1.
PRESENTER – Dr. R.P.RAGHAVENDRA RAJU

2.
DEFINITION
 Osteoporosis is a systemic skeletal disease
characterized –
 1. low bone density
 2. a micro- architecture deterioration of bone
tissue
 3. that enhances bone fragility
 4. increases the risk of fracture

3.
Osteoporosis by WHO
BMD 2.5 SD or more below the mean for young healthy
adult of same gender(T-score at or below -2.5).

4.
Epidemiology
 1 in 3 women over 50 years suffer from osteoporosis.
 1 in 5 men over 50 years suffer from osteoporosis.
 15% - 30% men and 30%- 50% women suffer fractures
related to osteoporosis in their life time.
 Peak incidence-
western – 70 – 80 years
india – 50 – 60 years

5.
In women it isThree times more common
than men
1.low peak bone mass (PBM)
2.hormonal changes at menopause
3.live longer than men
 vertebral #s and wrist #s more common in women

6.
CONSTITUENTS OF BONE

7.
CELLS
 1.OSTEOCYTES-
 Are mononuclear cells in mineralized matrix
 Under influence of PTH, participate in bone
resorption and calcium ion transport.
 2.OSTEOBLASTS-
 Mesenchymal cells derived from marrow stromal cells.
 Responsible for mineralization of bone matrix.
 Resonsible for secretion of type 1 collagen and large
number of non collagenous bone proteins.

8.
 3.OSTEOCLASTS-
 EXCLUSIVELY BONE RESORBING CELLS.
 Appear at sites of high bone turnover.
 Contain characteristic TRAP and carbonic anhydrase.

9.
MATRIX
 Mainly consists of collagenous and non collagenous
matrix-
 A.TYPE 1 COLLAGEN-
 Forms a scaffold on which mineralization occurs.
 Produced by osteoblasts.
 Makes upto 80% of unmineralized bone matrix.

10.
 B. NON COLLAGENOUS PROTEINS-
 Osteopontin, osteonectin, osteocalcin, alkaline phosphate
 Function is regulation of bone cells and matrix
mineralisation.
 C.BONE MORPHOGENIC PROTEINS-
 A collection of growth factor proteins.
 Important in inducing differentiation of progenitor cells.
 Used in treatment of bone defects, non unions , delayed
unions.

11.
1.PEAK BONE MASS
2.BONE REMODELLING

12.
1.Peak bone mass & Osteoporosis
 Peak bone mass is the maximum mass of bone achieved
by an individual at skeletal maturity, typically between
ages 25 and 35
 After peak bone mass is attained, both men and
women lose bone mass over the remainder of their
lifetimes
 Because of the subsequent bone loss, peak bone
mass is an important factor in the development of
osteoporosis 13

13.
Determinants Of Peak Bone Mass
Peak Bone Mass
Physical activity Gonadal status
Nutritional statusGenetic factors

14.
Peak Bone Mass in Women
10 20 30 40 50 60
•Women achieve lesser peak bone mass than men
15

15.
BONE MODELLING AND
REMODELLING
 MODELLING- during growth, skeleton increases in
size by apposition of new bone tissue on outer surface
of cortex.
 REMODELLING- It is a cellular process of bone
activity by which both cortical and cancellous bone are
maintained.

16.
 OSTEOPOROSIS results from bone loss due to age
related changes in bone remodelling as well as
extrinsic and intrinsic factors that exagerate this
process.
 Bone remodelling has two main functions-
 1.to repair micro damage within skeleton to maintain
skeletal strength.
 To supply calcium to maintain serum calcium levels.

17.
RANK – RANKL RECEPTOR
PATHWAY FOR BONE
REMODELLING
 RANK L- the cytokine responsible for communication
between osteoblasts and other marrow cells and
osteoclasts.( receptor activated nuclear factor kappa
ligand)
 Secreted by osteoblats and certain cells of immune
system.
 RANK- receptor present on osteoclast.
 Activation of RANK by RANKL is final common
pathway for osteoclast differentiation and functioning.
 Osteoprotegerin is humoral decoy for RANK secreted
by osteoblasts.

