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Osteoporosis - Dr S L Yadav

Osteoporosis
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Osteoporosis - Dr S L Yadav

  1. 1. Osteoporosis Dr S L Yadav, MD Department of Physical Medicine & Rehabilitation All India Institute of Medical Sciences, New Delhi
  2. 2. OSTEOPOROSIS Osteoporosis Consensus Development Conference “ A Metabolic Disease Characterized By: Decreased Bone Mass Micro-Architectural Deterioration of Bone Tissue Increased Bone Fragility and Consequent Increase in Fracture Risk” • Social impact • Osteoporosis represents an increasingly serious health and economic problem around the world . • Many individuals, male and female, experience pain, disability, and diminished quality of life as a result of having this condition. • Arch Intern Med. Jan 12 2009;169(1):25-31 • Endocr Dev. 2009;16:170-90
  3. 3. WHO definition of osteoporosis The World Health Organization’s (WHO) definitions of osteoporosis based on BMD measurements in white women are summarized in Table below. Definition Bone Mass Density Measurement T-Score Normal BMD within 1 SD of the mean bone density for young adult women T-score ≥ –1 Low bone mass (osteopenia) BMD 1–2.5 SD below the mean for young-adult women T-score between –1 and –2.5 Osteoporosis BMD ≥2.5 SD below the normal mean for young-adult women T-score ≤ –2.5 Severe or “established” osteoporosis BMD ≥2.5 SD below the normal mean for young-adult women in a patient who has already experienced ≥1 fractures T-score ≤ –2.5 (with fragility fracture[s]) World Health Organization (WHO). Accessed February 6, 2012
  4. 4. OSTEOPOROSIS The “SILENT THEIF”, • Remains asymptomatic until the weakened bone fractures. • Already pandemic proportions and it is going to get worse • Common sites of fractures are spine, femoral neck and distal radius.
  5. 5. The Concentric Circles of Osteoporosis: Fundamental Concepts, related diseases, and broader dimensions of Osteoporosis.
  6. 6. Osteoporosis Prevalence • 1990 (World) ~ 1.7 million hip #. • By 2050 this will rise to 6.3.millions • Frequency of osteoporosis – life time fracture risk: In Sweden - of a 59 yr old woman – Hip fracture – 20% – FA fracture –20% – Spine or Shoulder fracture – 12-16% – Combined risk for suffering any one of these 46% • Corresponding risk for man is approximately half
  7. 7. Classification Of Osteoporosis Type I • Post-menopausal osteoporosis (due to deficiency of estrogen and subsequent osteoclastic activation) • After menopause women undergo accelerated bone loss due to loss of protection offered by the hormone estrogen Type II • Age related or Senile osteoporosis Type III • Drug induced osteoporosis (due to chronic intake of drugs such as corticosteroids or phenytoin which interfere with the metabolism of vitamin D and lead to vitamin D deficiency) Am Fam Physician. 2009 Feb 1;79(3):193-200.
  8. 8. Symptoms Of Osteoporosis • Low back pain • Easy fractures of bones (particularly of the hip, wrist and spine) after minor trauma (low impact trauma fractures). • Symptoms of vertebral fracture • The pain is described variably as sharp, nagging, or dull; movement may exacerbate pain; in some cases, pain radiates to the abdomen • Pain is often accompanied by paravertebral muscle spasms exacerbated by activity and decreased by lying supine • Patients often remain motionless in bed because of fear of causing an exacerbation of pain Am Fam Physician. 2009 Feb 1;79(3):193-200 Dana Jacobs-Kosmin, et al medscape, updated on 15th oct 2014
  9. 9. Who may have osteoporosis • Weight <51 kg, kyphosis • Self-reported humped back • <20 teeth. • Wall-occiput distance >2 cm and rib- pelvis distance ⩽2 finger breadths are the most useful physical examination signs for detecting spinal fractures. • Height measurement with a stadiometer at each visit may be useful. Evid Based Med 2005;10:123
  10. 10. DIAGNOSIS Imaging options include • X rays • Densitometry • Single-photon absorptiometry (SPA) • Dual-photon absorptiometry (DPA) • Dual-energy x-ray absorptiometry (DXA) • Quantitative computed tomography (QCT) scanning • Magnetic resonance imaging (MRI) • Bone scanning • Single-photon emission computed tomography (SPECT) scanning. Dana Jacobs-Kosmin, et al medscape, updated on 15th oct 2014
  11. 11. Assessment of Fracture Risk by Using the Fracture Risk Assessment Tool (FRAX) • The aim of FRAX is to provide an assessment tool for the prediction of fractures in men and women with use of clinical risk factors with or without femoral neck bone mineral density. Arch Osteoporos. 2015 Dec;10(1):204.
