Way forward in osteoporosis: a disease which is no longer silent
Outline <ul><li>Introduction to the condition </li></ul><ul><li>Definition </li></ul><ul><li>Prevalence </li></ul><ul><li>...
Osteoporosis <ul><li>Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposin...
Fractures in Women Are Common: Incidence of Chronic Diseases 1. Riggs BL, Melton LJ III.  Bone.  1995;17(suppl):505S–511S....
Prevalence in India <ul><li>Expert groups peg the number of osteoporosis patients at ~26 million (2003 figures) with the n...
WHO Risk Factors  <ul><li>Age (50-90), gender and clinical risk factors: </li></ul><ul><li>BMI </li></ul><ul><li>Prior fra...
Pathogenesis of Osteoporosis-Related Fractures Reference: Cooper C, Melton LJ. Epidemiology of osteoporosis.  Trends Endoc...
Osteoporosis Diagnosis—from bone mineral density to structure imaging
NOF 2008 Guidelines Who Should be Tested? <ul><li>Women age 65 and older </li></ul><ul><li>Men age 70 and older </li></ul>...
DXA (Dual X-ray absorptiometry) <ul><li>DXA overtook QCT (quantitative computed tomography) and is currently the standard ...
Multi-detector CT (MD-CT) scanners <ul><li>Bone structure analysis was applied to crosssectional imaging techniques employ...
Multi-detector CT (MD-CT) scanners Skeletal Radiol (2010) 39:943–955
High resolution peripheral CT (hrp-QCT) scanner <ul><li>Recently a high resolution peripheral CT (hrp-QCT) scanner (Xtreme...
Ultra-short echo time (UTE) imaging technique <ul><li>Technique to assess water content of the cortical bone as a potentia...
Vertebral fracture assessment <ul><li>Previous studies have found a circa 10% prevalence of vertebral fractures in women i...
Semiquantitative grading system <ul><li>According to this score, a vertebral deformity of T4-L4 of more than 20% loss in h...
Identifying high risk patients: WHO Fracture Risk Assessment – FRAX Tool   <ul><li>Provides a valuable resource for determ...
Pyramid for Osteoporosis Prevention and Treatment Leading the Effort to Help Prevent and  Treat Osteoporosis US Department...
Calcium <ul><li>An essential cotherapy in osteoporosis treatment. </li></ul><ul><li>Many older women with osteoporosis hav...
Recommended daily calcium intakes <ul><li>Recommended daily calcium intakes(in mg/day) for populations vary between countr...
Vitamin D <ul><li>Vitamin D is also essential for the development and maintenance of bone, both for its role in assisting ...
Vitamin D Metabolites <ul><li>A synthetic form of calcitriol (1,25 dihydroxycholecalciferol; 1,25-dihydroxyvitamin D3), th...
Calcitriol <ul><li>Synthetic vitamin D analogue </li></ul><ul><li>Promotes calcium absorption </li></ul><ul><li>Approved b...
<ul><li>Bone growth retardation: a common finding in various conditions associated with dietary zinc deficiency. </li></ul...
Primary Types of Pharmacotherapy <ul><li>Antiresorptive Agents (reduce bone loss) </li></ul><ul><li>Anabolic Agents (build...
Osteoporosis Current pharmacotherapy options Source: Alexander I, Andrist L. Menopause. In: F Likis, K. Shuiling, eds. Wom...
Source: Alexander I, Andrist L. Menopause. In: F Likis, K. Shuiling, eds. Women’s Gynecologic Health. Sudbury, MA: Jones a...
Source: Alexander I, Andrist L. Menopause. In: F Likis, K. Shuiling, eds. Women’s Gynecologic Health. Sudbury, MA: Jones a...
FDA Indications for Osteoporosis  Ann Babbitt. Osteoporosis Update 2010 Drug PMO GIO (Women, Men) Men Prevention Treatment...
Fracture Risk Reduction in RCTs Ann Babbitt. Osteoporosis Update 2010 Medication Spine Nonvertebral Hip Estrogen       ...
Risedronate <ul><li>Approved by the FDA for the prevention and treatment of postmenopausal osteoporosis. </li></ul><ul><li...
Calcitonin <ul><li>FDA-approved for the treatment of osteoporosis in women who are at least five years postmenopausal. </l...
Novel Therapies <ul><li>Novel anti-resorptives that can target the formation or the activity of osteoclasts include: </li>...
