How to treat osteoporosis

1. 8-12-2015
1
HOT Lecture
How tO Treat
osteoporosis?
EULAR, Rome, 2015
Piet Geusens, MD, PhD
Professor of Rheumatology
Maastricht UMC, Netherlands
& UHasselt, Belgium
How to identify 50+ women and men
at high risk for fractures,
And how to reduce their fracture risk?
Maastricht UMC & UHasselt
Maastricht UMC & UHasselt
Bone quality ↓
Estrogen/
androgen
deficiency
Calcium
homeostasisAgeOxidative
stress
Diseases,
medications
Fracture
Falls ↑
Immune
system
Multifactorial etiology
and multifacetted results of fractures
Nutrition
Muscle
force
Frailty
Morbidity Mortality
Re-fracture
Fracture prevention in women and men older
than 50 years : A 5-step decision plan
MUMC&UHasselt Netherlands Guidelines “Osteoporosis and Fracture Prevention”, 2011
van den Bergh, Nature Rev Rheum, 2012, 568
1
Case finding
2
Risk evaluation
3
Differential
diagnosis
4
Therapy
5
Follow
up
1/ After recent fracture
2/ Diseases/medications
3/ Other clinical risk factors
Clinical risk factors
DXA
Imaging of the spine
Medical history
Clinical examination
Laboratory examination
Communication
Life style
Calcium and vitamin D
Medication (PO, IV, SC)
Fall prevention
Compliance
Tolerance
Efficiency
Duration of therapy
2/ Diseases/
medications
3/ Other
risk factors
1
Case finding
2
Risk evaluation
1/ Recent fracture
Vertebral
NHNV
Hip
Tools:
BMD
Imaging of the spine
Clinical risk factors
Aims:
Diagnosis
osteoporosis
presence of subclinical vertebral fracture
Fracture risk calculation
BMD
presence of vertebral fracture
clinical risk factors
Therapeutic decisions at start and during follow up
vertebral or hip fracture
osteoporosis
osteopenia
+ vertebral fracture
+ clinical risk factors
MUMC&UHasselt
Fracture Rates, Population BMD Distribution and Number of Fractures in NORA
Siris, E. S., et al. Arch Intern Med 2004 164:1108-12,MaastrichtUMC & UHasselt
Osteopenia Osteoporosis
Osteopenia
Copyright
P. Geusens

2. 8-12-2015
2
The relationship between femoral neck T-score
and the 23-month total fracture risk
MUMC&UHasselt Siris, OI, 2007, 761
The relationship between femoral neck T-score
and the 23-month total fracture risk
MUMC&UHasselt Siris, OI, 2007, 761
The fracture cascade
in 834 consecutive fracture patients in the Fracture
Liaison Service (Maastricht University)
Risk factors Only Bone Bone + Fall RFs Only Fall No RFs
RFs RFs
Number 183 334 170 147
% 22% 40% 20% 18%
Huntjens, BMC Musculoskelet Disord. 2013
MUMC&UHasselt
RF: risk factor
MUMC&UHasselt
Leslie, OI, 2014
Clinical risk factors to calculate fracture risk
Fracture risk calculators
(externally validated and accessible via web)
AUCs for fracture risk
prediction
• FRAX, +/- BMD 0.64-0.89
+ SECOB
• Garvan, +/- BMD 0.67-0.80
+ fall risk
• Qfracture, no BMD 0.67-0.89
+ SECOB + fall risk
www.shef.ac.uk/FRAX
www.garvan.org.au
http://www.qfracture.orgMUMC&UHasselt
Marques, ARD, 2015
Rubin, JBMR, 2013SECOB: secondary osteoporosis and other metabolic bone diseases
AUC: area under the curve
DXA
+
VFA
+
Fall
risk
T -2.5
T 1.0 and
>-2.5
T >-1.0
Vertebral
fracture
Other
risk
factors
