Osteoporosis is a disease characterized by low bone mass and deterioration of bone structure. It increases the risk of fractures. The World Health Organization defines osteoporosis as a bone density 2.5 standard deviations or more below the mean bone density of healthy young adults. Dual-energy x-ray absorptiometry (DXA) is the gold standard test used to diagnose osteoporosis by measuring bone mineral density at sites like the hip and spine. Lifestyle factors like diet, exercise, smoking and alcohol as well as certain medical conditions and medications can impact bone health and increase the risk of osteoporosis.

1. BY:DR ABHISHEK CHAUDHARY(DNB ORTHO SGITO)

2.  Osteoporosisis defined as a reduction in the
strength of bone that leads to an increased risk
of fractures. Loss of bone tissue is associated
with deterioration in skeletal microarchitecture.
 The World Health Organization (WHO)
operationally defines osteoporosis as a bone
density 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

6. 1. Disuse osteoporosis
2. Sudecks osteodystrohy
3. Transient osteoporosis
4. Regional migratory osteoporosis
5. Idiopathic chondrolysis of hip

7.  BY FAR IT’S THE MOST COMMEN METABOLIC
DISEASE
 Age demographics –
 senile osteoporosis most common in >70 yr
 Secondary osteoporosis can occur at any age
 Post menopausal women have early
maximum incidence in age group 50-70years

8.  Prevelance of vertibral # is 27% in women of
aga>65.
 90 % hip # occur in patiens age >50.

9.  Over all male to female ratio is 1:4.
 50 % of postmenopausal women have
osteoporosis related # in their lifetime. 25%
develop vertebral deformity.
 Men have higher prevalence of secondary
osteoporosis .
 20 % of all men >50 years suffers
osteoporosis related # in their lifetime

13.  In the embryo and the growing child, bone develops
mostly by remodeling and replacing previously
calcified cartilage (endochondral bone formation) or,
in a few bones, is formed without a cartilage matrix
(intramembranous bone formation).
 During endochondral bone formation, chondrocytes
proliferate, secrete and mineralize a matrix, enlarge
(hypertrophy), and then die, enlarging bone and pro-
viding the matrix and factors that stimulate
endochondral bone formation.

 This program is regulated by both local factors, such
as IGF-I and -II, Ihh, PTH-related peptide (PTHrP), and
FGFs, and by systemic hormones, such as growth
hormone, glucocorticoids, and estrogen.

18.  In young adults, resorbed bone is replaced by
an equal amount of new bone tissue. Thus, the
mass of the skeleton remains constant after
peak bone mass is achieved in adult-hood.
After age 30–45,
 however, the resorption and formation
processes become imbalanced, and resorption
exceeds formation. This imbalance may begin
at different ages and varies at different
skeletal sites; it becomes exaggerated in
women after menopause.
 osteoporosis is primarily a disease of
disordered skeletal architecture

19.  The recommended daily required intake of 1000–
1200 mg for adults
 Peak bone mass may be impaired by inadequate
calcium intake during growth among other
nutritional factors (calories, protein, and other
minerals), leading to increased risk of osteoporosis
later in life.
 Over 99% of the 1–2 kg of calcium present normally
in the adult human body resides in the skeleton,
where it provides mechanical sta-bility and serves
as a reservoir sometimes needed to maintain
extracel-lular fluid (ECF) calcium concentration.

23.  Vitamin D insufficiency may be more
prevalent than previously thought,
particularly among individuals at increased
risk such as the elderly; those living in
northern latitudes; and individuals with poor
nutrition, malabsorption, or chronic liver or
renal disease.
 Normal level of 25 hydroxyvitamin D is 20-30
ng/ml.
 To achieve this level for most adults requires
an intake of 800–1000 units/d

24.  Some studies have shown that >50% of
inpatients on a general medical service
exhibit biochemical features of vitamin D
deficiency, including increased levels of PTH
and alkaline phosphatase and lower levels of
ionized calcium

25.  Estrogen deficiency probably causes bone loss by
two distinct but interrelated mechanisms:
 (1) activation of new bone remodeling sites and
 (2) exaggeration of the imbalance between bone
formation and resorption
 Marrow cells (macrophages, monocytes, osteoclast
precursors, mast cells) as well as bone cells
(osteoblasts, osteocytes, osteoclasts) express ERs
α and β. Loss of estrogen increases production of
RANKL and may reduce production of OPG,
increasing osteoclast recruitment.
 Estrogen also may play an important role in
determining the life span of bone cells by
controlling the rate of apoptosis

