Osteoporosis PMR Refresher Course

1. Osteoporosis
Dr S L Yadav, MD
Department of Physical Medicine & Rehabilitation
All India Institute of Medical Sciences, New Delhi

2. OSTEOPOROSIS
Osteoporosis Consensus
Development Conference
“ A Metabolic Disease Characterized By:
Decreased Bone Mass
Micro-Architectural Deterioration of Bone Tissue
Increased Bone Fragility and Consequent Increase in Fracture Risk”
• Social impact
• Osteoporosis represents an increasingly serious health and economic problem
around the world .
• Many individuals, male and female, experience pain, disability, and diminished
quality of life as a result of having this condition.
• Arch Intern Med. Jan 12 2009;169(1):25-31
• Endocr Dev. 2009;16:170-90

3. WHO definition of osteoporosis
The World Health Organization’s (WHO) definitions of osteoporosis based on
BMD measurements in white women are summarized in Table below.
Definition
Bone Mass Density
Measurement
T-Score
Normal BMD within 1 SD of the mean
bone density for young adult
women
T-score ≥ –1
Low bone mass (osteopenia) BMD 1–2.5 SD below the mean
for young-adult women
T-score between –1 and –2.5
Osteoporosis BMD ≥2.5 SD below the normal
mean for young-adult women
T-score ≤ –2.5
Severe or “established”
osteoporosis
BMD ≥2.5 SD below the normal
mean for young-adult women
in a patient who has already
experienced ≥1 fractures
T-score ≤ –2.5 (with fragility
fracture[s])
World Health Organization (WHO). Accessed February 6, 2012

4. OSTEOPOROSIS
The “SILENT THEIF”,
• Remains asymptomatic until the
weakened bone fractures.
• Already pandemic proportions
and it is going to get worse
• Common sites of fractures are
spine, femoral neck and distal
radius.

5. The Concentric Circles of Osteoporosis: Fundamental Concepts, related
diseases, and broader dimensions of Osteoporosis.

6. Osteoporosis Prevalence
• 1990 (World) ~ 1.7 million hip #.
• By 2050 this will rise to 6.3.millions
• Frequency of osteoporosis – life time fracture
risk: In Sweden - of a 59 yr old woman
– Hip fracture – 20%
– FA fracture –20%
– Spine or Shoulder fracture – 12-16%
– Combined risk for suffering any one of these 46%
• Corresponding risk for man is approximately half

7. Classification Of Osteoporosis
Type I
• Post-menopausal
osteoporosis
(due to
deficiency of
estrogen and
subsequent
osteoclastic
activation)
• After menopause
women undergo
accelerated bone
loss due to loss
of protection
offered by the
hormone
estrogen
Type II
• Age related or
Senile
osteoporosis
Type III
• Drug induced
osteoporosis
(due to chronic
intake of drugs
such as
corticosteroids
or phenytoin
which interfere
with the
metabolism of
vitamin D and
lead to vitamin D
deficiency)
Am Fam Physician. 2009 Feb 1;79(3):193-200.

8. Symptoms Of Osteoporosis
• Low back pain
• Easy fractures of bones (particularly of the hip, wrist and spine) after minor
trauma (low impact trauma fractures).
• Symptoms of vertebral fracture
• The pain is described variably as sharp, nagging, or
dull; movement may exacerbate pain; in some
cases, pain radiates to the abdomen
• Pain is often accompanied by paravertebral muscle
spasms exacerbated by activity and decreased by
lying supine
• Patients often remain motionless in bed because of
fear of causing an exacerbation of pain
Am Fam Physician. 2009 Feb 1;79(3):193-200
Dana Jacobs-Kosmin, et al medscape, updated on 15th oct 2014

9. Who may have osteoporosis
• Weight <51 kg, kyphosis
• Self-reported humped back
• <20 teeth.
• Wall-occiput distance >2 cm and rib-
pelvis distance ⩽2 finger breadths are the most
useful physical examination signs for detecting
spinal fractures.
• Height measurement with a stadiometer at each
visit may be useful.
Evid Based Med 2005;10:123

