Download - Metabolic disorders of bone

By

Dr Akkad Rafiq

Bone Structure

Three main functions of bone support,

protection

leverage

Composition Type I collagen fibers,

mineral component

Other non-collagenous proteins Osteopontin

osteonectin

Osteocalcin

alkaline phosphatases

Bone morphogenetic protein

Bone Minerals

Almost half the bone volume is mineral

matter

mainly calcium and phosphate in the

form of crystalline hydroxyapatite

‘demineralization’ of bone occurs only by

resorption of the entire matrix

Bone Cells

Osteoblasts - concerned with bone

formation and osteoclast activation

Osteocytes -These cells can be

regarded as spent osteoblasts

Osteoclasts- These cells are the

principal mediators of bone resorption

Bone structure

The mature tissue is lamellar

bone, in which the collagen

fibres are arranged parallel to

each other to form multiple

layers with the osteocytes

lying between the lamellae.

Minerals of bone

Calcium

Magnesium

Vit D

Phosphorus

Calcitonin

Osteoporosis

clinical disorder characterized by an

abnormally low bone mass and effects

in bone structure, which renders the

bone fragile and at greater risk of

fracture in a person of that age, sex and

race.

Pathology:

• results from an unhealthy imbalance between two normal activities of bone: bone resorption and bone formation.

• The combined processes of bone resorption and bone formation allow the healthy skeleton to be maintained continually by the removal of old bone and its replacement with new bone.

Pathology

the destruction of bone begins to exceed the formation of bone; this imbalance leads to a net loss of bone, and the beginnings of osteoporosis.

PRIMERY RISK FACTORS

Caucasoid (white) or Asiatic ethnicity

Family history of osteoporosis

History of anorexia nervosa and/or amenorrhoea

Low peak bone mass in the third decade

Early onset of menopause

Unusually slim or emaciated build

Early hysterectomy

Nutritional insufficiency

Chronic lack of exercise

Causes of secondary

osteoporosis Nutritional

Malabsorption

Malnutrition

Scurvy

Inflammatory disorders Rheumatoid disease

Ankylosing spondylitis

Tuberculosis

Drug induced Corticosteroids

Excessive alcohol consumption

Anticonvulsants

Heparin

Immunosuppressives

Endocrine disorders Gonadal insufficiency

Hyperparathyroidism

Thyrotoxicosis

Cushing’s disease

Malignant disease Carcinomatosis

Multiple myeloma

Leukaemia

Other Smoking

Chronic obstructive

pulmonary disease

Osteogenesis imperfecta

Chronic renal disease

Investigations

X-ray findings are generally insufficient

• cannot reliably measure bone density

• useful to identify spinal factures, explains back pain, height loss or kyphosis.

• X-rays may detect osteopenia only when bone loss is > 30%.

Patient who had a severe fracture and a moderate fracture in her spine. Three years later a second xray revealed a new fracture. These fractures were in the lower spine.

Radiographic Fracture Assessment

DEXADual energy x-ray absorptiometry (DEXA)

• This is the most popular and accurate test to date

• non-invasive

• involves no special preparation.

• Radiation exposure is minimal,

• Can be used to measure bone mineral density in the spine, hip, wrist, or total body.

•expensive

•not portable.

Screening- Ultrasound Densitometry

inexpensive,

portable\

no radiation

can be used only in peripheral

sites (eg, the heel),

Fracture Reduction

Goal: prevent fracture, not just treat

BMD

Osteoporosis treatment options

Calcium and vitamin D

Calcitonin

Bisphosphonates

Selective Estrogen Receptor Modulators

Parathyroid Hormone

Osteoporosis Treatment: Calcium and Vit

D 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

Osteoporosis Treatment:

Bisphosphonates Decrease bone resorption

decrease hip and vertebral fractures

Alendronate, risodronate PO

IV: pamidronate, zolendronate

Ibandronate : once/month

Calcetonin not as effective as Bisphosphonates

200 IU nasally/day


Selective Estrogen Receptor Modulators

Raloxifene

Decrease bone resorption like estrogen

No increased risk cancer (decrease risk

breast cancer)


PTH

Teriparatide

INTERMITTENT PTH: overall improvement

in bone density

Current Guidelines

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

Rickets:

Etiology, pathogenesis, clinical

features, diagnostics, treatment and

prevention

Rickets is a childhood disorder

involving softening and

weakening of the bones.

It is primarily caused by lack of

vitamin D, calcium, or

phosphate.

