Osteoporosis is a kind of global chronic bone disease characterized by progressive loss of bone mass and bone quality reduction, leading to a largely increased risk of bone fragility. In clinics, the current treatment of osteoporosis relies on the inhibition of bone damage by osteoclasts but ignores the function of immune cells in the progress of osteoporosis, leading to much compromised therapeutic efficacy. In this work, a highly effective osteoporosis-immunotherapeutic modality is established for the treatment of osteoporosis based on acid neutralization in synergy with immune microenvironment regulation by a specially designed nanocatalytic medicine, calcein functionalized calcium-aluminum-layered double hydroxide (CALC) nanosheets. Briefly, the mildly alkaline CALC nanosheets could neutralize the acidic microenvironment of osteoporosis accompanying the acidity-responsive LDH degradation. Subsequently, calcium phosphate nanoparticles (CAPs) are generated by the reaction between the released Ca2+ from LDH degradation and endogenous phosphates, resulting in M2 phenotype anti-inflammatory differentiation of bone macrophages through a c-Maf transcriptional factor pathway and the following activity enhancements of regulatory T cells (Treg) and the deactivation of T helper 17 cells (TH17). Both in vitro and in vivo results show an excellent therapeutic efficacy on osteoporosis featuring a significant BV/TV (%) enhancement of femurs from 6.2 to 10.7, demonstrating high feasibility of this therapeutic concept through the combined acid neutralization and immune regulation. Such an inorganic nanomaterial-based strategy provides a novel, efficient, and biosafe therapeutic modality for intractable osteoporosis treatment, which will benefit patients suffering from osteoporosis.

Acid Neutralization and Immune Regulation by Calcium-Aluminum-Layered Double Hydroxide for Osteoporosis Reversion.

Osteoporosis is a prevalent bone disorder characterized by bone mass reduction and deterioration of bone microarchitecture leading to bone fragility and fracture risk. In recent decades, knowledge regarding the etiological mechanisms emphasizes that inflammation, oxidative stress and senescence of bone cells contribute to the development of osteoporosis. Studies have demonstrated that heme oxygenase 1 (HO-1), an inducible enzyme catalyzing heme degradation, exhibits anti-inflammatory, anti-oxidative stress and anti-apoptosis properties. Emerging evidence has revealed that HO-1 is critical in the maintenance of bone homeostasis, making HO-1 a potential target for osteoporosis treatment. In this Review, we aim to provide an introduction to current knowledge of HO-1 biology and its regulation, focusing specifically on its roles in bone homeostasis and osteoporosis. We also examine the potential of HO-1-based pharmacological therapeutics for osteoporosis and issues faced during clinical translation.

HO-1 in Bone Biology: Potential Therapeutic Strategies for Osteoporosis

Osteoporosis in patients with rheumatoid arthritis is associated with serum immune regulatory cellular factors

Abstract Osteoporosis is a common skeletal disease with marked bone loss, deterioration of the bone microstructure and bone fragility. An abnormal bone remodelling cycle with relatively increased bone resorption is the crucial pathophysiological mechanism. Bone remodelling is predominantly controlled by osteoblasts and osteoclasts, which are specialized cell types that are regulated by a variety of osteogenic and osteoclastic factors, including cytokines expressed within the bone microenvironment under local or systemic inflammatory conditions. Signal transducer and activator of transcription 3 (STAT3) plays a prominent role in the communication between cytokines and kinases by binding downstream gene promotors and is involved in a wide range of biological or pathological processes. Emerging evidence suggests that STAT3 and its network participate in bone remodelling and the development of osteoporosis, and this factor may be a potent target for osteoporosis treatment. This review focuses on the role and molecular mechanism of the STAT3 signalling pathway in osteogenesis, osteoclastogenesis and osteoporosis, particularly the bone-related cytokines that regulate the osteoblastic differentiation of bone marrow stromal cells and the osteoclastic differentiation of bone marrow macrophages by initiating STAT3 signalling. This review also examines the cellular interactions among immune cells, haematopoietic cells and osteoblastic/osteoclastic cells. 

