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Vitamin D

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Vitamin D in general and in oral health

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Vitamin D

  1. 1. VITAMINS - IN GENERAL AND -IN ORAL HEALTH By: Dr. Monali Prajapati MDS Oral Medicine and radiology
  2. 2. Index 1. Vitamins 2. Vitamin D 3. Sources of vitamin D 4. Metabolism of vitamin D 5. Sources 6. Functions of vitamin D 7. Recommended dietary allowance 8. Disorders of vitamin D 9. Rickets 10. Vitamin D deficient rickets 11. Vitamin D resistant rickets 12. Renal rickets 13. Osteomalacia 14. Hypervitaminosis 15. References
  3. 3. Vitamins: The vitamin theory was suggested by Hopkins in 1912 (Nobel prize 1929). The term “VITAMINE” was coined from the words ‘VITAL+ AMINE’ , since the earlier identified ones had amino groups. Later work showed that most of them did not contain amino groups, so last letter ‘e’ was dropped in the modern term of vitamin. Definition:Vitamins are a group of organic nutrients required in small quantities for a variety of biochemical functions and which, generally, cannot be synthesized by the body and must therefore be supplied in the diet. The vitamins are mainly classified into two: 1. The fat soluble vitamins are A, D, E and K 2. Water soluble vitamins are named as Bcomplex and C
  4. 4. Fat soluble vitamins Water soluble vitamins Solubility in fat Soluble Not soluble Water solubility Not soluble soluble Absorption Along with lipids. Require bile salts Absorption simple Carrier protein Present No carrier proteins Storage Stored in liver No storage excretion Not excreted Excreted deficiency Manifests only when stores depleted Manifests rapidly as no storage Toxicity Hypervitaminosis may result Unlikely, as excess is excreted Treatment of deficiency Single large doses may prevent deficiency Regular dietary supply is required Major vitamins A, D, E and K B and C Vitamin D Angus and coworkers isolated vitamin D in 1931 and named it as calciferol, which was later identified as vitamin D3. The structuralelucidation was done independently by Otto Diels and Kurl Alder. Both were awarded nobel prizein 1950. Other names: 1,25 dihydroxycholecalciferol Calcitriol Sunshinevitamin
  5. 5. Vitamin D is a fat soluble vitamin. Itoccurs in 2 activated forms: 1. Calciferol(vitamin D2) 2. Cholecalciferol(vitamin D3) 1 non activated form: 1. Ergocalciferol(vitamin D1) Vitamin D is really a hormone  Vitamin D is not strictly a vitamin since it can be synthesized in the skin, and under most conditions that is its major source.  Only when sunlightis inadequate is a dietary sourcerequired  The main function of vitamin D is in the regulation of Calcium absorption and homeostasis, mostof its action are mediated by way of nuclear receptors that regulate gene expression. Sources:  Endogenous source(90%)- action of ultraviolet light(290-315nm) on 7- dehydrocholesterol, available in malpighian layer of epidermis  Exogenous source(10%) -fish liver oil -flesh of fatty fish -eggs -milk -cheese
  6. 6. Metabolismof Vitamin D 1. Photochemical synthesis of vitamin D from7-dehydrocholesterolin the skin, via the energy of solar or artificial UV light in the range of 290 to 315nm(UVBradiation) and absorption of vitamin D from foods and supplements in the gut 2. Binding of vitamin D fromboth of these sources to plasma α 1 globulin (D- binding protein or DBP) and transportinto the liver. 3. Conversion of vitamin into 25-hydroxycholecalciferal (25-OH-D) in the liver, through the effect of 25 hydroxylases (25 hydroxylasethatinclude CYP27A1 and other CYPs ) 4. Conversion of 25-hydroxycholecalciferolinto 1,25 dihydroxyvitamin D[1α,25(OH)2D3] in thekidney, the most active formof vitamin D, through the activity of 1 α hydroxylase. Storage: -25(OH)D is themajor circulating and storageformof vitamin D. -Approximately 88% of 25(OH)Dcirculates bound to vitamin D binding protein(α1- globulin). 0.03% is free -restcirculates bound to albumin -Half life of 25(OH)D is approximately 2-3 weeks which is dramatically shortened when vitamin D binding protein levels are reduced as can occur with increased urinary losses in nephritic syndrome.
