Metabolic Bone Disease

Metabolic bone disease

A diseases are caused by disturbances

in the metabolism of calcium and

phosphate resulting in inadequate

mineralization of bone matrix.

The fundamental problem in metabolic bone diseases is an imbalance between bone formation and resorption in the normal remodeling process of bones

Conditions considered to be metabolic bone disorders

Osteomalacia and rickets

• These are disorders of bone in which the essential defect is failure of calcification in newly formed bone.
• Rickets is referred to disease affecting the growing children
• Osteomalacia is a disease of adults (mainly lactating females).

Osteomalacia and rickets Causes:

Mainly due to vitamin D deficiency, which could be caused by:

Most commonly:

Reduced dietary intake of calcium and Vit D.

Limited exposure to sunlight.

Less commonly:

Malabsorption ( disease in the small intestine).

Liver disease  ( defective synthesis).

Renal disease ( increased excretion).

Rickets :

Clinical effects;

Bone pain and tenderness

weakness of bones with, tendency of distortion

Microfractures (linear partial fractures)

Stunting of growth

Bowing of lower limbs

Enlargement of costochondral junctions.

Frontal bossing

Pigeon breast deformity (due to pull of respiratory muscles)

In females, permanent deformity of pelvic bone leads to serious difficulty during child birth.

Deformity or curvature of the spine

Treatment of Rickets

Vitamin D. therapy: 300,000-600,000 iu orally or IM in 2-4 divided doses over one day.

High dose vit D 2000-5000 iu orally for 4-6wks followed by 400iu daily orally as maintenance.

Adequate dietary Calcium & phosphorus provided by milk, formula & other dairy products.

Symptomatic hypocalcaemia need IV ca as 20mg/kg or ca gluconate as 100mg/kg as a bolus, followed by oral calcium tapered over 2-6 weeks.

Osteomalacia

Age: adults

Defective mineralization of newly formed bone during bone remodeling.

Soft bone – result from impaired mineralization in matrix bone.

Site:  vertebral bodies and femoral neck

Osteomalacia

Causes:

Inadequate concentration of extrcellular fluid phosphate &/or calcium.

Deficiency of vit. D dietary plus inadequate sunlight exposure.

Malabsorption; gastric surgery, celiac disease, defect bile salt production.

Renal disease; decrease conversion of 25 (OH) D à 1, 25 (OH)₂ D.

Hepatic disease; less common à decrease 1, 25 (OH)₂ D.

Due to phenytoin, barbiturate

Clinical manifestation

Bone pain, deformities, fracture.

Muscle weakness, growth retardation.

Muscle pain & tenderness (sub clinical fracture).

Proximal myopathy à waddling gait.

In children à characteristic picture of rickets.

PAGET DISEASE

It is a localized & progressive disorder characterized by increase bone remodeling, bone hypertrophy with abnormal structure

Cause unknown ?virus- males > females

Common in Europe à 3% of general population > 50 years old

PAGET DISEASE

This unique skeletal disease is characterized by: repetitive episodes of regional osteoclastic activity and bone resorption (osteolytic stage), followed by exuberant bone formation (mixed osteoclastic-osteoblastic stage) , and finally by an apparent exhaustion of cellular activity (osteosclerotic stage).

The net effect of this process is a gain in bone mass; however, the newly formed bone is disordered and lacks strength.

PAGET DISEASE MORPHOLOGY

There are three phases in the development of Paget disease:

an initial phase of osteoclastic activity, hypervascularity, and bone loss.

a mixed osteoclastic-osteoblastic phase, which ends with a predominance of osteoblastic activity.

a burnt-out quiescent osteosclerotic stage.

Paget's Disease: clinical manifestations

Bone pain

Joint pain

Deformity

Spontaneous fractures

Paget Disease

Renal Osteodystrophy

is a bone disease that occurs when your kidneys fail to maintain the proper levels of calcium and phosphorus in your blood. It's a common problem in people with kidney disease and affects 90 percent of dialysis patients .

Renal Osteodystrophy

is a bone disease that occurs when your kidneys fail to maintain the proper levels of calcium and phosphorus in your blood. It's a common problem in people with kidney disease and affects 90 percent of dialysis patients .

Renal Osteodystrophy

Renal failure

Phosphate retention

reduce 1,25 (OH)2 vit D production à Reduce à

Ca absorption à low Ca à increase PTH

Increase bone resorption

Treatment

Controlling PTH levels prevents calcium from being withdrawn from the bones. Usually, overactive parathyroid glands are controllable with a change in diet, dialysis treatment, or medication. The drug cinacalcet hydrochloride (Sensipar), approved by the Food and Drug Administration in 2004, lowers PTH levels by mimicing calcium. If PTH levels can't be controlled, the parathyroid glands may need to be removed surgically

Osteoporosis

Definition:

The most common metabolic bone disorder

Is a disorder characterized by reduction of bone mass resulting in increased porosity

The structural changes predispose to bone fragility and fractures.

