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1 
HOPE SELLING
2 
EVALUATION AND MEDICAL 
MANAGEMENT OF FRAGILITY 
FRACTURES 
Thomas jeffersonian hospital and Rothman institute article in orthopedic 
clinical of North America April 2014 
Presented By: Harjot Singh Gurudatta 
Moderator: DR. RAJAN SHARMA
3 
Definition of fragility fracture: (WHO) 
Fracture during activity that would not normally injure 
young healthy bone (i.e., fall from standing height or 
less) 
• Fragility fractures are a large and growing health issue 
– 1 in 2 women and 1 in 4 men over 50 yrs of age will suffer a fracture in their remaining lifetime 
• A prior fracture increases the risk of a new fracture 2- to 5-fold 
• Yet few fracture patients receive evaluation and treatment of osteoporosis, the underlying 
cause of most fragility fractures 
– Calls for action to improve the evaluation and treatment of fracture patients have been published 
around the World
4 
Fragility fractures are common 
• 1 in 2 women and 1 in 5 men over age 50 will suffer a 
fracture in their remaining life time 
• 55% of persons over age 50 are at increased risk of 
fracture due to low bone mass 
• At age 50, a woman’s lifetime risk of fracture exceeds 
combined risk of breast, ovarian & uterine cancer 
• At age 50, a man’s lifetime risk of fracture exceeds risk of 
prostate cancer
5 
Osteoporotic fractures: 
Comparison with other diseases 
1996 new cases, 
annual estimate 
women 30+ 
184 300 all ages 
annual incidence 
all ages 
250 000 
hip 
250 000 
forearm 
250 000 
other sites 
750 000 
vertebral 
2000 
1500 
1000 
500 
0 
Osteoporotic 
fractures 
annual estimate 
women 29+ 
Heart 
attack 
Stroke Breast 
cancer 
Annual incidence x 1000 
1 500 000 
513 000 
228 000 
American Heart Association, 1996 
American Cancer Society, 1996 
Riggs & Melton, Bone, 1995; 17(5 suppl):505S-511S
6 
Consequences of hip fracture 
Permanent 
disability 
Death within 
one year 
Cooper. Am J Med 1997; 103(2A):12s-19s. 
Unable to carry out at 
least one independent 
activity of daily living 
Unable to 
walk 
independently 
40% 
30% 
20% 
80% 
One year after hip fracture
7 
Consequences of vertebral fractures 
• Acute and chronic pain 
– Narcotic use, decrease mobility 
• Loss of height & deformity 
– Reduced pulmonary function 
– Kyphosis, protuberant abdomen 
• Diminished quality of life: 
– Loss of self-esteem, distorted body image, sleep disorders, 
depression, loss of independence 
• Increased fracture risk 
• Increased mortality
8 
Consequences of distal radius fractures 
• The most common fracture in women at 
middle age 
– Incidence increases just after menopause 
• The most common fracture in men below 
70 years 
• Only 50% report good functional outcome 
at 6 months 
• Up to 30% of individuals suffer long-term 
complications 
O'Neill et al. Osteoporos Int. 2001; 12:555-558
9 
Fragility fractures are common and have 
severe consequences 
Fragility fractures lead to major morbidity, decreased quality of life 
and increased mortality 
– 10-25% excess mortality 
– 50% unable to walk independently after hip fracture 
– 50% show substantial decline from prior level of function (many lose 
ability to live independently) 
– Increased depression, chronic pain, disability 
– Increased risk of subsequent fracture
10 
Definition of osteoporosis 
“…a systemic skeletal disease 
characterized by low bone mass and 
micro-architectural deterioration of 
bone tissue, leading to enhanced 
bone fragility and a consequent 
increase in fracture risk.” 