  12. 12. Components of Management • Prevention – Risk factor Reduction – Nutritional Counseling • Treatment of disease – Pharmacotherapy – Exercise Program for conditioning & Wt. bearing – Mechanical Stimulation (Physical Modality) • Prevention & treatment of complications – Patient & Family Education in Posture Care & Fall Prevention – Orthosis – Specific problems – Pain management
  13. 13. Risk Factors Reduction • Endogenous – Genetic Factors • White and Asian • Petite body habitus • Family history – Age • Advanced – Sex • Female – Loss of ovarian function • Premature menopause • Amenorrhea • Exogenous – Nutrition • Low calcium intake • High phosphorous intake • High protein intake • High sodium intake – Lifestyle factors • Smoking • High caffeine intake • Inactivity – Immobilization – Medications • Glucocorticoids • Thyroid hormones
  14. 14. Nutritional Counseling • Calcium : 1000-1500 mg/day: Calcium carbonate (40 percent elemental calcium), Calcium citrate (21 percent elemental calcium), Calcium gluconate (9 percent elemental calcium), Calcium lactate (13 percent elemental calcium), CCM highest bioavailability. Supplementation • Vitamin D : 400-800 I.U./day • Phosphorus : 1250mg/day • Magnesium : 360 mg/day • Foods High in Oxalates and Phytates: Spinach, Soy Nuts, Almonds, Cashews, Sesame Seeds etc.
  15. 15. Calcium and Vitamin D • Most common is calcium citrate and calcium carbonate. • Calcium carbonate requires acidic environment - should be taken with meals and not be taken with antacids (achlorhydria). • Vitamin D deficiency results in failure to attain peak bone mass in adolescence, has a key role in the pathogenesis of osteoporosis in the elderly, • Vitamin D deficiency in the elderly has been recognized as an epidemic. • Holick MF (2005) J Nutr 135: 2739S–2748S
  16. 16. • Sun exposure is insufficient for adequate levels of vitamin D • Holick MF (2006) Mayo Clin Proc 81: 353–373 • Current recommendations: – 5–10 minutes of exposure of the arms and legs or the hands, arms, and face – 2 or 3 times per week – With at least 800 IU of Vitamin D orally daily • Holick MF (2004) Am J Clin Nutr 80: 1678S–1688S Sunlight and Vitamin D
  17. 17. Pharmacologic Options Antiresorptive: Act on osteoclasts and stabilize bone • Calcium • Estrogen • Calcitonin • Bisphosphonates • Selective estrogen receptor modulators • Thaizide diuretics • Ipriflavone (Investigational) Formation: Act on osteoblasts and increase bone formation • Vitamin D • Anabolic steroids • Parathyroid hormone • Growth factors (Investigational) • Fluoride (Investigational)
  18. 18. Rational for Non-Pharmacological Approach • Though, Pharmacologic approaches represent the cornerstone of treatment, • Limitations: – Long term compliance with medication regimens – Adverse effects of drugs – Affordability of newer medications – Conflict in acceptability of long term treatment.