27. Factor Target cells and
tissue
Effect
Parathyroid hormone Kidney and bone Stimulates the production
of vit D and mobilizes
calcium from bone into
the blood stream
Calcitonin Bone osteoclasts Inhibits resorptive action
of osteoclasts .
Calcitriol Bone osteoblasts
Intestine
Stimulates synthesis of
collagenous & Non
Collegenous proteins
Stimulates activity of the
osteoclasts
Stimulates clacium
absorption
Estrogen Bone Stimulates formation of
calcitonin receptors,
inhibits bone resorption

28. Factor Target cell and tissue Effect
Testosterone Muscle, bone Stimulates muscle growth,
placing stress on the bone,
increasing bone formation
Prostaglandins Osteoclasts Stimulates resorption and
formation
Bone morphogenic
protein
Mesenchyme Stimulates cartilage protein
and bone matrix formation
Transforming
growth factor
Osteoblasts ,
chondrocytes
Stimulates differentiation
Interleukins
( IL- 1,3 , 6,11 )
Bone marrow,
osteoclasts
Stimulates osteoclast
formation
Tumour necrosis
factor ( TNF-a)
Osteoclasts Stimulates bone resorption

29.  Inactivity, such as prolonged bed rest or
paralysis, results in significant bone loss.
Concordantly, athletes have higher bone mass
than does the general population.
 These changes in skeletal mass are most marked
when the stimulus begins during growth and
before the age of puberty. Adults are less capable
than children of increasing bone mass after
restoration of physical activity.
 More active indivudauls suffer lesser fall and
further less #.

30.  Various genetic and acquired diseases are
associated with an increase in the risk of
osteoporosis.
 Mechanisms that contribute to bone loss are
unique for each disease and typically result
from multiple factors, including nutrition,
reduced physical activity levels, and factors
that affect rates of bone remodeling.

31.  Glucocorticoids are the most common cause
of medication-induced osteoporosis.

32.  The use of cigarettes over a long period has
detrimental effects on bone mass. These
effects may be mediated directly by toxic
effects on osteoblasts or indirectly by
modifying estrogen metabolism.

35.  Age > 70
 Menopause < 45
 Hypogonadism
 Fragility fracture
 Hip fracture in parents
 Glucocorticoids
 Malabsorption
 Anorexia nervosa
 BMI< 18
 Immobilisation
 Chronic renal failure
 Transplantation
 Calcium intake < 500mg/dl
 Primary hyperparathyroidism
 Rheumatoid arthritis
 Estrogen deficiency
 Anticonvulsant therapy
 Hyperthyroidism
 Diabetes mellitus
 Smoking
 Alcohol
MAJOR MODERATE

38.  Routine blood investigations
 Serum and 24 hr urine ca levels,LFT,RFT and 25(OH)D level
 S. PTH level,PTHrp levels,x ray evaluation
 Bone mineral density
 single-energy x-ray absorptiometry (SXA)
 dual-energy x-ray absorptiometry (DXA)
 High resolution quantitative CT
 Biochemical markers
 Others
 TSH,urine cortisol,(s.albumin,cholesterol,antigliadin
antibody)
 Tetracycline labelling,bone biopsy

39.  Radiography
1. Ground glass appearance and cortical thinning
2. Vertebral bodies become bi concave , loss of height &
wedging is seen is seen in vertebral fractures
3. Conventional radiographs are an insensitive way to
determine osteoporosis as bone loss becomes
apparent only after 30-50% reduction
KLEER KOPER Score:
 Normal - grade 0
 Biconcave deformity - grade 1
 Wedge deformity – grade 2
 Compression deformity – grade 3

42. Grade VI:
- all normal trabecular groups are visible
- upper end of femur seems to be
completely occupied by cancellous bone;
- Grade V:
- principal tensile & principal compressive
trabeculae is accentuated;
- Ward's triangle appears prominent;
- Grade IV:
- principal tensile trabeculae are markedly
reduced but can still be
traced from lateral cortex to upper part
of the femoral neck;
- Grade III:
- there is a break in the continuity of the
principal tensile
trabeculae opposite the greater
trochanter;
- this grade indicates definite osteoporosis;
- Grade II:
- only principal compressive trabeculae
stand out prominently;
- remaining trabeculae have been essentially
absorbed;
- Grade I:
- principal compressive trabeculae are
markedly reduced in number and
are no longer prominent;

