The VERT study found that daily treatment with risedronate significantly reduced the risk of new vertebral fractures by 41% and new morphometric vertebral fractures by 49% compared to placebo in postmenopausal women with osteoporosis over 3 years. Risedronate also reduced the risk of hip fractures by 39% and other nonvertebral fractures by 25%, although the results for nonvertebral fractures were not statistically significant. The study demonstrated that risedronate is a safe and effective treatment for reducing fracture risk in postmenopausal osteoporosis.
Multiple atraumatic osteoporotic vertebral fractures: Unusual cause of pain i...Apollo Hospitals
Secondary osteoporosis may not be detected early, and thus the condition remains clinically silent until the patient presents with multiple atraumatic compression fractures. It is devastating for a young patient to develop multiple vertebral fractures in view of the associated morbidity and mortality. To decrease the risk of additional fractures and preserve the quality of life in these patients, interventions should be initiated early. Hence, it is important to consider multiple osteoporotic vertebral fractures as a complication in any patient on prolonged steroid therapy.
We report the 11-year follow-up of a premenopausal woman with osteogenesisimperfecta (OI) who
was treated with alendronate. A 41-year-old Japanese premenopausal woman with OI type I who had
frequently experienced painful fragility fractures consulted our clinic because of chronic back pain associated
with spinal osteoporosis. She had undergone heart surgery (aortic valve replacement) because of aortic
regurgitation 5 years before her first consultation with our clinic. After surgery, she began taking warfarin (3
mg/day), and this treatment was continued during our follow-up period. She was treated with alendronate (5
mg/day or 35 mg/week) for 11 years. The patient’s urinary cross-linked N-terminal telopeptides of type I
collagen and serum alkaline phosphatase levels decreased, while the bone mineral density of her lumbar
spine (L2–L4) increased, as measured using dual energy X-ray absorptiometry. The serum calcium and
phosphorus levels stayed within the normal ranges. Three non-vertebral fractures occurred at the hip, ankle,
and ring finger during the 11-year treatment period, but no adverse effects were observed. Thus, the present
case report showed the long-term outcome and safety of alendronate treatment in a premenopausal woman
with OI type I.
Update on the 18th International Conference on Co-morbidities and Adverse Drug Reactions in HIV
Daniel Lee, M.D.
January 20th, 2017
UCSD HIV & Global Health Rounds
Multiple atraumatic osteoporotic vertebral fractures: Unusual cause of pain i...Apollo Hospitals
Secondary osteoporosis may not be detected early, and thus the condition remains clinically silent until the patient presents with multiple atraumatic compression fractures. It is devastating for a young patient to develop multiple vertebral fractures in view of the associated morbidity and mortality. To decrease the risk of additional fractures and preserve the quality of life in these patients, interventions should be initiated early. Hence, it is important to consider multiple osteoporotic vertebral fractures as a complication in any patient on prolonged steroid therapy.
We report the 11-year follow-up of a premenopausal woman with osteogenesisimperfecta (OI) who
was treated with alendronate. A 41-year-old Japanese premenopausal woman with OI type I who had
frequently experienced painful fragility fractures consulted our clinic because of chronic back pain associated
with spinal osteoporosis. She had undergone heart surgery (aortic valve replacement) because of aortic
regurgitation 5 years before her first consultation with our clinic. After surgery, she began taking warfarin (3
mg/day), and this treatment was continued during our follow-up period. She was treated with alendronate (5
mg/day or 35 mg/week) for 11 years. The patient’s urinary cross-linked N-terminal telopeptides of type I
collagen and serum alkaline phosphatase levels decreased, while the bone mineral density of her lumbar
spine (L2–L4) increased, as measured using dual energy X-ray absorptiometry. The serum calcium and
phosphorus levels stayed within the normal ranges. Three non-vertebral fractures occurred at the hip, ankle,
and ring finger during the 11-year treatment period, but no adverse effects were observed. Thus, the present
case report showed the long-term outcome and safety of alendronate treatment in a premenopausal woman
with OI type I.
Update on the 18th International Conference on Co-morbidities and Adverse Drug Reactions in HIV
Daniel Lee, M.D.
January 20th, 2017
UCSD HIV & Global Health Rounds
Prof. Richard Eastell's presentation from Osteoporosis 2016: Patients receiving bisphosphonates should take holidays from treatment. The case for holidays.
