International Journal of Molecular Sciences

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Open AccessEditorial

Secondary Osteoporosis: A Still Neglected Condition

by Vittoria Favero, Cristina Eller-Vainicher and Iacopo Chiodini

Int. J. Mol. Sci. 2023, 24(10), 8558; https://doi.org/10.3390/ijms24108558 - 10 May 2023

Cited by 2 | Viewed by 1766

Abstract

The condition of “secondary osteoporosis” is defined as a bone loss that results from specific well-defined clinical disorders [...] Full article

(This article belongs to the Special Issue Secondary Osteoporosis in Adults 2.0)

Research

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15 pages, 3826 KiB

Open AccessArticle

Systemic Administration of Recombinant Irisin Accelerates Fracture Healing in Mice

by Silvia Concetta Colucci, Cinzia Buccoliero, Lorenzo Sanesi, Mariella Errede, Graziana Colaianni, Tiziana Annese, Mohd Parvez Khan, Roberta Zerlotin, Manuela Dicarlo, Ernestina Schipani, Kenneth M. Kozloff and Maria Grano

Int. J. Mol. Sci. 2021, 22(19), 10863; https://doi.org/10.3390/ijms221910863 - 8 Oct 2021

Cited by 25 | Viewed by 2838

Abstract

To date, pharmacological strategies designed to accelerate bone fracture healing are lacking. We subjected 8-week-old C57BL/6 male mice to closed, transverse, mid-diaphyseal tibial fractures and treated them with intraperitoneal injection of a vehicle or r-irisin (100 µg/kg/weekly) immediately following fracture for 10 days [...] Read more.

To date, pharmacological strategies designed to accelerate bone fracture healing are lacking. We subjected 8-week-old C57BL/6 male mice to closed, transverse, mid-diaphyseal tibial fractures and treated them with intraperitoneal injection of a vehicle or r-irisin (100 µg/kg/weekly) immediately following fracture for 10 days or 28 days. Histological analysis of the cartilaginous callus at 10 days showed a threefold increase in Collagen Type X (p = 0.0012) and a reduced content of proteoglycans (40%; p = 0.0018). Osteoclast count within the callus showed a 2.4-fold increase compared with untreated mice (p = 0.026), indicating a more advanced stage of endochondral ossification of the callus during the early stage of fracture repair. Further evidence that irisin induced the transition of cartilage callus into bony callus was provided by a twofold reduction in the expression of SOX9 (p = 0.0058) and a 2.2-fold increase in RUNX2 (p = 0.0137). Twenty-eight days post-fracture, microCT analyses showed that total callus volume and bone volume were increased by 68% (p = 0.0003) and 67% (p = 0.0093), respectively, and bone mineral content was 74% higher (p = 0.0012) in irisin-treated mice than in controls. Our findings suggest that irisin promotes bone formation in the bony callus and accelerates the fracture repair process, suggesting a possible use as a novel pharmacologic modulator of fracture healing. Full article

(This article belongs to the Special Issue Secondary Osteoporosis in Adults 2.0)

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20 pages, 6408 KiB

Open AccessArticle

A Neuroprotective Bovine Colostrum Attenuates Apoptosis in Dexamethasone-Treated MC3T3-E1 Osteoblastic Cells

by Sagrario Martin-Aragon, Paloma Bermejo-Bescós, Juana Benedí, Carlos Raposo, Franklim Marques, Eirini K. Kydonaki, Paraskevi Gkiata, Yiannis Koutedakis, Georgia Ntina, Andres E. Carrillo and Tânia Amorim

Int. J. Mol. Sci. 2021, 22(19), 10195; https://doi.org/10.3390/ijms221910195 - 22 Sep 2021

Cited by 7 | Viewed by 3821

Abstract

Glucocorticoid-induced osteoporosis (GIO) is one of the most common secondary forms of osteoporosis. GIO is partially due to the apoptosis of osteoblasts and osteocytes. In addition, high doses of dexamethasone (DEX), a synthetic glucocorticoid receptor agonist, induces neurodegeneration by initiating inflammatory processes leading [...] Read more.

