Abstract
ABSTRACTGlucocorticoids increase bone fragility in patients in a manner that is underestimated by bone mass measurement. This study aimed to determine if the adult mouse could model this bone strength/bone mass discrepancy. Forty‐two 13‐week‐old BALB/cJ mice were randomized into vehicle and glucocorticoid groups, implanted with vehicle or 6‐methylprednisolone pellets, and necropsied after 60 and 120 days. Bone strength and bone mass/microarchitecture were assessed at the right central femur (CF; cortical‐bone–rich) and sixth lumbar vertebral body (LVB6; trabecular‐bone–rich). Bound water (BW) of the whole right femur was analyzed by proton‐nuclear magnetic resonance (1H‐NMR) relaxometry. Data were analyzed by two‐factor ANOVA with time (day 60 and day 120) and treatment (vehicle and glucocorticoid) as main effects for all data. Significant interactions were further analyzed with a Tukey's post hoc test. Most bone strength measures in the CF were lower in the glucocorticoid group, regardless of the duration of treatment, with no time × treatment interaction. However, bone mass measures in the CF showed a significant time × treatment interaction (p = 0.0001). Bone strength measures in LVB6 showed a time × treatment interaction (p < 0.02) such that LVB6 strength was lower after 120 days of glucocorticoids compared with 120 days of vehicle treatment. Whole‐femur–BW was lower with both glucocorticoid treatment (p = 0.0001) and time (p < 0.02), with a significant time × treatment interaction (p = 0.005). Glucocorticoid treatment of male BALB/cJ mice resulted in the lowering of bone strength in both cortical and trabecular bone that either appeared earlier or was greater than the treatment‐related changes in bone mass/microarchitecture. The adult mouse may be a good model for investigating the bone strength/mass discrepancy observed in glucocorticoid‐treated patients. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.
Highlights
A few studies have noted that glucocorticoid-related differences in cortical bone strength in mice emerge as early as 28 days.[16,17,18] Because our earliest time point was day 60, our data leave open the possibility that the glucocorticoid-related differences in cortical bone strength plateau as early as 28 days of treatment
Ct.Ar/Tt.Ar, and Ct.Th, showed an effect of glucocorticoid treatment and an interaction of glucocorticoid treatment with duration of treatment. This indicates both that the glucocorticoid-related bone mass/micoarchitecture difference was significantly greater at day 120 than at day 60 and that cortical bone loss continued after the decline in cortical bone strength seemingly plateaued
Because our experiment ended at day 120, we cannot be certain that bone mass changes had plateaued in Balb/cJ male mice
Summary
Current data indicate that the adult mouse model of glucocorticoid-induced osteoporosis is sufficiently reliable to evaluate its potential relevance as a model of the glucocorticoid-induced bone strength/mass discrepancy in patients treated with glucocorticoids. Though the existing studies are promising, too few studies measure both bone 1 of 10 n strength/bone mass at the same site to allow evaluation of the bone strength/bone mass discrepancy in patients treated with glucocorticoids. The universal reporting of only one time point per study leaves open the possibility that bone strength and bone mass/microarchitecture evolve at different rates during glucocorticoid treatment
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