Find out more at: https://nos.org.uk/conference
OSTEOPOROSIS:A Barebone guide to diagnosis and managementGovindRankawat1
“Progressive systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk”
True Definition: bone with lower density and higher fracture risk
WHO: utilizes Bone Mineral Density as definition (T score <-2.5)
Osteoporosis is silent because there are no symptoms initially.
The most common are fractures of the spine, hip, and wrist.
Osteoporosis is not an inevitable part of aging, but is a disease that can be prevented and treated, provided it is detected early.
The main goal of treating osteoporosis is to prevent such fractures in the first place.
Bare bone term used for “necked bone with necked eye”
“There is clearly a problem of underdiagnosis and undertreatment of osteoporosis and we want to raise awareness about the risk factors for osteoporosis so that those who need treatment get treatment”.
Learning Objectives
Utilize recent recommendations for osteoporosis prevention and treatment and how to apply them in practice.
Explain controversies surrounding pharmacologic osteoporosis therapy including side effects and the risk/benefit ratio of therapy.
Determine when and how to utilize the current pharmacologic therapies including anabolic versus anti-resorptive approaches and how to transition or discontinue treatment
Osteoporosis only causes symptoms when it is far advanced.
Symptoms include loss of height, deformed spine (“dowager’s hump”), unexplained back pain, and fractures.
It is best to detect problems at an early stage, when treatment is most effective.
The best test for detecting osteoporosis is bone densitometry, done with a technique called “Dual-energy X-ray Absorptiometry” or DXA.
In the presentation, I discussed new concepts in OA pathogenesis and identified possible targets of treatment. This was followed by a review of new treatment options for osteoarthritis. Presented during the Joint RA OA SIG Symposium at the F1 Hotel last 28 November 2014.
Background: The spectrum of pathological bone lesions ranges from inflammatory to neoplastic conditions. Bone tumours are comparatively uncommon among wide array of lesions. The roentgenogram helps in defining exact location of lesion but becomes difficult to differentiate them. They often pose diagnostic problem as they constitute a small portion of diagnostic experience among pathologist.
Objective: To study histopathological spectrum of bone lesions & correlate them with age, gender and site of occurrence.
Results: All bone biopsies from January 2011 to December 2015 received at department of pathology, S.Nijalingappa Medical College, India. Total 121 cases of bone biopsies were analysed. They were decalcified & processed routinely. Out of 121 bone biopsies, 35 (28.9%) cases are non- neoplastic, 77 (63.6%) are neoplastic and 9 (7.4%) were inadequate for evaluation. The incidence of benign lesions are more than malignant with 51(66.2%) and 26(33.7%) cases respectively. Chronic osteomyelitis is the most common non-neoplastic lesion. Giant cell tumor and osteosarcoma are common benign and malignant lesions respectively. Femur is the common bone involved and metaphysis, the commonest site. The maximum numbers of cases are in the age group between 11-30 years with male preponderance.
Conclusion: Though bone lesions are less common, if viewed in perspective of clinico-radiology and histopathology, correct diagnosis can be reached.
Key-words- Bone lesions, Chronic osteomyelitis, Osteosarcoma, Giant cell tumor, Histopathology
Frequency of Osteoporotic Fractures, Parameters of Bone Mineral Density and T...CrimsonPublishersOPROJ
Frequency of Osteoporotic Fractures, Parameters of Bone Mineral Density and Trabecular Bone Score in Postmenopausal Women by Grygorieva N* in Orthopedic Research Online Journal
Prof. Richard Eastell's presentation from Osteoporosis 2016: Patients receiving bisphosphonates should take holidays from treatment. The case for holidays.
Find out more at: https://nos.org.uk/conference
OSTEOPOROSIS:A Barebone guide to diagnosis and managementGovindRankawat1
“Progressive systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk”
True Definition: bone with lower density and higher fracture risk
WHO: utilizes Bone Mineral Density as definition (T score <-2.5)
Osteoporosis is silent because there are no symptoms initially.
The most common are fractures of the spine, hip, and wrist.
Osteoporosis is not an inevitable part of aging, but is a disease that can be prevented and treated, provided it is detected early.
The main goal of treating osteoporosis is to prevent such fractures in the first place.
