1 DISORDERS OF THE PARATHYROID GLANDSMona Fouda Neel MBBS,FRCPEdin.,FACE Associate professor of medicine Cosultant Endocrinologist

2 Disorders of the Parathyroid GlandsMaintenance of calcium, phosphate and magnesium homeostasis is under the influence of two polypeptide hormones; parathyroid hormone(PTH), and calcitonin (CT), as well as a sterol hormone, 1,25 dihydroxy cholecalciferol (1,25 (OH)2D3.

3 Disorders of the Parathyroid GlandsThese hormones regulate the flow of minerals in and out of the extracellular fluid compartments through their actions on intestine, kidneys, and bones.

4 Disorders of the Parathyroid GlandsThe PTH acts directly on the bones and kidneys and indirectly on the intestine through its effect on the synthesis of 1,25 (OH)2D3. Its production is regulated by the concentration of serum ionized calcium. Lowering of the serum calcium levels will induce an increased rate of parathyroid hormone secretion

5 Disorders of the Parathyroid GlandsCalcitonin is released by the “C” cells (parafollicular cells in the thyroid gland) in response to small increases in plasma ionic calcium. It acts on the kidney and bones to restore the level of calcium to just below a normal set point which in turn inhibits secretion of the hormone.

6 Disorders of the Parathyroid GlandsCalcitonin is therefore the physiological antagonist of PTH. The two hormones act in concert to maintain normal concentration of calcium ion in the extracellular fluid.

7

8

9 Disorders of the Parathyroid FunctionHyperparathyroidism Primary hyperparathyroidismis due to excessive production of PTH by one or more of hyper functioning parathyroid glands. This leads to hypercalcemia which fails to inhibit the gland activity in the normal manner.

10 Disorders of the Parathyroid FunctionHyperparathyroidism The cause of primary hyperparathyroidism is unknown. A genetic factor may be involved. The clonal origin of most parathyroid adenomas suggests a defect at the level of the gene controlling the regulation and/or expression of parathyroid hormone.

11 Disorders of the Parathyroid FunctionHyperparathyroidism The incidence of the disease increases dramatically after the age of 50 and it is 2-4 folds more common in women. A single adenoma occurs in about 80% of patients with primary hyperparathyroidism. Four glands hyperplasia account for 15-20% of cases. A parathyroid carcinoma could be the etiology in a rare incidence of less then 1%.

12 Disorders of the Parathyroid FunctionClinical Features: The two major sites of potential complications are the bones and the kidneys. The kidneys may have renal stones (nephrolithiasis) or diffuse deposition of calcium-phosphate complexes in the parenchyma (nephrocalcinosis). Now a days such complications are seen less commonly and around 20% of patients or less show such complications.

13 Other Complications Deterioration of renal functionMetabolic disturbance e.g. hypomagnesia, pancreatitis, gout or pseudogout

14 Disorders of the Parathyroid FunctionClinical Features: In skeleton a condition called osteitis fibrosa cystica could occur with subperiosteal resorption of the distal phalanges, distal tappering of the clavicles, a “salt and pepper” appearance of the skull as well as bone cysts and brown tumors of the long bones. Such overt bone disease even though typical of primary hyperparathyroidism is very rarely encountered.

15 Disorders of the Parathyroid FunctionClinical Features: Now a days almost 90% of diagnosed cases in the developed countries are picked up by routine screening for calcium level using the new automated machines.

16 Disorders of the Parathyroid FunctionClinical Features: Other symptoms include muscle weakness, easy fatigability, peptic ulcer disease, pancreatitis, hypertension, gout and pseudo gout as well as anemia and depression have been associated with primary hyperparathyroidism.