18.
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

19.
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

20.
CLASSIFICATION-
1.NORDIN – 1. generalized
2. localized
2. RIGGS AND MELTON-
a.Primary osteoporosis –type 1 post menopausal
type 2 senile
b.Secondary osteoporosis

21.
Post-Menopausal Osteoporosis
 Caused by a lack of estrogens, which helps to
regulate, the incorporation of calcium into bone in
women.
 Lack of estrogen increased bone resorption
 AGE RELATED OSTEOPOROSIS
 Usually affects people over 70 y.
 Results from age-related calcium deficiency.
 There is decreased bone formation.
 Patients usually present with fractures of the hip and
the vertebrae.
23

22.
SECONDARY OSTEOPOROSIS

23.
CLINICAL FEATURES
 A/K SILENT DISEASE.
 Low back ache- usually mild.
 Loss of height
 KYPHOSIS
 Fractures- mc vertebral and hip.

24.
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

25.
DIFFERENTIAL DIAGNOSIS
 HYPERPARATHYROIDISM
 PAGETS DISEASE
 OSTEOMALACIA
 OSTEOGENESIS IMPERFECTA
 MULTIPLE MYELOMA
 SECONDARY TUMOURS

26.
WORK UP FOR SECONDARY
OSTEOPOROSIS

27.
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.

28.
INDICATIONS FOR VERTEBRAL
IMAGING
1.ALL WOMEN AGE 70 AND OLDER AND ALL MEN
AGE 80 AND OLDER IF BMD T SCORE AT THE
SPINE, TOTAL HIP OR FEMORAL NECK IS <-1.0
2.WOMEN AGE 65 TO 69 YEARS AND MEN AGE 70 TO
79 IF BMD T SCORE AT THE SPINE, TOTAL HIP OR
FEMORAL NECK <-1.5

29.
3.POSTMENOPAUSAL WOMEN AND MEN AGE 50 AND
OLDER WITH SPECIFIC RISK FACTORS LIKE
A.LOW TRAUMA FRACTURE DURING ADULTHOOD{AGE
50}
B.HISTORICAL HEIGHT LOSS OF 1.5 INCHES OR
MORE{4cm}
C.PROSPECTIVE HEIGHT LOSS OF 0.8INCHES OR
MORE{2cms}
D.RECENT OR ONGOING LONG TERM
GLUCOCORTICOID TRATMENT

30.
CONVENTIONAL RADIOGRAPHY
 LS SPINE-
 Generalized osteopenia
 Thining and accentuation of cortex
 Accentuation of primary trabeculae and thinning of
secondary trabaculae.
 Vertically striated appearance vertebral body.

31.
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.

32.
HIP X RAY

33.
 Disadvantages-
 Subjective
 Affected by body habitus , exposure, positioning.
 >30% bone loss should be present.

34.
INDICATIONS FOR BMD TESTING
 In women age 65 and older and men age 70 and older
 In postmenopausal women and men above age 50–69,
based on risk factor profile
 In postmenopausal women and men age 50 and older
who have had an adult age fracture, to diagnose and
determine degree of osteoporosis
 At dual-energy X-ray absorptiometry (DXA) facilities
using accepted quality assurance measures

35.
Sites of measurement are the spine, the hip, calcaneum
and the wrists.

36.
DEXA SCAN
 Commercially introduced in 1987.
 Principle – 2 x ray of 70Kv and 140kv are fired on site of
measurement with lag time 0f 4ms.
 Detector detects accentuation of 2 beams.
 Data is fed into computer powered with complex
algorithm and calculates BMD.
 SITES-
 Central dexa- lumbar spine, hip, whole body.
 Peripheral dexa- forearm , calcaneum.

37.
 CONTRAINDICATIONS-
 PREGNANCY.
 RECENT ADMINISTRATION OF CONTRAST.
AGENT,NUCLEAR MEDICINE SCAN.
 RADIOPAQUE IMPLANT IN MEASUREMENT AREA.
 MARKED OBESITY.

38.
BONE TURN OVER MARKERS

39.
BIOCHEMICAL MARKERS OF BONE
TURNOVER
1.PREDICT THE RISK OF FRACTURE
INDEPENDENTLY OF BONE DENSITY IN
UNTREATED PATIENTS
2.PREDICT RAPIDITY OF BONE LOSS IN UNTREATED
PATIENTS
3.PREDICT EXTENT OF FRACTURE RISK REDUCTION
WHEN REPEATED AFTER 3-6 MONTHS OF
TREATMENT WITH FDA APPROVED THERAPIES

40.
4.PREDICT MAGNITUDE OF INCREASE IN BMD
WITH FDA APPROVED THERAPIES
5.HELP DETERMINE DURATION OF DRUG HOLIDAY
AND WHEN AND IF MEDICATION SHOULD BE
RESTARTED

41.
WHO FRAX SORING TOOL
 A web based algorithm designed to calculate the 10
year probability of major osteoporosis related fracture
based on clinical risk factors and BMD.
 Results evaluated are given in % of risk of patient
developing fracture in next 10 years.