World Health Organization (WHO), 1994
11 
Major risk factors for fractures 
• Prior fragility fracture 
• Increased age 
• Low bone mineral density 
• Low body weight 
• Family history of osteoporotic fracture 
• Glucocorticoid use 
• Smoking
12 
Assessing bone density 
• X-ray observation 
– “Osteopaenic on x-ray” implies significant 
bone loss already – decreased opacity, 
thin cortices, wide canals, current fracture, 
healing fractures 
– A “late finding” in the course of the 
disease, but may be the “first finding” for a 
patient
13 
Assessment of bone mineral density by DXA 
Current gold standard for diagnosis of osteoporosis 
BMD (g/cm2) = Bone mineral content (g) / area (cm2) 
Diagnosis based on comparing patient’s 
BMD to that of young, healthy individuals of 
same sex
14 
WHO criteria for diagnosis of osteoporosis 
T-score: Difference expressed as standard deviation compared 
to young (20’s) reference population 
Kanis et al. J Bone Miner Res 1994; 9:1137-41 
T-score 
Normal - 1.0 and above 
Osteopaenia - 1.0 to - 2.5 
Osteoporosis - 2.5 and below 
Severe (established) 
osteoporosis 
- 2.5 and below, plus one or 
more osteoporotic 
fracture(s)
15 Bone strength is more than BMD 
BMD is surrogate criteria for OP as BP for Stroke 
young 
elderly 
Images from L. Mosekilde, Technology and 
Health Care. 1998 
Image courtesy of David Dempster
16 
Determinants of whole bone strength 
• Geometry 
– Gross morphology (size & shape) 
– Microarchitecture 
• Properties of bone material / bone matrix 
– Mineralization 
– Collagen characteristics 
– Microdamage 
Applied load 
Bone strength 
> 1  fracture 
Factor of 
risk
17 
Bone remodelling balance influences bone 
strength 
Bone strength 
SIZE & SHAPE 
macroarchitecture 
microarchitecture 
MATERIAL 
tissue composition 
matrix properties 
BONE REMODELLING 
formation / resorption 
AGEING, DISEASE and THERAPIES
18 
High Bone Turnover 
Resorption > Formation 
Decreased Bone 
Strength 
Decreases Bone Mass 
Disrupts Trabecular Architecture 
Increases Cortical Porosity 
Decreases Cortical Thickness 
STOCHASTIC REMODELLING 
Alters Bone Matrix Composition 
L. Mosekilde 
Tech and Health Care, 1998
19 
But bone quality is not the only factor… 
Bone size (mass) 
Bone shape 
Architecture 
Matrix properties 
Fall 
incidence 
Fall characteristics 
Energy absorption 
External protection 
Fall 
impact 
Bone 
strength 
Fracture risk 
Neuromuscular function 
Environmental risks 
Age
20 
Optimal care of the fragility fracture patient 
• Diagnosis of “fragility” fracture 
– Identify “fragility” fracture & underlying disease, incorporate into 
existing workup 
– Influences treatment plan from the onset 
• General fracture management 
– Stabilize patient, pain relief, fracture care 
• Rehabilitation 
– Minimize dependence, maximize mobility 
• Secondary prevention 
– Treat and monitor underlying disease, prevent future fractures
21 
Optimal care of the fragility fracture patient 
• Diagnosis of “fragility” fracture 
– Identify “fragility” fracture & underlying disease, incorporate into 
existing workup 
– Influences treatment plan from the onset
22 
High risk for secondary osteoporosis 
• Severe chronic liver or kidney diseases 
• Steroid medication (>7.5mg for more than 6 months) 
• Malabsorption (eg. Crohn´s disease) 
• Rheumatoid arthritis 
• Systemic inflammatory disorders 
• Hyperthyroidism 
• Primary hyperparathyroidism 
• Antiepileptic medication
23 
Fragility fracture patient assessment 
* In addition to routine pre-op or fracture evaluation 
• Family history of OP 
• Menarche / Menopause 
• Nutrition 
• Medications 
– (past and present) 
• Level of activity 
• Fracture history 
• Fall history & risk factors for falls 
• Smoking, alcohol intake 
• Risk factors for secondary OP 
• Prior level of function 
History 
should include:
24 
Fragility fracture patient assessment 
In addition to routine pre-op or fracture evaluation 
• Height 
• Weight 
• Limb exam 
– ROM, strength, deformity, pain, 
neurovascular status 
• Spine exam 
– pain, deformity, mobility 
• Functional status 
Physical exam 
should include:
25 
Laboratory tests* 
• SR / CRP 
• Blood count 
• Calcium 
• Phosphate 
• Alkaline Phosphatase (AP) 
• GGT 
• Renal function studies 
• Basal TSH 
• Intact PTH 
• Protein-immunoelectrophoresis 
• Vit D (25 and 1.25) 
NOTES: 
- * These are in addition to 
routine pre-op labs such as 
coagulation studies 
- These are screening labs, 
more may be indicated based 
on these results
26 
Bone mineral density and spine radiograph for 
vertebral fracture assessment 
• Bone mineral density assessment by DXA 
– Establish severity of osteoporosis 
– Baseline for monitoring treatment efficacy 
• Consider spine radiographs (thoracic and lumbar, AP and 
ML views) for patients with: 
– Back pain 
– Loss of height > 4 cm 
– Progressive kyphosis
27 
DEXA– Flaws? 
• DEXA overestimate the bone mineral density of 
taller subjects and underestimate the bone mineral 
density of smaller subjects. 
• In DEXA, bone mineral content is divided by the 
area of the site being scanned. 
• DEXA calculates BMD using area (aBMD: areal 
Bone Mineral Density), it is not an accurate 
measurement of true bone mineral density, which 
is mass divided by a volume.
28 
DEXA– Flaws? 
• The confounding effect of differences in bone size 
is due to the missing depth value in the calculation 
of bone mineral density. 
• The radiation dose is approximately 1/10th that of 
a standard chest X-ray 
• BMD testing with DXA is very susceptible to 
operator error.
29 
DEXA– Flaws? 
• A repeat BMD measurements should be done on the 
same machine each time, or at least a machine from the 
same manufacturer. 
