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Article ; Online: Bone diseases and the COVID-19 pandemic

Francisco Bandeira / John P. Bilezikian

Archives of Endocrinology and Metabolism, Vol 66, Iss 5, Pp 589-

2022 Volume 590

Keywords	Medicine ; R ; Diseases of the endocrine glands. Clinical endocrinology ; RC648-665
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	Brazilian Society of Endocrinology and Metabolism
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Long-term consequences of osteoporosis therapy with denosumab

Francisco Bandeira / Lucian Batista de Oliveira / John P. Bilezikian

Archives of Endocrinology and Metabolism, Vol 66, Iss 5, Pp 717-

2022 Volume 723

Abstract: ABSTRACT Denosumab (DMAb) is a human monoclonal antibody used as an antiresorptive drug in the treatment of osteoporosis. Approval at a dosage of 60 mg every 6 months was based on the results of the randomized, placebo-controlled trial (FREEDOM). The ... ...

Abstract	ABSTRACT Denosumab (DMAb) is a human monoclonal antibody used as an antiresorptive drug in the treatment of osteoporosis. Approval at a dosage of 60 mg every 6 months was based on the results of the randomized, placebo-controlled trial (FREEDOM). The design of this 3-year study included an extension for up to 10 years. Those who were randomized to DMAb continued on drug, while those who were randomized to placebo transitioned to DMAb. The 10-year experience with DMAb provides data on efficacy of drug in terms of reduced fractures and continued increases in bone mineral density (BMD). The 10-year experience with denosumab also provides information about rare complications associated with the use of DMAb, such as osteonecrosis of the jaw (ONJ), and atypical femoral fractures (AFF). This experience provided new insights into the reversibility of effects upon discontinuation without follow-on therapy with another agent. This review focuses upon prolonged treatment with DMAb, with regard to beneficial effects on fracture reduction and safety. Additionally, its use in patients with impaired renal function, compare its results with those of bisphosphonates (BPs), the occurrence/frequency of complications, in addition to the use of different tools, from imaging techniques to histological findings, to evaluate its effects on bone tissue.
Keywords	Denosumab ; osteoporosis ; fractures ; osteonecrosis ; bone remodeling ; Medicine ; R ; Diseases of the endocrine glands. Clinical endocrinology ; RC648-665
Subject code	610
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	Brazilian Society of Endocrinology and Metabolism
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Controversies in the treatment of postmenopausal osteoporosis

Francisco Bandeira / Wesdrey Dantas / John P. Bilezikian

Archives of Endocrinology and Metabolism, Vol 64, Iss 4, Pp 331-

How long to treat with bisphosphonates?

2020 Volume 336

Abstract: ABSTRACT Osteoporosis is a systemic skeletal disease characterized by reduced bone mass and deterioration of bone tissue microarchitecture leading to an increased risk of fractures. Fragility fractures, especially hip fractures, are associated with a ... ...

Abstract	ABSTRACT Osteoporosis is a systemic skeletal disease characterized by reduced bone mass and deterioration of bone tissue microarchitecture leading to an increased risk of fractures. Fragility fractures, especially hip fractures, are associated with a significant reduction in the physical function and quality of life of affected patients, as well as increased mortality, leading to a major financial impact on health care. Many drugs have been registered for the treatment of osteoporosis and very recently, a new anabolic agent, romosozumab, has been approved in some countries. Despite the expansion of efficacious antiresorptive and anabolic therapies in recent years, a concomitant increase in concerns have been raised by physicians, patients and the lay press about the potential for adverse events, especially atypical femoral fractures (AFF) following prolonged use of bisphosphonates. Whatever the mechanism(s) may be, direct or indirect, linking prolonged bisphosphonate use to atypical femoral fractures, this adverse event is very rare in comparison to the magnitude of risk reduction of typical osteoporotic fractures. An estimated 162 osteoporosis-related fractures are prevented for each atypical femoral fracture associated with an anti-resorptive medication. Until a risk calculator for predicting risk of atypical fractures, becomes available in clinical practice, and we view this as an unlikely scenario, it is up to the physician to consider continuing or discontinuing bisphosphonate use after the critical 3-5 year period of treatment with zoledronic acid or alendronate, but close monitoring for the residual bone effects overtime should be planned. For other bisphosphonates, in which no residual effects are expected, drug holiday is usually not applied.
Keywords	Osteoporosis ; bisphosphonates ; drug holiday ; atypical femoral fractures ; Medicine ; R ; Diseases of the endocrine glands. Clinical endocrinology ; RC648-665
Subject code	610
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	Brazilian Society of Endocrinology and Metabolism
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Musculoskeletal effects of obesity and bariatric surgery – a narrative review

