Osteoprosis: Evaluation, Management and Prevention by Dr Shahjada Selim

Burden of Osteoporosis
Dr Shahjada Selim
Assistant Professor
Department of Endocrinology
Bangabandhu Sheikh Mujib Medical University, Dhaka
Email: selimshahjada@gmail.com, info@shahjadaselim.com

Definition of Osteoporosis
World Health Organization (WHO), 1994
Osteoporosis is a
skeletal disorder
characterized by
compromised bone
strength predisposing
to an increased risk
of fracture.
5/4/2017 Burden Osteoporosis by Dr Selim 2

osteoporotic
Osteoporotic bone

Normal bone vs. Osteoporotic bone
• The normal bone shows a pattern of
strong interconnected plates of bone.
• Much of this bone is lost in
Osteoporosis and the remaining bone
has a weaker rod-like structure &
some of the rods are completely
disconnected.
• These bits of disconnected bone may
be measured as bone mass but
contribute nothing to bone strength.

Normal has appearance of a honeycomb matrix
(left) .Under a microscope , osteoporotic bone
looks more porous.

• Osteoporosis is characterized by
progressive decrease in bony mass that
results in increased bone fragility and
higher fracture risk, which can be primary
or secondary.
Clinician's guide to prevention and treatment of osteoporosis.20105/4/2017 Burden Osteoporosis by Dr Selim 6

• Osteoporotic fracture account 0.83% of
global burden of non communicable
diseases.
• Patients may confuse osteoporosis with
degenerative conditions
• Acute pain in vertebral fracture usually
resolve in 4-6 weeks.
Clinician's guide to prevention and treatment of osteoporosis.20105/4/2017 Burden Osteoporosis by Dr Selim 7

Cont…
• Fracture spine typically by OP is
generally compression fracture or
wedge fracture.
• Fractures can anywhere in the spine,
rarely above the T7
• Wedge-shaped vertebra on back -
stooped posture called dowager’s
hump.
• Fractures of OP increases
dramatically with ageing, (4 “I”) and
Sarcopenia.

 Osteoporosis, despite being a common
metabolic bone disease, has attracted little
attention and even less action in many
developing countries.
There are several reasons for this state of
neglect.

Definition by DXA scoring
T score Category
> -1 Normal
< -1 to > 2.5 Osteopenia
<-2.5 Osteoporosis
<-2.5 with
fragility fracture
Established/severe
osteoporosis
WHO Criteria

Rosen, Endotext.com, Chap.11
Epidemiology
• 3,00,000 new cases per year
• Osteoporosis affects 65% of Indians aged 50 and
above. Of these, approximately 80% are women.
• 50% of women over age 50 will sustain a fracture
in their lifetime
• The condition is responsible for millions of
fractures annually, mostly involving the lumbar
vertebrae, hip, and wrist.
• Fragility fractures of ribs are also common in men.

Contd.
 200 million women worldwide.
 40% of women over 50 have osteopenia.
 7% of women over 50 have osteoporosis.
 Causes >8.9 million fracture worldwide
annually, resulting a osteoporotic fracture
every 3 second.
http://www.iofbonehealth.org,2012.
5/4/2017 Burden Osteoporosis by Dr Selim
12

Prevalence
2000
(in millions)
2015
(in millions)
Osteoporosis 10 41
Osteopenia 14 80

10-Year Probability of Fracture in
Women by Age and T-Score
Data from Kanis JA, et al. Osteoporos Int. 2008;12:989-995.
30.824.519.415.211.89.17.0
28.422.818.314.611.59.07.1
23.919.315.612.610.08.06.3
20.216.213.010.48.26.55.1
16.813.410.78.56.75.34.1
14.111.39.27.45.94.73.8
75
70
65
60
55
50
T-Score
–3.0
T-Score
–2.5
T-Score
–2.0
T-Score
–1.5
T-Score
–1.0
T-Score
–0.5
T-Score
0
Age
(years)
30.824.519.415.211.89.17.0
28.422.818.314.611.59.07.1
23.919.315.612.610.08.06.3
20.216.213.010.48.26.55.1
16.813.410.78.56.75.34.1
14.111.39.27.45.94.73.8
75
70
65
60
55
50
T-Score
–3.0
T-Score
–2.5
T-Score
–2.0
T-Score
–1.5
T-Score
–1.0
T-Score
–0.5
T-Score
0
Age
(years)
30.824.519.415.211.89.17.0
28.422.818.314.611.59.07.1
23.919.315.610.08.06.3
20.216.210.48.26.55.1
16.813.410.78.56.75.34.1
14.19.27.45.94.73.8
75
70
65
60
55
50
T-Score
–3.0
T-Score
–2.5
T-Score
–2.0
T-Score
–1.5
T-Score
–1.0
T-Score
–0.5
T-Score
0
Age
(years)
12.6
13.0
11.3

0
200,000
400,000
600,000
800,000
1,000,000
1,200,000
1,400,000
1,600,000
Breast
Cancer
Heart
Disease
Osteoporotic
Fractures
Cases/Year
Women’s Health Facts and Figures. Washington, DC: ACOG; 2000.
• Osteoporotic Fracture Incidence Is High
Contd.
16

Taiwan, Singapore, and Hong Kong-
400 to 500 per 100,000 women; similar to Caucasian
populations
Japan - > 200 - 300 per 100,000 women
Malaysia and Thailand- 200 - 250 hip fracture per
100,000 women
Korea and China- 100 hip fracture per 100,000 women;
increased over a short period
By 2050 more than 50% of all osteoporotic fracture
will occur in Asia
The Asian Audit 20095/4/2017 Burden Osteoporosis by Dr Selim 17
In Asian….