Glucocorticoid-induced osteoporosis (GIO) is one of the most common secondary forms of osteoporosis. GIO is partially due to the apoptosis of osteoblasts and osteocytes. In addition, high doses of dexamethasone (DEX), a synthetic glucocorticoid receptor agonist, induces neurodegeneration by initiating inflammatory processes leading to neural apoptosis. Here, a neuroprotective bovine colostrum against glucocorticoid-induced neuronal damage was investigated for its anti-apoptotic activity in glucocorticoid-treated MC3T3-E1 osteoblastic cells. A model of apoptotic osteoblastic cells was developed by exposing MC3T3-E1 cells to DEX (0–700 μM). Colostrum co-treated with DEX was executed at 0.1–5.0 mg/mL. Cell viability was measured for all treatment schedules. Caspase-3 activation was assessed to determine both osteoblast apoptosis under DEX exposure and its potential prevention by colostrum co-treatment. Glutathione reduced (GSH) was measured to determine whether DEX-mediated oxidative stress-driven apoptosis is alleviated by colostrum co-treatment. Western blot was performed to determine the levels of p-ERK1/2, Bcl-XL, Bax, and Hsp70 proteins upon DEX or DEX plus colostrum exposure. Colostrum prevented the decrease in cell viability and the increase in caspase-3 activation and oxidative stress caused by DEX exposure. Cells, upon colostrum co-treated with DEX, exhibited higher levels of p-ERK1/2 and lower levels of Bcl-XL, Bax, and Hsp70. Our data support the notion that colostrum may be able to reduce DEX-induced apoptosis possibly via the activation of the ERK pathway and modulation of the Hsp70 system. We provided preliminary evidence on how bovine colostrum, as a complex and multi-component dairy product, in addition to its neuroprotective action, may affect osteoblastic cell survival undergoing apoptosis. Full article

(This article belongs to the Special Issue Secondary Osteoporosis in Adults 2.0)

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15 pages, 2024 KiB

Open AccessArticle

Antiepileptic Stiripentol May Influence Bones

by Agnieszka Matuszewska, Beata Nowak, Anna Nikodem, Anna Merwid-Ląd, Benita Wiatrak, Tomasz Tomkalski, Diana Jędrzejuk, Ewa Szeląg, Tomasz Sozański, Maciej Danielewski, Paulina Jawień, Ireneusz Ceremuga, Marta Szandruk-Bender, Marek Bolanowski, Jarosław Filipiak and Adam Szeląg

Int. J. Mol. Sci. 2021, 22(13), 7162; https://doi.org/10.3390/ijms22137162 - 2 Jul 2021

Cited by 4 | Viewed by 2846

Abstract

Bone structure abnormalities are increasingly observed in patients chronically treated with antiepileptic drugs (AEDs). The majority of the available data concern older conventional AEDs, while the amount of information regarding newer AEDs, including stiripentol, is limited. The aim of the study was to [...] Read more.

Bone structure abnormalities are increasingly observed in patients chronically treated with antiepileptic drugs (AEDs). The majority of the available data concern older conventional AEDs, while the amount of information regarding newer AEDs, including stiripentol, is limited. The aim of the study was to assess the effect of stiripentol on bones. For 24 weeks, male Wistar rats, received 0.9% sodium chloride (control group) or stiripentol (200 mg/kg/day) (STP group). In the 16th week of the study, we detected lower serum PINP levels in the STP group compared to the control group. In the 24th week, a statistically significant lower 1,25-dihydroxyvitamin D₃ level, higher inorganic phosphate level and higher neutrophil gelatinase-associated lipocalin (NGAL) levels in serum were found in the STP group compared to the control. Micro X-ray computed tomography of the tibias demonstrated lower bone volume fraction, lower trabecular thickness, higher trabecular pattern factor and a higher structure model index in the stiripentol group. Considering the results of this experiment on rats which suggests that long-term administration of stiripentol may impair the cancellous bone microarchitecture, further prospective human studies seem to be justified. However, monitoring plasma vitamin D, calcium, inorganic phosphate and kidney function in patients on long-term stiripentol therapy may be suggested. Full article

(This article belongs to the Special Issue Secondary Osteoporosis in Adults 2.0)

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Review

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16 pages, 653 KiB

Open AccessReview

Effects of Biological/Targeted Therapies on Bone Mineral Density in Inflammatory Arthritis

by Tai-Li Chen, Kai-Hung Chang and Kuei-Ying Su

Int. J. Mol. Sci. 2022, 23(8), 4111; https://doi.org/10.3390/ijms23084111 - 8 Apr 2022

Cited by 8 | Viewed by 3788

Abstract

Inflammatory arthritis has been reported to be associated with the development of osteoporosis. Recent research has investigated the mechanisms of bone metabolism in chronic inflammatory arthritis such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). Progress in both animal and clinical studies has provided [...] Read more.

