Background/Purpose: Osteoporosis (OP) is characterized by low bone mass and microarchitectural deterioration, increasing fracture risk. Bone Mineral Density (BMD), T-score, and Trabecular Bone Score (TBS) are key diagnostic and monitoring tools. Systemic inflammatory markers linked to cardiovascular risk such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) have been proposed as potential indicators of and other cardiovascular events. Romosozumab (ROMO), a sclerostin inhibitor with dual anabolic and antiresorptive action, is approved for high-risk postmenopausal OP patients. This study evaluated the association between changes in TBS, T-score, BMD, and inflammatory ratios in women treated with ROMO.

Methods: We conducted a retrospective observational study of postmenopausal women with OP treated with ROMO. Pre- and post-treatment measurements of TBS, T-score, BMD, NLR, PLR, and MLR were analyzed. Delta changes (post-treatment minus baseline) were calculated for each parameter. Correlation analyses and linear regression models assessed the predictive value of inflammatory ratios on bone parameter changes.

Results: Thirty-seven postmenopausal women (mean age 46.0 years) completed ROMO therapy and follow-up. Fracture history included single (62%), multiple (32%), or no fractures (5%). Comorbidities included inflammatory diseases (8%), COPD (14%), dyslipidemia (38%), hypertension (43%), and smoking (14%). Significant improvements were observed in TBS (mean +0.85 units, p< 0.001), T-score (mean +0.61 units, p< 0.001), and BMD (mean +0.06 g/cm², p< 0.001). A moderate positive correlation was found between NLR change and TBS improvement (r=0.45, p< 0.05). No significant associations were found for PLR or MLR. Regression models showed low predictive capacity of NLR, PLR, or MLR on changes in TBS, T-score, or BMD (R²< 0.1 in all models). Baseline ratios also showed negligible predictive value (R² TBS=-0.75, T-score≈0.00, BMD≈0.005).

Conclusion: Romosozumab significantly improves bone quality and density in postmenopausal women with OP. While NLR changes moderately correlate with TBS improvement, inflammatory ratios NLR, PLR, and MLR lack predictive utility for treatment response. Additionally, ROMO treatment did not significantly alter these inflammatory markers of cardiovascular risk in various clinical contexts, supporting a neutral effect on subclinical systemic inflammation linked to cardiovascular risk. These findings may be relevant in the context of cardiovascular safety discussions surrounding ROMO. References: McClung MR, Betah D, Leder BZ, et al. Romosozumab improves microarchitecture as assessed by tissue thickness-adjusted trabecular bone score in postmenopausal women with osteoporosis. J Bone Miner Res. 2025 Feb;40(2):193–200.Liu YC, Yang TI, Huang SW, et al. Associations of the Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio with Osteoporosis: A Meta-Analysis. Diagnostics (Basel). 2022 Nov 28;12(12):2968.

Figure 1. Relationships Between Baseline Inflammatory Ratios (NLR, PLR, MLR) and Changes in Trabecular Bone Score (TBS), T-score, and Bone Mineral Density (BMD) in Postmenopausal Women Treated With Romosozumab. Regression analyses show no significant predictive capacity (R² < 0.1) across all models.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-between-changes-in-bone-quality-parameters-and-inflammatory-ratios-in-postmenopausal-women-treated-with-romosozumab-a-retrospective-observational-study/