Osteoporosis is a progressive systemic skeletal disease characterized by low bone mass and microarchitecture deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk.

1. Osteoporosis
Presenter – Dr. Arun Vasireddy
Moderator – Dr.Lakshmaiah
30th March,2015

2. Introduction
• A Major global health problem. (WHO estimate >200 mill)
• Definition: progressive systemic skeletal disease characterized by
low bone mass and microarchitecture deterioration of bone tissue,
leading to enhanced bone fragility and a consequent increase in
fracture risk.
• Age, generic and lifestyle variables (i.e., nutrition, exercise,
smoking), chronic disease, and exposure to drugs (such as steroids)
known to be associated with rapid bone loss.
• Consequences:
o Bone fragility
o increased risk of fractures

3. Bone Structure
Types of bone:
 Cortical bone – 80% total bone mass.
 Cancellous(trabecular) bone – 20% total bone mass.
• Cancellous bone is formed by an interconnected structure of latticework. It
is porous and is often referred to as the spongy inner structure of the bone.
Because it is more metabolically active and, has a larger surface area, it is
more susceptible to bone loss and fracture.
• Cortical bone is the more dense type of bone that surrounds the cancellous
bone to form the outer, more durable layer bearing the majority of the
body’s Weight.

4. Constituents of Bone
Inorganic (65%) –
• Crystalline Hydroxyapatite
• Amorphous CaPO4
• Trapped ions: citrate, fluoride, Na, Mg, K
Organic (25%)
• Cells - 4%
• Intercellular Matrix – 21%

6. Types of Bone cells
At the cellular level, bone is made up of three types of specialized bone cells:
1. Osteoblasts,
2. Osteocytes, and
3. Osteoclasts
• interact with a variety of minerals, proteins, hormones, water, and other
molecules to nourish the bone, and resorption of old/worn bone tissue and
replace it with new bone in a process called remodelling.
• Both the osteoblasts and the osteocytes are derived from not yet differentiated
precursor (mesenchymal stem cells)cells that can also be stimulated to become
muscle, fat, or cartilage but under the right conditions can differentiate to form
new bone cells.
• During the remodelling process, osteoblasts lay down orderly layers of bone
that add strength to the matrix.
• Some of the osteoblasts are buried in the matrix as it is being produced,
becoming osteocytes (bone cells).

7. • Other osteoblasts remain as thin bone cells that cover the surface of the bone, called
lining cells.
• Osteoclasts are the cells that remove old or damaged bone by dissolving the mineral
and breaking down the matrix in a process called bone resorption.
• Under normal conditions, the functions of the osteoblasts and osteoclasts are
coupled, with signals from one affecting the other, to maintain the balance between
bone breakdown and new bone formation.
• Osteoporosis results from an imbalance between bone resorption and formation, in
which case bone resorption significantly exceeds bone formation.
• The body begins to lose bone more rapidly, leaving the bones weaker and more
susceptible to fracture.

8. Bone Remodelling
The removal and replacement of bone in the remodelling cycle involves four
phases:
1. Activation,
2. Resorption,
3. A period of reversal,
4. Bone formation.
• Signalling the start of the activation stage, the cells of the osteoblast lineage
act on blood cell precursors (i.e., hematopoietic cells) to produce more bone-
resorbing osteoclasts.
• The resorption process may take place under a layer of lining cells. During
this stage, the new army of osteoclasts removes worn/damaged bone by
dissolving the mineral and breaking down the matrix, leaving small cavities in
the surface of the bone.

10. Bone remodelling continued..
• After a period of quiescence (reversal), the osteoblasts then appear
in increased numbers and repair the bone by filling the recently
excavated cavities with new bone.
• During this process, some of the osteoblasts remain inside the bone
tissue and are converted to (osteocytes). Once the new bone has
been mineralized, the remodelling process in that particular area of
bone is complete.
• The resorption phase lasts only a few Weeks, but the formation
phase may take several months. To complete, as layer after layer of
new bone is created by the osteoblasts.
• Bone remodelling continues throughout adulthood, with each
remodelling process lasting 6—49 months.
• During the adult lifetime, the bone is replaced about every 10 years.‘