Bare bone term used for “necked bone with necked eye”
“There is clearly a problem of underdiagnosis and undertreatment of osteoporosis and we want to raise awareness about the risk factors for osteoporosis so that those who need treatment get treatment”.
Learning Objectives
Utilize recent recommendations for osteoporosis prevention and treatment and how to apply them in practice.
Explain controversies surrounding pharmacologic osteoporosis therapy including side effects and the risk/benefit ratio of therapy.
Determine when and how to utilize the current pharmacologic therapies including anabolic versus anti-resorptive approaches and how to transition or discontinue treatment
Osteoporosis only causes symptoms when it is far advanced.
Symptoms include loss of height, deformed spine (“dowager’s hump”), unexplained back pain, and fractures.
It is best to detect problems at an early stage, when treatment is most effective.
The best test for detecting osteoporosis is bone densitometry, done with a technique called “Dual-energy X-ray Absorptiometry” or DXA.
In the presentation, I discussed new concepts in OA pathogenesis and identified possible targets of treatment. This was followed by a review of new treatment options for osteoarthritis. Presented during the Joint RA OA SIG Symposium at the F1 Hotel last 28 November 2014.
Background: The spectrum of pathological bone lesions ranges from inflammatory to neoplastic conditions. Bone tumours are comparatively uncommon among wide array of lesions. The roentgenogram helps in defining exact location of lesion but becomes difficult to differentiate them. They often pose diagnostic problem as they constitute a small portion of diagnostic experience among pathologist.
Objective: To study histopathological spectrum of bone lesions & correlate them with age, gender and site of occurrence.
Results: All bone biopsies from January 2011 to December 2015 received at department of pathology, S.Nijalingappa Medical College, India. Total 121 cases of bone biopsies were analysed. They were decalcified & processed routinely. Out of 121 bone biopsies, 35 (28.9%) cases are non- neoplastic, 77 (63.6%) are neoplastic and 9 (7.4%) were inadequate for evaluation. The incidence of benign lesions are more than malignant with 51(66.2%) and 26(33.7%) cases respectively. Chronic osteomyelitis is the most common non-neoplastic lesion. Giant cell tumor and osteosarcoma are common benign and malignant lesions respectively. Femur is the common bone involved and metaphysis, the commonest site. The maximum numbers of cases are in the age group between 11-30 years with male preponderance.
Conclusion: Though bone lesions are less common, if viewed in perspective of clinico-radiology and histopathology, correct diagnosis can be reached.
Key-words- Bone lesions, Chronic osteomyelitis, Osteosarcoma, Giant cell tumor, Histopathology
Frequency of Osteoporotic Fractures, Parameters of Bone Mineral Density and T...CrimsonPublishersOPROJ
Frequency of Osteoporotic Fractures, Parameters of Bone Mineral Density and Trabecular Bone Score in Postmenopausal Women by Grygorieva N* in Orthopedic Research Online Journal
Similar to Osteoporosis, How to diagnose and treat _ Oral and Infusion Treatment.pptx (20)
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
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
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
- 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
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
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!
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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.