10. DIAGNOSIS
Imaging options include
• X rays
• Densitometry
• Single-photon absorptiometry (SPA)
• Dual-photon absorptiometry (DPA)
• Dual-energy x-ray absorptiometry (DXA)
• Quantitative computed tomography (QCT) scanning
• Magnetic resonance imaging (MRI)
• Bone scanning
• Single-photon emission computed tomography (SPECT)
scanning.
Dana Jacobs-Kosmin, et al medscape, updated on 15th oct 2014

11. Assessment of Fracture Risk by Using the
Fracture Risk Assessment Tool (FRAX)
• The aim of FRAX is to provide an assessment tool for the
prediction of fractures in men and women with use of clinical
risk factors with or without femoral neck bone mineral density.
Arch Osteoporos. 2015 Dec;10(1):204.

12. Components of Management
• Prevention
– Risk factor Reduction
– Nutritional Counseling
• Treatment of disease
– Pharmacotherapy
– Exercise Program for conditioning & Wt. bearing
– Mechanical Stimulation (Physical Modality)
• Prevention & treatment of complications
– Patient & Family Education in Posture Care & Fall Prevention
– Orthosis
– Specific problems
– Pain management

13. Risk Factors Reduction
• Endogenous
– Genetic Factors
• White and Asian
• Petite body habitus
• Family history
– Age
• Advanced
– Sex
• Female
– Loss of ovarian function
• Premature menopause
• Amenorrhea
• Exogenous
– Nutrition
• Low calcium intake
• High phosphorous intake
• High protein intake
• High sodium intake
– Lifestyle factors
• Smoking
• High caffeine intake
• Inactivity
– Immobilization
– Medications
• Glucocorticoids
• Thyroid hormones

14. Nutritional Counseling
• Calcium : 1000-1500 mg/day: Calcium carbonate
(40 percent elemental calcium), Calcium citrate
(21 percent elemental calcium), Calcium
gluconate (9 percent elemental calcium), Calcium
lactate (13 percent elemental calcium), CCM
highest bioavailability.
Supplementation
• Vitamin D : 400-800 I.U./day
• Phosphorus : 1250mg/day
• Magnesium : 360 mg/day
• Foods High in Oxalates and Phytates: Spinach, Soy
Nuts, Almonds, Cashews, Sesame Seeds etc.

15. Calcium and Vitamin D
• Most common is calcium citrate and calcium
carbonate.
• Calcium carbonate requires acidic environment -
should be taken with meals and not be taken with
antacids (achlorhydria).
• Vitamin D deficiency results in failure to attain
peak bone mass in adolescence, has a key role in
the pathogenesis of osteoporosis in the elderly,
• Vitamin D deficiency in the elderly has been
recognized as an epidemic.
• Holick MF (2005) J Nutr 135: 2739S–2748S

16. • Sun exposure is insufficient for adequate
levels of vitamin D
• Holick MF (2006) Mayo Clin Proc 81: 353–373
• Current recommendations:
– 5–10 minutes of exposure of the arms and legs or
the hands, arms, and face
– 2 or 3 times per week
– With at least 800 IU of Vitamin D orally daily
• Holick MF (2004) Am J Clin Nutr 80: 1678S–1688S
Sunlight and Vitamin D

17. Pharmacologic Options
Antiresorptive: Act on
osteoclasts and stabilize
bone
• Calcium
• Estrogen
• Calcitonin
• Bisphosphonates
• Selective estrogen
receptor modulators
• Thaizide diuretics
• Ipriflavone
(Investigational)
Formation: Act on
osteoblasts and increase
bone formation
• Vitamin D
• Anabolic steroids
• Parathyroid hormone
• Growth factors
(Investigational)
• Fluoride (Investigational)

18. Rational for Non-Pharmacological
Approach
• Though, Pharmacologic approaches represent
the cornerstone of treatment,
• Limitations:
– Long term compliance with medication regimens
– Adverse effects of drugs
– Affordability of newer medications
– Conflict in acceptability of long term treatment.