11. Biologic Messenger Molecules
Osteoblastic and Osteoclastic functions and bone metabolism are
regulated by numerous systemic and local factors, including the
following:
• Systemic factors involved in calcium homeostasis.
• Local factors influencing bone cell function.
• Cytokines and colony-stimulating factors associated with the
regulation of osteoclast/development.
• Growth regulator factors that stimulate osteoblastic proliferation and
differentiation from progenitor cells.
‘

12. Bone Remodelling

13. • The Osteoblastic cells produce several proteins that regulate osteoblast formation and
activity . One is macrophage colony stimulating factor(M-CSF), which acts on its
receptor to increase the no. of precursors available to form osteoclasts.
• The osteoclasts also produce a protein called receptor activator of nuclear factor kappaB
ligand (RANKL), which can bind to a receptor on the osteoclast precursors (RANK) and
stimulate them to develop into fully differentiated osteoclasts.
• The RANKL/RANK interaction also increases osteoclast activity.
• Finally the osteoblastic cells can produce osteoprotegerin (OPG), a protein that can be
secreted outside the cell and then bind RANKL and prevent it from interacting with
RANK, thus blocking the formation and activation of osteoclasts.
• Hormones and local factors such as parathyroid hormone (PTH), calcitriol or 1,25
dilhydroxyD (1,25D), prostaglandin F2(PGF2) and Interleukin-1(IL-1) act on the
osteoblastic cells to increase production of RANKL, and decrease production of OPG.
• The balance between RANKL and OPG production determines how fast bone breaks
down

14. Hormones & Growth factors regulating bone formation
Factor Target cells & tissue Effect
Interleukins
(IL-l, IL-3, lL-6, IL-ll)
Bone marrow, osteoclasts Stimulate osteoclast
formation & resorption
Tumor necrosis factor
(TNF-a) ;
Granulocyte macrophage
stimulating factor
(GM-CSF)
Osteoclasts Stimulates bone
resorption
Leukemic inhibitory
Factor
Osteoblasts, osteoclasts Stimulates osteoblast and
Osteoclast formation in
marrow

15. Factor Target cells Effect
Parathyroid Hormone
(PTH)
Kidney & Bone Stimulate production of Vit-D &
helps resorption of calcium
Calcitonin Bone osteoclasts Inhibits resorptive action of
osteoclasts: lowers circulating
Calcium.
Calcitriol
(1.25-dihydroxy vit-D3)
Bone Osteoblasts
Bone Osteoclasts,
Kidney,
Intestine
-Stimulates collagen, osteopontin,
osteocalcin synthesis;
-stimulates cell differentiation;
-Stimulates Calcium retention
-Stimulates calcium absorption
Estrogen Bone Stimulates formation of calcitonin
receptors, inhibiting resorption,;
Stimulate bone formation
Testosterone Muscle, Bone Muscle growth, placing stress on
bone to stimulate bone formation
Prostaglandins Osteoclasts Stimulate resorption and bone
formation
Bone Morphogenic
protein
Mesenchyme Stimulate cartilage protein & bone
matrix formation; replication

16. 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.

17. What is BMD?
• amount of mineral matter per square unit area of bone.
• Measured by DXA Scan (Dual-energy X-ray absorptiometry)
• Measures density in radius, lumbar spine and greater trochanter
• Mass of bone mineral in the path of the beam divided by the cross sectional area of
the beam, expressed as g/cm2
Other Methods:
• Single photon absorptiometry
• Vertebra fracture assessment (VFA)
• Quantitative computed tomography(QCT)
• Quantitative ultrasonography(QUS)

18. BMD Interpretation
• Results are generally scored by two measures,
 T-score
 Z-score.
• T-Score is the BMD at the site when compared to the young normal
reference mean.
• Z-score is the comparison to the age-matched normal and is usually
used in cases of severe osteoporosis.
• Negative scores indicate lower bone density, and positive scores
indicate higher.
• Normal : -1.0 or higher
• Osteopenia : -1.0 and -2.5
• Osteoporosis : -2.5 or lower

19. WHO Definition
• Osteopenia:
o BMD 1 to 2.5 standard deviations below young normal female mean (T score)
• Osteoporosis:
o BMD that falls 2.5 standard deviations (SD) below the mean for young healthy
adults of the same sex, also referred to as a T-score of –2.5.
o Postmenopausal women who fall at the lower end of the young normal range (a
T-score <–1.0) are defined as having low bone density and are also at increased
risk of osteoporosis.

