OSTEOPOROSIS,

OSTEOMALACIA & PAGET

DISEASE
WIDIYATMIKO
OSTEOPOROSIS
Introduction
Become major health problem
Canada: 1 of 4, 1 0f 8
USA: > 1 million fragility fracture
cost US$ 10 billion
In 2041, elderly people > 25%
Preventable disease
 Bone Remodeling Cycle
Bone lining cells
Bone

Osteoclasts

Resorption by
osteoclasts

Osteoblasts
Bone remodelling

Sincere thanks to Dr. Susan Ott from the University of

Washington for permission to use the above images
 Normal Bone
Osteoporosis
Bone loss associated with sex and
etnis
Bone
Regulatio
n
 Low bone mass + micro structure damaged

Decreased bone quality

Decreased bone strength

Fragile

Increased # risk
Definition
Consensus Development Conference
(1993)
a systemic skeletal disease
characterized by low bone mass and
microarchitectural deterioration of
bone tissue, leading to enhanced
bone fragility and a consequent
increase in fracture risk
Definition
United States National Institutes of
Health (2000)
a skeletal disorder characterized by
compromised bone strength
predisposing a person to an increased
risk of fracture. Bone strength reflects
the integration of 2 main features:
bone density and bone quality.
 Osteoporosis according
World Health Organization
(WHO)
 Severe
Osteo- Osteo- Osteo-
Normal penia porosis porosis

Cortical

Trabecular

Sincere thanks to Dr. Susan Ott for

permission to use the above images
Classification
Primary Osteoporosis
Type 1 high turnover
Type 2 low turnover

Secondary Osteoporosis (type 3)

Classification
Type I (high turnover)
Early menopause 10 yrs after

Estrogen osteoclast activity

Losses 3% annualy fast bone

depletion
Classification
Type 2 low turnover
7th or 8th Decade

Osteoblast activity due to aging,

nutritional insufficiency
Losses 0,5% annually

# at minor trauma
Classification
Type 3
Careful : < 50 yo, rapid bone loss

Underlying disease
Risk Factors
Clinical signs and
symptoms
"silent disease"
Back pain
Decreased in height

Kyposis

Fracture caused by minor

trauma (Pathological fracture)

Bone fracture in osteoporosis
Osteoporosis
Fracture locations
Osteoporosis detection
Radiographic findings

BMD (Bone Mineral Density)

measurement

Biochemical markers
BMD (Bone Mineral
Density) measurement
Indication:
Assess degree & progressivity

bone metabolic disease

Screening high risk

Follow up
BMD (Bone Mineral
Density) measurement
1. Dual-energy x-ray absorptiometry
(DEXA)
2. Calcaneal quantitative
ultrasonometry (QUS)
3. Quantitative CT
4. Radiographic absorptiometry
5. Single-energy x-ray absoprtiometry
Singh Index
DXA
Prevention & Treatment
Aim: early intervention to ensure
retention of bone mass, preserve
structural integrity, prevent
fragility fracture
Prevention & Treatment
Consist of:
Non-pharmacological intervention

Pharmacological intervention

Operative therapy
Non-pharmacological
intervention
Adequate Ca & Vit D intake
RDA for Ca:
4 8 yo: 800 mg
9 18 yo: 1300 mg
Premenopause: 1000 mg
Male < 50 yo : 1000 mg
Menopause & male > 50 yo: 1500 mg
Pregnant & lactating: 1000 mg
Non-pharmacological
intervention
RDA for Vit D:
< 50 yo: 400 IU
> 50yo: 800 IU
Vit D3 more potent than D2
Maintain adequate protein intake
Physical activity imapct type
Prevention of fall
Osteoporosis prevention
Exercise
Fall Prevention
Tranqualizer
Visus problem
Gait abnormality
Pharmacological
intervention
1. Estrogen (hormone replacement
therapy/HRT)
2. Biphosphonate
3. Calcitonin
4. Selective estrogen-receptor
modulator (SERM)
5. Iprivlafone
Pharmacological
intervention
Operative treatment
If theres any fracture
Vertebrae vertebropalsty,
kyphoplasty
Hip ORIF, hemiarthroplasty
Wrist ORIF
Surgery
Osteomalacia
 Definition
Osteomalacia is the general term for the
softening of the bones due to defective
bone mineralization.
 Definition
Osteomalacia in children is
known as rickets, and
because of this, it is often
restricted to the milder, adult
form of the disease.
It may show signs as diffuse
body pains, muscle
weakness, and fragility of
the bones.
General
characteristics
Osteomalacia is derived from Greek:

