Clinical practice guidelines for the diagnosis and treatment of osteoporosis secondary to ankylosing spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory disease that primarily affects the axial skeleton and is often associated with secondary osteoporosis. Currently, there are no established international consensus or guidelines for managing AS-related osteoporosis (AS-OP). This guideline was jointly developed by several Chinese academic institutions, adhering to the Oxford grading system and the RIGHT reporting standards. It provides evidence-based recommendations on key clinical questions to improve the diagnosis, treatment, and patient-centred care for AS-OP. Ankylosing spondylitis (AS) is a chronic autoimmune inflammatory disorder. Osteoporosis (OP) with related fractures is one of the most serious. Osteoporosis and fractures are now recognized as major causes of disability in AS patients.1 However, comprehensive guidelines remain lacking. To address this gap, we convened a multidisciplinary expert panel to develop evidence-based recommendations (Supporting Information). Recommendation: High inflammatory activity and high bone turnover are identified as risk factors for AS-related osteoporosis (AS-OP) (Evidence quality: 2b; Recommendation level: B).2 Recommendation: Recommend bone mineral density (BMD), testing for AS patients upon diagnosis to screen for OP, with assessment sites including the hip (femoral neck and total hip) and lumbar spine (Evidence quality: 2a; Recommendation level: B).3 Testing methods: Use dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) to measure BMD in AS-OP patients (Evidence quality: 2b; Recommendation level: B).4, 5 Testing sites: DXA targets the hip (femoral neck and total hip) and lumbar spine (L1–L4), while QCT is recommended for the lumbar spine (Evidence quality: 2b; Recommendation level: B).5, 6 For newly diagnosed AS patients, baseline BTMs measurement could be considered before treatment, with follow-up assessments conducted 3–6 months after initiating anti-osteoporotic therapies (Evidence quality: 1b; Recommendation level: A).7 Blood samples should be collected while patients are fasting, ideally between 7:30 and 10:00 AM (Evidence quality: 1b; Recommendation level: A).8, 9 It is recommended to focus on monitoring β-carboxy-terminal cross-linked telopeptide of type I collagen (β-CTX) and procollagen type I N-terminal propeptide (P1NP) as primary BTMs, while considering other markers as supplementary (Evidence quality: 4; Recommendation level: C).10, 11 For β-CTX and P1NP measurements, electrochemiluminescence or enzyme-linked immunosorbent assay are preferred methods (Evidence quality: 3b; Recommendation level: B).9 The diagnosis of AS is recommended based on the 1984 modified New York criteria. For axial spondyloarthritis (SpA) with secondary OP, the AS-OP diagnostic criteria may serve as a reference, while axial SpA diagnosis should follow the 2009 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria (Evidence quality: 5; Recommendation level: D). AS-OP diagnostic criteria include the assessment of BMD through DXA and/or the presence of fragility fractures. Alternatively, lumbar spine BMD measurement via QCT may be used based on clinical judgment (Evidence quality: 3b; Recommendation level: B).4 It is recommended to diagnose AS-OP following the diagnostic flowchart (Figure 1) (Evidence quality: 5; Recommendation level: D). Meeting one or more of the following OP diagnostic criteria: T-score ≤ −2.5 SD based on BMD measurement; Fragility fractures in the hip or vertebrae; Fragility fractures in the proximal humerus, pelvis, or distal forearm, combined with low BMD (−2.5 SD < T-score < −1.0 SD).12 Lumbar QCT-measured BMD < 80 mg/cm³.13 A 10-year hip fracture probability ≥3% or major osteoporotic fracture probability ≥20%, as calculated by the FRAX tool.14 Z-score ≤ −2 SD; anti-OP treatment may be considered depending on clinical judgment.15 General treatment principles: Alongside managing AS, prioritize early screening and prompt treatment for OP (Evidence quality: 5; Recommendation level: D).16 Early prevention of AS-OP, including lifestyle adjustments and appropriate supplementation of vitamin D and calcium, is recommended as part of AS management. For patients with OP, anti-OP medications should be administered (Evidence quality: 5; Recommendation level: D).17 For the initial treatment of AS-OP, therapy should be tailored to the patient′s fracture risk. Denosumab or bisphosphonates (e.g., alendronate, risedronate, or zoledronic acid) could be considered (Evidence quality: 1b; Recommendation level: A).18, 19 Due to the unique pathology of bone loss in AS, anabolic bone-forming agents are not routinely recommended (Evidence quality: 5; Recommendation level: D). Recommendation: It is advised to monitor BTMs every 3–6 months to assess the therapeutic response and patient adherence. Additionally, an annual BMD assessment is recommended. For patients with prolonged disease duration, trabecular bone score evaluation may be incorporated to assess fracture risk and predict prognosis in AS-OP patients (Evidence quality: 5; Recommendation level: D).20, 21 Recommendation: Preventing OP in AS patients may involve managing inflammatory disease activity, providing health education, offering lifestyle guidance, addressing risk factors, and ensuring adequate calcium and vitamin D supplementation (Evidence quality: 5; Recommendation level: D).22 Recommendation: For AS patients with vitamin D deficiency or insufficiency, routine supplementation with calcium and vitamin D is advised to mitigate the risk of OP (Evidence quality: 2b; Recommendation level: B).23 Yasong Li and Liang Wang conceived the presented idea. Han Wang wrote the first draft of the manuscript. All authors revised it for intellectual content and approved the final version for publication. This study was supported by the National Administration of Traditional Chinese Medicine- Key Projects jointly built by the Administration of Traditional Chinese Medicine of Zhejiang Province (No. GZY-ZJ-KJ-23047). All authors declare no conflict of interest. The authors have nothing to report. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.