Introduction

The moderator welcomes the participants and introduces the speaker, Professor Jorge Canata Andia.

• The webinar is about the clinical and molecular basis of the links between bone and the vascular system.

• Participants are encouraged to ask questions during the webinar by typing them in the question box of the control panel.

Speaker Introduction

The moderator introduces Professor Jorge Canata Andia, who is head of bone and mineral research at the Hospital Universitario Central of Asturias and full professor of medicine at the University of Oviedo in Spain.

• Professor Canata Andia is also co-chair of the IOF UH Working Group on Bone and Cardiovascular Diseases.

• He has published over 400 peer-reviewed papers and received numerous awards, distinctions, and honorary memberships.

Presentation Overview

Professor Canata Andia provides an overview of his presentation, which will be divided into two parts: epidemiological aspects related to vascular calcification, bone loss, fractures, aging, and age-dependent reduction in renal function; mechanisms linking vascular calcification with bone loss; medical management for associated bone and muscular link disorders.

• In part one, he will discuss epidemiological aspects related to vascular calcification, bone loss, fractures, aging, and age-dependent reduction in renal function.

• In part two, he will discuss mechanisms linking vascular calcification with bone loss as well as medical management for associated bone and muscular link disorders.

Epidemiology

Professor Canata Andia discusses how clinical biochemical and molecular aspects of vascular and bond disorders are increased due to age-related reduction in renal function.

• Vascular calcification and osteoporosis are common among patients with a glomerular filtration rate between 30-70 ml.

• The main biochemical parameters affected by the reduction in glomerular filtration rate are FGF23, PTH, phosphate 125, and glottal.

• Patients with osteoporosis and vascular calcification have a glomerular filtration rate between 70 to 40 ml per minute.

Mechanisms Linking Vascular Calcification with Bone Loss

Professor Canata Andia discusses mechanisms linking vascular calcification with bone loss.

• MicroRNAs play a role in the link between vascular calcification and bone loss.

• The RANK/RANKL/OPG system is involved in the regulation of bone metabolism and may also be involved in vascular calcification.

• The Wnt/beta-catenin pathway inhibitor may also play a role in the link between vascular calcification and bone loss.

Medical Management for Associated Bone and Muscular Link Disorders

Professor Canata Andia discusses medical management for associated bone and muscular link disorders.

• It is unclear whether medical management can improve outcomes for patients with associated bone and muscular link disorders.

Biochemical Changes and Vascular Calcification

In this section, the speaker discusses the relationship between biochemical changes and vascular calcification.

Age and Prevalence of Vascular Calcification

• The prevalence of vascular calcification increases with age.

• As age increases, the level of 25-hydroxy decreases.

• A 10 ng/mL increase in 25-hydroxy is equivalent to a 33% progression in aortic calcification, which is equivalent to being almost 10 years older.

Hemodynamic Changes and Arterial Calcification

• Higher pulse wave velocity is associated with lower levels of 125.

• Arterial calcification increases as pulse wave velocity increases.

• An increase in mortality and vertebral fracture is associated with low mass or an increase in fractures.

Promoters and Inhibitors of Vascular Calcification

• There are many inhibitors of vascular classification present in our blood circulation, including phateline, OPG, MGP, and pyrophosphate.

• Alkaline phosphatase, calcium phosphorus, PTH, rank rank lpg system, micrornas, and wind beta catenin pathway are potent promoters of vascular classification.

• Some factors are released into circulation as metric vesicles or exosol but also partake in the inflammation pathway.

Aging and Vascular Calcification

• Young people have a preponderance of inhibitors for vascular classification resulting in no vascular mineralization or normal bone mineralization.

• With aging comes an increase in vascular calcification promoters and less inhibitors of vascular calcification.

• Vascular calcification is associated with increased bone loss.

Vascular Calcification and Bone Loss

The speaker discusses the relationship between vascular calcification and bone loss. Patients with severe vascular organization showed lower mass after four years of follow-up, which was associated with an increase in fractures. The speaker explores possible links between these two conditions.

