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Osteoporosis
Consirable cause of back pain
2015
Back Pain2nd most common cause for office visit60-80% of population will have lower back pain at some time in their livesEach year, 15-20% will have back painMost common cause of disability for persons < 45 years1% of US population is disabledCosts to society: $20-50 billion/year
3/4/03Steven Stoltz, M.D.
Low Back Pain“One would have thought by now that the problem of diagnosis and treatment would have been solved, but the issue remains mysterious and clouded with uncertainty.”
– Rosomoff HL, Rosomoff RS. Low back pain: Evaluation and management in the primary care setting. Med Clin North Am 1999;83:643-62.
3/4/03Steven Stoltz, M.D.
3/4/03Steven Stoltz, M.D.
- AnatomyLesson #1
3/4/03Steven Stoltz, M.D.
- AnatomyLesson #2
% of Back Pain due to Herniated Disk?
1. 4%2. 14%3. 40%4. None of the above
3/4/03Steven Stoltz, M.D.
Causes of Low Back PainLumbar “strain” or “sprain” – 70%Degenerative changes – 10%Herniated disk – 4%Osteoporosis compression fractures – 4%Spinal stenosis – 3%Spondylolisthesis – 2%
3/4/03Steven Stoltz, M.D.
Causes of Low Back Pain…Spondylolysis, diskogenic low back pain or other instability – 2%Traumatic fracture - <1%Congenital disease - <1%Cancer – 0.7%Inflammatory arthritis – 0.3%Infections – 0.01%
3/4/03Steven Stoltz, M.D.
Steven Stoltz, M.D.
Red Flags
History of cancerUnexplained weight lossIntravenous drug useProlonged use of
corticosteroidsOlder age
Major TraumaOsteoporosisFeverBack pain at rest or at
nightBowel or bladder
dysfunction
3/4/03
10
What is osteoporosis?• Bones are fragile and more likely to
break (or fracture) easily
• Fractures = broken bones
• Fragility fractures occur with minimal trauma
• Fractures can lead to pain, changes in body shape and disability
11
Healthy bone Osteoporotic bone
The Living Skeleton
Changes in bone mass with age
Bone mass
Age (years)
Women
0 10 20 30 40 50 60 70 80
• Nutrition?• Vitamin D in the womb
Adapted from J Compston 1990
Menopause
Peak bone mass • Age related bone loss• Reduced physical activity
• Genes• Nutrition• Exercise
Men
14
15
Common fracture sites
Wrist Compressedvertebrae in spine
Hip
16
Vertebral compression fractures (multiple and severe)• Back pain – acute and chronic
• Height loss and curvature
• Activities of daily living affected; eating, breathing and mobility
© IOF developed with Prof. Dieter Felsenberg for Stop the Stoop campaign
17
A broken hip can lead to serious disability
Cooper. 1997
Unable to walk independently
Difficulty with daily activities
Restricted driving & shopping
Admitted to nursing home
0 20 40 60 80 100% affected within 1yr
18
The impact of fractures on health and social services
Every year in the UK:
• 300,000 osteoporotic fractures
• Over £2.3 billion per year on hospital and social care costs for hip fracture alone -
(approx. £6 million/day)
PATHOPHYSIOLOGY
HALLMARK: reduced skeletal mass due to imbalance btn bone resorption and formationFailure to build bone reserve from childhoodBone lossAging with loss of gonadal functionBone loss accelerates rapidly in women during the first years after menopause
a) Estrogen deficiency leads to…
↑ expression of RANKL by osteoblasts↓ release of OPG↑recruitment of pre-osteoclasts→↑differentiation and prolonged survival of osteoclasts via IL-1,IL-6,TNFᾳ.T-Cells inhibit osteoblastic differentiation and activity with premature apoptosis of osteoblasts through cytokines e.g. IL-7
Increased sensitization of bone to the effects of PTH↑osteoclastic apoptotic activity via ↑production of TGFᵝ
b) Aging
Progressive ↓ in supply of osteoblasts Reduced Ca2+ uptake from GITBone resorption exceeds bone formation from 3rd decadeWomen lose-30-40% of cortical bone -50% of trabecular boneMen lose-15-20% of cortical bone -25-30% of trabecular bone
c) Ca²⁺deficiency
→2° hyperPTH -↓ renal excretion of Ca2+ -↑ renal production of 1,25-(OH)2-D (calcitriol)→↑ca2+ absorption from the gut →↑bone resorption
d) Vit D Deficiency
Impaired absorption of Ca2+ from gutCompensatory mechanism:-Leads to hyperPTH→↑production of calcitriol from the kidneysPTH and vit.D have their effect on bone being mediated via binding to osteoblasts and stimulating RANK/RANKL pathwayOsteoclasts do not have receptors for Vit.D or PTH
Osteoporotic Fractures
Insufficiency/ fragility fracturesMostly from low-energy trauma/minor loadsVertebral bodies-1rly cancellous with interconnected horizontal and vertical trabeculae.
