METABOLIC BONE DISEASE Bone Cell Types ◻ Osteoblast • ◻ Osteocyte • • ◻ Forms bone & mineralization of matrix Transformed osteoblast Maintains bone found in matrix Osteoclast • • Breaks down bone salts Responsible for bone reabsorption Bone Remodeling Process PHASE I PHASE II PHASE III Hormonal, Biochemical Physiological Indicators Osteoclasts Resorb Bone Osteoblasts Form Bone Activate Precursors Creates Cavities in Cortical & Cancellous Bone Create New Bone In Formed Cavities Osteoclast Formation Anti-Resorptive Medication ◻ Estrogen • Prevents bone resorption(Increased osteoblast activity and Retention of calcium and phosphate) • Most commonly used • Start within 3 Yrs of menopause • Positive effect of calcium absorption & calcitonin • ↑ risk of endometrial cancer – progesterone MUST be added if no hysterectomy • Oral / Transdermal • New data shows no change in CV risk Anti-Resorptive Medication ◻ Calcitonin • • • • • • Inhibits osteoclasts – prevents bone resorption Tx. postmenopausal osteoporosis Males & females In conjunction with calcium & Vitamin D Analgesic properties Intranasal administration Anti-Resorptive Medication ◻ Bisphosphonates Non-Hormonal agent • • • • Highly selective osteoclast inhibitor Indicated for treatment & prevention & osteoporosis in men BMD 2 standard dev. below norm for young adults SE – GI disorders / Esophageal & gastric ulcers Anti-Resorptive Medication ◻ SERM - Selective Estrogen Receptor Modulator • • • Indicated for prevention Enhances beneficial effects of estrogen without increasing risks to breast / uterus Caution use in patients at risk for DVT Bone Forming Agents ◻ Slow-Release calcium fluoride • • • • Stimulate osteoblast activity New bone matrix remains brittle Not effective with severe demineralization Must have adequate calcium intake Metabolic bone disease • 1. 2. 3. Metabolic bone disease are of 3 main types: Osteoporosis : the quantity of bone mass is abnormally low Osteomalacia : osteoid tissue is present but poorly mineralized Osteitis fibrosa :PTH over production leads to bone resorption and replacement by fibrous tissue Clinical assessment The clinical features are those of : • Skeletal failure : pain , fracture , deformity • Hypercalcaemia : anorexia , nausea , vomiting , abdominal pain , depression , renal stone • Clinical features of underlying disorder • * history : duration of symptoms , relation to previous disorders , drug history , previous operation ,,,etc • * Examination : patient general appearance Clinical assessment • • • X-ray :decreased bone radio density is a late sign ( up to 30 % decrease is needed to be detected radiologically) The earliest sign is the loss of horizontal trabeculae of the vertebral bodes , vertical trabeculae are more clear , the vertebral cortices are sharply etched There may be signs of fractures old or new in the spine , ribs , pubic rami , cortico-canclous junction of the long bones Clinical assessment In the vertebra , there may be compression fracture , minor wedging at multiple levels bi concave distortion of end plates ◻ There may be x-ray finding of the underlying disorder ◻ Clinical assessment *Measurement of bone mass Radiographic absorptiometry ◻ Single energy x-ray absorptiometry ◻ Dual energy x-ray absorptiometry ◻ Quantitative CT ◻ Clinical assessment Biochemical tests ◻ Serum calcium and phosphate ◻ Serum alkaline phosphatase ◻ PHT activity ◻ Vit D activity ◻ Urinary calcium and phosphate ◻ Urinary hydroxyl proline * bone biopsy Osteoporosis A state of which the bone is fully mineralized , but it’s structure is abnormally porous and it’s length is less than normal for the person at the same age and sex ◻ i.e. there is significant decrease in the bone mass per unit volume of bone tissue and this is accompanied by increase fragility ◻ Osteoporosis can be regional where it is confined to bone or group of bones or generalized ◻ Osteoporosis Type I - Postmenopausal Type II - Senile Secondary Predominantly in Females Affects Males & Females Affects Males & Females 10-15 Years Postmenopause Common After Age 70 Occurs At Any Age Decreased Levels of Estrogen Related to Nutrition Decreased Physical Activity Result of Disease Process Or Medical Treatment Loss of Trabecular Bone Loss of Cortical & Trabecular Bone Loss of Cortical & Trabecular Bone Accelerated Bone Loss Non-Accelerated Bone Loss Osteoporosis • 1. 