• Metabolic Bone Disease

 

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

 

•        Paget disease

 

•        Renal osteodystrophy

 

•        Osteoporosis

 

•           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:

1- Most commonly:

–       Reduced dietary intake of calcium and Vit D.

–       Limited exposure to sunlight.

2- 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  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  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:

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

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

3- 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

•           à 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

•           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.