Bone Disruption and Environmental Pollutants

2021 ◽  
Vol 21 ◽  
Author(s):  
Raffaele Giannattasio ◽  
Giuseppe Lisco ◽  
Vito Angelo Giagulli ◽  
Silvio Settembrini ◽  
Giovanni De Pergola ◽  
...  
Keyword(s):  
Bone Metabolism ◽  
Environmental Pollutants ◽  
Free Text ◽  
Bone Homeostasis ◽  
Medical Subject Headings ◽  
Mineral Density ◽  
Hormonal Imbalance ◽  
The Impact ◽  
Final Effect

Background: Endocrine Disrupting Chemicals (EDCs) are ubiquitous and may significantly contribute in environmental pollution, thus contaminating humans and wildlife. Environmental pollutants could interfere with bone homeostasis by means of different mechanisms, which include hormonal imbalance, direct osteoblasts toxicity and enanchment of osteoclasts activity, thus leading to osteopenia or osteoporosis. Among these, bisphenols, dioxins, polycyclic aromatic hydrocarbons, polychlorobiphenyls, poly- and perfluoroalkyls, phthalates, parabens, organotins and cadmium may play a role in bone distuption. Methods: PubMed/MEDLINE, ISI-web of knowledge and Google scholar databases were searched for medical subject headings terms and free-text word related to the aforementioned classes of chemicals and bone metabolism and remodelling for better clarifying and understanding the main mechanisms of bone disruption. Results: Several of EDCs act as xenoestrogens. Considering that estrogens play a significant role in regulating bone remodeling, most of these chemicals generate hormonal imbalance with possible detrimental consequences on bone tissue structure and its mechanical and non-mechanical properties. Discussion: A lot of evidences about bone distruptors came from in vitro studies or animal models, and conduct to equivocal results. In addition, a few data derived form humans and most of these data focused on the impact of EDCs on bone mineral density without considering their influence on long-term fracture risk. Moreover, it should be taken into account that humans are exposed to a mixture of EDCs and the final effect on bone metabolism might be the result of either a synergism or antagonist effects among them. Age of first exposure, cumulative dose exposure over time, and the usually observed non-monotonic dose-response curve for EDCs should be considered as other important variable influencing the final effect on bone metabolism. Conclusion: Taking into account these variables, observational studies are needed to better analyze this issue both for echological purpose and to preserve bone health.

scholarly journals Evaluation of the Impact of Different Pain Medication and Proton Pump Inhibitors on the Osteogenic Differentiation Potential of hMSCs Using 99mTc-HDP Labelling

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 339
Author(s):  
Tobias Grossner ◽  
Uwe Haberkorn ◽  
Tobias Gotterbarm
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Bone Metabolism ◽  
Negative Impact ◽  
Pain Medication ◽  
Group 3 ◽  
Group 5 ◽  
The Impact

First-line analgetic medication used in the field of musculoskeletal degenerative diseases, like Nonsteroidal anti-inflammatory drugs (NSAIDs), reduces pain and prostaglandin synthesis, whereby peptic ulcers are a severe adverse effect. Therefore, proton pump inhibitors (PPI) are frequently used as a concomitant medication to reduce this risk. However, the impact of NSAIDs or metamizole, in combination with PPIs, on bone metabolism is still unclear. Therefore, human mesenchymal stem cells (hMSCs) were cultured in monolayer cultures in 10 different groups for 21 days. New bone formation was induced as follows: Group 1 negative control group, group 2 osteogenic differentiation media (OSM), group 3 OSM with pantoprazole (PAN), group 4 OSM with ibuprofen (IBU), group 5 OSM with diclofenac (DIC), group 6 OSM with metamizole (MET), group 7 OSM with ibuprofen and pantoprazole (IBU + PAN), group 8 OSM with diclofenac and pantoprazole (DIC + PAN), group 9 OSM with metamizole and pantoprazole (MET + PAN) and group 10 OSM with diclofenac, metamizole and pantoprazole (DIC + MET + PAN). Hydroxyapatite content was evaluated using high-sensitive radioactive 99mTc-HDP labeling. Within this study, no evidence was found that the common analgetic medication, using NSAIDs alone or in combination with pantoprazole and/or metamizole, has any negative impact on the osteogenic differentiation of mesenchymal stem cells in vitro. To the contrary, the statistical results indicate that pantoprazole alone (group 3 (PAN) (p = 0.016)) or diclofenac alone (group 5 (DIC) (p = 0.008)) enhances the deposition of minerals by hMSCS in vitro. There is an ongoing discussion between clinicians in the field of orthopaedics and traumatology as to whether post-surgical (pain) medication has a negative impact on bone healing. This is the first hMSC in vitro study that investigates the effects of pain medication in combination with PPIs on bone metabolism. Our in vitro data indicates that the assumed negative impact on bone metabolism is subsidiary. These findings substantiate the thesis that, in clinical medicine, the patient can receive every pain medication needed, whether or not in combination with PPIs, without any negative effects for the osteo-regenerative potential.