2/ Diseases/
medications
3/ Other
risk factors
High fall risk
1
Case finding
2
Risk evaluation
1/ Recent fracture
Vertebral
NHNV
Hip
Copyright
P. Geusens

3. 8-12-2015
3
Prevalence of known and new SECOBs
in 50+ patienyts with a recent fracture at the FLS
according to sex, age, fracture location and BMD
0
10
20
30
40
50
60
Known SECOB New SECOB Any SECOB
SECOB: secondary oseoporosis and other metabolic bone diseases
FLS: Fracture Liaison Servoce Bours, JCEM, 2011
Bours, Curr Opin Rheum, 2014MUMC&UHasselt
Calcium supplements
Normal physiologic need:
calcium 1000-1200 mg/d
Controversy about CV risk of calcium supplements
(some signals, not confirmed in other studies)
Bolland, BMJ, 2011
Reid, J Cell Biochem, 2015
Paik, OI, 2014
Weaver, Curr Osteoporosis Rep, 2014
Adebamowo Am J Clin Nutr 2015MUMC&UHasselt
Medical treatment:
calcium and vitamin D
– Optimalisation of calcium intake:
• Total intake: 1000-1200 mg calcium/day
– e.g.: no milk products* + 4 milk products or 1000 mg
calcium supplement
– e.g.: 2 milk products/day + 2 milk products/day or +500 mg
calcium supplement
– e.g.: 4 milk products/day no adaptation necessary
– Vitamin D: 800 IU/day
• With anti-osteoporosis medication
• In subjects in rest homes
MUMC&UHasselt
*milk product:
- 1 cup of milk
- or yaghourt
- or 1 slice of cheese Maastricht UMC & UHasselt
Bone remodeling during life
ACTIVATIONFREQUENCY(#/yr)
0.0
0.2
0.4
0.6
0.8
1.0
1.2
Pre-
meno
1 yr
post-
meno
13 yr
post-
meno
Osteo-
porosis
Recker et al, JBMR 2004; 10 : 1628-1633
MUMC & UHasselt
Postmenopausal bone remodeling:
increased bone remodeling with bone loss
http://courses.washington.edu/bonephys/
Anderson, Am J Pathol, 2009, 239
Baron, Nature Med, 2013, 179
ANTI-RESORPTIVE TREATMENT
Copyright
P. Geusens

4. 8-12-2015
4
Osteoclastpre-
osteoclast
• Estrogens: decrease fracture risk, side effects
(CV and breast cancer)
• Calcitonin: limited fracture prevention data, risk of cancer?
• Selective estrogen receptor modulators (SERMs):
Raloxifene, Bazedoxifene, Lasofoxifene
Decrease risk of vertebral fractures (and non-
vertebral fractures with lasofoxifene)
Decrease of risk of breast cancer (raloxifene)
CV side effects Roth, Ann Intern Med. 2014;160:594
Overman, Ann Pharmacother, 2013, 1675
Martinkovitch, Clin Intervent aging, 2014, 1437MUMC&UHasselt
Effect of Denosumab and
Bisphosphonates on Osteoclasts
RANKL= RANKligand;OPG = osteoprotegerin
RANKL
RANK
OPG
Denosumab
Denosumab, a
soluble inhibitor,
blocks RANKL
Denosumab inhibits
osteoclast formation, function,
and survival
X
Bone
Precursor
osteoclast
BPs bind to bone mineral
at sites of bone resorption
BP are engulfed
(endocytosed) by osteoclasts
during the process of bone
resorption
BP BP
BPBP
BP
BPBP BP
BP
Bone
BPs cause loss of resorptive
function (via inhibition of FPPS
and prenylation of GTP-ases),
but ‘disabled’ osteoclasts may
persist
BP
BPBP BP
BP
BP
BP
BP
BP
Bone
BP BP
BPBP
BP = bisphosphonate;FPPS= farnesyl pyrophosphate synthase;GTP= guanosine-5'-triphosphate
Baron et al.,Bone 2011;48(4):677-692.
Russell RG,et al. Osteoporos Int.2008;19:733-759.