17

18 Differential DiagnosisCauses of Hypercalcemia Parathyroid - related Vitamin D – related Primary hyperparathyroidism Solitary adenomas Multiple endocrine neoplasia Lithium therapy Familial hypocalciuric hypercalcemia Vitamin D intoxication 1,25(OH)2D; sarcoidosis and other granulomatous diseases Idiopathic hypercalcemia of infancy

19 Differential DiagnosisCauses of Hypercalcemia Associated with high bone turnover Malignancy - related Solid tumor with metastases(breast) Solid tumor with humoral mediation of hypercalcemia (lung kidney) Hematologic malignancies (multiple myeloma, lymphoma, leukemia) Hyperthyroidism Immobilization Thiazides Vitamin A intoxication Associated with Renal Failure: Severe secondary hyperparathyroidism Aluminum intoxication Milk alkali syndrome

20 Diagnosis The presence of established hypercalcaemia in more than one serum measurement accompanied by elevated immunoreactive PTH is characteristic (iPTH)

21 Diagnosis Serum phosphate is usually low but may be normal. Hypercalcaemia is common and blood alkaline phosphatase (of bone origin) is slightly elevated .

22 Other Diagnostic testsThe Glucocortisoid suppression test: The heypercalcaemic of non-parathyroid origin e.g., vitamin D intoxication, sarcoidosis and lymphoproliferative syndromes generally respond to the administration of prednisolone in a dose of mg daily for 10 days by a decrease in serum calcium level.

23 Other Diagnostic testsThe Glucocortisoid suppression test: The response is unusual in hypercalcaemia secondary to primary hyperparathyroidism and ectopic PTH production. A positive test result i.e. significant decrease in serum calcium is a contraindication to neck exploration and signals the need for investigation for a non-parathyroid cause of the hypercalcaemia.

24 Other Diagnostic testsRadiograph: Plain X-ray of hands can be diagnostic showing subperiosteal bone resorption usually on the radial surface of the distal phalanx with distal phalangeal tufting as well as cysts formation and generalized osteopenia.

25 Other Diagnostic testsPre-operative localization of the abnormal parathyroid gland(s): Ultrasonography MRI CT Thallium 201 – Tehcnichum99m scan (subtraction study) Sestemebi scan

26

27 Treatment A large proportion of patients have “biochemical” hyperparathyroidism but with prolonged follow up they progress to overt clinical presentation. Resection of the parathyroid lesion is curative with recurrences observed mainly in the multiple glandular disease.

28 Medical Treatment of the hypercalcaemiaIn acute severe forms the main stay of therapy is adequate hydration with saline and forced diuresis by diuretics to increase the urinary excretion of calcium rapidly along with sodium and prevent its reabsorption by the renal tubules.

29 Other agents Glucocostiroids MythramycinIn hypercalcaemia associated the hematological malignant neoplasms Mythramycin A toxic antibiotics which inhibit bone resorption and is used in hematological and solid neoplasms causing hypercalcaemia.

30 Other agents Calcitonin BisphosphonatesAlso inhibit osteoclast activity and prevent bone resorption Bisphosphonates They are given intravenously or orally to prevent bone resorption.

31 Other agents Phosphate EstrogenOral phosphate can be used as an antihypercalcaemic agent and is commonly used as a temporary measure during diagnostic workup. Estrogen It also decrease bone resorption and can be given to postmenopausal women with primary hyperparathyroidism using medical therapy

32 Surgery Surgical treatment should be considered in all cases with established diagnosis of primary hyperparathyroidism. During surgery the surgeon identifies all four parathyroid glands (using biopsy if necessary) followed by the removal of enlarged parathyroid or 3 ½ glands in multiple glandular disease.

33 Secondary hyperparathyroidismAn increase in PTH secretion which is adaptive and unrelated to intrinsic disease of the parathyroid glands is called secondary hyperparathyroidism. This is due to chronic stimulation of the parathyroid glands by a chronic decrease in the ionic calcium level in the blood

34

35 Major causes of chronic hypocalcemia other than hypoparathyroidismDeficiency of vitamin D or calcium Decreased intestinal absorption of vitamin D or calcium due to primary small bowel disease, short bowel syndrome, and post-gastrectomy syndrome. Drugs that cause rickets or osteomalacia such as phenytoin, phenobarbital, cholestyramine, and laxative.

