OSTEOPOROSIS DR ZUBAIR PG SCHOLAR

1. OSTEOPOROSIS

2. DEFINITION
 Osteoporosis is a common metabolic bone disease characterized by
 1. Reduced bone mass,
 2. Microarchitectural deterioration of bone tissue, and
 3. An increased risk of fragility fracture.

3. Osteoporosis byWHO
 Individuals with BMD values more than 2.5 standard
deviations below the average in young healthy subjects (T-
score <-2.5) are classified as having osteoporosis.
 People with lesser reductions in BMD (T-score between −1
and −2.5) are classified as having osteopenia whereas
 People with T-score values between −1 and +2.5 are said to
have normal bone mass.

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 countries : 70 – 80
years
 India : 50 – 60 years

5.  In women it is Three times morecommon 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 mineralizedmatrix
 Under influence of PTH, participate inbone resorption and
calcium ion transport.
 2.OSTEOBLASTS-
 Mesenchymal cells derived from marrow stromal cells.
 Responsible for mineralization of bonematrix.
 Responsible for secretion of type 1 collagen and large number of non
collagenous boneproteins.

8.  3.OSTEOCLASTS-
 EXCLUSIVELY BONE RESORBING CELLS.
 Appear at sites of high boneturnover.
 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, alkalinephosphate
 Function is regulation of bone cells and matrix mineralisation.
 C.BONE MORPHOGENIC PROTEINS-
 A collection of growth factor proteins.
 Important in inducing differentiation of progenitorcells.
 Used in treatment of bone defects, non unions ,delayed unions.

11. PATHOPHYSIOLOGY
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. 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
•Womenachieve lesserpeak bone mass than men
15

15. BONE REMODELLING CYCLE : The bone remodeling cycle is responsible for renewal and repair of bone
throughout life. Bone is removed by multinucleated osteoclasts which are thought to be able to detect and
remove areas of micro damage. After about 10 to 12 days osteoclasts undergo programmed cell death
(apoptosis) and are replaced by osteoblasts which lay down new bone in the resorption lacuna. Some
osteoblasts become trapped in bone matrix and differentiate into osteocytes which are responsible for
detecting and responding to mechanical strain. When bone formation is complete the matrix mineralizes and
the bone surface becomes quiescent and covered with flat lining cells.

16.  Bone resorption is carried out by osteoclasts which are multinucleated cells derived
from the monocytes/macrophage lineage.
 The RANK signaling pathway plays a critical role in regulating osteoclast
differentiation and bone resorption.
 The RANK receptor is a member of the tumor necrosis factor (TNF) receptor
superfamily which is expressed on osteoclast precursors and mature osteoclasts.
 It is activated by a molecule called RANK ligand (RANKL) which is a member of the
TNF superfamily

17. MOLECULAR REGULATION OF BONE TURNOVER: Osteocytes play a central role in regulating bone resorption and
formation. They regulate bone resorption (left side) by releasing RANKL which binds to RANK on osteoclast precursors
triggering osteoclast differentiation and bone resorption, which is mediated by secretion of hydrochloric acid (HCl) and
cathepsin K (CatK) onto the bone surface. Osteoprotegerin (OPG) inhibits bone resorption by binding to RANKL and
preventing it activating RANK. Other sources of RANKL include T-cells and stromal cells. Osteocytes regulate bone
formation by secreting sclerostin (SOST) which binds to the LRP5/frizzled (LRP5/ frz) coreceptor, preventing its activation
by Wnt family members, thereby suppressing
bone formation.

18.  OSTEOPOROSIS results from bone loss due to age related changes in
bone remodelling as well as extrinsic and intrinsic factors that exaggerate
this process.

