Disuse Osteoporosis: Clinical and Mechanistic Insights

Tim Rolvien,Michael Amling

doi:10.1007/s00223-021-00836-1

Tim Rolvien, Michael Amling

Open Access

https://doi.org/10.1007/s00223-021-00836-1

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Abstract

Disuse osteoporosis describes a state of bone loss due to local skeletal unloading or systemic immobilization. This review will discuss advances in the field that have shed light on clinical observations, mechanistic insights and options for the treatment of disuse osteoporosis. Clinical settings of disuse osteoporosis include spinal cord injury, other neurological and neuromuscular disorders, immobilization after fractures and bed rest (real or modeled). Furthermore, spaceflight-induced bone loss represents a well-known adaptive process to microgravity. Clinical studies have outlined that immobilization leads to immediate bone loss in both the trabecular and cortical compartments accompanied by relatively increased bone resorption and decreased bone formation. The fact that the low bone formation state has been linked to high levels of the osteocyte-secreted protein sclerostin is one of the many findings that has brought matrix-embedded, mechanosensitive osteocytes into focus in the search for mechanistic principles. Previous basic research has primarily involved rodent models based on tail suspension, spaceflight and other immobilization methods, which have underlined the importance of osteocytes in the pathogenesis of disuse osteoporosis. Furthermore, molecular-based in vitro and in vivo approaches have revealed that osteocytes sense mechanical loading through mechanosensors that translate extracellular mechanical signals to intracellular biochemical signals and regulate gene expression. Osteocytic mechanosensors include the osteocyte cytoskeleton and dendritic processes within the lacuno-canalicular system (LCS), ion channels (e.g., Piezo1), extracellular matrix, primary cilia, focal adhesions (integrin-based) and hemichannels and gap junctions (connexin-based). Overall, disuse represents one of the major factors contributing to immediate bone loss and osteoporosis, and alterations in osteocytic pathways appear crucial to the bone loss associated with unloading.

Highlights

Skeletal integrity is maintained by the process of bone remodeling, i.e., the balanced removal of old bone matrix by bone-resorbing osteoclasts and the deposition of new bone tissue by bone-forming osteoblasts [1]
To obtain more detailed data on the bone loss associated with disuse beyond Dual-energy X-ray absorptiometry (DXA)-based observations, volumetric and microstructural approaches, primarily peripheral quantitative computed tomography and, more recently, high-resolution peripheral quantitative computed tomography (HR-pQCT), have been introduced
Previous pQCT studies with cross-sectional study designs have demonstrated negative associations between the duration of disuse and bone microstructural parameters in patients with spinal cord injury, where steady states were reached after 3–8 years and the total amount of bone loss ranged from 25–35% to 50–60% [60]

Summary

Introduction

Skeletal integrity is maintained by the process of bone remodeling, i.e., the balanced removal of old bone matrix by bone-resorbing osteoclasts and the deposition of new bone tissue by bone-forming osteoblasts [1]. To further address the magnitude and mechanisms of disuse-induced bone loss, a number of bed rest studies have been performed, with different approaches. In previous clinical studies focusing on laboratory changes in bone turnover, disuse or unloading was associated with increased bone turnover (primarily bone resorption) across different disuse conditions such as spinal cord injury [23, 24], vegetative state [35] or spaceflight [38].

Results

Conclusion