New and Emerging Treatments <ul><li>Antiresorptive  (anti-catabolic) </li></ul><ul><li>Denosumab  </li></ul><ul><li>Odanac...
Differences Between Denosumab and Bisphosphonates <ul><li>Ref:Ernesto Canalis. New Treatment Modalities In Osteoporosis 20...
Advantages and Disadvantages of Denosumab  (an antibody) <ul><li>Ref:Ernesto Canalis. New Treatment Modalities In Osteopor...
Advantages and Disadvantages of SERMS (Eg: Lasofoxifene, Bazedoxifene) <ul><li>Ref:Ernesto Canalis. New Treatment Modaliti...
Advantages and Disadvantages of Cathepsin K Inhibitors (Eg: odanacatib, balicatib and relacatib) <ul><li>Ref:Ernesto Canal...
<ul><li>The last 3 decades indicates that substantial progress in diagnostic techniques to diagnose and monitor osteoporos...
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  • Fractures in Women Are Common: Incidence of Chronic Diseases This slide demonstrates that the incidence of new cases of osteoporotic fracture in women each year is far greater than the incidence of heart attack, stroke, and breast cancer combined. 1 – 3 Hip fracture incidence alone exceeds that of breast cancer. 1 This information, with the information on the previous slide, further emphasizes that osteoporosis should be considered a major health concern among postmenopausal women in the United States. The point is not to suggest that osteoporosis is more important than the other diseases but that it should be managed as routinely as are the other diseases. References: 1. Riggs BL, Melton LJ III. The worldwide problem of osteoporosis: insights afforded by epidemiology. Bone . 1995;17(suppl):505S – 511S. 2. American Stroke Association. Heart disease and stroke statistics––2005 update. Available at: http://www.americanheart.org/downloadable/heart/1105390918119HDSStats2005Update.pdf. Accessed August 24, 2005. 3. American Cancer Society. Cancer facts &amp; figures: 2005. Available at: http://www.cancer.org/downloads/STT/CAFF2005f4PWSecured.pdf. Accessed August 24, 2005.
  • Am J Clin Nutr. 2010 Jul;92(1):101-5. Epub 2010 May 19. Phosphate and carbonate salts of calcium support robust bone building in osteoporosis. Heaney RP , Recker RR , Watson P , Lappe JM . Osteoporosis Research Center, Creighton University, Omaha, NE, USA. rheaney@creighton.edu Abstract BACKGROUND: Calcium is an essential cotherapy in osteoporosis treatment. The relative effectiveness of various calcium salts for this purpose is uncertain. Many older women with osteoporosis have phosphorus intakes of &lt;70% of the Recommended Dietary Allowance. OBJECTIVE: Our objective was to test the hypothesis that calcium phosphate would better support anabolic bone building than would calcium carbonate. DESIGN: This study was a 12-mo, randomized, positive-comparator, 2-arm, single-blind clinical trial in 211 patients treated with teriparatide who consumed &lt;1000 mg phosphorus/d. Participants were randomly assigned to receive, in addition to teriparatide and 1000 IU cholecalciferol, 1800 mg calcium/d as either tricalcium phosphate or calcium carbonate. The primary endpoints were changes in lumbar spine and total hip bone mineral densities (BMDs); secondary endpoints were changes in bone resorption biomarkers and serum and urine calcium and phosphorus concentrations. RESULTS: In the combined group, the lumbar spine BMD increased by 7.2%, and total hip BMD increased by 2.1% (P &lt; 0.01 for both). However, there was no significant difference between calcium-treatment groups, and there were no significant between-group differences in serum calcium and phosphorus concentrations or in urine calcium concentrations. Bone resorption biomarkers increased in both groups, as expected with teriparatide, but the increases in the 2 calcium groups did not differ significantly. CONCLUSIONS: Tricalcium phosphate and calcium carbonate appear to be approximately equally effective in supporting bone building with a potent anabolic agent; phosphate salt may be preferable in patients with restricted phosphorus intakes. This trial was registered at clinicaltrials.gov as NCT00074711.