• Error between machines, or trying to convert 
measurements from one manufacturer's standard to 
another can introduce errors large enough to wipe out the 
sensitivity of the measurements. 
• DEXA results need to be adjusted if the patient is 
taking strontium, and calcium supplements. 
• Metallic artifacts in cloths or pockets cause errors. 
• Osteomalacia, Osteoarthritis of spine, old Fractures of 
spine and hip, aortic calcification affect BMD readings.
30 
Who should be screened? 
• Problem of over-interpretation of results, & healthy 
average people think they are at a much higher 
risk. 
• In 2000 an NIH consensus conference concluded: 
"Until there is good evidence to support the cost-effectiveness 
of routine screening, or the efficacy 
of early initiation of preventive drugs, an 
individualized approach is recommended.
31 
Who to screen 
• Women > 65 years. 
• Men > 70 years. 
• Postmenopausal women /men >50 years with 
clinical risk factors. 
• H/o fracture at age > 50 years. 
• Chronic steroid use. 
• Risk factor for secondary OP
32 
Bone density at various sites for prediction of hip fractures 
Cummings SR, Black DM, Nevitt MC, Browner W, Cauley J, Ensrud K, et 
al. The Study of Osteoporotic Fractures Research Group. Lancet 1993; 34: 72-75. 
• BMD poor predictor of fractures. 
• When different scanners are used on the same 
patients, the proportion of patients diagnosed with 
osteoporosis varies from 6% up to 15%. 
• Over 80% of low trauma fractures occur in people 
who do not have osteoporosis (T score – 
2.5).
33 
NOF recommendations 
• National Osteoporosis Foundation US and the 
American Association of Clinical 
Endocrinologists recommend routine monitoring 
of bone mineral density within two years of 
starting treatment. 
NHS no recommendation 
• The UK National Osteoporosis Guidelines Group, 
US National Institutes of Health, and the 
Osteoporosis Society of Canada do not make a 
recommendation either way on monitoring.
34 
FRAX 
Do you know what is your T – Score? 
Take one minute test! 
Do you know what are your chances of 
getting fractures in next 10 years? 
Go online FRAX site! 
For Treatment consult your physician 
or your “Osteoporosis Society”
35
36 
Dr. Judith Brenner New York University 
power of the FRAX tool 
• Add daily consumption of two or more alcoholic 
drinks, and the risk becomes 9 percent. 
• Instead of 60, say the woman is 80 years old, 
slender and with no family or personal history of 
fractures, smoking or steroid use. Dr. Brenner 
calculated her risk of fracturing a hip in 10 years 
as 10 percent and of having any major 
osteoporotic fracture at 35 percent.
37 
Rehabilitation in the fragility fracture patient 
Goal is to improve strength, 
balance, position sense, 
reactions to: 
– Improve level of function / 
independence 
– Decrease risk of falls 
– Decrease risk of fractures 
Balance (position sense, reaction) 
Mechanical vibration plate 
Limb and core strength 
Mobility in activities of daily living 
Safety in gait and transfers 
Sensory and visual limitations 
Home safety evaluation and adaptation
38 
Interventions to reduce future fracture risk 
• Basics 
– Nutrition, exercise, fall prevention strategies 
– Modify risk factors as able (smoking, excess alcohol) 
– Treat co-morbidities (i.e., endocrine disorder?) 
• Pharmacological agents
39 
Interventions: General recommendations 
• Regular physical activity 
– Maintaining safe ambulatory status, indep ADLs 
– Daily limb and core home exercise routine 
• Sufficient intake of calcium and vitamin D 
– daily 1000-1500 mg calcium, 400-800 IU vitamin D 
– by foods or foods and supplements combined 
• Adequate nutrition 
• Avoid cigarettes, excess alcohol
40 
Who to treat ? 
Postmenopausal women 
/men > 50 yrs 
with 
Prior h/o hip/vertebral # 
or 
T Score < -2.5 
or 
T Score -1 to -2.5 & 
10 yr risk (FRAX) : 
HIP # > 3 % or 
major osteoporotic # > 20 %
41 
Pharmacological agents for treatment of 
osteoporosis 
Effective therapies are widely available and 
can reduce vertebral, hip and other fractures 
by 30% to 65%, 
even in patients who have already suffered a 
fracture
42 
Pharmacological agents shown to reduce 
fracture risk 
Bisphosphonates 
• Alendronate (FOSAMAX®) 
• Risedronate (ACTONEL®) 
• Ibandronate (BONVIVA®) 
• Zolendronate (ACLASTA®) 
SERMs 
• Raloxifene (EVISTA®) 
Stimulators of bone formation 
• rh-PTH (FORTEO®) 
Mixed mode of action 
• Strontium ranelate (PROTELOS®) 
Hormone therapy 
• Estrogen / progestin
43 
Bone marrow precursors 
Osteoblasts 
Osteoclast 
Lining cells 
Stimulators of 
Bone Formation 
Fluoride 
PTH analogs 
Sr Ranelate (?) 