  7. 7. Functions of Vitamin D: 1. Maintenance of adequate levels of calcium and phosphorus to support metabolic functions, bonemineralization and neuromuscular transmission a. Stimulation of intestinal calcium absorption -1,25-dihydroxycholecalciferolitself functions as a type of hormoneto promote intestinal absorption of calcium. Itdoes this by increasing the formation of calcium binding protein (calbindin) in the intestinal epithelial cells, over a period of 2days. -This protein functions in the brush borders of these cells, to transport calcium into the cell cytoplasmand the calcium then moves through the basolateral membraneof the cell by facilitated diffusion. -The rate of calcium absorption is directly propotionalto the quantity of calcium binding protein. -This protein remains in the cells for several weeks, after the 1,25 dihydroxycholecalciferolhas been removed from the body, thus causing a prolonged effect on calcium absorption. -Other effects of 1,25(OH)D thatmightplay a role in promoting calcium absorption are formation of: i. a calcium stimulated ATPasein the brush border of epithelial cells ii. an alkaline phosphatasein epithelial cells b. Stimulation of calcium reabsorption in the kidney: Vitamin D also increases calcium and phosphateabsorption by epithelial cells of the renal tubules, thereby tending to decrease excretion of these substances in the urine. c. Interaction with parathyroid hormone(PTH) in the regulation of blood calcium: Vitamin d maintains calcium and at the supersaturated levels in the plasma. The parathyroid glands havea key role in regulation of
  8. 8. extracellular calcium concentrations. These glands have a calcium receptor that senses even small changes in the blood calcium concentrations. In addition to their effects on calcium absorption in the intestine and kidney already described, both 1,25 dihydroxycholecalciferoland parathyroid hormoneenhance the expression of RANKL(receptor activator of NF-KBligand ) on osteoblasts. Rankl binds to its receptors (RANK) located in preosteoclasts, inducing the differentiation of these cells into mature osteoclasts. Through the secretion of hydrochloric acid and activation of proteases such as cathepsin k, osteoclasts dissolvebone and release calcium and phosphorus into the circulation. d. Mineralization of bone: -Vitamin D contributes to the mineralization of osteoid matrix and epiphyseal cartilage in the formation of both flat and long bones in the skeleton. -Itstimulates osteoblasts to synthesizecalciumbinding protein, osteocalcin, involved in the deposition of calcium during bone development. -Calcitriol also stimulates osteoblasts which secrete alkaline phosphatase. Dueto this enzyme, the local concentration of phosphate is increased. The ionic productof calcium and phosphorus increases, leading to mineralization. e. Neuromuscular transmission: -Vitamin D plays an important role in calcium hemostasis and calcium plays a role in neuromuscular transmission -When the extracellular fluid concentration of calcium ions falls below normal, the nervous systembecomes moreexcitable, because this causes increased neuronal membranepermeability to sodiumions, allowing easy initiation of action potentials.
  9. 9. -When the level of calcium in the body fluids rises above normal, the nervous systembecomes depressed and reflex activities of CNS are sluggish. 2. Immuneregulation: Vitamin D has anti-inflammatory and anti-bacterial roles. Itplays a role in activation of both acquired and innate immunity through upregulation of T-cells and antigen presenting cells and increased VDR activation, when monocytes and macrophages areinfected by bacteria. Calcitriol also inhibits production of interleukin by activated T-lymphocytes and immunoglobulin by activated B-lymphocytes. Toll like receptor activation of monocytes and macrophages results in the upregulation of VDR and VDRtarget genes, with subsequentinduction of cathelicidin antimicrobial peptide(CAMP) and killing of mycobacterium tuberculosis. 3. Cancer cells: Vitamin D inhibits proliferation and induces differentiation. Recommended Dietary Allowance(RDA): The average daily dietary nutrient intake level sufficient to meet the nutritional requirements of nearly all(97-98%) healthy persons in a particular life stageand gender group. VitaminD RDA in IU/day: <1yr of age- 400IU/day >1yr of age- 600IU/day Pregnant/lactating-600IU/day
  10. 10. Normal blood levels: 25,hydroxycholecalciferol- 20-100ng/ml Calcium- 9-11mg/dl Phosphorus- 3-4mg/dlin adults -4-5mg/dlin children Alkaline phosphatase- 44-147IU/L Alteredstates: 1. Vitamin D  Hypovitaminosis- <20ng/ml  Hypervitaminosis- >150ng/ml 2. Calcium  Hypocalcemia- 6mg/dl causes tetany -4mg/dlis lethal  Hypercalcemia-12mg/dldepresses nervoussystemand muscleactivity -15mg/dlmarked depression -17mg/dlcalcium phosphatecrystalprecipitate 3.