36 Major causes of chronic hypocalcemia other than parathyroprival hypoparathyroidismStates of tissue resistance to vitamin D Excessive intake of inorganic phosphate compunds Psudohypoparathyroidism Severe hypomagnesemia Chronic renal failure

37 Hypoparathyroidism Deficient secretion of PTH which manifests itself biochemically by hypocalcemia, hyperphospatemia diminished or absent circulating iPTH and clinically the symptoms of neuromuscular hyperactivity.

38 Surgical hypoparathyroidism – the commonestCauses: Surgical hypoparathyroidism – the commonest After anterior neck exploration for thyroidectomy, abnormal parathyroid gland removal, excision of a neck lesion. It could be due to the removal of the parathyroid glands or due to interruption of blood supply to the glands.

39 Idiopathic hypoparathyroidismCauses: Idiopathic hypoparathyroidism A form occuring at an early age (genetic origin) with autosomal recessive mode of transmission “multiple endocrine deficiency –autoimmune-candidiasis (MEDAC) syndrome” “Juvenile familial endocrinopathy” “Hypoparathyroidism – Addisson’s disease – mucocutaneous candidiasis (HAM) syndrome”

40 Idiopathic hypoparathyroidismCauses: Idiopathic hypoparathyroidism Circulating antibodies for the parathyroid glands and the adrenals are frequently present. Other associated disease: Pernicious anemia Ovarian failure Autoimmune thyroiditis Diabetes mellitus

41 Idiopathic hypoparathyroidismCauses: Idiopathic hypoparathyroidism The late onset form occurs sporadically without circulating grandular autoantibodies. Functional hypoparathyroidism In patients who has chronic hypomagesaemia of various causes. Magnesium is necessary for the PTH release from the glands and also for the peripheral action of the PTH.

42 Hypoparathyroidism Clinical Features: NeuromuscularThe rate of decrease in serum calcium is the major determinant for the development of neuromuscular complications. When nerves are exposed to low levels of calcium they show abnormal neuronal function which may include decrease threshold of excitation, repetitive response to a single stimulus and rarely continuous activity.

43 Hypoparathyroidism Clinical Features: Neuromuscular Parathesia TetanyHyperventilation Adrenergic symptoms Convulsion (More common in young people and it can take the form of either generalized tetany followed by prolonged tonic spasms or the typical epileptiform seizures. Signs of latent tetany Chvostek sign Trousseau sign Extrapyramidal signs (due to basal ganglia calcification)

44 Other clinical manifestationHypoparathyroidism Clinical Features: Other clinical manifestation Posterio lenticular cataract Cardiac manifestation: Prolonged QT interval in the ECG Resistance to digitalis Hypotension Refractory heart failure with cardiomegally can occur.

45 Other clinical manifestationHypoparathyroidism Clinical Features: Other clinical manifestation Dental Manifestation Abnormal enamel formation with delayed or absent dental eruption and defective dental root formation. Malabsorption syndrome Presumably secondary to decreased calcium level and may lead to steatorrhoea with long standing untreated disease.

46 Hypoparathyroidism Diagnosis: In the absence of renal failure the presence of hypocalcaemia with hyperphosphataemia is virtually diagnostic of hypoparathyroidism. Undetectable serum iPTH confirms the diagnosis or it can be detectable if the assay is very sensitive.

47 Hypoparathyroidism Treatment: The mainstay of treatment is a combination of oral calcium with pharmacological doses of vitamin D or its potent analogues. Phosphate restriction in diet may also be useful with or without aluminum hydroxide gel to lower serum phosphate level.

48 Emergency Treatment for HypocalcaemicTetany: Calcium should be given parenterally till adequate serum calcium level is obtained and then vitamin D supplementation with oral calcium should be initiated.

