osteoporosis

1. Dr Debasis Mukherjee
IPGME&R, KOLKATA
Dept. of Orthopaedics

2.  Older patients have frequent admissions and increased
length of stay, increasing possible points of contact
 Patients from nursing facilities, those at greatest risk, may
have little continuity
 Discharge medications for patients going to skilled nursing
facilities can have LARGE impact
 Study: Only 6% of patients admitted with hip fracture to a
tertiary care hospital were adequately treated for
osteoporosis at discharge, only 12% at 5 years!
 Another study: only 21% medicare beneficiaries with hip
fracture had any prescription treatment; patients older than
74 and those with other comorbidities were least likely to
receive treatment

3.  "A disease characterised by low bone mass
and microarchitectural deterioration of bone
tissue, leading to enhanced bone fragility and
a consequent increase in fracture risk".
 WHO: utilizes Bone Mineral Density as
definition (T score <-2.5); surrogate marker

4.  Cortical Bone
 Dense and compact
 Runs the length of the long bones, forming a
hollow cylinder
 Trabecular bone
 Has a light, honeycomb structure
 Trabeculae are arranged in the directions of
tension and compression
 Occurs in the heads of the long bones
 Also makes up most of the bone in the vertebrae

5.  Principal organizing feature of compact
bone
 Haversian canal – place for the nerve blood
and lymphatic vessels
 Lamellae – collagen deposition pattern
 Lacunae – holes for osteocytes
 Canaliculi – place of communication between
osteocytes

6.  Osteocytes - derived from
osteoprogenitor cells
 Osteoblasts
 Osteoclasts

7.  Trapped osteoblasts
 In lacunae
 Keep bone matrix in good condition and
can release calcium ions from bone matrix
when calcium demands increase
 Osteocytic osteolysis

8.  Make collagen
 Activate nucleation of hydroxyapatite
crystallization onto the collagen matrix,
forming new bone
 As they become enveloped by the
collagenous matrix they produce, they
transform into osteocytes
 Stimulate osteoclast resorptive activity

9.  Resorb bone matrix from sites where it is
deteriorating or not needed
 Digest bone matrix components
 Focal decalcification and extracellular
digestion by acid hydrolases and uptake of
digested material
 Disappear after resorption
 Assist with mineral homeostasis

10. Matrix
Mineral

11.  Collagen type I and IV
 Layers of various orientations (add to the
strength of the matrix)
 Other proteins 10% of the bone protein
 Direct formation of fibers
 Enhance mineralization
 Provide signals for remodeling

12.  A calcium phosphate/carbonate compound
resembling the mineral hydroxyapatite
Ca10(PO4)6(OH)2
 Hydroxyapatite crystals
 Imperfect
 Contain Mg, Na, K

13.  Calcification occurs by extracellular
deposition of hydroxyapatite crystals
 Trapping of calcium and phosphate ions in
concentrations that would initiate deposition of
calcium phosphate in the solid phase, followed by
its conversion to crystalline hydroxyapatite
 Mechanisms exist to both initiate and inhibit
calcification

14. Proceeds in cycles –
first resorption than
bone formation
The calcium
content of bone
turns over with a
half-life of 1-5 years

16.  Phase I
 Signal from osteoblasts
 Stimulation of osteoblastic precursor cells to
become osteoclasts
 Process takes 10 days

17.  Phase II
 Osteoclast resorb bone creating cavity
 Macrophages clean up
 Phase III
 New bone laid down by osteoblasts
 Takes 3 months

19.  Vitamin D
 Parathyroid Hormone
 Calcitonin
 Estrogen
 Androgen

20.  Osteoblast have receptors for (1,25-(OH)2-D)
 Increases activity of both osteoblasts and
osteoclasts
 Increases osteocytic osteolysis (remodeling)
 Increases mineralization through increased
intestinal calcium absorption
 Feedback action of (1,25-(OH)2-D) represses
gene for PTH synthesis

21.  Accelerates removal of calcium from bone to
increase Ca levels in blood
 PTH receptors present on both osteoblasts and
osteoclasts
 Osteoblasts respond to PTH by
 Change of shape and cytoskeletal arrangement
 Inhibition of collagen synthesis
 Stimulation of IL-6, macrophage colony-stimulating
factor secretion
 Chronic stimulation of the PTH causes
hypocalcemia and leads to resorptive effects of
PTH on bone

22.  C cells of thyroid gland secrete calcitonin
 Straight chain peptide - 32 aa
 Synthesized from a large preprohormone
 Rise in plasma calcium is major stimulus of
calcitonin secretion
 Plasma concentration is 10-20 pg/ml and half
life is 5 min

23.  Osteoclasts are target cells for calcitonin
 Major effect of clacitonin is rapid fall of
plasma calcium concentration caused by
inhibition of bone resorption
 Magnitude of decrease is proportional to the
baseline rate of bone turnover

24.  Estrogens
 Increase bone remodeling
 Androgens
 Increase bone formation

25.  Growth hormone
 Increases bone remodeling
 Glucocorticoids
 Inhibit bone formation
 Thyroid hormones
 Increase bone resorption
 Increase bone formation