  19. 19. Rational for Non-Pharmacological Approach • Nonpharmacologic therapies should, therefore, complement the traditional pharmacologic treatment of osteoporosis – Calcium and vitamin D supplementation – Exercise programs – Fall prevention – Orthoses – Kyphoplasty
  20. 20. Osteoporosis: Rehabilitation Program Individualized- Need Based Active Involvement of Patient & Family Goal- Return to Highest Level of Functional Independence Improving Quality of Life Focus- Minimize Further Bone Loss, Care of Fragile Skeleton, Help Prevent Fracture and Decrease Pain
  21. 21. • Strong back extensors reduce the risk of developing thoracic vertebral compression fractures Sinaki M et al. (1996) Mayo Clin Proc 71: 951–956 • Spinal mobility in patients with osteoporotic vertebral fractures also improved with the strengthening of back extensors • Spinal mobility is likely to be associated with back extensor strength. Miyakoshi N et al. (2005) Osteoporos Int 16: 1871–1874 Evidence for Exercise
  22. 22. Benefits of Exercise • Increased bone mass • Restoration of bone architecture and strength • Increased muscle strength • Improved balance and coordination • Better flexibility • Decreased falls and better post-fall condition
  23. 23. The osteoporotic patient should participate in – Regular weight-bearing • Weight-bearing exercise stimulate osteoblasts • Walking, running, and impact exercises. – Thoracic-stabilization exercises. • Thoracic stabilization exercises strengthen the back extensor, help to improve posture and reduce the risk of falls. • Instruct in appropriate body mechanics and precautions in order to minimize fracture risk. Recommendation for Exercise
  24. 24. Activities restriction • Flexion-based exercises such as abdominal crunches, lifting heavy weights, and excessive twisting and bending should be avoided
  25. 25. Fall Risk Statement • Falls a significant cause of morbidity and mortality • Each year, falls occur in 1/3 of older adults • The incidence of fall is the best predictor of future fractures in people >80yrs old. • Patients with osteoporosis at highest risk for developing fracture and resulting functional limitations secondary to falls. Tinetti ME et al. (2006) Gerontologist 46: 717–725
  26. 26. Fall Risk Statement • Associated factors for Falls: –Gait And Balance Disorders –Weakness, Dizziness –Environmental Hazards –Confusion –Visual Impairment –Postural Hypotension. –Sedating and Psychoactive Medications –Use of Diabetes Medications, and increased patient-to-nurse ratio. • Rubenstein LZ et al. (1996) Clin Geriatr Med 12: 881–902 • Krauss MJ et al. (2005) J Gen Intern Med 20: 116–122
  27. 27. • Assistive devices such as properly-fitted canes and walkers should be used to facilitate a more steady gait. • Concomitant conditions result in abnormal gait and, therefore, increase fall risk: Cervical myelopathy, lumbar spinal stenosis, vitamin B12 deficiency, normal pressure hydrocephalus, and PD Lim MR et al. (2007) J Am Acad Orthop Surg 15: 107–117 • These diagnoses should be considered in the differential diagnosis of recurrent falls; require aggressive, appropriate treatment in order to reduction of further risk of fracture. Fall Risk Statement
  28. 28. Hip Protectors • Most hip fractures are a result of a direct fall onto the hip (~90%) – Cummings et al. J Gerentol 1989;44;M107-11 – Lauritzen JB (1996) Bone 18: 65S–75S • Absorb the impact of a fall and, therefore, reduce the risk of hip fracture.
  29. 29. Hip Protectors • As a part of undergarments with padding over the trochanters • Energy shunting & Energy absorbing • In vitro biomechanical studies have demonstrated the force- attenuation properties of hip protectors. • Demonstrate a 68% reduction in peak force delivered to hip at the time of impact – Kannus P et al. (1999) Bone 25: 229–235
  30. 30. Hip Protectors : Compliance • Compliance is only 25%. Van Schoor NM et al. (2002). Osteoporos Int 13: 917–924. • Noncompliance one of the main limiting factors in the effectiveness particularly with regard to long- term adherence. Kannus P and Parkkari J (2006). Age Ageing 35: ii51–ii54. • Factors associated with noncompliance include – Discomfort on wearing, – Dislike of their personal appearance – Disagreement about their fracture risk Patel S et al. (2003). Rheumatology (Oxford) 42: 769–772.