19. GROWTH FACTORS AND HORMONES REGULATING BONE REMODELLING
Factor Target cells & tissue Effect
Interleukins
(IL-l, IL-3, lL-6, IL-ll)
Bone marrow,osteoclasts Stimulate osteoclast
formation & resorption
Tumor necrosisfactor (TNF-a) ;
Granulocyte macrophage
stimulating factor
(GM-CSF)
Osteoclasts Stimulates boneresorption
Leukemic inhibitory Factor Osteoblasts, osteoclasts Stimulates osteoblastand Osteoclast
formation in marrow

20. Factor Targetcells Effect
Parathyroid Hormone
(PTH)
Kidney & Bone Stimulate production of Vit-D &
helps resorption of calcium
Calcitonin Boneosteoclasts Inhibits resorptive action of osteoclasts:
lowerscirculating Calcium.
Calcitriol
(1.25-dihydroxyvit-D3)
Bone Osteoblasts
Bone Osteoclasts, Kidney,
Intestine
-Stimulates collagen,osteopontin, osteocalcin
synthesis;
-stimulates celldifferentiation;
-Stimulates Calcium retention
-Stimulates calciumabsorption
Estrogen Bone Stimulates formation of calcitonin receptors,
inhibiting resorption,; Stimulate bone formation
Testosterone Muscle, Bone Muscle growth, placing stress on bone to
stimulate boneformation
Prostaglandins Osteoclasts Stimulate resorption and bone
formation
Bone Morphogenic protein Mesenchyme Stimulate cartilage protein &bone matrix
formation; replication

21. CLASSIFICATION
 NORDIN – 1. Generalized
2. Localized
 RIGGS AND MELTON
 A. Primary osteoporosis – type 1 postmenopausal
type 2 senile
 B. Secondary osteoporosis

22. PRIMARY OSTEOPOROSIS
 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 age of 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. SECONDARY OSTEOPOROSIS

24. SECONDARY OSTEOPOROSIS

25. CLINICAL PRESENTATION
 A/K SILENT DISEASE.
 The most common clinical presentation of osteoporosis is with fractures of
various types.
 Vertebral fractures present with acute back pain which can be localized to
the affected site or can radiate to the anterior chest wall or abdomen.
 Many patients with vertebral fractures present insidiously with height loss
or kyphosis and chronic back pain.
 In addition to pain and height loss, patients with multiple vertebral
fractures may experience abdominal discomfort and distension due to
compression of abdominal organs by severe kyphosis.
 Other common sites of fracture include hip and wrist.

26. Risk Factors for Fracture
(Major) with relative risk>2 (Minor) with relative risk1-2
Age >70 Estrogen deficiency
Menopause <45 Calcium intake <500mg/day
Hypogonadism Primary hyperparathyroidism
Fragility fracture Rheumatoid arthritis
Hip fracture h/o inparents Hypercalciuria
Glucocorticoids Anticonvulsants
High boneturnover Diabetes mellitus
Anorexia nervosa Smoking
<18 BMI Alcohol
Immobilisation/sedentary life
Chr. Renal failure
Transplantation
Chronic Inflammatorydiseases

28. DIFFERENTIAL DIAGNOSIS
 HYPERPARATHYROIDISM
 PAGETS DISEASE
 OSTEOMALACIA
 OSTEOGENESIS IMPERFECTA
 MULTIPLE MYELOMA
 SECONDARYTUMOURS

29. DIAGNOSIS:
WORK UP FOR SECONDARY OSTEOPOROSIS
 1. History and physical examination with focus on secondary causes of
osteoporosis.
 2. Perform CBC.
 3. Perform routine biochemical tests.
 4. Determine creatinine, blood urea nitrogen, total calcium, phosphate, albumin
and alkaline phosphatase levels.
 5. Determine serum 25- hydroxyvitamin D levels.
 6. Perform PTH and TSH levels.
 7. Determine total and free testosterone levels (for men).