NIH/ORBD National Resource Center. October 2000.
Vertebral
46%
(700,000)
Wrist
16%
(250,000)
Hip
19%
(300,000)
Other
19%
(300,000)
• Distribution of Fractures
Clinical features & Consequences
18

• Non- Vertebral/spine fractures
 Almost all - traumatic & easy to diagnose clinically
• Vertebral fractures
 Only 1/3 diagnosed clinically.
 Of clinically diagnosed vertebral fractures, only 14%
follow severe trauma whereas > 83% follow
moderate or no trauma.
 Sudden onset of pain is an useful marker of fracture
Endocrine Metab Clin North Am 1998;27:289-301
J Bone Miner Res 1997;12:663-6755/4/2017 Burden Osteoporosis by Dr Selim 19

 About 2/3 of the fractures causes no
symptoms. 1/3 of vertebral fractures, with
acute back pain
 50% of women and 20% of men above 50 will
have an OP related fracture in their lifetime
 85% of OP patients with low back pain is
considered the prevalent musculoskeletal
pain, particularly in elderly.
Endocrine Metab Clin North Am 1998;27:289-301
J Bone Miner Res 1997;12:663-6755/4/2017 Burden Osteoporosis by Dr Selim 20

Common Fracture Sites
21
Hip
Spine
Wrist
 Humerus, Ribs, Tibia, Pelvis
Uncommon sites
5/4/2017 Burden Osteoporosis by Dr Selim

SITE INCREASE IN
MORTALITY RISK
Vertebrae 8.6
Hip 6.7
Any Clinical Fracture 2.2
Fracture and Mortality Risk

COMPLICATIONS:-
• Fractures are most frequent and serious
complications of osteoporosis.
• Often occurs in spine and hips – bones that
directly support your weight.
• Hip fractures and wrist fractures from fall are
common.
• Compression fractures can cause severe pain
and require a long recovery

Consequence of Fracture
 After the ﬁrst hip fracture, 30% of patients will fracture
the second hip.
 Nearly 20% of the women who develop a new
vertebral fracture will fracture again within a year.
 5 year survival rate following a vertebral fracture is
equally worse as a Hip fracture.
 It is clear that bone loss cannot be completely
reversed but fracture risk can be decreased by
intervention.
 One year mortality following a hip fracture in men is
twice that of female

PREVENTION
Do exercise such as walking , running ,
skipping rope , jogging regularly.
Avoid smoking , it can reduce the level of
estrogen and increases bone loss.
Avoid excessive alcohol.
 Avoid caffeine , which is very harmful.
 Consider hormone therapy.

Whom and How to Evaluate
Osteoporosis

Osteoporosis
• Reduction in bony mass/ density or
• Presence of fragility fracture,
• associated with loss of structural integrity of
internal architecture
NOF

Operational Definition: WHO
• BMD: T < - 2.5 SD of mean for healthy adults
of same race and gender.
WHO

Z-score:
• Z score:
– men younger than 50 years or
– premenopausal women.
– secondary causes of osteoporosis.
•NOF: National Osteoporosis Foundation. Clinician's guide to prevention and treatment of
osteoporosis. Washington, DC: National Osteoporosis Foundation, 2010;1–56
•Lewiecki EM, Watts NB, McLund MR, et al. Official positions of the International
Society for Clinical Densitometry. JCEM 2004;89:3651–3655
Z < −2.0

Main outcome
• Threshold for Fracture is reduced > Fracture
– Vertebra
– Hip
– Wrist
– Pelvis
– Proximal humerus
– Other bones
NOF Kling et al 2014

Osteoporosis
Whom to Evaluate
Types Pathogenesis
Risk/
Conditions: 2nd

Primary
Postmenopausal Osteoporosis
Senile Osteoporosis, > 70 y
Secondary
NOF

Pathogenesis: Osteoporosis
• Prevalent among postmenopausal women,
most women meet diagnostic criteria at 70-80
years of age.
• Increasing age: Men and women.
• Commonly found: Men and women with
conditions or risk factors associated with bone
demineralization
Kasper et al. 2005, Kling et al 2014

Bone remodeling
Peak Bone Mass
Osteoblast Osteoclast
Aging
Altered
remodeling
Bone loss/
Osteoporosis/ Fracture
Nutrition: Ca, Vit
D, Calorie, Protein,
other minerals
Physical activity
Hormone
Chronic disease/
Disease favors bone
demineralization
Medications
Risk factors
Genetics: Race,
Family Hormone