  • Abstract Zinc is known as an essential nutritional factor in the growth of the human and animals. Bone growth retardation is a common finding in various conditions associated with dietary zinc deficiency. Bone zinc content has been shown to decrease in aging, skeletal unloading, and postmenopausal conditions, suggesting its role in bone disorder. Zinc has been demonstrated to have a stimulatory effect on osteoblastic bone formation and mineralization; the metal directly activates aminoacyl-tRNA synthetase, a rate-limiting enzyme at translational process of protein synthesis, in the cells, and it stimulates cellular protein synthesis. Zinc has been shown to stimulate gene expression of the transcription factors runt-related transcription factor 2 (Runx2) that is related to differentiation into osteoblastic cells. Moreover, zinc has been shown to inhibit osteoclastic bone resorption due to inhibiting osteoclast-like cell formation from bone marrow cells and stimulating apoptotic cell death of mature osteoclasts. Zinc has a suppressive effect on the receptor activator of nuclear factor (NF)-κB ligand (RANKL)-induced osteoclastogenesis. Zinc transporter has been shown to express in osteoblastic and osteoclastic cells. Zinc protein is involved in transcription. The intake of dietary zinc causes an increase in bone mass. β-Alanyl-L-histidinato zinc (AHZ) is a zinc compound, in which zinc is chelated to β-alanyl-L-histidine. The stimulatory effect of AHZ on bone formation is more intensive than that of zinc sulfate. Zinc acexamate has also been shown to have a potent-anabolic effect on bone. The oral administration of AHZ or zinc acexamate has the restorative effect on bone loss under various pathophysiologic conditions including aging, skeletal unloading, aluminum bone toxicity, calcium- and vitamin D-deficiency, adjuvant arthritis, estrogen deficiency, diabetes, and fracture healing. Zinc compounds may be designed as new supplementation factor in the prevention and therapy of osteoporosis.
  • Adherence - Osteoporosis The 2 primary types of pharmacotherapy for osteoporosis are antiresorptive agents that reduce bone loss and anabolic agents that build bone Antiresorptive agents work by reducing bone loss and include Bisphosphonates estrogen (hormone replacement therapy, or HRT) Selective estrogen receptor modulators (SERMs) Calcitonin Anabolic agents work by building bone and include synthetic parathyroid hormone US Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: US Department of Health and Human Services, Office of the Surgeon General; 2004.
  • Ann Babbitt. Osteoporosis Update 2010
  • Ann Babbitt. Osteoporosis Update 2010
  • Skeletal Radiol (2010) 39:943–955
  • Way+forward+in+osteoporosis%3aa+disease+which+is+no+longer+silent

    1. 1. Way forward in osteoporosis: a disease which is no longer silent
    2. 2. Outline <ul><li>Introduction to the condition </li></ul><ul><li>Definition </li></ul><ul><li>Prevalence </li></ul><ul><li>Etiology </li></ul><ul><li>Pathophysiology </li></ul><ul><li>Diagnosis </li></ul><ul><li>Emerging Diagnostic Measures </li></ul><ul><li>Pharmacotherapy therapy measures </li></ul><ul><li>Emerging Pharmacotherapy therapy measures </li></ul><ul><li>Summary </li></ul>
    3. 3. Osteoporosis <ul><li>Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. </li></ul><ul><li>NIH Consensus Development Conference, March 2000 </li></ul>WHO T-score interpretation
    4. 4. Fractures in Women Are Common: Incidence of Chronic Diseases 1. Riggs BL, Melton LJ III. Bone. 1995;17(suppl):505S–511S. 2. American Stroke Association. Heart disease and stroke statistics––2005 update. Available at: http://www.americanheart.org. Accessed August 24, 2005. 3. American Cancer Society. Cancer facts & figures; 2005. Available at: http://www.cancer.org. Accessed August 24, 2005. 1,500,000 345,000 373,000 211,240 250,000 0 0.5 1.0 1.5 2.0 Fracture 1 Heart attack 2 Stroke 2 Breast cancer 3 Annual Incidence, million Risk of osteoporotic fracture in 1 year is greater than combined risk of heart attack, stroke, and breast cancer. Hip fracture 1 Women with osteoporosis All women
    5. 5. Prevalence in India <ul><li>Expert groups peg the number of osteoporosis patients at ~26 million (2003 figures) with the numbers projected to increase to 36 million by 2013. </li></ul><ul><li>In a study among Indian women aged 30-60 years from low income groups, BMD at all the skeletal sites were much lower than values reported from developed countries, with a high prevalence of osteopenia (52%) and osteoporosis (29%) thought to be due to inadequate nutrition </li></ul>1.Osteoporosis Society of India (2003) Action Plan Osteoporosis: Consensus statement of an expert group. New Delhi 2.Shatrugna V, Kulkarni B, Kumar PA, et al. (2005) Bone status of Indian women from a low-income group and its relationship to the nutritional status. Osteoporos Int 16:1827.)