2. Apakah Osteoporosis?
• Penyakit tulang yang ditandai dengan menurunnya massa tulang
(kepadatan tulang) secara keseluruhan 1
• 1 dari 4 perempuan di Indonesia dengan rentang usia 50-80 tahun
memiliki resiko terkena osteoporosis 1
• Gejala umum osteoporosis mulai dari patah tulang, tulang punggung yang
semakin membungkuk, menurunnya tinggi badan, dan nyeri punggung1
• Diagnosis osteoporosis berdasarkan pengukuran BMD dan terjadinya
fraktur (WHO Criteria) 2
1. Infodatin, 2015
2. Szule P, et al. IOF-VFI part I,
3. Tulang Normal vs. Osteoporosis
https://www.bookingdokter.com/article/mengenal-osteoporosis-dan-osteomalasia
8. Pemeriksaan Fisis & Riwayat Pasien
• Faktor resiko, termasuk informasi tentang fraktur terakhir
• Riwayat keluarga, termasuk osteoporosis
• Riwayat pengobatan, termasuk pengobatan yang menyebabkan
pengurangan massa tulang (mis, glucocorticoid)
• Konsumsi Kalsium dan Vitamin D
• Pola hidup (mis, olahraga, diet tinggi lemak, merokok, dan
penyalahgunaan obat-obatan dan minuman keras)
• Penyakit yang menyebabkan osteoporosis sekunder (Cushing’s
syndrome, thyroid disease, hyperthyroidism, hypogonadism)
https://www.alomedika.com/penyakit/reumatologi/osteoporosis/diagnosis
9. Faktor Resiko Osteoporosis
• Jenis kelamin: perempuan
• Usia lanjut
• Etnis Kaukasia atau Asia
• Riwayat patah tulang setelah usia 50 tahun
• Riwayat keluarga terkena osteoporosis
• Gaya hidup pasif
• Struktur kerangka kecil
• Patah tulang yang keropos
• Massa tulang Rendah
• Beberapa kondisi medis yang kronis
• Defisiensi Estrogen karena
menopause
• Kadar testosteron yang
rendah pada pria
• Asupan rendah kalsium atau
vitamin D
• Penggunaan obat-obatan
tertentu (misalnya,
kortikosteroid)
• Merokok
• Konsumsi alkohol berlebihan
https://hellosehat.com/muskuloskeletal/osteoporosis/penyebab-osteoporosis/
10. Bone Mineral Densitometry/BMD
• Untuk menentukan kepadatan tulang
• Saat ini digunakan dual-energi sinar-X
absorptiometry (DEXA)
• Penggunaannya pada pinggul, tulang belakang, pergelangan tangan, tumit,
jari
• Standar emas untuk diagnosis dan memantau efek pengobatan osteoporosis
• Lama pemeriksaan 10-30 menit
https://www.radiologyinfo.org/en/info
16. etidronate
pamidronate zoledronic acid
HO
HO OH
OH
OH
O
O
P
P
CH3
OH
OH
OH
OH
O
O
P
P
Cl
Cl
HO
OH
OH
OH
O
O
P
P
S
Cl
clodronate
tiludronate
alendronate
ibandronate
risedronate
BPs yang mengandung Nitrogen
Bisfosfonat Non-Nitrogen
Bisfosfonat (BP)
H2N
HO
HO
OH
OH
OH
O
O
P
P
HO
N
O
O
=
=
P
P
OH
OH
OH
OH
HO
O
O
P
P
OH
OH
OH
OH
H2N
OH
OH
OH
O
O
N P
P
OH
HO
CH3
CH3 N
N
O
O
P
P
HO OH
OH
OH
OH
Konstanta Afinitas (KL) untuk adsorpsi bisphosponate untuk pertumbuhan Hidroxyapatite (pH 7.4)
adalah: zoledronate > alendronate > ibandronate > risedronate > etidronate > clodronate
Adapted from Nancollas GH, et al. Bone 2006;38:617-27
21. Farmakokinetik Zoledronate
• Setelah infus Zoledronate, konsentrasi
plasma mencapai puncaknya di akhir
periode Infus, diikuti dengan adanya
penurunan kadar di plasma tersisa
sebanyak :
< 10% setelah 4 jam
< 1% setelah 24 jam
• Dalam 24 jam, Zoledronate 61% terikat
di tulang
• Dan dieliminasi melalui ginjal sebanyak
39+ 16%
Chen T, et al. J Clin Pharmacol, 2002;42; 1228-1236
22. Yearly infusions with Aclasta® significantly reduced fracture
risk at different sites1 (hip, vertebral, non-vertebral†)
Only Zoledronate has demonstrated efficacy for three different types of
fracture protection2-5 (hip, vertebral, non-vertebral†)
†Non-vertebral fracture: includes wrist, rib, arm, shoulder, or hip fracture; excludes finger, toe, or craniofacial fracture
Cumulative incidence of new clinical fractures over 3 years1
1) Black et al. N Engl J Med. 2007;356:1809-1822; 2) Fosamax® weekly tablets SmPC; 3) Actonel® weekly tablets SmPC; 4) Bonviva® tablets SmPC; 5) Aclasta® SmPC
Values above bars are 3 year cumulative event based on Kaplan-Meier estimates.