49 Emergency Treatment for HypocalcaemicHungry bone syndrome: In patients with hyperparathyroidism and severe bone disease who undergo successful parathyroidectomy hypocalcaemia may be severe and parenteral calcium infusion with later supplementation with oral calcium and vitamin D.

50 Pseudohypoparathysoidism and PseudopseudohypoparathyroidismA rare familial disorders with target tissue resistance to PTH. There is hypocalcaemia, hyperphosphataemia, with increased parathyroid gland function. There is also a variety of congenital defects in the growth and development of skeleton including: Short statue Short metacarpal and metatarsal bones

51 Pseudohypoparathysoidism and PseudopseudohypoparathyroidismIn pseudopseudohypoparathyroidism they have the developmental defects without the biochemical abnormalities The diagnosis is established when low serum calcium level with hyperphosphataemia is associated with increased serum iPTH as well as diminished nephrogenous CAMP and phosphature response to PTH administration

52

53 METABOLIC BONE DISEASESMona Fouda Neel MBBS,FRCPEdin.,FACE Associate professor of medicine Cosultant Endocrinologist

54 Bone has three major functions:Provide rigid support to extrimities and body cavities containing vital organs. Provide efficient levers and sites of attachment of muscles which are all crucial to locomotion. Provide a large reservoir of ions such as calcium, phosphorus, magnesium and sodium which are critical for life and can be mobilized when the external environment fails to provide them

55 Types of Bone I. Cortical Bone:The compact bone of Haversian systems such as in the shaft of long bones. II. Trabecular Bone: The lattice – like network of bone found in the vertebrae and the ends of long bones. The difference pattern of bone loss affecting trabecular and cortical bone results in two different fracture syndrome.

56 Disorders in which cortical bone is defective or scanty lead to fractures of long bones whereas disorders in which trabecular bone is defective or scanty lead to vertebral fractures and also may help in fractures of lone bones because of the loss of reinforcement. Bone is resorbed and formed continuously throughout life and these important processes are dependent upon three major types of bone cells.

57 I. Osteoblasts: II. Osteocytes: III. Osteoclasts:The bone forming cells which are actively involved in the synthesis of the matrix component of bone (primarily collagen) and probably facilitate the movement of minerals ions between extracellular fluids and bone surfaces. II. Osteocytes: The are believed to act as a cellular syncytium that permits translocation of mineral in and out of regions of bone removed from surfaces. III. Osteoclasts: The bone resorption cells.

58 Osteomalacia Failure of organic matrix (osteoid) of bone to mineralize normally. A number of factors are critical for normal bone mineralization. An absence or a defect in any one of them may lead to osteomalacia, the most common biochemical causes are a decrease in the product of concentrations of calcium and phosphate in the extra-cellular fluid so that the supply of minerals to bone forming surfaces is inadequate.

59 Osteomalacia Other causes include abnormal or defective collagen production and a decrease in the PH at sites of mineralization.

60 Etiology of OsteomalaciaVitamin D deficiency: Inadequate sunlight exposure without dietary supplementation. House- or institution bound people. Atmosphere smog. Long term residence in far northern & far southern latitudes. Excessive covering of body with clothing. Gastrointestinal diseases that interrupts the normal enterohepatic recycling of vit. D & its metabolites, resulting in their fecal loss. Chronic steatorrhea (pancreatic) Malabsorption (gluten-sensitive enteropathy) Surgical resection of large parts of intestine. Formation of biliary fistulas.

61 Etiology of OsteomalaciaVitamin D deficiency: Impaired synthesis of 1,25(OH)2D3 by the kidney. Nephron loss, as occurs in chronic kidney disease Functional impairment of 1,25(OH)2D3 hydroxylase (eg. In hypoparathyroidism) Congenital absence of 1,25(OH)2D3 hydroxylase (vit. D-dependency rickets type I). Suppression of 1,25(OH)2D3 production by endogenously produced substance (cancer). Target cell resistance to 1,25(OH)2D3 e.g. absent, or diminished number of 1,25(OH)2D3 receptors, as in vit.D-dependency rickets type II.

