노인병학회 호남지회
New NOF Guidelines for osteoporosis
Outline of Presentation 1. Impact & Overveiw 2. Approach to Diagnosis 3. Intervention threshold & Treatment decisions 4. Universal recommendations & pharmacotherapy
Sang-Yong Kim Chosun University Hospital
Today osteoporosis is …..,
Impact & Overveiw
Major public health problem In the US, 10 million (osteoporosis, F:M = 8:2) 34 million (low bone mass)
Medical impact : fracture - chronic pain - disability - death - psychological symptoms (e.g., depression)
Today osteoporosis is ….., (continued)
Pathogenesis of osteoporosis-related fracture
Economic Toll : Each year broken bones - over 432,000 hospital admissions - almost 2.5 milion medical office visits - about 180,000 nursing home admissions - osteoporosis-related fracture ($ 17 billion for 2005) : Hip fractures(72% of fracture costs) • Under recognized • Under-treated
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National Osteoporosis Fundation 2008 Clinician’s Guide For clinicians on the prevention, diagnosis, & treatment of osteoporosis in the USA
National Osteoporosis Fundation 2008 Clinician’s Guide Key differences (2003 Guide)
Incoporates the World Health Oranization(WHO) 10year fracture risk model
Guidelines beyond Caucasian postmenopausal women to include African-American,, Asian,, Latina & other postmenopausal women
Accompanying economic analysis prepared by NOF
Addresses men age 50 & older for the first time Updated Calcium & vitamin D recommendations
Clinical Evaluation & Diagnosis Clinical evaluation
Approach to the diagnosis (+ risk assessment )
1. Detailed history (clinical risk factors, risk factor for falls) 2. Physical examination (osteoporosis signs, secondary causes) 3. Check for secondary cause
Diagnosis 1. By measurement of BMD, biochemical markers of bone turnover, Vertebral fracture assessment 2. Clinical diagnosis : sustained a low-trauma fracture ¾ US-FRAX™
Clinical risk factor Lifestyle factors
Low calcium intake, Vit D deficiency, alcohol, smoking
Genetic factors
Cystic fibrosis, Marfan syndrome, hemochromatosis
Hypogonadal states
Hyperptolactinemia, Panhypopituitarism, Turner’s syndrome, Anorexia nervosa, Premature ovarian failure
Endocrine disorders
Adrenal insufficiency, DM, thyrotoxicosis, Cushing’s syndrome, Hyperparathyroidism
G-I disorders
Celiac disease, Inflammatory bowel disease, malabsorption, Gastric bypass, Pancreatic disease
Hematologic disorders
Hemophilia, Multiple myeloma, Leukemia, Lymphoma,
Rheumatic disorders
Ankylosing spondylitis, SLE, RA
Micellaneous conditions
Alcoholism, Amyloidosis, ESRD, Parenteral nutrition, CHF, Depression, Epilepsy
Medications
Anticoagulants, Anticonvulsants, Glucocorticoid, Lithium, GnRH agonist
Risk factors for falls Environmental risk factors
Lack of assistive devices in bathrooms Low level lightning Loose throw rugs Slippery outdoor conditions
Medical risk factors
Age, Angiety, Arrhythmias Dehydration, Depression Female gender Malnutrition Medication causing oversedation Orthostatic hypotension
Neuro and musculoskeletal risk factors
Kyphosis Poor balance Reduced proprioception Weak muscles
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NOF: WHO TO SCREEN
Current osteoporosis diagnosis
Indications for BMD testing • All women ≥65 and men ≥ 70 • In postmenopausal women & men age 50-69 (risk factor profile) • Women in the menopausal transition (specific risk factor) g 50 • Adults who have a fracture after age • Adults with a condition (e.g, rheumatoid arthritis) or taking a medication (e.g, glucocorticoids ≥ 5mg prednisolone or equivalent for ≥ 3 months) • Anyone being considered for pharmacologic therapy for osteoporosis • Anyone being treated for osteoporosis, to monitor treatment effect • Postmenopausal women discontinuing estrogen