26.  Cytokines
 IL-6
 IL-1
 Prostaglandins
 Growth factors
 IGF-I
 TGF-β

27. A disease characterized by:
 low bone mass
 microarchitectural deterioration of the bone
tissue
Leading to:
 enhanced bone fragility
 increase in fracture risk

28.  Normal: Not less than 1 SD below the avg. for
young adults
 Osteopenia: -1 to -2.5 SD below the mean
 Osteoporosis: More than 2.5 SD below the
young adult average
 70% of women over 80 with no estrogen
replacement therapy qualify
 Severe osteoporosis
 More than 2.5 SD below with fractures

29.  Although exact numbers are not available,
based on available data and clinical
experience, on estimated 25 million Indians
may be affected. [Indian J Med Res.
2008 Mar;127(3):263-8.]
 Increase in the incidence related to
decreasing physical activity
 1 of 3 women are affected with osteoporosis
 1 of 5 men are affected with osteoporosis

34.  Mechanisms causing osteoporosis
 Imbalance between rate of resorption and
formation
 Failure to complete 3 stages of remodeling
 Types of osteoporosis
 Type I
 Type II
 Secondary

35. 1. Genetics / family Hx..
2. Race /Asians
3. Gender /( F-estrogen, M-androgen )
4. Age / intake,absorption, Ca loss↓ ↑
5. Nutrition / Ca,Vit-D intake↓
6. Physical exercise /sedentary occupation ,immobility
7. Physical build / small frames,undreweights
8. Habits/life style / Smoking,Alcohol,carb.Bevereges ,/ Sunlight?↓
9. Medication /Heparin,Corticosteroids
10. Underlying pathologies /ESRD,Hyperthyroidism,
04/25/15 2973 NRS P&P-1 /ziad.khaled@iat.ac.ae/FCHS 35

38.  All women 65 years and older
 Postmenopausal women <65 years of age:
 If result might influence decisions about
intervention
 One or more risk factors
 History of fracture

39.  Healthy premenopausal women
 Healthy children and adolescents
 Women initiating ET/HT for menopausal
symptom relief (other osteoporosis therapies
should not be initiated without BMD
measurement)

40.  Outcome of interest: Fracture Risk!
 Outcome measured (surrogate): BMD
 Key: Older women at higher risk of fracture than younger
women with SAME BMD!
 Other factors: risk of falling, bone fragility not all related
to BMD
 Osteoporosis: disease of bone that increases risk of
fracture; more than BMD goes into causing a fracture;
BMD is important, but in reducing fractures must also
consider falls risk, age and other factors!!!

41.  Laboratory Data
 Limited value in diagnosis
 Markers of bone turnover (telopeptide) more useful in
monitoring effects of treatment than in diagnosis
 Helpful to exclude secondary causes
▪ Hyperthyroidism
▪ Hyperparathyroidism
▪ Estrogen or testosterone deficiency
▪ Malignancy
▪ Multiple myeloma
▪ Calcium/Vitamin D deficiency

42.  Quantitative Ultrasonography
 Quantitative computed tomography
 Dual Energy X-ray Absorptiometry (DEXA)
 ?”gold standard”
 Measurements vary by site
 Heel and forearm: easy but less reliable (outcome of
interest is fracture of vertebra or hip!)
 Hip site: best correlation with future risk hip fracture
 Vertebral spine: predict vertebral fractures; risk of falsely
HIGH scores if underlying OA/osteophytes

43. Relative Risk of Fracture
per SD Decrease in BMD
0
0.5
1
1.5
2
2.5
3
Forearm
HipVertebral
AllSites
RelativeRisk
Forearm
Hip
Spine
DXA-assessed content is a proven
effective method for assessing
osteoporosis related fracture risk.
Population surveys and research
studies demonstrate a decrease in bone
density measured by DXA predicts
fracture at specific sites.
Marshall, D, et al: Meta-analysis of how well
measures of bone mineral density predict
occurrence of osteoporotic fractures. British
Medical Journal. 312:1254-1259, 1996.

44. 0
0.5
1
1.5
2
2.5
3
Hans, et al Bauer, et al Frost, et al
Research Study
RelativeRiskofFracture
BUA
BMD
Hans, D, et al: Ultrasonographic heel measurements to predict hip fracture in elderly women:
the EPIDOS prospective study. Lancet. 348:511-514, 1996.
Bauer, DC, et al: Broadband ultrasound attenuation predicts fractures strongly and
independently of densitometry in older women. Archives of Internal Medicine. 157:629-634,
1997.
Frost, ML, et al: A comparison of fracture discrimination using calcaneal quantitative
ultrasound and dual x-ray absorptiometry in women with a history of fracture at sites other
than the spine and hip. Calcified Tissue International. 71:207-211, 2002.

45.  T score: standard deviation of the BMD from the average sex
matched 35-year-old
 Z score: less used; standard deviation score compared to age
matched controls
 WHO: Osteoporosis: T score <-2.5
 Osteopenia: T score -1 - -2.5
 For every 1 decrease in T score, double risk of fracture
 1 SD decrease in BMD = 14 year increase in age for predicting
hip fracture risk
 Regardless of BMD, patients with prior osteoporotic fracture
have up to 5 times risk of future fracture!

