Axial spondyloarthritis (axSpA), particularly radiographic axSpA (ankylosing spondylitis, AS), is a chronic inflammatory disease mainly involving the axial skeleton and sacroiliac joints, typically presenting in young adults with inflammatory back pain (IBP) and characteristic imaging findings 1, 2. Laboratory features such as HLA-B27 positivity 3 and elevated inflammatory markers may support the diagnosis, while bone marrow edema (BME) on MRI is regarded as a key feature of active sacroiliitis and is incorporated into the Assessment of SpondyloArthritis International Society (ASAS) classification criteria 2, 4. However, BME is not disease-specific and may also occur in mechanical stress, trauma, metabolic bone disease, or osteoporosis (OP). OP reduces bone mass and disrupts microarchitecture. Common in older adults, secondary OP also affects younger individuals due to nutritional, endocrine, or mechanical factors 5. The resulting BME can mimic inflammatory lesions on imaging, complicating diagnosis. Here, we first report a young woman with extensive OP-related BME initially misdiagnosed as axSpA and discuss the key distinctions between the two conditions. An 18-year-old woman presented with low back pain for over 6 months (Figure 1). In 2023, she experienced Achilles tendon pain with normal MRI findings. In September 2024, MRI at Hospital A revealed extensive BME in both sacroiliac joints changes and small bilateral hip effusions (Figure 1a–c). She was HLA-B27 positive and suspected of having axSpA. In October 2024, Hospital B diagnosed axSpA based on the ASAS criteria (Figure 2) and initiated adalimumab. After six injections, there was no clinical or radiologic improvement. In January 2025, she was admitted again for persistent low back pain. Further review of her medical history revealed scoliosis and a suspected occult S1 fracture in 2021. From September 2022, after ridiculed for “thick legs,” she had undergone extreme dieting and 5–6 h of daily high-intensity exercise, losing 10 kg (160 cm/50 kg to 161 cm/40 kg, BMI 15.43 kg/m2). She was subsequently diagnosed with anorexia nervosa and sleep disorder and developed fatigue, alopecia, and secondary amenorrhea for over 1 year. Leukopenia (2–3 × 109/L) was noted in May 2023. Imaging at that time demonstrated multifocal BME involving the femoral head, acetabulum, and epiphyseal regions, which are rich in trabecular (cancellous) bone (Figure 1d–h). Dual-energy X-ray absorptiometry revealed OP (Z-score: −3.0). Serum 25-hydroxyvitamin D (25-OH-VitD, including D2 and D3) measured by LC-MS/MS was markedly reduced at 7 ng/mL (reference range: < 12 ng/mL, deficient; 12–20 ng/mL, insufficient; ≥ 20 ng/mL, sufficient). On reassessment, spinal mobility was preserved (modified Schober's test within normal limits), and sacroiliac provocation tests were unremarkable. Clinically, the pain was aggravated by physical activity and relieved by rest, without typical nocturnal pain or significant morning stiffness. Therefore, she did not fulfill the ASAS definition of IBP 6. Given the markedly reduced bone mineral density (BMD), symptomatic BME, and persistent hypoestrogenism, treatment with alendronate sodium 70 mg/qw, caltrate 1#/qd, and alfacalcidol 0.25 μg/qd was initiated after a multidisciplinary risk–benefit evaluation to improve BMD, reduce fracture risk, and stabilize bone turnover. Follow-up MRI in March (Figure 1i) and May 2025 (Figure 1j) demonstrated marked resolution of sacroiliac and hip BME. BMD improved substantially (Z-score: −1.3), and serum 25-OH-VitD increased to 11.8 ng/mL. Inflammatory markers (ESR, hsCRP), autoimmune panels, endocrine tests, and infection screening were all normal. A final diagnosis of secondary OP-related mechanical insufficiency BME was established based on clinical evolution, imaging response, and multidisciplinary evaluation. The most likely etiology was energy deficiency-related functional hypothalamic amenorrhea caused by prolonged extreme dieting and excessive exercise. Chronic energy imbalance suppresses the hypothalamic–pituitary–gonadal axis, leading to hypoestrogenism, which disrupts bone remodeling homeostasis, accelerates trabecular bone loss, compromises mechanical strength of cancellous bone, and increases skeletal fragility. This pathophysiological mechanism aligns with that described in the Female Athlete Triad and Relative Energy Deficiency in Sport (RED-S) 7, 8. The distinguishing features from axSpA are summarized in Figure 2 based on the literature review (Tables S1 and S2 and Figure S1) and multidisciplinary consultation. AxSpA typically affects young individuals and presents with chronic low back pain, sacroiliac involvement, BME, and HLA-B27 positivity, features that initially led to misdiagnosis in this case. According to the ASAS criteria of axSpA, the diagnosis follows two pathways (Figure 2): one based on sacroiliitis detected by X-ray or MRI and the other on HLA-B27 positivity 2, 4. Among these, bilateral sacroiliitis of grade ≥ 2 or unilateral sacroiliitis of grade ≥ 3 on X-ray, or the presence of BME or osteitis on MRI, constitute the imaging basis for the diagnosis of sacroiliitis 9, 10. However, only subchondral BME on the sacroiliac joint surface qualifies as “positive MRI for sacroiliitis” 5. In this patient, early imaging showed nonspecific periarticular edema without definite erosions, followed by fatty changes that blurred bony margins, highlighting a well-recognized diagnostic pitfall in daily practice. A key factor