scholarly journals Copper as Dietary Supplement for Bone Metabolism: A Review

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2246
Author(s):  
Mariangela Rondanelli ◽  
Milena Anna Faliva ◽  
Vittoria Infantino ◽  
Clara Gasparri ◽  
Giancarlo Iannello ◽  
...  
Keyword(s):  
Bone Metabolism ◽  
Bone Mineral ◽  
Animal Studies ◽  
Small Sample ◽  
Blood Levels ◽  
Mineral Density ◽  
Dietary Copper ◽  
Slowing Down ◽  
Copper Supplementation

While in vitro and animal studies of osteoblastic and osteoclastic activity as well as bone resistance for copper are numerous, and the results encouraging in terms of regulation, human studies are scarce. The aim of this narrative review was to investigate the correlation of blood copper, daily copper intake, and copper supplementation with bone mineral density. This review included 10 eligible studies: five studies concerned copper blood levels, one study concerned daily copper intake, and four studies concerned copper supplementation. Blood copper levels did not show statistically significant differences in four of the studies analyzed, while only one study showed differences between osteoporotic and healthy women, although only with women between 45 and 59 years of age and not between 60 and 80 years of age. The dietary copper intake among women with or without osteoporosis did not show any differences. Only one study with a small sample of subjects carried out these assessments; therefore, it is a topic that the literature must deepen with further studies. The two studies that analyzed the integration of copper (2.5–3 mg/day) only showed good results in terms of slowing down bone mineral loss and reducing resorption markers, confirming the effectiveness of copper supplementation on bone metabolism.

scholarly journals Transformed notochordal cells trigger chronic wounds destabilizing the vertebral column and bone homeostasis

2020 ◽  
Author(s):  
Paco Lopez-Cuevas ◽  
Luke Deane ◽  
Yushi Yang ◽  
Chrissy L Hammond ◽  
Erika Kague
Keyword(s):  
Vertebral Column ◽  
Wound Response ◽  
Transformed Cells ◽  
Bone Homeostasis ◽  
Mineral Density ◽  
Notochordal Cells ◽  
Notochord Cells ◽  
Ivd Degeneration ◽  
The Impact ◽  
Sheath Cells

Notochordal cells play a pivotal role in vertebral column patterning, contributing to the formation of the inner architecture of intervertebral discs (IVDs). Their disappearance during development has been associated with reduced repair capacity and IVD degeneration. Notochordal remnants are known to cause chordomas, a highly invasive bone cancer associated with late diagnosis. Understanding the impact of neoplastic cells during development and on the surrounding vertebral column could open avenues for earlier intervention and therapeutics. We investigated the impact of transformed notochord cells in the zebrafish skeleton using a RAS expressing line in the notochord under the control of the Kita promoter, with the advantage of adulthood endurance. Transformed cells caused damage in the notochord and destabilised the sheath layer triggering a wound repair mechanism, with enrolment of sheath cells (col9a2+) and expression of wt1b, similar to induced notochord wounds. Moreover, increased recruitment of neutrophils and macrophages, displaying abnormal behaviour in proximity to the notochord sheath and transformed cells, supported parallels between chordomas, wound and inflammation. Cancerous notochordal cells interfere with differentiation of sheath cells to form chordacentra domains leading to fusions and vertebral clefts during development. Adults displayed IVD irregularities reminiscent of degeneration; reduced bone mineral density, increased osteoclast activity; while disorganised osteoblasts and collagen indicate impaired bone homeostasis. By depleting inflammatory cells, we abrogated chordoma development and rescued the skeletal features of the vertebral column. Therefore, we showed that transformed notochord cells alter the skeleton during life, causing a wound-like phenotype and activating chronic wound response, suggesting parallels between chordoma, wound, IVD degeneration and inflammation, highlighting inflammation as a promising target for future therapeutics.

