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Osteoporosis
Definition
Systemic skeletal
disease.
Low bone mass.
Microarchitectural
deterioration of bone
tissue.
Damage accumulation
Low strength

Increase in bone fragility.

Susceptibility to fracture.
Hip,spine,wrist ,ankle
,humerus

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 Osteoporosis
A major health problem.

Consequences include - illness, pain,

functional limitations, reduced quality of
life, loss of independence, inability to work
and even death.

1 out of 3 women (33.3%) &1 out of 8 men

(12.5%) suffer from osteoporosis related
fracture in lifetime

Grave disease, highly under diagnosed

and under treated.
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 Diagnosis: x-ray -No
Insensitive

Apparent only after 50 -70 %

reduction in bone mass

High radiation

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 Bone Mineral Density
DEXA :DUAL Energy
ULTRASONIC BONE X-ray Absorptiometry-
DENSITOMETER Gold standard

Single X-ray
Lower accuracy Absorptiometry /
No ionizing Quantitative CT
radiation

GOLD STANDARD
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 WHO Classification
Normal : BMD within 1 to -1 SD

Osteopenia :BMD -1 - 2.5 SD

Osteoporosis :BMD -2.5 SD or more

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 MANAGEMENT
Change of life style most
important

Regular exercise must

Stop smoking and alcohol

intake

If on steroids / phenytoin
taken for long then
alendronate must be given

Adequate exposure to sun

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 CALCIUM AND VITAMIN D
Calcium and Vit D are main stay.
Calcium 1000 mg /day with SERM/Alendronate/HT

1500 mg /day if no therapy

Calcium carbonate does not cause renal calculi

Vitamin D :Dose 400 IU < 70 yrs

700 1000 IU > 70 yrs

CALCITRIOL
watch for Hypercalcemia / Hypercalciurea on long
term use
No extra benefit for idiopathic postmenopausal
osteoporosis

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 Updated National Osteoporosis Foundation
(NOF) guidelines 2008
After introduction of FRAX pharmacologic treatment is
recommended for postmenopausal women over age 50 with
A hip or vertebral (clinical or morphometric) fracture.
T-score 2.5 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 3% or a 10-
year probability of any major osteoporosis-related fracture 20%
based on US-adapted WHO absolute fracture risk model (FRAX).

NOF. Clinicians Guide. 2008;1-36.

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Drugs available and on horizons
Antiresoptives- Inhibit Anabolic stimulate bone
osteoclastic activity fromation
HT PTH

Strontium
SERMS
Flouride
Bishphosphonates
IGF-1

New drugs in pipeline PREVOS / SOTI / TROPOS

Tibolone

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 ESTROGEN
Womens Health Initiative (WHI)

16,608 postmenopausal women

E-P combination to assess CHD / breast CA

RR spine and hip fractures = 0.66

Heart and Estrogen/progestin Replacement Study (HERS)-No

reduction in fracture incidence

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 HT
Indicated :

For relief of vasomotor symptoms

Urogenital symptoms

Not for prevention or treatment of osteoporosis.

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 SERMS- RALOXIFENE (EVISTA)
Raloxifene
Non-steroidal benzothiopene binds Estrogen receptor, Inhibits bone
resorption without stimulating endometrium

Multiple Outcomes of Raloxifene Evaluation (MORE)

- Studied 60 mg and 120 mg doses on patients with and without

VCF(vertebral clinical fracture)
- 2.6% BMD compared to placebo

- 30% (prior VCF) and 50% (no prior VCF) reduction in VCF

- RR of DVT = 3
- Significant reduction in incidence of breast CA

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 SERM- Bazedoxifene

Bazedoxifene binds to both ERs with high affinity

Agonist on skeletal tissue, with bone turnover reduced

by 2025% with doses of 20 or 40 mg daily

Antagonist on breast tissue and uterine tissue

Side effects are hot flashes

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 Selective Estrogen Receptor- Agonist, MF-101
( 22 chinese herbal medicines)
MF-101-isolated active compounds, liquiritigen and
chalcone, demonstrated selectivity for ER-

No effect on growth of breast cancer cells

No stimulation endometrium in Phase II trial

Effective in reducing the frequency and severity of hot

flashes in postmenopausal women.