Narriane Holanda / Nara Crispim / Ingrid Carlos / Taíssa Moura / Eduardo Nóbrega / Francisco Bandeira

Archives of Endocrinology and Metabolism, Vol 66, Iss 5, Pp 621-

2022 Volume 632

Abstract: Abstract Obesity affects several areas of the human body, leading to increased morbidity and mortality and the likelihood of other diseases, such as type 2 diabetes mellitus, cardiovascular diseases and musculoskeletal disorders. These conditions ... ...

Abstract	Abstract Obesity affects several areas of the human body, leading to increased morbidity and mortality and the likelihood of other diseases, such as type 2 diabetes mellitus, cardiovascular diseases and musculoskeletal disorders. These conditions predispose to bone fractures and sarcopenic obesity, defined by the presence of an obesity-associated decrease in muscle mass and strength. Both bone fragility and sarcopenic obesity disease are consequences of several factors, such as a low degree of chronic inflammation, insulin resistance, hormonal changes, nutritional deficiencies, ectopic fat deposits and sedentary lifestyle. The diagnosis of obesity-related musculoskeletal disorders is limited by the lack of sarcopenia criteria and lower accuracy of bone mineral density measurement by dual-energy X-ray absorptiometry in overweight people. Reducing body weight provides undeniable benefits to this population, however treating cases of severe obesity with bariatric surgery can cause even greater damage to bone and muscle health, especially in the long term. The mechanisms involved in this process are not yet fully understood, but factors related to nutrient malabsorption and mechanical discharge as well as changes in gut hormones, adipokines and bone marrow adiposity should be taken into account. Depending on the surgical technique performed, greater musculoskeletal damage may occur, especially in cases of malabsorptive surgeries such as Roux-en-Y gastric bypass, when compared to restrictive techniques such as sleeve gastrectomy. This difference is probably due to greater weight loss, nutrient malabsorption and important hormonal changes that occur as a consequence of the diversion of intestinal transit and loss of greater absorptive surface. Thus, people undergoing bariatric procedures, especially malabsorptive ones, should have their musculoskeletal health supervised to allow early diagnosis and appropriate therapeutic interventions to prevent osteoporotic fractures and preserve the functionality of the skeletal ...
Keywords	Obesity ; bariatric surgery ; bone ; sarcopenia ; Medicine ; R ; Diseases of the endocrine glands. Clinical endocrinology ; RC648-665
Subject code	616
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	Brazilian Society of Endocrinology and Metabolism
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Skeletal consequences of heart failure

Francisco Bandeira / Lucian Batista de Oliveira / Rodrigo Botelho Caldeira / Leticia Saldanha Toscano

Women's Health, Vol

2022 Volume 18

Abstract: Heart failure (HF) is a prevalent clinical syndrome that causes significant physical limitations. Osteoporosis is also an important cause of loss of functionality, and it mainly affects women. There are several reports linking HF and osteoporosis, and ... ...