Etiology

1. Lack of sunshine due to:

1) Lack of outdoor activities

2) Lack of ultraviolet light in fall and winter

3) Too much cloud, dust, vapour and smoke

Etiology

2. Improper feeding:

1) Inadequate intake of Vitamin D

Breast milk 0-10IU/100ml

Cow’s milk 0.3-4IU/100ml

Egg yolk 25IU/average yolk

Herring 1500IU/100g

2) Improper Ca and P ratio

Etiology

3. Fast growth, increased requirement

(relative deficiency)

4. Diseases and drug:

Liver diseases, renal diseases

Gastrointestinal diseases

Antiepileptic

Glucocorticosteroid

The history in patients with rickets may include the following:

The infant's gestational age, diet and degree of sunlight exposure should be noted.

A detailed dietary history should include specifics of vitamin D and calcium intake.

A family history of short stature, orthopedic abnormalities, poor dentition, alopecia, parental consanguinity may signify inherited rickets.

Evaluation

Clinical signs

Rickets

is a systematic disease with

skeletons involved most, but the

nervous system, muscular system

and other system are also involved.

• Skeletal deformities

1. Bow legs

2. pigeon chest 3. Bumps" in the rib

cage

4. odd-shaped skull;

Generalized muscular hypotonia is observed in the

most patients with clinical signs of rickets.

Clinical signs

• If rickets occurs at a later age,

thickening of the skull

develops. This produces

frontal bossing and delays

the closure of the anterior

fontanelle.

Frontal bossing

Protruding foreheadasymmetrical or odd-shaped skull

Chest deformity

Funnel chest – pectus

excavatum

Pigeon chest

Clinical signs In the chest, knobby deformities results in the rachitic rosary along the costochondral junctions.

Rib beading

(rachitic rosary)

Bowlegs and

knock-knees.

Clinical signs

Knock knee deformity

(genu valgum)Bowleg deformity

(genu varum)

A teenage male with rickets.

Note deformities of legs (bow legs)

and compromised height.

The ends of the long bones demonstrate that same

knobby thickening. At the ankle, palpation of the tibial

Clinical signs

malleolus gives

the impression

of a double

epiphysis

(Marfan sign).

Pain in the bones of Arms, Legs, Spine, Pelvis.

Dental deformities

Delayed formation of teeth

Defects in the structure of teeth

Holes in the enamel

Increased incidence of cavities in the teeth (dental

caries)

Clinical signs

Progressive weakness

Decreased muscle tone (loss of muscle strength)

Muscle cramps

Impaired growth

Short stature (adults less than 5 feet tall)

Fever or restlessness, especially at night

Clinical signs

The entire skeletal system must be palpated to search for tenderness and bony abnormalities.

Rickets should be suspected in older bowlegged children and in cases associated with asymmetry, pain, or progression in severity.

Physical examination

Gait disturbances and neurologic abnormalities (such as hyperreflexia) in

all children should be sought.

muscle cramps, numbness, paresthesias,

tetany and seizures.

Decreases

in serum calcium,

serum phosphorus,

calcidiol, calcitriol,

urinary calcium.

The most common laboratory findings in

nutritional rickets are:

Parathyroid hormone,

alkaline phosphatase,

urinary phosphorus

levels are elevated.

Classic radiographic findings

include:

widening of the distal epyphysis, fraying

and widening of the metaphysis, and

angular deformities of the arm and leg

bones.

Classic radiographic findings include

Anteroposterior and lateral radiographs of the wrist of an 8-year-

old boy with rickets demonstrates cupping and fraying of the

metaphyseal region

Classic radiographic findings include:

Radiographs of the knee of a 3-year-old girl with hypophosphatemia

depict severe fraying of the metaphysis.

Rickets in wrist - uncalcified lower ends of bones

are porous, ragged, and saucer-shaped

(A) Rickets in 3 month old infant

(B) Healing after 28 days of

treatment

(C) After 41 days of

treatment

A

B C

Radiographic image of wrist and

forearm showing pathologic

fractures of radius and ulna with

rachitic changes of distal end of

radius and ulna.

X-ray in rickets

Clinical manifestation

Stages Early stage

Usually begin at 3 months old

Symptoms: mental psychiatric symptoms

Irritability, sleepless, hidrosis

Signs: occipital bald

Laboratory findings: Serum Ca, P normal or

decreased slightly, AKP normal or elevated

slightly, 25(OH)D3 decreased

Roentgen-graphic changes: normal or

slightly changed


Advanced stage

On the base of early rickets, osseous changes become marked and motor development becomes delayed.