Inhibitors of 
Bone 
Resorption 
Estrogen, SERMs 
Bisphosphonates 
Calcitonin 
Inhibitors of 
RANKL 
Cathepsin K 
Therapeutic strategies
44 
Mainstay of treatment : 
Bisphosphonates 
Approval in US for osteoporosis 
• Alendronate week : 1995 
• Risedronate : 2000 
• Ibandronate mnth: 2005 
• Zoledronate yearly.iv : 2007.
45 
Treatments & Efficacy 
Vertebral Fx Non-vertebral Fx 
Other Fx Hip Fx 
Oral 
HRT Yes Yes Yes 
Etidronate* Yes 
Alendronate* Yes Yes Yes 
Risedronate* Yes Yes Yes 
Ibandronate* Yes [Yes] 
Raloxifene* Yes 
Calcitriol* Yes 
Strontium Ranelate* Yes Yes [Yes]
46 
Vertebral Fx Non-vertebral Fx 
Other Fx Hip Fx 
Subcutaneous 
Teriparatide* Yes Yes 
1-84 PTH* Yes 
Denosumab* Yes Yes Yes 
Intravenous 
Pamidronate 
Ibandronate* 
Zoledronate* Yes Yes Yes 
Intranasal or Subcutaneous 
Calcitonin* Yes
47 
Appropriate use of appropriate treatments can 
halve the incidence of fractures 
Vertebral Fx Nonvertebral Fx 
Other Fx Hip Fx 
Alendronate* Yes Yes Yes 
Risedronate* Yes Yes Yes 
Zoledronic acid* Yes Yes Yes 
PTH* Yes Yes ??? 
Strontium ranelate* Yes Yes ??? 
Denosumab* Yes Yes Yes 
plus calcium + vitaminD
48 
Taking Bisphosphonates
49 
Contraindications
50 
Hot topics
51 
Vitamin D levels 
• 25-OHD Vit D status Manifestation Management 
• <25 nmol/l Deficient Rickets/ Osteomalacia High-dose 
calciferol 
• 25-50 nmol/l Disease risk Vit D supps 
• 50-75 nmol/l Adequate Healthy Lifestyle advice 
• >75 nmol/l Optimal Healthy None 
– Divide by 2.5 for ug/L
52 
Patients who did not need treatment in the first place 
Discontinue Treatment 
Lower risk patients, if DXA is stable/increasing 
Consider a drug holiday after 3-5 years of treatment 
Higher risk patients (fractures, corticosteroid Rx, very low BMD) 
Consider a drug holiday after 10 years of therapy 
May use teriparatide or raloxifene (but not another potent 
antiresorptive agent – ie. denosumab) during the holiday from 
bisphosphonates
53 
Treatment of vitamin D deficiency 
Deficiency (25-OHD <25 nmol/l) 
10 000 IU calciferol daily or 60 000 IU 
calciferol weekly for 8-12 weeks* 
or 
Calciferol 300 000 or 600 000 IU orally 
or by intramuscular injection once or 
twice
54 
Treatment of vitamin D insufficiency 
Insufficiency (25-OHD 25-50 nmol/l) or 
maintenance therapy following deficiency 
1000-2000 IU calciferol daily 
or 
10 000 IU calciferol weekly 
–
55 
Hormone replacement therapy
56 
HRT: A CONSENSUS 
• Prime role of HRT is relief of menopausal Sx 
• Risks/benefits need to be explained to each 
woman (breast Ca extra 2-6 cases per 1000 
women treated with HRT for 5 years) 
• Use lowest effective estrogen dose, assess CV 
risk 
• Review need annually (esp aged>60)
57 
HRT: A CONSENSUS 
• Can give up to age 50 if prem 
menopause 
• Do not use as primary or secondary 
prev. of CAD/CVA, or Alzheimers 
• Transdermal estrogen has lower DVT 
risk
58 
RALOXIFENE 
• SERM licensed for OP 
• Reduces vertebral (not non-vertebral) fracture risk, 
just as does calictonin 
• Reduces development of new breast Ca. 
• No increased risk of CVD (reduces CV events!) 
• Increased risk of thromboembolism 
• May worsen flushes 
• Well tolerated, easy dosing
59 
NICE 2005: 
(secondary prevention) 
• Teriparatide – use in women >65 
years unresponsive to / intolerance 
of bisphosphonates, and: 
–with extremely low BMD (<-4) 
–with very low BMD (<-3), multiple 
fractures PLUS an additional risk 
factor 
National Institute for Clinical Excellence, Technology Appraisal 87, Jan 2005
60 
Emerging Rx’s in osteoporosis 
Prof Compston 
2010 
• Denosumab 
– Monoclonal Ab to RANKL which drives osteoclasts 
– Subcut every 6m/12m! 60mg 
– Dramatic and quick effect 
– Fracture reduction similar to Zoledronate 
– Cost similar to risedronate (in 2010)! 