*p = .002; †p < .001; ‡p < .001; relative risk reduction vs placebo
§Hip fracture was not excluded from analysis of non-vertebral fracture
Cumulative
incidence
(%)
of
new
clinical
fractures
over
3
years
Hip Fracture Clinical vertebral fracture Non-vertebral fracture§
Adapted from reference 14
23. Zoledronic Acid 5 mg Reduced Subsequent Fracture Risk
Over Time
0
2
4
6
8
10
12
14
16
18
20
Clinical
Fractures
Non-Vertebral
Fractures
Clinical
Vertebral
Fractures
Hip
Fractures
10.7%
(107/1062)
8.6%
(92/1065)
13.9%
(139/1062)
7.6%
(79/1065)
3.8%
(39/1062)
1.7%
(21/1065)
3.5%
(33/1062)
2.0%
(23/1065)
35%*
(16%, 50%)
27%†
(2%, 45%)
46%‡
(8%, 68%)
30%
(-2%, 59%)
*P = .0012; †P = .0338; ‡P = .0210, relative risk reduction vs placebo; NS = not significant.
Values above bars are cumulative event rates based on Kaplan-Meier estimates at Month 24.
Event
Rate
(%)
ZOL 5 mg
Placebo
Lyles KW, et al. N Engl J Med. 2007;357:1799-809
23
24. Zoledronic Acid 5 mg Produced Significant Increases in Total Hip BMD and
Femoral Neck Over 3 Years vs. Placebo
Excludes Center 829. Bracketed values are least-squares mean difference, ZOL vs placebo.
*P < .0001; P = .0003; P-value computed from 2-way ANOVA with treatment and region in the model.
24 Lyles KW, et al. N Engl J Med. 2007;357:1799–09.
Total Hip BMD Femoral Neck BMD
27. Zoledronate is safe and well tolerated
Most common adverse events (“flu-like symptoms”) were transient post-dose symptoms1,2
Additional Key Safety Findings
Renal function Over 3 years, no significant difference in mean creatinine clearance between treatment groups1
Over-suppression Bone turnover normalized to premenopausal levels with no evidence of oversuppression2
Osteonecrosis of the jaw 1 Zoledronate-treated patient, 1 placebo-treated patient1,2
Atrial fibrillation AE reported in 2.4% of Aclasta®-treated patients (94/3862) vs. 1.9% (73/3852) in the placebo group and SAE in 1.3%
(50/3862) vs. 0.5% (20/3852) of patients, respectively1
This imbalance has not been observed in other clinical trials with zoledronic acid1
Most common adverse events within 3 days after annual infusion3
Incidence
(%)
Year of infusion
Placebo values cross-hatched
1) Black et al. N Engl J Med. 2007;356:1809-1822; 2) Aclasta® SmPC 3) Heggland J et. al. Data on file. Novartis Pharma AG
31. Osteoporosis Indications for Bisphosphonate Based on FDA Approved
Zoledronic acid is the only bisphosphonate, investigated in an RCT and
approved by the CHMP and FDA for the treatment of osteoporosis in women
and men with a recent surgical repair of low-trauma hip fracture2
1Clinician’s Guide To Prevention And Treatment Of Osteoporosis. National Osteoporosis Foundation 2013: 1-
53; 2Lyles KW, et al. N Engl J Med. 2007;357:1799–1809
34. 34
Clinical Study
From slide #11 to #24 - i will be developing slide from
those references :
• Harris, et al. JAMA. 1999;282:1344-52.
• Reginster, et al. Osteoporos Int (2000) 11:83–91
Risedronate
35. Effects of Risedronate Treatment on Vertebral
and Nonvertebral FractUREs in Women With
PostmenopaUSAl Osteoporosis
Harris, Steven T., et al. "Effects of risedronate treatment on vertebral and nonvertebral
fractures in women with postmenopausal osteoporosis: a randomized controlled
trial." Jama 282.14 (1999): 1344-1352.
