Background/Purpose: Patients with ankylosing spondylitis (AS) are susceptible to osteoporosis (OP) and have high fracture risk. Currently, no specific strategies are established to treat OP in these patients. TNF inhibitors are now increasingly used for treating AS. If TNF inhibitors are shown to prevent or reverse bone loss, use of bisphosphonates can be avoided.  We did a systematic review and meta-analysis to study the effect of TNF inhibitors on spine and hip BMD in patients with AS.

Methods: Two authors searched MEDLINE, EMBASE & Cochrane databases, reviewed abstracts, and extracted data. A third author resolved discrepancies. Eligible studies had at least 70% of subjects satisfying Modified New York AS criteria and a minimum follow-up of 1 year. Case reports and studies on children and adolescents were excluded. The quality of the studies was assessed by Newcastle–Ottawa Quality Assessment Scale. Primary outcomes (BMD at spine, hip &femoral neck) were analyzed at 1 and 2 years. BMD was expressed as the percent change from baseline. Publication bias was assessed by Funnel plots. Statistical heterogeneity was assessed using Q statistic. The overall summary estimate was determined using the random effects model, which was weighted by the inverse variance of the effect size.

Results: Our search was narrowed down to 8 studies (7 observational studies and 1 RCT). BMD data available from 470 patients were included in the meta-analysis. Most subjects were males and their proportion varied from 70-92%. Mean age at enrolment ranged from 36-48 years, and mean disease duration was 9-17 years. Bisphosphonate use was negligible. Little data was available on intake of calcium and vitamin D. The use of TNF inhibitors led to significant improvement in spine and total hip BMD after 1 and 2 years when compared to baseline (Table 1). Femoral neck BMD remained stable at 1 year. The BMD gain was also significant in those treated with TNF inhibitors when compared to controls. In the RCT (TNF inhibitors vs. placebo), the gain in BMD was significantly higher in those treated with TNF inhibitors for 2 years versus those treated with placebo for the first 6 months.

Conclusion: Treatment with TNF inhibitors is associated with improvement in spine and hip BMD in patients with AS. More studies of longer duration and larger sample sizes are needed to better understand the effect of TNF inhibitors on fracture risk.

Table 1: Summary estimates of the effect of TNF inhibitors on BMD in patients with AS

Duration of follow up (Years)	Lumbar spine Mean difference, % (95% CI)	Total hip Mean difference, % (95% CI)	Femoral neck Mean difference, % (95% CI)
1 year	5.1 (4.0-6.1)	1.8 (1.0-2.5)	0.73 (-0.8-2.2)
2 years	8.6 (6.8-10.3)	2.5 (1.9-3.0)	Insufficient data

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/effect-of-tnf-inhibitors-on-bone-mineral-density-in-patients-with-ankylosing-spondylitis-a-systematic-review-and-meta-analysis/