1. Osseous changes:

1) Head: craniotabes, frontal bossing, boxlike appearance of skull, delayed closure of anterior fontanelle

2) Teeth: delayed dentition with abnormal order, defects

3) Chest: rachitic rosary, Harrison’s groove, pigeon chest, funnel-shaped chest, flaring of ribs


4) Spinal column: scoliosis, kyphosis, lordosis

5) Extremities: bowlegs, knock knee, greenstick fracture

6) Rachitic dwarfism

2. Muscular system: potbelly, late in standing and walking

3. Motor development: delayed

4. Other nervous and mental symptoms


Laboratory findings: Serum Ca and P decreased

Ca and P product decreased

AKP elevated

Roentgen-graphic changes: Wrist is the best site for watching the changes

Widening of the epiphyseal cartilage

Blurring of the cup-shape metaphyses of long bone

I Mild form: small changes of nervous system, changes of one part of the skeleton;

II Moderate form: changes of all organs and systems, changes of two parts of the skeleton;

III Severe form: damaging function of all organs and systems, changes of three parts of the skeleton;

Classification

Types of Rickets

Nutritional

Nutritional rickets results from inadequate

sunlight exposure or inadequate intake of

dietary vitamin D, calcium, or phosphorus.

Vitamin D dependent

Vitamin D-dependent rickets, type I is secondary to a defect in the gene that codes for the production of renal 25(OH)D3-1-alpha-hydroxylase.

Vitamin D-dependent rickets, type II is a rare autosomal disorder caused by mutations in the vitamin D receptor. Type II does not respond to vitamin D treatment; elevated levels of circulating calcitriol differentiate this type from type I.

Vitamin D resistant

Rickets refractory to vitamin D treatment may be

caused by the most common heritable form,

known as vitamin D-resistant rickets or familial

hypophosphatemic rickets.

Other Conditions That Can Cause Rickets Medications

Antacids Anticonvulsants Corticosteroids Loop diuretics

Malignancy Prematurity Diseases of organs associated with vitamin D and

calcium metabolism Kidney disease Liver and biliary tract disease

Malabsorption syndromes Celiac disease Cystic fibrosis (rare)

Diagnosis

Assessed according to the followings:

1. History

2. Physical examination

3. Laboratory findings

4. Roentgen-graphic changes

Treatment for rickets The replacement of Vitamin D may correct rickets

using these methods of

ultraviolet light and medicine.

4000 IU of oral vitamin D per day for one month.

Parents are instructed to take their infants outdoors

for approximately 20 minutes per day with their faces

exposed.

Foods that are good sources of vitamin D include

cod liver oil,

egg yolks,

butter

oily fish.

Some foods, including milk and breakfast cereals, are also

fortified with synthetic vitamin D.

Treatment

1. Special therapy: Vitamin D therapy

A. General method: Vitamin D 2000-4000 IU/day

for 2-4 weeks, then change to

preventive dosage – 400 IU.

TREATMENT

1 STAGE

VITAMINE D – - 2000 IU 1 TIME\DAY 30 DAYS

2 STAGE


3 STAGE


Then profilactic dose – 500 iu till the end of the second – third year of life

Vitamin D

Fat-soluble vitamin used to treat vitamin D

deficiency or for prophylaxis of deficiency.

Cholecalciferol (Delta-D)

Vitamin D-3 1 mg provides 40000 IU vitamin D

activity

Treatment

4. Calcium supplementation: Dosage: 1-3

g/day

only used for special cases, such as baby

fed mainly with cereal or infants under 3

months of age and those who have already

developed tetany.

5. Plastic therapy:

In children with bone deformities after 4

years old plastic surgery may be useful.

Prevention

Vitamin D supplements

Because of human milk contains only a small amount

of vitamin D, the American Academy of Pediatrics

(AAP) recommends that all breast-fed infants receive

400 IU of oral vitamin D daily beginning during the

first two months of life and continuing until the daily

consumption of vitamin D-fortified formula or milk

is two to three glasses, or 500 mL.

AAP also recommends that all children and

adolescents should receive 400 IU a day of vitamin D.

Prevention

Vitamin D supplementation:

In prematures, twins and weak babies, give Vitamin D 800IU per day,

For term babies and infants the demand of Vitamin D is 400IU per day,

For those babies who can’t maintain a daily supplementation, inject muscularly

Vitamin D3 100000-200000 IU.

Prevention

Calcium supplementation:

0.5-1gm/day, for premature, weak babies and babies fed mainly with

cereal

Recommended daily intake of calcium is as follows: 1 to 3 years of age. 500 mg (two servings of dairy products a day)

4 to 8 years of age. 800 mg (two to three servings of dairy products a day)

9 to 18 years of age. 1,300 mg (four servings of dairy products a day)

19 to 50 years of age. 1,000 mg a day (three servings of dairy products a day)

Sources of Vitamin D

Sunlight is the most important source

Fish liver oil

Fish & sea food (herring & salmon)

Eggs

Plants do not contain vitamin D3

Download - Metabolic disorders of bone

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