36. 36
Effects of Risedronate Treatment on Vertebral and Nonvertebral
Fractures in Women With Postmenopausal Osteoporosis
(VERT – 1999 – Europe & Aus)
Metode : Acak, double-blind, placebo-controlled trial, parallel-group study, dilakukan di 110 pusat penelitian di Amerika Utara
Tujuan: Menguji kemanjuran dan keamanan terapi harian risedronate dalam mengurangi risiko patah tulang belakang dan
patah tulang lainnya pada wanita pascamenopause yang mengalami osteoporosis
Kriteria Inklusi:
• Wanita pascamenopause
• rawat jalan
• < 85 tahun
• setidaknya 1 patah tulang belakang
Outcome utama:
Kejadian patah tulang belakang baru seperti yang terdeteksi oleh penilaian kuantitatif dan semikuantitatif radiografi;
Kejadian patah tulang nonvertebral yang dikonfirmasi secara radiografis dan perubahan dari baseline dalam kepadatan
mineral tulang (BMD)
Kriteria Eksklusi:
• Kondisi yang mengganggu evaluasi spinal
bone loss
• calcitonin, calcitriol atau cholecalciferol
supplements (1 bulan sebelum penelitian)
• Anabolic steroids, estrogen /
estrogenrelated, / progestins selama 3
bulan
• bisphosphonates, fluoride, implan estrogen
selama 6 bulan
0 1 2 3 yr.
N=2458
Placebo + Ca suppl ~1000mg/d
Risedronate, 2.5 mg/d +
Ca suppl ~1000mg/d
Risedronate, 5 mg/d+ Ca suppl ~1000mg/d
N=815
N=811
N=813
Harris, Steven T., et al. "Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal
osteoporosis: a randomized controlled trial." Jama 282.14 (1999): 1344-1352.
37. 37
Effects of Risedronate Treatment on Vertebral and Nonvertebral
Fractures in Women With Postmenopausal Osteoporosis
(VERT – 1999 – Europe & Aus)
Harris, Steven T., et al. "Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal
osteoporosis: a randomized controlled trial." Jama 282.14 (1999): 1344-1352.
Incidence of New Vertebral
Fractures by Groups Over Time
Incidence of Nonvertebral
Fractures by Study Group Over Time
38. 38
Effects of Risedronate Treatment on Vertebral and Nonvertebral
Fractures in Women With Postmenopausal Osteoporosis
(VERT – 1999 – Europe & Aus)
Harris, Steven T., et al. "Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal
osteoporosis: a randomized controlled trial." Jama 282.14 (1999): 1344-1352.
Mean Percent Change From Baseline in Bone Mineral Density
5.4%
1.6%
3.3%
39. 39
Effects of Risedronate Treatment on Vertebral and Nonvertebral
Fractures in Women With Postmenopausal Osteoporosis
(VERT – 1999 – Europe & Aus)
Harris, Steven T., et al. "Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal
osteoporosis: a randomized controlled trial." Jama 282.14 (1999): 1344-1352.
Median Percentage Change From Baseline in Bone-Specific Alkaline Phosphatase
and Deoxypyridinoline-Creatinine Ratio
40. 40
Kesimpulan
Harris, Steven T., et al. "Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal
osteoporosis: a randomized controlled trial." Jama 282.14 (1999): 1344-1352.
• Terapi risedronate oral dapat ditoleransi dengan baik dan menghasilkan penurunan
yang cepat dan penting secara klinis dalam risiko patah tulang pada wanita dengan
osteoporosis pascamenopause.
• Penurunan yang signifikan dalam kejadian patah tulang belakang baru diamati pada
tahun pertama pengobatan, sedangkan penurunan yang sama pada patah tulang
belakang terlihat setelah 3 tahun.
Risedronate adalah efektif dan dapat ditoleransi dengan
baik untuk pengobatan osteoporosis pascamenopause.
41. Randomized Trial of the Effects of Risedronate
on Vertebral Fractures in Women with
Established Postmenopausal Osteoporosis
Reginster, J-Y., et al. "Randomized trial of the effects of risedronate on vertebral fractures in women
with established postmenopausal osteoporosis." Osteoporosis international 11.1 (2000): 83-91.
42. 42
Randomized Trial of the Effects of Risedronate on Vertebral Fractures
in Women with Established Postmenopausal Osteoporosis
(VERT NA – 2000 – Europe & Aus)
Metode : Acak, double-masked, placebo-controlled trial, dilakukan di 80 pusat penelitian di Eropa dan Autralia
Tujuan: Untuk menilai kemanjuran dan keamanan risedronate dalam pencegahan patah tulang belakang pada wanita
pascamenopause yang mengalami osteoporosis
Kriteria Inklusi:
• Wanita pascamenopause (min. 5 thn)
• rawat jalan
• < 85 tahun
• setidaknya terkonfirmasi Ro fraktur T4-L4
Outcome utama: Kejadian patah
tulang belakang selama dalam waktu
3 tahun
Kriteria Eksklusi:
• Kondisi yang mengganggu evaluasi spinal
osteoporosis.