19. Rational for Non-Pharmacological
Approach
• Nonpharmacologic therapies should, therefore,
complement the traditional pharmacologic
treatment of osteoporosis
– Calcium and vitamin D supplementation
– Exercise programs
– Fall prevention
– Orthoses
– Kyphoplasty

20. Osteoporosis: Rehabilitation Program
Individualized- Need Based
Active Involvement of Patient & Family
Goal- Return to Highest Level of Functional
Independence
Improving Quality of Life
Focus- Minimize Further Bone Loss,
Care of Fragile Skeleton,
Help Prevent Fracture and
Decrease Pain

21. • Strong back extensors reduce the risk of developing
thoracic vertebral compression fractures
Sinaki M et al. (1996) Mayo Clin Proc 71: 951–956
• Spinal mobility in patients with osteoporotic
vertebral fractures also improved with the
strengthening of back extensors
• Spinal mobility is likely to be associated with back
extensor strength.
Miyakoshi N et al. (2005) Osteoporos Int 16: 1871–1874
Evidence for Exercise

22. Benefits of Exercise
• Increased bone mass
• Restoration of bone architecture and strength
• Increased muscle strength
• Improved balance and coordination
• Better flexibility
• Decreased falls and better post-fall condition

23. The osteoporotic patient should participate in
– Regular weight-bearing
• Weight-bearing exercise stimulate osteoblasts
• Walking, running, and impact exercises.
– Thoracic-stabilization exercises.
• Thoracic stabilization exercises strengthen the
back extensor, help to improve posture and
reduce the risk of falls.
• Instruct in appropriate body mechanics and
precautions in order to minimize fracture risk.
Recommendation for Exercise

24. Activities restriction
• Flexion-based exercises such as abdominal crunches,
lifting heavy weights, and excessive twisting and
bending should be avoided

25. Fall Risk Statement
• Falls a significant cause of morbidity and mortality
• Each year, falls occur in 1/3 of older adults
• The incidence of fall is the best predictor of future
fractures in people >80yrs old.
• Patients with osteoporosis at highest risk for
developing fracture and resulting functional
limitations secondary to falls.
Tinetti ME et al. (2006) Gerontologist 46: 717–725

26. Fall Risk Statement
• Associated factors for Falls:
–Gait And Balance Disorders
–Weakness, Dizziness
–Environmental Hazards
–Confusion
–Visual Impairment
–Postural Hypotension.
–Sedating and Psychoactive Medications
–Use of Diabetes Medications, and increased
patient-to-nurse ratio.
• Rubenstein LZ et al. (1996) Clin Geriatr Med 12: 881–902
• Krauss MJ et al. (2005) J Gen Intern Med 20: 116–122

27. • Assistive devices such as properly-fitted canes and
walkers should be used to facilitate a more steady gait.
• Concomitant conditions result in abnormal gait and,
therefore, increase fall risk:
Cervical myelopathy, lumbar spinal stenosis, vitamin B12
deficiency, normal pressure hydrocephalus, and PD
Lim MR et al. (2007) J Am Acad Orthop Surg 15: 107–117
• These diagnoses should be considered in the
differential diagnosis of recurrent falls; require
aggressive, appropriate treatment in order to
reduction of further risk of fracture.
Fall Risk Statement

28. Hip Protectors
• Most hip fractures are a result of a direct fall onto
the hip (~90%)
– Cummings et al. J Gerentol 1989;44;M107-11
– Lauritzen JB (1996) Bone 18: 65S–75S
• Absorb the impact of a fall and, therefore, reduce the
risk of hip fracture.

