OsteoporosIs: EpIdemIology and dIagnosIs Endo Bridge 2013 Antalya, Turkey OsteoporosIs: EpIdemIology and dIagnosIs Dilek Gogas Yavuz , MD Marmara University School of Medicine Section of Endocrinology and Metabolism Istanbul ,Turkey

Silent disease until complicated by fractures OP is the most common bone disease and a serious health problem osteoporosis has been termed a silent disease because until a fracture occurs symptoms are absent . Chief clinical manifestations are vertebal and hip fractures

Osteoporosis: silent epidemic 385 pts with fragility fractures Have you ever heard of osteoporosis? NO:20% YES:80% Do you think that the fracture you have experienced could be due to fragility of your bones? NO:73 % YES:27 % Osteoporosis is called the silent epidemic because of  the lack of public awareness Chavalley et al. Osteoporosis Int 2002;13:450

Definition of osteoporosis NIH Consensus Development Conference, March 2000 A skeletal disorder characterized by Compromised bone strength An increased risk of fracture Bone strength =bone density+ bone quality Osteoporosis is defined as a systemic skeletal disease characterised by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. Notice that that definition does not include a specific bone density criteria. It is an overall effect on bone health, which includes issues such as bone density, but also other issues of bone quality, not the least of which includes architectural change shown in this famous scanning electron microscopic picture from David Dempster So it is not just less bone. It is less architecture, less connection, poor bone quality. normal osteoporosis Low bone mass and microarchitectural deterioration

Osteoporosis is a Serious Public Health Problem Every 3 second an osteoporotic fracture occcur Worldwide, osteoporosis causes more than 8.9 million fractures annually Osteoporosis affects an estimated 75 million people in Europe, USA and Japan, 2.2 million in Australia, 70 million in China only 10 to 20% are diagnosed and treated Osteoporosis int.2013:24;23-57

Prevalance of osteoporosis in men and women by gender-spesific scores Osteoporosis is estimated to affect 200 million women worldwide approximately one-tenth of women aged 60, one-fifth of women aged 70, two-fifths of women aged 80 and two-thirds of women aged 90 Schuit et al. Bone 2004;34:195

Prevalance of Osteoporosis At age 50 lifetime risk of fracture is 1:2 women 1:5 men Over 50% of women and 30-45% of men over age 50 have osteopenia/osteoporosis Men over age 60 has 25% risk osteoporotic fracture 70% over age 80 have osteoporosis At age 50 lifetie risk of fracture is 1 of every 2 women 1 of every 5 men

Osteoporotic Fractures in Women: Comparison with Other Diseases 1 500 000* 500 1000 1500 2000 Osteoporotic Fractures *annual incidence all ages † annual estimate women 29+ ‡annual estimate women 30+ §1996 new cases, all ages 513 000† 228 000‡ 184 300§ 750 000 vertebral 250 000 other sites 250 000 forearm 250 000 hip Heart Attack Stroke Breast Cancer Annual incidence x 1000 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. incidence of new osteoporotic fracture in 1 year is greater than combined incidence of heart attack, stroke, and breast cancer. Hip fracture incidence alone exceeds that of breast cancer. Riggs BL, Melton LJ. Bone 1995 Heart and Stroke Facts, 1996, American Heart Association Cancer Facts & Figures, 1996, American Cancer Society

Osteoporotic Fractures in Men and Women As with women, hip fractures in men increase dramatically with age Common sites for osteoporotic fracture are the spine, hip, distal forearm and proximal humerus. As with women, hip fractures in men increase dramatically with age The remaining lifetime probability in women, at menopause, of a fracture at any one of these sites exceeds that of breast cancer (approximately 12 %), and the likelihood of a fracture at any of these sites is 40 % or more inWestern Europe Osteoporotic Fractures in Men and Women .1,2 References: 1. Cooper C, Melton LJ III. Epidemiology of osteoporosis. Trends Endocrinol Metab. 1992;3:224–229. 2. Cooper C, Atkinson EJ, O’Fallon WM, et al. Incidence of clinically diagnosed vertebral fractures: a population-based study in Rochester, Minnesota, 1985–1989. J Bone Miner Res. 1992;7:221–227. Common sites of osteoporotic fractures Distribution of Fractures Cooper C, Melton LJ. Trends Endocrinol Metab. 1992;3:224–229.