Hormonal/ Paracrine/ Cytokines
Peak Bone Mass
Osteoblast Osteoclast
Aging
Altered
remodeling
Bone loss/ Osteoporosis/
Fracture
Estrogens
Androgens
Vit D
IGF-I, II, IL-1ra,
TGF-β
RANKL
PTH
IL-1, IL-6, IL-11
TNF-α
OPG

Risk factors: Osteoporosis/ #
Non-modifiable Potentially modifiable
Prior # in adulthood Current smoking
Family H/O Osteoporotic # LBW (<58 kg)
Female sex: Low peak bone mass,
Menopause
Inadequate physical activity
Achieved peak bone mass Early menopause (<45 y) or BLO
Advanced age Prolong Premenstrual amenorrhea (>1y)
Caucasian race Low calcium intake
Dementia Alcoholism > 2/3U/day, excessive caffaine
Impaired eye sight
Recurrent falls: Chronic disease, PD, MS
Poor health/ frailty
NOF 2013, Kasper et al. 2005, Kling et al 2014

Disease/ Conditions associated with
Osteoporosis: 2nd Osteoporosis
Hypogonadal states Endocrine disorders
Premature menopause Cushing’s syndrome
Turners syndrome Hyperparathyroidism
Klinefelter syndrome Hyperthyroidism (3 yrs)
Other primary/ secondary
hypogonadanadal states
Type 1 DM
Low estrogen >Amen> 6 months Adrenal insufficiency
Hyperprolactinemia GH deficiency
Anorexia nervosa Acromegaly with hypogonadism
Athletic amenorrhea
NOF 2013 Kasper et al. 2005, Kling et al 2014

Nutrition & Gastrointestinal
disorders
Rheumatological disorders/
inflammatory conditions
Malnutrition, lactose intolerance RA
Prolonged parenteral nutrition Ankylosing spondylitis
Malabsorption syndrome: Coeliac, CD
Gastrectomy
Severe/ chronic liver disease

Hematological disorders &
malignancies
Inherited disorders
Multiple myeloma Osteogenesis imperfecta
Leukemia Marfan syndrome
Paraneoplastic syndrome (PTHrP) Ehlers’s Danlos syndrome
Thalassemia
Hemophilia

Other disorders Drugs
Immobilization Systemic glucocorticoids GCs> 3m>
7.5 mg pred
COPD Cytotoxic drugs/ chemotherapy
Multiple sclerosis Cyclosporin
Sarcoidosis Anticonvulsants (long term)
Heparin long term
Excessive thyroxine

• Whom to evaluate: No uniform
recommendations.

National Osteoporosis
Foundation
and
American College of
Preventive
Medicine
Postmenopausal women Age ≥ 65 years without
risk factors or ≤ 65
years
with risk factors
Men Age ≥ 70 years without
risk factors or ≥ 50
years
with risk factors
Kling et al 2014

North American
Menopause
Society
Postmenopausal women Age ≥ 65 years without
risk factors or ≤ 65 years
with risk factors
Postmenopausal women
with medical causes of
bone loss or fragility
fracture, regardless of
age
Postmenopausal women
≥ 50 years with
additional
risk factors

U.S. Preventive
Services Task
Force
Postmenopausal
women
Age ≥65 years or ≤
65 years with risk
factors
Men None
Kling et al 2014

Institute for
Clinical
Systems
Improvement
Postmenopausal
women
Age ≥ 65 years and in
younger women
whose
fracture risk is ≥
9.3% from FRAX
analysis or
are considered to be
at risk of fracture
Kling et al 2014

Osteoporosis
How to Evaluate
Clinical
History
Clinical
Examinations
Investigations

Clinical Presentations: History and physical
findings
• Usually asymptomatic unless fracture
• Doesn’t cause generalized skeletal pain
• Sudden onset of localized pain with or without
H/o injury
• Persistent back pain
• Height loss (.1 to 1.5 inch)
• Kyphosis
• Fragility fractures

Complications: Hip
• Pain, mobility
• Cause of death
FRACTURE
DVT, Pul embolism
Hip #: 5% to 20% during year of
surgery

Vertebra
• Long term morbidity
Multiple # > height loss, kyphosis,
Thoracic #: restrictive lung disease
Lumber #: abdominal distention,
early satiety, constipation.

Assess
• Risk factors
• Conditions/ diseases/ Medications associated
with 2nd Osteopororsis

Two major tool
• BMD:
– Diagnosis/ Status
– Treatment decision
• FRAX Tool (WHO)
– Risk assessment
– Treatment decision
Dennis M, NEJM 2016.

