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METABOLIC BONE DISEASE

1. OSTEOPOROSIS
2. RICKETS
3. OSTEOMALACIA
4. HYPERPARATHYROIDISM
5. PAGETS DISEASE

Dr. Franky Hartono, dr., SpOT.

This teaching material is copyrighted.


No part of this work may be reproduced, including photocopied, without written permission of Universitas Pelita Harapan .
BONE
Individual bone AS A STRUCTURE Bone skeleton AS A ORGAN

Important role of anatomy and Important role of biochemistry and


histology of bone especially the physiology of bone
blood supply
As rigid framework for trunk & Store place of Calcium & Phosphorus
extremity, as levers for locomotoric and of Hematopoetic myeloid type
role, as protector for viscera tissue

The bony reactions serve as a mirror of disease:


they reflect of the underlying abnormality
They may cause pain, deformity, disability
Detected by clinical and radiological
BONES, like the framework of an aircraft, have evolved to be light
yet strong, thanks to their like a rope bony filament architecture
and tubular in shape, with a strong CORTICAL layer, surrounding a
softer spongier core called TRABECULAR bone.
OBJECTIVES
1. OSTEOPOROSIS (porous but well calcified)
Introduction
Pathogenesis
Diagnosis (X-ray, BMD, Lab)
Risk factors
Management

2. RICKETS (decrease calcification of matrix in children)


3. OSTEOMALACIA (decrease calcification of matrix in adults)
4. HYPERPARATHYROIDISM (general osteoporosis combined with a
disseminated osteolytic lesions)
5. PAGETS DISEASE (osteolytic followed by osteosclerotic phase)
OSTEOPOROSIS
(porous bone but
well calcified)
GENERALIZED REACTIONS of ALL BONE as AN ORGAN
Bone deposition < bone resorption (generalized decrease in bone)

Osteoporosis (osteopenia): too little bone.


A decreased OSTEOBLASTIC formation of matrix (osteoid) and
an increased OSTEOCLASTIC resorption of bone, with a
resultant decrease in the total amount of bone in the
skeleton.
Bone is thin and porous but well calcified, associated with
increased fragility and brittleness, and susceptibility to
fracture.
Examples are: disuse osteoporosis, steroid-induced
osteoporosis, and postmenopausal osteoporosis.
Also congenital osteogenesis imperfecta (fragile bone)
DEFINITION

A disease characterized by low bone mass and


microarchitectural deterioration of bone tissue, leading
to enhanced bone fragility and a consequent INCREASE
IN FRACTURE RISK
US National Institute of Health
EPIDEMIOLOGY

OSTEOPOROSIS IS:
THE MOST COMMON FORM OF METABOLIC BONE
DISEASE 15 % 19 %
THE MOST IMPORTANT CAUSE OF ELDERLY 19 %
FRACTURE, ESPECIALLY IN WOMEN
46 %
IN USA:
22 million adults osteoporosis per year
> 1,5 million osteoporosis fracture per year. Other
Expected will be 4x increase in 2050 Vertebral
Spine and hip fracture are most common Hip
Wrist
The cumulative life time risk of having an
osteoporotic fracture : = 3 : 1.
3250
EPIDEMIOLOGY In 2050, Asia
will have
3,25 million
Hip fracture
PREDICTION OF HIP FRACTURE PREVALENCE
Total of Hip fracture

668
estimation per 1000s

742

400
378

600
629
1950 2050

1950 2050
Total of Hip fracture:
1950 = 1,66 juta
2050 = 6,26 juta 100 1950 2050

1950 2050

Adapted from Cooper C et al, Osteoporosis Int, 1992;2:285-289


EPIDEMIOLOGY
MORTALITY ASSOCIATED WITH FRACTURE
Women controls Women with fractures
Men controls Men with fractures
450
Mortality (deaths/1,000

400
350
person-years)

300
250
200
150
100
50
0
60-69 70-79 80 and older

Center et al. Lancet 1999.


