Poor bone quality is a major factor in skeletal fragility in elderly individuals. The molecular mechanisms that establish and maintain bone quality, independent of bone mass, are unknown but are thought to be primarily determined by osteocytes. We hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling (PLR), which maintains bone material properties. We examined bones from young and aged mice with osteocyte-intrinsic repression of TGFβ signaling (TβRII^ocy−/−) that suppresses PLR. The control aged bone displayed decreased TGFβ signaling and PLR, but aging did not worsen the existing PLR suppression in male TβRII^ocy−/− bone. This relationship impacted the behavior of collagen material at the nanoscale and tissue scale in macromechanical tests. The effects of age on bone mass, density, and mineral material behavior were independent of osteocytic TGFβ. We determined that the decline in bone quality with age arises from the loss of osteocyte function and the loss of TGFβ-dependent maintenance of collagen integrity.

骨质量差是老年人骨骼脆弱的一个主要因素。建立和维持骨质量（与骨量无关）的分子机制尚不清楚，但被认为主要由骨细胞决定。我们假设与年龄相关的骨质量下降是由于骨细胞腔周/骨小管重塑（PLR）受到抑制造成的，而骨细胞维持骨材料特性。我们检查了年轻和老年小鼠的骨骼，这些小鼠的骨细胞固有地抑制了 TGFβ 信号传导 ( TβRII ^ocy−/− )，从而抑制了 PLR。对照老化骨骼显示 TGFβ 信号传导和 PLR 降低，但衰老并没有恶化男性TβRII ^ocy−/−骨骼中现有的 PLR 抑制。这种关系影响了宏观力学测试中胶原材料在纳米尺度和组织尺度上的行为。年龄对骨量、密度和矿物质行为的影响与骨细胞 TGFβ 无关。我们确定，随着年龄的增长，骨质量下降是由于骨细胞功能丧失和 TGFβ 依赖性胶原蛋白完整性维持能力丧失所致。