    6. 6. WHO Risk Factors <ul><li>Age (50-90), gender and clinical risk factors: </li></ul><ul><li>BMI </li></ul><ul><li>Prior fragility fracture </li></ul><ul><li>Parental history of hip fracture </li></ul><ul><li>Current tobacco smoking </li></ul><ul><li>Ever long-term use of Glucocorticoids </li></ul><ul><li>Rheumatoid arthritis or other secondary causes </li></ul><ul><li>Alcohol intake 3 or more units daily </li></ul>Kanis Osteoporos Int 2008;19:385-397
    7. 7. Pathogenesis of Osteoporosis-Related Fractures Reference: Cooper C, Melton LJ. Epidemiology of osteoporosis. Trends Endocrinol Metab. 1992;3(6):224-229.
    8. 8. Osteoporosis Diagnosis—from bone mineral density to structure imaging
    9. 9. NOF 2008 Guidelines Who Should be Tested? <ul><li>Women age 65 and older </li></ul><ul><li>Men age 70 and older </li></ul><ul><li>Women and men over 50 with risk factors </li></ul><ul><li>Patients with a fracture after age 50 </li></ul>
    10. 10. DXA (Dual X-ray absorptiometry) <ul><li>DXA overtook QCT (quantitative computed tomography) and is currently the standard for bone densitometry measurements. </li></ul><ul><li>DXA has been used in multiple cross-sectional and longitudinal studies to differentiate individuals with and without fractures, assess fracture risk, and analyze therapy effects; thus the fund of knowledge for DXA is currently superior to QCT. </li></ul><ul><li>Though DXA only assesses areal BMD of the lumbar spine, proximal femur, and distal radius, which includes cortical and trabecular bone, and has limitations in patients with degenerative disease, it has been shown to be robust and a good technique to determine fracture risk and measure response to therapy. </li></ul>Skeletal Radiol (2010) 39:943–955
    11. 11. Multi-detector CT (MD-CT) scanners <ul><li>Bone structure analysis was applied to crosssectional imaging techniques employing high resolution CT, and promising results were found in predicting biomechanically determined bone strength using various texture measures including fractal dimension. </li></ul><ul><li>With the development of multi-detector CT (MD-CT) scanners, higher spatial resolutions and better depiction of the trabecular bone structure in vivo became available </li></ul><ul><li>Ito et al. showed that vertebral microarchitecture can be visualized on MD-CT images, and microstructure parameters obtained by MD-CT, together with volumetric BMD, provided better diagnostic performance for differentiating subjects with and without osteoporotic vertebral fractures than DXA measurement </li></ul>Skeletal Radiol (2010) 39:943–955
    12. 12. Multi-detector CT (MD-CT) scanners Skeletal Radiol (2010) 39:943–955
    13. 13. High resolution peripheral CT (hrp-QCT) scanner <ul><li>Recently a high resolution peripheral CT (hrp-QCT) scanner (XtremeCT, Scanco Medical, Brüttisellen, Switzerland) was developed for clinical imaging of trabecular and cortical bone architecture in the distal tibia and radius. </li></ul><ul><li>provides an isotropic spatial resolution and a voxel size of 82 μm3. </li></ul><ul><li>Compared to MD-CT, the effective radiation dose is substantially lower with a reported dose of 0.003 mSv </li></ul><ul><li>The precision of these measurements was 2.5–4.4% for trabecular architecture parameters. </li></ul><ul><li>Also allows analysis of cortical structural parameters </li></ul>Skeletal Radiol (2010) 39:943–955
    14. 14. Ultra-short echo time (UTE) imaging technique <ul><li>Technique to assess water content of the cortical bone as a potential parameter to assess bone strength. </li></ul><ul><li>UTE allows the detection of signal components with T2 relaxation times on the order of only a few hundred microseconds. </li></ul><ul><li>These components are found in highly ordered tissues such as cortical bone and tendons and can not be detected with conventional imaging techniques, where TE is limited to 1– 2 ms </li></ul><ul><li>Techawiboonwong et al. reported UTE imaging with radial MR pulse sequences to characterize cortical bone water. </li></ul><ul><li>The quantitative analysis showed that bone water content was 135% higher in the patients on maintenance dialysis than in the premenopausal women and 43%higher than in the postmenopausal women. </li></ul>Skeletal Radiol (2010) 39:943–955
    15. 15. Vertebral fracture assessment <ul><li>Previous studies have found a circa 10% prevalence of vertebral fractures in women in their 50s and 25–45% in women in their 80s </li></ul><ul><li>The results of studies showed that chest radiography has potential as a screening tool for revealing previously undiagnosed vertebral fractures, but that radiologists have limited awareness of the significance of these findings. </li></ul>Skeletal Radiol (2010) 39:943–955 Vertebral Fracture Assessment