Abstract	Heart failure (HF) is a prevalent clinical syndrome that causes significant physical limitations. Osteoporosis is also an important cause of loss of functionality, and it mainly affects women. There are several reports linking HF and osteoporosis, and both share risk factors. Most of the data available so far point to bone fragility as a consequence of HF, and several mechanisms have been identified to explain this relationship. Among the proposed pathophysiological mechanisms are the hyperactivation of the renin–angiotensin–aldosterone system and the increase in parathyroid hormone, functional limitation, production of inflammatory mediators and the use of drugs for HF. The role of osteoprotegerin has gained attention owing to its cardiovascular and skeletal effects, its observed deficiency during the postmenopausal period along with its compensatory increases in HF and severe osteoporosis. The objective of this review was to perform a literature search for the main evidence on skeletal impairment in HF, with emphasis on women. As for epidemiological studies, we selected data from 3 meta-analyses and 20 individual observational studies, which together showed the interrelationship between the two clinical conditions in terms of both decreased bone density and increased fracture risk. In conclusion, HF and osteoporosis are interrelated conditions mediated by complex pathophysiological mechanisms which may be more relevant for postmenopausal women, considered to be a vulnerable population for both cardiovascular diseases and bone fragility.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	SAGE Publishing
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A obesidade realmente fortalece os ossos?

Francisco Bandeira

Arquivos brasileiros de Endocrinologia e Metabologia, Vol 51, Iss 6, Pp 895-

2007 Volume 897

Keywords	Diseases of the endocrine glands. Clinical endocrinology ; RC648-665 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Internal medicine ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Language	Portuguese
Publishing date	2007-08-01T00:00:00Z
Publisher	Sociedade Brasileira de Endocrinologia e Metabologia
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cellular therapy of corneal epithelial defect by adipose mesenchymal stem cell-derived epithelial progenitors

Francisco Bandeira / Tze-Wei Goh / Melina Setiawan / Gary Hin-Fai Yam / Jodhbir S. Mehta

Stem Cell Research & Therapy, Vol 11, Iss 1, Pp 1-

2020 Volume 13

Abstract: Abstract Background Persistent epithelial defects (PED), associated with limbal stem cell deficiency (LSCD), require ocular surface reconstruction with a stable corneal epithelium (CE). This study investigated CE reformation using human adipose ... ...

Abstract	Abstract Background Persistent epithelial defects (PED), associated with limbal stem cell deficiency (LSCD), require ocular surface reconstruction with a stable corneal epithelium (CE). This study investigated CE reformation using human adipose mesenchymal stem cells (ADSC), which derived epithelial progenitors via mesenchymal-epithelial transition (MET). Methods STEMPRO human ADSC were cultured with specific inhibitors antagonizing glycogen synthase kinase-3 and transforming growth factor-β signaling, followed by culture under a defined progenitor cell targeted-epithelial differentiation condition to generate epithelial-like cells (MET-Epi), which were characterized for cell viability, mesenchymal, and epithelial phenotypes using immunofluorescence and flow cytometry. Tissue-engineered (TE) MET-Epi cells on fibrin gel were transplanted to corneal surface of the rat LSCD model caused by alkali injury. Epithelial healing, corneal edema, and haze grading, CE formation were assessed by fluorescein staining, slit lamp bio-microscopy, anterior segment optical coherence tomography, and immunohistochemistry. Results CD73high/CD90high/CD105high/CD166high/CD14negative/CD31negative human ADSC underwent MET, giving viable epithelial-like progenitors expressing δNp63, CDH1 (E-cadherin), epidermal growth factor receptor, integrin-β4, and cytokeratin (CK)-5, 9. Under defined epithelial differentiation culture, these progenitors generated MET-Epi cells expressing cell junction proteins ZO1 and occludin. When transplanted onto rat corneal surface with LSCD-induced PED, TE-MET-Epi achieved more efficient epithelial healing, suppressed corneal edema, and opacities, when compared to corneas without treatment or transplanted with TE-ADSC. CE markers (CK3, 12, and CDH1) were expressed on TE-MET-Epi-transplanted corneas but not in other control groups. Conclusion Human ADSC-derived epithelial-like cells, via MET, recovered the CE from PED associated with LSCD. ADSC can be a viable adult stem cell source for potential autologous ...
Keywords	Corneal epithelium ; Limbal stem cell deficiency ; Adipose mesenchymal stem cells ; Mesenchymal-epithelial transition ; Epithelial reconstruction ; Medicine (General) ; R5-920 ; Biochemistry ; QD415-436
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A Framework for Human Corneal Endothelial Cell Culture and Preliminary Wound Model Experiments with a New Cell Tracking Approach