Morphological Links

• Blood supply to the bone is important for maintaining bone health.

• Differences in vessel size can affect blood supply to the bone.

• Extreme differences in vessel size are not the only reason for decreased bone mass.

Mechanisms Linking Vascular Calcification with Bone Loss

The speaker describes mechanisms linking vascular calcification with bone loss, focusing on three main systems: RANK/RANKL/OPG, microRNAs, and Wnt/beta-catenin pathway.

MicroRNAs

• MicroRNAs are small non-coding RNAs that regulate gene expression.

• A model using rats fed a high-phosphorus diet induced vascular calcification and mild reduction of renal function.

• Changes were observed in bone but not vascular calcification.

• Human models using epigastric arteries from donor transplantation serum also showed changes in microRNA expression.

RANK/RANKL/OPG System

The speaker discusses the role of the RANK/RANKL/OPG system in linking vascular calcification with bone loss.

Key Points

• Osteoprotegerin (OPG) inhibits osteoclast differentiation by binding to receptor activator of nuclear factor kappa-B ligand (RANKL).

• High levels of OPG have been associated with increased risk of cardiovascular disease and mortality.

• Inhibition of OPG has been shown to reduce arterial calcification and improve bone mass.

Wnt/beta-catenin Pathway

The speaker discusses the role of the Wnt/beta-catenin pathway in linking vascular calcification with bone loss.

Key Points

• Activation of the Wnt/beta-catenin pathway has been shown to promote osteoblast differentiation and inhibit osteoclast differentiation.

• Inhibition of the Wnt/beta-catenin pathway has been associated with increased arterial calcification and decreased bone mass.

• The relationship between the Wnt/beta-catenin pathway, vascular calcification, and bone loss is complex and requires further study.

Introduction to Bone Formation and Vascular Calcification

The speaker introduces the topic of bone formation and vascular calcification, highlighting the potential diagnostic and therapeutic implications of data obtained from lab studies.

Bachelor Classification and Inhibitors of Bark or Vacuolar Classification

• Bachelor classification (29b in yellow) and inhibitors of bark or vacuolar classification (marked in blue) are two ways to classify bone formation.

• These classifications provide basic data that could have future diagnostic and therapeutic implications in medicine.

Rank LPG System

• PTH and other molecules can stimulate the Rank LPG system, which activates osteoclastogenesis, inducing osteoclast proliferation, activity, and increasing bone resorption.

• To balance this action, there is a decoy receptor called OPG that blocks the Rank signaling pathway.

• Denosumab is a human antibody that fully mimics the OPG action by blocking the Rank signaling pathway.

• A new receptor called LG R4 has been discovered that promotes bone formation as well as vascular calcification.

Role of Wind Catalan Pathway

• The Wind Catalan pathway plays a role in both bone formation and vascular calcification.

• When wind binds to LRP5/6 receptors, it stimulates beta-catenin transcription on target genes leading to an increase in bone formation.

• However, when other molecules such as DKK1 or SFRP are present between wind and LRP5/6 receptors or when serum-free related products are present like Klotho then there is no stimulation of beta-catenin transcription leading to decreased bone formation.

Bone Formation and Vascular Calcification

The speaker discusses the relationship between bone formation and vascular calcification, as well as the gene expression in the aorta and bones.

Relationship Between Bone Formation and Vascular Calcification

• When studying bone formation with a phosphate model, researchers found that stimulating with phosphate led to vascular calcification.

• In bone biopsies, severe cortical and trabecular bone loss was only present in those with vascular calcification.

• Gene expression analysis showed a generalized repression of muscle-related genes in the calcified aorta, while there was over-expression of bone-related genes in the vessels.

• Serum free celebrator protein four was found to be one of the most affected inhibitors of wind pathway.

Gene Expression in Aorta and Bones

• Muscle-related genes were repressed in the calcified aorta, while bone-related genes were over-expressed.

