Long-Term Immobilization in Elderly Females Causes a Specific Pattern of Cortical Bone and Osteocyte Deterioration Different From Postmenopausal Osteoporosis

Abstract

Immobilization as a result of long-term bed rest can lead to gradual bone loss. Because of their distribution throughout the bone matrix and remarkable interconnectivity, osteocytes represent the major mechanosensors in bone and translate mechanical into biochemical signals controlling bone remodeling. To test whether immobilization affects the characteristics of the osteocyte network in human cortical bone, femoral diaphyseal bone specimens were analyzed in immobilized female individuals and compared with agematched postmenopausal individuals with primary osteoporosis. Premenopausal and postmenopausal healthy individuals served as control groups. Cortical porosity, osteocyte number and lacunar area, the frequency of hypermineralized lacunae, as well as cortical bone calcium content (CaMean) were assessed using bone histomorphometry and quantitative backscattered electron imaging (qBEI). Bone matrix properties were further analyzed by Fourier transform infrared spectroscopy (FTIR). In the immobilization group, cortical porosity was significantly higher, and qBEI revealed a trend toward higher matrix mineralization compared with osteoporotic individuals. Osteocyte density and canalicular density showed a declining rate from premenopausal toward healthy postmenopausal and osteoporotic individuals with peculiar reductions in the immobilization group, whereas the number of hypermineralized lacunae accumulated inversely. In conclusion, reduced osteocyte density and impaired connectivity during immobilization are associated with a specific bone loss pattern, reflecting a phenotype clearly distinguishable from postmenopausal osteoporosis. Immobilization periods may lead to a loss of survival signals for osteocytes, provoking bone loss that is even higher than in osteoporosis states, whereas osteocytic osteolysis remains absent.

Disuse Osteoporosis: Clinical and Mechanistic Insights

“…To decipher the mechanisms of disuse-induced bone loss, loading and unloading conditions have been modeled in a variety of human and animal studies. In one of our previous experimental human cadaveric studies analyzing the micromorphology of cortical bone, we found increased cortical porosity in long-term immobilization compared to controls and postmenopausal osteoporosis [79] (Fig. 3a), which supports previous clinical findings of a primary effect on cortical porosity after disuse [38].…”

Influence of Prednisolone and Alendronate on the de novo Mineralization of Zebrafish Caudal Fin

“…Osteoporotic‐like bones are characterized by the mineral resorption caused by increased osteoclasts activity that often reconfigure bone's microarchitecture. ( 3,13,46 ) Following the overall trend in this research, the proximal areas verified by AFM revealed a different appearance from those obtained from distal sites. The frequent and low amplitude peaks images found in the bones extracted from the proximal regions are characteristic from highly mineralized tissues.…”

A novel, multi-level approach to assess allograft incorporation in revision total hip arthroplasty

“…For example, although load has been found to have only minor influences on graft incorporation 41 , this study was based on a goat model with only short-term follow-up. It is generally known that mechanical loads have a remarkable impact on skeletal remodeling and overall integrity 42 . Especially the comparison between the acetabular and the femoral specimens could help to answer this question.…”