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Response to ‘Correspondence on “Tumour necrosis factor inhibitors slow radiographic progression in patients with ankylosing spondylitis: 18-year real-world evidence” by Zhang et al
  1. Bon San Koo1,
  2. Ji Seon Oh2,
  3. Seo Young park3,
  4. Ji Hui Shin4,
  5. Ga Young Ahn5,
  6. Seunghun Lee6,
  7. Kyung Bin Joo6,
  8. Tae-Hwan Kim4
  1. 1 Department of Internal Medicine, Inje University Seoul Paik Hospital, Inje University College of Medicine, Seoul, Republic of Korea
  2. 2 Department of Biomedical Informatics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
  3. 3 Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
  4. 4 Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea
  5. 5 Department of Rheumatology, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea
  6. 6 Department of Radiology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea
  1. Correspondence to Dr Tae-Hwan Kim, Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seongdong-gu 04763, Republic of Korea; thkim{at}

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We thank Zhang et al 1 for their interest in our study, titled “Tumour necrosis factor inhibitors slow radiographic progression in patients with ankylosing spondylitis: 18-year real-world evidence.” We investigated long-term observational data using advanced statistical methods to determine whether changes in radiographic progression are affected by tumour necrosis factor inhibitors (TNFi) in patients with ankylosing spondylitis (AS).2 However, our study did not consider the risk of osteoporosis or vertebral fractures while evaluating the effects of TNFi.

There are several studies on bone mineral density (BMD) in patients with AS. Compared with the general population, patients with AS have a lower BMD.3–5 Furthermore, it is interesting that an increase in the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) correlated with the decreased lumbar BMD.4 These results are possibly related to decreased physical activity and functional capacity owing to pain and stiffness.6 Importantly, AS is a chronic inflammatory disease, and inflammation plays a key role in bone loss. Therefore, it is conceivable that anti-inflammatory drugs can affect not only mSASSS but also BMD.

Tumour necrosis factor-α is an important cytokine for the regulation of bone homoeostasis in arthritis. Therefore, there are various experimental results showing that TNFi can affect osteoblast differentiation and osteoclastogenesis.7 Studies have also assessed how TNFi affect osteoporosis in patients with rheumatic disease.8 9 TNFi differ from existing osteoporosis medications (such as bisphosphonate or denosumab) with respect to the mechanism that affects bone remodelling in rheumatic diseases such as ankylosing spondylitis. However, the effect of TNFi on BMD in AS is unclear. In addition, there is insufficient evidence for determining the effects of TNFi on BMD because of time consuming and confounding by indication . Studying the role of TNFi in osteoporosis and fractures will provide important experimental and clinical evidence for pathogenesis of AS.

However, showing the effect of TNFi on osteoporosis was difficult using our data. First, patients with AS in our electronic medical records (EMR) were young (mean age, 33.1±9.8 years) and mostly men (90%). Moreover, there is no reason to routinely measure BMD in young patients in real-world clinical practice. Therefore, there is limited or no information on BMD in the EMR, and hence, it was impossible to study the relationship between TNFi and osteoporosis. Second, dual-energy X-ray absorptiometry and quantitative computed tomography along with several laboratory indicators have been used for measuring BMD using data from the EMR. However, incorporating these various methods into statistical models was difficult.

Notably, we showed that TNFi can affect the radiographic progression of AS with either direct or indirect effects via inflammation. Although further research is needed, these effects of TNFi may be considered similarly in the study for BMD.

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  • Handling editor Josef S Smolen

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Commissioned; internally peer reviewed.

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