Fluctuations in intramedullary pressure (IMP) drive interstitial fluid flow throughout bone, activating osteocytes and osteoblasts. We previously reported declines in IMP in old vs. young rats. Thus, reduced IMP in aging may relate to declines in interstitial fluid flow-mediated activation of bone cells. We hypothesized that enhancing in vivo IMP will elicit bone cellular activity. To induce bone formation, the objective was to test the efficacy of a fabricated micropump in stimulating fluctuations in IMP. METHODS: Male Fischer-344 rats were divided into young (6 mon; n=14) and old (24 mon; n=11) groups. Additionally, we designed a pressure-sensing system to monitor IMP (mmHg). Under anesthesia (3% isoflurane to O 2 balance), two bone defects were created (20G needle) in the right (experimental, EXP) femoral shaft, catheterized (PE50), and instrumented to the micropump and pressure sensor. The micropump was activated for 10 min and the last 5 min of IMP fluctuations were averaged and reported. Left femora underwent the same surgical procedure but was not instrumented to the equipment and served as a contralateral control (CON). After 7 days, both femora were scanned by μCT (15µm) to assess bone microarchitecture (BV/TV, %; Tb.Th, µm; Tb.N, /mm; and Tb.Sp, µm) and density (mg HA/ccm) in the proximal and distal femoral metaphyses, cortical parameters at the midshaft (cortical thickness Ct.Th, µm, porosity %, and density mg HA/ccm), and new bone volume (BV, µm) and density (mg HA/ccm) at the periosteal and endosteal surfaces. General Linear Models were used to analyze the data. A p-value of 0.05 was set a priori. RESULTS: Body mass was lower (p< 0.05) in young (314±23g) vs. old (387±18g) rats. Mean IMP fluctuation did not differ between young (42±26mmHg) and old (46±24mmHg) groups. Trabeculae in the proximal metaphysis were thicker (p< 0.05) in old CON (125±12µm vs. 116±5µm, respectively) and EXP (125±10µm vs. 115±5 µm, respectively) femora vs. the young. Trabeculae in the proximal metaphysis were denser (p< 0.05) in old CON (1084±14 mg HA/ccm vs. 1040±8 mg HA/ccm, respectively) and EXP (1086±14 mg HA/ccm vs. 1036±7 mg HA/ccm, respectively) femora vs. the young. In the distal metaphysis, trabeculae were denser (p< 0.05) in old CON (1084±12 mg HA/ccm vs. 1031±22 mg HA/ccm, respectively) and EXP (1081±11 mg HA/ccm vs. 1038±9mg HA/ccm, respectively) femora vs. young. No other bone microarchitectural property differed. The cortical shell was thicker (p< 0.05) in young vs. old rats (CON: 550±20µm vs. 452±19µm, respectively, and EXP: 555±21µm vs. 452±25µm, respectively). However, cortical density was higher in the old vs. young femora (CON: 1269±17mg HA/ccm vs. 1198±17mg HA/ccm, respectively, and EXP: 1265±17mg HA/ccm vs. 1195±16 mg HA/ccm, respectively). No differences in porosity were observed. New bone volume at the endosteal and periosteal surfaces was higher (p< 0.05) in the CON (7±7µm vs. 1±1µm, respectively) and EXP (14±7µm vs. 4±2µm, respectively) femora of the young vs. old rats; however, the new bone was less (p< 0.05) dense in the young vs. old CON (627±37 mg HA/ccm vs. 731±104 mg HA/ccm, respectively) and EXP (601±42 mg HA/ccm vs. 712±82mg HA/ccm, respectively). Finally, new bone volume was higher (p< 0.05) in the EXP (14±7µm) vs. CON (7±7µm) femora in the young rats. CONCLUSION: A single 10-min session of induced IMP fluctuation elicited an early (i.e., 7 days) osteogenic response at the periosteal and endosteal surfaces of the femur in young but not old rats. Optimization of the protocol in terms of IMP magnitude, duration and/or frequency may promote a more robust bone anabolic response in both age groups. Grant Support: NSF ECCS 1710948 (RDP), NSF ECCS 1710824 (JBL), AHA 16IRG27550003 (RDP). This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Hosseini et al. (Fri,) studied this question.