20. 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.

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

22. 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

23. Risk Factors for Fracture
(Major) with relative risk >2 (Minor) with relative risk 1-2
Age >70 Estrogen deficiency
Menopause <45 Calcium intake <500mg/day
Hypogonadism Primary hyperparathyroidism
Fragility fracture Rheumatoid arthritis
Hip fracture h/o in parents Hypercalciuria
Glucocorticoids Anticonvulsants
High bone turnover Diabetes mellitus
Anorexia nervosa Smoking
<18 BMI Alcohol
Immobilisation/sedentary life
Chr. Renal failure
Transplantation
Chronic Inflammatory diseases

24. Groups That Should Be Tested With DXA
• All women over the age of 65
• Postmenopausal women with major risk factors
• All individuals over the age of 50 who suffer an osteoporotic fracture
• All individuals who are taking long term corticosteroids(7.5mg of
prednisone daily for 3mnths)
• Men with hypogonadal conditions
• Men over the age of 65
• Patients with diseases associated with bone loss and fracture

25. Classification of Osteoporosis
Nordin’s Classification:
 Generalised: Primary & Secondary
 Localised
Riggs & Melton Classification
 Primary osteoporosis
• Type-1 (Post menopausal)
• Type-2 (Senile)
 Secondary osteoporosis
 Osteogenesis Imperfecta
 Idiopathic Juvenile osteoporosis

26. Post menopausal osteoporosis (Type 1 )
• Characteristically affects women, between 10 and 20 years
following menopause.
• Sex ratio 5:2
• PTH and Ca metabolism is decreased.
• Characterized by high bone turnover and rapid loss of
trabecular bone.
• Suffer acutely painful crushing fractures of vertebrae and
colle’s fracture of distal radius

27. Senile osteoporosis (Type 2 )
• Affects men and women aged Over 70 years.
• Sex ratio 2:1
• Due to chronic effect of bone loss since peak bone mass attained in
the 4th decade with a superimposed senile lowering of the rate of
bone turnover.
• Affects both cortical and trabecular bone.
• PTH is increased - Reduced Ca absorption and 25OHVit D
synthesis
• Decreased Insulin like growth factor concentration characterized by
multiple wedge fractures of the vertebrae (often pain free ) and
fractures of the femoral neck and intertrochanteric femoral fractures

28. Secondary Osteoporosis
Pharmacotherapy:
• Glucocorticoids
• Thyroid over replacement
• Anticonvulsants (phenytoin, phenobarbital)
• Lithium, aluminium
• Heparin (long-term)
• Drugs producing hypogonadism (aromatase inhibitors, antimetabolite
chemotherapy, medroxyprogestrone, gonadotropin-releasing hormone
agonists)
Endocrine Disorders:
• Cushing syndrome
• Hyperparathyroidism
• Hypogonadism
• Hyperthyroidism

29. Gastrointestinal disorders:
• i. Alcohol abuse related diseases
• ii. Malabsorption syndromes
• iii. Eating disorders
• iv. Celiac disease
• v. Inflammatory bowel diseases
• vi. Chronic liver diseases
• vii. Gastrectomy
Genetic diseases:
• i. Osteogenisis imperfecta
• ii. Hypophosphatasia
Miscellaneous causes:
• i. Organ transplant
• ii. Rheumatoid arthritis
• iii. Neurological diseases
• iv. Spinal cord injury
• v. Multiple sclerosis
• vi. Prolonged bed rest
• vii. Multiple myeloma
• viii. Marrow infiltrative diseases

30. Tests That Should Be Considered When Evaluating
Secondary Causes of Osteoporosis
• History and physical examination
• 25-OH vitamin D
• Hi - Serum calcium : Hyperparathyroidism or malignancy Low
Serum calcium: Malnutrition or osteomalacia.
• Serum phosphorus, alkaline phosphatase, creatinine
• Parathyroid hormone: Increased in Hyperparathyroidism
Decreased in Malignancy.
• Low - Urine calcium(<50mg/day): osteomalacia, malnutrition,
malabsorption
• High - Urine calcium(>300mg/day) male osteoporosis,
granulomatous disease or malignancy with increased bone turnover
• Thyroid function tests
• Serum protein electrophoresis - to r/o multiple myeloma
• Serum testosterone (in men)

