Diagnosis and management strategies in Osteoporosis Farooq Rathore Consultant and HOD Department of Rehabilitation Medicine, PNS Shifa
Outline
• Introduction • Problem statement • Diagnosis • Treatment strategies • Local perspectives • Call for action
Medline
• Osteoporosis: 64271 • Osteoporosis AND Treatment - 8525 • Human Clinical Trials - 3580 • Review Articles – 3117
Search strategy
• Medline • Time limit ( 2000-2018) • Randomized Controlled Trials ,Systematic Reviews, Meta-analysis
Introduction
Osteoporosis is a disease in which the density and quality of bone are reduced -International Osteoporosis Foundation
• Bone becomes porous and fragile • The loss of bone occurs silently and
Problem statement
progressively • High risk of fragility fractures
• Fracture is the first manifestation (Silent disease)
Osteoporotic fractures
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Spine
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Hip
Wrist
-
-
...
Hip and Spinal fractures
• Vertebral fractures can result in serious consequences, including loss of height,
intense back pain and deformity (Dowager's Hump).
Dowager’s Hump
http://www.chiropractorsannapolis.com/dowager-hump/
Hip and Spinal fractures
• Vertebral fractures can result in serious consequences, including loss of height,
intense back pain and deformity (Dowager's Hump).
• A hip fracture often requires surgery and may result in loss of independence or death.
Who’s at risk of Osteoporosis ?
Fixed Risk Factors
• Age • Female gender • Family history of osteoporosis
• Previous fracture • Menopause/hysterectomy • Long term glucocorticoid therapy • Rheumatoid arthritis • Primary/secondary hypogonadism in men
Tella SH, Gallagher JC. Prevention and treatment of postmenopausal osteoporosis. J Steroid Biochem Mol Biol. 2014 Jul;142:155-70. doi: 10.1016/j.jsbmb.2013.09.008. Unni S, Yao Y, Milne N, Gunning K, Curtis JR, LaFleur J. An evaluation of clinical risk factors for estimating fracture risk in postmenopausal osteoporosis using an electronic medical record database. Osteoporos Int. 2015 Feb;26(2):581-7.
Modifiable Risk Factors
• Alcohol • Smoking • Low body mass index
• Poor nutrition • Vitamin D deficiency • Insufficient exercise • Low dietary calcium intake • Frequent falls Unni S, Yao Y, Milne N, Gunning K, Curtis JR, LaFleur J. An evaluation of clinical risk factors for estimating fracture risk in postmenopausal osteoporosis using an electronic medical record database. Osteoporos Int. 2015 Feb;26(2):581-7.
Baccaro LF, Conde DM, Costa-Paiva L, Pinto-Neto AM. The epidemiology and management of postmenopausal osteoporosis: a viewpoint from Brazil. Clin Interv Aging. 2015 Mar 20;10:583-91.
Diagnosis
http://www.jrheum.org/content/36/11/2621
• X-rays – Not reliable
• DXA (dual-energy X-ray absorptiometry) measures bone mass at the forearm, hip,
Assessment of BMD
spine, finger and heel • QCT (Quantitative Computed Tomography) measures the spine ,hip and forearm • QUS (Quantitative Ultrasound) measures the heel or finger
DXA (dual-energy X-ray absorptiometry) • A DEXA scan compares patient’s bone density with the bone density
expected for a young healthy adult or a healthy adult of his/her own age, gender and ethnicity.
• The difference is calculated as a standard deviation (SD) score • The difference between patient’s measurement and that of a young healthy adult is known as a T score, and the difference between patient’s measurement and that of someone of the same age is known as a Z score
World Health Organization (WHO) classification of T-score Status
Hip BMD
• Normal
T-score of -1 or above
• Osteopenia
T-score between-1 and -2.5
• Osteoporosis
T-score of -2.5 or lower
• Severe osteoporosis
T-score of -2.5 or lower, and presence of at least
one fragility fracture
Indications for DXA scan Fracture after a minor fall or injury Early menopause, or Hysterectomy (before 45) without HRT Family history of hip fractures or body mass index (BMI) of less than 21
Conditions that lead to Osteoporosis Oral Glucocorticoids more than 3 months
Treatment options
Management options
Prevention and Life style modification Calcium and Vitamin –D supplements Anti- resorptive and anabolic agents
Surgical management
Prevention Identifying and treating patients at risk of
fracture, but who have not yet sustained a fracture, will substantially reduce the long
term burden of osteoporosis.