In osteoporosis there’s ↓ in both bone mass and this internal interconnectivity(BUT preferentially disruption is in the horizontal trabeculae)→? Reason→?overaggresive osteoclastic resorption
26
How do I know if my bones are fragile?
Signs and symptoms:
• Osteoporosis is painless unless bones break (fracture)
• Fragile bones may break easily without too much force
• Significant height loss and curvature of the spine may indicate compression fractures
27
How do I know if my bones are fragile?
• Risk factors will make fragile bones more likely
• A bone density scan will indicate if bones are less dense than average, but it is not needed by everyone
28
Risk factors for osteoporosis and fractures
• Age• Race• Gender• Some medicines -
e.g. glucocorticoids (‘steroids’), breast and prostate cancer drugs
29
Risk factors (continued) • Some medical conditions e.g. rheumatoid arthritis and early
menopause
• Medical conditions causing immobility, affecting food absorption, or affecting hormone levels
• Low body weight
• Family history
• Current smoking
• Alcohol more than 3 units daily
• Bones have already broken easily
Vertebral compression fractures
2/3 are asymptomatic and occur slowlyAssociated with ↑morbidity and mortalityMortality also correlates with number of vertebral #Often occurs with minimal stressMostly affected-middle/lower thoracic and upper lumbar
As posture worsens and kyphosis progresses→difficulty with balance, back pains, resp. compromise,↑ risk of pneumonia
↓ QOL
Presence of a # at one vertebral level→5-fold ↑ risk of getting another
CLINICAL PRESENTATIONS
Episode of acute back pain after bending, coughing,lifting, a fall, minor traumaPain-sharp, nugging, dull; exacerbated by movt; may radiate to the abdomen
Progressive kyphosis with loss of height+/- localised painParavertebral muscle spasm exacerbated by activity/ reduced by lying supine.
Complications:
Chronic pain↑morbidity and mortality↓ QOLProlonged immobilitySevere kyphosisSpinal deformities→”dowager’s hump”→loss of 1-2’ of height by 7th decade of lifeLoss of self-esteem→depression
PHYSICAL EXAM
InspectionPalpationHeight measurementActive/passive ROMNeurological exam
DDX
OsteomalaciaTumors(osteolytic)InfectionsOsteonecrosisOther bone-softening metabolic disorders Leukaemia/lymphomaOsteogenesis imperfectaRenal osteodystrophyMultiple myelomaScurvyPaget’s diseaseSickle cell anaemiaHomocystinuria/homocystinaemia
WHO-Fracture-Risk algorithm(FRAX)
Developed to calculate 10yr probability of any major osteoporotic # in a given patientTake into a/c BMD and other clinical risk fxtrsNOF recommends RX for patients with WHO-10yr-probability of major osteoporosis-related # of >20% (or >3% for hip #)This algorithm is useful in identifying patients most likely to benefit from Rx.