EPIDEMIOLOGY

MORBIDITY ASSOCIATED WITH FRACTURE


Unable to carry out at
least one independent
activity of daily living

Unable to walk
80%
independently
Permanent
Death disability 40%
within
one year 30%
20%
TYPES

PRIMARY:
Type I :Postmenopausal osteoporosis (50 to 65 years)
o Due to decrease Estrogen;
o Affects spine and wrist
Type 2 :Seniele osteoporosis (65years and above)
o Induced by smoking, alcohol, less intake of calcium,
o White ras, thin, less activity
o Affects hip and spine

SECONDARY:
Caused by hormonal (hyperthyroid, hyperparathyroid, corticosteroid,
hypogonadism), multiple myeloma, malnutrition, chronic renal failure,
medications or disuses (immobilization due to stroke or casting,
weightlessness)
PATHOGENESIS
CHANGES IN:
Dietary intake of Calcium and Vitamin D
Activity musculoskeletal function
Genetic determinants
Systemic factors :
Calcitonin
Vit D3
Parathyroid hormone (PTH)
Estrogen
Local factors:
Cytokines
Growth factors
Peptide prostaglandine
are important factors in both formation and resorption of bone in men and
women, resulting in OSTEOPOROSIS
PATHOGENESIS

Bone is alive and must be able to grow, heal, and respond to its
environment: BONE REMODELING
The balance between bone resorption and bone deposition is
determined by the activities of OSTEOCLASTS and OSTEOBLASTS,
which are from two different origins.
Osteoclasts are activated first, leading to bone resorption. Then,
after a brief reversal phase, during which the resorption pit is
occupied by osteoblasts precursors, bone formation begins as
progressive waves of osteoblasts form and lay down fresh bone
matrix
PATHOGENESIS
PATHOGENESIS
Normal bone remodeling
Activation Osteoblast
precursors
Osteoclasts

Resorption
by osteoclasts Reversal
Osteoblasts

Osteocyte
Resting Formation
PATHOGENESIS

COMPONENTS THAT STIMULATE OSTEOCLAST ACTIVITY


A cell surface receptor called RANK (for receptor activator of NFkB) prods
osteoclasts precursor cells to develop into fully differentiated osteoclasts when
RANK is activated by its cognate partner RANK ligand (RANKL) which is produced
by osteoblasts
OSTEOPROTEGERIN (OPG), another protein released by osteoblasts, can also
bind to RANKL, acting as a decoy to prevent RANK and RANKL from coming in
contact.
The balance of RANKL/OPG may be crucial in osteoporosis. Increased
production of OPG leads to an increase in bone mass. Inhibitors of RANKL
promise as potential th/ for OP in humans
PATHOGENESIS
Bone Remodeling is coupling process of Osteoblasts & Osteoclasts acts

STROMAL STEM CELL T-CELL HEMATOPOITIC STEM CELL


OPG
osteoblast/stromal cells (RANK HOMOLOG)
osteoclast precursors.

RANKL
(RANK LIGAND) RANK

RANKL molecule found on osteoblasts/stromal cells, serves to activate osteoclasts


RANK molecule found on osteoclasts precursors cells
OSTEOPROTEGERIN (OPG) is a cytokine, a RANK homolog, produced by osteoblast
which can inhibit the production of osteoclasts by binding to RANKL, thus blocking the
RANKL-RANK interaction between osteoblast/stromal cells and osteoclast precursors.
PATHOGENESIS
FACTORS AFFECTING BONE MASS & BONE LOSS

Heredity Inactivity
Hormonal Diet
Diet Vitamin D
Exercise

Secondary
causes

rd th
PATHOGENESIS

FACTORS
AFFECTING
BONE MASS &
BONE LOSS

20
DIAGNOSIS

CLINICAL SYMPTOMS
OSTEOPOROSIS IS A SILENT DISEASE: The loss of the bone
mass occurred slowly and progressively for years without
any symptom (thief in the night) and manifest clinically as
fractures with minimal trauma