scholarly journals Serum Levels of miR-148a and miR-21-5p Are Increased in Type 1 Diabetic Patients and Correlated with Markers of Bone Strength and Metabolism

2018 ◽  
Vol 4 (4) ◽  
pp. 37 ◽  
Author(s):  
Giuseppina E. Grieco ◽  
Dorica Cataldo ◽  
Elena Ceccarelli ◽  
Laura Nigi ◽  
Giovanna Catalano ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Type 1 Diabetes ◽  
Bone Loss ◽  
Bone Metabolism ◽  
Bone Remodeling ◽  
Bone Mineral ◽  
Bone Fragility ◽  
Bone Homeostasis ◽  
Mineral Density

Type 1 diabetes (T1D) is characterized by bone loss and altered bone remodeling, resulting into reduction of bone mineral density (BMD) and increased risk of fractures. Identification of specific biomarkers and/or causative factors of diabetic bone fragility is of fundamental importance for an early detection of such alterations and to envisage appropriate therapeutic interventions. MicroRNAs (miRNAs) are small non-coding RNAs which negatively regulate genes expression. Of note, miRNAs can be secreted in biological fluids through their association with different cellular components and, in such context, they may represent both candidate biomarkers and/or mediators of bone metabolism alterations. Here, we aimed at identifying miRNAs differentially expressed in serum of T1D patients and potentially involved in bone loss in type 1 diabetes. We selected six miRNAs previously associated with T1D and bone metabolism: miR-21; miR-24; miR-27a; miR-148a; miR-214; and miR-375. Selected miRNAs were analyzed in sera of 15 T1D patients (age: 33.57 ± 8.17; BMI: 21.4 ± 1.65) and 14 non-diabetic subjects (age: 31.7 ± 8.2; BMI: 24.6 ± 4.34). Calcium, osteocalcin, parathormone (PTH), bone ALkaline Phoshatase (bALP), and Vitamin D (VitD) as well as main parameters of bone health were measured in each patient. We observed an increased expression of miR-148a (p = 0.012) and miR-21-5p (p = 0.034) in sera of T1D patients vs non-diabetic subjects. The correlation analysis between miRNAs expression and the main parameters of bone metabolism, showed a correlation between miR-148a and Bone Mineral Density (BMD) total body (TB) values (p = 0.042) and PTH circulating levels (p = 0.033) and the association of miR-21-5p to Bone Mineral Content-Femur (BMC-FEM). Finally, miR-148a and miR-21-5p target genes prediction analysis revealed several factors involved in bone development and remodeling, such as MAFB, WNT1, TGFB2, STAT3, or PDCD4, and the co-modulation of common pathways involved in bone homeostasis thus potentially assigning a role to both miR-148a and miR-21-5p in bone metabolism alterations. In conclusion, these results lead us to hypothesize a potential role for miR-148a and miR-21-5p in bone remodeling, thus representing potential biomarkers of bone fragility in T1D.

scholarly journals Can Hypoxic Conditioning Improve Bone Metabolism? A Systematic Review

2019 ◽  
Vol 16 (10) ◽  
pp. 1799 ◽  
Author(s):  
Marta Camacho-Cardenosa ◽  
Alba Camacho-Cardenosa ◽  
Rafael Timón ◽  
Guillermo Olcina ◽  
Pablo Tomas-Carus ◽  
...  
Keyword(s):  
Bone Metabolism ◽  
Critical Role ◽  
Hypoxia Inducible Factor ◽  
Experimental Studies ◽  
Hormonal Responses ◽  
Hypoxia Exposure ◽  
Ambient Oxygen ◽  
The Impact