  31. 31. • Literature controversies • A recent review analyzed 14 clinical trials – Marginally statistically significant reduction in hip fracture in nursing care or residential care settings, – No reduction in hip fracture incidence in community dwelling settings. Parker MJ et al. (2006) BMJ 332: 571–574. • More favorable studies have identified hip protectors as a cost-effective strategy • Despite the controversies, hip protectors offer a safe, noninvasive option and might reduce hip fracture risk (reduce risk of fractures by 53%). Fleurence RL (2004). Int J Technol Assess Health Care 20: 184–191. Singh S et al. (2004) J Rheumatol 31: 1607–1613. Hip Protectors: Effectiveness
  32. 32. Spinal Supports: Objectives • To minimize the incidence of kyphosis in at risk population • To decrease anterior wedging and compressive forces on fragile vertebral bodies as a preventive measure • To compensate for the weak erector spinae muscles, the anatomic extrinsic support of the spine • Proprioceptive reminder to extend the thoracic spine.
  33. 33. Spinal Supports : Types • Hyper extension brace • TLSO : Taylors brace • Jewet type
  34. 34. PTS: Weighted Kypho-Orthosis • Counteract spinal flexion and weight of anterior section of upper trunk • Helps to shift COG and encourages use of back extensors for upright posture. • Weighted pouch provides tactile stimulus for posture training
  35. 35. Posture-Training Support • 17 of 23 patients reported “Significant" improvement in their symptoms following use of the brace (i.e., pain reduction in patients with acute vertebral compression fracture). Kaplan RS and Sinaki M (1993). Mayo Clin Proc 68: 1171–1176 • Improved back extensor strength correlate with decreased kyphosis and diminished vertebral fracture risk. Sinaki M et al. (2002). Bone 30: 836–841 Kaplan RS et al. (1996). Mayo Clin Proc 71: 235–241 Sinaki M et al. (1996) Mayo Clin Proc 71: 951–956
  36. 36. The American Society for Bone and Mineral Research (ASBMR) published guidelines on long- term bisphosphonate use, 2016 After 5 years of oral bisphosphonates or 3 years of intravenous bisphosphonates, reassessment of risk should be considered. In women at high risk (e.g., older women, those with a low hip T-score or high fracture risk score, those with previous major osteoporotic fracture, or those who fracture on therapy), continuation of treatment for up to 10 years (oral) or 6 years (intravenous), with periodic evaluation, should be considered. The risk of atypical femoral fracture, but not osteonecrosis of the jaw, clearly increases with the duration of bisphosphonate therapy, but such rare events are outweighed by vertebral fracture risk reduction in high- risk patients. For women not at high fracture risk, a drug holiday of 2 to 3 years can be considered after 3 to 5 years of BP treatment.