  11. 11. Disorders of Vitamin D Hypovitaminosis D HypervitaminosisD -Rickets -Vitamin D deficient rickets -Vitamin D resistant rickets (Familial hypophosphatemia; Refractory phosphate diabetes) -Renal Rickets(Renal Osteodystrophy) -Osteomalacia -Hypopcalcemic tetany CAUSES OF IMPAIRED ACTION OF VITAMIN D 1. Vitamin D deficiency  Impaired cutaneous production -Inhabitants of northern latitude -In winter months -Bedridden people-Use of sunscreen -Darker skin colour
  12. 12.  Dietary absence  malabsorption- malabsorpton of lipids due to lack of bile salts such as intrahepatic biliary obstruction, pancreatic insufficiency and malabsorption syndrome 2. Accelerated loss of Vitamin D -Increased metabolism(barbiturates, phenytoin,rifampin) -Impaired enterohepatic circulation 3. Impaired 25-hydroxylation -Liver disease -isoniazid 4. Impaired 1 α hydroxylation -Hypoparathyroidism -Renal failure -Ketaconazole -1 α hydroxylasemutation -Oncogenic osteomalacia -X-linked hypophosphatamic rickets 5. Target organ resistance -Vitamin D receptor mutation -phenytoin
  13. 13. RICKETS Rickets is a diseaseof growing bone that is due to unmineralised matrix of growth plate and occurs in children only before fusion of epiphysis. Because growth plate cartilage and osteoid continue to expand but mineralization is inadequate so the growth plate thickens. MORPHOLOGY :  Overgrowth of epiphysealcartilage due to inadequate provisional calcification and failure of cartilage cells to mature and disintegrate.  Persistenceof distorted, irregular masses of cartilage, which projectinto the marrow cavity.  Deposition of osteoid matrix on inadequately mineralized cartilage remnants.  Disruption of the orderly replacement of cartilage by osteoid matrix, with enlargement and lateral expansion of the osteochondraljunction.  Abnormalovergrowth of capillaries and fibroblasts in the disorganized zone resulting frommicrofractures and stresses on the inadequately mineralized, weak, poorly formed bone.  Deformation of the skeleton due to loss of structuralrigidity of developing bones.  There is also an increasein the circumferenceof the growth plate and metaphysis increasing bone width at the location of growth plates causing widening of wrists and ankles. There is a generalized softening of bone. ETIOLOGY: There are many causes of rickets including: 1. Vitamin D disorders 2. Calcium deficiency 3. Phosphorus deficiency 4. Distal renal tubular acidosis
  14. 14. CLINICAL FEATURES OF RICKETS 1. GENERAL: i. Failure to thrive ii. Listlessness iii. Protruding abdomen iv. Muscle weakness(especially proximal) v. Fractures 2. HEAD: i. Craniotabes: softening of the cranial bones and can be detected by applying pressureat the occiput or over the parietal bones. ii. Frontalbossing: an excess of osteoid produces frontalbossing and squared appearanceof the head. iii. Delayed frontalclosure iv. Craniosynostosis: itis a condition in which one or moreof the fibrous sutures in infant skull, prematurely fuse by turning into bone thereby changing growth pattern of skull. 3. Chest: i. Rachitic rosary: overgrowth of cartilage or osteoid tissue at the costochondraljunction, produces “rachitic rosary”. Itfeels like the beads of rosary as the examiner’s finger moves along the costochondraljunctions fromrib to rib. ii. Harrison groove: occurs frompulling of the softened ribs by diaphragm during inspiration. iii. Pigeon breastdeformity: the weakened metaphysealareas of the ribs are subjectto the pull of respiratory muscles and thus bend inward, creating anterior protrusion of sternum. iv. Respiratory infections and atelectasis: softening of ribs impairs air movement and predisposepatients to atelectasis and pneumonia
  15. 15. 4. Back: i. Scoliosis: it is a condition in which spine is curved side to side. ii. Kyphosis: it is condition in which there is overcurvatureof the thoracic vertebrae iii. Lordosis: inward curvatureof a portion of lumbar and cervical vertebral column. 5. Extremities: i. Enlargement of wrists and ankles ii. Valgus and varus deformities: valgus condition in which bone or joint is twisted outward fromcenter of body . Varus is a condition in which joint is twisted inward from the center of body. iii. Windsweptdeformity: combination of valgus deformity of 1leg with varus deformity of the other. iv. Anterior bowing of tibia and femur v. Coxa vara: deformity of hip whereby the angle between head and shaftof femur is reduced to <120 degree vi. Leg pain 6. Hypocalcemic symptoms: i. Tetany ii. Seizures iii. Stridor due to laryngeal spasms iv. Oral manifestation: 1. Dentition: i. Delayed eruption of both primary and permanent dentition ii. Enamel  Hypoplastic  Thin enamel  Attrition present  Fractures common  Long internal cracks