Measures of Bone Mass (BMD)
• DXA: Standard for BMD
• Others
– SXA
– Computed tomography–based absorptiometry
(quantitative computed tomography),
– Quantitative ultrasound densitometry,
WHO, NOF, USPSTF

WHO Criteria for BMD
Category T-score
Normal -1.0 and above
Low bone mass
(osteopenia)
-1.0 to -2.5
Osteoporosis -2.5 and below
Established severe
Osteoporosis
-2.5 and below
With fragility fracture
http://www.who.int/chp/topics/Osteoporosis.pdf. Accessed August 2014.
WHO Study Group. World Health Organ Tech Rep Ser. 1994;843:1-129.

• Developed by the WHO
• Designed for primary care use
– in postmenopausal women and
– men older than 50 years
– (but validated for men and women aged 40–90
years)

• Risk factors are combined with femoral neck
BMD to calculate 10 y probability of fracture
– major osteoporotic
– hip fracture risk
NOF 2010

• FDA–approves: therapy can be initiated for
patients with 10-year risk of
• hip fracture of at >3% or
• a risk of a major osteoporotic fracture 20% or
higher.
FDA, NOF 2010

Most useful Others
CBC, ESR Oestradiol, FSH
LFT Serum & Urine electrophoresis
(BJP), Punch out lesion X rays
RFT Endomysial ab, TTG ab, biopsy
Calcium, P, albumin, alk Phos,
24 h U ca, PTH
U free cortisol, Overnight DST
Vitamin D Isotope bone scan
Thyroid function tests Albumin, cholesterol, Vit B12,
folate, iron profile
Testosterone, LH, SHBG
X-rays for evidence of previous
fractures/ fragility fracture
As appropriate for secondary
causes

Biochemical markers
• Bone-specific alkaline phosphatase,
• osteocalcin,
• urinary hydroxyproline,
• Collagen crosslinks such as C-terminal-
telopeptide and N-terminal telopeptide
• Useful for aiding in osteoporosis diagnosis and
monitoring treatment response

• Not included in screening algorithm
• Being used to monitor osteoporosis treatment

• At appropriate age for sex.
• Having other risk of Primary osteoporosis.
• At risk of developing secondary osteoporosis.
• Having fragility fractures
Whom to Evaluate

• Appropriate clinical history: Risk assessment
• Clinical examination: signs, complications,
conditions
• Investigations:
– Diagnosis
– Risk assessment
– Complications
– Evaluation of secondary causes as relevant.
How to Evaluate

Management aspect of
osteoporosis

Goals of treatment
• Prevent further bone loss
• Increase or at least stabilize bone density
• Prevent further fractures
• Relieve deformity (e.g., kyphoplasty)
• Relieve pain
• Increase level of physical functioning
• Increase quality of life

Lifestyle Advice
Diet Exercise
Smoking
Stop smoking
Alcohol
Nutr Rev 2008;66(suppl 2):5182-5194
Endocr Pract 2009;15:95-103
Cangussu LM et al. Osteoporos Int 2015;26:2413-21
Wang J et al. J Bone Miner Res 2015;30:1641-50
Ann N Y Acad Sci 2006;1068:429-446
Sunlight Exposure

Bone Health PMO
• Vitamin D
– Measure 25-OH vitamin D in those at risk for insufficiency
– Preferable range 25-OHD : 30 ng/ml to 50ng/ml
– Supplementation if needed: generally in range of 1000-2000 IU daily with higher
amounts in some patients
• Calcium
– Counsel on adequate dietary intake of calcium – about 1200 mg daily
• Exercise
– Active lifestyle, weight –bearing and balance exercises
• Limit alcohol to ≤ 2 servings daily
• Limit caffeine intake
• Refer PT and OT as needed
77

Nonpharmacologic Measures in
PMO Treatment
• Maintain adequate protein intake
• Use proper body mechanics
• Consider use of hip protectors in individuals
with high fall risk
• Take measures to reduce fall risk
• Consider referral to PT and OT
78

Common Medications Possibly Associated With
Increased Fracture Risk
• Proton-pump inhibitors (PPI’s)
– ↑ hip fracture after long-term, high-dose therapy in observational
studies1
• Selective-serotonin reuptake inhibitors (SSRI’s)
– 2x ↑ risk fragility fracture seen with daily use2
• Thiazolidinediones (TZD’s)
↑ risk peripheral fractures in post-menopausal womenwith type 2 diabetes
on rosiglitazone compared to metformin or glyburide3
• 1Yang YX et al. JAMA 2006;296:2947-2953
• 2Richards JB et al. Arch Int Med 2007;167:188-194
• 3Kahn SE et al. Diabetes Care 2008;31:845-851, Loke YK et al CMAJ 2009;180:32-9
79

Who Needs Pharmacologic Therapy?
• Those patients with a history of a fragility
fracture of the hip or spine with osteopenia
• Patients without a history of fractures but
with a T-score of -2.5 or lower
• Patients with a T-score between -1.0 and -2.5
if FRAX 10 year major osteoporosis related
fracture probability at 20% or more or hip
fracture probability at 3% or more
80