46.  Postmenopausal women with T-score
below –2.0 with no risk factors
 Postmenopausal women with T-score
below –1.5 with one or more risk factors

47.  Goal: prevent fracture, not just treat BMD
 Osteoporosis treatment options
 Calcium and vitamin D
 Calcitonin
 Bisphosphonates
 Estrogen replacement
 Selective Estrogen Receptor Modulators
 Parathyroid Hormone

48.  Fewer than half adults take recommended amounts
 Higher risk: malabsorption, renal disease, liver
disease
 Calcium and vit D supplementation shown to
decrease risk of hip fracture in older adults
 1000 mg/day standard; 1500 mg/day in
postmenopausal women/osteoporosis
 Vitamin D (25 and 1,25): 400 IU day at least;
 Frail older patients with limited sun exposure may need up
to 800 IU/day

50.  Likely not as effective as bisphosphonates
 200 IU nasally/day (alternating nares)
 Decrease pain with acute vertebral
compression fracture

51.  Decrease bone resorption
 Multiple studies demonstrate decrease in hip and
vertebral fractures
 Alendronate, risodronate
 IV: pamidronate, zolendronate (usually used for
hypercalcemia of malignancy, malignancy related
fractures, and multiple myeloma related
osteopenia)
 Ibandronate (boniva): once/month
 Those at highest risk of fracture (pre-existing
vertebral fractures) had greatest benefit with
treatment

52.  Jaw osteonecrosis
 Underlying significant dental disease
 Usually associated with IV formulations
 Case reports associated with oral
formulations

53.  Renal failure
 Esophageal erosions
 GERD, benign strictures, most benign GI problems
are NOT a contraindication
 Concern for esophageal irritation/erosions from
direct irritation, recommendations to drink water
after and not lie down at least 30 minutes
 Reality: no increased GI side effects compared to
placebo group in multiple studies

54.  Reduction in bone resorption
 Proven benefits in treatment
 FDA approval, now limited because of recent
concerns from HERS trial and other data
suggesting possible increased total risks with
HRT (?increased cardiac risk, increased risk
VTE, increased risk cancer)

55.  Raloxifene
 FDA recommended
 Decrease bone resorption like estrogen
 No increased risk cancer (decrease risk breast
cancer)
 Increase in vasomotor symptoms associated
with menopause

56.  Teriparatide
 Why PTH when well known association with
hyperparathyroidism and osteoporosis???
 INTERMITTENT PTH: overall improvement in bone
density
 Optimal bone strength relies upon balance between bone
breakdown and bone build up; studies with increased
density but increased fracture risk/fragility with flouride
show that just building up bone is not enough!!!

57.  Studies suggest improved BMD and decreased
fractures
 ?risk osteosarcoma with prolonged use (over 2
years): studies with rats
 SQ, expensive
 Option for severe osteoporosis, those on
bisphophonates for 7-10 years, those who can not
tolerate oral bisphosphonate
 Optimal effect requires bone uptake
 Not for use in combination with Bisphosphonate!
 May need to stop bisphosphonate up to 1 year prior

64. First Line Therapies with Evidence for Fracture
Prevention in Postmenopausal Women

67.  1. Decrease osteoporosis/improve BMD
 2. Decrease risk of break: hip protectors
 3. Decrease risk of fall

68.  Padding that fits under clothing
 Multiple studies demonstrate effectiveness at
preventing hip fractures
 Likely cost effective
 Problem: adherence!

69.  Falls are a marker of frailty
 Hip fracture is a marker of frailty
 Mortality after hip fracture:?due to hip fracture or hip fracture as
marker for those who are declining?
 Increased risk of falls:
 Prior fall (fear of falling)
 Cognitive decline
 Loss of vision
 Peripheral neuropathy
 Weakness
 Stroke
 Medications: anticholinergics, tcas, benzos…
 ETOH

70.  US Preventive Task Force
 Test Bone Mineral Density in all women over age
65, younger postmenopausal women with at least
one risk factor, and postmenopausal women with
a history of fracture
 Treat patients with T score <-2 and no risk factors,
T score <1.5 if any risk factors, and anyone with
prior vertebral/hip fracture

71.  Older men
 Not included in recommendations
 Screening not recommended or paid for
 Significant problem, risk of osteoporosis, risk of
fracture, especially after age 70, even more so
after age 80
 Significant evidence that men with osteoporosis
benefit from treatment

72. •Osteoporosis is characterized by low bone mass with
micro-architectural deterioration of bone tissue leading
to enhance bone fragility, thus increasing susceptibility
to fracture.
•The management of osteoporosis should be guided by an assessment
of the patient’s absolute risk of osteoporosis related fractures.
•Fragility fracture increases the risk of further fractures and should be
considered in the assessment.
•Lifestyle modification and pharmacologic therapy should be
individualized to enhance adherence to the treatment plan.

73. Thank YouThank You