  16. 16. iii. Dentin  Increased width of predentin  Many calcospherites separated by irregular zones of interglobular dentin iv. Pulp  Very large pulp chambers which may be taurodont  Pulp horns arehigh in primary teeth and can extend upto the DEJ  Spontaneous multiple dental abscess, acute and chronic, with no history of trauma or dental caries is frequently found in patients with hypophosphatemic rickets mostcommonly involving the primary dention v. Cementum  Hypomineralized 2. Bone: i. Hypoplastic alveolar ridge ii. Reduced anterior cranial baselength iii. Decreased ramus height iv. Decreaseramus cranial baseangle v. Reduced lower facial height vi. A class III skeletalrelationship vii. Concavefacial profile 3. Soft tissue i. Gingiva: -Vitamin D has anti-inflammatory and antibacterial roles in the oral cavity. -Its anti-inflammatory effect are a result of many different interactions including activation of both acquired and innate immunity through the upregulation of T-cells and antigen presenting
  17. 17. cells as well as a feedback loop of increased VDR activation when monocytes and macrophages areinfected by bacteria. -The presence of vitamin D also provides indirect antimicrobial effects through increasing cathelicidin levels which destroy gram negative and gram positivebacteria allow bacterial growth in the oral cavity ultimately increasing local inflammation leading to gingivitis. ii. Periodontium -Because of the well established link of vitamin D and its relationship to calcium hemostasis and regulation in bone , as well as its role in hostimmunity, there is a biological possibility to assumea relationship between vitamin D and periodontal health. -In animal models, vitamin D deficiency has been shown to increase osteoblastic activity and bone resorption. -Patients with vitamin D deficiency also have a hereditary defect in vitamin D metabolism, frequently present with chronic periodontal disease. -Also among patients receiving periodontal therapy, thosewith high serumvitamin D level show less bleeding sites, lower mean pocket depth and clinical attachment.
  18. 18. INVESTIGATIONS A. LABORATORY I. Blood test Sr no. Components Normal values 1. 25(OH)vitamin D 20-100ng/ml 2. 1,25(OH)vitamin D 24-65pg/ml 3. Serumcalcium 9-11mg/dl 4. SerumPhosphorus 3-4mg/dlin adults 4-5mg/dlin children 5. SerumParathyroid hormone 13.9-7.5pg/ml 6. SerumAlkaline phosphatase 44-147IU/L 7. Blood urea nitrogen 6-20mg/dl 8. Blood creatinine(Jaffe’s reaction) 0.7-1.3mg/dlin male 0.6-1.1mg/dlin female 9. Ionized calcium 0.9-1.3mmol/l II. Urine test Sr no. Components Normal values 1. Urine Calcium 0.2g/l 2. Urine Phosphate 2g/l 3. Urine creatine 14-20mg/kg body mass in male 11-20mg/kg body mass in female III. Creatinine clearance Normal values: 97-137ml/min in male 88-125ml/min in female
  19. 19. B. RADIOGRAPHICINVESTIGATIONS 1. Bone X-rays 2. Ultrasonic and CT Scan(renaldisorder) C. OTHER TESTS 1. Bone density test 2. Bone biopsy RADIOGRAPHIC FINDINGS -Rachitic changes are moreeasily visualized on posteroanterior radiographs of wrists although characteristic rachitic changes can be seen at other growth plates. -Decreased calcifications leads to thickening of growth plate. -The edge of metaphysic loses its sharp border, which is described as fraying. -The edge of metaphysis changes fromconvex or flat surfaceto a more concave surface. -Change to a concavesurfaceis termed cupping and most easily seen at the distal end of radius, ulna, fibula -There is widening of the distal end of the metaphysic, corresponding to the clinical observation of thickened wrists and ankles as well as rachitic rosary. -Other radiologic features includes coarsetrabeculation of diaphysis and generalized rarefactions. -Bow legs -Craniosynostosis in skullX-rays and skullappears box shaped.