Pharmacologic approaches to
osteoporosis
Antiresorptive agents
• Calcium
• Vitamin D and calcitriol
• Estrogen
• SERMs
• Calcitonin
• Bisphosphonates
• RANK-ligand inhibition
Bone-forming agents
• Fluoride
• Androgens
• Parathyroid hormone
• Strontium ranelate
82

What Drugs Can Be Used to Treat PMO
Use Drugs with Proven Antifracture Efficacy
first line therapy
• alendronate, risedronate, zoledronic acid, and denosumab
Second line therapy
• ibandronate
Third line therapy
• Raloxifene
Last line of therapy
• calcitonin
• Use teriparatide for patients with very high fracture risk or patients in whom
bisphosphonate therapy has failed
• Advise against the use of combination therapy
– Cost, improved efficacy not documented, safety
83

84
Estrogen meets up the hormonal scarcity in postmenopausal women
Elevates the calcium level in circulation
Decreases bone resorption
Estrogen

85
• Raloxifene, a Selective estrogen receptor modulator (SERM) has been
used to treat Osteoporosis.
• It has estrogen agonist activity in some tissues and antagonist in other
tissues.
• It has been introduced to overcome the side effects of ERT/HRT
• Not a very good option for Severe Osteoporosis & Osteoporotic pain
SERM

86
• Must be used with other treatment options
• A very good option to treat Osteopenia
• Insufficient to treat Osteoporosis
Calcium & Vitamin D

87
• A good option to treat Postmenopausal Osteoporosis
• Very effective to control Osteoporotic Pain
• Can reduce vertebral fracture rate
• Convenient treatment option
• Difficult to treat severe Osteoporotic patients
Calcitonin

Strontium Ranelate
• Side effect- Headache, Diarrhea, MI, VTE,
Dermatitis, eczema.
• Not used in USA.
• Strontium is alternative to BP in some situation.
J Clin Endocrinol Metab 2005;90:2816-2822
Clin Instrum in Aging 2008;3(2): 315-329
J Clin Endocrinol Metab 2005;90:2816-2822
Clin Instrum in Aging 2008;3(2): 315-329

Testosterone Therapy
• Studies of testosterone in men with osteoporosis
are limited, Effective in hypogonadal adolescents,
and with low testosterone level.
Ref: Basic Prescribing Information,2012

90
Effects of Bisphosphonates on Osteoclast Function
Normal Osteoclast
Osteoclast Following Uptake
of Bisphosphonate
Cytoskeletal
disorganization1
Altered vesicular
trafficking3
Loss of ruffled
border1
Cell death by apoptosis2
1. Sato, M, et al. J Clin Invest. 1991;88:2095-2105. 2.
2. Hughes DE, et al. J Bone Miner Res. 1995;10:1478-1487.
3. Rogers M. Curr Pharm Des. 2003;9:2643-2658.

Evolution of BP’s for the Treatment of OP
Etidronate
Alendronate
Once a day
Alendronate
Once weekly
Risedronate
Once weekly
Ibandronate
Once daily
Ibandronate Once
monthly
Ibandronate
Quarterly
1991 1995 2000 2002 2003 2005 2006
Zoledronic acid
Once yearly
2007
Risedronate
Once daily
2000 2007
Risedronate
Once monthly
Contd….

Bisphosphonate- side effects
• Low bioavailability in contrast to IV, poor
compliance with oral BP
• Having chance of GERD, PUD with oral BP.
• Other side effects are common for all BP - atypical
fracture of femur, ONJ, AF, esophageal cancer
The Journal of Family Medicine June2010;59:200-6

• Although IV BPs are generally safe, transient influenza-like
symptoms.
• ONJ- 1-19 per 100,000 (IV: oral = 3:1).
• Upto 18.6% in oncology patients
• Denosumab had lower ORs than all BPs for ONJ.
• Atypical fracture of femur with bisphosphonate for as long as
10 years – large studies – FIT, FLEX, HORIZON did not support
Contd….
Patricia |Sieber et al.Clinical Drug Investigation (2013) 33:117 122. DOI 10.1007/s40261 012 0041 1
Zhang X et al. J Bone Miner Res 2015; doi:10.1002/jbmr.2693
Khan A et al.Osteoporos Int.DOI 10.1007/s00198-015-3335-3
N Engl J Med 2010:1761-71

Cont-ONJ
• IV Bisphosphonate
• Cancer & anti-cancer therapy
• Dental extraction, oral bone manipulating surgery
• Poor fitting dental appliances
• Intraoral trauma
• Duration of exposure to bisphosphonate treatment
• Comorbidity- malignancy, alcohol abuse, use of tobacco
• Periodontal disease
Formulary 2011;46:432-446
Contd….