2. Osteoporosis is usually divided into : Primary Osteoporosis : no cause is found , usually due to aging and decrease gonadal activity Secondary Osteoporosis : due to a variety of metabolic , endocrine , neoplastic disorders Primary Osteoporosis • 1. 2. There is 2 types : Early post menopausal syndrome : due to rapid increase in the osteoclastic resorption ( type I or high turn over Osteoporosis ) Senile Osteoporosis : due to decrease in osteoblastic activity and the appearance of the dietary insufficiency and chronic ill health ( type II or low turn over Osteoporosis ) Post menopausal Osteoporosis women at menopause and next 10 years loose bone at rate of 3 % per year , compared to 0.3 % during the preceding decade , due to increased bone resorption ◻ Risk factors : white , positive family history , amenorrhea , early hysterectomy , alcoholism , cigarette smoking , lack of exercise ◻ Post menopausal Osteoporosis • • • • Clinical features :bone pain , backache , increase thoracic kyphosis X-ray :wedging or compression of one or more vertebral bodies Diagnosis : mentioned previously Prevention and treatment :women approaching menopause should maintain adequate dietary levels of calcium and phosphate and vitamin D ,and keep a high level of physical activity , no smoking , no alcohol consumption Post menopausal Osteoporosis • 1. 2. 3. 4. Drugs used : Estrogen medication (hormone replacement therapy ) Biphosphonates Calcitonin Fluride Bisphosphonates – Antiresorptive Agents ◻ Agents FDA-approved for: • ◻ Prevention and treatment of osteoporosis in postmenopausal women Mechanism: inhibits bone resorption by attaching to bony surfaces undergoing active resorption and inhibiting action of osteoclasts • Leads to increases in bone density and reduced fracture risk Senile osteoporosis Fifty years after menopause or in the seventh or eighth decade in men there is loss of bone mass by 0.5 % per year , this is universal to be considered as physiological manifestations of aging ◻ Risk factors : similar to post menopausal osteoporosis , but in addition there is prolonged menopausal bone loss , chronic illness , dietary insufficiency , lack of exposure to sun light ◻ Senile osteoporosis Clinical features : exaggeration of sign and symptoms of post menopausal osteoporosis, there is fracture ribs , pubic rami , the classical fracture is neck of femur with minimal trauma ◻ X-ray : decrease trabecular marking of neck of femur and spine ◻ Serum biochemistry are normal unless there is a sign of osteomalacia ◻ Senile osteoporosis Treatment : correction of the underlying disorder ◻ Drugs have very limited role because of the very slow bone turn over at this age ◻ Sometimes we can use HRT , biphosphonate ◻ Rickets and osteomalacia They are different expression to the same disease : defective mineralization of the bone , the bone tissue throughout the skeleton is incompletely calcified and softened ◻ In the children there are effects on physical growth and ossification , resulting iin deformity of endochondral ossification (rickets ) ◻ Rickets and osteomalacia ◻ Causes: calcium diffecincy , defects any ehre in the metabolic pathway for vitamin D , decrease intake , lack of exposure to sunlight , intestinal malabsorption , defective hydroxylation in the liver and kidney Rickets and osteomalacia Clinical fetures :children : tetany , convulsions , failure to thrive , muscle flaccidity , deformity in the skull ( craniotabes ) , thickening of the knees , ankle , wrist from physeal over growth , enlargement of costochondral junction ( rickety rosary ) , lateral indentation of the chest ( Harrison sulcus ) tibial bowing ◻ When the child starts to walk , there is knock n\knees , bow legs , swollen joints , disturbed gait ◻ Rickets and osteomalacia Adults ◻ Coarse is slow , patients complains of backache , bone pain , muscle weakness, vertebral collapse causes loss of weight Unexplained pain in the hip or one of the long bones precede the stress fractures ◻ X-ray : in active rickets there is thickening , widening of growth plate , cupping of metaphysis , bowing of the diaphysis ( which may remain after healing ) ◻ Rickets and osteomalacia In osteomalacia : the looser zone which is a thin transverse band of rarefaction in an other wise normally looking bone , in the shaft of long bones and the axillary border of the scapula , due to incomplete stress fracure which heal with callus lacking of calcium ◻ There is also biconcave vertebrae from disk pressure ) lateral indentation of the acetabulum , spontaneous fracture of ribs , pubic rami , femoral neck ◻ Rickets and osteomalacia • • • • Biochemistry : changes common in all types of Rickets and osteomalacia are : Decrease serum calcium and phosphate , increase serum alkaline phosphatase , decrease urinary excretion of calcium The calcium phosphate product derived by multiplying calcium and phosphate pruduct expressed in mmol per liter normally about 3 , it is decreased in Rickets and osteomalacia and value below 2.4 is diagnostic Treatment : according to the cause Hyperparathyroidism Paget disease (osteitis deformans ) ◻ Characterized by enlargement and thickening of bone , the internal architecture of the bone is abnormal and the bone is brittle ◻ Hyperparathyroidism ◻ Mainly two types • • ◻ Primary- cause unknown but thought to be familial and characterized by excessive secretion of PTH Secondary-usually due to disease state such as renal failure which causes decrease in ionized serum calcium levels Excess Secretion of PTH • Interrupts metabolism of calcium / phosphate / Bone Hyperparathyroidism- Pathophysiology ◻ Although primary/secondary cause either hypo or hypercalcemia, end result remains elevated levels of PTH which causes eventual hypercalcemia and multisystem problems Hyperparathyroidism ◻ Primary Results in: Hypercalcemia Causes Adenoma / Carcinoma Genetic / Multiple Endocrine Disorder ◻ Secondary Results in initial hypocalcemia followed by hypercalcemia Causes Chronic Renal Failure / Malabsorption Syndromes / Vitamin D Deficiency Hyperparathyroidism ◻ Clinical manifestations •Bones – Demineralization due to excessive osteoclast and osteocyte activity •Kidneys – renal calculi, UTI •GI– Anorexia / NV, pancreatitis, peptic ulcers, constipation, hypergastrinemia •Psychiatric issues •Muscle weakness, myalgias Hyperparathyroidism ◻ Diagnostics • All other causes of hypercalcemia must be eliminated first • 6 month history of symptoms of hypercalcemia ■Kidney stones, hypophosphatemia, hypochloremia • Serum Calcium Levels - ↑ >10mg/dl • • PTH Assay – ↑1° Radioactive Iodine Uptake Test - ↓ ■Subclinical / Post- Partum / Acute Thyroiditis • Urinary Calcium – ↑(24 Hr Specimen) • DEXA Bone Density - ↓ Hyperparathyroidism ◻ Clinical Management • • • ◻ Adequate Hydration Increase urinary excretion of Ca++ with diuretics Drugs that decrease resorption of Ca++ by bonebiphosphates, calcitonin Surgery • Parathyroidectomy – NOT Often Recommended ■ Leaves ½ of one Lobe of the Parathyroid ■ Remove Adenoma Paget disease Pathlogy ◻ It affects one or more sites , it starts at one end of the bone and extends towards the diaphysis , the characteristic cellular changes is a marked increase in osteoblastic and osteoclastic activity at an alternating pattern at both endosteal and periosteal surface leading to increased thickness of bone it’s structure is weak and easily deformed ◻ Paget disease Clinical features :men and women are affected equally , usually after 50 year of age and the commonest sites are the pelvis , tibia , while the femur , skull and spine are next common ◻ It’s asymptomatic , it’s discovered because of pain , deformity and complication ◻ Pain is dull ache , constant , worse in bed , if it is severe , it is due to fracture or sacromatous comlication ◻ Paget disease Deformity seen mainly in the lower limbs where long bones tend to bend , the tibia anteriorly , the femur anteriolaterally , the limb look bend , feel thick , with worm skin hence called osteitis deformans , if the skull is affected it enlarges ◻ Cranial nerves entrapment : leads to impaired vision , fascial palsy , trigeminal neuralgia , deafness, vertebral thickening lead to spinal stenosis , nerve entrapment ◻ Paget disease Radiology ◻ During the resorptive phase , there are localized areas of osteolysis , later the bone becomes thick and sclerotic with coarse trabeculae with or without fine cracks on the convex sides of the shaft of long bones ◻ Paget disease Biochemistry ◻ Serum calcium and phosphate are normal , serum alkaline phosphatase is increase , increased hydroxyl purine excretion ◻ Paget disease Complications ◻ Pathological fracture , OA , nerve compression , spinal stenosis , high output cardiac failure , hypercalcaemia sacromatous transformation ◻ Paget disease • • • 1. 2. 3. 4. 5. • Treatment Most patients have never symptoms and require no treatment Indications for specific treatment : Persistent bone pain Repeated fracture Neurological complications High output cardiac failure Hypercalcaemia Drugs that suppress bone turn over are :cacitonin and biphosphonates THANK YOU….