• Biopsies showed multi-nucleated giant cells surrounding areas of calcification, indicating active bone resorption.

• Evidence suggests that this is a defensive mechanism to avoid further mineralization.

Medical Management for Bone and Vascular Link Disorders

The speaker reviews factors affecting medical management for associated bone and vascular link disorders.

Factors Affecting Medical Management

• Measurement of key molecules represented by activity of wind beta cutting pathway has shown controversial results.

• It is unclear whether vascular calcification drives osteoporosis or vice versa.

• Medical management for associated bone and vascular link disorders is still an area of research.

The Role of Renal Function in Vascular Calcification and Bone Loss

In this section, the speaker discusses the role of renal function in vascular calcification and bone loss.

Renal Function and Pathogenesis

• Age-related reduction in renal function plays a pathogenic role in both vascular calcification and bone loss.

• General measures such as exercise, balanced diet, adequate phosphorus consumption, avoiding excess fats and overweight can help manage these issues.

Active Drugs for Managing Vascular Calcification and Bone Loss

• Bisphosphonates have been shown to decrease vascular calcification but with limited evidence.

• Nursing map is a drug used to manage osteoporosis but has not demonstrated an influence on vascular calcification.

• Rheumatoid map has many doubts about negatively impacting vascular calcification.

Take Home Messages

• Vascular and bone metabolism share several proteins and molecular mechanisms that act as a link between bone and vessels.

• Age-dependent reduction in renal function plays an important role in the pathogenesis of vascular classification, bone loss, and fractures.

Crosstalk between Vessel and Bone

In this section, the speaker discusses the potential for crosstalk between vessel and bone in the next decade. They also discuss the role of inhibiting the Wnt pathway in vessels and its possible negative impact on vascular calcification.

Potential for Crosstalk Between Vessel and Bone

• The speaker envisions that in the next decade, we will learn a lot about crosstalk between vessel and bone.

• This could help solve many doubts we currently have.

Inhibiting Wnt Pathway in Vessels

• Inhibiting the Wnt pathway in vessels plays a role as a defensive auto protect mechanism to reduce vascular calcification.

• Experimental studies suggest that inhibiting the inhibitor (i.e., anterior exclusion treatment or Wnt pathway) may have a possible negative role in vascular calcification.

• However, clinical studies have failed to demonstrate this up to now.

No Specific Drug Available

• There is no specific drug available that can simultaneously reduce vascular calcification, reduce bone loss, and reduce bone fracture.

• Both are antagonistic events.

Non-pharmacological Measures

• General non-pharmacological and nutritional measures can reduce the progression of vascular calcification and increase bone mass.

Acknowledgments

In this section, the speaker thanks their group for their involvement in their research. They also acknowledge two postdocs who made significant contributions to a paper they published on cardiovascular disease.

Thanks to Group Members

• The speaker thanks their group members for their involvement in many of the things presented.

Acknowledgment of Postdocs

• Two postdoc senior members from our lab made great contributions to a paper published by our youth working group on cardiovascular board: Natalia Garrigio Lopez and Sarah Vanessa Garcia.

IOF Working Group on Osteoporosis and Chronic Cardiovascular Disease

In this section, the speaker mentions a paper published by the IOF working group on osteoporosis and chronic cardiovascular disease. They also mention that they will provide a reference to the paper in their mailing.

Paper Published by IOF Working Group

• The speaker co-chairs an IOF working group on osteoporosis and chronic cardiovascular disease.

• The group published a paper on that topic in Nutrient last September.

Reference to be Provided

• A reference to the paper will be provided in their mailing that will go out to every participant tomorrow.

Vascular Calcification

In this section, the speaker answers a question about vascular calcification, specifically where it appears and if it is related to high blood pressure or high blood flow.

Appearance of Vascular Calcification

• Until 2007, it was thought that the appearance of vascular calcification (both medial and intima) was related to the pressure of blood.

• However, a study demonstrated that vascular smooth cells come from eight different origins, meaning they are from different progenitors.