31. Bone Turnover Markers
Measures of osteoblast function:
• Alkaline phosphatase (AP): The bone alkaline phosphatase is specific for
bone and reflects cellular activity of osteoblasts.
• Osteocalcin (OC): a hydroxyapatite binding protein synthesized by
osteoblasts
Measures of osteoclast function:
• Hydroxyproline (OHP): This reflects breakdown of collagen in bone,
cartilage & skin.
• Collagen crosslinks: These reflect bone resorption. They tend to be
specific markers of bone resorption.
These include the following:
1) N—telopeptide (NTX) measured in the urine and in serum by an
immunoassay termed Osteomark
2) C-telopeptide (CTX) measured in Serum by an immunoassay termed
Crosslaps
3) Deoxypyridinoline (DPD)

32. Steroid Induced Osteoporosis:
1. Reduces bone formation and accelerates bone resorption.
2. Reduced bone formation.
• Direct inhibitory effect and increase apoptosis in osteoblasts
• Decreased production of IGF-I (insulin growth factor-I)
• Decreased testosterone production
3. Increased in bone resorption. (non-mature osteoclasts)
• Increased osteocyte apoptosis.
• Inhibition of gonadotropin secretion thus causing a decrease in
estrogen and androgen secretion
• Increased PTH secretion resulting in Hyperparathyroidism which
causes decreased intestinal calcium absorption and increases renal
calcium excretion
 Note : Bone loss is related to dose. Doses as little as 10mg a day
may have adverse effects on BMD.

33. LOCALISED OSTEOPOROSIS
• Disuse osteoporosis
• Sudecks osteodystrophy
• Transient osteoporosis
• Regional migratory osteoporosis
• Idiopathic chondrolysis of hip

34. Diagnosis of Osteoporosis
Clinical features:
• Low back ache which radiates around the trunk Or down the
limbs.
• Loss of height and appearance of thoracic kyphosis and
approximation of the rib margin to the iliac crests.
• Patient appears Older than his or her years.
• H/o Fractures

35. Physical examination
• Measurement of height.
• Detection of kyphosis
• Blue sclera ,thin skin (0 I )
• Hepatosplenomegaly (systemic disease)
• Skin pigmentation (Cushing's synd.)

36. X-ray
• Post menopausal osteoporosis :Trabecular resorption and
cortical resorption
• Senile osteoporosis: Endosteal resorption
• Hyperparathyroidism: Sub periosteal resorption
• Note: Osteoporosis produces increased radiolucency of
vertebral bone. Approximately 30 to 80 per cent of bone tissue
must be lost before a recognizable abnormality can be detected
on spinal radiographs.
• Lesions less than 2cm may escape detection.

37. KLEER KOPER score
 Osteoporosis produces increased radiolucency of vertebral bone.
Approximately 30 to 80 per cent of bone tissue must be lost before a
recognizable abnormality can be detected on spinal radiographs. Lesions
less than 2cm may escape detection.

38. Pharmacological Management
The four major goals in the treatment of osteoporosis are:
 To prevent fracture,
 To stabilize bone mass or achieve increased bone mass,
 To relieve symptoms of fractures and skeletal deformity,
 To maximize physical function

39. Bisphosphonates
• BPN’S are analogues of pyrophosphate.
• BPN therapy should be considered first line therapy for the treatment of
osteoporosis, in conjunction with lifestyle modifications and appropriate
doses of calcium plus Vit-D.
• 1st generation include Etidronate and Tiludronate.
• 2nd generation BPN’s(Alendronate, Pamidronate & Ibandronate) for the
prevention and treatment of postmenopausal osteoporosis.
• 3rd generation include Risedronate and Zoledronate

40. Ibandronate efficacy

41. Bisphosphonates – Mode of Action
• Accelerated apoptosis of osteoclasts reducing their number.
• Disruption of cytoskeleton and ruffled border of osteoclasts.
• Affect osteoclast precursors and inhibit their differentiation by suppressing
IL-6.
• 2nd & 3rd gen BPN’s have important metabolic effects in the mevalonate
pathway for isoprenoid lipid synthesis.
• Interference with mevalonate pathway may impart antitumor action on
bony metastasis.