Clinical History : disease, medication, fracture

Clinical Appearance : thin, short

Clinical Examination : bone pressure pain


DIAGNOSIS
NO SPECIAL SYMPTOMES or SIGNS OF OSTEOPOROSIS, UNTILL
THERE ARE FRACTURES EITHER MACRO OR MICRO OR
REDUCTION OF BODY HEIGHT

gb
DIAGNOSIS
CLINICAL PREDICTION OF OSTEOPOROSIS
Bone and joint pain:
snapshot pain in the back
followed by muscle stiffness
is the result of a micro trabeculair fracture

Deformity:
Kyphosis (Dowagers hump)
Varus knees
Loss of Height

Bone fracture:
Fracture with minimal trauma in Spine (T12-L1), Hip (Neck &
trochanter) and Wrist
DIAGNOSIS

Radiographic diagnosis:
X-rays:
Rarefaction of all bones
Thin cortices
Deformity especially in vertebral bodies
DEXA: dual energy X-ray absorptiometry:
The # risk doubles with every decrease of standard
deviation in BMD T-score
Laboratorium:
The serum calcium, phosphorus, and alkaline phosphatase are
normal
X-RAY DIAGNOSIS
OSTEOPENIA IS NOT DETECTED ON CONVENTIONAL RADIOGRAPH
UNTIL 20 TO 40% BONE MASS HAS BEEN LOST

Normal

Mild

Severe
Radiography is inadequate when used alone for diagnosing osteoporosis in
women without vertebral fractures.

Genant HK, et al. J Bone Miner Res 1996;11:98496


http://courses.washington.edu/bonephys/opclin.html
DEXA BMD DIAGNOSIS

Dual-Energy X-ray Absorptiometry (DEXA)

Peak bone mass

Osteoporosis

Normal Osteopenia

0 1 2 2.5
T-score

DEXA = Dual-Energy X-ray Absorptiometry


DEXA BMD DIAGNOSIS

DEXA (Lunar DEXA (Lunar


DPX-IQ) measurements of femoral DPX-IQ) measurements of lumbar
neck bone density in an osteoporotic spine bone density in an
woman (AP view). osteoporotic woman (AP view).
DEXA - BMD DIAGNOSIS
Guidelines for Bone Density Testing

All women aged >65


All postmenopausal women <65 who have one or
more additional risk factors
Postmenopausal women who present with
fractures
No recommendation for or against routine
screening in women <60

www.nof.org National Osteoporosis Foundation


DEXA - BMD DIAGNOSIS

T-score is the standard deviation (SD) variance


of the patient's BMD compared to a healthy
young-adult reference population
WHO consensus
Normal : T Score 1 SD
Osteopenia : T Score 1 SD to 2.5 SD
Osteoporosis : T Score < 2.5 SD
Severe Osteoporosis : T Score < 2.5 SD plus one or
more osteoporotic factures.
The changes in the interconnectivity of the trabecular are
not reflected in the BMD measurement.
DEXA BMD T SCORE DIAGNOSIS

T-score is the standard deviation (SD) variance of the


patient's BMD compared to a healthy young-adult
reference population

BMD and SD expressed as g/cm2

T-score is dependent on factors other than the


patient's BMD, and that a change in the mean or SD of
the reference population can result in a different T-
score
DEXA BMD Z SCORE DIAGNOSIS

Z-score is the standard deviation (SD) variance of the


patient's BMD compared to an age- and sex-
matched reference population, and should not be
used to diagnose osteoporosis.
It is calculated according to the same formula as the
T-score, except that the reference population is age-
and ethnicity-matched instead of young-adult
matched.
Useful for determining an underlying disease or
condition that is causing bone loss
DIAGNOSIS
BIOMARKERS OF BONE TURNOVER

FORMATION (OSTEOBLAST) RESORPTION (OSTEOCLAST)


Serum Osteocalcin Urinary pyridinoline and
Serum totale and bone deoxypiridinoline
Alkaline Phosphatase Urinary and serum CTX
Serum type I collagen Urinary and serum N
propeptide telopeptide of the chain
of type I collagen (NTX)

These tests provide information about the dynamics of bone


resorption and formation throughout the skeleton.
The serum calcium, phosphorus, and alkaline phosphatase are normal
ESTIMATING RISK of FRACTURE DIAGNOSIS
FRAX score Tool
Menilai risiko patah tulang dalam 10 tahun www.keropos.com.