FRAX
Proton Pump Inhibitors and Osteoporosis
Jacob L, Hadji P, Kostev K. The use of proton pump inhibitors is positively associated with osteoporosis in postmenopausal women in Germany. Climacteric. 2016 Oct;19(5):478-81. doi: 10.1080/13697137.2016.1200549. van der Hoorn MMC, Tett SE, de Vries OJ, Dobson AJ, Peeters GMEEG. The effect of dose and type of proton pump inhibitor use on risk of fractures and osteoporosis treatment in older Australian women: A prospective cohort study. Bone. 2015 Dec;81:675-682.
Yang SD, Chen Q, Wei HK, Zhang F, Yang DL, Shen Y, Ding WY. Bone fracture and the interaction between bisphosphonates and proton pump inhibitors: a meta-analysis. Int J Clin Exp Med. 2015 Apr 15;8(4):4899-910. eCollection 2015.
Zhou B, Huang Y, Li H, Sun W, Liu J. Proton-pump inhibitors and risk of fractures: an update meta-analysis. Osteoporos Int. 2016 Jan;27(1):339-47..
Recommendations for PPI use • Start only when there is a clear indication that benefit will outweigh risk and at the lowest effective dose.
• Patients with chronic PPI use should be checked periodically to see whether there is still an indication.
• If any of the side effects occur, it is advisable to consider PPI as a possible cause. Leontiadis GI, Moayyedi P. Proton pump inhibitors and risk of bone fractures. Curr Treat Options Gastroenterol. 2014 Dec;12(4):41423.
Management options
Role of exercise and mobility Nutrition and risk of osteoporosis
Tea consumption and Osteoporosis
Tea consumption can reduce the risk of osteoporosis
Sun K, Wang L, Ma Q, Cui Q, Lv Q, Zhang W, Li X. Association between tea consumption and osteoporosis: A meta-analysis. Medicine (Baltimore). 2017 Dec;96(49):e9034.
Guo M, Qu H, Xu L, Shi DZ. Tea consumption may decrease the risk of osteoporosis: an updated meta-analysis of observational studies. Nutr Res. 2017. doi: 10.1016/j.nutres.2017.02.010.
Management options
Role of exercise and mobility Nutrition and risk of osteoporosis Calcium and Vitamin D supplements
Compliance to treatment
Pharmacologic agents for Management of Osteoporosis
• Oestrogen
Anti-resorptive agents
• Selective estrogen receptor modulators(SERM) • Bisphosphonates
• Parathyroid hormone (PTH1-84)
Anabolic agents
• Teriparatide (PTH1-34) • Strontium Ranelate
• Bisphosphonates (BP) are potent inhibitors of bone resorption that inhibit the activity of osteoclasts.
Bisphosphonates
• All approved BP have been shown to reduce vertebral fracture risk and increase BMD, whereas some have demonstrated reductions in non-vertebral and hip
fracture risk as well.
Indications for Treatment
Hip or Vertebral fracture T-score less than -2.5 at the femoral neck, total
Postmenopausal women and in men 50 years who present with any of these
hip, or spine after appropriate evaluation to exclude secondary causes Low bone mass and a 10-year probability of hip
fracture 3% 10-year probability of major osteoporosis related fracture 20% based on the FRAX calculation
Alendronate (O)
Bisphosphonates used in Osteoporosis
Risendronate (O)
Ibandronate (O, IV) Zoledronic acid (IV)
Davis S, Martyn-St James M, Sanderson J, Stevens J, Goka E, Rawdin A, Sadler S, Wong R, Campbell F, Stevenson M, Strong M, Selby P, Gittoes N. A systematic review and economic evaluation of bisphosphonates for the prevention of fragility fractures. Health Technol Assess. 2016 Oct;20(78):1-406.
Which drug to prescribe ? • Preference • Convenience • Adherence to the dosing schedule • Cost
Cost efficacy of different drugs • The most cost-effective initial therapy of postmenopausal osteoporosis is generic oral alendronate or generic parenteral zoledronate.
