Molecular Targeted Therapy for the Bone Loss Secondary to Pyogenic Spondylodiscitis Using Medications for Osteoporosis: A Literature Review.

Takashi Ohnishi,Norimasa Iwasaki,Yuki Ogawa,Kota Suda,Akio Minami,Satoko Matsumoto Harmon,Mitsuru Asukai,Miki Komatsu,Masahiko Takahata

doi:10.3390/ijms22094453

Takashi Ohnishi, Norimasa Iwasaki + Show 7 more

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https://doi.org/10.3390/ijms22094453

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Abstract

Pyogenic spondylodiscitis can cause severe osteolytic and destructive lesions in the spine. Elderly or immunocompromised individuals are particularly susceptible to infectious diseases; specifically, infections in the spine can impair the ability of the spine to support the trunk, causing patients to be bedridden, which can also severely affect the physical condition of patients. Although treatments for osteoporosis have been well studied, treatments for bone loss secondary to infection remain to be elucidated because they have pathological manifestations that are similar to but distinct from those of osteoporosis. Recently, we encountered a patient with severely osteolytic pyogenic spondylodiscitis who was treated with romosozumab and exhibited enhanced bone formation. Romosozumab stimulated canonical Wnt/β-catenin signaling, causing robust bone formation and the inhibition of bone resorption, which exceeded the bone loss secondary to infection. Bone loss due to infections involves the suppression of osteoblastogenesis by osteoblast apoptosis, which is induced by the nuclear factor-κB and mitogen-activated protein kinase pathways, and osteoclastogenesis with the receptor activator of the nuclear factor-κB ligand-receptor combination and subsequent activation of the nuclear factor of activated T cells cytoplasmic 1 and c-Fos. In this study, we review and discuss the molecular mechanisms of bone loss secondary to infection and analyze the efficacy of the medications for osteoporosis, focusing on romosozumab, teriparatide, denosumab, and bisphosphonates, in treating this pathological condition.

Highlights

The Peculiarity of Bone Loss Secondary to Pyogenic SpondylodiscitisThe peculiarity of the spine versus other regions regarding the locus of infection is a high propensity of patients losing ambulatory competencies
Introduction iationsPyogenic spondylodiscitis is an infection that occurs at an intervertebral disc and the adjacent vertebrae, and it can lead to bone loss and subsequent instability of the spine.Elderly and immunocompromised people are susceptible to spondylodiscitis, have a high risk of being bedridden, and experience a deterioration of their physical condition [1]
We review the molecular signaling pathways involved in bone loss secondary to infection and discuss the potential role of the currently available osteoporosis medications, including romosozumab, teriparatide, denosumab, and bisphosphonates (BPs), in the treatment of this intractable pathological condition

Summary

The Peculiarity of Bone Loss Secondary to Pyogenic Spondylodiscitis

The peculiarity of the spine versus other regions regarding the locus of infection is a high propensity of patients losing ambulatory competencies. Bone loss in pyogenic spondylodiscitis patients is usually rapidly progressive and highly destructive [4]; patients tend to become bedridden and cannot recover ambulatory function without restoring the support and stability of the spine. Major bone loss is due to the causal bacteria and the disuse of the spine owing to bed rest, brace immobilization, and limited sunlight exposure from long hospitalization for intravenous antibiotic administration [5]. Another factor that may lead to abrogating ambulatory competence is neurological deficits. Fast-acting medications for bone loss are ideal for restoring the structure and function of the spine before the general body condition and neurological function deteriorates

Molecular Mechanisms of Bone Resorption Secondary to Infection

Osteoporosis Medications as a Treatment for Bone Loss Secondary to Infection

Anabolic Drug

Antiresorptive Drug

Findings

Conclusions