Denosumab
• A anti-resorptive therapy.
• Monoclonal antibody against RANK ligand.
• Approved for postmenopausal osteoporosis in USA.
• Dose- 60mg s/c injection every 6 month

PTH and Teriparatide
• PTH 1-34 (teriparatide) and PTH 1-84, anabolic drug
• Not beyond 2 years.
• Highest BMD achievement & reduction of vertebral
fracture - Add on therapy.
• Side effects-
 Orthostatic hypotension, nausea, myalgia, and
arthralgia, risk of osteosarcoma
97

98
Osteoporosis Treatments Have Different
Effects on the Bone Remodeling Cycle
1. FORTEO Prescribing Information. 2. Arlot M, et al. J Bone Miner Res. 2005;20:1244–1253. 3. Jiang Y, et al. J Bone Miner Res. 2003;18:1932–1941.
4. Fleisch H.. Endocr Rev. 1998;19:80-100. 5. Russell RG, et al. Osteoporos Int 1999;9:S66-S80. 6. Riggs BL, Parfitt AM. J Bone Miner Res 2005;20:177-184.
Function
Primary
effect
Secondary
effect
Bone
turnover
BMD
effect
Bone
volume
Antiresorptive
agents
(bisphosphonates,
denosumab, raloxifene)
Anabolic
agent
teriparatide
Fill in the
remodeling
space;
mineralization
of existing
bone4-6
Bone
resorption4,5
Osteoclast
activity4,5
Osteoblast
activity4,5
Turnover4,5 No
effect
Information regarding mechanisms of action does not provide
evidence of comparative fracture protection
Action
New bone
formation;
skeletal mass1
Turnover2 Bone
volume3Osteoblast
activity1
New bone
formation1 Osteoclast
activity1

Who Should Not be Considered
for Teriparatide Therapy?
• Hypercalcemia
• Paget’s disease
• Osteogenic sarcoma
• Unfused epiphysis
• Previous irradiation to the skeleton
• Pregnancy or breast-feeding
• Bone cancer or metastatic cancer to bone
• Allergic reaction to PTH or to ingredients in the vehicle
99

Osteoporosis
Medication Options
Broad spectrum
– Alendronate, risedronate, zoledronic
acid,denosumab
Parenteral options if needed
– Denosumab, zoledronic acid,teriparatide
Spine specific efficacy
– Ibandronate, raloxifene
100

• Combined denosumab and teriparatide
achieves improved BMD response vs either
agent alone but data for fracture risk are
lacking.
• Strongly recommend antiresorptive therapy
following teriparatide therapy
103

BMD after discontinuation of PTH (QCT)
Months
0 6 18
0
5
10
15
20
25
36
No antiresorptive after discont.
Antiresorptive after discont.

How is
Treatment Monitored?
• Obtain a baseline DXA, and repeat DXA every 1-2 years until
stable. Continue follow-up every 2 years or at a less frequent
interval
• Monitor changes in spine or total hip BMD
• Follow-up same facility, same machine, and if possible, the
same technologist
• Bone turnover markers may be used at baseline to identify
patients with high bone turnover and can be used to follow
the response to therapy
105

What is Successful Treatment of Osteoporosis?
• BMD is stable or increasing and no fractures are
present
• For patients taking antiresorptive agents, bone
turnover markers at or below the median value for
premenopausal women are achieved
• One fracture is not necessarily evidence of failure.
• Consider alternative therapy or reassessment for
secondary causes of bone loss for patients who have
recurrent fracture while receiving therapy
106

How long ?
• Teriparatide –limited to 2 yrs
• For oral bisphosphonates, consider a “bisphosphonate holiday” after 5
years of stability in moderate-risk patients .
• For oral bisphosphonates, consider a “bisphosphonate holiday” after 6 to
10 years of stability in higher-risk patients
• For intravenous (IV) zoledronic acid, consider a drug holiday after 3 annual
doses in moderate-risk patients and after 6 annual doses in higher-risk
patients.
• Teriparatide or raloxifene may be used during the “bisphosphonate
holiday” period for higher-risk patients
107

Drug holiday
• A drug “holiday” is not recommended with denosumab
• The ending of the “holiday” for bisphosphonate treatment should be
based on individual patient circumstances (fracture risk or change in BMD
or BTMs)
• Other therapeutic agents should be continued for as long as clinically
appropriate
108

When Should Patients Be Referred
to Clinical Endocrinologists?
• When a patient with normal BMD sustains a fracture without
major trauma
• When recurrent fractures or continued bone loss occurs in a
patient receiving therapy without obvious treatable causes of
bone loss
• When osteoporosis is unexpectedly severe or has unusual
features
• When a patient has a condition that complicates management
(for example: renal failure, hyperparathyroidism,
malabsorption)
112

Glucocorticoid induced osteoporosis
113

Clinical factors that may shift an individual to a greater risk
category for glucocorticoid-induced osteoporosis
• Low body mass index
• Parental history of hip fracture
• Current smoking
• ≥3 alcoholic drinks per day
• Higher daily glucocorticoid dose
• Higher cumulative glucocorticoid dose
• Intravenous pulse glucocorticoid usage
• Declining central bone mineral density measurement that exceeds the
least significant change
114

Background
• Generally unrecognized 20 yrs ago.
• An important public health problem.
• 30% of osteoporotic fractures occur in men.