Osteoporosis

Osteoporosis is often called a "silent

disease" because bone loss occurs

without symptoms.

Osteoporosis is a disease of the elderly

(>65 years).

􀂄 A woman’s hip fracture risk equals her

combined risk of breast, uterine and

ovarian cancer.

Normal versus osteoporotic bone

Prevalence

Osteoporosis is a major public health problem

worldwide. During 2006, ten million

individuals in the U.S. are estimated to have

the disease.

􀂄 Of the ten million, eight million are women

and two million are men.

Morbidity and mortality

Osteoporosis leads to:

􀂄 Loss of height.

􀂄 Fracture of the vertebrae leading to

kyphosis.

􀂄 Fracture of the hip (neck of the femur)

leading to death and disability.

Morbidity and mortality

Osteoporosis fractures are a major

cause of morbidity and mortality in

elderly.

􀂄 1.66 million hip fractures occur each

year worldwide.

􀂄 15-20% of hip fractures lead to death

within the year following the fracture.

􀂄 50% of hip fractures lead to significant

disability.

Risk Factors

Certain people are more likely to develop this disease than others.

Age

Estrogen deficiency

Testosterone deficiency

Family history/genetics

Female sex

Low calcium/vitamin D intake

Poor exercise

Smoking

Risk Factors

Alcohol

Low  body weight/anorexia

Hyperparathyroidism

Prednisone use

Liver and renal disease (think about vit. D synthesis)

Low sun exposure

Medications (antiepileptic, heparin)

Hemiplegia , CVA/ immobility

Pathophysiology

In healthy individuals who get enough

calcium and physical activity, bone

production exceeds bone destruction up

to the age of 30. After that, bone

destruction exceeds production.

􀂄 Skeletal mass starts to decline in

women after the age of 35, and in men

after the age of 45.

Pathophysiology

People typically lose bone as they age,

despite consuming the recommended

intake of calcium. This is due to several

factors, including genetic factors,

physical inactivity, and lower levels of

circulating hormones (estrogen and

testosterone).

Pathophysiology

Postmenopausal women account for

80% of all cases of osteoporosis

because estrogen production declines

rapidly at menopause.

􀂄 Men are also at risk of developing

osteoporosis, but this occurs 5-10 years

later than women, as testosterone

levels do not fall abruptly.

Osteoporotic Fractures in Women Compared With Other Diseases

A

Osteoporosis

Prevention

Building strong bones in childhood and adolescence is the best defense.

A balanced diet rich in calcium and Vitamin D

Weight bearing exercise

A healthy lifestyle with no smoking or excessive alcohol intake.

Bone density testing and medication when appropriate.

Prevention

-Avoid  long periods of immobilization

-Estrogen supplementation.

-Adequate dietary calcium intake before age of 30  appears to reduce the risk of osteoporosis. 

-Calcium supplementation in life may  moderate the  reduction of bone loss.

Public Health Recommendations

1-1.5 g of daily calcium

400-800 of vitamin D daily

Weight-bearing exercise

Discourage smoking

Recommendations

Get adequate calcium intake from milk,

yogurt and low-oxalate vegetables

rather than cheese.

􀂄 Maintain an adequate store of vitamin D

whether through diet, exposure to

sunshine, diet or supplements

Recommendations

Get an adequate protein intake. Make

plant foods your main source of protein.

􀂄 Include omega-3 F.A.s in your diet.

􀂄 Reduce sodium intake. Don’t smoke.

􀂄 Limit soft drinks and caffeine intake.

Avoid high Retinol consumption which

simulate osteoclast activity mainly in elderly.

Get vitamin A from carotenes.

􀂄 Get regular weight-bearing physical exercise.

Recommendations

Do not add salt at table.

􀂄 Decrease salt during cooking.

􀂄 Limit the intake of salty foods (olives,

pickles, chips, cheese, salted nuts,

salted fishes and salted red pepper).

􀂄 Decrease the intake of canned foods,

stock cubes and commercial biscuits

Recommendations

Nacl increases urinary calcium excretion

due to competition between Na and Ca

for kidney reabsorption.

Take adequate vitamin D.

􀂄 Magnesium helps calcium absorption

from the gut.

􀂄 Oxalate, phytic acid, and caffeine

reduces calcium absorption from the

gut.