62 Etiology of OsteomalaciaPhosphate deficiency: Dietary Low intake of phosphate. Excessive ingestion of aluminum hydroxide. Impaired renal tubular reabsorption of phosphate X-linked hypophosphataemia. Adult-onset hypophosphataemia. Other acquired & hereditary renal tubular disorders associated with renal phosphate loss (Fanconi’s sydnrome, Wilson’s disease). Tumor-associated hypophosphataemia

63 Etiology of OsteomalaciaSystemic Acidosis: Chronic renal failure Distal renal tubular acidosis Ureterosigmoidoscopy Chronic acetazolamide & ammonium chloride administration Drug induced Osteomalacia:

64 Laboratory & Radiological FindingsPatients with osteomalacia go through three phases of development characterized by unique changes in the serum concentration of calcium, phosphate, PTH and vit D3 levels and the radiographically assessed bone lesions.

65 Laboratory & Radiological FindingsIn the first stage there is mild hypocalcaemia, appropriately increased serum PTH, normal or slightly decreased serum phosphate and decreased serum 25OHD3.

66 Laboratory & Radiological FindingsIn the second stage serum 25OHD3 decreases slightly or not at all, the serum calcium concentration is restored to normal, but paradoxically there is only a small decrease in serum PTH. Hypophosphataemia and bone lesions worsern.

67 Laboratory & Radiological FindingsIn the third stage, when florid osteomalacia manifests, serum 25OHD3 decreases to almost undetectable levels, Hypocalcaemia is again apparent and is more severe than in stage I and the degree of hypophosphataemia is as severe as in stage II and serum PTH increases further and is appropriate for the degree of hypocalcaemia.

68 Laboratory & Radiological FindingsThe underlying defect leading to these changes is the decrease in the production of 1,25(OH)2D3 which is due to diminished availability of the major circulating metabolites of vit D 25OHD3. The decreased 1,25(OH)2D3 results in decreased intestinal calcium absorption, decreased bone resorption, hypocalcaemia, increased PTH secretion and hypophosphatemia .

69 Laboratory & Radiological FindingsThe resulting decreased CaxPho. Product in serum is insufficient for the normal mineralization of bone and the osteomalacic process is initiated. The increased PTH secretion and hypophosphatemia occur at the expense of osseous demineralization caused by hyperparathyroidism.

70 Laboratory & Radiological FindingsAs stage I shifts to stage II, the serverity of hyperparathyroidism restores serum calcium towards normal and this probably occurs depending on increased production of 1,25(OH)2D3. This increased production is the result of stimulation of 1 alpha hydroxylase by increased serum levels of PTH.

71 Clinical Features The clinical manifestations of osteomalacia in adults usually go unrecognized because of the non-specific skeletal pain and muscular weakness. Only when the disease is extensive, deformities occur with fractures of ribs, vertebrae and long bones. Clinically patients with osteomalacia have a characteristic waddling gait, that is due to the proximal muscle weakness and to the pain and discomfort during movements of the limbs. Some patients have severe muscular hypotonia and paradoxically brisk deep tendon reflexes.

72 Treatment Patients with osteomalacia due to simple dietary deficiency of vit D or lack of exposure to sunlight will respond well to small daily doses of vit D and calcium. Administration of oral doses of ergocalciferol(D2) or cholecalciferol (D3)(2000 IU daily) for several months will heal the bone disease and restores biochemical and hormonal values to normal in most cases. 1,25(OH)2D3 (calcitriol) has also been successful in the treatment of simple osteomalacia.