37
Fracture risk estimation
SCREENING
Women >50yrs of ageFor men, not carried out routinelyUS preventive Services Task Force(USPSTF)/ American College of Physicians(ACP) recommendations:Indications for screening in menThose with 10yr risk for osteoporotic # equal to or greater than that for 65yr old women who have no additional risk factors
INVESTIGATIONS
i) LAB WORKUPa) To establish baseline conditions:-CBC-Serum Ca²⁺,mg²⁺,po4-,Fe2+/ferritin levels-LFTs-TFTs-Vit. D levels-Cr/BUN
b) To exclude 2° causes
24 hr-urinary Ca2+ levelsPTH levelTestosterone/gonadotropin levelESR/ CRPUrinary free cortisol levels/ dexamethasone suppression testBMASerum/Urinary protein electrophoresis
ii) Biochemical markers of bone turnover
Reflect bone formation and resorption
Maybe ↑in high-bone turnover states and may also be useful in some patients for monitoring early response to treatment
SERUM MARKERS OF BONE FORMATION
Bone specific alkaline phosphatase(BSAP)Osteocalcin(OC)-if high, indicates a high turnover osteoporosisCarboxyterminal propeptide of type 1 collagen(PICP)Aminoterminal propeptide of type 1 collagen(PINP)
SERUM MARKERS OF BONE RESORPTION
Cross-linked C-Telopeptide of type 1 collagen(ICTP)Tartrate-resisitant acid phosphataseN-Telopeptide of collagen cross-links(NTx)C-telopeptide of collagen cross-links(CTx)
URINARY MARKERS OF BONE RESORPTION
HydroxyprolineFree and total pyridinolines(Pyd)Free and total deoxypyridinolines(Dpd)NTxCTx
46
Diagnosis OSTEOPOROSIS
-Measurement of BMD or-Occurrence of adulthood hip or vertebral fracture in the absence of major trauma
• Excellent diagnostic tools– Bone densitometry with DXA –
noninvasive test
– FRAX® – new tool to help with management decisions in patients with reduced bone mineral density
• Effective and safe treatments
National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2013. Available at: http://www.nof.org/hcp/clinicians-guide. Accessed September 13, 2013.
Z- and T-scores in Women
48
Who should be tested?
BMD measurement is not recommended in children or adolescents and is not routinely indicated in healthy young men or premenopausal women unless there is a significant fractures history or there are specific risk factors for bone loss
49
Consider vertebral imaging tests for the following individuals:
All women age 70 and older and all men age 80 and older if BMD T-score at the spine, total hip or femoral neck is < -1.0.
Women age 65 to 69 and men age 70 to 79 if BMD T-score at the spine, total hip or femoral neck is < -1.5
Postmenopausal women and men age 50 and older with specific risk factors:
Low trauma fracture during adulthood (age 50) Historical height loss of 1.5 inches or more (4 cm)* Prospective height loss of 0.8 inches or more (2 cm)** Recent or ongoing long term glucocorticoid treatment
Vertebral Imaging
* Current height compared to peak height during young adulthood** Cumulative height loss measured during interval medical assessment*** If bone density testing is not available, vertebral imaging may be considered based on age alone
(b) Densitometry1) Dual-Energy X-Ray Absorptiometry(DXA)-quantifies bone loss-standard for evaluation of BMD-not as sensitive as QCT for detecting early
trabecular bone loss, but it provides rapid scanning times, is less costly and precise
-used to calculate BMD at the lumbar spine, hip, prox. femur and wrist
-data is reported as T and Z-scores
5) U/S
Quantitative U/S of the Calcaneus(QUS)
-The heel is the only validated skeletal site for clinical use of QUS in osteoporosis mx.
-low cost, no radiation
-not as accurate.
Osteoporosis diagnosed on a scan
Bone density scanning of hip and spine:dual energy X-ray absorptiometry (DXA)
53
Osteoporosis on a DXA bone density scan
-1 SD
-2.5 SD
NORMAL
LOW BONE MASS (OSTEOPENIA)
NO FRACTURE (OSTEOPOROSIS)
WITH FRACTURE(SEVERE OSTEOPOROSIS)
WHO Study Group 1994
54
Bone density (DXA) scanning
Useful:• For those with significant risk factors • when it is uncertain if bones are fragile• to decide whether drug treatment is
necessary
May be useful:• In those taking drug treatments • to see if a treatment is working (this may
not always be helpful)
Not useful:• As a ‘screening’ tool
56
How can the risk of fragility fractures be reduced?
Fragility fractures
Poor bone strengthFalls
(except fracturesin the spine)
Impact of fallslack of padding
LifestyleExercise
Healthy eatingSunlight
Healthy pregnancyNo smoking/ excessive alcohol
& Other interventions for falls prevention
Flooring,hip protectors
Drugs,including Vit D
57
What can I do to keep my bones strong and prevent fractures?
• Healthy, balanced, calcium-rich diet• Weight-bearing exercise• Maintain appropriate body weight• Not smoking• Not excessive alcohol• Adequate vitamin D
58© Crown copyright 2011. Department of Health in association with the Welsh Assembly Government, the Scottish Government and the Food Standards Agency in Northern Ireland.