    16. 16. Semiquantitative grading system <ul><li>According to this score, a vertebral deformity of T4-L4 of more than 20% loss in height with an area of reduction in height of more than 10–20% is defined as a fracture. </li></ul><ul><li>This approach has been applied and tested extensively in a number of clinical drug trials and epidemiological studies </li></ul><ul><li>Four grades are differentiated: grade 0 = no fracture, grade 1 = mild fracture (reduction in vertebral height 20–25%, compared to adjacent normal vertebrae), grade 2 = moderate fracture reduction in height 25–40%), and grade 3 = severe fracture (reduction in height more than 40%) </li></ul>Skeletal Radiol (2010) 39:943–955
    17. 17. Identifying high risk patients: WHO Fracture Risk Assessment – FRAX Tool <ul><li>Provides a valuable resource for determining when it may be cost effective to initiate pharmacotherapy in patients with T-scores in the osteopenic range. </li></ul><ul><li>To assess individual 10-year fracture risk. </li></ul><ul><li>The online tool incorporates 11 risk factors and the femoral neck raw BMD value in g/cm2 to calculate the 10-year fracture risk probability. </li></ul><ul><li>If the femoral neck BMD is not known, BMD of the total hip can be used instead; however, the use of nonhip BMD has not been validated and is not recommended. </li></ul><ul><li>The site also offers downloadable charts for calculating fracture risks using body mass index (BMI) or BMD. </li></ul><ul><li>However, is applicable only for patients who have not received pharmacotherapy. </li></ul>www.shef.ac.uk/FRAX/
    18. 18.
    19. 19. Pyramid for Osteoporosis Prevention and Treatment Leading the Effort to Help Prevent and Treat Osteoporosis US Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General . US Department of Health and Human Services, Office of the Surgeon General; 2004. Pharmacotherapy (antiresorptives and anabolics) Address Secondary Factors (drugs and diseases) Lifestyle Changes (nutrition, physical activity, and fall prevention)
    20. 20. Calcium <ul><li>An essential cotherapy in osteoporosis treatment. </li></ul><ul><li>Many older women with osteoporosis have phosphorus intakes of <70% of the Recommended Dietary Allowance. </li></ul><ul><li>In a review of 52 calcium intervention studies, 50 showed that increasing calcium intakes resulted in reduced bone remodeling, better calcium retention, reduced agerelated bone loss, and reduced fracture risk. </li></ul><ul><li>The review also reported that out of 86 observational studies, 64 reported relationships in favor of increased calcium intakes, with reduced fracture risk, bone loss or improved bone mass. </li></ul>Am J Clin Nutr. 2010 Jul;92(1):101-5. Arq Bras Endocrinol Metab. 2010;54/2
    21. 21. Recommended daily calcium intakes <ul><li>Recommended daily calcium intakes(in mg/day) for populations vary between countries, often as a result of differing use and interpretation of the available scientific data </li></ul>Arq Bras Endocrinol Metab. 2010;54/2
    22. 22. Vitamin D <ul><li>Vitamin D is also essential for the development and maintenance of bone, both for its role in assisting calcium absorption from the diet, and for ensuring the proper renewal and mineralization of bone tissue </li></ul><ul><li>Vitamin D insufficiency is also observed in 24% of women with osteoporosis </li></ul><ul><li>In a cross-sectional observational international study in 1,285 community-dwelling, postmenopausal women with osteoporosis, in 18 countries, the prevalence of vitamin D inadequacy (defined as < 30 ng/mL) was over 50% in all five world regions, and was highest in the Middle East (81%) and Asia (63%) </li></ul>Arq Bras Endocrinol Metab. 2010;54/2
    23. 23. Vitamin D Metabolites <ul><li>A synthetic form of calcitriol (1,25 dihydroxycholecalciferol; 1,25-dihydroxyvitamin D3), the most physiologically active metabolite of vitamin D, has shown efficacy in the treatment of postmenopausal osteoporosis and promise in corticosteroid-induced osteoporosis. </li></ul><ul><li>A clinical trial in 622 women with postmenopausal osteoporosis demonstrated that patients with mild to moderate disease who received calcitriol (0.25 microgram twice daily) had a significant 3-fold lower rate of new vertebral fractures after 3 years of treatment </li></ul>Drugs Aging. 1994 Oct;5(4):300-17.