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STAT3-mediated osteogenesis and osteoclastogenesis in osteoporosis

MicroRNAs (MiRNAs) are small endogenous non-coding RNAs that bind to the 3'-untranslated region of target genes and promote their degradation or inhibit translation, thereby regulating gene expression. MiRNAs are ubiquitous in biology and are involved in many biological processes, playing an important role in a variety of physiological and pathological processes. MiRNA-21 (miR-21) is one of them. In recent years, miR-21 has received a lot of attention from researchers as an emerging player in orthopedic diseases. MiR-21 is closely associated with the occurrence, development, treatment, and prevention of orthopedic diseases through a variety of mechanisms. This review summarizes its effects on osteoblasts, osteoclasts and their relationship with osteoporosis, fracture, osteoarthritis (OA), osteonecrosis, providing a new way of thinking for the diagnosis, treatment and prevention of these bone diseases.

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MicroRNA-21: An Emerging Player in Bone Diseases.

Osteoporosis is the most prevalent metabolic bone disease that affects half the women in the sixth and seventh decade of life. Osteoporosis is characterized by uncoupled bone resorption that leads to low bone mass, compromised microarchitecture and structural deterioration that increases the likelihood of fracture with minimal trauma, known as fragility fractures. Several factors contribute to osteoporosis in men and women. In women, menopause - the cessation of ovarian function, is one of the leading causes of primary osteoporosis. Over the past three decades there has been growing appreciation that the adaptive immune system plays a fundamental role in the development of postmenopausal osteoporosis, both in humans and in mouse models. In this review, we highlight recent data on the interactions between T cells and the skeletal system in the context of postmenopausal osteoporosis. Finally, we review recent studies on the interventions to ameliorate osteoporosis.

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T-Cell Mediated Inflammation in Postmenopausal Osteoporosis.

IntroductionCancer is the leading cause of death in the world. There was a high prevalence of high self-perceived burden (SPB) among cancer patients and this could bring adverse consequences to the physical and mental health of cancer patients, which can lead to suicide if not treated well. This review aims to determine the prevalence of SPB among cancer patients and its risk factors.MethodsPublished journals before September 2021, from five databases (PubMed, ScienceDirect, Springer, Cochrane, and CNKI) were retrieved according to the keywords. The keywords used included cancer patients, terminally ill patients, cancer, SPB, self-perceived burden, self-burden, self-perceived, factor, predictor, associated factor, determinants, risk factor, prognostic factor, covariate, independent variable, and variable. The quality of the inclusion and exclusion criteria was independently reviewed by three researchers.ResultsOut of 12,712 articles, there are 22 studies met the eligibility criteria. The prevalence of SPB among cancer patients ranged from 73.2 to 100% in Malaysia, China, and Canada. Most of them had moderate SPB. Out of the reported factors, age, gender, marital status, ethnicity, residence, educational level, occupational status, family income, primary caregiver, payment methods, disease-related factors, psychological factors, and physical factors were mostly reported across the studies.ConclusionsIn conclusion, SPB prevalence is high in cancer patients. Therefore, hospitals, non-governmental organizations, relevant policymakers, and communities can provide special programs for high-risk groups to provide psychological guidance or design corresponding interventions to reduce the SPB level of patients and improve the quality of life. 

https://www.researchsquare.com/article/rs-1472131/latest.pdf

Systematic review on factors associated with self-perceived burden among cancer patients

A great achievement of modern medicine is the increased lifespan of the human population. Unfortunately, the comorbidities of aging have created a large economic and health burden on society. Osteoporosis is the most prevalent age-related disease. It is characterized by uncoupled bone resorption that leads to low bone mass, compromised microarchitecture and structural deterioration that increases the likelihood of fracture with minimal trauma, known as fragility fractures. These fractures lead to disproportionally high mortality rate and a drastic decline in quality of life for those affected. While estrogen loss is one known trigger of osteoporosis, a number of recent studies have shown that osteoporosis is a multifactorial condition in both humans and rodent models. The presence or absence of certain factors are likely to determine which subset of the population develop osteoporosis. In this chapter, we review the factors that contribute to osteoporosis with an emphasis on its multifactorial nature and the therapeutic consequences.

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Di Wu

Papers

T-Cell Mediated Inflammation in Postmenopausal Osteoporosis.

Systematic review on factors associated with self-perceived burden among cancer patients

Osteoporosis: A Multifactorial Disease