73 Treatment It is important to administer calcium to provide adequate calcium for bone mineralization (1-2 gm of elemental calcium daily). Serum ALP and PTH decrease slowly over several weeks but improvement in radiological appearences may take several months. Other forms of osteomalacia may need different preparations and doses of treatment e.g., osteomalacia secondary to malabsorption may require huge doses of vit D (200,000 IU orally) because of the poor absorbtion of the drug or even I.V./I.M. vit D (40,000-80,000 IU).

74 Treatment Oral calciferol and calcitriol in larger than usual doses may also be effective. In patients with impaired synthesis of 1,25(OH)2D3 or target cell resistance calcitriol is usually given. In hypophosphataemic rickets the treatment is with phosphate supplement (1-5 gm/day) with vit. D to prevent hypocalcaemia and secondary hyperparathyroidism.

75

76 Osteoporosis “THE SILENT THIEF”

77 Definition Decrease in bone mass and strength associated with an increased tendency to fractures

78 Clinical Features It is usually an asymptomatic disease until fractures occur. The first manifestation of reduced bone mass is usually a wrist fracture or a vertebral crush fracture caused by a small amount of force which produces severe localized pain. Subsequent vertebral fractures may contribute to chronic back pain. In well established osteoporosis dorsal Kyphosis and loss of height occurs. Hip fractures with its fatal complications also occur commonly as osteoporosis become more severe.

79 Type I: Osteoporosis (Post Menopausal)Fractures of bones composed mainly of Trabecular bone. e.g., Distal Radius - Colle’s fracture Vertebra - Crush & Wedge fractures Usually affects woman within 15 years of menopause.

80 Type II: Osteoporosis (Senile)Fractures of bones composed of both cortical & Trabecular bone. e.g., Hip - Femure neck fracture Usually affects individual over age of 70 years.

81 Difference in the two type of involutional OsteoporosisType I Type II >70 2 : 1 Trabecular & Cortical Not accelerated Vertebrae (Multiple wedge), hip, pelvis, proximal humerus Increased Decreased Primary Factors related to aging 51 : 75 6 : 1 Mainly trabecular Accelerated Vertebrae (Crush) & distal radius Secondary Factors related to menpause Age (Yr.) Sex Ratio (F:M) Type of bone loss Rate of bone loss Fracture sites Parathyroid func. Ca absorption Metabolism of 25(OH)2D to 1,25(OH)2d Main causes

82 Sporadic Factors Affecting Bone LossFactors Associated with Decreased Bone desity Premature menopause Hypogonadism (in men) Liver disease Hyperthyroidism Hyperparathyroidism Hemiplegia Chronic obstructive lung dis. Glucocorticoids Anticonvulsants (Phenytoin, Phenobarbitone) ? Low calcium & Vit. D intake ? High phosphorus, protein, sodium, caffeine intake Smoking & Alcohol abuse Medical Conditions Drug Therapy Nutrition Behavioral factors

83 Sporadic Factors Affecting Bone LossFactors Associated with Increased Bone desity Obesity Hyperparathyroidism Thiazide diuretics High calcium intake Flouride intake Exercise ? Pregnancy, lactation Medical Conditions Drug therapy Nutrition Behavioral factors

84 Laboratory & Radiological FindingsALP and PTH are within normal in patients with osteoporosis due to sex hormones deficiency and aging. X-rays of skeleton do not show a decrease in osseous density until at least 30% of bone mass has been lost.

85 Assessment of bone mass available methodsSingle-Photon absorptiometry SPA Dual-Photon absorptiometry DPA Computed Tomography CT Dual-Energy X-ray Absorptiometry DEXA Measure bone mass by the ability of the tissue to absorb the photons emitted from the radionuclide source or the X-ray tube. Age related bone loss particularly trabecular bone in the spine begins in women before menopause.

