2025-01-28 スイス連邦工科大学ローザンヌ校 (EPFL)
<関連情報>
- https://actu.epfl.ch/news/an-injectable-hydrogel-for-local-bone-densificat-2/
- https://www.sciencedirect.com/science/article/pii/S8756328224003624?via%3Dihub
全身的および局所的骨粗鬆症治療の併用: 卵巣摘出ラットを用いた縦断的生体内マイクロCT研究 Combining systemic and local osteoporosis treatments: A longitudinal in vivo microCT study in ovariectomized rats
Vincent A. Stadelmann, Estelle Gerossier, Ulrike Kettenberger, Dominique P. Pioletti
Bone Available online: 13 December 2024
DOI:https://doi.org/10.1016/j.bone.2024.117373
Highlights
- We studied the interactions of local and systemic anti-osteoporotic drugs on bone microstructure in ovariectomized rats.
- OVX rats received systemic vehicle, PTH, or ALN; tibias were injected with HA2 hydrogel, HA2+ZOL, or NaCl, with 8-week in vivo microCT tracking.
- HA2 and HA2-ZOL increased bone mass locally in vehicle rats within 2 weeks, but bone resorption resumed afterward.
- ALN rats showed extended bone gains, while PTH rats showed the greatest benefit from ZOL, indicating a cumulative drug effect.
- The hydrogel effects were localized to the injection site, promoting site-specific bone formation compatible with systemic treatments.
Abstract
Introduction
Managing osteoporotic patients at immediate fracture risk is challenging, in part due to the slow and localized effects of anti-osteoporotic drugs. Combining systemic anti-osteoporotic therapies with local bone augmentation techniques offers a promising strategy, but little is known about potential interactions. We hypothesized that integrating systemic treatments with local bone-strengthening biomaterials would have an additive effect on bone density and structure. This study investigated interactions and synergies between systemic therapies and injectable biomaterials, HA2 and HA2-ZOL, designed for local bone strengthening. HA2-ZOL incorporates Zoledronate, a bisphosphonate, to enhance anti-resorptive effects. These materials were tested in an in vivo rat model of osteoporosis using microCT and histology.
Methods
Thirty-six ovariectomized Wistar rats were treated systemically with vehicle (VEH), alendronate (ALN), or parathyroid hormone (PTH). One week later, their tibiae were randomly assigned to local treatment groups: HA2, HA2-ZOL, or NaCl control. Bilateral injections targeted metaphyseal trabecular bone, with microCT scans tracking changes over 8 weeks. Regions of interest (ROIs) were identified and analyzed for bone volume fraction (BV/TV), tissue mineral density (TMD), and trabecular morphology. Histological analyses were performed at week 8 to assess bone structure and mineral inclusions.
Results
VEH animals with NaCl injections experienced marked bone loss, partially mitigated by ALN and PTH. HA2 injections increased BV/TV by factors of 2.5 to 3.4 across treatments compared to baseline, with effects confined to the injected material. HA2-ZOL amplified this response, with BV/TV increases up to 4.8-fold, particularly in VEH and PTH animals. The effects peaked at 2–4 weeks post-injection, followed by remodeling and restoration. Both local treatments increased trabecular thickness, with HA2-ZOL showing slower post-peak resorption.
Discussion
HA2 injections significantly densified bone, independent of systemic therapy. Zoledronate in HA2-ZOL enhanced bone formation and delayed resorption in control and PTH animals, but offered no additional benefit when combined with systemic bisphosphonate. These findings support the hypothesis of an additive effect, suggesting that injectable hydrogels with localized drug delivery can complement systemic therapies by rapidly increasing local bone density, thereby potentially preventing fractures in high-risk osteoporotic patients.