  20. 20. ORTHOPANTOMOGRAM: Bone: - indistinct cortex - Hypoplastic alveolar ridge - Coarsetrabeculation Teeth: - multiple missing teeth -Taurodontteeth- shortroots - Wide pulp chambers -poorly defined lamina dura -multiple periapical abscess in primary dentition -thin enamel -Wide predentin VITAMIN D DEFICIENT RICKETS: ETIOLOGY: 1. Poor dietary intake 2. Inadequate cutaneous synthesis CLINICAL FEATURES: Are typical of rickets already mentioned previously.
  21. 21. INVESTIGATIONS: A. LABORATORY I. Blood test Sr no. Components Alteration 1. 25(OH)vitamin D Decreased 2. 1,25(OH)vitamin D Decreased, normalor increased* 3. Serumcalcium Normal or slightly decreased 4. SerumPhosphorus Decreased^ 5. Serum Parathyroid hormone increased 6. SerumAlkaline phosphatase Normal 7. Blood urea nitrogen Normal 8. Blood creatinine(Jaffe’s reaction) normal 9. Ionized calcium Normal *due to upregulation of 1αhydroxylasedueto concomitant hypophosphstemia and hyperparathyroidism. Becauseserumlevels of 1,25 vitamin D are much lower than the levels of 25,vitamin D even with low levels of 25,vitamin D there is still enough 25,vitamin D to act as a precursor. 1,25 vitamin D is only low in severe deficiency. #due to PTH induced renal losses combined with reduced intestinal absorption
  22. 22. II. Urinetest Sr no. Components Alteration 1. Urine Calcium Decreased 2. Urine Phosphate Increased 3. Urine creatine normal III. Creatinine clearance Alteration: B. RADIOGRAPHICINVESTIGATIONS 1. Bone X-rays 2. Ultrasonic and CT Scan(renaldisorder) C. OTHER TESTS 1. Bone density test 2. Bone biopsy TREATMENT: -Children with nutritional vitamin D deficiency should receive vitamin D and adequate nutritional intake of calcium and phosphorus. -There are 2 strategies for administration of vitamin D. 1. With stoss therapy- 300,000-600,000 IU of vitamin D are administered orally or intramuscularly as 2-4 doses over 1 day. Because the doses are observed, stoss therapy is ideal in situations where adherence to therapy is questionable. 2. The alternative is daily, high-dose vitamin D, with doses ranging from 2,000- 5,000 IU/day over 4-6 wk. -Either strategy should be followed by daily vitamin D intake of 400 IU/day if <1 yr old or 600 IU/day if >1 yr, typically given as a multivitamin.
  23. 23. -It is important to ensure that children receive adequate dietary calcium and phosphorus;this dietary intake is usually provided by milk, formula, and other dairy products. -Children who have symptomatic hypocalcemia might need intravenous calcium acutely, followed by oral calcium supplements, which typically can be tapered over 2-6 wk in children who receive adequate dietary calcium. -Transient use of intravenous or oral 1,25-D (calcitriol) is often helpful in reversing hypocalcemia in the acute phase by providing active vitamin D during the delay as supplemental vitamin D is converted to active vitamin D. -Calcitriol doses are typically 0.05 µg/kg/day. Intravenous calcium is initially given as an acute bolus for symptomatic hypocalcemia (20 mg/kg of calcium chloride or 100 mg/kg of calcium gluconate). -Some patients require a continuous intravenous calcium drip, titrated to maintain the desired serum calcium level. These patients should transition to enteral calcium, and most infants require approximately 1,000 mg of elemental calcium. PREVENTION: Most cases of nutritional rickets can be prevented by universal administration of a daily multivitamin containing 400 IU of vitamin D to infants who are breast-fed. Older children should receive 600 IU/day. VITAMIN D RESISTANT RICKETS (FAMILIAL HYPOPHOSPHATEMIA, REFRACTORYRICKETS, PHOSPHATE DIABETES) -Hypophosphatemic rickets is a form of rickets that is characterized by low serum phosphatelevels and resistant to treatment with ultraviolet radiation, or vitamin D ingestion. -Familil occurrenceof this condition led to the diagnosis of familial hypophosphatemic rickets.