43.  It is a measure of bone mass divided by bone area
which increases with age until peak bone density
is achieved.
 Currently there is no practical measure of bone
strength. Bone mineral density (BMD) is used as a
proxy measure of bone strength.
 It is used to quantitatively screen and diagnose
patients with osteoporosis.
 It is the only method for diagnosing and
confirming osteoporosis in the absence of a
fracture
 In subjects with a BMD in the osteoporosis range,
there is approximately a five times increase in the
occurrence of osteoporotic fractures

45. NOF GUIDELINE FOR DIAGNOSIS& TREATMENT
Postmenopausal below
the age of 50
Postmenopausal
between
50-65
Post menopausal
Above 65 years
Any postmenopausal
With fracture
Assess risk of osteoporosis
Check secondary reasons
Assess risk of
osteoporosis
DEXA
Calcium 1200 mg &
VIT D 400 IU
DEXA
DEXA
Calcium 1200 mg &
VIT D 400 IU
no
Yes
National Osteoporosis Foundation – February 2008

46. 1. First method employed
2. Involves passing a high energy photon from a
radioactive source through a peripheral bone
such as radius or calcaneus.
3. Bone density was estimated based on degree
of attenuation of the beam.

47.  Gold standard method to determine bone
mineral density.
 Advantages
1. Rapid and non invasive technique
2. Radiation exposure is minimal
3. Precise measurements at clinically
relevant sites like hip, spine.
 Disadvantages
1. Not portable
2. Expensive

48. •Used to measure bone mineral density at the hip, spine , wrist or total
body.
•Patient is made to lie supine over the machine and dual X ray source is
used to liberate the energy source.
•The attenuation of the photon is measured .
•The time duration for the procedure ranges from 5 to 15 minutes

51.  Provide an integrated assessment of global disease activity .
 Markers of both formation and resorption are increased in osteopororis
 It also obviates the need for repeated BMD measurement , here
immunoassays are done at 3 mts and a decrese in 30% level is
considered a good response
 Mesures of osteoblast function
1. Alkaline phosphatase
2. Osteocalcin
 Mesurement of osteoclast function
1. Hydroxyproline
2. Collagen crosslinks
A. N- Telopeptide
B. C – telopeptide
C. Deoxypyridinoline

52. ◦ Pros:
 -similar accuracy to DEXA
 -may have slightly better predictive value in risk
of vertebral fracture
◦ Cons:
 -more expensive (than DEXA)
 -less reproducible (bigger variance)
 -higher radiation

53. ◦ It is in use since 1984
◦ Relies on transmission of ultrasound waves through
accessible bone like calcaneum and phalanges
◦ Pros:
 -studies thus far have suggested similar predictive ability of
fracture to DEXA
 -No radiation
 -Portable
◦ Cons:
 -unable to provide true Bone Density Measurements (less
applicable to current diagnostic standards and treatment goals
based on BMD)

54.  It relies on transmission of ultrasound
waves through accessible limb bones or
the reflectance of waves from the bone
surface.
 water is used as a coupling agent

55.  Treatment considerations
 RISK ASSESMENT tools
 PREVENTION is far better and easier then treatment
of osteoporotic #.
 Four major goals:
1. To prevent fracture
2. To stabilize bone mass or achieve increased bone
mass
3. To relieve symptoms of fractures and skeletal
deformity
4. To maximize physical function

56.  FRAX tool, developed by a working party for the
WHO, and available as part of the report from
many DXA machines
 In the United States, it has been estimated that it
is cost-effective to treat a patient if the 10-year
major fracture risk (including hip, clinical spine,
proximal humerus, and tibia) from FRAX is ≥20%
 Imperfect tool because any assessment of fall
risk and secondary causes are excluded when
BMD is entered

59.  The National Health and Nutrition Examination Surveys
(NHANES) have consistently documented that average
calcium intakes fall considerably short of these
recommendations.
 Excellent Food sources of calcium are dairy products
(milk, yogurt, and cheese)
 If a calcium supplement is required, it should be taken in
doses sufficient to supplement dietary intake to bring
total intake to the required level (1000–1200 mg/d).
 Doses of supplements should be ≤600 mg at a time,
because the calcium absorption fraction decreases at
higher doses