Consequences of Fractures All Osteoporotic fractures are associated with significant morbidity Death 10%-20% inrease in mortality with hip fractures Disability hip fractures 20% of patients require long-term nursing home care 60% of patients fail to return to prefracture level of function vertabral fractures chronic back pain,kyphosis,height loss, impaired pulmonary function Reduced quality of life Loss of independence All osteoporotic fractures are associated with significant morbidity, but both hip and vertebral fractures are also associated with excess mortality Clinician’s Guide To The Prevention And Treatment Of Osteoporosis US Department Of Health And Human Sciences

Diagnosis of Osteoporosis Based on T score (T Score : standart deviation by which the individual’s BMD differs from the mean value expected in young healthy individuals) Operational definition of osteoporosis: BMD -2.5 SD or more below the Young female adult mean Reference technique :DXA Reference site: femoral neck Applies to men and to women Operational definition of osteoporosis is based on t score for BMD assesed at femoral neck and its defined as a value for BMD 2.5 SD or more below the young female adult mean Osteoporosis international 2013;24:23-57

WHO criteria for diagnosis of osteoporosis T-score : Difference expressed as standard deviation compared to young reference population T score normal -1.0 and above osteopenia -1.0 and -2.5 osteoporosis -2.5 and below Severe (established) osteoporosis -2.5 and below ,plus one or more osteoporotic fracture(s) Operational diagnosis Kanis et al. J Bone Mineral Res 1994;9:1137

WHO classification with a T-score cannot be applied to: premenopausal women men under age 50 children Z score Low Z-score (less than -2.0) has been suggested by some to increase likelihood of secondary osteoporosis

Who Should Have a Bone Density Test? Women age 65 and older and men age 70 and older Younger postmenopausal women and men ages 50–69 with clinical risk factors Adults who have a fracture after age 50 Adults with a condition (e.g., rheumatoid arthritis) or taking a medication (e.g., glucocorticoids) associated with low bone mass or bone loss Conditions, Diseases and Medications That Cause or Contribute to Osteoporosis and Fractures Lifestyle factors Alcohol Abuse High salt intake Falling Low calcium intake Inadequate physical activity Excessive thinness Vitamin D insufficiency Immobilization Excess vitamin A Smoking (active or passive) Genetic factors Cystic fibrosis Homocystinuria Osteogenesis imperfecta Ehlers-Danlos Hypophosphatasia Parental history of hip fracture Gaucher’s disease Idiopathic hypercalciuria Porphyria Glycogen storage diseases Marfan syndrome Riley-Day syndrome Hemochromatosis Menkes steely hair syndrome Hypogonadal states Androgen insensitivity Hyperprolactinemia Premature ovarian failure Anorexia nervosa and bulimia Premature menopause Athletic amenorrhea Turner’s & Klinefelter’s syndromes Panhypopituitarism Endocrine disorders Adrenal insufficiency Cushing’s syndrome Central Adiposity Diabetes mellitus (Types 1 & 2) Hyperparathyroidism Thyrotoxicosis Gastrointestinal disorders Celiac disease Inflammatory bowel disease Primary biliary cirrhosis Gastric bypass Malabsorption GI surgery Pancreatic disease Hematologic disorders Multiple myeloma Monoclonal gammopathies Sickle cell disease Hemophilia Leukemia and lymphomas Systemic mastocytosis Thalassemia Rheumatologic and autoimmune diseases Ankylosing spondylitis Lupus Rheumatoid arthritis Other rheumatic and autoimmune diseases Central nervous system disorders Epilepsy Parkinson’s disease Stroke Multiple sclerosis Spinal cord injury Miscellaneous conditions and diseases AIDS/HIV Congestive heart failure Muscular dystrophy Alcoholism Depression Post-transplant bone disease Amyloidosis End stage renal disease Sarcoidosis Chronic metabolic acidosis Hypercalciuria Weight loss Chronic obstructive lung disease Idiopathic scoliosis Medications Aluminum (in antacids) Cyclosporine A and tacrolimus Proton pump inhibitors Anticoagulants (heparin) Depo-medroxyprogesterone (premenopausal contraception) Selective serotonin reuptake inhibitors Anticonvulsants Glucocorticoids (≥ 5 mg/d prednisone or equivalent for ≥ 3 months) Tamoxifen® (premenopausal use) Aromatase inhibitors GnRH (Gonadotropin releasing hormone) antagonists and agonists Thiazolidinediones (such as Actos® and Avandia®) Barbiturates Lithium Thyroid hormones (in excess) Cancer chemotherapeutic drugs Methotrexate Parenteral nutrition 1. Sweet MG, et al. Am Fam Physician. 2009;79(3):193-200. 2. National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. www.nof.org. Accessed February 2013.