MUMC & UHasselt
Anti-resorptives
- suppress the birth of new remodeling units
- newly deposited bone partly maintains bone structure
- more complete secondary mineralization of new and old bone
- slow increase in BMD
- remodeling continues, but fewer and more shallow resorption cavities remove less bone
Seeman, NEJM
Long‐term effects of osteoporosis
treatments on total hip BMD
4 | ADVANCEONLINEPUBLICATION
on which tobasethemanagement of thesedrugholidays
isavailable. Sometimes, levelsof boneturnover markers
aremonitored, with levelsof PINP(aserum marker of
amino-terminal propeptideof type I collagen) >35μg/l
providingevidenceof offset of thedrugeffect,andrepeat-
ingBMD measurementsat ~2 yearsiscommon practice.
However, neither measurements have been shown to
predict fractures.37
Safety
Oral bisphosphonatesareassociated with adverseeffects
on theupper gastrointestinal tract in ~20%of patients,38
and intravenous aminobisphosphonates produce an
acute-phaseresponsein about one-third of patients.39
Adequaterenal function (that is, glomerular filtration
rate>35ml/min/1.73m2
) isaprerequisitefor theuseof
intravenous bisphosphonates. The long-term safety
of thesedrugshasbeen reviewed elsewhere.15
Two conditionsremain aconcern for bisphosphonate
use: osteonecrosisof thejaw (ONJ) and atypical sub-
trochanteric femoral fractures(AFFs). ONJisclearly
an issuefor patientswith disseminated cancer who are
treated with monthly infusionsof intravenousbisphos-
phonates(or denosumab), and occursin ~5%of these
patients.40
Similar nonhealing oral lesions have been
described in patientswith osteoporosis, irrespectiveof
whether or not theyaretreatedwithbisphosphonates.41–43
Postmarketingreportshavesuggested that theincidence
of ONJin patientswith osteoporosiswhoaretreatedwith
bisphosphonatesis ~2:100,000 patient-years.40
These
individualsseem to present with lessadvanced ONJ,44
and a high percentage of their lesions heal.45
Given
that ONJisarareevent and thecausal roleof bisphos-
phonatesisunclear, ONJisnot amajor consideration in
themanagement of osteoporosis.
By contrast, theoccurrenceof stressfracturesin the
lateral cortex of thefemoral shaft (referred toasAFFs) is
agrowingconcern.Thesefractur
versefractures,which occur after
incidenceof femoral stressfrac
sharplywith bisphosphonateuse
femoral stressfracturesarethree
alendronateusethan with risedr
arerarewith zoledronateuse.47,4
theUSA showed that Asian patie
to femoral stressfracturesthan
groups.49
Theincidenceof femor
todropdramatically1–2 yearsaft
drug.50
Caseseries, which haver
femoral fracturesand AFFs,have
to beasmall minority (for examp
12,777 femoral fracturesin Swe
A 2014 Swedish study reported
4 yearsof bisphosphonatetreatm
per 10,000person-years,47
which
AFFsisapproachingthat of hipfr
tionsof elderly individualsand t
phonateusemight causeasman
prevents.Thissuggestion isincon
data.TheFLEX study,51
for examp
year 5andyear 10of alendronate
trochantericfractureswas6fract
years, whereastheproximal fem
10-fold higher at 63 fracturespe
Whether anyof thesubtrochante
theFLEX studywereatypical isu
werenot available; however, the
subtrochantericfracturesisusua
Prospectively collected trial
clearly documented bisphospho
not suggest that theincidenceo
that of conventional femoral fra
need for continued bisphospho
periodically reviewed and drug
patientswho areno longer defi
BMD measurements.Theseactio
tiveinterventionscontinuetobep
osteoporosisat high risk of fractu
Estrogen and SERMs
Given that thedeclinein ovarian
thecritical changethat resultsin
loss, provision of estrogen from
maintainsBMD and reducesfrac
estrogen receptorsarewidelydist
administration of estrogen can
outcomes. Thiscaveat wasmad
Health Initiative, in which benef
and colon cancer incidencewe
changesin cardiovascular, cereb
thromboembolic events.54,55
Th
different for estrogen alonein co
plusprogestins, and islikely to
to thespecificestrogen and prog
in thisareahascaused many pat
loseenthusiasmfor estrogen asab
even though itsefficacyisbeyond
0 1 2 3
Time (year)
TotalhipBMDchange(%)
4 5 9
0
8
4
2
Nature Reviews | Endocrinology
6 7 8 10
10
6
Denosumab
Zoledronate
Alendronate
Figure 3 | Long-term effects of osteoporosis treatments on total hip BMD. Data derived
from long-term follow-up studies of the FLEXtrial28
(alendronate, 5–10mg per day), the
HORIZON trial30
(zoledronate, 5 mg per year) and the FREEDOM trial69
(denosumab,
60mg subcutaneous injection every6 months). As data are derived from separate
studies, formal comparisons between changes in BMD have not been made.