SD = standard deviation
ESTIMATING RISK of FRACTURE DIAGNOSIS
BMD
Low BMD is considered a major predictor of fracture risk.
An individuals fracture risk approximately doubles for each
standard deviation (SD) of BMD below baseline

SD = standard deviation
ESTIMATING RISK of FRACTURE DIAGNOSIS

BMD
ESTIMATING RISK of FRACTURE DIAGNOSIS

BMD & DISEASE RISK FACTORS:

30

25

Rate of 20
27.3
Hip Fracture/
1000 15
Woman-Years 14.7
10 9.4
5
5
3-4 Number of
0 0-2 Risk Factors
Lowest Third Middle Third Highest Third
Bone Density

Cummings SR et al. N Engl J Med. 1995;332:767-773.


ESTIMATING RISK of FRACTURE DIAGNOSIS

BMD & BONE TURNOVER MARKERS


Population Odds Ratio (95% CI) Likelihood Ratio Probability of Fracture
Over 5 y, %

All women (N = 435) ... ... 12.6

Women with low femoral neck 2.8 (1.4-5.6) 2.80 39


BMD (T score <-2.5)

Women with high serum CTX 2.1 (1.2-3.8) 1.70 25


(T score >2)

Women with high urine DPD (T 1.8 (1.0-3.4) 1.68 24


score >2)

Women with low BMD + high 3.8 (1.9-7.3) 3.70 54


CTX

Women with low BMD + high 2.1 (0.7-6.2) 3.04 45


free DPD
RISKS FACTORS

Risk factors that cannot be changed:


Gender Woman has less bone tissue and loses bone
faster than man
Age The bones become thinner and weaker as they age.
Body size Small, thin-boned women are at greater risk.
Ethnicity Caucasian and Asian women are at highest risk.
Family history Fracture risk may be due to heredity.
RISKS FACTORS
Risk factors that can be changed:
Sex hormones amenorrhea, low estrogen and testosterone
Anorexia nervosa
Calcium and vitamin D intake
Medication use: glucocorticoids and some anticonvulsants
Lifestyle: inactive lifestyle or extended bed rest
Cigarette smoking
Alcohol intake
THE CAUSE OF BMD DETERIORATION
MEDICATIONS THAT CAN CAUSE SECONDARY BONE LOSS INCLUDE:
Aluminum-containing antacids Lithium

Antiseizure medications (only some) suchas Medroxyprogesterone acetate for


Dilantin or Phenobarbital contraception (Depo-Provera)

Aromatase inhibitors such as Arimidex, Methotrexate


Aromasin and Femara
Proton pump inhibitors (PPIs) such as
Cancer chemotherapeutic drugs Nexium, Prilosec and Prevacid

Cyclosporine A and FK506 (Tacrolimus) Selective serotonin reuptake inhibitors


(SSRIs) such as Lexapro, Prozac and
Glucocorticoids such as cortisone and Zoloft
prednisone
Tamoxifen (premenopausal use)
Gonadotropin releasing hormone (GnRH)
such as Lupron and Zoladex Thiazolidenediones (Actos and Avandia)

Heparin Thyroid hormones in excess Aromatase


inhibitors
THE CAUSE OF BMD DETERIORATION

Co-morbid factors
In addition to preliminary tests (serum calcium, full blood-count,
TSH and kidney and liver function) the following tests were
performed:

Condition Test/signs

Celiac disease IgA transglutaminase (tTGA), endomysial antibodies

Cushing syndrome Urinary free cortisol

Hyperparathyroidism Intact PTH

Rickets, osteomalcia Vitamin D

Rheumatoid arthritis Rheumatoid factor


RISKS FACTORS

42
MANAGEMENT OF OSTEOPOROSIS
BASED ON ACCURACY OF THE DIAGNOSIS, SEVERITY OF DISEASE, AND
THE REGIMEN STRATEGY
Treatment combines:
nutrition
exercise
safety measures
medications
orthopaedic procedures

