Research Centre, Shriners Hospital for Children-Canada, Montreal, Canada; Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, Canada; Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany.
Department of Internal Medicine II, Hematology and Oncology, University Hospital of Würzburg, Würzburg, Germany.
Biomater Adv. 2025 Jan;166:214047. doi: 10.1016/j.bioadv.2024.214047. Epub 2024 Sep 15.
Multiple myeloma bone disease (MMBD) is characterized by the growth of malignant plasma cells in bone marrow, leading to an imbalance in bone (re)modeling favoring excessive resorption. Loss of bone mass and altered microstructure characterize MMBD in humans and preclinical animal models, although, no study to date has examined bone composition or material properties. We hypothesized that MMBD alters bone composition, mineral crystal properties and mechanical properties in the MOPC315.BM.Luc model after intra-tibial injection of myeloma cells and three weeks of daily in vivo tibial loading. Decreased cortical bone elastic modulus and hardness measured by nanoindentation of tibiae were observed in MM-injected mice compared to PBS-injected mice, whereas cortical bone composition, mineral crystal properties measured by Fourier-transform infrared imaging or small angle X-ray scattering, respectively remained unchanged. However, MM-injected mice had thinner cancellous bone mineral particles compared to PBS-injected mice. Mechanical loading did not lead to altered cortical bone composition, mineral structure, or mechanical properties in the context of MM. Unexpectedly, we observed the intra-tibial injection itself altered the material composition of bone, manifested by increased matrix mineralization and crystal size of the hydroxyapatite crystals in the bone matrix. In conclusion, our data suggest that mechanical stimuli can be used as an adjuvant bone anabolic therapy in patients with MMBD to rebuild bone with unaltered composition and mineral structure to reduce subsequent fracture risk.
多发性骨髓瘤性骨病（MMBD）的特征是骨髓中恶性浆细胞的生长，导致骨（重塑）平衡偏向于过度吸收。人类和临床前动物模型的 MMBD 表现为骨量减少和微观结构改变，但迄今为止尚无研究检查过骨成分或材料特性。我们假设在骨髓瘤细胞的胫骨内注射和三周的每日体内胫骨加载后，MMBD 会改变 MOPC315.BM.Luc 模型中的骨成分、矿物质晶体特性和机械性能。与 PBS 注射小鼠相比，MM 注射小鼠的胫骨纳米压痕测量的皮质骨弹性模量和硬度降低，而皮质骨成分、矿物质晶体特性分别通过傅里叶变换红外成像或小角 X 射线散射测量，保持不变。然而，与 PBS 注射小鼠相比，MM 注射小鼠的松质骨矿物质颗粒更薄。在 MM 的情况下，机械加载不会导致皮质骨成分、矿物质结构或机械性能发生改变。出乎意料的是，我们观察到胫骨内注射本身改变了骨的材料组成，表现为骨基质中基质矿化和羟磷灰石晶体的晶体尺寸增加。总之，我们的数据表明，机械刺激可以作为 MMBD 患者的辅助骨合成治疗方法，用未改变的成分和矿物质结构重建骨骼，以降低随后骨折的风险。