86 Assessment of bone mass available methodsIt is appropriate to begin to look for risk factors that predispose a person to osteoporosis and develop a rational prevention program tailored to person’s risk before the menopause. e.g., Women with thin light frame, history of low calcium intake, decreased physical activity, high alcohol or caffein cumsumption, smoking, family history of osteoporosis, history of prior menstrual disturbances or history of drug like antiepileptics or steroids are all high risk groups and in the presence of one or more of such risk factors measurement of BMD provides further information to the risk of fractures.

87 Strategy for Management of OsteoporosisPrevent Osteoporosis Detect and treat early to decrease further progression Limit disability and provide rehabilitation

88 Treatment “Senile Osteoporosis is a pediatric disease”.The Adolescent Female (Peak bone mass attainment) “Senile Osteoporosis is a pediatric disease”. Adequate calcium intake of 1200 mgm/day is recommended. Adequate sun exposure or vit D supplementation to ensure adequate level. A reasonable exercise program is recommended. ? Genetic influence on peak bone mass attainment.

89 Treatment The Premenopausal Female (Maintenance of bone mass)Adequate calcium intake; mgm/day disease. Adequate sun exposure or vit D supplementation A reasonable exercise program is recommended, but not to the point of amenorrhea. Avoidance of osteopenia-producing conditions/medications/lifestyles: Smoking & excessive alcohol intake, excessive caffeine/protein intake. Amenorrhea/oligomenorrhea. Cortisone, excessive thyroid hormone replacement (?), loop diuretics, prolonged heparin exposure.

90 Treatment The Immediately Postmenopausal Female (Prevention of bone mass loss) Consideration of estrogen replacement therapy If intact uterus, consideration of medroxyprogesterone

91 Treatment The Immediately Postmenopausal Female (Prevention of bone mass loss) Other modalities of therapy Bisphosphonates SERMS (Selective estrogen receptor modulators) e.g., Evista, Livial Protelos ( strontium ranelate) Forteo (Teripratide) Prolia ( Denosumab)

92 Treatment The elderly postmenopausal female with low bone mass but no compression fractures (Prevention of bone mass loss & restoration of bone mass previously lost) Adequate calcium intake: mg/day Adequate supply of vit D ( IU) A reasonable exercise program with physical therapy instruction in para spinous muscle group strengthening exercise. Avoidance of osteopenia-producing conditions/medications/lifestyles: Smoking & excessive alcohol intake, excessive caffeine/protein intake. Cortisone, excessive thyroid hormone replacement (?), loop diuretics, prolonged heparin exposure.

93 Treatment Other modalities of therapy BisphosphonatesSERMS (Selective estrogen receptor modulators) e.g., Evista, Livial Protelos ( strontium ranelate) Forteo (Teripratide) Prolia ( Denosumab)

94 Treatment The elderly (age>62) postmenopausal female with fractures (spine &/hip) (Prevention of further fractures.)

95 Treatment The male with low bone mass and/or fractures (Prevention of bone mass loss & restoration of bone mass previously lost; prevention of further fractures.) A program of reasonable calcium intake (1000 mg daily), exercise, short term back bracing and avoidance of osteopenia-producing situation is indicated. Consideration of testosterone therapy if total and free testosterone levels are low: 200 mgm q 3 week of Depo-testosterone Prostate concerns Cholesterol concerns

96 Treatment Other modalities of therapyThe male with low bone mass and/or fractures (Prevention of bone mass loss & restoration of bone mass previously lost; prevention of further fractures.) Other modalities of therapy Salmon calcitonin. Bisphosphonates Anabolic steroids (side effects) iPTH anabolic fragments Growth factors & cutokines D metobolites Thiazide diuretics

97 Treatment The male or female with corticosteroid induced osteopenia (Prevention of bone mass loss & restoration of bone mass previously lost) Bone mass measurement if possible to identify bone mass loss Lowest possible dose of corticosteroids: ? Deflazacort A program of reasonable calcium intake ( mgm daily, depending upon urinary calcium), exercise, & avoidance of other osteopenia-producing situations is indicated.