61.  Carbonates vs citrate
 Several controlled clinical trials of calcium, mostly
plus vitamin D, have confirmed reductions in clinical
fractures, including fractures of the hip (~20–30%
risk reduction).
 standard practice to ensure an adequate calcium
and vitamin D intake in patients with osteoporosis
whether they are receiving additional pharmacologic
therapy or not.
 A/E- eructation and constipation with ca carbonate.
h/o renal stones is relative contraindication. high
intakes of calcium from supplements are associated
with an increase in the risk of heart disease.

62. AGE
GROUP
RDA
<50
years
200 IU
50-70
years
400IU
>70
years
600IU
Large segments
of the population do not obtain
sufficient vitamin D to maintain
what is now considered an adequate
supply [serum 25(OH)D conSistently
>(30 ng/mL)]
Vitamin D supplementation at doses that
would achieve these serum levels is safe
and inexpensive,.
Higher doses (≥1000 IU) may be
required in the elderly and chronically
ill
It is safe to take up to 4000 IU/d

63.  Adequate vitamin K status is required for optimal
carboxylation of osteocalcin.
 Magnesium is abundant in foods, and magnesium
deficiency is quite rare in the absence of a serious
chronic disease.
 Dietary phytoestrogens, which are derived primarily
from soy products and legumes (e.g., garbanzo beans
[chickpeas] and lentils), exert some estrogenic activity
but are insuf-ficiently potent to justify their use in
place of a pharmacologic agent in the treatment of
osteoporosis

64.  Exercise in young individuals increases the
likelihood that they will attain the maximal
genetically determined peak bone mass.
 Weight bearing exercise in post menopausal
women helps prevent bone loss but does not
appear to result in substantial gain of bone
mass.
 A walking program is a practical way to start.
 Water exercises.

66.  Estrogens
 Reduce bone turnover, prevent bone loss, and induce
small increases in bone mass of the spine, hip, and total
body.
 Estrogens are efficacious when administered orally or
transdermally.
 standard recommended doses have been 0.3 mg/d for
esterified estrogens, 0.625 mg/d for conjugated equine
estrogens, and 5 μg/d for ethinyl estradiol. For
transdermal estrogen, the commonly used dose
supplies 50 μg estradiol per day

67.  Epidemiologic databases indicate that women who
take estrogen replacement have a 50% reduction,
on average, of osteoporotic fractures, including
hip fractures.
 The beneficial effect of estrogen is greatest among
those who start replacement early and continue
the treatment; the benefit declines after
discontinuation to the extent that there is no
residual protective effect against fracture by 10
years after discontinuation.
 relative risks included a 40% increase in stroke, a
100% increase in venous thromboembolic disease,
and a 26% increase in risk of breast cancer

69.  Two SERMs are used currently in postmenopausal
women: raloxifene (60 mg/d) and tamoxifen.
 A third SERM, bazedoxifene, has been complexed with
conjugated estrogen, creating a tissue selective
estrogen complex (TSEC). This agent has been
approved for prevention of osteoporosis.proved even
better then raloxifene.
 Unlike estrogens tamoxifen has reduced a/e of breast
cancer especially er positive ca breast(upto 65%)
 Raloxifene, with positive effects on breast cancer and
vertebral fractures, has become a useful agent for the
treatment of the younger asymptomatic
postmenopausal woman,but increase dvt and stroke
so avoided in >70 yrs age.

70.  Alendronate, risedronate, ibandronate, and
zoledronic acid are approved for the prevention and
treatment of postmenopausal osteoporosis.
 Zoledronic acid is a potent bisphosphonate with a
unique administration regimen (5 mg by slow IV
infusion annually). The data confirm that it is highly
effective in fracture risk reduction.
 Bisphosphonates are structurally related to pyro-
phosphates, compounds that are incorporated into
bone matrix.
 Bisphosphonates specifically impair osteoclast
function and reduce osteoclast number, in part by
inducing apoptosis

72.  There was an increased risk of transient postdose
symptoms (acute phase reaction) manifested by fever,
arthralgia, myalgias, and headache. The symptoms
usually last less than 48 h.other a/e atrial fibrillation
and transient reduction in renal function.
 Recent 2 potential side effects
 The first is osteonecrosis of the jaw (ONJ) following
dental procedure.
 The second side effect is called atypical femur
fracture. These are unusual fracture. Pain precedes
these #