  37. 37. Guidelines from the American Association of Clinical Endocrinologists (AACE, 2010) 1. First-line agents: alendronate, risedronate, zoledronic acid, denosumab 2. Second-line agent: ibandronate 3. Second- or third-line agent: raloxifene 4. Last-line agent: calcitonin Treatment for patients with very high fracture risk or in whom bisphosphonate therapy has failed: teriparatide
  38. 38. A clinical practice guideline from the American College of Physicians (ACP) recommends offering pharmacologic treatment to women with known osteoporosis, to reduce the risk of hip and vertebral fractures. The ACP recommends use of any of the following agents: Alendronate Risedronate Zoledronic acid Denosumab
  39. 39. The ACP recommends against the use of estrogen or estrogen plus progestogen or raloxifene for the treatment of osteoporosis in postmenopausal women. Additional recommendations, based on low-quality evidence, include the following: In women with osteoporosis, pharmacologic treatment should last for 5 years; generic drugs should be used when possible. Monitoring of bone mineral density (BMD) during the 5 years of treatment in women with osteoporosis is not advised, as evidence suggests that fracture risk may be reduced regardless of BMD changes For women aged 65 and older who have osteopenia and are at high fracture risk, decisions to treat should take into account patient preference, fracture-risk profile, benefits, harms, and price of medications
  40. 40. According to a study funded by the National Institutes of Health (NIH), osteoporosis will develop in fewer than 10% of older, postmenopausal women during the following rescreening intervals Women with normal BMD or mild osteopenia - Approx 15 years Women with moderate osteopenia - Approximately 5 years Women with advanced osteopenia - Approximately 1 year
  41. 41. Clinical factors that may shift an individual to a greater risk category for glucocortIcoid- induced osteoporosis Low body mass index Parental history of hip fracture Current smoking 3 alcoholic drinks per day Higher daily glucocorticoid dose Higher cumulative glucocorticoid dose Intravenous pulse glucocorticoid usage Declining central bone mineral density measurement that exceeds the least significant change
  42. 42. Medications Antiresorptive Agents Anabolic Therapies  Bisphosphonates  Alendronate  Risedronate  Ibandronate (Oral and IV)  Zoledronic Acid (IV)  Estrogen Agonist/Antagonists  Raloxifene  Estrogen/Estrogen-Progestin Combinations  Calcitonins (Nasal spray)  Teriparatide In addition, potentially treatable underlying causes of osteoporosis such as hyperparathyroidism and hyperthyroidism should be ruled out or treated if detected. Ann Intern Med. Dec 6 2011;155(11):751-61
  43. 43. Pharmacologic Therapy Recommendations The National Osteoporosis Foundation (NOF) recommends that pharmacologic therapy should be reserved for postmenopausal women and men aged 50 years or older who present with the following: • A hip or vertebral fracture (vertebral fractures may be clinical or morphometric [i.e. identified on a radiograph alone]) • T-score of -2.5 or less at the femoral neck or spine after appropriate evaluation to exclude secondary causes • Low bone mass (T-score between -1.0 and -2.5 at the femoral neck or spine) and a 10-year probability of a hip fracture of 3% or greater or a 10-year probability of a major osteoporosis-related fracture of 20% or greater based on the US-adapted WHO algorithm National Osteoporosis Foundation. Clinician's Guide to Prevention and Treatment of Osteoporosis Accessed January 13, 2011.
  44. 44. 2014 NOGG guidelines: Global strategies Intervention Effect on outcomes BMD Spine fracture Hip fracture Exercise A B B Calcium (± vitamin D) A B B Dietary calcium B B B Smoking cessation B B B Reduced alcohol consumption C C B Fall prevention programmes C C Hip protectors B Osteoporosis is defined operationally on the level of bone mass, measured as BMD. Two thresholds of BMD have been defined by the World Health Organization, on the basis of the relationship of fracture risk to BMD. ‘Osteoporosis’ denotes a value for BMD that is 2.5 standard deviations (SDs) or more below the young adult mean value for women (T-score equal to or less than –2.5 SD). A second, higher threshold more appropriate for epidemiological studies describes ‘low bone mass’ as a T-score that lies between –1 and –2.5 SD. ‘Severe’ or ‘established’ osteoporosis denotes osteoporosis as defined above in the presence of one or more documented fragility fractures.