The main purpose is to prevent the further bone loss and the
possibility of pathological fractures and to build up the bone
deposition: Healthy lifestyle since childhood
NON-DRUG TREATMENT

NUTRITION containing Ca and Vit D3


1000MG CALCIUM AND 800IU VITAMIN D3 PER DAY IS NECESSARY
Normal levels are:
24-hour urinary calcium: 250mg/day
25-hydroxyvitamin D in serum: 80nmol/L

In cases where 24-hour urinary calcium is >400mg/day, the patient


should be advised to stop taking calcium supplements for 710
days, and the test repeated
In menopouse women : a negative calcium balance 50 mg/day,
excreted in urine, is the result of more bone resoption than bone
formation. The plasma calcium rises at the menopouse
1. Kanis J, et al. Osteoporosis Int 2008:19;399428
NON-DRUG TREATMENT

EXERCISES

Regular walking 5x/week, 4.5km/h for 50 minutes


Back, hip and leg muscles excercises for strengthening
and balancing
NON-DRUG TREATMENT

SAFETY MEASURES

Eating a balance diet rich in calcium, no tobacco,


no alcohol
Prevention of falls in the elderly post menopausal
women by reducing sedatives, wearing good foot
wear, no slippery floor, and sufficient room lighting
Wearing hip protectors
DRUG TREATMENT MEDICATIONS
Anti Resorption Drug: retard bone resorption (inhibit oclasts activity):
give increasing BMD 5-10% after 2 years
1. ESTROGENS (HRT) for prevention of post menopausal oporosis. Increases
BMD, but may not change the bone architecture. Reduce the risk of
fracture up to 33 %.

2. SERM (Selective Estrogen Receptor Modulator). (Raloxifine) Inhibits the


bone loss without stimulating the endometrium

3. CALCITONIN: Decreasing the oclasts number and activity. Reduce the risk
of osteoporotic fracture up to 57 %. Usefull as osteoporotic pain
treatment.

4. BIPHOSPHONATES (Alendronate, Risendronate, Ibandronate): Inhibiting


oclasts activity. Persists in the skeleton for many month so their duration
of action is prolonged beyond the period of administration
DRUG TREATMENT MEDICATIONS

Anabolic Drug: stimulate bone formation(stimulate oblasts activity):


give increasing BMD 20%

1. Strontium ranelate (Protos).

2 gr/day orally

1. Parathyroid hormone (Teriparatide).

20 g/day S.C , improve skeletal architecture

3. Growth hormone (IGF-1)


IF FRACTURES OCCURED: Orthopaedic treatment

To relief the pain and to restore the body


function immediately by means:
Immediate fracture fixation
Early mobilisation

Modalities :
Brace and support
Casting
Surgical intervention
Rehabilition programs

49
IF FRACTURES OCCURED: Osteoporosis management

GOALS OF THERAPY :

1. Prevention the future fractures


2. Increasing the bone mass
3. Improving mobility and functional status
MANAGEMENT OF OSTEOPOROSIS

HEALTHY
LIFESTYLE
SINCE
CHILDHOOD

51
Thank you

52
RICKETS
(decrease calcification of
growing bone matrix in children)
GENERALIZED REACTIONS of ALL BONE as AN ORGAN
Bone deposition < bone resorption (generalized decrease in bone)

Decrease calcification (hypocalcification) of bone matrix

(too little calcified bone) :

o in children: Rickets

o in adults : Osteomalacia
DEFINITION

Generalized disease of growing bone IN CHILDREN with defective


mineralization or calcification of bones before epiphyseal closing
(CALCIUM SALTS MINERALIZATION FAILURE), which is occured in
the organic bone matrix (osteoid) and the preosseous cartilage of
epihyseal plate.

