Osteoporosis

Umar Zein
FK UNPRI

Two Components of the Bone

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

Osteons

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

Bone Cells

Osteocytes - derived from

osteoprogenitor cells
Osteoblasts
Osteoclasts

Osteocytes

Trapped osteoblasts
In lacunae

Keep bone matrix in good condition and can release

calcium ions from bone matrix when calcium demands
increase

Osteocytic osteolysis

Osteoblasts

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

Osteoclasts

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

Chemistry of the Bone

Matrix
Mineral

Matrix - Osteoid

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

Mineral

A calcium phosphate/carbonate compound

resembling the mineral hydroxyapatite
Ca10(PO4)6(OH)2
Hydroxyapatite crystals
Imperfect
Contain Mg, Na, K

Mineralization of the Bone

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

Bone Remodeling Process

Proceeds

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

Bone Remodeling Process

Coordination of Resorption and

Formation

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

Coordination of Resorption and

Formation

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

Pathways of Differentiation of
Osteoclasts and Osteoblasts

Hormonal Influence

Vitamin D
Parathyroid Hormone
Calcitonin
Estrogen
Androgen

Vitamin D

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

Parathyroid Hormone

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

Calcitonin

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

Actions of Calcitonin

Osteoclasts are target cells for calcitonin

Major effect of calcitonin 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

Definition
A systemic skeletal
disease characterized by
low bone mass and micro
architectural deterioration
of bone tissue lead to
bone fragility and
susceptibility to fracture

Prevalence of osteoporosis
Osteopenia

Osteoporosis

Female
Age > 50
year

37-50%

13-18%

Male
Age > 50
year

28-47%

3-6%

NHANES III. J Bone Miner Res.1997

Melton L. J. J Bone Miner Res.1992

Incidence of osteoporotic
Fx
Vertebral
Fracture

Forearm
Fracture

Hip
Fracture

No Bones About It

25

Typical comments from

people with osteoporosis
Ive lost six inches in height and none of my clothes fit
me anymore.

26

Pathogenesis

Q ui ckT
i me and a TI FF ( Uncompressed) decompressor are needed to see thi s pi ct ure.

Pathogenesis

Pathogenesis

Quic kTime and a TIF F (Unc ompressed) dec ompressor are needed to see this pic ture.

Microdamage

Peak bone
mass

Quic kTime and a TIF F (Unc ompressed) dec ompressor are needed to see this pic ture.

Precipitating
factors

Loss of
Estrogen

Diagnosis of
osteoporosis

Diagnosis of Osteoporosis

Physical examination
Measurement of bone mineral
content
Dual X-ray absorptiometry (DXA)
Ultrasonic measurement of bone
CT scan
Radiography

Physical examination

Osteoporosis
Height loss
Body weight
Kyphosis
Humped back
Tooth loss
Skinfold
thickness
Grip strength

Vertebral fracture
Arm span-height
difference
Wall-occiput
distance
Rib-pelvis
distance

Physical examination

Amanda D. Green. JAMA 2001 vol.292(23)

Physical examination
LR +ve

95% CI

Wt < 51 kg

7.3

5.0-10.8

Tooth < 20

3.4

1.4-8.0

RP distance < 2 FB

3.8

2.9-5.1

WO distance > 0 cm

4.6

2.9-7.3

Humped backed

3.0

2.2-4.1

Amanda D. Green. JAMA 2001 vol.292(23)

Physical examination
No single maneuver is sufficient to rule
in or rule out osteoporosis or vertebral
fracture without further testing

Amanda D. Green. JAMA 2001 vol.292(23)

Dual X-ray absorptiometry

2-dimensional study
BMD = Amount of
mineral
Area
Accuracy at hip > 90%
Low radiation exposure
Error in Osteomalacia
Osteoarthritis
Previous fracture

Dual X-ray absorptiometry

WHO criteria - Hip
BMD
Normal
Low bone mass
(Osteopenia)
Osteoporosis
Severe osteoporosis

Dual X-ray absorptiometry

Normal
Low bone mass ( Osteopenia )

BMD compare with

young adult female

T score

< 1 SD below

>/= -1

1-2.5 SD below

< -1
> -2.5

Osteoporosis

>/= 2.5 SD below

Severe osteoporosis

>/= 2.5 SD below

PLUS Fracture

</= -2.5

Ultrasonic measurement
Broad-band ultrasound
attenuation or ultrasound
velocity
No radiation exposure
Cannot be used for
diagnosis
Preferred use in
assessment of fracture
risk

CT scan
True volumetric study
Most useful in cancellous
bone assessment
Avoid effect of
degenerative disease
Drawback
High cost

Plain radiography

Q ui ckT
i me and a TI FF (Uncompressed) decompressor are needed to see thi s pi ct ure.

Low sensitivity
High availability
Subclinical vertebral
fracture is a strong risk
factor for subsequent
fractures at new
vertebral site and other
sites

Who Gets Osteoporosis?

Age
Estrogen deficiency
Testosterone deficiency
Family history/genetics
Female sex
Low calcium/vitamin D intake
Poor exercise
Smoking
Alcohol
Low body weight/anorexia
Hyperthyroidism
Hyperparathyroidism
Prednisone use
Liver and renal disease (think about vit d synthesis)
Low sun exposure
Medications (antiepileptics, heparin)
Malignancies (metastatic disease; multiple myeloma can present as osteopenia!)
Hemiplegia s/p CVA/ immobility

Fracture Reduction

Goal: prevent fracture, not just treat BMD

Osteoporosis treatment options

Calcium and vitamin D

Calcitonin
Bisphosphonates
Estrogen replacement
Selective Estrogen Receptor Modulators
Parathyroid Hormone

Osteoporosis Treatment: Calcium and

Vitamin D

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

Osteoporosis Treatment: Calcitonin

Likely not as effective as

bisphosphonates
200 IU nasally/day (alternating nares)
Decrease pain with acute vertebral
compression fracture

Osteoporosis Treatment:
Bisphosphonates

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

Bisphosphonate Associated
Osteonecrosis (BON)

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

Bisphosphonates: Contraindications

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

Osteoporosis Treatment: Estrogen

Replacement

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
cardiac risk, cancer)

Osteoporosis Treatment: Selective

Estrogen Receptor Modulators

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

Osteoporosis Treatment: PTH

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!!!

Intermittent PTH: Teriparatide

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

Reducing Fractures

1. Decrease osteoporosis/improve BMD

2. Decrease risk of break: hip protectors
3. Decrease risk of fall

Hip Protectors

Padding that fits under clothing

Multiple studies demonstrate effectiveness at
preventing hip fractures
Likely cost effective
Problem: adherence!

Falls Reduction

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

Hip Fracture Prevention: Falling

How do Younger Adults Fall?

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Hip Fracture Prevention: Falling

How do Older Adults Fall?

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Hip Fracture Prevention:

Hip Protectors

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