59
UK recommended daily calcium intake (mg): COMA report 1998
Children aged 7-12 years 550Teenagers – males 1000Teenagers – females 800Adult males 700Adult females 700Pregnant women 700Lactating women* 1250
A daily intake of about 1000mg may benefit those with osteoporosis on treatment, but excessive amounts taken as a supplement could be harmful
*May not be necessary
60
Keeping steady and safe as we get older to prevent hip fracture
• Medical conditions – get them diagnosed and properly treated
• Medicines – get them checked Do you need them all? Get a Review
• Vitamin D – supplements?
61
Keeping steady and safe as we get older to prevent hip fracture
• Keep fit and active as you get older
• Specific exercises help to improve balance and muscle strength
• Tai Chi
• Safe home environment
• Hip protectors?
62
Drug treatments: bisphosphonates• Alendronic acid or alendronate (Fosamax and
Fosamax once weekly)
• Risedronate (Actonel and Actonel once weekly)
• Ibandronate (Bonviva)*
• Zoledronate (Aclasta)*
63
Drug treatments: others • Raloxifene (Evista)
• Denosumab (Prolia)*
• Parathyroid hormone (PTH) - (teriparatide - Forsteo)*
• Strontium ranelate (Protelos)**
• Hormone replacement therapy (HRT)• Calcium and vitamin D supplements
• Calcitriol (Rocaltrol) (active form of vitamin D)
10-year risk of fractures: ≥3% for hip fracture
or ≥20% for a major osteoporotic fracture
T-scores between -1.0 and -2.5 and
NOF Guidelines 2014:Whom to Treat
After exclusion of secondary causes, treat postmenopausal women and men
age 50 and older who have…
OsteoporosisClinical diagnosis:
Hip or spine fracture
DXA diagnosis: T-score -2.5 or below
in the spine or hip
National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2014. Available at: http://www.nof.org/hcp/clinicians-guide..
Prevention Treatment
FDA-Approved Therapeutic Options
EstrogenAlendronateRisedronate
Ibandronate Zoledronic acid
Raloxifene
Calcitonin
PTH (teriparatide)Denosumab
US FDA Approved Therapies with Evidence for Fracture Prevention in Postmenopausal Women*
Type of Fracture
Antiresorptive therapyBone
formation therapy
Bisphosphonates(As first line therapy)
Calcitonin RaloxifeneHormone therapy
(Estrogen)**Teriparatide
Ibandronate,Risedronate, Alendronate, Zolendronic Acid
Vertebral Hip - - -
Non-vertebral+ - -
* For postmenopausal women, indicates first line therapies and Grade A recommendation. For men requiring treatment,alendronate, risedronate, and zoledronic acid can be used as first line therapies for prevention of fractures [Grade D]. + In clinical trials, non-vertebral fractures are a composite endpoint including hip, femur, pelvis, tibia, humerus, radius, and clavicle. ** Hormone therapy (estrogen) can be used as first line therapy in women with menopausal symptoms.
Ibandronate: Konsisten dalam mengurangi resiko fraktur vertebra
100
80
60
40
20
0
RR
R in
ver
tebr
al fr
actu
re (%
)
BONE study. Ibandronate 2.5mg daily vs. placeboChesnut CH, et al. J Bone Miner Res 2004;19:1241–1249
0–1 0–2 0–3Years
58%RRR p=0.0561
61%RRR p<0.001
62%RRR p<0.001
New Morphometric Vertebral FracturesData in: Chesnut CH, et al. J Bone Miner Res 2004;19:1241–9
10.750.50.25
Year 1
Year 2
Year 3
58%
61%
62%
Efficacy BONVIVA yang cepat dan konsisten dari waktu ke waktu
Year 1
Year 2
Year 3
10.750.50.25
65%
55%
41%
New Morphometric Vertebral FracturesRisedronate USPIHarris ST, et al. JAMA 1999;282:1344–52
BONVIVA® RISEDRONATE®
Alendronate(5/10mg)
Risedronate (5mg)
BONVIVA (2.5mg)
70
60
50
40
30
20
10
0
RR
R fo
r ver
tebr
al fr
actu
re a
t 3 y
ears
(%)
41%
VERT-NA3
62%70
60
50
40
30
20
10
0
BONE1
47%
FIT2 70
60
50
40
30
20
10
0
Efek Bisphosphonate pada fraktur new vertebral dalam 3 tahun
NOT COMPARATIVE STUDIES1Chesnut CH, et al. J Bone Miner Res 2004;19:1241–92Black DM, et al. Lancet 1996;348:1535–413Harris ST, et al. JAMA 1999;282:1344–52
VIBE STUDY
Ibandronate terbukti menurunkan resiko fraktur vertebra yang lebih tinggi dan menurunkan resiko fraktur non vertebra yang sebanding dengan Bisphosphonat mingguan
Mobile LTE: IBandronate meningkatkan BMD secara berkesinambungan hingga >5 tahun
Miller PD et al. Osteoporos Int. 2012 Jun;23(6):1747-56.