REVIEWS
© 2015 Macmillan Publishers Limited. All rights reserved
Reid, Nat Rev Endo, online
MUMC&UHasselt
Raloxifene
Patterns of Fluorochrome Labeling in the Proximal
Femur in adult monkeys on high dose of denosumab
Representative epifluorescent images of proximal femurs from the A) Sham and B) DMAb 25 mg/kg groups.
Fields within B were magnified to show C) trabecular bone (yellow), D) inferior periosteum, and E) superior
endocortex. F) A polarized light photomicrograph illustrates the collagen orientation in C, with the smooth
underlying cement lines highlighted in red.
Ominsky, JBMR, 2015, online
OSTEO-ANABOLIC TREATMENT
Copyright
P. Geusens

5. 8-12-2015
5
Maastricht UMC & UHasselt
Bone remodeling during life
ACTIVATIONFREQUENCY(#/yr)
0.0
0.2
0.4
0.6
0.8
1.0
1.2
Pre-
meno
1 yr
post-
meno
13 yr
post-
meno
Osteo-
porosis
Recker et al, JBMR 2004; 10 : 1628-1633 MUMC & UHasselt
Teriparatide injections act as anabolics:
remove old bone and deposit new bone
Cathepsin K
Osteoclast
Collagen degradation
RANK
Osteoblast
Wnt signaling
LRP Frizzeld
Wnt
DKK
Osteocyte
RANKL
Denosumab
rhPTH (1-34) (Teriparatide)
Sclerostin
pre-
osteoclast
pre-
osteoblast
RANKL Sclerostin
BP
BP
Bisphosphonates
BP
MUMC&UHasselt
Lems, Geusens, Curr Opin Rheumatol, 2014, 245
Efficacy of treatments for the prevention of
non-vertebral and hip fractures
Murad, JCEM, 2012, 1871
Russell, Curr Opin Pharmacother, 2015, 115
Incidence of fragility fracture at 36 months
in the FREEDOM study
Figurelegends
Figure1 Incidence of fragility fracture at 36 months in the FREEDOM
study. Values above the bars are risk reduction (95% confidence interval).
ARR, absolute risk reduction; n, number of subjects with a new fragility
fracture; N, number of subjects randomized; RRR, relative risk reduction
ClimactericDownloadedfrominformahealthcare.combyUniversityofMaastrichton06/09/15
Forpersonaluseonly.
Palacios, Climacteric, 2015
New vertebral or low-trauma nonvertebral fractures
MUMC&UHasselt
Teriparatide Reduces Risk of New Vertebral Fractures
Fracture Prevention Trial
RR = relative risk vs. placebo
ARR = absolute risk reduction
Multiple New Fractures
%ofwomenwith
>1vertebralfracture
0
1
2
3
4
5
Placebo
(22 / 448)
TPTD20
(5 / 444)
%ofwomenwith
>1fracture
Placebo
(22 / 448)
TPTD20
(5 / 444)
ARR = 3.78%
RR  77%*
Multiple
Neer, et al.N Engl J Med 2001; 344:1434-1441
*P<0.001 vs. placebo
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P. Geusens

6. 8-12-2015
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Teriparatide Reduces Risk of Nonvertebral Fractures
Fracture Prevention Trial
%ofwomenwith
>1fracture
Nonvertebral Fragility Fractures
%ofwomenwhohad
>1fragilityfracture
0
1
2
3
4
5
6
Placebo
(30 / 544)
TPTD20
(14 / 541)
*P=0.02 vs. placebo
ARR = 2.92%
RR  53%*
Nonvertebral fragility
Neer, et al. N Engl J Med 2001; 344:1434-41
Anti-resorptive drugs
Side effects
• Osteonecrosis of the jaw (ONJ, BONJ, BRONJ)
– Rare during osteoporosis treatment, risk range between 1 in 1000 and 1 in 263,000
patient-years, with minimal evidence for an association of risk with duration of therapy
– Frequent in cancer patients on zoledronate or denosumab
– Frequent questions in daily practice from patients, dentists, maxillo-facial surgeons
• Prevention: elimination or stabilization of oral disease prior to initiation of
antiresorptive agents, as well as maintenance of good oral hygiene
• Conservative therapy includes topical antibiotic oral rinses and systemic antibiotic
therapy
• Localized surgical debridement is indicated in advanced nonresponsive disease and
has been successful
• Early data have suggested enhanced osseous wound healing with teriparatide in
those without contraindications for its use.