29. Hip Protectors
• As a part of undergarments with
padding over the trochanters
• Energy shunting & Energy
absorbing
• In vitro biomechanical studies
have demonstrated the force-
attenuation properties of hip
protectors.
• Demonstrate a 68% reduction in
peak force delivered to hip at the
time of impact
– Kannus P et al. (1999) Bone
25: 229–235

30. Hip Protectors : Compliance
• Compliance is only 25%.
Van Schoor NM et al. (2002). Osteoporos Int 13: 917–924.
• Noncompliance one of the main
limiting factors in the effectiveness
particularly with regard to long-
term adherence.
Kannus P and Parkkari J (2006). Age Ageing 35: ii51–ii54.
• Factors associated with
noncompliance include
– Discomfort on wearing,
– Dislike of their personal appearance
– Disagreement about their fracture risk
Patel S et al. (2003). Rheumatology (Oxford) 42: 769–772.

31. • Literature controversies
• A recent review analyzed 14 clinical trials
– Marginally statistically significant reduction in hip fracture in nursing care
or residential care settings,
– No reduction in hip fracture incidence in community dwelling settings.
Parker MJ et al. (2006) BMJ 332: 571–574.
• More favorable studies have identified hip protectors as a cost-effective
strategy
• Despite the controversies, hip protectors offer a safe, noninvasive option and
might reduce hip fracture risk (reduce risk of fractures by 53%).
Fleurence RL (2004). Int J Technol Assess Health Care 20: 184–191.
Singh S et al. (2004) J Rheumatol 31: 1607–1613.
Hip Protectors: Effectiveness

32. Spinal Supports: Objectives
• To minimize the incidence of kyphosis in at risk population
• To decrease anterior wedging and compressive forces on fragile vertebral
bodies as a preventive measure
• To compensate for the weak erector spinae muscles, the anatomic
extrinsic support of the spine
• Proprioceptive reminder to extend the thoracic spine.

33. Spinal Supports : Types
• Hyper extension brace
• TLSO : Taylors brace
• Jewet type

34. PTS: Weighted Kypho-Orthosis
• Counteract spinal
flexion and weight of
anterior section of
upper trunk
• Helps to shift COG and
encourages use of back
extensors for upright
posture.
• Weighted pouch
provides tactile stimulus
for posture training

35. Posture-Training Support
• 17 of 23 patients reported “Significant" improvement
in their symptoms following use of the brace
(i.e., pain reduction in patients with acute vertebral compression fracture).
Kaplan RS and Sinaki M (1993). Mayo Clin Proc 68: 1171–1176
• Improved back extensor strength correlate with
decreased kyphosis and diminished vertebral fracture
risk.
Sinaki M et al. (2002). Bone 30: 836–841
Kaplan RS et al. (1996). Mayo Clin Proc 71: 235–241
Sinaki M et al. (1996) Mayo Clin Proc 71: 951–956

37. The American Society for Bone and Mineral
Research (ASBMR) published guidelines on long-
term bisphosphonate use, 2016
After 5 years of oral bisphosphonates or 3 years of intravenous
bisphosphonates, reassessment of risk should be considered.
In women at high risk (e.g., older women, those with a low hip T-score or high fracture
risk score, those with previous major osteoporotic fracture, or those who fracture on
therapy), continuation of treatment for up to 10 years (oral) or 6 years (intravenous),
with periodic evaluation, should be considered.
The risk of atypical femoral fracture, but not osteonecrosis of the jaw,
clearly increases with the duration of bisphosphonate therapy, but such
rare events are outweighed by vertebral fracture risk reduction in high-
risk patients.
For women not at high fracture risk, a drug holiday of 2 to 3 years can be considered
after 3 to 5 years of BP treatment.

