Reversibility of marrow adipose accumulation and reduction of trabecular bone in the epiphysis of the proximal tibia.

Mechanical stimuli play an important role in the homeostasis of trabecular bone and marrow adipose tissue, particularly for the weight-bearing skeleton. Prolonged immobilization and disuse have been shown to reduce trabecular bone content and increase marrow adipose tissue in the bones of lower limb joints such as the knee. However, details on the temporal response of this relationship to prolonged immobilization and its reversibility is limited. Forty rats had one knee immobilized at 45° of flexion for 2, 4, 8, or 16 weeks and subsequently remobilized for 0 or 8 weeks. The contralateral knees were used as controls. Histomorphometric measures of trabecular bone and marrow adipose tissue (MAT) areas were conducted in the epiphysis of the proximal tibia. Knee immobilization for 4, 8, and 16 weeks significantly reduced trabecular bone area by -0.125, -0.139, and -0.161 mm2/mm2, respectively, with corresponding 95 % CIs of [-0.012, -0.239], [-0.006, -0.273], and [-0.101, -0.221]. MAT area significantly increased at 2 and 16 weeks by +0.008 and +0.027 mm2/mm2, respectively, with 95 % CIs of [0.014, 0.002] and [0.039, 0.016]. Remobilization for 8 weeks restored trabecular bone area compared to the contralateral knee and the magnitude of change was significantly greater for 8 and 16 weeks of immobilization with effect sizes of 1.69 and 1.86, respectively. The difference in MAT area between immobilized and contralateral knees were eliminated with remobilization. These results characterize the temporal response of trabecular bone and MAT in the epiphysis of the proximal tibia to joint immobilization and remobilization.

Hyperplasia and accelerated hypertrophy of marrow adipocytes with knee immobilization were sustained despite remobilization.

Skeletal disuse can cause an accumulation of bone marrow adipose tissue (MAT) characterized by a combination of marrow adipocyte hyperplasia and/or hypertrophy. The malleability of MAT accumulation and of the hyperplasia and hypertrophy upon remobilization is unknown. In this study, we showed extensive hyperplasia and accelerated hypertrophy of bone marrow adipocytes in the proximal tibia epiphysis of rat knees immobilized for durations between 1 and 32 wk. Similar histomorphometric measures of adipocytes carried out in unoperated controls allowed distinguishing the effects of immobilization from the effects of aging. Although both knee immobilization and aging led to adipocyte hypertrophy, adipocyte hyperplasia was the hallmark signature effect of immobilization on MAT. Both bone marrow adipocyte hyperplasia and hypertrophy were sustained despite knee remobilization for durations up to four times the duration of immobilization. These results suggest that adipocyte hyperplasia is the predominant mechanism explaining MAT accumulation in skeletal disuse. In this model, the changes were unremitting for the investigated time points. Investigating the cellular and molecular mechanisms of marrow adipocyte mechanoregulation will be important to better understand how adipocytes adapt to changes in mechanical environments.NEW & NOTEWORTHY This longitudinal study elucidates the response of marrow adipose tissue adipocytes in weight-bearing joints to changes in different mechanical environments, and we provide insight on the malleability of the changes over time. In a rat animal model, knee immobilization induced hyperplasia and accelerated the age-dependent hypertrophy of adipocytes. Changes in adipocyte number and size were sustained despite unassisted remobilization. Multimodal distributions of cell size were characteristic of bone marrow adipocytes.