Osteoporosis is a disease of bone that leads to an increased risk of fracture. In osteoporosis the bone mineral density (BMD) is reduced, bone micro architecture is disrupted, and the amount and variety of proteins in bone is altered. Osteoporosis is defined by the World Health Organization (WHO) in women as a bone mineral density 2.5 standard deviations below peak bone mass (20-year-old healthy female average) as measured by DXA; the term "established osteoporosis" includes the presence of a fragility fracture.
Osteoporosis is musculoskeletal disorder. thiS PPT describes about
`defination
`atiology
`clinical manifestations
`types
`bone resorption process
`pathophysiology
`diagnosis
`treatment.
Proteins are the most versatile macromolecules and responsible for almost all cellular functions .Protein homeostasis (or proteostasis) is state of a balanced proteome, , depends on an extensive network of different types molecular chaperones, proteolytic systems (e.g. proteosome, autophagy) and their regulators. The dysfunction in proteostasis, leading to formation of misfolded proteins or the accumulation of protein aggregates which leads to many diseases e.g. sickle cell anaemia ; neurodegenerative diseases. Also The chaperon dysfunction leads to diseases called chaperonopathy e.g. Neurodegenerative diseases, cancers. .The pharmacological intervention to treat proteostasis dysfunction diseases are pharmacological chaperones, chemical chaperon, Heat shock transcription factor-1 activator; chaperon inhibitors,proteosome inhibitors and autophagy enhancers (activators).
Osteoporosis is a disease of bone that leads to an increased risk of fracture. In osteoporosis the bone mineral density (BMD) is reduced, bone micro architecture is disrupted, and the amount and variety of proteins in bone is altered. Osteoporosis is defined by the World Health Organization (WHO) in women as a bone mineral density 2.5 standard deviations below peak bone mass (20-year-old healthy female average) as measured by DXA; the term "established osteoporosis" includes the presence of a fragility fracture.
Osteoporosis is musculoskeletal disorder. thiS PPT describes about
`defination
`atiology
`clinical manifestations
`types
`bone resorption process
`pathophysiology
`diagnosis
`treatment.
Proteins are the most versatile macromolecules and responsible for almost all cellular functions .Protein homeostasis (or proteostasis) is state of a balanced proteome, , depends on an extensive network of different types molecular chaperones, proteolytic systems (e.g. proteosome, autophagy) and their regulators. The dysfunction in proteostasis, leading to formation of misfolded proteins or the accumulation of protein aggregates which leads to many diseases e.g. sickle cell anaemia ; neurodegenerative diseases. Also The chaperon dysfunction leads to diseases called chaperonopathy e.g. Neurodegenerative diseases, cancers. .The pharmacological intervention to treat proteostasis dysfunction diseases are pharmacological chaperones, chemical chaperon, Heat shock transcription factor-1 activator; chaperon inhibitors,proteosome inhibitors and autophagy enhancers (activators).
Microbiata
A main player in immunityThe microbiome is an environmental factor in intricate symbiotic relationship with its hosts' immune system, potentially shaping:
anticancer immunity,
autoimmunity, and
transplant responses
Daptomycin is a semi-synthetic cyclic lipopeptide bactericidal antibiotic with outstanding activity against aerobic and anaerobic Gram-positive organisms including drug-resistant staphylococcai, Enterococcus spp. and Streptococci Spp
Microbiome: The genes and genomes of the microbiota, as well as the products of the microbiota and the host environment” [the collective genomes of the micro-organisms in a particular environment. Although the composition of the gut microbiota varies between individuals, the community in each individual is relatively stable over time.
Microbiota: the community of micro-organisms themselves
Microbiome: The genes and genomes of the microbiota, as well as the products of the microbiota and the host environment” [the collective genomes of the micro-organisms in a particular environment. Although the composition of the gut microbiota varies between individuals, the community in each individual is relatively stable over time
genes addiion\deeion\ediionthat lead to a therapeutic, prophylactic or diagnostic effect
Plasmid DNA
•Viral vectors
•Genetically engineered micro-organisms
•Human gene-editing technology
•Patient-derived cellular gene therapy products
cells or tissues that have been manipulated to change their biological characteristics or cells or tissues not intended to be used for the same essential/original functions in the body.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
1. CALCIUM HOMEOSTASIS AND DISORDERS
BY
Mohie-Aldien A Sherif
Professor of Pharmacology, Faculty of Medicine, Benha
University, Benha, Egypt
2.
3. Porous/Cancellous/Trabecular/ spongy Compact Bone
*Low mineral & high collagen) → flexible
→ Shock absorption ( change shape) e.g.,
vertebrae
*metabolically active
*High mineral & low collagen) → Stiffer →
Withstanding stress in high loads areas e.g. Long
bones( has some trabecular bone- near to the marrow)
* Less metabolically active
4. Osteoblast Ostycte Osteoclast
Func-tion *Bone forming cells.