In order to confirm the safety and efficacy of MF-101,

larger Phase III trials have been planned for 2009.
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 TSEC & SERMS
An appealing alternative strategy is the use of a tissue-
specific estrogen complex (TSEC). TSECs combine an
estrogen and a SERM, taking advantage of the tissue-
specific anti-estrogenic properties of the SERM in order
to counteract the effects of estrogen on the uterus and
breast. This combination, therefore, requires no
progestogen.

Pinkerton JV, Utian W, Constantine G, Olivier MD, Pickar J. SMART-2: A phase III study of the
efficacy and safety of bazedoxifene/conjugated estrogens for treatment of menopausal
vasomotor symptoms. Proceedings and abstract. Menopause. 2007;14(Suppl. 2):1081.

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 BISPHOSPHONATES

Adverse effect
Poor intestinal absorption

N2 containing

GI upset

Oesophagitis

Patient should remain upright

,take with a glass of water

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 Alendronate (Bishphonate)
Non hormonal

FDA approved

For prevention as well as treatment

Increases BMD by 8.8% in lumbar spine and 6% in fracture

NOF

48% reduction in # NOF and spine fractures

Can be given for 5- 10 yrs or treatment free holidays can

be givne.
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DOSE:daily or weekly

Except very elderly and poor renal function

PREVENTION :5mg per day,35 mg /week

Treatment : 10 mg/day , 70 mg/week

CARE
Empty stomach consumption

Calcium to be taken after 4 hrs

Longest duration tried upto 5 yrs

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 RISEDRONATE (ACTONEL)
The Vertebral Efficacy with Risedronate
Therapy (VERT) Study
North American and Multinational Arms

Randomized, double-blind, placebo-controlled study of 2458

postmenopausal women c >1 VCF

Treatment with 5mg/day for 3 years:

incidence of new VCF by 41%

- BMD 5.4% vs. 1/1% (placebo)

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 RISEDRONATE
Not recommended in patients with renal impairment

Contra Indications Side Effects

Hypocalcaemia Dysphagia
Hypersensitivity Esophagitis
Inability to sit upright for Esophageal
30 min.
Gastric ulcer

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 CALCITONIN
32 amino acid polypeptide produced by the parafollicular C cells of the
thyroid in response in plasma Calcium

Binds to osteoclast cell receptor (-) effect)

FDA approved for treatment but NOT prevention of

postmenopausal osteoporosis

Women > 5yrs after menopause

Consider in women with estrogen-dependent neoplasm, H/o DVT, renal

insufficiency, or active GI pathology

Nasal spray (preferred) and injectable forms

Miacalcin: 200 IU qd
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 CALCITONIN
Prevent Recurrence of Osteoporotic Fracture
Study (PROOF)
5-yr, multicenter, double-blind, randomized
study 1255 patients

817 pts c 1-5 previous VCF

Nasal spray salmon calcitonin (100, 200, 400 IU)

36% reduction in VCF (33% for entire group)

Lumbar BMD 1.2% during only 1st yr

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 CALCITONIN
Analgesic Effects

Analgesic for acute and chronic pain of VCF

Apparent by = 1 week

Mechanism likely a central effect (hypothalamus,PAG,

dorsal horn)
Side Effects
Minimal: rhinitis, back/joint pain, HA
Resistance
Antibodies in 20% PROOF patients

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 CALCITONIN

INJECTABLE 100 IU/day s/c BIOCALCIN

NASAL SPRAY 200 IU /day MIACALCIN

Inhibits osteoclast

Increases BMD by inhibiting osteoclast, decrease vertebral

fractures

Good for pain in spinal fractures

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 ANABOLIC AGENTS
PTH

Fluoride

IGF-1

Strontium

PREVOS / SOTI / TROPOS

Tibolone

Statins
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 PTH
Forteo
Teriparatide = generic name
Synthetic teriparatide has been used in many clinical trials
Forteo is the recombinant DNA PTH 1-34 manufactured by
Eli Lilly
Genetically engineered fragment of native PTH (84 amino
acids)
FDA approved in US and Europe
24 month treatment period
$ 600/month
A Recombinant DNA prep with all 84 amino acids (Preos) is
in clinical trials

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 PTH (Forteo)
Neer et al. (2001) NEJM 344(19), 1434-1441

Landmark Placebo controlled, randomized trial of 1637

postmenopausal women with prior vertebral fracture

20g vs 40g Forteo

RR VCF = 0.35 for 20g dose and 0.31 for 40g

Lumbar spine BMD - 9%

Femoral neck BMD - 3%

Distal radius BMD - 2%

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 PTH (Forteo)
Side Effects
Hypercalcemia (rare clinical significance)
Leg cramps, dizziness
Dose dependent increase in osteosarcoma in rats
None in 2000 Forteo patients