38. Guidelines from the American Association
of Clinical Endocrinologists (AACE, 2010)
1. First-line agents: alendronate, risedronate,
zoledronic acid, denosumab
2. Second-line agent: ibandronate
3. Second- or third-line agent: raloxifene
4. Last-line agent: calcitonin
Treatment for patients with very high fracture risk
or in whom bisphosphonate therapy has failed:
teriparatide

39. A clinical practice guideline from the American
College of Physicians (ACP) recommends offering
pharmacologic treatment to women with known
osteoporosis, to reduce the risk of hip and
vertebral fractures.
The ACP recommends use of any of the following
agents:
Alendronate
Risedronate
Zoledronic acid
Denosumab

40. The ACP recommends against the use of estrogen or estrogen
plus progestogen or raloxifene for the treatment of osteoporosis
in postmenopausal women. Additional recommendations,
based on low-quality evidence, include the following:
In women with osteoporosis, pharmacologic treatment
should last for 5 years; generic drugs should be used when
possible.
Monitoring of bone mineral density (BMD) during the 5
years of treatment in women with osteoporosis is not
advised, as evidence suggests that fracture risk may be
reduced regardless of BMD changes
For women aged 65 and older who have osteopenia and
are at high fracture risk, decisions to treat should take into
account patient preference, fracture-risk profile, benefits,
harms, and price of medications

41. According to a study funded by the National
Institutes of Health (NIH), osteoporosis will
develop in fewer than 10% of older,
postmenopausal women during the following
rescreening intervals
Women with normal BMD or mild osteopenia - Approx 15 years
Women with moderate osteopenia - Approximately 5 years
Women with advanced osteopenia - Approximately 1 year

42. 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

43. Medications
Antiresorptive Agents Anabolic Therapies
 Bisphosphonates
 Alendronate
 Risedronate
 Ibandronate (Oral and IV)
 Zoledronic Acid (IV)
 Estrogen Agonist/Antagonists
 Raloxifene
 Estrogen/Estrogen-Progestin
Combinations
 Calcitonins (Nasal spray)
 Teriparatide
In addition, potentially treatable
underlying causes of
osteoporosis such as
hyperparathyroidism and
hyperthyroidism should be ruled
out or treated if detected.
Ann Intern Med. Dec 6 2011;155(11):751-61

44. Pharmacologic Therapy
Recommendations
The National Osteoporosis Foundation (NOF) recommends that
pharmacologic therapy should be reserved for postmenopausal
women and men aged 50 years or older who present with the
following:
• A hip or vertebral fracture (vertebral fractures may be clinical or
morphometric [i.e. identified on a radiograph alone])
• T-score of -2.5 or less at the femoral neck or spine after appropriate
evaluation to exclude secondary causes
• Low bone mass (T-score between -1.0 and -2.5 at the femoral neck or
spine) and a 10-year probability of a hip fracture of 3% or greater or a
10-year probability of a major osteoporosis-related fracture of 20% or
greater based on the US-adapted WHO algorithm
National Osteoporosis Foundation. Clinician's Guide to Prevention and Treatment of
Osteoporosis Accessed January 13, 2011.

45. 2014 NOGG guidelines: Global
strategies
Intervention Effect on outcomes
BMD Spine fracture Hip fracture
Exercise A B B
Calcium (± vitamin D) A B B
Dietary calcium B B B
Smoking cessation B B B
Reduced alcohol consumption C C B
Fall prevention programmes C C
Hip protectors B
Osteoporosis is defined operationally on the level of bone mass, measured as BMD.
Two thresholds of BMD have been defined by the World Health Organization, on the basis
of the relationship of fracture risk to BMD.
‘Osteoporosis’ denotes a value for BMD that is 2.5 standard deviations (SDs) or more
below the young adult mean value for women (T-score equal to or less than –2.5 SD).
A second, higher threshold more appropriate for epidemiological studies describes ‘low
bone mass’ as a T-score that lies between –1 and –2.5 SD.
‘Severe’ or ‘established’ osteoporosis denotes osteoporosis as defined above in the
presence of one or more documented fragility fractures.