Kahn, JBMR, 2015, 3
McClung, Am J Med, 2013
Atypical Femur Fractures
There was no significant increase in risk associated with bisphosphonate use, but
the study was underpowered for definitive conclusions
Black, NEJM, 2010, 1761
McClung, Am J Med, 2013
Shane, JBMR, 2014
ESCEO, OI, 2014
Incidence: 1.8/10,000 patients/year for up to 2 years of treatment and 8.4/10,000
patients/year with use of more than 2 years
Incidence much lower than hip fracture reduction
Prodromes of thigh or groin in >50% of cases
Imaging: RX, bone scintigraphy,MRI
Anti-resorptive drugs
Side effects
• Atrial fibrillation
– Only in zoledronate HORIZON trial
– Conflicting results in meta-analysis and cohort studies
• Flu-like symptoms
– Zoledronate, mainly after first infusion
• Hypocalcemia
– Measure calcium before BPs and denosumab
– Examples of high risk:
• Renal insufficiency CKD stage 4-5
• Vitamin D definciency
• Hypoparathyroidism
• Decreased calcium absorption, e.g. gastric bypass
• Fracture healing
– No negative effetcs of anti-resorptive treatment
Black, NEJM, 2007
Dave, Am J Nephrol, 2015
Kreutl, Swiss Med Weekly, 2014
Abrahamson, J Int Med, 2009
Ng, ANZ Surg, 2014MUMC&UHasselt
Oral Bisphosphonate Prescriptions,
Intertrochanteric Hip Fractures and AFF 1996-
2012 US
This article is protected by copyright. All rights reserved 21
Figure 3
This article is protected by copyright. All rights reserved 23
Figure 5
Intertrochanteric fractures AFF
This article is protected by copyright. All rights reserved 20
Figure 2
Bisphosphonate use
Jha, JBMR, 2015, online
This article is protected by copyright. All rights reserved 19
Figure 1
US Google search activity for the term “Fosamax”®
ONJ
AtrFibr
AFF
“may represent better targeting of bisphosphonate therapy”
Cumulative incidence of hospitalized infection
comparing denosumab vs. zoledronate
Curtis, A&R, 2015, onlineMedicare in 2006-2012
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P. Geusens

7. 8-12-2015
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Bisphosphonates and mortality
and quality of life
• Mortality
– Compared to placebo: reduced mortality after
recent hip fracture with zoledronate and in meta-
analysis of BPs
– DUBBO study in women (Australia)
– Compared to normal population: decrease in
women >60 yrs, not in men (Denmark)
• Quality of life
– Alendronate, zoledronate Black, NEJM, 2007
Center, JCEM, 2011
Abramson, JBMR, 2015, online
Cauley, JBMR, 2011MUMC&UHasselt
Death hazard as a function of sex and age at
beginning treatment
Abrahamsen, JBMR, 2015
Residual life expectancy after beginning osteoporosis
treatment:
real world experience
50-year-old women: 26 years man: 18 years
75-year-old women: 14 years man: 8 years
MUMC&UHasselt
Abrahamsen, JBMR, 2015
MUMC&UHasselt
Freemantle, Osteoporos Int. 2012, 317
Time to treatment non-adherence
Denosumab vs. alendronate
Persistence with and adherence to
denosumab at 12months
Hadji, OI, 2015, onlineMUMC&UHasselt
Non-vertebral
fracture after 1 yr
therapy
Doubt,
questions