DIVA STUDY
BONVIVA IV TERBUKTI MEMPERTAHANKAN KENAIKAN BMD SELAMA 5 TAHUN
73 2013
Ibandronat IV memiliki insiden AE yang lebih kecil jika dibandingkan Zolendronat IV
DIVINE Study: Profil keamanan Bonviva® injeksi setara dengan BP oral
Miller PD et al. Bone. 2011 Dec;49(6):1317-22.
Patients expressing a preference, modified intent-to-treat (mITT)=298; 93% of population expressed preference between the two regimensEmkey R, et al. Curr Med Res Opin 2005;21:1895–903Hadji P, et al. Osteoporos Int 2006;17(Suppl.1):S69 (Abstract P259)
BALTO II
71% memilih once-monthly ibandronate(p<0.0001)
BALTO I and II menunjukkan positive preference dan kenyamanan
BALTO II77% considered
once-monthly ibandronate convenience
(p<0.0001)
BONVIVA: a bisphosphonatedengan potensi untuk meningkatkan kepatuhan
Cannot tolerate oral administration
Do not respondto oral therapy
The need for I.V. bisphosphonatesin osteoporosis
Cannot follow Dosing instructions
e.g. bedridden
Are takingmultiple oralmedications
Postmenopausal osteoporosis patients best suited for i.v. administration are those who
Have problems with adherence to oral bisphosphonates
i.v. = intravenous
Have cognitive difficulties
Have abnormalities delaying oesophageal
emptying
Bonviva Indication and Dosage Form
● Indikasi : Treatment of osteoporosis in postmenopausal women at increased risk of fracture. A reduction in the risk of vertebral fractures has been demonstrated, efficacy on femoral neck fractures has not been established.
● Sediaan:
MEKANISME KERJAIbandronate bekerja dengan cara : Menghambat aktivitas osteoklas Menghambat pembentukan osteoklas Menghambat pematangan ( maturation ) osteoklas
Adapted from : Russell RG, Rogers MJ. Bone 1999;25:97–106
● Hypocalcemia● Hypersensitive terhadap Ibandronic Acid
Kontraindikasi
●Hypocalcemia harus ditangani sebelum memulai terapi Bonviva diperlukan suplementasi Ca dan vitamin D yang cukup
●Tidak direkomendasikan untuk pasien dengan creatinine clearance di bawah 30 ml/min
●Tidak direkomendasikan untuk ibu hamil no adequate data
Special Warning (Peringatan)
81
Living with broken bones: help after vertebral compression fractures - 1
• Pain relieving drugs• Physiotherapy and specific exercises• Corsets?? (short-term)• Hydrotherapy – warm water• Complementary therapies
e.g. acupuncture• Heat and cold / gentle massage
82
Living with broken bones: help after vertebral compression fractures - 2• TENs machines
• Pain clinics / management courses
• Self management classes(e.g. Expert Patient)
• Percutaneous vertebroplasty / balloon kyphoplasty
• Charity’s website, publications and Helpline
83
Living with broken bones: help after a hip fracture • Effective assessment and operation to help with healing• Adequate pain relief • Physiotherapy and rehabilitation• Return to own home if at all possible• Appropriate social care• Osteoporosis and falls risk assessment• Drug treatment to reduce risk of further fracture • Help to prevent further falls
84
Summary 1
• Osteoporosis is a common condition that can lead to painful and disabling fractures
• Those at risk need appropriate assessment of their bone fragility
• A healthy lifestyle can help to build and maintain strong bones and prevent fractures
85
Summary 2
• Drug treatments to reduce the risk of fractures are available for those at the highest risk
• Help and pain management after fractures are essential so that people regain a good quality of life and further fractures are prevented