46. Vertebral
fracture
Non-vertebral
fracture Hip fracture
Alendronate A A A
Etidronate A B nae
Ibandronate A A# nae
Risedronate A A A
Zoledronic acid A A A
Denosumab A A A
CalcitrioL A B nae
Raloxifene A nae nae
Strontium ranelate A A A#
Teriparatide A A nae
Recombinant human PTH (1-
84) A nae nae
HRT A A A
2014 NOGG guidelines: Anti-fracture efficacy of approved
treatments for postmenopausal women with osteoporosis when
given with calcium and vitamin D

47. Bisphosphonates
• Bisphosphonates are the most commonly used agents for osteoporosis. They have
been employed for both treatment and prevention. Oral and intravenous options
are available
• Alendronate is approved for the treatment of osteoporosis in men, in
postmenopausal women, and in patients with glucocorticoid-induced
osteoporosis. It has been shown to increase spinal and hip mineral density in
postmenopausal women
• Risedronate is a delayed-release, given daily, weekly, or monthly. Risedronate
reduces vertebral fractures by 41% and nonvertebral fractures by 39% over 3
years. Ibandronate is another bisphosphonate that can be given orally once a
month.
• Ibandronate : Ibandronate, a newer BP, has the greatest number of options in
terms of route and frequency of administration. Ibandronate has the potential
advantage in comparison to other BP options of offering patients and clinicians a
highly variable choice that may align most closely with an individual’s preference
and as a consequence could improve compliance and adherence.
1. Arch Intern Med. Jun 13, 2011;171(11):998-1004
2. Int J Womens Health. 2014 Dec 17;7:7-17

48. Frequency Time of day Instructions
Alendronate
10 mg (treatment)
every day first thing in morning, at least 1/2
hour before eating
Take with 250ml (8 oz) plain water.
Stay upright (don’t bend or lie down)
for the first 1/2 hour AND until after
the first food of the day
Alendronate
70 mg
70 mg + 2800 IU vitamin D or
70 mg + 5600 IU vitamin D
once a week same as above same as above
Etidronate
400 mg
The white etidronate
tablet is taken daily for
two weeks followed by
a blue calcium tablet
taken daily for an
additional 10 weeks
Take the white etidronate tablet (first
two weeks) mid morning, mid
afternoon or evening (at least two
hours before and after eating)Take the
blue calcium tablet (next 10 weeks)
with food
Take the white etidronate tablet with a
full glass of water. Do not eat or take
any additional supplements or
vitamins for 2 hours before or after
taking etidronate. Take the blue
calcium tablet with food.
Risedronate
5 mg
every day first thing in morning, at least 1/2
hour before eating
Take with a full glass of water. Stay
upright (don’t bend or lie down) for
the first 1/2 hour AND until after the
first food of the day
Risedronate
35 mg
once a week same as above same as above
35 mg (DR=delayed release) once a week Take first thing in morning WITH
breakfast
Take with full glass of water. Stay
upright (don’t bend or lie down) for
the first 1/2 hour
Ibandronate One 150 mg tablet
taken once monthly or
one 2.5 mg tablet taken
once daily
Zoledronic acid
5 mg
once a year not applicable Given as a 15-minute intravenous (IV)
infusion

49. Bisphosphonates
• Bind to hydroxyapatite crystals at sites of active bone resorption
inhibiting osteoclast function
First Generation
Bisphosphonates
• Contain minimally
modified side
chains (R1, R2) e.g.
medronate,
clodronate,
etidronate &
tiludronate
Second generation
bisphosphonates
• 10 to 100 times
more potent e.g.
alendronate and
pamidronate
Third generation
bisphosphonates
• Upto 10000 times
more potent than
first generation e.g.
risedronate and
zoledronate
15P91-037FContent developed by Clinical Medicine Informatics – India for Abbott Healthcare Private Limited. © 2015 Abbott. All rights reserved.

