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
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
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
15.
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
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
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
30.
31.
32.
33.
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
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
49.
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
58.
59.
60.
61.
62.
63.
64. First Line Therapies with Evidence for Fracture
Prevention in Postmenopausal Women
65.
66.
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.