• calcitonin, calcitriol atau Vit D supplements
(1 bulan sebelum penelitian)
• Anabolic steroids, estrogen /
estrogenrelated, / progestins selama 3
bulan
• bisphosphonates, fluoride, implan estrogen
selama 6 bulan
0 1 2 3 yr.
N=1226
Placebo + Ca suppl ~1000mg/d or Vit D 500IU/d
Risedronate, 2.5 mg/d +
Ca suppl ~1000mg/d or
Vit D 500IU/d
Risedronate, 5 mg/d+ Ca suppl ~1000mg/d or Vit D 200IU/d
N=407
N=408
N=407
Reginster, J-Y., et al. "Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal
osteoporosis." Osteoporosis international 11.1 (2000): 83-91.
43. 43
Randomized Trial of the Effects of Risedronate on Vertebral Fractures
in Women with Established Postmenopausal Osteoporosis
(VERT NA – 2000 – Europe & Aus)
Reginster, J-Y., et al. "Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal
osteoporosis." Osteoporosis international 11.1 (2000): 83-91.
Incidence of a new vertebral fractures Nonvertebral osteoporosis-related fractures
44. 44
Randomized Trial of the Effects of Risedronate on Vertebral Fractures
in Women with Established Postmenopausal Osteoporosis
(VERT NA – 2000 – Europe & Aus)
Reginster, J-Y., et al. "Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal
osteoporosis." Osteoporosis international 11.1 (2000): 83-91.
Percentage change from baseline in bone mineral density of:
a. lumbar spine b. femoral neck c. midshaft radius
45. 45
Kesimpulan
Reginster, J-Y., et al. "Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal
osteoporosis." Osteoporosis international 11.1 (2000): 83-91.
Risedronate 5 mg efektif dan dapat ditoleransi dengan
baik terapi untuk osteoporosis pascamenopause yang
berat, mengurangi kejadian patah tulang belakang dan
meningkatkan kepadatan tulang pada wanita dengan
osteoporosis pascamenopause
46. Risedronate Reverses Bone Loss in
Postmenopausal Women with Low Bone
Mass: Results From a Multinational,
Double-Blind, Placebo-Controlled Tria
(BMD MN – 2015)
47. Hasil
BMD
• ACTONEL mencegah terjadinya Bone Loss pada wanita (usia 42-63 th) selama 3 tahun.
• Peningkatan BMD ditunjukkan pada pemberian ACTONEL selama 3 bulan
• ACTONEL secara signifikan meningkatkan BMD pada Lumbar Spine, Femoral Neck dan Trochantar
dibanding Placebo pada akhir Studi
48. 48
KESIMPULAN
1. Zoledronic Acid 5mg (Aclasta) terbukti efektif mencegah terjadinya Fraktur Osteoporosis di ketiga titik
penting yaitu vertebrae 70%, hip 41% dan non-vertebrae 25%
2. Zoledronic Acid 5mg memiliki potensi penghambatan sintesa enzim FPPs, sehingga memiliki potensi anti
resorpsi paling maksimal dan dapat digunakan satu tahun sekali.
3. Dalam 24 jam, 61% Zoledronate Acid 5mg terikat di tulang, dan +39% dieliminasi melalui ginjal
4. Zoledronic Acid 5mg terbukti aman dan ditoleransi dengan baik oleh tubuh, AE yang umumnya muncul
bersifat sementara dan dapat diatasi dengan obat-obatan seperti paracetamol ataupun ibuprofen
5. ACLASTA tersedia di JKN
6. Relative Fracture Risk Reduction Aclasta® (Zoledronic Acid) untuk ketiga titik penting (Vertebrae, Hip, &
Non Vertebrae) memiliki nilai yang relative lebih baik dibanding bisphosponate lain (data not from
comparative trial)
7. Risedronate 5 mg (Actonel®) efektif dan dapat ditoleransi dengan baik terapi untuk osteoporosis
pascamenopause yang berat, mengurangi kejadian patah tulang belakang dan meningkatkan kepadatan
tulang pada wanita dengan osteoporosis pascamenopause
8. ACTONEL mencegah terjadinya Bone Loss pada wanita (usia 42-63 th) selama 3 tahun