Intolerance
Teriparatide in severe osteoporosis
Strongly recommended
Can be useful
Clinical suspicion of
new vertebral fracture
DXA after 2-3 yrs
Non
Compliance
Consult
Bone markers
Other medication or IV, SC
RX
Structured clinical monitoring (min. after 3 months, then yearly)
Start
therapy
Follow up
MUMC&UHasselt
Copyright
P. Geusens

8. 8-12-2015
8
Long-term studies with alendronate and
zoledronate
Reid, Nat Rev Endo, 2015
Alendronate 5 + 5 years
Clinical vertebral fractures were reduced by ~50%
In those with femoral neck T-scores <–2.5,
continuation of alendronate reduced
nonvertebral fractures by 50%
Zoledronate 3 + 3 years
Partial loss of vertebral fracture efficacy associated
with drug discontinuation, particularly in women
whose femoral neck T-score remained <–2.5
MUMC&UHasselt
Yearly Incidence of New Vertebral Fractures Through 8
Years
The Pivotal Phase 3 Study – Extension
n = number of subjects
with ≥ 1 fracture.
N = number of
randomized subjects who
remained on study at the
beginning of each period.
*Annualized incidence:
(2-year incidence) / 2.
Lateral radiographs
(lumbar and thoracic)
were not obtained at years
4 and 7 (years 1 and 4 of
the extension).
Placebo Long-term Denosumab Cross-over Denosumab
1/2* 4/5*3
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
YearlyIncidenceof
NewVertebralFractures(%)
Years of Denosumab Treatment
1980
34
1514
25
1496
50
N
n
3691
82
3186
98
3702 3247
35
3453
24
3400
32 107
2.2
3.1 3.1
0.9
0.7
1.1
0.9
1.7 1.7
FREEDOM EXTENSION
2101
58
1614
18
1567
38
4/5* 7/8*6
N
n
3691
82
3186
98
3702 3247
35
3453
24
3400
32 107
2.2
3.1 3.1
0.9
0.7
1.1
1.4
1.1 1.2
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
YearlyIncidenceof
NewVertebralFractures(%)
Years of Denosumab Treatment
FREEDOM EXTENSION
1 2 3
Adapted from Papapoulos S, et al. Presented at: American Society of Bone and Mineral Research Annual Meeting; October 4-7, 2013; Baltimore, Maryland.
After 3-5 yr therapy
Re-evaluation,
including clinical
risks and DXA (and
VFA or Xray when
suspicion of
vertebral fracture)
High risk:
- T <-2.5 in femoral neck
- New fracture
- Severe secondary
osteoporosis
-Glucocorticoids 7.5 mg/d
Low risk:
- No new clinical risk factors
- T >-2.5 in femoral neck
Continue
bisphosphonates or
other medication or
SC, IV
Teriparatide if new
fracture
- Life style
- Calcium + vit.D
- Stop medication
Follow up after 2-3 yrs
or if new fractures
and including clinical risks
and DXA (and VFA or Xray
when suspicion of vertebral
fracture)
Structured clinical
follow up
After 1.5-2 yr therapy
with teriparatide/PTH
(1-84):
Re-evaluation, including
clinical risks and DXA
(and VFA or Xray when
suspicion of vertebral
fracture)
Anti-resorptive
drugs
Recommended
Strongly recommended
Can be useful
Duration of therapy
Guideline Netherlands, 2011
McClung, Am J Medicine, 2013MUMC&UHasselt
Denosumab Re-treatment and Changes in
Lumbar Spine and Total Hip BMD
Phase 2: Postmenopausal Women With Low BMD
Adapted from Miller PD, et al. Bone. 2008;43:222-229.