30.  Determine estradiol, FSH, LH and prolactin levels in young amenorrheic women.

31. IMAGING
 Standard radiographs have poor sensitivity for the detection and monitoring of
osteoporosis, since large amounts of bone mineral (up to 30%) must be lost or
gained from the skeleton before it can be reliably detected on plain radiographs.
 The principal application of radiographic examination in the assessment of patients
with osteoporosis is in the diagnosis of fractures.

32. 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 70TO 79 IF BMD T SCORE AT
THE SPINE, TOTAL HIP OR FEMORAL NECK < -1.5.

33. 3. POSTMENOPAUSAL WOMEN AND MEN AGE 50 AND OLDER WITH SPECIFIC
RISK FACTORS LIKE
A. LOW TRAUMA FRACTURE DURING ADULTHOOD.
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 TREATMENT.

34. CONVENTIONAL RADIOGRAPHIC
FINDINGS
 LS SPINE
 Generalized osteopenia
 Thinning and accentuation ofcortex
 Accentuation of primary trabeculae and thinning of secondary trabaculae.
 Vertically striated appearance vertebralbody.

36. SINGH INDEX – GRADE 3 AND BELOW INDICATE DEFINITE OSTEOPOROSIS

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

38. BONE MINERAL DENSITY MEASUREMENT
INDICATIONS FOR BMD TESTING
 In women age 65 and older and men age 70 and older
 In postmenopausal women (Estrogen-deficient women) and men age 50 and older
who have had an adult age fracture, to diagnose and determine degree of
osteoporosis
 Individual with vertebral abnormalities - plain film
 More than 3 months of steroid treatment
 Primary hyperparathyroidism
 Pt. with strong Family History of osteoporosis.

39. DEXA SCAN
 Commercially introduced in 1987.
 Principle – 2 x ray of 70Kv and 140kv are fired on site of measurement with lag time
0f4ms.
 Detector detects accentuation of 2 beams.
 Data is fed into computer powered with complex algorithm and calculates
BMD.
 SITES
 Central dexa- lumbar spine, hip, wholebody.
 Peripheral dexa- forearm , calcaneum.

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

42. 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 andBMD.
 Results evaluated are given in % of risk of patient developing fracture in next
10years.

43. FRAX

44.  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 recalculatethe 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 measurementmay sometimes be appropriate, particularly in younger
postmenopausal women -
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 riskfactors

45. MANAGEMENT

48. 2.LIFESTYLE MODIFICATIONS-
 a. Physical activity-weight bearing andmuscle strengthing exercises.
Exercise improves bone strength by 30%to50%. Exercise should be life
long.
 b. Cessation of smoking, alcohol,high caffeineintake.
 c. Adequate sun exposure.

49. 3. Prevention of falls
 a. Exercises like balance training, lowerlimb strengthing exercises.
 b. Correction of sensory impairment like correction of low vision and hearing
impairments.
 c. Reduce environmental hazards.
 d. Appropriate reduction ofmedications.
 e. Education of individual in behaviorstrategies.

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

51. PHARMACOLOGICAL PREVENTION OF
OSTEOPOROSIS
 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 mayincrease the risk of developing kidney
stones, cardiovascular disease, and stroke.

52. VITAMIN D
 800 to 1000 international units (IU) of vitamin D per day for adults age 50 andolder.
 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.

53. 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 obtainedif monitoring of treatment is
planned

54. Who should be considered for treatment?
Postmenopausal women and men age 50 and older presenting with the
following should beconsidered-
 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 %.

55. Bisphosphonates: Are analogues ofpyrophosphates.
MOA- attach to bone remodeling sites.
Cause apoptosis of osteoclasts by by disrupting cytoskeleton.

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

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

58.  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 patientshould sit upright for 1hr.

59.  Ibandronate, 3 mg/3 ml prefilled syringe, is given by intravenous injection over 15
to 30 s. Serumcreatinine should be checked before eachinjection.
 Zoledronic acid, 5 mg in 100 ml is given byintravenous infusion over at least 15min.
 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).