Inflammatory arthritis has been reported to be associated with the development of osteoporosis. Recent research has investigated the mechanisms of bone metabolism in chronic inflammatory arthritis such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). Progress in both animal and clinical studies has provided a better understanding of the osteoclastogenesis-related pathways regarding the receptor activator of nuclear factor-κB ligand (RANKL), anti-citrullinated protein antibodies (ACPAs), and Wnt signaling and Dickkopf-related protein 1 (Dkk-1). The complex interplay between inflammatory cytokines and bone destruction has been elucidated, especially that in the interleukin-17/23 (IL-17/23) axis and Janus kinase and signal transducer and activator of transcription (JAK-STAT) signaling. Moreover, advances in biological and targeted therapies have achieved essential modifications to the bone metabolism of these inflammatory arthritis types. In this narrative review, we discuss recent findings on the pathogenic effects on bone in RA and SpA. Proinflammatory cytokines, autoantibodies, and multiple signaling pathways play an essential role in bone destruction in RA and SpA patients. We also reviewed the underlying pathomechanisms of bone structure in biological and targeted therapies of RA and SpA. The clinical implications of tumor necrosis factor inhibitors, abatacept, rituximab, tocilizumab, Janus kinase inhibitors, and inhibitors of the IL-17/23 axis are discussed. Since these novel therapeutics provide new options for disease improvement and symptom control in patients with RA and SpA, further rigorous evidence is warranted to provide a clinical reference for physicians and patients. Full article

(This article belongs to the Special Issue Secondary Osteoporosis in Adults 2.0)

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26 pages, 1285 KiB

Open AccessReview

Bone Fragility in Gastrointestinal Disorders

by Daniela Merlotti, Christian Mingiano, Roberto Valenti, Guido Cavati, Marco Calabrese, Filippo Pirrotta, Simone Bianciardi, Alberto Palazzuoli and Luigi Gennari

Int. J. Mol. Sci. 2022, 23(5), 2713; https://doi.org/10.3390/ijms23052713 - 28 Feb 2022

Cited by 12 | Viewed by 4928

Abstract

Osteoporosis is a common systemic disease of the skeleton, characterized by compromised bone mass and strength, consequently leading to an increased risk of fragility fractures. In women, the disease mainly occurs due to the menopausal fall in estrogen levels, leading to an imbalance [...] Read more.

Osteoporosis is a common systemic disease of the skeleton, characterized by compromised bone mass and strength, consequently leading to an increased risk of fragility fractures. In women, the disease mainly occurs due to the menopausal fall in estrogen levels, leading to an imbalance between bone resorption and bone formation and, consequently, to bone loss and bone fragility. Moreover, osteoporosis may affect men and may occur as a sequela to different diseases or even to their treatments. Despite their wide prevalence in the general population, the skeletal implications of many gastrointestinal diseases have been poorly investigated and their potential contribution to bone fragility is often underestimated in clinical practice. However, proper functioning of the gastrointestinal system appears essential for the skeleton, allowing correct absorption of calcium, vitamins, or other nutrients relevant to bone, preserving the gastrointestinal barrier function, and maintaining an optimal endocrine-metabolic balance, so that it is very likely that most chronic diseases of the gastrointestinal tract, and even gastrointestinal dysbiosis, may have profound implications for bone health. In this manuscript, we provide an updated and critical revision of the role of major gastrointestinal disorders in the pathogenesis of osteoporosis and fragility fractures. Full article

(This article belongs to the Special Issue Secondary Osteoporosis in Adults 2.0)