  45. 45. Vertebral fracture Non-vertebral fracture Hip fracture Alendronate A A A Etidronate A B nae Ibandronate A A# nae Risedronate A A A Zoledronic acid A A A Denosumab A A A CalcitrioL A B nae Raloxifene A nae nae Strontium ranelate A A A# Teriparatide A A nae Recombinant human PTH (1- 84) A nae nae HRT A A A 2014 NOGG guidelines: Anti-fracture efficacy of approved treatments for postmenopausal women with osteoporosis when given with calcium and vitamin D
  46. 46. Bisphosphonates • Bisphosphonates are the most commonly used agents for osteoporosis. They have been employed for both treatment and prevention. Oral and intravenous options are available • Alendronate is approved for the treatment of osteoporosis in men, in postmenopausal women, and in patients with glucocorticoid-induced osteoporosis. It has been shown to increase spinal and hip mineral density in postmenopausal women • Risedronate is a delayed-release, given daily, weekly, or monthly. Risedronate reduces vertebral fractures by 41% and nonvertebral fractures by 39% over 3 years. Ibandronate is another bisphosphonate that can be given orally once a month. • Ibandronate : Ibandronate, a newer BP, has the greatest number of options in terms of route and frequency of administration. Ibandronate has the potential advantage in comparison to other BP options of offering patients and clinicians a highly variable choice that may align most closely with an individual’s preference and as a consequence could improve compliance and adherence. 1. Arch Intern Med. Jun 13, 2011;171(11):998-1004 2. Int J Womens Health. 2014 Dec 17;7:7-17
  47. 47. Frequency Time of day Instructions Alendronate 10 mg (treatment) every day first thing in morning, at least 1/2 hour before eating Take with 250ml (8 oz) plain water. Stay upright (don’t bend or lie down) for the first 1/2 hour AND until after the first food of the day Alendronate 70 mg 70 mg + 2800 IU vitamin D or 70 mg + 5600 IU vitamin D once a week same as above same as above Etidronate 400 mg The white etidronate tablet is taken daily for two weeks followed by a blue calcium tablet taken daily for an additional 10 weeks Take the white etidronate tablet (first two weeks) mid morning, mid afternoon or evening (at least two hours before and after eating)Take the blue calcium tablet (next 10 weeks) with food Take the white etidronate tablet with a full glass of water. Do not eat or take any additional supplements or vitamins for 2 hours before or after taking etidronate. Take the blue calcium tablet with food. Risedronate 5 mg every day first thing in morning, at least 1/2 hour before eating Take with a full glass of water. Stay upright (don’t bend or lie down) for the first 1/2 hour AND until after the first food of the day Risedronate 35 mg once a week same as above same as above 35 mg (DR=delayed release) once a week Take first thing in morning WITH breakfast Take with full glass of water. Stay upright (don’t bend or lie down) for the first 1/2 hour Ibandronate One 150 mg tablet taken once monthly or one 2.5 mg tablet taken once daily Zoledronic acid 5 mg once a year not applicable Given as a 15-minute intravenous (IV) infusion
  48. 48. Bisphosphonates • Bind to hydroxyapatite crystals at sites of active bone resorption inhibiting osteoclast function First Generation Bisphosphonates • Contain minimally modified side chains (R1, R2) e.g. medronate, clodronate, etidronate & tiludronate Second generation bisphosphonates • 10 to 100 times more potent e.g. alendronate and pamidronate Third generation bisphosphonates • Upto 10000 times more potent than first generation e.g. risedronate and zoledronate 15P91-037FContent developed by Clinical Medicine Informatics – India for Abbott Healthcare Private Limited. © 2015 Abbott. All rights reserved.