– NICE appraised
61 
Denosumab Binds RANK Ligand and Inhibits 
Osteoclast Formation, Function, and Survival 
RANKL 
RANK 
OPG 
Denosumab 
Osteoclast Formation, Function, 
and Survival Inhibited 
Bone Formation Bone Resorption 
Inhibited 
CFU-GM Prefusion 
Osteoclast 
Osteoblasts 
Hormones 
Growth Factors 
Cytokines 
Adapted from: Boyle WJ, et al. Nature. 2003;423:337-342.
62 Few Simple ways 
You need not know about your T-score 
• If you are or consider your self Obese, 
• If you are exposed to Sun during your shopping 
in open markets at least twice a week, 
• If you take Milk and you are a vegetarian, 
• If you are taking regular Morning walk, 
• If you are regular about exercises (YOGA). 
• Your Relatives’ Death is not due to Fractures but 
due to age and co morbidity.
63 Summary 
There is an acute need for reconsidering 
– Globalization of Diagnosis of Osteoporosis & 
Osteopenia, 
– BMD screening, 
– Redefining Risk factors & role of fall and BMD in 
fractures, 
– Cost effectiveness of drug treatment, 
– Hype about Hip fractures, 
– Role of Big Pharma in propaganda of diagnosis, 
management, corruption in scientific literature, misuse 
political system and creation a state of 
“Fear psychosis & Hope selling”.
64

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osteoporotic Fragility fractures treatment

  • 2. 2 EVALUATION AND MEDICAL MANAGEMENT OF FRAGILITY FRACTURES Thomas jeffersonian hospital and Rothman institute article in orthopedic clinical of North America April 2014 Presented By: Harjot Singh Gurudatta Moderator: DR. RAJAN SHARMA
  • 3. 3 Definition of fragility fracture: (WHO) Fracture during activity that would not normally injure young healthy bone (i.e., fall from standing height or less) • Fragility fractures are a large and growing health issue – 1 in 2 women and 1 in 4 men over 50 yrs of age will suffer a fracture in their remaining lifetime • A prior fracture increases the risk of a new fracture 2- to 5-fold • Yet few fracture patients receive evaluation and treatment of osteoporosis, the underlying cause of most fragility fractures – Calls for action to improve the evaluation and treatment of fracture patients have been published around the World
  • 4. 4 Fragility fractures are common • 1 in 2 women and 1 in 5 men over age 50 will suffer a fracture in their remaining life time • 55% of persons over age 50 are at increased risk of fracture due to low bone mass • At age 50, a woman’s lifetime risk of fracture exceeds combined risk of breast, ovarian & uterine cancer • At age 50, a man’s lifetime risk of fracture exceeds risk of prostate cancer
  • 5. 5 Osteoporotic fractures: Comparison with other diseases 1996 new cases, annual estimate women 30+ 184 300 all ages annual incidence all ages 250 000 hip 250 000 forearm 250 000 other sites 750 000 vertebral 2000 1500 1000 500 0 Osteoporotic fractures annual estimate women 29+ Heart attack Stroke Breast cancer Annual incidence x 1000 1 500 000 513 000 228 000 American Heart Association, 1996 American Cancer Society, 1996 Riggs & Melton, Bone, 1995; 17(5 suppl):505S-511S
  • 6. 6 Consequences of hip fracture Permanent disability Death within one year Cooper. Am J Med 1997; 103(2A):12s-19s. Unable to carry out at least one independent activity of daily living Unable to walk independently 40% 30% 20% 80% One year after hip fracture
  • 7. 7 Consequences of vertebral fractures • Acute and chronic pain – Narcotic use, decrease mobility • Loss of height & deformity – Reduced pulmonary function – Kyphosis, protuberant abdomen • Diminished quality of life: – Loss of self-esteem, distorted body image, sleep disorders, depression, loss of independence • Increased fracture risk • Increased mortality
  • 8. 8 Consequences of distal radius fractures • The most common fracture in women at middle age – Incidence increases just after menopause • The most common fracture in men below 70 years • Only 50% report good functional outcome at 6 months • Up to 30% of individuals suffer long-term complications O'Neill et al. Osteoporos Int. 2001; 12:555-558
  • 9. 9 Fragility fractures are common and have severe consequences Fragility fractures lead to major morbidity, decreased quality of life and increased mortality – 10-25% excess mortality – 50% unable to walk independently after hip fracture – 50% show substantial decline from prior level of function (many lose ability to live independently) – Increased depression, chronic pain, disability – Increased risk of subsequent fracture
  • 10. 10 Definition of osteoporosis “…a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk.” World Health Organization (WHO), 1994
  • 11. 11 Major risk factors for fractures • Prior fragility fracture • Increased age • Low bone mineral density • Low body weight • Family history of osteoporotic fracture • Glucocorticoid use • Smoking
  • 12. 12 Assessing bone density • X-ray observation – “Osteopaenic on x-ray” implies significant bone loss already – decreased opacity, thin cortices, wide canals, current fracture, healing fractures – A “late finding” in the course of the disease, but may be the “first finding” for a patient
