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Background <p>In both aging and osteoporosis conditions, bone loss was positively correlated to bone marrow adiposity; however, the associated lipid signature remains to be clarified. This study aims to explore local lipid variations in relation to bone alteration during aging and after ovariectomy, in order to identify potential lipid markers of bone loss and, ultimately, to provide new insights for improving strategies to prevent osteoporotic fractures and, consequently, ameliorate well-being of these vulnerable populations.</p> Methods <p>Seventy-two female SD rats of 6&#xa0;months-old for skeletal maturity were divided into 3 groups and studied at 6–11-18&#xa0;months-old (AGE group), and at 1–3-5&#xa0;months post-surgery (ovariectomized (OVX) <i>vs.</i> control (SHAM) groups). Femoral diaphysis was chosen as bone site. Fatty acids (FA) were analyzed by high-performance liquid chromatography and bone microarchitecture by micro-computed tomography.</p> Results <p>Data confirmed bone loss and different lipid changes in bone marrow under both AGE and OVX conditions. Strong linear regressions were observed between bone microarchitecture parameters and lipids, mostly implying oleic acid (18:1) level, 18:1/18:0 ratio (Δ9-desaturase index), arachidonic acid (20:4n-6) level and total FA amount. Interestingly, 18:1/18:0 was negatively correlated with cortical thickness and positively with cortical porosity, while 20:4n-6 showed diametrically opposite correlations with these two cortical parameters. FA amount was closely associated with several trabecular parameters in a negative manner. By principal components (PC) analysis, three PCs (PC1-3) were identified and their combinations allowed to segregate the OVX group from the two others (mainly explained by PC1xPC2 combination vs. PC1 alone, respectively), with PC1 associated with cortical bone loss, 18:1/18:0 and 20:4n-6, and PC2 with trabecular bone volume, FA amount, n-6/n-3 polyunsaturated FA ratio and 16:1/16:0.</p> Conclusions <p>Current findings highlight strong local associations between bone marrow lipids and bone microarchitecture parameters during bone loss, and suggest two lipid pathways—de novo synthesis of 18:1 from 18:0 by Δ9-desaturase and catabolism of 20:4n-6 – as potential markers of cortical bone loss and the increase in marrow FA content as key marker of trabecular bone loss. Finally, ovariectomy-related bone loss seemed does not appear simply an exacerbated process of age-related bone loss in terms of local lipid metabolism and actions.</p>

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Changes in local lipids are correlated with bone microarchitecture alterations during aging and ovariectomy-induced osteoporosis in rat femur: focus on the Δ9-desaturase 18:1/18:0 index and arachidonic acid level

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  • 发表日期：

    2026年1月13日

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  • Jérôme Delattre,
  • Nicolas Bertheaume,
  • Cécile Olejnik,
  • Alexandrine During

摘要

Background

In both aging and osteoporosis conditions, bone loss was positively correlated to bone marrow adiposity; however, the associated lipid signature remains to be clarified. This study aims to explore local lipid variations in relation to bone alteration during aging and after ovariectomy, in order to identify potential lipid markers of bone loss and, ultimately, to provide new insights for improving strategies to prevent osteoporotic fractures and, consequently, ameliorate well-being of these vulnerable populations.

Methods

Seventy-two female SD rats of 6 months-old for skeletal maturity were divided into 3 groups and studied at 6–11-18 months-old (AGE group), and at 1–3-5 months post-surgery (ovariectomized (OVX) vs. control (SHAM) groups). Femoral diaphysis was chosen as bone site. Fatty acids (FA) were analyzed by high-performance liquid chromatography and bone microarchitecture by micro-computed tomography.

Results

Data confirmed bone loss and different lipid changes in bone marrow under both AGE and OVX conditions. Strong linear regressions were observed between bone microarchitecture parameters and lipids, mostly implying oleic acid (18:1) level, 18:1/18:0 ratio (Δ9-desaturase index), arachidonic acid (20:4n-6) level and total FA amount. Interestingly, 18:1/18:0 was negatively correlated with cortical thickness and positively with cortical porosity, while 20:4n-6 showed diametrically opposite correlations with these two cortical parameters. FA amount was closely associated with several trabecular parameters in a negative manner. By principal components (PC) analysis, three PCs (PC1-3) were identified and their combinations allowed to segregate the OVX group from the two others (mainly explained by PC1xPC2 combination vs. PC1 alone, respectively), with PC1 associated with cortical bone loss, 18:1/18:0 and 20:4n-6, and PC2 with trabecular bone volume, FA amount, n-6/n-3 polyunsaturated FA ratio and 16:1/16:0.

Conclusions

Current findings highlight strong local associations between bone marrow lipids and bone microarchitecture parameters during bone loss, and suggest two lipid pathways—de novo synthesis of 18:1 from 18:0 by Δ9-desaturase and catabolism of 20:4n-6 – as potential markers of cortical bone loss and the increase in marrow FA content as key marker of trabecular bone loss. Finally, ovariectomy-related bone loss seemed does not appear simply an exacerbated process of age-related bone loss in terms of local lipid metabolism and actions.