osteo bone
malacia softness
most commonly found in:
dark-skinned
diet-disbalanced subjects (mainly lactating
females).

Age: adults
Site: WEIGHT-BEARING BONES such as
vertebral bodies and femoral neck
General
characteristics
Physiology
Normal bone metabolism: CA
CALCIUM 99% in bone.
Main functions muscle /nerve function, clotting.
Plasma calcium 50% free, 50% bound to albumin.
Dietary needs:
Kids: 600mg/day
Adolescent 1300mg/day,
Adult: 750mg/day
Pregnancy: 1500mg/day,
Breastfeeding: 2g/day,
Fractures: 1500mg/day
Absorbed in duodenum (active transport) and
jejunum (diffusion), 98% reabsorbed in kidney prox.
tubule, may be excreted in stool.
 Physiology
Normal bone metabolism: PHOSPHATE

PHOSPHATE 85% in bone.

Functions: metabolite and buffer in enzyme
systems.
Plasma phosphate mainly unbound.
Daily requirement: 1-1.5g/day
Physiology
Regulation of Calcium & Phosphate Metabolism:
Peak bone mass at 16-25 years.
Bone loss 0.3- 0.5% per year (2-3% per year after 6 th decade).
1. Parathyroid Hormone (PTH)
2. Vitamin D3
3. Calcitonin
4. Other Hormones: Estrogen:
Prevents bone loss
Corticosteroids: Increases bone loss
Thyroid hormones: Leads to osteoporosis
Growth hormones: Cause positive calcium
balance Growth factors
Physiology
Physiology
 Physiology
Serum Ca & Phosphate in equilibrium with Ca &
Phosphate in bone.
Physiology
Patho physiology
Kidney disease

Defect in phosphate No hydroxylation

execration of Vit.D3
Patho physiology
,Hypocalcaemia So

Stimulation of PTH

Bone.. Kidney
.Relase of Ca Ca absorption
 Etiology
Calcium deficiency
Hypo-phosphataemia
Defect in Vitamin D metabolism
Nutritional
Diet: oily fish, eggs, breakfast cereals
Antacid abuse, causing reduced dietary phosphate
binding

underexposure to sunlight
Elderly individuals with minimal sun
exposure
Dark skin, skin covering when outside
 Etiology
Calcium deficiency
Hypo-phosphataemia
Defect in Vitamin D metabolism
intestinal mal-absorption
Coeliac
Intestinal bypass
Post-Gastrectomy
Chronic pancreatitis
Biliary disease (reduced absorption of Vitamins)
Small bowel disease
Etiology
Calcium deficiency
Hypo-phosphataemia
Defect in Vitamin D metabolism
liver & kidney diseases
Fat mal-absorption syndromes

Kidney failure: RTA, Renal osteodystrophy

Epilepsy: phenytoin, phenobarbitorate

Genetic disease
Etiology
Other Etiologies:
Receptor Defects
Altered phosphate homeostasis
Pathology
 Symptoms &

Signs
Bone pain , backache
Muscle weakness
Vertebral collapse: kyphosis
loss of height
Deformities & stress fractures
 Symptoms &
Signs
Osteomalacia in adults starts insidiously as aches
and pains in the lumbar region and thighs,
spreading later to the arms and ribs.
Pain is non-radiating, symmetrical, and
accompanied by tenderness in the involved bones.
Proximal muscles are weak, and there is difficulty in
climbing up stairs and getting up from a squatting
position
 Symptoms &