42.
FRAX

43.
 Following assessment of fracture risk using FRAX, the
patient can be classified according to the NOGG
intervention thresholds: -
 Low risk – reassure, give lifestyle advice and reassess in
≤5 years depending on the clinical context.
 Intermediate risk - measure BMD and recalculate the
fracture risk to determine whether the individual's
risk lies above or below the intervention threshold.
 –
 High risk - can be considered for treatment without
the need for BMD, although BMD measurement may
sometimes be appropriate, particularly in younger
postmenopausal women -

44.
 Recalculate- after a minimum of 2 years if the original
calculated risk was in the region of the intervention
threshold or if the individual’s risk factors

45.
1.NON
PHARMACOLOGICAL –
PREVENTION OF
OSTEOPOROSIS AND
OSTEOPOROTIC
FARCTURE.
A.NUTRITION
B.LIFE STYLE
MODIFICATIONS
C.PREVENTION OF
FALL
D.HIP PROTECTORS
2. BASIC THERAUPETIC
MEASURES
A. VIT D AND
CALCIUM
SUPPLEMENTATIO
N
B. ESTEROGEN AND
HRT
3.ANTI RESORBTIVE
AGENTS
A.CALCITONIN
B. BISPHOSHPHANTES
C.SERM
D.DONESUMAB
4. DRUGS STIMULATE
BONE FORMATION
A.SODIUM FLOURIDE
B.EXOGENOUS PTH
C.VIT D ANALOGUES
5. DRUGS WITH DUAL
ACTION
A.STRONTIUM
RANELATE

46.
2.LIFESTYLE MODIFICATIONS-
a.Physical activity-weight bearing and muscle
strengthing exercises.
Exercise improves bone strength by 30%to 50%.
Exercise should be life long.
b.Cessation of smoking,alcohol,high caffeine intake.
c.Adequate sunexposure

47.
Prevention of falls
 a. Exercises like balance training, lower limb
strengthing exercises
 b. Correction of sensory impairment like
correction of low vision and hearing impairments
 c. Reduce environmental hazards
 d. Appropriate reduction of medications
 e. Education of individual in behavior strategies

48.
4.HIP PROTECTORS-PREVENT DIRECT IMPACT ON
PELVIS.
1.Energy absorption type
2.Energy shunting types
3.Crash helmet type
4.Airbag type

49.
 Men age 50–70 should consume 1000 mg/day of
calcium.
 Women age 51 and older and men age 71 and older
consume 1200 mg/day of calcium.
 Intakes in excess of 1200 to 1500 mg/day may increase
the risk of developing kidney stones, cardiovascular
disease, and stroke.
PHARMACOLOGICAL PREVENTION
OF OSTEOPOROSIS

50.
VIT D
 800 to 1000 international units (IU) of vitamin D per day
for adults age 50 and older.
 Treatment of vitamin D deficiency-
Adults should be treated with 50,000 IU once a week or the
equivalent daily dose (7000 IU vitamin D2 or vitamin D3)
for8–12 weeks to achieve a 25(OH)D blood level of
approximately 30 ng/ml.
This regimen should be followed by
maintenance therapy of 1500–2000 IU/day.

51.
Pharmacologic therapy
 All patients being considered for treatment of
osteoporosis should also be counseled on risk factor
reduction including the importance of calcium,
vitamin D, and exercise as part of any treatment
program for osteoporosis.
 Prior to initiating treatment, patients should be
evaluated for secondary causes of osteoporosis and
have BMD measurements by central DXA, when
available, and vertebral imaging studies when
appropriate.
 Biochemical marker levels should be obtained if
monitoring of treatment effects is planned.

52.
Who should be considered for
treatment?
Postmenopausal women and men age 50 and older
presenting with the following should be considered-
 A hip or vertebral fracture (clinically apparent or found
on vertebral imaging).
 T-score ≤−2.5 at the femoral neck, total hip, or lumbar
spine.
 Low bone mass (T-score between −1.0 and −2.5 at the
femoral neck or lumbar spine)
 a 10-year probability of a hip fracture ≥3 % or a 10-year
probability of a major osteoporosis-related fracture
≥20 %.

53.
Bisphosphonates
 Are analogues of pyrophosphates.
 MOA- attach to bone remodelling sites.
 Cause apoptosis of osteoclasts by by disrupting
cytoskeleton.