Contraindications
Patients with open epiphysis
Paget disease
Prior skeletal malignancy
Metabolic bone diseases
Pre-existing hypercalcemia (Primary hyperparathyroidism)

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 New Drug Denosumab
Denosumab is a fully human monoclonal
antibody to the receptor activator of
nuclear factor- kB ligand (RANKL) that
blocks its binding to RANK, inhibiting the
development and activity of osteoclasts,
decreasing bone resorption , and
increasing bone density

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 Dose of Denosumab
Denosumab given 60 mg subcutaneously
twice yearly for 36 months associated
with reduced risk of vertebral, nonvertebral
and hip fractures in postmenopausal
women with osteoporosis

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 ORTHOSIS
Improved back extensor strength (A) The posture training support vest
correlate with decreased kyphosis and contains 680 g (1.5 pound) weights to
diminished vertebral fracture risk. remind the patient to extend their
thoracic spine.
(B) The Spinomed brace consists of
a back pad and strap system to
strengthen the trunk muscle and
improve posture.
(C) Hip protectors contain padding
over the trochanters to help absorb the
impact of a fall
Hip protectors dont reduce incidence of Sinaki M et al. (2002) Stronger back muscles
hip fractures reduce the incidence of vertebral fractures: a
prospective 10 year follow-up of postmenopausal
Van Schoor NM, Smit JH, Twisk JWR, et al. Prevention of hip fractures by
external hip protectors: a randomized controlled trial. JAMA. women. Bone 30: 836841
2003;289(15):19571962

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 FALL PREVENTION
Frailty and associated deconditioning;
Poor visual acuity;
Gait disturbances;
Impaired hearing;
Use of medications with that are sedating or
compromise balance; and
Dangers in the environment, including loose
rugs, lack of hand rails in the bathroom, etc.

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 To SummariseDrugs for prevention&treatment
Estrogens/only in early menopause and premature menopause

Alendronate- 5-10mg daily,35-70 mg /weekly

Risendronate daily2.5-5mg/day or weekly
Ibandronate 150 mg monthly,3 monthly
Zolendronic acid yearly 3mg I/V over 10-15min
Calcitonin nasal spray 200 IU daily
Raloxifene 60mg daily,lipid friendly ,lowers LDL
Teriparatide s/c20 40 g/day .can be given*18-24months
Strontium ranelate 2 gm/day
Osteoprotegrin 3 mg/kg s/c N-Telopeptide decreases in 5day
Tibolone(not FDA approved for osteoporosis)
Progesterone and growth hormones are being studied&also flourides

ePocrates. Computerized pharmacology and prescribing reference. updated daily. Available at: ePocrates.com Accessed September 19, 2008 .

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Osteoporosis Therapy Algorithm
Postmenopausal Women
Post Vasomotor Symptoms
During Hot Post Fracture
Flashes Pre fracture

PTH
Risk
of Fracture
Raloxifene Bisphosphonates

HRT
HRT Calcitonin

AGE
STAGE At Risk/Osteopenia Osteoporosis Severe Osteoporosis

Higher Lower
BMD (T-score) -2.5
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 OSTEOPOROSIS
HIP FRACTURES

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 OSTEOPOROSIS
HIP FRACTURES
Operate Early

High mortality &

morbidity by non-operative
Treatment

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 OSTEOPOROSIS
SPINE FRACTURES

Acute # :

NSAIDS & rest

Calcitonin
Orthosis
Reduction in rate of bone loss
Reduction of rate of #

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 Final Word
The real need in osteoporosis treatment is
for additional anabolic agents
"Our success or failure in combating
osteoporosis increasingly depends not so
much on the drugs available to us but
rather on our ability to engage our patients
and ensure that they take the medications
we prescribe

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 Final Message

ADD LIFE TOYEARS,

NOT YEARS TO LIFE.

AGE GRACEFULLY

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 ACKNOWLEDGEMENT
Dr.Sonal Bathla
MD,FICOG,FICMCH
SANT PARMANAND HOSPITAL

Dr. Shekhar Agarwal

Executive Director ,HOD of Orthopaedics
SANT PARMANAND HOSPITAL

Dr.Maninder Ahuja Chairperson Geriatric Gynecology Committee FOGSI

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