Due to deficiency or impaired metabolism of vitamin D,


Phosphorus, or Calcium, potentially leading to fractures and
deformity.
DEFINITION
Characterized by:
increase in uncalcified matrix (in osteoid and
epiphyseal plate)

decrease in calcified matrix (bone)

Developping A SOFT BONE which is prone for


progressive deformities (Calcium provides the
hardness of bone)

The most frequent childhood diseases in


developing countries, mostly due to severe
malnutrition.
ETIOLOGY

The predominant cause is a Vitamin D deficiency

Lack of adequate dietary Calcium, Phosphate and Vitamin D

Lack of sunlight (sunlight induce the production of Vit D from the skin)

Diseases such as G I malabsorption, Chronic liver disease, Chronic


kidney disease

Drugs that increases catabolism of vitamin D in the liver

Hereditary

Vitamin d dependent rickets ( type 1& 2)

Vitamin D resistant rickets


PATHOGENESIS

The physiological levels of Calcium and Phosphorus in


serum are dependent on the balance of:
their absorption from intestine,

their excretion in kidneys and intestine,

the rate of movement into and out of bone

This calcium and phosphorous balance are maintained


by Vitamin D and Parathyroid hormone (PTH)

Vit D is produced especially from the skin


PATHOGENESIS

Vitamin D3 metabolism
PATHOGENESIS

Interaction between Calcium, Phosphate, Vit D3 and PTH

Ca Reabsorption
(kidney)

Ca absorption
Ca PTH Vit D3 (gut) Ca

CALCITONIN
Bone
resorption
(bone)
PATHOGENESIS

Interaction between Calcium, Phosphate, Vit D3 and PTH

Hypocalcemia due to Vit D deficiency induce subsequently:


the secretion of PTH (secondary hyperparathyroidism)
the excretion of Phosphate in the urine
(hypophosphatemia)
the production of Alkaline Phosphatase
CLASSIFICATION
I. VITAMIN D-RELATED RICKETS
1. Vitamin D deficiency
2. Vitamin D-dependent rickets
a. Type 1 (25-Hydroxyvitamin D3 1-alpha-hydroxylase deficiency)
b. Type 2 (Calcitriol mutation)

II. HYPOCALCEMIA-RELATED RICKETS


1. Hypocalcemia
2. Chronic renal failure

III. HYPOPHOSPHATEMIA-RELATED RICKETS


1. Congenital
a. Vitamin D-resistant rickets
b. Autosomal dominant hypophosphatemic rickets(ADHR)
c. Autosomal recessive hypophosphatemic rickets (ARHR)
2. Hypophosphatemia (typically secondary to malabsorption)
3. Fanconi's syndrome

IV. SECONDARY TO OTHER DISEASES


1. Tumor-induced osteomalacia
2. McCune-Albright syndrome
3. Epidermal nevus syndrome
4. Dent's disease
SIGNS AND SYMPTOMS

Bone tenderness
Muscle weakness
Tetany or convulsion due to hypocalcemia in early stages
Dental problems
Growth disturbance and bone deformity as small stature,
craniotabes, genu varum, genu valgum, pelvic deformity,
kyphoscoliosis or lumbar lordosis, square skull
Greenstick fractures
SIGNS AND SYMPTOMS
SIGNS AND SYMPTOMS
DIAGNOSIS

X ray shows rickets bony lesions (a widened radioluscent


zone in epiphyseal plate and a generalized coarse
appearance of trabeculation) as bow legs, cupping wrist
and "rosary beads" chest of rickets.

X-ray shows also hyperparathyroid bony lesions


(disintegration of metaphysis and erosion of cortical bone)
due to a secondary hyperparathyroidism, if exist
DIAGNOSIS
DIAGNOSIS
LABORATORY changes: low serum vit D, hypocalcaemia,
hypophosphataemia, elevated serum alkaline phosphatase, and
elevated serum PTH
TREATMENT

The treatments both causative and symptomatic are


directed toward:
the rickets

the secondary hyperparathyroidism

the etiology of rickets such as the renal insufficiency

It responds well to diet rich on CALCIUM and VIT D and oral


1,25- di-OH Vit-D3
ORTHOPAEDIC MANAGEMENT OF DEFORMITIES
Controlling the underlying cause of rickets
Once the rickets has been controlled, bony deformities
tend to regress
Apply the appropriate night splint
Perform the osteotomy correction
Aware of the potential danger of hypercalcemia during
immobilization after surgery. Therefore the vit D therapy
should be stopped 1 month before operation
Thank you