  • 13. 13 Assessment of bone mineral density by DXA Current gold standard for diagnosis of osteoporosis BMD (g/cm2) = Bone mineral content (g) / area (cm2) Diagnosis based on comparing patient’s BMD to that of young, healthy individuals of same sex
  • 14. 14 WHO criteria for diagnosis of osteoporosis T-score: Difference expressed as standard deviation compared to young (20’s) reference population Kanis et al. J Bone Miner Res 1994; 9:1137-41 T-score Normal - 1.0 and above Osteopaenia - 1.0 to - 2.5 Osteoporosis - 2.5 and below Severe (established) osteoporosis - 2.5 and below, plus one or more osteoporotic fracture(s)
  • 15. 15 Bone strength is more than BMD BMD is surrogate criteria for OP as BP for Stroke young elderly Images from L. Mosekilde, Technology and Health Care. 1998 Image courtesy of David Dempster
  • 16. 16 Determinants of whole bone strength • Geometry – Gross morphology (size & shape) – Microarchitecture • Properties of bone material / bone matrix – Mineralization – Collagen characteristics – Microdamage Applied load Bone strength > 1  fracture Factor of risk
  • 17. 17 Bone remodelling balance influences bone strength Bone strength SIZE & SHAPE macroarchitecture microarchitecture MATERIAL tissue composition matrix properties BONE REMODELLING formation / resorption AGEING, DISEASE and THERAPIES
  • 18. 18 High Bone Turnover Resorption > Formation Decreased Bone Strength Decreases Bone Mass Disrupts Trabecular Architecture Increases Cortical Porosity Decreases Cortical Thickness STOCHASTIC REMODELLING Alters Bone Matrix Composition L. Mosekilde Tech and Health Care, 1998
  • 19. 19 But bone quality is not the only factor… Bone size (mass) Bone shape Architecture Matrix properties Fall incidence Fall characteristics Energy absorption External protection Fall impact Bone strength Fracture risk Neuromuscular function Environmental risks Age
  • 20. 20 Optimal care of the fragility fracture patient • Diagnosis of “fragility” fracture – Identify “fragility” fracture & underlying disease, incorporate into existing workup – Influences treatment plan from the onset • General fracture management – Stabilize patient, pain relief, fracture care • Rehabilitation – Minimize dependence, maximize mobility • Secondary prevention – Treat and monitor underlying disease, prevent future fractures
  • 21. 21 Optimal care of the fragility fracture patient • Diagnosis of “fragility” fracture – Identify “fragility” fracture & underlying disease, incorporate into existing workup – Influences treatment plan from the onset
  • 22. 22 High risk for secondary osteoporosis • Severe chronic liver or kidney diseases • Steroid medication (>7.5mg for more than 6 months) • Malabsorption (eg. Crohn´s disease) • Rheumatoid arthritis • Systemic inflammatory disorders • Hyperthyroidism • Primary hyperparathyroidism • Antiepileptic medication
  • 23. 23 Fragility fracture patient assessment * In addition to routine pre-op or fracture evaluation • Family history of OP • Menarche / Menopause • Nutrition • Medications – (past and present) • Level of activity • Fracture history • Fall history & risk factors for falls • Smoking, alcohol intake • Risk factors for secondary OP • Prior level of function History should include:
  • 24. 24 Fragility fracture patient assessment In addition to routine pre-op or fracture evaluation • Height • Weight • Limb exam – ROM, strength, deformity, pain, neurovascular status • Spine exam – pain, deformity, mobility • Functional status Physical exam should include:
  • 25. 25 Laboratory tests* • SR / CRP • Blood count • Calcium • Phosphate • Alkaline Phosphatase (AP) • GGT • Renal function studies • Basal TSH • Intact PTH • Protein-immunoelectrophoresis • Vit D (25 and 1.25) NOTES: - * These are in addition to routine pre-op labs such as coagulation studies - These are screening labs, more may be indicated based on these results
  • 26. 26 Bone mineral density and spine radiograph for vertebral fracture assessment • Bone mineral density assessment by DXA – Establish severity of osteoporosis – Baseline for monitoring treatment efficacy • Consider spine radiographs (thoracic and lumbar, AP and ML views) for patients with: – Back pain – Loss of height > 4 cm – Progressive kyphosis
  • 27. 27 DEXA– Flaws? • DEXA overestimate the bone mineral density of taller subjects and underestimate the bone mineral density of smaller subjects. • In DEXA, bone mineral content is divided by the area of the site being scanned. • DEXA calculates BMD using area (aBMD: areal Bone Mineral Density), it is not an accurate measurement of true bone mineral density, which is mass divided by a volume.
  • 28. 28 DEXA– Flaws? • The confounding effect of differences in bone size is due to the missing depth value in the calculation of bone mineral density. • The radiation dose is approximately 1/10th that of a standard chest X-ray • BMD testing with DXA is very susceptible to operator error.