Among other functions, hypoxia-inducible factor plays a critical role in bone–vascular coupling and bone formation. Studies have suggested that hypoxic conditioning could be a potential nonpharmacological strategy for treating skeletal diseases. However, there is no clear consensus regarding the bone metabolism response to hypoxia. Therefore, this review aims to examine the impact of different modes of hypoxia conditioning on bone metabolism. The PubMed and Web of Science databases were searched for experimental studies written in English that investigated the effects of modification of ambient oxygen on bone remodelling parameters of healthy organisms. Thirty-nine studies analysed the effect of sustained or cyclic hypoxia exposure on genetic and protein expression and mineralisation capacity of different cell models; three studies carried out in animal models implemented sustained or cyclic hypoxia; ten studies examined the effect of sustained, intermittent or cyclic hypoxia on bone health and hormonal responses in humans. Different modes of hypoxic conditioning may have different impacts on bone metabolism both in vivo and in vitro. Additional research is necessary to establish the optimal cyclical dose of oxygen concentration and exposure time.

scholarly journals Role of PTH1R internalization in osteoblasts and bone mass using a phosphorylation-deficient knock-in mouse model

2010 ◽  
Vol 207 (3) ◽  
pp. 355-365 ◽  
Author(s):  
Nabanita S Datta ◽  
Tareq A Samra ◽  
Chandrika D Mahalingam ◽  
Tanuka Datta ◽  
Abdul B Abou-Samra
Keyword(s):  
Mouse Model ◽  
Cyclin D1 ◽  
Intracellular Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Bone Homeostasis ◽  
Low Calcium Diet ◽  
High Calcium ◽  
The Impact

Phosphorylation, internalization, and desensitization of G protein-coupled receptors, such as the parathyroid hormone (PTH) and PTH-related peptide (PTHrP) receptor (PTH1R), are well characterized and known to regulate the cellular responsiveness in vitro. However, the role of PTH1R receptor phosphorylation in bone formation and osteoblast functions has not yet been elucidated. In previous studies, we demonstrated impaired internalization and sustained cAMP stimulation of a phosphorylation-deficient (pd) PTH1R in vitro, and exaggerated cAMP and calcemic responses to s.c. PTH infusion in pdPTH1R knock-in mouse model. In this study, we examined the impact of impaired PTH1R phosphorylation on the skeletal phenotype of mice maintained on normal, low, and high calcium diets. The low calcium diet moderately reduced (P<0.05) bone volume and trabecular number, and increased trabecular spacing in both wild-type (WT) and pd mice. The effects, however, seem to be less pronounced in the female pd compared to WT mice. In primary calvarial osteoblasts isolated from 2-week-old pd or WT mice, PTH and PTHrP decreased phosphorylated extracellular signal-regulated kinases 1/2 (pERK1/2), a member of mitogen-activated protein kinase, and cyclin D1, a G1/S phase cyclin, in vitro. In contrast to WT osteoblasts, down-regulation of cyclin D1 was sustained for longer periods of time in osteoblasts isolated from the pd mice. Our results suggest that adaptive responses of intracellular signaling pathways in the pd mice may be important for maintaining bone homeostasis.

scholarly journals Hormonal alterations in PCOS and its influence on bone metabolism

2017 ◽  
Vol 232 (2) ◽  
pp. R99-R113 ◽  
Author(s):  
Abhaya Krishnan ◽  
Sridhar Muthusami
Keyword(s):  
Bone Metabolism ◽  
Polycystic Ovary ◽  
Human Subjects ◽  
The United States ◽  
Reproductive Age ◽  
World Health ◽  
Hormonal Changes ◽  
Mineral Density ◽  
Hormonal Imbalance ◽  
Health Organization