Lumbar Spine Total Hip
PercentChange
(LSMean±SE)
Months
-6
-4
-2
0
2
4
6
8
Months
0 6 12 18 24 36 48
-4
-2
0
2
4
6
8
10
12
14
0 6 12 18 24 36 48
Re-treatment
60 mg Q6M
Discontinued
Treatment
Re-treatment
60 mg Q6M
Discontinued
Treatment
Placebo
30 mg Q3M
PercentChange
(LSMean±SE)
Treatment failure
• Lack of definition (Diez-Perez, OI, 2014)
– “Effective”:
• No new vertebral fracture (imaging!)
• No new other fracture
– “Ineffective”:
• New fracture after 1 year adequate anti-resorptive treatment
• Bone loss in spite of adequate anti-resorptive treatment
• Teriparatide in case of new fracture during adequate
treatment with anti-resorptives > 1 year
MUMC&UHasselt
DXA
+
VFA
+
Fall
risk
T -2.5
T 1.0 and
>-2.5
T >-1.0
Vertebral
fracture
Low risk:
- Life style
- No medication
Medical
therapy
Follow
Up
High risk:
- Therapy or follow up
- Life style
Other
risk
factors
2/ Diseases/
medications
3/ Other
risk factors
High fall risk
Investigation
&
correction of
new
secondary
osteoporosis
1
Case finding
2
Risk evaluation
3
Differential
diagnosis
4
Therapy
5
Follow
up
1/ Recent fracture
Vertebral
NHNV
Fall prevention strategies
Investigation
&
correction
Hip
Copyright
P. Geusens

9. 8-12-2015
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Components of bone and muscle and resistance
to fracture
Torres, Curr Rheumatol Rep, 2013
Bone remodeling and modeling
Neuromuscular
performance
Muscle
- Mass
- Power
- Strength
- Remodeling
- Damage
Balance
Cathepsin K
Osteoclast
Collagen degradation
RANK
Osteoblast
Wnt signaling
LRP Frizzeld
Wnt
DKK
Osteocyte
RANKL
Denosumab Anti-sclerostin
rhPTH (1-34) en (1-84)
Sclerostin
pre-
osteoclast
pre-
osteoblast
RANKL Sclerostin
BP
BP
Bisphosphonates
BP
Odanacatib
Lems & Geusens, Curr Opin Rheumatol. 2014, 245
Questions for the (next) future
• Can we ameliorate case finding?
– FLS and alternatives EULAR/EFORT
• Role of new measurement techniques of bone quality in daily practice
• Can we further reduce the risk of NVNH fractures?
• Direct comparisons between drugs on fracture prevention
• Can we decrease post-fracture morbidity?
• Can we treat to target, and what is the definition of target?
• Role of future therapies:
– Odanacatib, a specific cathepsin-K inhibitor
– New osteo-anabolics: anti-sclerostin antibodies
• Effect of combination and sequential therapies on fracture risk
• How to improve adherence?
• Cost-effectiveness of case finding and therapy?
• What is real-life evidence?
• Can we improve fracture healing?
• Sarcopenia: definition, treatment?
• Fracture prevention in <50 years old?
MUMC&UHasselt
Fracture prevention in women and men older
than 50 years : A 5-step decision plan
MUMC&UHasselt Netherlands Guidelines “Osteoporosis and Fracture Prevention”, 2011
1
Case finding
2
Risk evaluation
3
Differential
diagnosis
4
Therapy
5
Follow
up
1/ After recent fracture
2/ Diseases/medications
3/ Other clinical risk factors
Clinical risk factors
DXA
Imaging of the spine
Medical history
Clinical examination
Laboratory examination
Communication
Life style
Calcium and vitamin D
Medication (PO, IV, SC)
Fall prevention
Compliance
Tolerance
Efficiency
Duration of therapy
Copyright
P. Geusens

10. 8-12-2015
10
Capucijnen Crypte
Capuchin Church
of the Immaculate Conception
(1645), Via Veneto, Rome
How tO Treat osteoporosis?
a HOT Lecture, … a HOT Topic,
… in a HOT city
Körperwelten
Professor anatomie Günther von Hagens
Copyright
P. Geusens