  • 29. 29 DEXA– Flaws? • A repeat BMD measurements should be done on the same machine each time, or at least a machine from the same manufacturer. • Error between machines, or trying to convert measurements from one manufacturer's standard to another can introduce errors large enough to wipe out the sensitivity of the measurements. • DEXA results need to be adjusted if the patient is taking strontium, and calcium supplements. • Metallic artifacts in cloths or pockets cause errors. • Osteomalacia, Osteoarthritis of spine, old Fractures of spine and hip, aortic calcification affect BMD readings.
  • 30. 30 Who should be screened? • Problem of over-interpretation of results, & healthy average people think they are at a much higher risk. • In 2000 an NIH consensus conference concluded: "Until there is good evidence to support the cost-effectiveness of routine screening, or the efficacy of early initiation of preventive drugs, an individualized approach is recommended.
  • 31. 31 Who to screen • Women > 65 years. • Men > 70 years. • Postmenopausal women /men >50 years with clinical risk factors. • H/o fracture at age > 50 years. • Chronic steroid use. • Risk factor for secondary OP
  • 32. 32 Bone density at various sites for prediction of hip fractures Cummings SR, Black DM, Nevitt MC, Browner W, Cauley J, Ensrud K, et al. The Study of Osteoporotic Fractures Research Group. Lancet 1993; 34: 72-75. • BMD poor predictor of fractures. • When different scanners are used on the same patients, the proportion of patients diagnosed with osteoporosis varies from 6% up to 15%. • Over 80% of low trauma fractures occur in people who do not have osteoporosis (T score – 2.5).
  • 33. 33 NOF recommendations • National Osteoporosis Foundation US and the American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment. NHS no recommendation • The UK National Osteoporosis Guidelines Group, US National Institutes of Health, and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring.
  • 34. 34 FRAX Do you know what is your T – Score? Take one minute test! Do you know what are your chances of getting fractures in next 10 years? Go online FRAX site! For Treatment consult your physician or your “Osteoporosis Society”
  • 35. 35
  • 36. 36 Dr. Judith Brenner New York University power of the FRAX tool • Add daily consumption of two or more alcoholic drinks, and the risk becomes 9 percent. • Instead of 60, say the woman is 80 years old, slender and with no family or personal history of fractures, smoking or steroid use. Dr. Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent.
  • 37. 37 Rehabilitation in the fragility fracture patient Goal is to improve strength, balance, position sense, reactions to: – Improve level of function / independence – Decrease risk of falls – Decrease risk of fractures Balance (position sense, reaction) Mechanical vibration plate Limb and core strength Mobility in activities of daily living Safety in gait and transfers Sensory and visual limitations Home safety evaluation and adaptation
  • 38. 38 Interventions to reduce future fracture risk • Basics – Nutrition, exercise, fall prevention strategies – Modify risk factors as able (smoking, excess alcohol) – Treat co-morbidities (i.e., endocrine disorder?) • Pharmacological agents
  • 39. 39 Interventions: General recommendations • Regular physical activity – Maintaining safe ambulatory status, indep ADLs – Daily limb and core home exercise routine • Sufficient intake of calcium and vitamin D – daily 1000-1500 mg calcium, 400-800 IU vitamin D – by foods or foods and supplements combined • Adequate nutrition • Avoid cigarettes, excess alcohol
  • 40. 40 Who to treat ? Postmenopausal women /men > 50 yrs with Prior h/o hip/vertebral # or T Score < -2.5 or T Score -1 to -2.5 & 10 yr risk (FRAX) : HIP # > 3 % or major osteoporotic # > 20 %
  • 41. 41 Pharmacological agents for treatment of osteoporosis Effective therapies are widely available and can reduce vertebral, hip and other fractures by 30% to 65%, even in patients who have already suffered a fracture
  • 42. 42 Pharmacological agents shown to reduce fracture risk Bisphosphonates • Alendronate (FOSAMAX®) • Risedronate (ACTONEL®) • Ibandronate (BONVIVA®) • Zolendronate (ACLASTA®) SERMs • Raloxifene (EVISTA®) Stimulators of bone formation • rh-PTH (FORTEO®) Mixed mode of action • Strontium ranelate (PROTELOS®) Hormone therapy • Estrogen / progestin
  • 43. 43 Bone marrow precursors Osteoblasts Osteoclast Lining cells Stimulators of Bone Formation Fluoride PTH analogs Sr Ranelate (?) Inhibitors of Bone Resorption Estrogen, SERMs Bisphosphonates Calcitonin Inhibitors of RANKL Cathepsin K Therapeutic strategies
  • 44. 44 Mainstay of treatment : Bisphosphonates Approval in US for osteoporosis • Alendronate week : 1995 • Risedronate : 2000 • Ibandronate mnth: 2005 • Zoledronate yearly.iv : 2007.