42. Bisphosphonates -continued
Risedronate: approved for the treatment and prevention of
corticosteroid induced osteoporosis. Dose - monthly 75mg on 2
consecutive days every month that has proven just as efficacious as the
5 mg daily dose
Ibandronate: Quarterly iv 3mg as a 15-30 second infiision. It can be
used as a 2.5 mg once daily as Well as in a 150 mg once-monthly dose
Zoledronate: Indicated in hypercalcemia, bony metastases and Paget’s
disease
• Proliferation of bony metastasis of prostate/breast cancer and
multiple myeloma cells may be arrested.
• Renal toxicity may be encountered- Dose: 4mg diluted in 100ml
saline/glucose solution and infused iv over 15mins, may be repeated
after 7days and then at 3-4week intervals. Women who received
infusion of 5mg once yearly had a‘70% reduction in the risk of spine
fractures and 41% reduction in risk of hip fractures

43. Parathyroid Hormone Therapy (PTE) :
• The recombinant human parathyroid hormone, teriparatide is
administered as a once-daily injection and is approved for use
for up to 24 months.
• Dose: 20mcg OD (65-80% reduced # risk) administered as a
daily subcutaneous injection.
• Indications: Used for treatment of patients with osteoporosis
(both men &women) at high risk of fracture (BMD<-3.5) and
those with pre-existing fragility fractures. Daily subcutaneous
injections are used in corticosteroid induced Osteoporosis

44. PTH Efficacy

45. Hormone replacement (Estrogen) Therapy
• Estrogen is effective in inhibiting bone resorption and increasing
BMD by binding to estrogen receptors on bone and blocking the
production of specific cytokines that increase the number of
osteoclasts and prolong their life span.
• Administration and Adverse Events: Estrogens can be
administered orally, intravaginal, transdermal, parenteral, and by
topical application to the skin.
• Estrogen is usually taken in a continuous daily dosage regimen or
in a cyclic regimen.
• Cyclically administered estrogen is usually taken once daily for 3
weeks followed by 1 week off the drug, or once daily for 23 days
followed by 5 days without the drug.

46. Hormone replacement (Estrogen) Therapy
• Regarding the safety of the long-term use of HT, this treatment
should be reserved for Women unable to tolerate non-estrogen
therapy.
• Research evidence has shown that lower doses of CEE alone,
or CEE/MFA, 0.3 mg/1.5 mg daily, Significantly increased
spine and hip BMD from baseline within 2 years of therapy.

47. Product Dose Caution
Estradiol 0.5 mg, 1 or 2 mg; tabs OD Undiagnosed abnormal
genital bleeding
Estrone sodium as
estropipate
0.625, 1.25 ,2.5 mg tabs OD Known or suspected
breast cancer
Estropipate 0.75 mg, 1.5 mg;tabs; OD Known/suspected
estrogen dependant
neoplasia
Estradiol (Topical) 1.25 mg pump once qd
Conjugated equine
estrogens
0.3, 0.45, 0.625, 0.9, 1.25,
2.5 mg daily
Venous
thromboembolism or
pulmonary embolism

48. BIOIDENTICAL HORMONES
• Bioidentical hormones include estrogens estrone (E1), estradiol (E2), and
estriol(E3), progesterone, testosterone, dehydroepiandrosterone (DHEA),
and pregnenolone.
• Bioidentical hormones are prepared from either beta sitosterol extracted
from the soybean or from diosgenin extracted from the Mexican wild yam
root.
• administered - oral (capsules, drops, sublingual), transdermal/topical,
vaginal, rectal, and pellet implants.
• Biestrogen - estriol 80% + estradiol 20%
• Triestrogen - estriol 80% + estradiol 10% + estrone 10%

49. SELECTIVE ESTROGEN RECEPTOR
MODULATORS (SERMS)
• Raloxifene hydrochloride is a nonsteroidal benzothiophene derivative with
mixed estrogen agonist or antagonist activity in specific tissues.
• Indication: prevention of osteoporosis in post menopausal women
• The biological actions of SERMs 'are principally mediated via binding to
estrogen receptors. This binding results in the activation of specific
estrogenic pathways and the blockade of others
• Thus, raloxifene acts like estrogen to prevent bone loss.
• Dose: 60mg tab OD
• Adverse effect: venous thromboembolic disease (sedentary patients)