50. Bisphosphonates: Zoledronic acid
Zoledronic acid
• Intracellular accumulation of Zolephos inhibits osteoclastic activity by
inhibiting enzymes like Farnesyl pyrophosphate synthase (FPPS) &
Geranylgeranyl pyrophosphate synthase (GGPPS) & also leads to
osteoclast apoptosis-Therefore, loss of resorptive function.
• It is the most potent bisphosphonate available. It increases BMD at
the spine by 4.3-5.1% and the hip by 3.1-3.5%, as compared with
placebo.
• Over 3 years, it reduces the incidence of spine fractures by 70%, hip
fractures by 41%, and non-vertebral fractures by 25%.
N Engl J Med. Nov 2012;367(18):1714-23
Biochim Biophys Acta. 2014 Apr 4;1841(4):569-73

51. HORIZON Pivotal Fracture Trial
(PFT)
Objective:
• To evaluate the potential of once yearly zoledronic acid 5 mg to
decrease fracture risk in postmenopausal women with osteoporosis
• 3-year, randomized, double-blind, placebo-controlled clinical trial
• 7736 women from 240 clinical centers in 27 countries
• Treatment Annual infusion of either zoledronic acid 5 mg or placebo
• Calcium 1000–1500 mg/d; vitamin D 400–1200 IU/d
• Follow-up visits at 6, 12, 24 and 36 months
• Telephone interviews every 3 months
J Bone Miner Res. 2014 Dec 26.
Maturitas. 2014 Mar;77(3):287-93
J Clin Endocrinol Metab. 2013 Feb;98(2):557-63

52. HORIZON-Recurrent Fracture Trial
(RFT)
Primary Objective
• Reduce the rate of new clinical
fractures after surgical
procedure for low-trauma hip
fracture
Secondary Objectives
• Reduce the risk of clinical
vertebral fractures
• Hip fractures , non-vertebral
fractures
• Increase BMD at the total hip
and femoral neck of the non-
fractured hip at months 12 and
24
• Double-blind, placebo-
controlled RCT
J Bone Miner Res. 2014 Dec 26.
Maturitas. 2014 Mar;77(3):287-93
J Clin Endocrinol Metab. 2013 Feb;98(2):557-63

53. Treatment
• Annual infusion of either zoledronic acid 5 mg or placebo
• Loading dose of vitamin D 50,000–125,000 IU
• Calcium 1000–1500 mg/d; vitamin D 800–1200 IU/d
• Follow-up visits at 6, 12, 24, and 36 months
• Telephone interviews every 3 months starting at month 9
J Bone Miner Res. 2014 Dec 26.
Maturitas. 2014 Mar;77(3):287-93
J Clin Endocrinol Metab. 2013 Feb;98(2):557-63

54. Conclusions
With zoledronic acid there is reduced :
• Risk of New vertebral fractures by
70% after 3 years
• Risk of Hip Fractures by 41% after 3
years
• Risk of Clinical Non-Vertebral
fracture by 25% after 3 years
• Zoledronic acid produced significant
increase in BMD over 3 years
 Hip – 6.01% from Baseline
 Femoral Neck – 5.06 % from Baseline
 Lumbar Spine – 6.75 %from Baseline
• Zoledronic acid reduced bone markers
after 1 year
 C-Telopeptide – 59%
 N Terminal Propeptide – 58%
 Bone specific alkaline Phosphatase –
30%
J Bone Miner Res. 2014 Dec 26.
Maturitas. 2014 Mar;77(3):287-93
J Clin Endocrinol Metab. 2013 Feb;98(2):557-63

55. Conclusions
• Zoledronic Acid had an absolute relative reduction of 35% for New
Clinical
Fractures as compared to Placebo
• Zoledronic acid had 28% reduction in mortality risk as compared to
placebo
• Zoledronic acid increased BMD
BMD at Hip increased 5.5% after 3 years
BMD at femoral neck increased 3.6% after 3 years
J Bone Miner Res. 2014 Dec 26.
Maturitas. 2014 Mar;77(3):287-93
J Clin Endocrinol Metab. 2013 Feb;98(2):557-63

56. Ibandronate: Mechanism of Action
• Drug binds to hydroxyapatite crystals in the bone matrix
• During osteoclast bone resorption, is released locally and taken
up by osteoclasts
• Inactivation and/or apoptosis of the osteoclasts
• Inhibits intracellular mevalonate (3-hydroxy-3-methylglutaryl-
coA reductase) pathway apparently at the farnesyl
pyrophosphate synthase
Nihon Yakurigaku Zasshi. 2014 Jun;143(6):302-9

