DIAGNOSIS AND RISK FACTORS

OF OSTEOPOROSIS

BY
PROFESSOR
HAZEM ABDEL AZEEM
CAIRO UNIVERSITY
March 2004
 OSTEOPOROSIS

A systemic skeletal disease:

Low bone mass
Microarchitecture deterioration of
bone tissue
Increased bone fragility and
susceptibility to fractures
 O s te o p o ro tic B o n e L o s s

O s te o p o ro s is N o rm a l
D em p ster D W , e t al. J B o n e M in R e s. 19 8 6 ;1 :1 5 -2 1 .
R e prin te d w ith p e rm issio n from th e A m erican S o cie ty fo r B o n e a n d M in era l R esea rch .
Relationship of
causes of
osteoporosis to
balance of bone
remodelling
CAUSES OF OSTEOPOROSIS
 RISK FACTORS OF
OSTEOPOROSIS
 Age.
 Sex.
 Genetic.
 Lifestyle
 Nutritional.
 Medical disorders.
 Drugs.
 Previous fracture.
Age-related changes

After age 60, subperiosteal

area slowly increases but
medullary cavity enlarges
faster, resulting in net
decrease of cortical
thickness and mass
 Gender related factors (female)
 Prolonged amenorrhoea:
 Anorexia nervosa
 Exercise induced
 Prolactinoma
 Premature menopause (<45 years)
 Idiopathic
 Cancer chemotherapy
 Pelvic irradiation
 Late menses (>15 years)
 Genetic factors
 White or asiatic ethnicity
 Family (maternal) history of fractures
 Paternal family history of hip fracture
 Small body frame
 Tallness
 Premature greying of hair
 Fair skinned
 Blue eyed
 Lifestyle

 Nulliparity
 Coffee
 Smoking
 Alcohol intake
 Parity
 Prolonged breast-feeding
 Inactivity
 Nutritional

 High Na diet
 High protein diet
 High phosphate diet
 Animal fat
 Leanness
 DRUGS RELATED RISKS
 Smoking
 Glucocorticoids and  Tamoxifen
ACTH
 Thyroxine
 Medroxyprogester-
 Anticonvulsants one acetate
 Heparin  Aluminium
 Lithium  Excess Vitamin D
 Cytotoxic
 Drugs causing falls
 Gonadotrophin-RH
agonists  Hyperoxia
 Effects of smoking
 Accelerated menopause
 Decreased fat mass
 -- peripheral production of oestrogen
 -- resistance to falls
 -- weight on skeleton
 ++ metabolism of endogenous oestrogen
 ++ metabolism of exogenous oestrogen
 Association with alcohol consumption and other
life-style factors
 Target tissue Action Effect

 Recruitment

Osteoblasts  Osteocalcin (rapid)

 Formation
 Collagen synthesis

Adrenals & gonads  Gonadal hormones

Bone loss
?
Parathyroid  Secretion

Gut  Sensitivity to Vit. D

 Resorption
Renal tubule  Calcium reabsorption

Muscle
 Skeletal load
EFFECTS OF
Bone: immobilization
GLUCOCORTICOIDS
 Heparin
 A likely direct effect on osteoclast
development and activation
 Substantial doses required (10-15000 units
daily)
 Rates of bone loss may be rapid
 Vertebral and rib fractures
 Doses in haemodialysis are too low
 Calcitonin and anabolic steroids may be
preventive
 Coffee (Caffeine)

 Can increase urinary excretion rate

of calcium
 For osteoporosis: data are
circumstantial and not convincing
 Association between coffee and hip
fracture are not consistent
 Alcohol excess
 Significant risk factor especially in men
 Effect:
 Direct (++resorption/--formation)
 Associated with protein undernutrition
 Changes in life style
 Liver disease
 Decrease in Testosterone
 Increase risk of falls
 In healthy individuals
 decrease secretion of PTH
 increase secretion of calcitonin
 High Sodium Intake

 Decreases tubular reabsorption of Ca due

to co-transport mechanism
 This may induce secretion of PTH
 There is increase in urinary cAMP
 Long-term experimental and
epidemiological studies provide little
evidence that variations in the normal
intake of Na affect skeletal mass
Assessment of osteoporosis (aim)

 Diagnosis.
 Identification of disorders mimicking
osteoporosis.
 Identification of risk factors.
 Methodology for prognosis.
 Selection of treatment.
 Baseline for response evaluation.
 DIAGNOSIS OF OSTEOPOROSIS

 CLINICAL DIAGNOSIS.
 RADIOLOGICAL DIAGNOSIS.
 LABORATORY DIAGNOSIS.
 BONE DENSITOMETRY.
 BONE BIOPSY.
 CLINICAL DIAGNOSIS

 History of positive risk factors.