*differentiated to osteocyte
*Secrete type I collagen, alkaline
phosphatase+ ,regulate osteoclast•
*Responsible for Ca+2
exchange with extra-
cellular fluid
*Bone resorption cells.
* Synthesize bone acid phosphatase
Stimu-
lated
IGF, vit. D (small dose ,Ca deficiency),
PGE2, fluride
PTH P.T.H. osteoblasts ↑osteoclasts , vit. D
(high dose) , IL1,6, heparin., RANK legend,
Inhibited glucocorticoid Calcitonin ,Estrogen, PGE2, ,
Bisphosphonate. OPG
1-produce RANK ligand → bind to RANK receptor
membrane/ free cytoplasmic) → ↑ cells differentiation
to osteoclasts ,
2-produce osteoprotegrin (OPG) is free RANK receptor
binds RANKL → prevent osteoclasts overstimulation . + a
marker of bone turnover, it ↑ in pts w/ a fracture or w/ lytic
bone lesions; ¾ comes from liver and ¼ comes from bone
so bone-specific alk phos is a better marker of bone
turnover
6. Gut
(dudon
um)
Vit.D
PO4 (3mg/dl): 78% is free (+) PTH
(+) calcitonin,
(-) PTH , Vit. D
Total calcium (9-11mg/dl):
*47% ionised (4-4.9mg/dl, by acidosis)
* 13% Anion-bound (PO4,citrate) ca: by alkalosis)
Protein bound ca: 40% ( 80-90% to albumin. It is
affected by Na& ph.
(+) Vit.D, PTH
.
(-) Phytate, oxalate,
cholecystokinin,
oil
(+) Vit.D
500mg/d(+) PTH (continous), IL-6
, IL-1 , TGF-B , Vit D (high dose),
glucocorticoid , heparin
(-) calcitonin(Miacalcic),
Bisphosphonate, PgE2,
androgen, Estrogen , NO
Bone accretion (500mg/d):
Passive as a concentration in
extracellular fluid of bone is less
than that in serum.
pH 7. 45
pH 7.35
Alkalosis: increased calcium binding to protein;
decreased ionized fraction
Acidosis: decreased calcium binding to protein;
increased ionized fraction
Each 0.1 decrease in pH increases ionized calcium by 0.05 mmol/L
Hydroxyapatite (98.9% = 31 mol= 1250g)
1% of which is available as an exchangeable pool
Ca intake (1000mg/d)
Cytosolic Ca(100 nmol/l)
*10000 fold lower than extracellular
calcium
*This steep gradient maintained by
plasma membrane Ca++ ATPase (PMCA)
9. The VDR regulates gene transcription by homo-dimerization and by heterodimerization to a retinoic acid X receptor (RXR). The complex binds
to target DNA sequences and regulates the transcription of several genes important in mediating vitamin D’s effects on calcium and skeletal
metabolism and its diverse biological effects.
15. ↑ bone
resorption
*Osteitis-fibrosa-cystica (↑PTH → focal resorption &reactive fibrosis + ↑ serum Ca →
ectopic Ca deposition. e.g. Kidney. (nephro lithiasis& nephrocalcinosis ;BV
*paget ( huge multi-nucleated OC→ intense bone resorption &vascular hypertrophy +
irregularly shaped trabecular bone
↓ bone
formation
↓ mineralization of matrix : *Adult →Osteomalacia
* Children → Rickets
↓ matrix – Osteogenesis Imperfecta ( often have blue sclera)
in both matrix & mineral : Osteoporosis
17. ↑ bone resor-ption *Osteitis-fibrosa-cystica (↑PTH → focal resorption &reactive fibrosis + ↑ serum Ca → ectopic Ca deposition. e.g.
Kidney. (nephro lithiasis& nephrocalcinosis ;BV
*paget ( huge multi-nucleated OC→ intense bone resorption &vascular hypertrophy + irregularly shaped trabecular bone
↓ bone form-ation ↓ mineralization of matrix : *Adult →Osteomalacia
* Children → Rickets
↓ matrix – Osteogenesis Imperfecta ( often have blue sclera)
in both matrix & mineral : Osteoporosis
18. Osteoporotic Bone Loss
• A skeletal disorder characterized by
compromised bone strength
predisposing to an increased risk of
fracture. Bone Strength:
• Bone Density: Grams of mineral per
area or volume (70% bone strength)
• Bone Quality:
– Architecture
– Turnover
– Damage accumulation
– Mineralization
Normal Bone
Osteoporosis
19. Z-score is used to compare your bone density to the
average values for a person of your same age and
gender.