Francisco Bandeira / Gustavo Teixeira Grottone / Joyce Luciana Covre / Priscila Cardoso Cristovam / Renata Ruoco Loureiro / Francisco Irochima Pinheiro / Ricardo Pedro Casaroli-Marano / Waleska Donato / José Álvaro Pereira Gomes

International Journal of Molecular Sciences, Vol 24, Iss 2982, p

2023 Volume 2982

Abstract: Cell injection therapy is emerging as an alternative to treat corneal endothelial dysfunction (CED) and to avoid corneal scarring due to bullous keratopathy. However, establishing a standardized culture procedure that provides appropriate cell yield ... ...

Abstract	Cell injection therapy is emerging as an alternative to treat corneal endothelial dysfunction (CED) and to avoid corneal scarring due to bullous keratopathy. However, establishing a standardized culture procedure that provides appropriate cell yield while retaining functional features remains a challenge. Here, we describe a detailed framework obtained from in vitro culture of human corneal endothelial cells (HCECs) and comparative in vivo experimental models for CED treatment with a new cell tracking approach. Two digestion methods were compared regarding HCEC morphology and adhesion. The effect of Y-27632 (ROCKi) supplementation on final cell yield was also assessed. Cell adhesion efficacy with two cell delivery systems (superparamagnetic embedding and cell suspension) was evaluated in an ex vivo human cornea model and in an in vivo rabbit CED model. The injection of supplemented culture medium or balanced salt solution (BSS) was used for the positive and negative controls, respectively. HCEC isolation with collagenase resulted in better morphology and adhesion of cultured HCEC when compared to EDTA. Y-27632 supplementation resulted in a 2.6-fold increase in final cell yield compared to the control. Ex vivo and in vivo adhesion with both cell delivery systems was confirmed by cell tracker fluorescence detection. Corneal edema and opacity improved in both animal groups treated with cultured HCEC. The corneas in the control groups remained opaque. Both HCEC delivery systems seemed comparable as treatments for CED and for the prevention of corneal scarring.
Keywords	corneal transplant ; cell therapy ; human corneal endothelial cells ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	570
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Effects of Rho-Associated Kinase (Rock) Inhibitors (Alternative to Y-27632) on Primary Human Corneal Endothelial Cells

Gary S. L. Peh / Francisco Bandeira / Dawn Neo / Khadijah Adnan / Yossa Hartono / Hon Shing Ong / Sacha Naso / Anandalakshmi Venkatraman / José A. P. Gomes / Viridiana Kocaba / Jodhbir S. Mehta

Cells, Vol 12, Iss 1307, p

2023 Volume 1307

Abstract: 1) Rho-associated coiled-coil protein kinase (ROCK) signaling cascade impacts a wide array of cellular events. For cellular therapeutics, scalable expansion of primary human corneal endothelial cells (CECs) is crucial, and the inhibition of ROCK ... ...