50. Calcitonin(Salmon) Therapy
• Calcitonin is an endogenous hormone secreted by the thyroid's Para
follicular gland in mammals.
• inhibits osteoclast development and activity and promotes osteoclast
apoptosis. It acts quickly in the treatment of osteoporosis.
• Calcitonin derived from a salmon’s ultimobranchial gland is utilized, due to
its greater potency and prolonged duration of action when compared to
mammalian calcitonin.
• Indications: Paget's disease, Hypercalcemia, osteoporosis in women >5yrs
after menopause.
• Used for pain associated with osteoporotic fractures. Patients with vertebral
crush fracture reported a significant decrease in pain.
• Dose: 200 IU daily nasal spray formulation.

51. COMBINATION ANTIRESORPTIVE THERAPY
• Bisphosphonates, HT, and SERMs are all classified as
antiresorptive drugs however, they operate through different
mechanisms of action suggesting that if used in combination
they could have an additive effect.
• Women receiving combination therapy had around an 8%
increase in BMD at the spine compared to 6% in women
taking alendronate or estrogen.

52. DEMOSUMAB (AMG 162):
• Human monoclonal IgG2 antibody that has high affinity for
RANKL and blocks the binding of RANKL to RANK.
• Administered subcutaneously 60mg every 6months. Increased
BMD at all skeletal sites and decreased bone turnover markers
at 24 months.
• Adverse effect : dysregulation of the immune. system,
potentially leading to infection or malignancy

53. NON PHARMACOLOGICAL MANAGEMENT
 Diet
 Physical Exercise
 Tobacco cessation & Alcohol Minimalisation

54. Calcium & Vitamin-D
• Calcium mainly exists in bone in the form of
hydroxyapatite(Ca)10 (PO4)6(OH)2, and bone mineral is
approximately 40% of bone weight.
• Vitamin D (calciferol) is vital for bone health because it assists
in the absorption and utilization of calcium.
• The major source of vitamin D is sunlight, which the human
body absorbs by exposure to sunlight through the conversion
of precursors in the skin to active vitamin-D

55. RDA
Age Calcium Dose(mg/day) Vitamin-D Dose(IU/day)
1-3 yrs 500 200
4-8 yrs 800 200
9-18 1300 200
19-50 1000 400
51-70 yrs 1200 600
>70 yrs 1200 800
• Recommended Treatment for Pts at Risk:
1,000—1,500 mg of elemental calcium and 400—800 IU of vitamin D daily
• Foods Rich in Calcium & Vit-D:
Fortified Milk & milk products, Fish & Fish oils

56. Phytoestrogens
• Phytoestrogens may be useful for preventing bone loss caused
by estrogen deficiency in women.
Dietary sources:
• Isoflavones (genistein, daidzein, glycitein, and equol)
Primarily found in soy beans and soy products, chickpeas, and
other legumes
• Lignans (enterolactone and enterodiol): Found in
oilseeds(primarily flaxseed), cereal bran, legumes, and alcohol
(beer and bourbon)
• Coumestans (coumestrol): Found in alfalfa and Clove

57. Pain Management
• Pain has been reported in up to 62% of female patients with
osteoporosis.
• There are various pain origins for osteoporosis, including concurrent
degenerative disk disease, osteoarthritis, and vertebral fracture.
Treatment:
• Improve posturing.
• Superficial heat like infra red therapy.
• If pain persists, penetrating heat like ultrasound or short wave
diathermy.
• If pain still persists rule out malignancy.
• Back strengthening extension exercises.

58. Pain Management (Analgesics)
Non-aspirin analgesic:
• Acetaminophen 500 mg every 4 hours as needed/1,000‘mg every 6 hours
as needed/4 grams daily(max)
(NSAIDS):
• Ibuprofen 400 mg every 4 hours as needed or 3,200 mg daily (max)
• Naproxen 500 mg every 12 hours or 1,500 mg daily (max)
• Indomethacin 25’10‘50 mg three times daily or 75 mg (extended release)
once to twice daily, Max 200 mg daily