in the misdiagnosis was the insufficient consideration of metabolic bone disease. The patient's significant weight loss and amenorrhea due to extreme dieting and excessive exercise suggested hormonal and bone metabolic dysregulation. Estrogen deficiency and potential glucocorticoid exposure may accelerate bone loss but are often overlooked 11. In 2025, low BMD and severe 25-OH-VitD deficiency further supported the diagnosis of secondary OP. Although trabecular bone score and bone turnover markers (e.g., β-CTX and P1NP) were not assessed, the profound reduction in BMD combined with clinical features such as low BMI and amenorrhea strongly indicated impaired bone quality and active metabolic bone loss. Overinterpretation of HLA-B27 positivity also contributed to misdiagnosis. The HLA-B27 positivity rate in the general population is 5%–8% 3. When combined with age under 45 and chronic low back pain 4, this can easily lead to a misdiagnosis of axSpA. However, this patient lacked characteristic IBP features (nocturnal pain, morning stiffness), persistently normal inflammatory markers (hsCRP, ESR), and showed no response to biologic therapy 12, all of which contradict the typical disease course of axSpA. Overreliance on MRI-detected BME without considering alternative causes such as mechanical stress, trauma, infection, or metabolic bone disease may also lead to misdiagnosis 9. Notably, BME in axSpA exhibits “anatomically site-specific distribution”, primarily concentrated in the sacroiliac joints, vertebral endplates, and entheses 13, reflecting localized inflammatory responses. In contrast, OP-associated BME demonstrates a “mechanically related distribution,” typically involving weight-bearing areas such as vertebral bodies, femoral heads, and proximal tibiae, often accompanied by trabecular microfractures or imbalanced bone remodeling 14. In this case, the multifocal and asymmetric edema pattern (involving femoral heads, acetabula, and bilateral femoral epiphyseal plates) radiographically aligns with the characteristics of OP-related BME. Unlike acute osteoporotic fractures, the gradual onset in this case characterizes a bone stress injury, where repetitive strain exceeds the repair capacity of the osteoporotic bone, leading to insidious pain and microdamage accumulation. The temporal evolution of imaging findings further aids differential diagnosis. In axSpA, BME correlates with disease activity and requires biological agent intervention for resolution 2, whereas OP-related edema is often self-limiting, gradually subsiding with anti-resorptive therapy or mechanical load adjustments 14. Notably, although current classification criteria facilitate axSpA identification, their overall performance remains suboptimal 15-17, with reported sensitivity of 82.9% and specificity of 84.4% 4. From a clinical perspective, misdiagnosis carries therapeutic consequences. AxSpA treatment targets inflammation via NSAIDs or biologics 12, but long-term NSAID use may exacerbate OP 11. Conversely, OP management addresses underlying causes (e.g., calcium/VitD supplementation) and uses anti-resorptive or bone-forming agents 18. OP-related BME requires bone repair and mechanical protection, including short-term analgesia, bracing, or weight-bearing restriction during the acute phase 11. For patients with concomitant mental health disorders, multidisciplinary care and psychosocial support are essential. Overall, this case highlights the importance of integrating clinical history, laboratory data, bone metabolism assessment, and MRI distribution patterns in young patients with BME to distinguish inflammatory from metabolic etiologies and avoid inappropriate treatment. Xinyue Zhang conducted the literature review, collected the data, and drafted the manuscript; Shaozhe Cai and Guifen Shen critically reviewed and revised the manuscript; Min Wang contributed to the interpretation and review of the radiological findings; Lingli Dong was responsible for the patient's clinical management and revised the manuscript. All authors read and approved the final manuscript. We sincerely thank the patient and the patient's family for their cooperation and support throughout the diagnosis, treatment, and follow-up process. This work was supported by the National Natural Science Foundation of China (No. 32450786 and No. 82271847), and Tongji Hospital High-Quality Clinical Research Funding (No. 2024TJCR008). This study was reviewed and approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (No. TJ-IRB202510024). All procedures involving human participants were conducted in accordance with the principles stated in the Declaration of Helsinki (https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/). No identifying information or personal data that could reveal the patient's identity is included in the manuscript. Written informed consent was obtained from the patient for publication of this case report and any accompanying images. The informed consent form and related documentation can be made available to the journal's editorial office upon request. The authors declare no conflicts of interest. Data available in article Supporting Information. Figure S1: Flowchart of literature selection. Table S1: Search strategy used for the literature review. Table S2: Summary of reported cases of osteoporosis-related bone marrow edema with spondyloarthritis-like clinical features. Data S1: apl70619-sup-0001-Supinfo.docx. 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