71
OSTEOMALACIA
(decrease calcification of
mature bone matrix in adults)
=rickets in adults
GENERALIZED REACTIONS of ALL BONE as AN ORGAN

Bone deposition < bone resorption (generalized decrease in bone)

Decrease calcification (hypocalcification) of bone matrix

(too little calcified bone) :

o in children: Rickets

o in adults : Osteomalacia
DEFINITION
Generalized disease of mature bone (ADULT RICKETS)
characterized by softening of the bones caused by defective
mineralization or calcification (CALCIUM SALTS
MINERALIZATION FAILURE which is occured in the organic
bone matrix / osteoid), secondary to:

inadequate levels of available phosphate and calcium, or

hyperparathyroidism due to overactive resorption of


calcium from the bone which causes hypercalcemia.
ETIOLOGY
A deficiency of vitamin D (which is normally derived from sunlight
exposure and from the diet). Home bound elderly population who
receve little sun exposure, is prone for this issue
A hereditary deficiencies of vitamin D or phosphate (which would
typically be identified in childhood)
Hypophosphatemia
Malabsorption secondary to gastrointestinal bypass surgery or
celiac disease
Malignancy induced osteomalacia.
Chronic kidney disease
Renal osteodystrophy
PATHOGENESIS

Two main pathogenesis:


1. Insufficient calcium absorption from the intestine
because of:
a) lack of dietary calcium
b) deficiency of vitamin D
c) resistance to the action of vitamin D
2. Phosphate deficiency caused by increased renal
losses.
SIGNS and SYMPTOMS
Anorexia, weight loss
Diffuse symetrical bone and joint pains (especially
of spine, pelvis, and legs)
Muscle weakness, difficulty walking, often with
waddling gait
Hypocalcemia (positive Chvostek sign)
Soft and fragile bones risk for pathological
deformities and fractures as compressed
vertebrae and diminished stature, pelvic
flattening, bowing of the legs
DIAGNOSIS
LABORATORY FINDINGS:
The most specific screening test for vitamin D deficiency in otherwise
healthy individuals is a serum 25(OH)D level.
Low serum Vit D3
Low serum Ca & P
Elevated Serum ALP (due to an increase in compensatory osteoblast
activity)
Elevated serum PTH

RADIOLOGICAL APPEARANCES:
Pseudofractures also called Looser's zones.
Protrusio acetabuli, a hip joint disorder
Technetium bone scan
Bone biopsy
TREATMENT

Oral administration of Vit D3 and Calcium

Correction of underlying cause of osteomalacia

Orthopaedic management as osteotomy deformity correction


Comparison of bone pathology
Alkaline Parathyroid
Condition Calcium Phosphate Comments
phosphatase hormone

OSTEOPENIA unaffected unaffected normal unaffected decreased bone mass

thick dense bones


OSTEOPETROSIS unaffected unaffected elevated unaffected also known as marble
bone

OSTEOMALACIA
decreased decreased elevated elevated soft bones
AND RICKETS

OSTEITIS
FIBROSA elevated decreased elevated elevated brown tumors
CYSTICA

variable
PAGET'S
(depending abnormal bone
DISEASE OF unaffected unaffected unaffected
on stage of architecture
BONE
disease)
Thank you

81
HYPERPARATHYROIDISM
(PARATHYROID OSTEODYSTROPHY)
(OSTEITIS FIBROSA CYSTICA)
(general osteoporosis combined
with a disseminated osteolytic
lesions)
DEFINITION
Increased serum PTH causes hypercalcemia and hypophosphatemia
due to increased bone resorption (PARATHYROID
OSTEODYSTROPHY)

The involved organs are bone, kidney, stomach, intestine, muscle, or


nerve

A combination of generalized and localized excessive osteoclastic


bone resorption with marrow fibrosis give the appearance of a
general osteoporosis with a disseminated osteolytic lesions (OSTEITIS
FIBROSA CYSTICA)
TYPES
Primary hyperparathyroidism due to:
Parathyroid adenoma

Parathyroid hyperplasia

Secondary hyperparathyroidism due to:


Chronic renal insufficiency associated with hypocalcemia

Intestinal malabsorption or Vit D deficiency with osteomalacia


CLINICAL SYMPTOMS
Two types:
Caused by hypercalcemia: Anorexia
Lethargy
Weakness
Symptoms of renal calculi

Caused by bone disease: Bone pain


Bone deformity
Lose of teeth
Pathological fractures
DIAGNOSIS

X-Ray: holes are earliest seen in tooth and phalanges


(Generalized rarefaction of all bones and disseminated
osteolytic lession of multiple bones, without sclerotic
reaction of the host bone (cystic brown tumour).