54.
 Alendronate-
 prevention -5 mg daily and 35 mg weekly tablets.
 treatment -10 mg daily tablet, 70 mg weekly tablet,
70 mg weekly tablet.
 Alendronate is also used in treatment of osteoporosis
in men and women taking glucocorticoids.

55.
 Ibandronate-
 Treatment-150 mg monthly tablet and 3 mg every
3 months by intravenous injection.
 Risedronate-
 prevention and treatment -5 mg daily tablet; 35 mg
weekly tablet ,150 mg monthly tablet.

56.
 Zoledronic acid
 prevention and treatment -5 mg by intravenous
infusion over at least 15 min once yearly for treatment
and once every 2 years for prevention.
 Drug administration-
 Oral tablets should be taken early morning on empty
stomach, 6o mins before breakfast ,and patient should
sit upright for 1 hr.

57.
 Ibandronate, 3 mg/3 ml prefilled syringe, is given by
intravenous injection over 15 to 30 s. Serum creatinine
should be checked before each injection.
 Zoledronic acid, 5 mg in 100 ml is given by intravenous
infusion over at least 15 min.
 Patients should be well hydrated and may be pre-
treated with acetaminophen to reduce the risk of an
acute phase reaction (arthralgia, headache, myalgia,
fever).

58.
Drug safety
 Side effects for all oral bisphosphonates
gastrointestinal problems such as difficulty swallowing
and oesophagitis and gastritis.
 All bisphosphonates are contraindicated in patients
with estimated GFR below 30–35 ml/min.
 osteonecrosis of the jaw (ONJ) can occur with long-
term use of bisphosphonates (>5year).
 Although rare, low-trauma atypical femur fractures
may be associated with the long-term use of
bisphosphonates (e.g., >5 years of use).

59.
Calcitonin
 Treatment of osteoporosis in women who are at least
5 years postmenopausal when alternative treatments
are not suitable.
 200 IU delivered as a single daily intranasal spray.
 Intranasal calcitonin can cause rhinitis, epistaxis, and
allergic reactions.
 Very small increase in the risk of certain cancers.

60.
E. HORMONE REPLACEMENT THERAPHY-
Esterogen with or without progestin is used.
Also relieves symptoms of postmenopausal symptoms,
vulvovaginal atrophy.
Dose-0.625mg daily.
Routes –oral,transdermal

61.
Side effects- increased incidence of coronary heart
disease events, strokes, pulmonary embolisms, and
invasive breast cancers
 The overall health risks from estrogen exceeds the
benefits from use.

62.
PTH, teriparatide
 Teriparatide is approved for the treatment of
osteoporosis in postmenopausal women and men at
high risk for fracture.
 It is also approved for treatment in men and women at
high risk of fracture with osteoporosis associated with
sustained systemic glucocorticoid therapy.
 DOSE-20 μg daily subcutaneous injection.
 Duration not to exceed 18 to 24 months.

63.
 When treatment is stopped, bone loss can be rapid
and alternative agents should be considered to
maintain BMD.
 SIDE EFFECTS- leg cramps, nausea, and dizziness.
 CONTRA INDICATIONS-increased risk of
osteosarcoma (e.g., Paget’s disease prior radiation
therapy of the skeleton), bone metastases,
hypercalcemia, or a history of skeletal malignancy.

64.
F.SERMS-used for both prevention and treatment of
osteoporosis.
RALOXIFENE-60mg/day.
Side effects-increased risk of DVT,hot flushes,leg
cramps.

65.
G.DONESUMAB[RANKL INHIBITOR]-
Dose-60mg/6months S.C
Used in postmenopausal women.
Side effects-hypocalcemia , cellulitis ,skin rash.

66.
H.Tissue selective esterogen complex- Bazedoxifene.
Progesterone can be avoided.
Only for postmenopausal women who are not
undergone hysterectomy.

