the VA health care system. The study ended in December 2020.
The analysis included 3,794 patients with AS and 1,152,805 comparator individuals. Among patients with AS, the rate of fractures per 1,000 patient-years increased from 7.9 in 2000 to 21.6 in 2020, according to the researchers. The rate also increased among the comparator population, with the ratio comparing those with and without AS remaining stable.
Meanwhile, in the interrupted time series analysis, the fracture rate among patients with AS increased, albeit non-significantly, in the years following the introduction of TNF inhibitors, compared with the pre-TNF inhibitor period.
“In this study, fracture rates increased over the past 2 decades for both individuals with AS and non-AS comparators,” Merjanah said. “These findings suggest a broader trend toward increased fracture occurrence for the general population overall, possibly through enhanced detection of fractures with more frequent or better resolution imaging, or through more accurate documentation of fractures within the medical records.
“In the interrupted time series, there was no reduction in fracture rates in AS patients with the introduction of TNF inhibitors, she added. “More work needs to be done to explore other potential interventions beyond screening and treating traditional risk factors for fractures among people with AS.”
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
Patients with advanced ankylosing spondylitis are at increased risk for fractures. These patients have many risks for falling, including trouble with balance and coordination with vestibular dysfunction, loss of proprioception, and difficulty with peripheral vision. There is also the rigid spine with thoracolumbar kyphosis and hip flexion displacing the body’s center of gravity anteriorly and interfering with horizontal gaze. A tub-shower arrangement commonly found in homes and hotel rooms is a major hazard for these patients.
The spine with syndesmophytes, ankylosis and osteoporosis (bamboo spine) makes it susceptible to fracture even with minor trauma, particularly after a fall. Spinal cord injury (SCI) is a major concern with AS and a bamboo spine. Spinal fractures involving the C3 to C7 region, subluxation or dislocation, spinal epidural hematoma, and severe spinal fracture, were found to be predictive of SCI, and SCI in patients with AS resulted in higher mortality and complication rates.
One very large study of spinal fractures in AS found the mean age was 71.6 years and nearly 80% were Caucasian and male. The thoracic region was the most common area of fracture, although those with SCI (16%) demonstrated predominantly cervical involvement. Approximately 45% of their patients underwent surgical treatment for the fractures, with a 40% complication rate — mostly pulmonary.
The present study shows an actual increase in spinal fractures in the AS group in the post-TNF inhibitor era, with a commensurate increase in the comparator group, most likely due to improvements in imaging in this time frame. The authors described limitations in their study — the more severe AS cases were more likely to be prescribed TNF inhibitors and more likely to sustain a fracture, and less likely to have a substantial benefit from treatment. Of the 3,800 patients with AS, 83% had taken a TNF inhibitor.
The use of TNF inhibitors in AS was likely a gradual change in therapeutics, with more prescribed later in the study period than in the early years. The total dose of TNF inhibitor is also missing from this analysis. A double-blind study would need to be done to show a fracture effect of TNF inhibitors and we all know how costly and difficult this is from the osteoporosis world.
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