OSTEITIS FIBROSA CYSTICA


DIAGNOSIS

Bone Scan:

may be negative

Laboratory:
Elevated serum PTH and alkaline phosphatase

Hypercalcemia and hypercalciuria

Hypophosphatamia and hypercalciuria


TREATMENT
Primary hyperparathyroidism:
Without symptom with mild hypercalcemia and no organ
damage: MEDICALLY
With severe symptoms: PARATHYROIDECTOMY and
CORRECTION OSTEOTOMY

Secondary hyperparathyroidism:
Directed to underlying chronic renal insufficiency or intestinal
malabsorption
Vit D high dose
Parathyroidectomy
Thank you

89
PAGETS DISEASE
(OSTEITIS DEFORMANS)
(osteolytic followed by
osteosclerotic phase)
DEFINITION

Disseminated bone disorders where the uninvolved bone remain normal,


characterized by:

Slow but progressive disorder that can result in enlarged and misshapen
bones. The pelvis, femur, lower limb, vertebrae and skull are the most
commonly affected bones.

Unexplained acceleration process of resorption (osteclastic activity) and


deposition (osteblastic activity) of extremely vascularized and fibrotic bone:
osteolytic followed by osteosclerotic phase, causing affected bone to weaken
ETIOLOGY

An unknown etiology:
thought that a slow virus affecting osteoclasts
Hereditary: Mutations in two genes, SQSTM1 and
RANK, and specific regions of chromosome 5 and 6
are involved in regulating the function of osteoclasts
in Paget's disease of bone.
Second most common bone disease after osteoporosis
More common in Caucasian, aged > 55 years
Male : Female = 3 : 2
in 4 stages: PATHOGENESIS
1. Osteoclastic activity: an advancing lytic wedge in long
bones or the skull (osteoporosis circumscripta)

2. Mixed osteoclastic - osteoblastic activity: The osteolysis is


followed by a compensatory increase in bone formation

3. Osteoblastic activity: The resorbed bone is replaced and


the marrow spaces are filled by an excess of fibrous
connective tissue with a marked increase in blood vessels,
causing the bone to become hypervascular.

4. Malignant degeneration
SIGNS and SYMPTOMS

Milder form : no symptoms

More severe form : bone pain, bowed limbs,


large heads, and shorter posture

The most severe form : can further evoluate to


degenerative arthritis, pathological fracture, and
even change to osteogenic sarcoma, deafness, spinal
stenosis, cardiac failure and hypercalcemia.
SIGNS and SYMPTOMS

Cotton Wool Skull


DIAGNOSIS

Laboratorium:
Elevated serum Alkaline Phosphatase

Elevated urinary Hydroxyproline

Normal Calcium and Phosphate

X-ray:
Skeletal survey

The affected bone become deformed,


enlarged and porotic

Technitium bone scan:


TREATMENT

Diet 10001500 mg of calcium and at least 400 units of vitamin D


daily, and adequate sunshine.
Treatment can control Paget's disease and lessen symptoms, but is
not a cure. The goal is to relieve bone pain and prevent the
progression of the disease.
Treatment is directed to inhibit the activity of osteoclasts:
Biphophonates
Calcitonin
Plicamycin
TREATMENT

There are generally three major complications of Paget's


disease for which SURGERY may be recommended:
o Fractures ORIF
o Severe degenerative arthritis THR / TKR
o Bone deformity OSTEOTOMY
Medical therapy prior to surgery helps to decrease bleeding
and other complications.
Thank you

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