67.
PREVENTATION TREATMENT
Calcium 500mg to 1500 mg 1000 to 1500
Vit – D 400IU 400IU – 800IU
Bi phosphonates
1. Alendronate 5mg/day 10mg/day
2. Ibandronate - 150mg/month
3. Rsidronate - 5mg/day
4. Zolendronic acid 5mg/2 year 5mg/ 1 year
SERMS
Rolaxifen 5mg/day 10mg/day
Calcitonin 200 IU 200IU
Parathyroid harmone 20ug/d 20-40ug/d
Donesumab - 60mg/6 months

68.
NON FDA APPROVED DRUGS-
1.SODIUM FLUORIDE
2.STRONTIUM
3.CALCITRIOL
4.TIBOLONE
5.GENISTEIN

69.
Role of Orthopaedicians &surgical
management
 The goals of surgical treatment of osteoporotic
fractures include
 rapid mobilization and return to normal function
and activities
 Avoid too much manipulations
 Progressive physio therapy

70.
VERTEBRAL FRACTURES
 Vertebroplasty to reduce vertebral fracture–associated
pain
 Kyphoplasty to restore height or to treat the deformity
associated with osteoporotic vertebral fractures
 Progressive vertebral collapse or
deformity-pedicle scrwe fixation

71.
CHOICE OF IMPLANTS

72.
by bending load
PULLOUT OF REGULAR
SCREWS
Slide 83

73.
RESISTANCE AGAINST BENDING
LOAD
Slide 84

74.
UNI- VS. BICORTICAL SCREW FIXATION
female
Slide 85

75.
Thin cortices: choose screw diameter as large as
possible
Slide 86
FAILURE WITH UNICORTICAL SCREWS

76.
10 months
postop.
5 days later
Slide 87

77.
+6%
+18%
+36%
0
100
200
300
400
500
600
Load (N)
4.5 mm
Cortex,
bicortical
5.0 mm
Locking,
bicortical
4.0 mm
Locking,
bicortical
4.0 mm Locking,
unicortical
BIOMECHANICS: NORMAL BONE
Slide 88

78.
+17%
+82% +91%
0
100
200
300
400
500
600
Load (N)
4.5 mm
Cortex,
bicortical
5.0 mm
Locking,
bicortical
4.0 mm
Locking,
bicortical
4.0 mm
Locking,
unicortical
BIOMECHANICS:
OSTEOPENIC BONE
Slide 89

79.
OSTEOPOROTIC TRABECULAR
BONE:
CLINICAL CONSEQUENCES
 Cut out
 Loss of screw fixation
 Spontaneous fractures
Slide 90

80.
Augmentation to Improve Screw Fixation
Enlarges the bone implant surface area
NOT FDA APPROVED!Slide 91

81.
If bone is very poor, consider
prosthetic replacement
Slide 93

82.
DON’T FORGET THE SOFT
TISSUES
The wound must heal also
Skin is also 98 years old
Slide 94

83.
TAKE-HOME MESSAGES
 Age & bone quality affect cortical and trabecular bone
in different ways
 Absolute stability often not possible
 Principles of fixation:
 Angular stability
 Fracture reduction
 Long bridging plates
 Enlarged surface area of implant / bone
 Augmentation
 Prosthetic replacement
Slide 95

84.
Latest in Osteoporosis Treatment
 1.Carotenoids, Lycopene Reduce Fracture Risk
(Antioxidants)
“…reactive oxygen intermediates may be involved in the bone-
resorptive process and that fruit and vegetable-specific
antioxidants, such as carotenoids, are capable of decreasing
this oxidative stress. Therefore carotenoids may help in
preventing osteoporosis.
In particular, an inverse relation of carotenoids and lycopene
with biochemical markers of bone turnover has recently
been demonstrated.”
J Bone Miner Res. 2009 Jun;24(6):1086-94.

85.
 2.Omega-3 Fatty Acids Reduce hs-CRP1
 “This study provides evidence that in healthy individuals,
plasma n-3 fatty acid concentration is inversely related to
hs-CRP…”
 “High sensitivity C-reactive protein (hs-CRP) is a marker of
low grade sustained inflammation.”
 “Increased hs-CRP by just 1SD increases fracture risk by an
amazing 23 percent2.”
 Consider supplementing the diet with omega-3 fatty acids
(fish oil). They’re a great way to help reduce
inflammation, hs-CRP, cardiovascular disease, and
fractures related to osteoporosis.
1. Micallef M A et al., European Journal of Clinical Nutrition, 2009; April 8 [Epub ahead of print].
2. Pasco et al. JAMA. 2006;296(11):1353-1355

86.
 3.Vitamin K Improves Bone Strength and Reduces
Fractures
 Review of RCTs showed that vitamin K(1) and vitamin K(2)
supplementation reduced serum undercarboxylated
osteocalcin levels regardless of dose but that it had
inconsistent effects on serum total osteocalcin levels and no
effect on bone resorption.”
Iwamoto J et al., Nutrition Research, 2009; 29(4): 221-228.