  • 45. 45 Treatments & Efficacy Vertebral Fx Non-vertebral Fx Other Fx Hip Fx Oral HRT Yes Yes Yes Etidronate* Yes Alendronate* Yes Yes Yes Risedronate* Yes Yes Yes Ibandronate* Yes [Yes] Raloxifene* Yes Calcitriol* Yes Strontium Ranelate* Yes Yes [Yes]
  • 46. 46 Vertebral Fx Non-vertebral Fx Other Fx Hip Fx Subcutaneous Teriparatide* Yes Yes 1-84 PTH* Yes Denosumab* Yes Yes Yes Intravenous Pamidronate Ibandronate* Zoledronate* Yes Yes Yes Intranasal or Subcutaneous Calcitonin* Yes
  • 47. 47 Appropriate use of appropriate treatments can halve the incidence of fractures Vertebral Fx Nonvertebral Fx Other Fx Hip Fx Alendronate* Yes Yes Yes Risedronate* Yes Yes Yes Zoledronic acid* Yes Yes Yes PTH* Yes Yes ??? Strontium ranelate* Yes Yes ??? Denosumab* Yes Yes Yes plus calcium + vitaminD
  • 51. 51 Vitamin D levels • 25-OHD Vit D status Manifestation Management • <25 nmol/l Deficient Rickets/ Osteomalacia High-dose calciferol • 25-50 nmol/l Disease risk Vit D supps • 50-75 nmol/l Adequate Healthy Lifestyle advice • >75 nmol/l Optimal Healthy None – Divide by 2.5 for ug/L
  • 52. 52 Patients who did not need treatment in the first place Discontinue Treatment Lower risk patients, if DXA is stable/increasing Consider a drug holiday after 3-5 years of treatment Higher risk patients (fractures, corticosteroid Rx, very low BMD) Consider a drug holiday after 10 years of therapy May use teriparatide or raloxifene (but not another potent antiresorptive agent – ie. denosumab) during the holiday from bisphosphonates
  • 53. 53 Treatment of vitamin D deficiency Deficiency (25-OHD <25 nmol/l) 10 000 IU calciferol daily or 60 000 IU calciferol weekly for 8-12 weeks* or Calciferol 300 000 or 600 000 IU orally or by intramuscular injection once or twice
  • 54. 54 Treatment of vitamin D insufficiency Insufficiency (25-OHD 25-50 nmol/l) or maintenance therapy following deficiency 1000-2000 IU calciferol daily or 10 000 IU calciferol weekly –
  • 56. 56 HRT: A CONSENSUS • Prime role of HRT is relief of menopausal Sx • Risks/benefits need to be explained to each woman (breast Ca extra 2-6 cases per 1000 women treated with HRT for 5 years) • Use lowest effective estrogen dose, assess CV risk • Review need annually (esp aged>60)
  • 57. 57 HRT: A CONSENSUS • Can give up to age 50 if prem menopause • Do not use as primary or secondary prev. of CAD/CVA, or Alzheimers • Transdermal estrogen has lower DVT risk
  • 58. 58 RALOXIFENE • SERM licensed for OP • Reduces vertebral (not non-vertebral) fracture risk, just as does calictonin • Reduces development of new breast Ca. • No increased risk of CVD (reduces CV events!) • Increased risk of thromboembolism • May worsen flushes • Well tolerated, easy dosing
  • 59. 59 NICE 2005: (secondary prevention) • Teriparatide – use in women >65 years unresponsive to / intolerance of bisphosphonates, and: –with extremely low BMD (<-4) –with very low BMD (<-3), multiple fractures PLUS an additional risk factor National Institute for Clinical Excellence, Technology Appraisal 87, Jan 2005
  • 60. 60 Emerging Rx’s in osteoporosis Prof Compston 2010 • Denosumab – Monoclonal Ab to RANKL which drives osteoclasts – Subcut every 6m/12m! 60mg – Dramatic and quick effect – Fracture reduction similar to Zoledronate – Cost similar to risedronate (in 2010)! – NICE appraised
  • 61. 61 Denosumab Binds RANK Ligand and Inhibits Osteoclast Formation, Function, and Survival RANKL RANK OPG Denosumab Osteoclast Formation, Function, and Survival Inhibited Bone Formation Bone Resorption Inhibited CFU-GM Prefusion Osteoclast Osteoblasts Hormones Growth Factors Cytokines Adapted from: Boyle WJ, et al. Nature. 2003;423:337-342.
  • 62. 62 Few Simple ways You need not know about your T-score • If you are or consider your self Obese, • If you are exposed to Sun during your shopping in open markets at least twice a week, • If you take Milk and you are a vegetarian, • If you are taking regular Morning walk, • If you are regular about exercises (YOGA). • Your Relatives’ Death is not due to Fractures but due to age and co morbidity.
  • 63. 63 Summary There is an acute need for reconsidering – Globalization of Diagnosis of Osteoporosis & Osteopenia, – BMD screening, – Redefining Risk factors & role of fall and BMD in fractures, – Cost effectiveness of drug treatment, – Hype about Hip fractures, – Role of Big Pharma in propaganda of diagnosis, management, corruption in scientific literature, misuse political system and creation a state of “Fear psychosis & Hope selling”.
  • 64. 64