    24. 24. Calcitriol <ul><li>Synthetic vitamin D analogue </li></ul><ul><li>Promotes calcium absorption </li></ul><ul><li>Approved by the FDA for managing hypocalcemia and metabolic bone disease in renal dialysis patients. </li></ul><ul><li>It is also approved for use in hypoparathyroidism, both surgical and idiopathic, and pseudohypoparathyroidism. </li></ul>Clinician’s guide to prevention and treatment of osteoporosis.2008
    25. 25. <ul><li>Bone growth retardation: a common finding in various conditions associated with dietary zinc deficiency. </li></ul><ul><li>Bone zinc content has been shown to decrease in aging, skeletal unloading, and postmenopausal conditions, suggesting its role in bone disorder. </li></ul><ul><li>Zinc has been demonstrated to have: </li></ul><ul><ul><li>a stimulatory effect on osteoblastic bone formation and mineralization </li></ul></ul><ul><ul><li>the metal directly activates aminoacyl-tRNA synthetase, a rate-limiting enzyme at translational process of protein synthesis, in the cells, and it stimulates cellular protein synthesis. </li></ul></ul><ul><li>Stimulates gene expression of the transcription factors runt-related transcription factor 2 (Runx2) that is related to differentiation into osteoblastic cells. </li></ul><ul><li>Inhibits osteoclastic bone resorption due to inhibiting osteoclast-like cell formation from bone marrow cells and stimulating apoptotic cell death of mature osteoclasts. </li></ul><ul><li>Has a suppressive effect on the receptor activator of nuclear factor (NF)-κB ligand (RANKL)-induced osteoclastogenesis. </li></ul>Mol Cell Biochem. 2010 May;338(1-2):241-54.
    26. 26. Primary Types of Pharmacotherapy <ul><li>Antiresorptive Agents (reduce bone loss) </li></ul><ul><li>Anabolic Agents (build bone) </li></ul>US Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: US Department of Health and Human Services, Office of the Surgeon General; 2004. <ul><li>Bisphosphonates </li></ul><ul><li>Estrogen (HRT) </li></ul><ul><li>Selective estrogen receptor modulators (SERMs) </li></ul><ul><li>Calcitonin </li></ul><ul><li>Synthetic parathyroid hormone </li></ul>
    27. 27. Osteoporosis Current pharmacotherapy options Source: Alexander I, Andrist L. Menopause. In: F Likis, K. Shuiling, eds. Women’s Gynecologic Health. Sudbury, MA: Jones and Bartlett, 2005:249-289.