59. Opioid combinations:
• Hydrocodone/APAP One 5/500 mg tablet every 4 hours as needed Eight 5/500 tablets
daily
• Hydrocodone/ibuprofen One 5/200 mg tab every 4 hrs as needed
• Oxycodone/APAP 0ne 5/325 mg tablet every-4 hours as needed
 NOTE: There are varying dose combinations & should be evaluated for a maximum
dose based on the daily maximum acetaminophen use.
Opiate analgesics:
• Morphine Starting 15 mg every 12 hours scheduled
• Oxycodone Starting 10 mg every 12 hours schedule
 Patient tolerance should be taken into consideration

60. Complications of Osteoporosis – “fragility fractures”
• The most significant complication of osteoporosis is a fracture, and while
fractures may occur at many sites, they most commonly occur in the hip,
spine, and wrist.
• Examples are fractures of the femoral neck, supracondylar fractures of
femur, fracture of the distal tibial metaphysis, Colle’s fracture, Fracture of
Radial neck, subcapital fracture of humerus and vertebral body fracture.
• Associated clinical complications include pain, disability, deformity,
postural changes associated with vertebral compression fractures, and
deconditioning secondary to physical inactivity.

61. Complications of Osteoporosis
• In wrist fractures the ratio of female to male is 10:1 but in Hip Fractures,
the ratio is 2:1.
• Most often fractures associated with osteoporosis are often referred to as
“fragility fractures” because they result from low level trauma that would
not cause normal bone to fracture.
• While vertebral fracture is the most common type of osteoporotic fracture,
hip fractures have a particularly high morbidity and mortality rate.

62. 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

63. Orthopaedic management
Prophylactic measures:
• Avoid lifting heavy weights & Prevent contact sports.
• Avoid lilting weight in forward bending position.
• Pectural stretching, deep breathing and back extension exercises.
• Avoid kyphotic posturing
• Low healed soft shoes and walking aids
Rehabilitation in established osteoporosis:
• Improve posture
• Relieve pain
• Activity and ambulation
• Low self esteem and depression have to be treated

64. Management of complications
• Vertebral/Rib/Pelvic Fractures - Usually Supportive care
• Long bone fractures - external or internal fixation
• Hip fracture
o Always require surgical repair
o Hemi arthroplasty with AMP
o Total hip replacement
o Pin and plate fixation
• Acute compression fractures
o Analgesics i narcotic agents
o Limited bed rest
o If pain persists, rigid back support for ambulation — TAYLOR brace
o Calcitonin
o Vertibroplasty or kyphoplasty

65. Osteoporosis in Men
• Often neglected.
• Raising awareness.
Risk factors:
• Genetics
• Tobacco
• Calcium supplementation
• Physical activity and muscle strength
• Low testosterone (Hypogonadism)
• Low estradiol levels

66. Osteoporosis in Men
Identified in 40-60% men with osteoporotic fractures:
• Hypogonadism
• Glucocorticoid therapy
• Gastrointestinal diseases
• Vitamin D deficiency
• Anticonvulsant use
• Alcohol abuse

67. Osteoporosis in Men - Management
• Treatment of the cause – tobacco/Alcohol/steroids abuse
• Weight bearing exercises
• Bisphosphonates - Alendronate 70mg/day, Pamidronate (60
mg iv over 2 hrs q.12 wks for 48 wks).
• Testosterone replacement-controversial
 All men at risk should be on Calcium 1000 mg/day and Vit D
800 IU/day

68. Osteogenesis imperfecta
• Other names for OI are Lobstein disease, brittle-bone disease, blue-sclera
syndrome, and fragile-bone disease.
• OI is one of the most common skeletal dysplasias.
• The basic defect is one of a qualitative or quantitative reduction in type 1
collagen.
• Pathologic changes are seen in all tissues of which type 1 collagen is an
important constituent (eg, bone, ligament, dentin, and sclera).
• It is a generalized disease of connective tissue that may manifest itself with one
or more of the following findings:
o Blue sclerae, Triangular facies, Macrocephaly
o Hearing loss, Defective dentition, Barrel chest, Scoliosis
o Limb deformities, Fractures, Joint laxity, Growth retardation.