74.  Its physiologic role is unclear because no skeletal
disease has been described in association with calcitonin
deficiency or excess
 mode of action Calcitonin suppresses osteoclast activity
by direct action on the osteoclast calcitonin receptor
 Calcitonin preparations are approved by the FDA for
Paget’s disease, hypercalcemia, and osteoporosis in
women >5 years past menopause.
 Calcitonin is not indicated for prevention of osteoporosis
and is not sufficiently potent to prevent bone loss in
early postmenopausal women. Calcitonin might have an
analgesic effect on bone pain, both in the subcutaneous
and possibly the nasal form

75.  mode of action Denosumab is a fully human
monoclonal antibody to RANKL, the final
common effector of osteoclast formation, activ-
ity, and survival. Denosumab binds to RANKL,
inhibiting its ability to initiate formation of
mature osteoclasts from osteoclast precursors.
 Denosumab was approved by the FDA in 2010 for
the treatment of postmenopausal women who
have a high risk for osteoporotic fractures,
including those with a history of fracture or
multiple risk factors for fracture, and those who
have failed or are intolerant to other
osteoporosis therapy

77.  mode of action Exogenously administered PTH
appears to have direct actions on osteoblast
activity, with biochemical and histomorphometric
evidence of de novo bone formation early in
response to PTH, before activation of bone
resorption.
 Teriparatide (1-34hPTH) is approved for the
treatment of osteoporosis in both men and
women at high risk for fracture
 Dose(Teriparatide (1-34hPTH )-20 ug SC OD x
maximum 2 years.

79.  Side effects of teriparatide are generally
mild leg cramps,
 muscle pain,
 weakness, dizziness, headache, and nausea.
 Rodents given prolonged treatment with PTH
in relatively high doses developed osteogenic
sarcomas. Long-term surveillance
 studies suggest no association between 2
years of teriparatide administration and
osteosarcoma risk in humans

80.  Despite incre-ments in bone mass of up to
10%, there are no consistent effects of
fluoride on vertebral or nonvertebral fracture
 The latter may actually increase when high
doses of fluoride are used. Fluoride remains
an experimental agent despite its long history
and multiple studies

81.  Not available in india
 MOA- by preventing resorption as well as
slightly promoting bone formation. Strontium is
incorporated into hydroxyapatite, replacing
calcium.
 in clinical trials, the drug reduced the risk of
vertebral fractures by 37% and that of
nonvertebral fractures by 14%.
 A/E-severe dermatologic reactions, seizures, and
 abnormal cognition,dvt

82.  Growth harmone
 Anabolic steroids
 Statins
 sclerostin antibodies, which inhibit sclerostin,
activate Wnt, and might be highly anabolic to
bone.
 Odanacatib is a mixed antiresorptive, partial
bone formation stimulator that is currently in
the late stages of development

83.  In all age group- Ca and vit D3
 Perimenopausal and early menopause :HRT
 Next 10 years :SERMS
 After 65 years :prefrebly biphosphonates
 High risk of # : PTH
 Severe pain due to #: calcironin
 Combination of above.

84.  There are currently no well-accepted
guidelines for monitoring treatment of
osteoporosis.
 it is reasonable to consider BMD as a
monitoring tool.
 BMD should be repeated at intervals >2 years
 Biochemical markers of bone turnover may
prove useful for treat-ment monitoring.

85.  Hip #/# long bones-almost always require
surgical repair if the patient is to become
ambulatory again. procedures may include open
reduction and internal fixation with nails and
plates, hemiarthroplasties, and total
arthroplasties.
 Other fractures (e.g., vertebral, rib, and pelvic
fractures) usually are managed with supportive
care, requiring no specific orthopedic treatment.
 Only ~25–30% of vertebral compression fractures
present with sudden-onset back pain treated with
analgesics,calcitonin,PERCUTANEOUS injection of
PMMA (vertebroplasty or kyphoplasty)

87.  Ganong physiology
 Harrison’s texbook of internal medicine.
 Turek’s orthopaedics
 Aplay system of orthopedics
 Tripathi pharmacology textbook
 Mescape
 Internet sources