  49. 49. Bisphosphonates: Zoledronic acid Zoledronic acid • Intracellular accumulation of Zolephos inhibits osteoclastic activity by inhibiting enzymes like Farnesyl pyrophosphate synthase (FPPS) & Geranylgeranyl pyrophosphate synthase (GGPPS) & also leads to osteoclast apoptosis-Therefore, loss of resorptive function. • It is the most potent bisphosphonate available. It increases BMD at the spine by 4.3-5.1% and the hip by 3.1-3.5%, as compared with placebo. • Over 3 years, it reduces the incidence of spine fractures by 70%, hip fractures by 41%, and non-vertebral fractures by 25%. N Engl J Med. Nov 2012;367(18):1714-23 Biochim Biophys Acta. 2014 Apr 4;1841(4):569-73
  50. 50. HORIZON Pivotal Fracture Trial (PFT) Objective: • To evaluate the potential of once yearly zoledronic acid 5 mg to decrease fracture risk in postmenopausal women with osteoporosis • 3-year, randomized, double-blind, placebo-controlled clinical trial • 7736 women from 240 clinical centers in 27 countries • Treatment Annual infusion of either zoledronic acid 5 mg or placebo • Calcium 1000–1500 mg/d; vitamin D 400–1200 IU/d • Follow-up visits at 6, 12, 24 and 36 months • Telephone interviews every 3 months J Bone Miner Res. 2014 Dec 26. Maturitas. 2014 Mar;77(3):287-93 J Clin Endocrinol Metab. 2013 Feb;98(2):557-63
  51. 51. HORIZON-Recurrent Fracture Trial (RFT) Primary Objective • Reduce the rate of new clinical fractures after surgical procedure for low-trauma hip fracture Secondary Objectives • Reduce the risk of clinical vertebral fractures • Hip fractures , non-vertebral fractures • Increase BMD at the total hip and femoral neck of the non- fractured hip at months 12 and 24 • Double-blind, placebo- controlled RCT J Bone Miner Res. 2014 Dec 26. Maturitas. 2014 Mar;77(3):287-93 J Clin Endocrinol Metab. 2013 Feb;98(2):557-63
  52. 52. Treatment • Annual infusion of either zoledronic acid 5 mg or placebo • Loading dose of vitamin D 50,000–125,000 IU • Calcium 1000–1500 mg/d; vitamin D 800–1200 IU/d • Follow-up visits at 6, 12, 24, and 36 months • Telephone interviews every 3 months starting at month 9 J Bone Miner Res. 2014 Dec 26. Maturitas. 2014 Mar;77(3):287-93 J Clin Endocrinol Metab. 2013 Feb;98(2):557-63
  53. 53. Conclusions With zoledronic acid there is reduced : • Risk of New vertebral fractures by 70% after 3 years • Risk of Hip Fractures by 41% after 3 years • Risk of Clinical Non-Vertebral fracture by 25% after 3 years • Zoledronic acid produced significant increase in BMD over 3 years  Hip – 6.01% from Baseline  Femoral Neck – 5.06 % from Baseline  Lumbar Spine – 6.75 %from Baseline • Zoledronic acid reduced bone markers after 1 year  C-Telopeptide – 59%  N Terminal Propeptide – 58%  Bone specific alkaline Phosphatase – 30% J Bone Miner Res. 2014 Dec 26. Maturitas. 2014 Mar;77(3):287-93 J Clin Endocrinol Metab. 2013 Feb;98(2):557-63
  54. 54. Conclusions • Zoledronic Acid had an absolute relative reduction of 35% for New Clinical Fractures as compared to Placebo • Zoledronic acid had 28% reduction in mortality risk as compared to placebo • Zoledronic acid increased BMD BMD at Hip increased 5.5% after 3 years BMD at femoral neck increased 3.6% after 3 years J Bone Miner Res. 2014 Dec 26. Maturitas. 2014 Mar;77(3):287-93 J Clin Endocrinol Metab. 2013 Feb;98(2):557-63
  55. 55. Ibandronate: Mechanism of Action • Drug binds to hydroxyapatite crystals in the bone matrix • During osteoclast bone resorption, is released locally and taken up by osteoclasts • Inactivation and/or apoptosis of the osteoclasts • Inhibits intracellular mevalonate (3-hydroxy-3-methylglutaryl- coA reductase) pathway apparently at the farnesyl pyrophosphate synthase Nihon Yakurigaku Zasshi. 2014 Jun;143(6):302-9
  56. 56. The MOVER trial • Examined the relationship between gains in BMD and the occurrence of vertebral fractures by analyzing the gains in hip BMD in the initial 6 months and the subsequent development of vertebral fractures over time. • Compared the hip BMD gains in ibandronate- or risedronate-treated patients who developed vertebral fractures with those who had not developed vertebral fractures during the 3 years of treatment • 376 patients in the ibandronate 0.5 mg group, 382 in the ibandronate 1 mg group, and 376 in the risedronate group • Greater gains in hip BMD during the first 6 months of treatment were associated with a reduction in the risk of subsequent vertebral fractures during the duration of treatment, and suggested that measurement of hip BMD gain at that time could lead to a prediction of the risk of the future vertebral fracture incidence Calcif Tissue Int. 2014; 95(6): 557–563.