In postmenopausal women & men aged 50+ The World Health Organization [BMD : spine, hip or one third(33%) radius site] category
definition (T-score)
Normal
> -1.0
Low bone mass (osteopenia)
< -1.0 -1 0 , >-2 >-2.5 5
Osteoporosis
< -2.5
Established or severe osteoporosis
< -2.5 & 골절
Diagnosis of osteoporosis
≠
Intervention threshold
Kanis JA et al. J Bone Miner Res. 1994
05ca fracture and BMD 085Osteoporotic National Osteoporosis Risk Assessment (NORA) Study Fractures/1,000 person-years 50 40
Number of fractures
Age*
Hip T-score
(women)
Fracture rate
400
Women with fractures
300
30
Relative Risk (a) (2.6)2.5
10-year Probability (b)
50
-2.5
17.6
1.9%
80
-2.5
17.6
19.4%
200
20
100
10 0
Predicting Hip Fractures:
1.0
0.5
0.0
-0.5
-1.0
-1.5
-2.0
-2.5
-3.0
-3.5
Relative Risk = (RR per SD)T-score or Z-score Difference 10-Year Probability from Swedish National Bureau of Statistics
0 (a) Marshall D et al. BMJ 1996, (b) Kanis JA et al. Osteoporos Int 2001
Siris. Surgeon General’s Workshop on Osteoporosis and Bone Health, December 2002
Absolute fracture risk Assure people with the highest fracture risk A better basis for shared decision making between patients & healthcare professionals than a BMD T-score alone Resolve Resol e much m ch of the uncertainty ncertaint abo aboutt management for people with low bone mass
WHO Fracture Risk Algorithm(FRAXⓇ) Available at http://www.shef.ac.uk/FRAX/
Calculate the 10-year probability of a hip fracture & the 10-year probability of a major osteoporotic fracture (d fi d as clinical (defined li i l vertebral, b l hi hip, fforearm or h humerus fracture) taking into account femoral neck BMD and the 9 clinical risk factors
WHO model : ‘10년내 골절 위험도(10- year fracture risk)’ femur neck BMD + Clinical risk factors [Kanis JA et al. Osteoporosis Int 2005]
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Clinical Risk Factors in the FRAX™ Model • Current age • Gender • A prior osteoporotic fracture (including morphometric vertebral fracture) • Femoral neck BMD • Low body mass index (kg/m2) • Ever long-term use of oral glucocorticoids
• • • • •
Rheumatoid arthritis Secondary osteoporosis Parental history of hip fracture Current smoking Alcohol intake (3 or more units/day)
Validation 12 prospectively studied population-based cohorts EVOS / EPOS
Hiroshima
CaMoS
Rochester
Sheffield
Rotterdam
Kuopio
Gothenburg I
Gothenberg II
EPIDOS
Dubbo
OFELY
n = 59,232 59 232
person-years = 249,898 249 898
Any fracture = 5,444
% ffemale l = 74
osteoporotic fractures = 3,495 hip fractures = 957
Hip BMD measurement(75%)
Each CRF independently contributes to fracture probability Presence of ≥1 CRF increases probability of fracture incrementally
11 additional study cohorts used for validation but not included in algorithm
*1 unit = 8~10g alcohol ~ ½ pt beer ~ 1 glass wine
Application of US-FRAX™ in the US • FRAX™ is intended for selected postmenopausal women and men age 50+ • FRAX FRAX™ applies only to previously untreated patients. • In the absence of femoral neck BMD : total hip BMD may be substituted use of BMD [non-hip sites in the algorithm - not recommended ] The 10-Year probability of fracture (%) - Major osteoporotic - Hip fracture
: spine BMD ?
Application of US-FRAX™ in the US (continued)
• Uses a single T-score reference standard (NHANES III young Caucasian female reference values)
: FRAX™ Patch (available at www.NOF.org) • When T-scores are inserted into FRAX™,
the secondary osteoporosis button is automatically inactivated
FRAX™. Available at: http://www.shef.ac.uk/FRAX/index.htm.
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Intervention threshold & Treatment decisions
FRAX™. Available at: http://www.shef.ac.uk/FRAX/index.htm.