21. Cholcalciferol (vit. D3) 25 OH-cholcolciferel(Calcidiol )*** Serum Level 1.25 dihydrotycholcalciferol (calcitril)
*Delayed onset (1week).
* Activated in kidney, liver.
* Long duration (stored in fat).
* Narrow theapeutic range.
* Delayed onset.
*Activated in kidney only.
* Short duration.
* wide therapeutic range.
* Rapide onset (2-4 d).
* Active form.
* Short duration.
* wide therapeutic range.
(hpercalcaemia, hyperclacuria, wide spread ectopic calcification
e.g. kidney)
Vit. D Supplementation (2,000- 4,000 IU/Day)
decrease: All cause mortality.IHD; cancers; Depression;
fractures. Relative Contraindications : Sarcoid Tuberculosis
Lymphoma 1ry Hyperparathyroidism ? Renal Calculi
22.
23.
24. Osteoclasts matured from bone marrow hematopoietic stem cells (BMMs) with the stimulation of two critical factors, M-CSF (activator of nuclear factor kappa-B ligand
(RANKL). When binding to its specific receptors [CSF-1R and receptor activatCSF-1) and receptor or of nuclear factor kappa-B (RANK)] on BMMs membrane, a series of
cascades are activated, and BMMs were then differentiated into matured osteoclast. Realizing the importance of M-CSF and RANKL in osteoclast differentiation, inhibitors
to CSF-1R and RANKL were considered as available strategy to suppress over-activated osteoclasts. Bisphosphonates, a widely used anti-osteoporosis agent, can be
absorbed by osteoclast and induce osteoclast apoptosis. Additionally, it has been indicated that GLP-2 is a negative regulator of osteoclast differentiation, thus, the exact
mechanisms are still unclear. Bone resorption is demonstrated as specific function of osteoclast, and bone matrix degradation is induced by the release of cathepsin K, as
well as H+, and the release of H+ is enabled by V-ATPase on the membrane of matured osteoclast. So that, cathepsin K and V-ATPase are considered as another two targets
to impair osteoclast function, especially, inhibitors of cathepsin K, such as Odanacatib, Balicatib are undergoing clinical trials. Front. Med., 20 December 2017
Biological procedures of osteoclast differentiation, bone resorption, and mechanisms of current or future
marrow
hemato
poietic
stem
cells
25. (romosozumab ; blosozumab)
Parathyroid Hormone Related-
Protein, PTHrP) analoge
Stimulate OB (Anticresorptive) Abaloparatide
Calcimitic (tt .hyper-parathroidism)
Calcilytic (
• CaR. agonist/ Alosteric activation →↓PTH release
• CaR. Antagonist→↑PTH ((Anticresorptive))
• Cinacalcet , etelcalcetide.
• No efficacy in trial for osteoporosis
SERMs Stimulate OB ((Anticresorptive) Lasofoxifene, Bazedoxifene
26.
27. Drug (Brand,
Manufacturer)
Treatment of PMO Prevention of
PMO
Treatment
(men)
Treatment of
GIO
Prevention of
GIO
Alendronate x x x x x
Alendronate/cholecalciferol x x
Alendronate effervescent x x
Risedronate IR x x x x x
Risedronate DR x
Ibandronate injection x
Ibandronate tablets x x
Zoledronic acid x x x x x
Denosumab x x
Raloxifene x x
Conjugated estrogens/ bazedoxifene x
Teriparatide x
c
x
Abaloparatide x
Calcitonin-salmon
d
x
Food and Drug Administration-Approved Indications for Osteoporosis Treatments4
aAlso indicated to increase bone mass in women and men at high risk of fracture without osteoporosis.
bTreatment only for those at high risk of fracture.
cIncreases bone mass in men with primary or hypogonadal osteoporosis at high risk of fracture.
dMiacalcin injection (Novartis) is indicated for the treatment of PMO in women more than five years postmenopause when alternative treatments are not suitable.
GIO = glucocorticoid-induced osteoporosis; PMO = postmenopausal osteoporosis.
28.
29.
30. High bone turn over( Paget’s
disease; Multiple myeloma
Fluid & diuretics(Forced diuresis, Loop diuretic)
Oral supplement: bisphosphate or calcitonine
Glucocorticoids,
Dialysis
Hg ,EDTA
excessive Mg
IV: gluconate or chloride with EKG change
Oral calcium with vitamin D
36. BONE ANABOLIC AGENTS
TERIPARATIDE
BISPHOSPHONATES
ESTROGEN ANALOGES
ANDROGEN ANALOGES
SERMS
CALCITONIN
RANKL INHIBITORS STRONTIUM
TREATMENT OF OSTEOPOROSIS
Replace what is missing….Ca, Vit D, Na fluoride
Reset back the balance of remodeling
ANTIRESORPTIVE AGENTS
Used to enhance the strength by the formation of fluorapatite.