Signs
Physical signs include deformities like lordosis.
Pathologic fractures due to weight bearing may
develop.
Most of the time, the only alleged symptom is
chronic and bony ache which is only revealed by
pressure or shocks.
 Symptoms &

Signs
Rickets
Tetanus , convulsions, failure to thrive
restlessness, muscular flaccidity
Flattening of skull (craniotabes)
Thickening of wrists from epiphyseal overgrowth,
Stunted growth, Rickety rosary, spinal curvature, Coxa
vara, bowing,
Fx of long bones
Osteomalacia
Aches and pains
muscle weakness loss of height
stress fx
 biochemistry
1.Hypo-calcaemia
2.Hypo-calcuria

3.High alkaline phosphatase

 biochemistry
Work up for Osteomalacia
Ca , P , Alk ph
24 h urinary Ca
25 (OH) Vit-D
1 , 25 (OH) Vit-D
PTH
Bone Biopsy
 biochemistry
1- ca P = Nl Alk ph
2- ca = Nl P Alk ph
3- ca P Alk ph

24 h Urinary ca < 100 mg / 24 h

24 h Urinary Hydroxyproline Excretion
 X-ray
*Rickets
- Growth plate widening & thickening
- Metaphyseal cupping
- Diaphyseal deformities
*Osteomalacia
- Looser zone , biconcave vertebra , protrusio
acetabuli
- Spontaneous fractures
*Signs of secondary
hyperparathyroidism
X-ray
Loosers zones
incomplete stress Fx
with healing lacking
calcium, on
compression side of
long bones.
Codfish vertebrae due
to pressure of discs
Trefoil pelvis, due to
indentation of
acetabulae stress fx
 X-ray

Loosers
zones
X-ray
X-ray
Treatment
Depends on the cause
Nutritional
Vitamin D deficiency
Dietary chelators of calcium

Phytates
Oxalates
Phosphorus deficiency (unusual)
Antacid abuse
Treatment
Depends on the cause
Gastro-intestinal absorption defects
Post-gastrectomy
Biliary disease
Enteric absorption defects
Short bowel syndrome
Rapid onset (gluten-sensitive enteropathy)
Inflammatory bowel disease
Crohns
Celiac
Treatment
Depends on the cause
Renal tubular defects
Vitamin D dependant
type I
type II
Treatment; High levels of vit D

Vitamin D resistant (familial hypophosphatemic rickets)

Treatment; Phosphate 1-3 gm daily, Vit D3 high
dose Fanconi syndrome I, II, III
Renal tubular acidosis
Treatment
Depends on the cause
Renal Osteodystrophy in chronic renal failure
Miscellaneous
Hypophosphatasia
Anticonvulsant therapy

SURGERY
For deformities
Treatment

Treatment
Natural sources cheese, sardines, salmon,
dark leafy vegetables & sesame seeds.

ALAT
ALAT SKRINING
SKRINING
Pagets Disease of Bone
 Aim and objectives
Aim
To increase knowledge regarding Pagets disease of

bone

Objectives
To understand the disease process

To discover what is known about its etiology

To know the clinical features

To understand assessment and diagnosis

To establish the treatment options

To discover the support available

 Pagets Disease

A condition where the normal cycle of bone

renewal and repair is disrupted (bone
remodelling).