 Clinical presentation:
 Loss of height.
 Diffuse kyphosis.
 Pains.
 Fractures.
 Worry and psychic effects.
 LOSS OF HEIGHT

 VERTEBRAL COMPRESSION.
 VERTEBRAL WEDGING.
 LOWER LIMB BONES BOWING.
 KYPHOSIS

 DIFFUSE.
 DORSAL.
 DORSO-LUMBAR.
 SLOWLY PROGRESSIVE.
 PAINS

 MICROFRACTURES.
 LONG STANDING KYPHOSIS.
 ASSOCIATED OSTEOMALACIA.
 OSTEOPOROTIC FRACTURES.
 MUSCULAR.
 FIBROMYOSITIS.
 FRACTURES
 FRAGILITY FRACTURES.
 MINOR TRAUMA.
 COMMON SITES:
 Spine.
 Proximal end of femur.
 Distal end of radius.
 Proximal end of
humerus.
Washed-out
Anterior wedge Severe kyphosis in postmenopausal
vertebrae without
compression with woman. Mild, multiple biconcavity and
vertebral collapse
kyphosis wedging of vertebrae.
or kyphosis
 Primary axial osteoporosis

65 year-old female with a few years history of pain in the back

 Fracture Neck of Femur

75 year-old female with a frail constitution, hospitalized in an institution for

chronic diseases; fractures of the right neck of femur at the age of 68,
intertrochanteric fracture at 72, in both instances due to a slight fall.
Fracture of the neck of the
humerus

77 year-old peasant woman. She was

being treated for an axial osteoporosis.
She wakes up in the morning with pain in
the shoulder and limitation of movement.
She has fracture of the anatomical neck of
the humerus, and the greater trochanter
with abduction displacement of the shaft in
relation to the elevated head.
 Radiographic findings in
osteoporosis

AB + CD >/=
medulla
AB+CD/XY >/=
1/2
In ostepenia <
1/2
Midshaft of index
finger is used for
measurement
 Laboratory diagnosis and
Biochemical assessment of
osteoporosis
 Serum and urine
calcium.  Crosslink assays
 Alkaline phosphatase.  Alpha2 HS
 Hydroxyproline. glycoprotein
 Ostecalcin.  Acid phosphatase
 Hydroxylysine  Biochemical
glycosides. estimation of bone
 Procollagen I loss.
extension peptides
 Biochemical estimation of bone
loss
 To assess rate of bone loss (slow,
intermediate or fast losers)
 More than one measurement.
 To predict age of reaching fracture
threshold
 To initiate preventive intervention.
 To avoid repeated bone density
measurement.
 Bone Densitometry
(why is it used?)
 Conventional radiograph:
 not sensitive (needs 30% reduction in
mineral content)
 not accurate
 Implications in Orthopaedic practice:
 evaluation and management of bone-loss
syndromes
 evaluation of periprosthetic bone-
remodeling
 Bone densitometry
(current methodology)

 Single-energy x-ray absorptiometry.

 Dual-energy x-ray absorptiometry.
 Quantitative computed tomography.
 Quantitative ultrasound.
 Single-energy x-ray
absorptiometry (SEXA, SPA)
 For distal end of radius or calcaneus
 Collimated photon beam from x-ray source (not
photon source)
 Advantages:
 relatively simple to perform
 negligible total body radiation
 good for peripheral long bones
 Disadvantages:
 poor for axial skeleton
Dual-Energy X-ray Absorptiometry
(DEXA)
 The most widely used modality
 DEXA (contd.)

 Used axially, peripherally and in total body

scans:
 spine scans = 1 minute
 femur scans = 2 minutes
 total body scans = 4 minutes
 Precision (0.5 to 2%)
 Accuracy (3 to 5%)
 Disadvantage: does not differentiate between
cortical and trabecular bone
DEXA of the Spine
Osteoporosis of the hip
DEXA of the spine
DEXA post-fixation
 Qantitative Computed
Tomography
 Can be performed in the axial or
appendicular skeleton.
 Advantages:
 separate assessment of trabecular and
cortical bone
 direct measurement of bone volume
(gm/cm3) accurate 3D bone geometry
measurement
 done with standard CT systems
A lateral CT scan localizes the
mid-plane of two, three or four
lumbar vertebral bodies
Quantitative readings are then
obtained from a region of
trabecular bone in the anterior
portion of the vertebra
The CT determinations of
vertebral bone density are
compared with known density
readings of solutions in the
phantoms
A software converts Hounsfield
units (from CT) into bone-
mineral equivalents.
 Qantitative Computed
Tomography
The principle disadvantage is the higher
dose of radiation compared to other bone
densitometry techniques

Investigation Dose in microsieverts

QCT 29

DEXA 0.5 – 5

Chest x-ray 50
 NOF/WHO Criteria for Assessing
Disease Severity
T-score

Normal  –1.0
Osteopenia –1.0 to –2.5
(low bone mass)

Osteoporosis  –2.5
Severe (established) osteoporosis  –2.5 with fracture

Bone mass T-score: The standard deviation in a patient’s bone mineral density
(BMD) compared with the peak bone mass in a young adult of the same gender

WHO = World Health Organization; NOF = National Osteoporosis Foundation.

Physicians Guide to Prevention & Treatment of Osteoporosis, 1998
12
 Quantitative Ultrasound

 Recent widespread attention:

 no radiation
 relatively simple to implement and process
 portable
 inexpensive
 may measure additional bone properties as
mechanical integrity
 Accessible sites: the calcaneus, the patella, the
radius, tibia and phalanges
 Quantitative Ultrasound
(contd.)
 Ultrasound assessment is based on:
 velocity of ultrasound wave
 attenuation of ultrasound wave
 Propagation of wave is affected by:
 bone mass
 bone architecture
 directionality of loading
 At the calcaneus, correlation with DEXA is 0.80 to
0.85
Bone Biopsy
 Bone Biopsy

Red-stained osteoid seams lined Tetracycline labeling on fluorescent

with OB (osteblasts) and OC
(osteoclasts) versus poor osteoid
seams and little osteoblasts and
osteclasts in bone resorption
microscopy showing normal bone with
yellow lines at mineralization front versus
absence of bone formation.
T= bone trabecula M= marrow