Moderate hyperhomocysteinemia induced by short-term dietary methionine overload alters bone microarchitecture and collagen features during growth

Abstract

Aims: In general, hyperhomocysteinemia is increasingly appreciated as a risk factor for various diseases, including osteoporosis. However, its effects in non-adults remain largely unknown. Our aim was to determine whether dietary-caused increased homocysteine levels have deleterious effects on bone structure during growth. Main methods: We developed a model of moderate hyperhomocysteinemia caused by short-term methionine nutritional overload in growing rats. 30-days-old male Wistar albino rats were randomly assigned to either experimental group subject to a 30-days hypermethionine diet or control group. High-resolution 3D assessment of bone geometry and microarchitecture, as well as fluorescence spectroscopic analysis of bone matrix were performed. Key findings: Short-term moderate hyperhomocysteinemia (similar to 30 mu mol/L) achieved in the study notably affected bone and cartilage characteristics. Parameters of the cortical bone geometry in the experimental group indicated peculiar reorganization of the bone cross-section. Trabecular bone microarchitecture was especially sensitive to hyperhomocysteinemia showing clearly negative bone balance in the experimental group (almost 30% reduced bone volume, mainly due to similar to 25% decrease in trabecular number as well as markedly reduced trabecular connections). Fluorescent spectroscopy of bone matrix revealed multiple alterations to collagen spectra due to homocysteine accumulation in bone, indicative of broken collagenous cross-links. Significance: Given that appropriate accrual of bone mass during growth has important effects on the risk of osteoporosis in adulthood, understanding the skeletal effects of dietary-induced hyperhomocysteinemia in nonadults is essential for interpreting its importance as a modifiable risk factor for osteoporosis and improving programs to preserve/re-establish bone health.