Secondary Osteoporosis in Men
• Hypogonadism
• Glucocorticoid excess
• Alcoholism, tobacco abuse
• Renal insufficiency
• Gastrointestinal, hepatic
disorders, malabsorption
• Hyperparathyroidism
• Hypercalciuria
• Anticonvulsants
• Thyrotoxicosis
• Chronic respiratory disorders
• Anaemias, hemoglobinpathies
• Immobilization
• Osteoporosis imperfecta (OI)
• Homocystinuria
• Systemic mastocytosis
• Neoplastic diseases
• Rheumatoid arthritis

Incidence of fracture in Men
(Reproduced from Sander et

Incidence of Hip fracture in Men

Incidence of Vertebral fracture in Men
(Adapted from The EPOS
Groups, 2002)

Evaluation
• 70 yrs ore more
• Younger(50-69 yrs)
– Delayed puberty
– Hypogonadism
– Hyperparathyroidism
– Hyperthyroidism
– COPD
– Glucocorticoid , GNRH analogue
– Alcohol ,smoking
123

Lifestyle (osteoporotic or at risk)
• Calcium-1000-1200 mg
• 25(OH)D keep at least 30ng/ml
• Weight bearing -30 -40 mins 3-4 perwks
• Alcohol reduce to 2 or less unit/day
• Stop smoking
124

Treatment
• All men
pharmacological therapy
• hip or vertebral fracture without major trauma
• no spine or hip fracture but whose BMD of the spine, 2.5 SD
or more below
• T-score between –1.0 and –2.5 plus a 10-yr risk of
experiencing any fracture ≥20% or 10-yr risk of hip fracture
≥3% using FRAX
• Men who are receiving long-term glucocorticoid therapy in
pharmacological doses (e.g. prednisone or equivalent >7.5
mg/d)
125

Selection of therapeutic agents
• FDA & EMA approved
– Alendronate
– Risedronate
– Zolendronic acid
– Teriparatide
– Denosumab( ATD for Ca prostate)
126

Not approved for men
• Calcitonin
• Ibandronate,
• Strontium ranelate
• should be used only if the approved agents for male osteoporosis cannot
be administered.
127

Hypogonadal At high risk of fracture
• High risk-Add bisphosphonate /teriparatide to
testosterone
• Borderline high risk & testosterone <6.9 nmol/l-
testosterone only
• High risk- testosterone only if contraindication to
other agents
Ca prostate on ADT & high risk- Pharmacological
treatment
128

Monitoring
• BMD
• at the spine and hip every 1–2 yr If reached a plateau, frequency may be
reduced
• Bone turnover marker (BTM)
• at 3–6 months after initiation of treatment
bone resorption marker-
• serum C-telopeptide of type I collagen (CTX)
• serum or urine N-telopeptide of type I collagen (NTX) for antiresorptive
therapy
bone formation marker
• serum procollagen I N-propeptide (PINP)] for anabolic therapy
129

Novel & Future Therapies- new armaments
• Wnt protein modulating drugs
• Monoclonal antibody Sclerostin antagonist –
Romosozumab.
• PTH & PTHrp analogues, possibly calcilytics-
JTT305/MK-5442
• Inhibitors of bone resorption as Cathepsin K inhibitors-
Odanacatib
• Sequential therapies with 2 or more bone active
substances.
Swiss Med Wkly 2012;142:124-36

Challenges & controversies
• Impact of osteoporosis is high.
• Underlying pathology – still in innovation.
• Racial variation of peak bone mass not known.
• DEXA measurement is not available everywhere.
• Expensive drugs.
• No pharmacologic agent can effectively increase both
non-spine and spine BMD.

Conclusion
• OP is under recognized & under treated, in
postmenopausal and Geriatric populations.
• Diagnostic Tools would be ( BMD & FRAX)
• Non Pharmacologic therapy- Vit D & Ca supplementations
• Pain management with analgesic ladder, physical therapy
and surgery.

• Currently approved drugs are HRT, SERM, Calcitonin,
PTH, Bisphosphonate, Denosumab.
• BP is foundation of therapy
• Newer drugs - Cathepcin K inhibitor-Odanacetib,
oral PTH, oral Calcitonin, Romosozumab.
• Sequential therapy is new theme to combat OP.
Contd….

Bone loss occurs without symptoms
– First sign may be a fracture due to weakened bones
– A sudden strain may lead to a fracture

The Clinical Challenge
• Often asymptomatic1
– Until fracture occurs1
– Even after some fractures (eg, 2/3 of
vertebral fractures are asymptomatic)2
• The challenge to clinicians1:
– Identify patients at high risk for fracture
– Prevent first fracture
1. South-Paul JE. Am Fam Physician. 2001;63:1121-1128.
2. Lenchnik L, et al. AJR. 2004;183:949-958.