According to the World Health Organization (WHO) polycystic ovary syndrome (PCOS) occurs in 4–8% of women worldwide. The prevalence of PCOS in Indian adolescents is 12.2% according to the Indian Council of Medical Research (ICMR). The National Institute of Health has documented that it affects approximately 5 million women of reproductive age in the United States. Hormonal imbalance is the characteristic of many women with polycystic ovarian syndrome (PCOS). The influence of various endocrine changes in PCOS women and their relevance to bone remains to be documented. Hormones, which include gonadotrophin-releasing hormone (GnRH), insulin, the leutinizing/follicle-stimulating hormone (LH/FSH) ratio, androgens, estrogens, growth hormones (GH), cortisol, parathyroid hormone (PTH) and calcitonin are disturbed in PCOS women. These hormones influence bone metabolism in human subjects directly as well as indirectly. The imbalance in these hormones results in increased prevalence of osteoporosis in PCOS women. Limited evidence suggests that the drugs taken during the treatment of PCOS increase the risk of bone fracture in PCOS patients through endocrine disruption. This review is aimed at the identification of the relationship between bone mineral density and hormonal changes in PCOS subjects and identifies potential areas to study bone-related disorders in PCOS women.

scholarly journals Impact of Monthly 120 Mg Denosumab on Bone Metabolism in Bone-metastatic Prostate Cancer Undergoing Androgen Deprivation Therapy

2017 ◽  
Vol 2 (3) ◽  
pp. 41-46
Author(s):  
Jimpei Miyakawa ◽  
Satoru Taguchi ◽  
Motofumi Suzuki ◽  
Kaori Endo ◽  
Yorito Nose ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lumbar Spine ◽  
Femoral Neck ◽  
Bone Metabolism ◽  
Androgen Deprivation Therapy ◽  
Metastatic Prostate Cancer ◽  
Androgen Deprivation ◽  
Mineral Density ◽  
Bone Metabolism Markers ◽  
The Impact

Background: While semiannual 60 mg denosumab is a common treatment for osteoporosis, impact of monthly 120 mg denosumab, the common treatment protocol for bone metastases from solid tumors, on bone metabolism is unclear.Materials and Methods: We reviewed 15 patients with bone-metastatic prostate cancer who initiated monthly 120 mg denosumab in conjunction with androgen deprivation therapy between 2013 and 2014. Bone mineral density (BMD) was measured at lumbar spine and femoral neck using dual energy X-ray absorptiometry (DXA), before treatment and annually thereafter. Bone metabolism markers, including urine N-terminal telopeptide (uNTx) and bone type alkaline phosphatase (BAP), were monitored monthly.Results: Twelve of 15 (80%) patients had evaluable DXA before treatment, and of them, eight underwent DXA after a year of initiation without discontinuation of denosumab. Percent changes in BMD from baseline were +6.2% at lumbar spine and +7.6% at femoral neck, both of which were significant increases (both P<0.01). Bone metabolism markers were evaluable in 11 (73%) patients: uNTx decreased rapidly, while BAP declined gradually after initiating denosumab. These effects were similar to those seen by the standardized dose for osteoporosis in previous literature. There were no denosumab-related severe adverse events during the follow-up period. Conclusions: The impact of monthly 120 mg denosumab on bone metabolism was significant, but almost equivalent to that of the standard dose for osteoporosis (60mg semiannually) in bone-metastatic prostate cancer undergoing androgen deprivation therapy. Whereas the higher dose has reportedly reduced skeleton-related events, the effect on bone metabolism seemed plateaued or showed no dose-dependency.

scholarly journals Transformed notochordal cells trigger chronic wounds destabilizing the vertebral column and bone homeostasis

2021 ◽  
pp. dmm.047001
Author(s):  
Paco López-Cuevas ◽  
Luke Deane ◽  
Yushi Yang ◽  
Chrissy L Hammond ◽  
Erika Kague
Keyword(s):  
Vertebral Column ◽  
Wound Response ◽  
Transformed Cells ◽  
Bone Homeostasis ◽  
Mineral Density ◽  
Notochordal Cells ◽  
Notochord Cells ◽  
Ivd Degeneration ◽  
The Impact ◽  
Sheath Cells