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

61. Calcitonin
 Treatment of osteoporosis in women who are at least 5 years postmenopausal when
alternativetreatments 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.

62.  HORMONE REPLACEMENT THERAPHY-
 Estrogen with or without progestin is used.
 Also relieves symptoms of postmenopausalsymptoms, vulvovaginal atrophy.
 Dose-0.625mg daily.
 Routes –oral,transdermal

63.  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.

64.  Teriparatide is approved for the treatment of osteoporosis in postmenopausal
women and menat high risk forfracture.
 It is also approved for treatment in men and women at high risk of fracture with
osteoporosis associated with sustained systemic glucocorticoidtherapy.
 DOSE-20 μg daily subcutaneous injection.
 Duration not to exceed 18 to 24months.

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

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

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

68. PREVENTION 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

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

70. FRACTURE FIXATION IN OSTEOPOROTIC
BONE
 The major technical problem the surgeon faces is the difficulty to produce
secure fixation of the implant to the bone.
 There is less cortical and cancellous bone for the screw threads to gain
purchase and the pullout strength of implants is significantly lower in
osteoporotic bone.
 If the load transmitted at the bone-implant interface exceeds the strain
tolerance of osteoporotic bone, microfracture and resorption of bone with
loosening of the implant and secondary failure of fixation will occur.
 The common mode of failure of internal fixation in osteoporotic bone is
bone failure rather than implant breakage.

71.  To decrease the risk of failure at the bone-implant interface the following
is recommended:
 techniques of relative stability including bridging and buttress fixation;
 devices providing angular stability;
 intramedullary nails;
 controlled bone impaction;
 bone augmentation;
 joint replacement.

72.  In osteoporotic bone it may not always be possible to obtain and maintain
anatomical reduction and compression with absolute stability because the
weakened cortical and cancellous bone may fail under compression.
 Thus, internal fixation techniques that provide absolute stability through
interfragmentary compression are usually not appropriate
 Intramedullary nails are load sharing and provide relative stability. They
seem to be the most efficient method of reducing strain at the bone-
implant interface

73.  Plates are load bearing: Due to their eccentric position,very long implants
fixed with few locking head screws should be applied to distribute the
stress.
 Short plates with every screw hole filled will cause concentration of forces,
which may exceed the strain tolerance of osteoporotic bone

74.  Sequential screw pullout always starts at the end of the plate where
motion (and strain) is greatest.
 Fixed-angle devices, such as the angled blade plate, DHS,
and DCS, are very useful in osteoporotic bone

75.  The internal fixator principle is based on the angular stability of the locking
head screws (LHS).
 In addition, these screws have a larger core diameter than conventional
screws, which results in a higher pullout strength and overall strength. This
is especially helpful in metaphyseal bone, where intramedullary nails may
fail.

77.  Bone impaction is a key element in the surgical management of
osteoporotic fractures as it reduces the risk of implant failure.
 Controlled impaction can be attained by tensioning internal fixation
devices. Implants, such as the dynamic hip screw (DHS), allow controlled
impaction of the fracture while preventing penetration of the joint by the
hip screw.

78.  Fixation strength can also be improved by bone augmentation using bone
autograft or allograft, bone cement, or bone substitutes.
 Joint replacement may be a good option in articular fractures and some
metaphyseal fractures where the complication rate of internal fixation is high

79. VERTEBRAL FRACTURES
 Vertebroplasty uses direct bone cement injection into the vertebral body.
 This is performed through a pedicular or extrapedicular approach and with control
of an image intensifier
 There is no reduction of the kyphotic deformity or restoration of vertebral height
and the aim is to prevent further collapse and relieve pain

80.  Kyphoplasty uses a balloon, which is introduced into the vertebral body and
inflated to reduce the fracture and restore vertebral height.
 The resulting cavity is then injected with low-pressure cement.
 Vertebroplasty and kyphoplasty lead to good pain relief in a high percentage of
patients

81. THANK YOU