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21 pages, 935 KiB

Open AccessReview

Management of Osteoporosis in Men: A Narrative Review

by Fabio Vescini, Iacopo Chiodini, Alberto Falchetti, Andrea Palermo, Antonio Stefano Salcuni, Stefania Bonadonna, Vincenzo De Geronimo, Roberto Cesareo, Luca Giovanelli, Martina Brigo, Francesco Bertoldo, Alfredo Scillitani and Luigi Gennari

Int. J. Mol. Sci. 2021, 22(24), 13640; https://doi.org/10.3390/ijms222413640 - 20 Dec 2021

Cited by 34 | Viewed by 6129

Abstract

Male osteoporosis is a still largely underdiagnosed pathological condition. As a consequence, bone fragility in men remains undertreated mainly due to the low screening frequency and to controversies in the bone mineral density (BMD) testing standards. Up to the 40% of overall osteoporotic [...] Read more.

Male osteoporosis is a still largely underdiagnosed pathological condition. As a consequence, bone fragility in men remains undertreated mainly due to the low screening frequency and to controversies in the bone mineral density (BMD) testing standards. Up to the 40% of overall osteoporotic fractures affect men, in spite of the fact that women have a significant higher prevalence of osteoporosis. In addition, in males, hip fractures are associated with increased morbidity and mortality as compared to women. Importantly, male fractures occur about 10 years later in life than women, and, therefore, due to the advanced age, men may have more comorbidities and, consequently, their mortality is about twice the rate in women. Gender differences, which begin during puberty, lead to wider bones in males as compared with females. In men, follicle-stimulating hormones, testosterone, estrogens, and sex hormone-binding levels, together with genetic factors, interact in determining the peak of bone mass, BMD maintenance, and lifetime decrease. As compared with women, men are more frequently affected by secondary osteoporosis. Therefore, in all osteoporotic men, a complete clinical history should be collected and a careful physical examination should be done, in order to find clues of a possible underlying diseases and, ultimately, to guide laboratory testing. Currently, the pharmacological therapy of male osteoporosis includes aminobisphosphonates, denosumab, and teriparatide. Hypogonadal patients may be treated with testosterone replacement therapy. Given that the fractures related to mortality are higher in men than in women, treating male subjects with osteoporosis is of the utmost importance in clinical practice, as it may impact on mortality even more than in women. Full article

(This article belongs to the Special Issue Secondary Osteoporosis in Adults 2.0)

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34 pages, 314 KiB

Open AccessReview

Congenital Metabolic Bone Disorders as a Cause of Bone Fragility

by Francesca Marini, Francesca Giusti, Teresa Iantomasi and Maria Luisa Brandi

Int. J. Mol. Sci. 2021, 22(19), 10281; https://doi.org/10.3390/ijms221910281 - 24 Sep 2021

Cited by 6 | Viewed by 2667

Abstract

Bone fragility is a pathological condition caused by altered homeostasis of the mineralized bone mass with deterioration of the microarchitecture of the bone tissue, which results in a reduction of bone strength and an increased risk of fracture, even in the absence of [...] Read more.

Bone fragility is a pathological condition caused by altered homeostasis of the mineralized bone mass with deterioration of the microarchitecture of the bone tissue, which results in a reduction of bone strength and an increased risk of fracture, even in the absence of high-impact trauma. The most common cause of bone fragility is primary osteoporosis in the elderly. However, bone fragility can manifest at any age, within the context of a wide spectrum of congenital rare bone metabolic diseases in which the inherited genetic defect alters correct bone modeling and remodeling at different points and aspects of bone synthesis and/or bone resorption, leading to defective bone tissue highly prone to long bone bowing, stress fractures and pseudofractures, and/or fragility fractures. To date, over 100 different Mendelian-inherited metabolic bone disorders have been identified and included in the OMIM database, associated with germinal heterozygote, compound heterozygote, or homozygote mutations, affecting over 80 different genes involved in the regulation of bone and mineral metabolism. This manuscript reviews clinical bone phenotypes, and the associated bone fragility in rare congenital metabolic bone disorders, following a disease taxonomic classification based on deranged bone metabolic activity. Full article

(This article belongs to the Special Issue Secondary Osteoporosis in Adults 2.0)

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