98 Treatment The male or female with corticosteroid induced osteopenia (Prevention of bone mass loss & restoration of bone mass previously lost) Adequate intake of caleium and vit D ( IU) Other modalities of therapy Estrogen (Females), testosterone (males) Bisphosphonates Forteo

99

100 Treatment The amenorrheic female (Exercise induced amenorrhea, eating disorders, etc) (Prevention of bone loss) General measures; decrease exercise if appropriate, regain body weight, adequate calcium intake ( mgm/dayu) and avoidance of other osteopenia-producing situations. Regain menses Other modalities of therapy Estrogen replacement ( mgm CEE or equivalent, oral contraceptives) Nasal spray calcitonin; bisphosphonates

101 In addition to other measures, consider tamoxifenTreatment The at risk or osteoporosis female with breast cancer. In addition to other measures, consider tamoxifen

102 Paget’s Disease Paget’s disease of the bone is disorder of bone remodelling characterized by histological and gross osseous deformities due to local uncontrolled bone resorption which is caused by excessive numbers of osteoclasts and osteoblasts and ultimately leads to formation of structurally fragile osseous tissue. Any bone in the body can be involved but the most frequent sites are the femur, tibia, skull, lumbosacral spine and pelvis. The disease is common in Germany and England, less common in North America and is rare in Scandinavia, Africa and in the near and far east.

103 Clinical Features Relatively few patients with radiologically proven Paget’s disease have significant symptoms. It is a disease of middle age and the diagnosis is often made as an incidental findings on x-rays taken for other reasons. The chief symptom is bone pain over lesions as well as joint pains which are difficult to distinguish from arthritis. Deafness can occur and is related to bony abnormalities of the internal and external auditory apparatus. Vertebral fractures occur frequently and fractures of the long bones may occur & usually heal rapidly.

104 Clinical Features *In rare cases severe neurological complications can occur due to spinal cord compression. *Redness with increased skin temperature over Pagetic bone is a common finding and rarely a bruit could be heard *Increased cardiac output is common in extensive disease. These vascular complications are probably due to increased blood flow in involved areas in both the bone and the overlying skin. *High output congestive cardiac failure may occur in patients with underlying heart disease. *There is high risk of developing osteogenic sarcoma in such patients.

105 Laboratory & Radiological FindingsSerum calcium, phosphate, magnesium & PTH are usually normal. Abnormalities could be due to a superimposed condition e.g., immobilization or a coexisting primary hyperparathyroidism. Serum ALP is markedly elevated and acid phosphatase may be increased.

106 Laboratory & Radiological FindingsUrinary hydroxyproline is usually markedly increased except in patients with mild disease. X-ray findings range from pure osteolysis lesions to areas that show both osteolysis and screlosis. In the extrimities a classical large uniform resorption front as a V-shaped wedge is seen on x-ray.

107 Laboratory & Radiological FindingsSclerotic bone is then laid behind it resulting in anterior or lateral bowing. Thick bony trabeculae are common. The skull is often grossly enlarged and the mixture of sclerotic and lytic areas gives rise to the classical appearance of cotton wool on x-ray. Initially the skull my show a purely osteolytic lesion (Osteoporosis circumscipta).

108 Laboratory & Radiological FindingsThickness of long bones and vertebrae occur frequently and crush fractures cause varying degree of Kyphosis. Radionuclide bone scars using Tc99m or others aid greatly in documenting the extent of the disease and reveal lesions that may not be apparent radiologically.

109 Treatment Only patients with symptoms should be treated. The available drugs are calcitonin, diphosphonates and mithramycin. They all suppresses the number and activity of the abnormal bone cells by acting through different mechanisms. Calcitonin decreases bone resorption by decreasing the number of active osteoclasts. The diphosphonates inhibit both bone resorbtion and formation. Mithramycin is a cytotoxic drug that inhibits bone resorbtion and should only be used under the most desperate conditions e.g., spinal cord compression.