70. Idiopathic osteoporosis
Idiopathic/juvenile osteoporosis
• Between 8 to 14 yrs
• Abrupt appearance of bone pain
• Fracture after minimal trauma
Cause:
• Malabsorption of calcium
• High urinary calcium loss
• Vertebra on x-ray
o Regular biconcavity with large disc space
• Self limited usually.
• No response to vitamin D or calcium therapy

71. Transient (regional) osteoporosis
• Rare (0.6%)
• Affect large joints
• Femoral head must common site.
• Young to middle age groups
• Males more than females.
• In females:
o Let hip most common site
o In 3rd trimester of pregnancy
• Resolves spontaneously in 4-6 months

72. Regional migratory osteoporosis
• Mainly knee, ankle, foot involved.
• Males > female.
• Between 30 to 50 yrs.
• Involvement of each joint lasts 9 months.
• Recurrence in other joints occur successively or be separated
by 2 yrs or more.

73. Treatment Advancements
• New Assessment Tools for Fracture Risks & Treatment
Decisions
• Anabolic Agents
• New Resorption Inhibitors

74. F R A X Scoring System
• The WHO developed a computer-generated algorithm, FRAX, which will
supply clinicians with a tool to estimate absolute, time-specific fracture risk
quantitatively
• This useful tool provides country- and ethnic-specific 10-year hip and
major osteoporotic fracture (hip, distal forearm, shoulder, vertebral body)
risks, based on information entered into the calculator, which is available
for free online.
• The information requested can be easily obtained from simple questioning;
it includes age, sex, weight, height, personal and family history of fracture,
current tobacco and alcohol consumption, corticosteroid usage, previous
conditions associated with secondary osteoporosis, and history of
rheumatoid arthritis

76. FRAX
• Threshold values for the instauration of bone-strengthening
medication are established for those individuals who have a
3% or more risk of a hip fracture and/or 20% risk or more of a
major osteoporotic fracture
• The FRAX calculator is particularly useful for younger,
healthy, postmenopausal females with osteopenia, a group of
people with a relatively low 10-year fracture risk.

77. αVβ3 INTEGRIN RECEPTOR INHIBITORS
• To bring about bone resorption, osteoclasts attach themselves to
Arg-Gly-Asp (RGD) sequences such as those found in osteopontin,
bone sialoprotein, and type I collagen in the extracellular matrix of
bone surface by means of the αVβ3 vitronectin receptor.
• The actual binding molecules for the vitronectin receptor in bone are
not known.
• Small molecular weight, orally active RGD - mimetics have been
developed that inhibit binding of the vitronectin receptor of
osteoclasts and bone resorption.
• At least one of these drugs is undergoing clinical trials to assess its
possible utility for treatment of osteoporosis.

78. OSTEOPROTEGERIN
• also known as osteoclastogenesis inhibitory factor (OCIF), or tumor necrosis
factor receptor superfamily member 11B(TNFRSF11B).
• The effects of OPG on bone markers were determined in a randomized,
prospective, double—blind, placebo controlled, 85 day, sequential dose-
escalation study (0.1, 0.3, 1.0 and 3.0 mg/kg body weight) that involved 52
healthy postmenopausal women.
• The drug was given as a single dose by s.c. injection.
• Urinary NTx had decreased at 12 hours after administration of the OPG and at
the highest dose, had decreased by 80 % at 4 days and by 14 % at 6 weeks.
• In contrast, serum BSAP did not change for 3 weeks and had declined by 30
percent at 6 weeks in response to the highest dose.
• OPG was well tolerated. These studies indicate that in human subjects
osteoprotegerin is a potent inhibitor of osteoclastic bone resorption, reduces the
rate of skeletal remodelling and is of potential Value for the treatment of
osteoporosis

79. Statins
• Statins are drugs that were developed and are widely used to
lower serum cholesterol by inhibiting HMG CoA reductase,
the rate-limiting Enzyme for cholesterol synthesis.
• Simvastatin was found to increase expression of BMP-2 in
bone cells.
• lovastatin, Simvastatin, mevastatin and fluvastatin were shown
to markedly increase bone formation in rodents, both intact
and ovariectomized.
• Thus, statins, particularly newer ones, are of potential value
for treatment of osteoporosis

80. References
• Harrison's Principles of Internal Medicine,18th edition.
• Current Medical Diagnosis and Treatment 2015, 54th edition.
• Apley's System of Orthopaedics and Fractures, 9th edition
• PubMed Central web archives.

81. Thank You