After middle age, in human bone, the resorption usually exceeds formation resulting in bone loss and increased risk of fractures in the aged population. Only few in vivo models in higher vertebrates are available for pathogenic and therapeutic studies about bone aging. Among these, male Danio rerio (zebrafish) can be successfully used as low vertebrate model to study degenerative alterations that affect the skeleton during aging, reducing the role of sex hormones.

In this paper, we investigated the early bone aging mechanisms in male zebrafish (3, 6, 9 months old) scales evaluating the physiological changes and the effects of prednisolone, a pro-osteoporotic drug.

The results evidentiated an age-dependent reduction of the mineralization rate in the fish scales, as highlighted by growing circle measurements. Indeed, the osteoblastic ALP activity at the matrix deposition site was found progressively downregulated.

The higher TRAP activity was found in 63% of 9-month-old fish scales associated with resorption lacunae along the scale border. Gene expression analysis evidentiated that an increase of the tnfrsf1b (homolog of human rank) in aging scales may be responsible for resorption stimulation.

Interestingly, prednisolone inhibited the physiological growth of the scale and induced in aged scales a more significant bone resorption compared with untreated fish (3.8% vs 1.02%). Bone markers analysis shown a significant reduction of ALP/TRAP ratio due to a prednisolone-dependent stimulation of tnfsf11 (homolog of human rankl) in scales of older fish.

The results evidentiated for the first time the presence of a senile male osteoporosis in lower vertebrate. This new model could be helpful to identify the early mechanisms of bone aging and new therapeutic strategies to prevent age-related bone alterations in humans.

中年之后，人体骨骼的吸收通常超过形成，导致骨质流失并增加老年人骨折的风险。只有少数高等脊椎动物的体内模型可用于骨老化的致病和治疗研究。其中，雄性斑马鱼可以成功地用作低等脊椎动物模型来研究衰老过程中影响骨骼的退行性改变，从而降低性激素的作用。

在本文中，我们研究了雄性斑马鱼（3、6、9 个月大）鳞片的早期骨老化机制，评估了促骨质疏松药物泼尼松龙的生理变化和作用。

结果证明，鱼鳞矿化率随年龄的增长而降低，正如生长圈测量所强调的那样。事实上，发现基质沉积位点的成骨细胞 ALP 活性逐渐下调。

在 63% 的 9 个月大的鱼鳞中发现了较高的 TRAP 活性，这与鳞片边缘的再吸收缺口有关。基因表达分析证明，衰老尺度中tnfrsf1b（人类等级同源物）的增加可能是吸收刺激的原因。

有趣的是，与未经处理的鱼相比，泼尼松龙抑制了鳞片的生理生长，并在老化的鳞片中诱导了更显着的骨吸收（3.8% vs 1.02%）。骨标志物分析显示，由于对老鱼鳞片中tnfsf11（人类Rankl的同源物）的泼尼松龙依赖性刺激，ALP/TRAP比率显着降低。

结果首次证明低等脊椎动物中存在老年男性骨质疏松症。这种新模型可能有助于确定骨骼老化的早期机制以及预防人类与年龄相关的骨骼改变的新治疗策略。