Notochordal cells play a pivotal role in vertebral column patterning, contributing to the formation of the inner architecture of intervertebral discs (IVDs). Their disappearance during development has been associated with reduced repair capacity and IVD degeneration. Notochord cells can give rise to chordomas, a highly invasive bone cancer associated with late diagnosis. Understanding the impact of neoplastic cells during development and on the surrounding vertebral column could open avenues for earlier intervention and therapeutics. We investigated the impact of transformed notochord cells in the zebrafish skeleton using a RAS expressing line in the notochord under the control of the Kita promoter, with the advantage of adulthood endurance. Transformed cells caused damage in the notochord and destabilised the sheath layer triggering a wound repair mechanism, with enrolment of sheath cells (col9a2+) and expression of wt1b, similar to induced notochord wounds. Moreover, increased recruitment of neutrophils and macrophages, displaying abnormal behaviour in proximity to the notochord sheath and transformed cells, supported parallels between chordomas, wound and inflammation. Cancerous notochordal cells interfere with differentiation of sheath cells to form chordacentra domains leading to fusions and vertebral clefts during development. Adults displayed IVD irregularities reminiscent of degeneration; reduced bone mineral density, increased osteoclast activity; while disorganised osteoblasts and collagen indicate impaired bone homeostasis. By depleting inflammatory cells, we abrogated chordoma development and rescued the skeletal features of the vertebral column. Therefore, we showed that transformed notochord cells alter the skeleton during life, causing a wound-like phenotype and activating chronic wound response, suggesting parallels between chordoma, wound, IVD degeneration and inflammation, highlighting inflammation as a promising target for future therapeutics.

scholarly journals Relationships Between Thyroid Hormones, Insulin-Like Growth Factor-1 and Antioxidant Levels in Hypothalamic Amenorrhea and Impact on Bone Metabolism

2019 ◽  
Vol 51 (05) ◽  
pp. 302-308
Author(s):  
Antonio Mancini ◽  
Edoardo Vergani ◽  
Carmine Bruno ◽  
Angelina Barini ◽  
Andrea Silvestrini ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Bone Metabolism ◽  
Bone Alkaline Phosphatase ◽  
Antioxidant Systems ◽  
Special Focus ◽  
Mineral Density ◽  
Hypothalamic Amenorrhea ◽  
Low T3 ◽  
Group A ◽  
The Impact

AbstractReduced bone mineral density (BMD) in Functional Hypothalamic Amenorrhea (FHA) is mainly related to hypoestrogenism, but other hormonal derangement (reduced conversion of T4–T3 and GH resistance) can play a role. These hormones are involved in antioxidant systems regulation. We evaluated the impact of hormonal alterations, with special focus on low T3 and IGF-1 levels, on antioxidant systems as a link with osteoporosis in FHA. Forty-three FHA patients, 15–34 years, with BMI range 17.3–23.4 kg/m2, were divided in 2 groups according to fT3 levels; group A (n=22), low fT3 (<2.4 pg/ml) and group B (n=21), normal fT3 (≥ 2.4 pg/ml). We evaluated hormonal parameters (fT3, fT4, TSH, IGF-1, FSH, LH, estradiol, DHEAS, testosterone, cortisol), bone metabolism (calcium, phosphorus, 25-OH Vitamin D, PTH, β-crosslaps, bone alkaline phosphatase) and total antioxidant capacity (TAC), expressed as LAG (latency time in radical species appearance using spectrophotometric method). BMD was assessed by DEXA. Group A patients exhibited significantly lower levels of IGF-1 (159.76±14.79 vs. 220.05±15.25 ng/ml) and osteocalcin (17.51±1.14 vs. 21.49±1.56 ng/ml); LAG values were significantly higher in A (66.33±1.74 s) vs. B (54.62±1.74 s). A significant direct correlation was found between both IGF-1 and fT3 with osteocalcin (r²=0.22, p=0.0049 and r²=0.34, p=0.0001, respectively). No difference in LAG between groups according to IGF-1 were found. These data show a correlation between altered bone turnover and low fT3, which is highly prevalent in FHA. Low fT3 levels may contribute to reduced BMD. Oxidative stress could be the link underlying different bone turnover pattern and endocrine dysfunction in FHA.

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