• Both pressure of blood flow and origin of vascular smooth cell can be important factors for vascular calcification.

MicroRNAs

In this section, the speaker answers a question about microRNAs involved in vascular calcification and bone tissue.

MicroRNAs Involved in Vascular Calcification

• When looking for microRNAs involved in vascular calcification, researchers first checked bone tissue because there were more studies available.

• MicroRNAs involved in vascular calcification are not the same as those found in bone tissue.

Clinical Role of MicroRNA in Vascular Classification

In this section, the speaker discusses the potential clinical role of microRNA in vascular classification and diagnosis.

MicroRNA Panel for Early Markers

• A panel of microRNAs could be used as early markers for vascular classification.

• This panel could help identify individuals with a higher risk of developing vascular calcification.

• However, there is still no clear clinical role for microRNAs in this context.

Vitamin D and Calcium Supplements for Osteoporosis

In this section, the speaker answers a question about whether vitamin D or calcium supplements given for osteoporosis can increase vascular calcifications such as coronary arteries.

Amount is Important

• Both low and high levels of vitamin D have negative effects on bone health and muscular qualification.

• Calcium also has a similar effect on bone health.

• The amount of these supplements is crucial to avoid increasing the possibilities of passive calcium deposition and vascular calcification.

Mechanisms Responsible for Vascular Calcification and Bone Loss

In this section, the speaker discusses the mechanisms responsible for both vascular calcification and bone loss.

Role of Inflammation and Oxidative Stress

• Inflammation is a common finding in both osteoporosis and vascular calcification.

• Oxidative stress also plays an important role in addition to other factors discussed earlier.

Sclerostin's Role in Osteoporosis Pathogenesis

In this section, the speaker briefly discusses the role of sclerostin in osteoporosis pathogenesis.

Inhibiting Osteoclasts

• Sclerostin inhibits osteoclasts, which can increase bone mass.

• However, the exact pathophysiological role of sclerostin in osteoporosis is not clear.

Circulating Sclerostin and Vascular Calcification

In this section, the speaker answers a question about whether circulating sclerostin increases vascular calcification and inhibits bone formation.

Evidence from Experimental Studies

• Experimental studies suggest that circulating sclerostin may increase vascular calcification and inhibit bone formation.

• The evidence suggests that circulating sclerostin has a greater effect than locally produced sclerostin.

Experimental Study on Bone and Vascular Classification

In this section, the speaker discusses an experimental study that demonstrates how molecules can reach circulation and affect bone. They also discuss the differences in trabecular and cortical bone between those with normal vascular classification and those with severe vascular classification.

Bisphosphonate's Role in Vascular Calcification

• Bisphosphonates have been studied to increase bone mass while decreasing vascular calcification.

• The most effective doses of bisphosphonates were able to reduce bone turnover, but reducing it too much could lead to increased vascular calcification.

• A potential risk of developing vascular calcification exists when there is a very low bone remodeling number.

Denosumab Therapy for People with Increased Cardiovascular Risk

• There is no clear reason for using denosumab therapy for people with increased cardiovascular risk.

• Denosumab has been used safely to treat osteoporosis in chronic kidney disease patients.

FGF23 as a Target for Treating Vascular Calcification

• FGF23's main action is phosphatory action in the kidney, but it can also act in the cardiovascular area.

• Antibodies are being considered as a way to target FGF23, but this may be dangerous since FGF23 has many other functions.

Inhibition to Growth

The speaker discusses the role of osteoclasts in vascular calcification and how it is affected by PTH.

Role of Osteoclast in Vascular Calcification

• There is no clear demonstration that stimulating osteoclasts with PTH reduces vascular calcification.

• The lack of balance between the action of osteoblasts and osteoclasts is the main problem in vascular calcification.

• Production of a new matrix and mineralized magic is important for vascular classification.

Conclusion

The speaker concludes the webinar, thanks participants, and invites them to fill out a survey.

• A recording of the webinar will be posted on the IOF website.

• Participants are invited to send questions or comments via email.