57. The MOVER trial
• Examined the relationship between gains in BMD and the occurrence of
vertebral fractures by analyzing the gains in hip BMD in the initial 6 months
and the subsequent development of vertebral fractures over time.
• Compared the hip BMD gains in ibandronate- or risedronate-treated patients
who developed vertebral fractures with those who had not developed vertebral
fractures during the 3 years of treatment
• 376 patients in the ibandronate 0.5 mg group, 382 in the ibandronate 1 mg
group, and 376 in the risedronate group
• Greater gains in hip BMD during the first 6 months of treatment were
associated with a reduction in the risk of subsequent vertebral fractures during
the duration of treatment, and suggested that measurement of hip BMD gain
at that time could lead to a prediction of the risk of the future vertebral
fracture incidence
Calcif Tissue Int. 2014; 95(6): 557–563.

58. Parathyroid hormone
• Teriparatide is a human recombinant parathyroid hormone (1-
34) (PTH [1-34]) and is the only available anabolic agent for the
treatment of osteoporosis.
• It is indicated for the treatment of women with postmenopausal
osteoporosis who are at high risk of fracture, who have been
intolerant of previous osteoporosis therapy, or in whom
osteoporosis treatment has failed, as well as to increase bone
mass.
• It is indicated in men with idiopathic or hypogonadal
osteoporosis who are at high risk of fracture, who have been
intolerant of previous osteoporosis therapy, or in whom
osteoporosis therapy has failed
Dana Jacobs-Kosmin, et al medscape, updated on 15th oct 2014

59. Teriparatide dose
• The dosage is 20 mcg/day as a subcutaneous inj. for a
period of max. 24 months
Rationale behind continuing teriparatide
therapy for 18-24 months:
• Anabolic effect of teriparatide is manifested both by an increase in bone
formation at previously quiescent surfaces, an effect termed
“modelling”, and by overfilling of remodelling sites, both of which lead
to increased bone mass
• Even though a single modelling cycle takes about 90-130 days this is
not indicative of restoration of bone strength to full potential
• This time interval may be enough to show fracture union but to prevent
fracture recurrence a much longer duration of treatment is warranted.

60. Calcitonin
• Calcitonin-salmon is a hormone that decreases osteoclast activity,
thereby impeding postmenopausal bone loss.
• It is indicated for the treatment of women who are more than 5 years
post menopause and have low bone mass relative to healthy
premenopausal women
• Calcitonin is an option for patients who are not candidates for other
available osteoporosis treatments.
• Calcitonin significantly reduced the severity of acute pain in recent
osteoporotic vertebral compression fractures . Pain at rest is reduced
by week
1.Dana Jacobs-Kosmin, et al medscape, updated on 15th oct 2014
2. Osteoporos Int. 2012 Jan;23(1):17-38.

61. Calcitonin dose
• Prolonged administration of parenteral calcitonin, by injections of 100 IU
every 1 or 2 days, can prevent postmenopausal or post-ovariectomy bone loss,
and is also able to increase trabecular bone mass among patients presenting an
established osteoporosis.
• In addition to the ease of administration compared with the injectable forms,
nasal calcitonin is much better tolerated, the side effects being rare and
generally negligible.
• A prolonged administration of 200 IU intranasal calcitonin acutely inhibits
parameters of bone resorption and can increase lumbar spine bone mineral
density (BMD) by 1.7%-3.3% after 1 year.
• Lower doses also appear to be efficient to prevent early postmenopausal bone
loss, but the data are conflictual.
Bone. 2002 May;30(5 Suppl):75S-79S.

62. End note
• Osteoporosis is the most common metabolic bone disease around the
world and can result in devastating physical, psychosocial, and economic
consequences.
• It is often overlooked and undertreated, however, in large part because it
is so often clinically silent before manifesting in the form of fracture.
• A planned approach to prevent osteoporosis and also the timely
diagnosis of this chronic disease entity prevents the disabling
consequences and fractures .

63. Thanks….