It is characterised by rapid bone remodelling and

the formation of bone that is structurally
abnormal.
 Pagets Disease
Occurs in 1 2 % of white adults over the age of 50
yrs
Uncommon under the age of 50
More common in men
UK has the greatest prevalence of PDB in the world
The prevalence and severity of the disease has
reduced
Occurs more commonly with advancing age. In the
UK, it presents in approx 8% of men & 5% of women,
by the age of 80.
Pagets Disease

How is bone
affected?
Normal Bone Remodelling
Abnormalities in Pagets Disease

Osteoclasts increase in number and size

Increased bone resorption

Increased osteoblast activity to form new bone

New bone is weaker, larger and

abnormal in shape and structure
 Which bones are affected by
PDB?
Any bone can be affected

May be monostotic (30-35%) affecting only a single

bone

May be polyostotic (65-70%) involving 2 or more

bones

The disease can progress within an affected bone

It is uncommon for new sites to appear after initial

Bones Commonly Affected
28% Skull

13% Collar Bone

23%
Sternum
4% Upper Arm
7%
Ribs
30% Spine

22% Pelvis

30% Femur

8%
Tibia
Pagets Disease Under the
Microscope

Normal Bone

Woven Bone in
Pagets Disease
Pagets Disease

What are the clinical features

& potential complications?
Pagets Disease

Many people are asymptomatic

Some have mild to moderate symptoms

Some have severe symptoms and

complications
Clinical features which may be
present
Pain is the most common symptom and is often
unrelieved by rest
Warmth at the affected site
Fracture - often following minor injury
Hearing problems when the skull is involved
Deformity
- Misshapen, enlarged bone
- bowing of long bones
- enlargement of the head
 Pagets Disease and Pain
Bone pain: caused by disease activity
- often described as Persistent and nagging
- pain at rest, often at night

Joint pain related to osteoarthritis

Muscle pain: caused by deformity

Nerve compression: caused by enlarged bone

Malignant change: very rare

 Analgesia
Regular Paracetamol (8 daily)

Combination therapies (e.g. Co-codamol)

NSAIDs
Ibuprofen (oral, gel)
Diclofenac
Cox-2 selective inhibitors

Amitryptylline, Gabepentin
Potential Complications

Fracture
(fissure or complete) Deafness
Deformity
Potential Complications

Osteoarthritis
Those with PDB are more prone to develop
osteoarthritis at joints adjacent to Pagetic bone

Heart Disease
PDB does not directly affect the heart but in
widespread disease, the heart may have to work
harder to pump extra blood to involved bones.
Pagets disease

Assessment &
diagnosis
 Assessment
Assessment should include

- Full history

- Family history (PDB has a strong genetic predisposition)

- Mobility and functional capacity

- Social history

- Pain
 Investigations

Blood test
A rise in Alkaline Phosphatase (ALP) can
indicate active Pagets disease

X- ray
Pagets may be found by chance when
an x-ray is carried out for another
reason
Isotope bone scan
This will show the extent and activity of
the disease.

This scan shows evidence of polyostotic

disease (Pagets in more than one bone)
Pagets disease

What causes Paget's disease?

 What causes Pagets disease?

We are still learning......

There is a general understanding that the disease is due to
a combination of inherited and environmental influences

It is thought that genetic factors account for about 86% of

the risk of developing Pagets disease
- mutations have been identified in several genes with
the most important being Sequestosome 1 (SQSTM1)

Research is inconclusive but exposure to certain viruses

such as measles and other environmental factors may
also influence the development of Pagets disease
Pagets Disease

Treatment
When to treat

Pain due to active disease

Consider treatment prior to surgery on an affected

bone

To prevent future problems that might occur if left

untreated
Treatment

Bisphosphonates (oral or intravenous) reduce

the abnormal bone turnover helping to restore
normal structure and reduce pain.
Treatment
 Bisphosphonates in Pagets
Disease
Deposited in the bone
Reduce abnormal bone turnover
Reduce pain caused by active disease
Clinicians find that oral bisphosphonates can
return ALP to normal within 6 months and
intravenous within 3 months
Benefits can last for several months or years

Zoledronate - shown to sustain remission up to 6.5

yrs
 When would surgery be
considered?
Joint replacement

Fracture repair

Osteotomy to correct deformity

Bone healing can take longer when

Pagets Disease is present