Most Women With Hip Fractures Do Not Have a T score ≤ -2.5 BMD measurements to predict future fracture risk has a high specificity but a low sensitivity Most Women With Hip Fractures Do Not Have a T score ≤ -2.5 Most women with hip fractures do not have a T score < -2.5 Wainwright et al JCEM 2005;90:2787

BMD and fracture risk BMD provides the cornerstone for the diagnosis of osteoporosis the use of BMD alone is less than optimal as an intervernation The fracture risk varies markedly in different countries ,but T-score varies by a small amount Any given T-score to fracture risk in women from any one country Depends on age Fracture risk depends of clinical risk factors Where as BMD provides the cornerstone for the diagnosis of osteoporosis the use of bmd alone is less than optimal as an intervernation For any BMD, fracture risk higher in the elderly than in the young 10 –year probability of hip fracture in women according to age and T-score for femoral neck BMD Osteoporosis int 2013,24:23-57

Clinical Risk Factors that Affect Fracture Risk A large number of risk factors have been ıdentified. For purposes of improving risk assesment,interest lies in those factors that contribute significantly to fracture risk over and above that provided by bmd measurement or age The use of BMD measurements to predict future fracture risk has a high specificity but a low sensitivity, and most postmenopausal women presenting with a fragility fracture have a BMD T-score higher than -2.5.47–51 Recently, the importance of clinical risk factors that affect fracture risk independently of BMD has been recognized

Fractures and Weight Fractures and weight Compston JE et al. Am J Med 2011;124:1043

Fracture risk assessment: risk engines guidelines have traditionally been based on BMD, the limitations stimulated the development of risk engines that integrate clinical risk factors for fracture Relative fracture risk BMD 10-year absolute fracture risk Risk Engines Garvan fracture risk calculator Q fracture FRAX Whereas assessment guidelines have traditionally been based on BMD, the limitations above have stimulated the development of risk engines that integrate several risk factors for fracture Previous OSC guidelines advised intervention based on WHO category as a marker of relative fracture risk. Now propose that an individual’s 10-year absolute fracture risk, rather than BMD alone, be used for fracture risk categorization

FRAX Computer-based algorithm (http://www.shef.ac.uk/FRAX) Objective: To estimate fracture risk in order to help with treatment decisions Rationale: BMD+CRFs predict fracture risk better than either alone Calculates the 10 year probability of a major fracture (hip, clinical spine,humerus,wrist) and 10-year probability of hip fracture designed only for postmenopausal women and men over the age of 40 who have not previously received bone-protective therapy

Fracture risk is calculated from age bmı, parantal history of hip fracture, current tovacco smoking, ever used long term oral GC,RA,other causes secondary osteoporosis Femoral bmd can be optional input to enhance fracture risk prediction These are shown in Table 1 and are used in the World Health Organization (WHO)-supported FRAX risk algorithm, with or without femoral neck BMD.52,53 FRAX expresses fracture risk as the 10-year probability of hip fracture and of major osteoporotic fracture (hip, wrist, spine, or humerus), from which intervention thresholds can be derived. Countryspecific versions of FRAX are available for several countries. It should be noted that FRAX is designed only for postmenopausal women and men over the age of 40 who have not previously received bone-protective therapy

frax is calibrated to those countries where the epidemiology of fracture and death is known Fracture probability differs markedly in different regions of the world. İn this slide heterogenity in europe is shown . For this reason frax is calibrated to those countries where the epidemiology of fracture and death is known Curently 45 countries

Absolute fracture risk in 10 years: low: <10% moderate: 10-20% Categorization Based on 10-year Fracture Risk Absolute fracture risk in 10 years: low: <10% moderate: 10-20% high: >20% The fracture risk category (low, moderate, high) is determined from the previous tables of corresponding T score and age. There are 3 categories for absolute risk: low (less than 10%, moderate (between 10-20%), and high (over 20%). Similar risk categories have been used for cardiovascular risk assessment. Similar risk categories have been used for cardiovascular risk assessment

Limitations of FRAX™ WHO Fracture Probability Tool Not valid in patients on treatment Only hip BMD is considered Risk is “yes/no” – there is no consideration of “dose” (e.g., fractures, glucocorticoids, smoking, alcohol) Not all risk factors are included (e.g., falls) “Major osteoporotic fracture” is not the same as all osteoporotic fractures Clinical judgment is required Watts NB, et al. J Bone Miner Res 2009;24:975-979.

At present there is no universally accepted policy for population screening to identify ptients with osteoporosis or those at high risk of fracture Patients are identifed opportunistically useing a case finding strategy on the finding of a previous fracture or the presence of significant risk factors A general approach to risk assesment is shown here Process begins with the asessment of racture probability and categorisation of fracture risk

Conclusion At Present there is no universally accepted policy for population screening to identify patients with osteoporosis or those at high risk of fracture Patients are identifed opportunistically useing a case finding strated Clinical evaluation and judement is essential for assessment of fracture risk and treatment disicion Osteoporosis is a disease that has a huge effect on public health. The imp act of osteoporotic fracture is far-reaching not only for the individuals themselves, but for the health service, economy, and population as a whole. Osteoporotic fractures are expected to rise in future generations. Recently several of the risk factors for this disease have been elucidated, and models are currently being developed to allow a more accurate assessment of fracture risk in patients to enable appropriate implementation of preventative and therapeutic measures

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