Albert SG, Reddy S. CLINICAL EVALUATION OF COST EFFICACY OF DRUGS FOR TREATMENT OF OSTEOPOROSIS: A META-ANALYSIS. Endocr Pract. 2017 Jul;23(7):841-856. doi: 10.4158/EP161678.RA.
Recommended Protocol for oral Bisphosphonates • Take the medication with a 2-3 glasses of water on an empty stomach. • Don't lie down or bend over or eat for 30 to 60 minutes to avoid
esophageal reflux. • When the recommended wait time is over, eat to neutralize the remaining medication
Optimal Duration of treatment
Bisphosphonates can persist in their efficacy for longer terms (7 to 10 years), with strong safety profiles Bilezikian JP. Efficacy of bisphosphonates in reducing fracture risk in postmenopausal osteoporosis. Am J Med. 2009 Feb;122(2 Suppl):S14-21. doi: 10.1016/j.amjmed.2008.12.003
The duration and potential discontinuation of treatment should be personalized for individual patients based on their response to treatment, fracture risk and comorbidities Eriksen EF, Díez-Pérez A, Boonen S. Update on long-term treatment with bisphosphonates for postmenopausal osteoporosis: a systematic review. Bone. 2014 Jan;58:126-35. doi: 10.1016/j.bone.2013.09.023.
Patients exhibiting T-scores −2.5 could be considered for discontinuation of active treatment while undergoing continued monitoring of their bone health. Eriksen EF, Díez-Pérez A, Boonen S. Update on long-term treatment with bisphosphonates for postmenopausal osteoporosis: a systematic review. Bone. 2014 Jan;58:126-35. doi: 10.1016/j.bone.2013.09.023.
Role of Zoledronic acid
Advantages of IV Therapy Reduced GI side effects
Ease of administration Better compliance
Protocol for Zoledronic acid
Black D.M, Delmas P.D, Eastell R, et al. Once-yearly Zoledronic acid for the treatment of postmenopausal osteoporosis. N Engl J Med 2007; 356:1809-1822.
• Check Creatinine • Ensure hydration , Ca and Vit-D supplementation • Detain in ward/emergency • Prophylactic Paracetamol 1g 30 minutes prior to the infusion • Single intravenous infusion over no less than 15 minutes • Check Vital signs and observe for 45 minutes
Single Dose also helps
Greenspan SL et al. Efficacy and safety of single-dose zoledronic acid for osteoporosis in frail elderly women: a randomized clinical trial. JAMA Intern Med. 2015 Jun;175(6):913-21 . doi: 10.1001/jamainternmed.2015.0747.
In 181 frail elderly women with osteoporosis, single dose of zoledronic acid improved BMD over 2 years
Zoledronic acid is safe
Hsieh PC. Effectiveness and Safety of Zoledronic Acid in the Treatment of Osteoporosis. Orthopedics. 2016 Mar-Apr;39(2):e263-70. doi: 10.3928/01477447-20160201-02.
Zoledronic acid had an acceptable safety profile; no adverse events were considered to be drug related. Treatment with ZA improved bone health, even in high-risk patients.
Zoledronic acid is helpful in long term
The antiresorptive activity of single zoledronate doses of 1-5 mg persist for at least 3 years in postmenopausal women with osteopenia.
Grey A, Bolland MJ, Horne A, Mihov B, Gamble G, Reid IR. Duration of antiresorptive activity of zoledronate in postmenopausal women with osteopenia: a randomized, controlled multidose trial. CMAJ. 2017 Sep 11;189(36):E1130-E1136. doi: 10.1503/cmaj.161207.
Common and underdiagnosed
Local Perspectives on Osteoporosis
The eye cannot see what the mind does not know Delayed diagnosis and Inappropriate investigations Increased cost of treatment
Identify high risk cases
How can you help ?
Appropriate Calcium and Vit D supplementation Prompt management of OP fractures Establish Fracture liaison services
Nayak S, Greenspan SL. How Can We Improve Osteoporosis Care: A Systematic Review and Meta-Analysis of the Efficacy of Quality Improvement Strategies for Osteoporosis. J Bone Miner Res. 2018 Apr 10. Wu CH et al Fracture liaison services improve outcomes of patients with osteoporosis-related fractures: A systematic literature review and meta-analysis. Bone. 2018 Mar 16;111:92-100.
Thank you
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