Abstract	(1) Rho-associated coiled-coil protein kinase (ROCK) signaling cascade impacts a wide array of cellular events. For cellular therapeutics, scalable expansion of primary human corneal endothelial cells (CECs) is crucial, and the inhibition of ROCK signaling using a well characterized ROCK inhibitor (ROCKi) Y-27632 had been shown to enhance overall endothelial cell yield. (2) In this study, we compared several classes of ROCK inhibitors to both ROCK-I and ROCK-II, using in silico binding simulation. We then evaluated nine ROCK inhibitors for their effects on primary CECs, before narrowing it down to the two most efficacious compounds—AR-13324 (Netarsudil) and its active metabolite, AR-13503—and assessed their impact on cellular proliferation in vitro. Finally, we evaluated the use of AR-13324 on the regenerative capacity of donor cornea with an ex vivo corneal wound closure model. Donor-matched control groups supplemented with Y-27632 were used for comparative analyses. (3) Our in silico simulation revealed that most of the compounds had stronger binding strength than Y-27632. Most of the nine ROCK inhibitors assessed worked within the concentrations of between 100 nM to 30 µM, with comparable adherence to that of Y-27632. Of note, both AR-13324 and AR-13503 showed better cellular adherence when compared to Y-27632. Similarly, the proliferation rates of CECs exposed to AR-13324 were comparable to those of Y-27632. Interestingly, CECs expanded in a medium supplemented with AR-13503 were significantly more proliferative in (i) untreated vs. AR-13503 (1 μM; * p < 0.05); (ii) untreated vs. AR-13503 (10 μM; * p < 0.001); (iii) Y-27632 vs. AR-13503 (10 μM; p < 0.005); (iv) AR-13324 (1 μM) vs. AR-13503 (10 μM; ** p < 0.005); and (v) AR-13324 (0.1 μM) vs. AR-13503 (10 μM; * p < 0.05). Lastly, an ex vivo corneal wound healing study showed a comparable wound healing rate for the final healed area in corneas exposed to Y-27632 or AR-13324. (4) In conclusion, we were able to demonstrate that various ...
Keywords	ophthalmology ; cornea ; corneal endothelium ; primary human corneal endothelial cells ; cell therapy ; cell injection ; Biology (General) ; QH301-705.5
Subject code	500
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Vitamin D Concentration Changes after Bariatric Surgery

Vanessa Mayana Alves Baad / Narriane Chaves Pereira de Holanda / Juliana Fonseca Nogueira Alves / Francisco Bandeira / Ana Célia Oliveira dos Santos / Amanda Alves Marcelino da Silva / Taisy Cinthia Ferro Cavalcante

Journal of Obesity, Vol

2023 Volume 2023

Abstract: Introduction. Bariatric surgery causes physiological and anatomical changes in the gastrointestinal tract that interfere with intestinal absorption and, consequently, with the nutritional status, especially about vitamin D. The aim of the study was to ... ...

Abstract	Introduction. Bariatric surgery causes physiological and anatomical changes in the gastrointestinal tract that interfere with intestinal absorption and, consequently, with the nutritional status, especially about vitamin D. The aim of the study was to evaluate the vitamin D levels and body composition of these patients in the Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) types of surgery. Methods. The retrospective cohort study included a population of 120 patients aged between 18 and 65 years, with class II or III obesity, undergoing bariatric surgery procedures (VSG or RYGB-type). Data were collected on the degree of obesity, age, average time since surgery, and gender. The individuals underwent a complete physical examination, measuring blood pressure, weight, height, waist, and neck circumference. In addition to calculating the percentage of loss of body weight and assessing body fat, the food frequency and physical activity of these patients were evaluated. Blood was collected, and the insulin variables, hydroxyvitamin D (25OHD), were analyzed. Results. There was a significant difference between groups only for PTH, total BMD, and insulin variables. A significant intragroup difference was found in the variables’ body mass index (BMI) and vitamin D for the vertical sleeve gastrectomy group and BMI for the RYGB group. Conclusion. The analysis between the groups of procedures, similarity in body composition and postsurgical vitamin D levels, with significant differences only for PTH, BMD, and insulin variables, demonstrates that both procedures are effective in reducing fat mass.
Keywords	Internal medicine ; RC31-1245
Subject code	796
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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