Is considered only when trabecular bone is in presence of normal cortical bones
Others; Thiazide diuretics, statins
37. Infections; urinary & respiratory
Eczema & skin rash
Constipation
Cataract
Joint pains
DENOSUMAB
Brain Uterus Vagina Breast Bone CVS
Estradiol ++ ++ ++ ++ ++ ++
Raloxifene — — — — + +
Synthetic steroid estrogen, androgen & progestin properties Can be used without CVS risks
Teriparatide: 1-34 fragment of recombinant PTH - anabolic on the bone
↑ bone mass, structural integrity and strength, number and activity of Obs,
↓ OB apoptosis - acts via G-protein-coupled PTH-1 receptors (AC and PL activation)
-well-tolerated , nausea, dizziness, headache, joint pain, mild hypercalcaemia, orthostatic hypotension, headache might occur
- s.c. injection once a day - Clinical use: osteoporosis; prevention and treatment of pathological fractures
44. Factor control bone remodling OB OC
Intermittent /low concentration PTH ↑ ↓
Vit D low conc./ Ca deficient ↑ ↓
Calcitonin → ↓
Estrogen/ Testosterone (↑OPG) ↑ ↓
Mechanical load →↑ osteocyte ↑ ↓
PTH related protein (PThrP )(OB precursor) ↑ →
FGF(bone marrow; OB; lineage cells) ↑ ↔
PDGF (inflammatory cells) ↑ ↔
TGFB (bone matrix) ↑ ↔
IGF (OB;bone mtrix) ↑ ↔
Ephrin (osteoclast) ↑ ↓
Wnt (wingless-type mouse mammary tumor virus integration site)-
↑ by PgE2 ;NO. ATP (OB)
↑ ↔
Osteoprotegerin (OPG//NO (OB)→↓ RANK-RANKL interaction) → ↓
Bone Morphogenetic Proteins (bone marrow) →↑ OPG → ↑OB ↑ ↔
Osteocalcin→ mineralization (OB );↑insulin secreation ↑ →
Osteonectin (OB) → binds ca →initiating mineralization in
bone and collagen.+ angiogenesis, proliferation and migration
↑ →
Leptin ↑ →
Sema4D (osteoclast) ↓ →
Leukemic inhibitory Factor (bone marrow) ↓ ↑
Receptor activator for nuclear factor κB RANK L.( osteocyte) → ↑
Osteopontin anchor OC to mineralized matrix →bone
remodling
→ ↑
Pg →↑RANKL/↓OPG (osteocyte) ↑ ↔
T3/T4 → ↑
Glucocorticoid (↑RANKl;↓↓ OPG) → ↑↑
IL1,6/TNF/TGFB/M-csf ↓ ↑
Sclerostin (SOS) & DDK(Dickkopf-related protein1) ; sFRP-1
(soluble frizzled-related protein) ; WIF-1 (Wnt-inhibitory factor-1)
(OC) →↓wnt → ↓ wnt (osteocyte)
↓ →
Heparin → ↑
Osteoclast
(Bone resor-
ption cells)
Osteoblast
(Bone forming
cells)
Ostycte
(bone
maintaining)
Function * Synthesize
bone acid
phosphatase
*Secrete type I
collagen, alkaline
phosphatase+ ,
regulate OC
Ca+2
exchange
with
extracellular
fluid;
Stimu-
lated
by
P.T.H.(High
conc./continuous
) ; vit. D ( High
dose) ; cortisone
; T3/T4 ;
IL1,6/TNF /
TGFB ; heparin.,
RANK legend,
PTH (low conc/
intermittent);vit. D
(low conc/↓ Ca in
bone), PGE2, fluride
; IGF ; Estrogen,
testosterone;
mechanical load;
GH , Osteocalcin
Bispho. Na;
PTH
Inhibite
d
by
Calcitonin ,
Estrogen,
testosterone;
PgE2; GH;
mechanical load;
fluoride, OPG;
Bisphos.
RANK legand.
Glucocorticoid;
IL1,6/TNF/TGFB;
cortisone;
Sclerostin (from
osteocyte)
-
45. Daily dietary calcium requirements
National Health and Medical Research Council. (2006) Executive Summary of Nutrient Reference Values for
Australia and New Zealand Including Recommended Dietary Intakes.
Commonwealth Department of Health and Aging, Australia, Ministry of Health, New Zealand.
40 mg = 1 mmol