Abstract
Age-related bone loss and associated fracture risk are major problems in musculoskeletal health. Osteocytes have emerged as key regulators of bone mass and as a therapeutic target for preventing bone loss. As aging is associated with changes in the osteocyte lacunocanalicular system, we focused on the responsible cellular mechanisms in osteocytes. Bone phenotypic analysis was performed in young-(5mo) and aged-(22mo) C57BL/6 mice and changes in bone structure/geometry correlated with alterations in osteocyte parameters determined using novel multiplexed-3D-confocal imaging techniques. Age-related bone changes analogous to those in humans were observed, including increased cortical diameter, decreased cortical thickness, reduced trabecular BV/TV and cortical porosities. This was associated with a dramatic reduction in osteocyte dendrite number and cell density, particularly in females, where osteocyte dendricity decreased linearly from 5, 12, 18 to 22mo and correlated significantly with cortical bone parameters. Reduced dendricity preceded decreased osteocyte number, suggesting dendrite loss may trigger loss of viability. Age-related degeneration of osteocyte networks may impair bone anabolic responses to loading and gender differences in osteocyte cell body and lacunar fluid volumes we observed in aged mice may lead to gender-related differences in mechanosensitivity. Therapies to preserve osteocyte dendricity and viability may be beneficial for bone health in aging.
Highlights
Aging is associated with osteoporosis, a disease of reduced bone mass and quality, which leads to increased fracture risk
As aging is associated with changes in the osteocyte lacunocanalicular system, we focused on the responsible cellular mechanisms in osteocytes
Bone phenotypic analysis was performed in young‐(5mo) and aged‐(22mo) C57BL/6 mice and changes in bone structure/geometry correlated with alterations in osteocyte parameters determined using novel multiplexed‐3D‐confocal imaging techniques
Summary
Aging is associated with osteoporosis, a disease of reduced bone mass and quality, which leads to increased fracture risk (reviewed in [1]). 40 million women in the U.S have low bone mineral density (BMD) and increased fracture risk [2]. These fractures can lower quality of life and lead to chronic pain. Hip fractures are associated with loss of mobility, loss of independence and the need for institutionalized care. Understanding the mechanisms behind bone loss and the changes in bone quality that occur with aging are critical in order to develop effective measures for prevention of osteoporosis and reduction of fracture risk in the elderly
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