    28. 28. Source: Alexander I, Andrist L. Menopause. In: F Likis, K. Shuiling, eds. Women’s Gynecologic Health. Sudbury, MA: Jones and Bartlett, 2005:249-289. Osteoporosis Current pharmacotherapy options (Continued…)
    29. 29. Source: Alexander I, Andrist L. Menopause. In: F Likis, K. Shuiling, eds. Women’s Gynecologic Health. Sudbury, MA: Jones and Bartlett, 2005:249-289. Osteoporosis Current pharmacotherapy options (Continued…)
    30. 30. FDA Indications for Osteoporosis Ann Babbitt. Osteoporosis Update 2010 Drug PMO GIO (Women, Men) Men Prevention Treatment Prevention Treatment Estrogen  Alendronate PO     Risedronate PO      Ibandronate PO   Ibandronate IV  Zoledronate IV      Calcitonin IN  Raloxifene PO   Teriparatide SC   
    31. 31. Fracture Risk Reduction in RCTs Ann Babbitt. Osteoporosis Update 2010 Medication Spine Nonvertebral Hip Estrogen    Alendronate    Risedronate    Ibandronate  Zoledronate    Calcitonin  Raloxifene  Teriparatide  
    32. 32. Risedronate <ul><li>Approved by the FDA for the prevention and treatment of postmenopausal osteoporosis. </li></ul><ul><li>Also approved for treatment to increase bone mass in men with osteoporosis and for the prevention and treatment of osteoporosis in men and women who are either initiating or taking glucocorticoids. </li></ul><ul><li>Reduces the incidence of vertebral fractures by about 41-49 percent and non-vertebral fractures by about 36 percent over three years, with significant risk reduction occurring after one year of treatment, in patients with a prior vertebral fracture. </li></ul>Clinician’s guide to prevention and treatment of osteoporosis.2008
    33. 33. Calcitonin <ul><li>FDA-approved for the treatment of osteoporosis in women who are at least five years postmenopausal. </li></ul><ul><li>Delivered as a single daily intranasal spray that provides 200 IU of the drug. </li></ul><ul><li>Subcutaneous administration by injection also is available. </li></ul><ul><li>Intranasal calcitonin is generally considered safe. </li></ul><ul><li>Oral calcitonin has been approved by the FDA for the treatment of osteoporosis. </li></ul><ul><li>Nasal calcitonin reduces the risk of vertebral fractures by about 30% to 35% and is well tolerated. </li></ul>Clinician’s guide to prevention and treatment of osteoporosis.2008
    34. 34. Novel Therapies <ul><li>Novel anti-resorptives that can target the formation or the activity of osteoclasts include: </li></ul><ul><ul><li>denosumab, an antibody to receptor activated nuclear factor kappa B, </li></ul></ul><ul><ul><li>new selective estrogen receptor modulators, such as bazedoxifene, and </li></ul></ul><ul><ul><li>cathepsin K inhibitors, such as odanacatib. </li></ul></ul><ul><ul><li>Src kinase inhibitors are in the early phases of development. </li></ul></ul><ul><li>Parathyroid hormone is the only approved anabolic agent for the treatment of osteoporosis. </li></ul><ul><li>Antibodies to Wnt antagonists, such as sclerostin, are under development as new therapeutic approaches for osteoporosis. </li></ul>
    35. 35. New and Emerging Treatments <ul><li>Antiresorptive (anti-catabolic) </li></ul><ul><li>Denosumab </li></ul><ul><li>Odanacatib </li></ul><ul><li>Lasofoxifene </li></ul><ul><li>Bazedoxifene </li></ul><ul><li>CE/bazedoxifene </li></ul><ul><li>New delivery systems - oral salmon calcitonin </li></ul><ul><li>Osteo-anabolic (bone-forming) </li></ul><ul><li>Sclerostin inhibitor </li></ul><ul><li>Variations of PTH </li></ul><ul><li>Endogenous PTH stimulation - calcium sensing receptor antagonist (calcilytic) </li></ul><ul><li>New delivery systems – transdermal PTH </li></ul>Strontium ranelate: Combination of antiresorptive and anabolic
    36. 36. Differences Between Denosumab and Bisphosphonates <ul><li>Ref:Ernesto Canalis. New Treatment Modalities In Osteoporosis 2010 </li></ul>
    37. 37. Advantages and Disadvantages of Denosumab (an antibody) <ul><li>Ref:Ernesto Canalis. New Treatment Modalities In Osteoporosis 2010 </li></ul>
    38. 38. Advantages and Disadvantages of SERMS (Eg: Lasofoxifene, Bazedoxifene) <ul><li>Ref:Ernesto Canalis. New Treatment Modalities In Osteoporosis 2010 </li></ul>
    39. 39. Advantages and Disadvantages of Cathepsin K Inhibitors (Eg: odanacatib, balicatib and relacatib) <ul><li>Ref:Ernesto Canalis. New Treatment Modalities In Osteoporosis 2010 </li></ul>
    40. 40. <ul><li>The last 3 decades indicates that substantial progress in diagnostic techniques to diagnose and monitor osteoporosis has been made. </li></ul><ul><li>We have moved from qualitative techniques increasingly to quantitative techniques, and we have achieved higher spatial resolutions to quantify bone structure while also developing new imaging techniques to quantify the biochemical composition of bone and cartilage. </li></ul><ul><li>These techniques have impacted and will in the future increasingly impact patient management to prevent, treat, and monitor osteoporosis. </li></ul><ul><li>New developments in the treatment of osteoporosis include novel anti-resorptive and anabolic agents. </li></ul><ul><li>Their success will depend on their long-term effectiveness and safety profile. </li></ul>

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