  57. 57. Parathyroid hormone • Teriparatide is a human recombinant parathyroid hormone (1- 34) (PTH [1-34]) and is the only available anabolic agent for the treatment of osteoporosis. • It is indicated for the treatment of women with postmenopausal osteoporosis who are at high risk of fracture, who have been intolerant of previous osteoporosis therapy, or in whom osteoporosis treatment has failed, as well as to increase bone mass. • It is indicated in men with idiopathic or hypogonadal osteoporosis who are at high risk of fracture, who have been intolerant of previous osteoporosis therapy, or in whom osteoporosis therapy has failed Dana Jacobs-Kosmin, et al medscape, updated on 15th oct 2014
  58. 58. Teriparatide dose • The dosage is 20 mcg/day as a subcutaneous inj. for a period of max. 24 months Rationale behind continuing teriparatide therapy for 18-24 months: • Anabolic effect of teriparatide is manifested both by an increase in bone formation at previously quiescent surfaces, an effect termed “modelling”, and by overfilling of remodelling sites, both of which lead to increased bone mass • Even though a single modelling cycle takes about 90-130 days this is not indicative of restoration of bone strength to full potential • This time interval may be enough to show fracture union but to prevent fracture recurrence a much longer duration of treatment is warranted.
  59. 59. Calcitonin • Calcitonin-salmon is a hormone that decreases osteoclast activity, thereby impeding postmenopausal bone loss. • It is indicated for the treatment of women who are more than 5 years post menopause and have low bone mass relative to healthy premenopausal women • Calcitonin is an option for patients who are not candidates for other available osteoporosis treatments. • Calcitonin significantly reduced the severity of acute pain in recent osteoporotic vertebral compression fractures . Pain at rest is reduced by week 1.Dana Jacobs-Kosmin, et al medscape, updated on 15th oct 2014 2. Osteoporos Int. 2012 Jan;23(1):17-38.
  60. 60. Calcitonin dose • Prolonged administration of parenteral calcitonin, by injections of 100 IU every 1 or 2 days, can prevent postmenopausal or post-ovariectomy bone loss, and is also able to increase trabecular bone mass among patients presenting an established osteoporosis. • In addition to the ease of administration compared with the injectable forms, nasal calcitonin is much better tolerated, the side effects being rare and generally negligible. • A prolonged administration of 200 IU intranasal calcitonin acutely inhibits parameters of bone resorption and can increase lumbar spine bone mineral density (BMD) by 1.7%-3.3% after 1 year. • Lower doses also appear to be efficient to prevent early postmenopausal bone loss, but the data are conflictual. Bone. 2002 May;30(5 Suppl):75S-79S.
  61. 61. End note • Osteoporosis is the most common metabolic bone disease around the world and can result in devastating physical, psychosocial, and economic consequences. • It is often overlooked and undertreated, however, in large part because it is so often clinically silent before manifesting in the form of fracture. • A planned approach to prevent osteoporosis and also the timely diagnosis of this chronic disease entity prevents the disabling consequences and fractures .
  62. 62. Thanks….

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