Optimizing Fracture Prevention
• Identifying patients at high risk
• Individualized risk assessment
• Management strategies
– Nonpharmacologic modalities
– Pharmacologic therapy
– Modalities to improve adherence and compliance

Identifying High-risk Patients in
Clinical Practice
• Primary goal: fracture prevention-therefore,
select patients based on risk of fracture
• Pharmacologic Therapy
– Patients with osteoporosis by DXA OR
– With a history of hip or spine fractures
• FRAX®
– Quantitative risk assessment
– Helps communicate risk to patients
– May increase treatment of high-risk patients and decrease
treatment of low-risk patients

Case study
• A 43 year old Bangladeshi women with family
history of mother with osteoporosis (mother just
had hip fracture at age 67 yrs).Now she inquires
about her osteoporosis screening as she had
fracture of clavicle during high impact RTA
accident 2 years back.
• She is hypertensive and have sedentary lifestyle.
• She is not habituated to take milk & dairy
products.
• Her BMI is 21.3 kg/m²

Risk factors for Osteoporosis
140
National Osteoporosis Foundation

Risk factors of osteoporosis
Modifible
• low estrogen/testosterone
• Low calcium and vitamin D
• Inactive lifestyle
• Excessive alcohol
• Cigarette smoking
• Hyperthyroidism
• GI conditions which impair
adequate nutrition
• Steroids or Cushing’s
• Proton pump inhibitors
Nonmodifible
• Age (increasing)
• Low BMI (small, low
weight;)
• Ethnicity: Caucasian >
Asian/Latino > African
American
• Family History of Fracture
• Rheumatoid Arthritis

Risk factors of osteoporosis
Modifible
• low estrogen/testosterone
• Low calcium and vitamin D
• Inactive lifestyle
• Excessive alcohol
• Cigarette smoking
• Hyperthyroidism
• GI conditions which impair
adequate nutrition
• Steroids or Cushing’s
• Proton pump inhibitors
Nonmodifible
• Age (increasing)
• Low BMI
• Ethnicity: Caucasian >
Asian/Latino > African
American
• Family History of Fracture
• Rheumatoid Arthritis

Risk factors
• If any of the red flag sign is present there is
high risk of Osteoporosis.

older than 65
 Had a fracture after age 50
 First degree relative has osteoporosis or fracture
 Low BMI
 Smoking
 menopause before age 45
 Low calcium intake
 Poor vision, even with glasses
 Sedentary
 Presence of medical condition
Medications

Medical conditions related to
osteoporosis:
 Hyperthyroidism
 Chronic lung disease
 Cancer
 Inflammatory bowel disease
 Chronic liver or kidney
disease
 Hyperparathyroidism
 Vitamin D deficiency
 Cushing's disease
 Multiple sclerosis
 Rheumatoid arthritis
Drugs :
 Oral glucocorticoids (steroids)
 Cancer treatments (radiation,
chemotherapy)
 Thyroxine treatment
 Antiepileptic medications
 Gonadal hormone
suppression
 Immunosuppressive agents

Case study
146
DEXA scan was done.
T Score was -2.3

DEXA
• "T score" and a "Z score."
• Measured in standard deviations above or
below normal.
• The risk for fracture doubles with every
standard deviation below normal. A person
with T score of -2.0 has an approximately
twofold increased risk of fracture as compared
to someone with a T score of -1.0.

Is osteopenia reversible?
• Mild osteopenia due to a secondery cause as
Vitamin D deficiency, malabsorption from
celiac disease and the underlying condition is
treated, then the osteopenia may reverse.
• Other than this osteopenia does not reverse,
but with the proper treatment, the bone
density can stabilize and the risk for a fracture
decreases.

Case study
• Check for causes of low bone density
• Check routine labs including S. Ca and 25-OH Vit D.
• Check for problems with absorption
» Such as IBD or Celiac Disease
150

Prevention Steps
• Step 1-Get daily recommended amounts of
calcium and vitamin D.
• Step 2-Be physically active everyday to
Improve strength and balance
• Step 3- Avoid smoking and excessive alcohol.
• Step 4- BMD test and treat when appropriate

Calcium and Vitamin D Intake
Recommendations
Life Stage Group
Recommended
Dietary Allowance
of vitamin D
(IU/day)
Recommended Dietary
Allowance Calcium (mg/day)
19–50 years old 600 1,000
31–50 years old 600 1,000
51–70-year-old male 600 1,000
51–70-year-old female 600 1,200
>70 years old 700 1,200
Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D: Report Brief. Washington, DC: IOM; 2010. Available at:
http://www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D.aspx. Accessed September 13, 2013.

Hip Fracture Prevention: Falling
How do Younger Adults Fall? How do Older Adults Fall?

Prevention Treatment
FDA-Approved Therapeutic Options
Estrogen
Alendronate
Risedronate
Ibandronate
Zoledronic acid
Raloxifene
Calcitonin
PTH (teriparatide)
Denosumab

The good news: Osteoporosis is preventable for
most people!
• Healthy diet and
lifestyle are important
for BOTH men and
women.
• Osteoporosis is
detectable and
treatable

Thanks for your patience
THANKS

Osteoprosis: Evaluation, Management and Prevention by Dr Shahjada Selim

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