Old NOF Treatment Guidelines Initiate therapy to reduce fracture risk in postmenopausal women with: 1. BMD T-scores below -2.0 by central DXA with no risk factor 2. BMD T-scores below -1.5 by central DXA with one or more risk factor 3. History of a prior vertebral or hip fracture • Major risk factor: 연령, 성인 이후의 골절병력, 어머니와 여자 형제의 대 퇴골절 병력, 저체중, 흡연, 스테로이드를 3개월 이상복용한 병력등
Therapeutic thresholds •
Clinical guidance only and are not rules.
• Decisions to treat : a case-by-case basis.
New NOF Treatment Guidelines [2008]
Postmenopausal women & men aged 50 + presenting with the following should be treated: - A hip or spine(clinical or morphometric) fracture - T-score T score ≤ -2.5 2 5 at the hip or spine after appropriate evaluation to exclude secondary causes - Low bone mass (T-score between -1.0 & -2.5 at the femoral neck, total hip, or spine) & 10-yr probability of hip fracture ≥ 3%, or a 10-yr probability of any major osteoporosis –related fracture ≥ 20% based on the U.S.-adapted WHO algorithm.
Universal Recommendations & Pharmacotherapy
White women on corticosteroids whose T-score is -2.0 & BMI is 21 kg/m2 -> 60-year old ( 10-year hip fracture probability 3.1%) 55-year old (10-year hip fracture probability 2.7%)
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Universal recommendations “ 5 Steps to Bone Heath” Get the daily recommended amounts of calcium & vitamin D Engage in regular weight-bearing & musclestrengthening exercise (precise components ?) Avoid smoking & excessive alcohol Talk to your healthcare provider about bone health Have a bone density test & take medication when appropriate.
Adequate Intake of Calcium and Vitamin D
• Advise on adequate amounts of calcium (at least 1200mg per day, including supplements if necessary) & vitamin D3 800 to 1000 IU per day for individuals aged 50 & older • Serum 25(OH)D levels should be measured in individuals at risk of deficiency and Vitamin D supplemented in amounts to bring the serum 25(OH)D levels to 30 ng/ml or higher.
• Fall prevention (walking aid, hip pad protectors)
NOF : HOW TO TREAT Advocate the use of drugs approved by the FDA for prevention & treatment of osteoporosis : The antifracture benefits of these drugs have mostly been studied in women with postmenopausal osteoporosis. There are no fracture data in men and limited fracture data in glucocorticoid osteoporosis
Assess the potential benefits & risks - intervention threshold - non-skeletal benefits or the risks that are associated with specific drug use
Current FDA-Approved Osteoporosis Therapies PMO
PMO
GIO
GIO
Generic Name
Prevention
Treatment
Prevention
Treatment
Estrogens
X
Alendronate
X
X
Risedronate
X
X
Ibandronate
X(oral)
X
X
X
Zoledronic acid Raloxifene
X
Men
X
X
X
X
X
Calcitonin
X
Teriparatide
X
X
PMO = postmenopausal. National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Available at: www.nof.org/professionals/Clinicians_Guide.htm. Accessed April 22, 2008.
Monitoring Effectiveness of Treatment
http://www.nof.org/professionals/NOF_Clinicians_Guide.pdf
Patients not requiring medical therapies at the time of initial evaluation should be clinically re-evaluated when medically appropriate. Patients taking FDA -approved approved medications should have laboratory and bone density re-evaluation after two years or more frequently when medically appropriate.
Many additional issues urgently need epidemiologic, clinical and economic research
감사합니다
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Intervention thresholds for the USA
A li ti off th Application the WHO fracture f t prediction di ti algorithm l ith iin conjunction j ti with ith an updated US economic analysis indicates that fragility fractures Drug cost($ 600/yr for 5 yrs with 35% Fx reduction), the duration of fracture sequale, willingness to pay($ 60,000 per quality-adjusted life years(QALYs) gained)
Application of the WHO risk prediction algorithm to identify individuals with a 3% 10-year hip fracture probability may facilitate efficient osteoporosis treatment
or osteoporosis, in older individuals at average risk and in younger persons with additional clinical risk factors for fracture, supporting existing practice recommendations. Select the subset of higher risk patients from among the large group with osteopenia
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