7500 Effect Of Orchiectomy On Bone Microarchitecture In Male Mice With Kidney Disease
Authors: Wu D , Patwardhan A , Marks O , Komaru Y , Kefalogianni E , Aurora R , Dhindsa S , Herrlich A 
Published: October 2024

Disclosure: D. Wu: None. A. Patwardhan: None. O. Marks: None. Y. Komaru: None. E. Kefalogianni: None. R. Aurora: None. S. Dhindsa: None. A. Herrlich: None.

Background: Chronic kidney disease (CKD) leads to decreased bone density and increased fracture risk. In males, an additional factor contributes to the low bone density. Around half of the men with CKD have low serum testosterone concentrations. We hypothesized that CKD and low testosterone would have an additive and detrimental effect on bone. Methods: Forty male C57BL/6 mice were divided into 4 groups: 1) renal injury, induced by ischemia-induced reperfusion (IRI) and sham orchidectomy (IRI-sham, N=8) at 2 months of age; 2) orchidectomy (ORX), performed 4 weeks after IRI (IRI + ORX, N=11); 3) sham-ORX, N=9; and 4) sham-sham surgery, N=12. 12 weeks after IRI, the mice developed renal fibrosis and decreased glomerular filtration rate, indicative of CKD. The mice were sacrificed when they were 7 months old. Femur and tibia were harvested for both histology and μCT analysis. Results: Bone volume to total volume fraction (BV/TV) was lower in the IRI-ORX (0.06±0.02) and sham-ORX (0.08±0.02), as compared to IRI-sham (0.10±0.03, p&lt;0.05) and sham-sham group (0.14±0.03, p&lt;0.05) respectively. Similarly, the volumetric bone mineral density (vBMD) in IRI-ORX (93±27 mgHA/cm3) and sham-ORX (112±39 mgHA/cm3) groups were lower than IRI-sham (150±43 mgHA/cm3, p&lt;0.05) and sham-sham (187±30 mgHA/cm3, p&lt;0.05) mice. Trabecular number (Tb.N) was decreased in the IRI-ORX group (2.7±0.7 #/mm) compared to IRI-sham group (4.1±1.1 #/mm, p&lt;0.05). Tb.N was also lower in sham-ORX (3.2±1.1 #/mm) mice than sham-sham (4.5±0.2 #/mm), but not IRI-sham mice. In contrast, trabecular thickness (Tb.Th) was lower in IRI-ORX (0.035±0.002 mm) and IRI-sham (0.038±0.002 mm) compared to sham-ORX (0.045±0.005 mm) and sham-sham (0.047±0.005 mm, p&lt;0.05). Trabecular spacing (Tb.Sp) was increased by 47% in IRI-ORX group compared to IRI-sham group (0.26±0.09 mm). Decreased trabecular numbers and increased spacing results in reduced connectivity density (Conn.Den), which was decreased by 60% in the IRI-ORX sham-ORX groups as compared to sham-sham group (423±58 #/mm3, p&lt;0.05). 2 way ANOVA analysis showed that ORX significantly contributed to the variance in BV/TV (p&lt;0.001), vBMD (p&lt;0.001), Tb.N (p&lt;0.01), Tb.Sp (p&lt;0.01) and Conn.Den (p&lt;0.001), while IRI contributed to Tb.Th (p&lt;0.0001). There was no significant interaction between IRI and ORX in all endpoints. Conclusions: Taken together, these data indicate that even in the presence of established CKD, ORX has a greater effect on bone mass. ORX decreased trabecular number (Tb.N) and increased trabecular spacing (Tb.Sp) to a greater extent than IRI. IRI decreased trabecular thickness (Tb.Th) while ORX had no effect on that parameter. Trabecular bone loss starts by trabecular thinning. Eventually, the trabeculae will be completely resorbed, resulting in decreased trabecular numbers and increased spacing. Our data indicate that IRI and ORX affect bone at different time points.

Presentation: 6/1/2024