  24. 24. -With recent advances in understanding of genetic basis of familial hypophosphstemic rickets, the name X-linked hypophosphatemia(XLH) has been more commonly used. -XLH is considered to be a systemic disorder, from mutation of phosphate regulating gene homologus to endopeptidases on the X chromosome(PHEX) -Renal tubular reabsorption of inorganic phosphates is reduced leading to hypophosphatemia and hyypophosphaturia -Filtered phosphatenot reabsorbed in the proximal tubule, become concentrated in thick descending loop of Henle, du to water retrieval. The thick descending limb becomes rich in mucopolysaccharides which attract calcium phosphate. Such crystals on migration to the papilla get precipitated as stones. CLINICAL FEATURES Classic picture is:  Shot stature  Bowing of lower limbs (especially of knees causing genu varum)  Rachitic changes of long bones  Coxa vara  Bow legs  Pseudofractures  Extraskeletal calcification of tendons, ligaments, and joint capsules  Craniosynostosis Oral manifestations:  Delayed dentition  Formation of globular, hypocalcified dentin  Clefts and tubular defect of pulp horn  Pulp horns are elongated and extend high resching DEJ  Because of these defects there is invasion of pulp by micro- organisms and destruction of tubular matrix
  25. 25.  Followimg this there is often periapical involvement of grossly normal appearing deciduous or permanent teeth, followed by development of multiple gingival fistulas  Abnormal cementum  Abnormal alveolar bone pattern  Lamina dura absent INVESTIGATIONS: A. LABORATORY I. Blood test Sr no. Components Alteration 1. 25(OH)vitamin D normal 2. 1,25(OH)vitamin D Normal or low 3. Serumcalcium Normal 4. SerumPhosphorus Decreased <2-5mg/dl 5. SerumParathyroid hormone normal 6. SerumAlkaline phosphatase increased 7. Blood urea nitrogen Normal 8. Blood creatinine(Jaffe’s reaction) Normal 9. Ionized calcium Normal II. Urinetest Sr no. Components Alteration 1. Urine Calcium Decreased 2. Urine Phosphate Increased 3. Urine creatine normal
  26. 26. III. Creatinine clearance Alteration: normal B. RADIOGRAPHICINVESTIGATIONS 1. Bone X-rays 2. Ultrasonic and CT Scan(renaldisorder) C. OTHER TESTS 1. Bone density test 2. Bone biopsy RADIOGRAPHIC FINDINGS SKELETAL RADIOGRAPHS: -Shortsquatlong bones -Coarseaxial skeletal trabeculations -More severerachitic knees than wrists DENTAL RADIOGRAPHS: Same as described under rickets TREATMENT: -Patients respond well to a combination of oral phosphorus and 1,25-D (calcitriol). -The daily need for phosphorus supplementation is 1-3 g of elemental phosphorus divided into 4-5 doses. -Frequentdosing helps to prevent prolonged decrements in serumphosphorus because there is a rapid decline after each dose. In addition, frequent dosing decreases diarrhea, a complication of high-doseoral phosphorus. -Calcitrol is administered 30-70 ng/kg/day divided into 2 doses.
  27. 27. -For children with significantshortstature, growth hormoneis an effective option. -Children with severedeformities might need osteotomies, but these procedures should be done only when treatment has led to resolution of the bone disease. RENAL RICKETS(RENAL OSTEODYSTROPHY) The term renalosteodystrophy is used to indicate a spectrumof bone disorders seen in patients with CKD. The mostcommon condition seen in children is high-turnover bonedisease caused by secondary hyperparathyroidism. The skeletal pathologic finding in this condition is osteitis fibrosa cystica. PATHOPHYSIOLOGY- The decrease in functional kidney mass leads to a decline in renal 1α-hydroxylase activity, with decreased production of activated vitamin D (1,25- dihydroxycholecalciferol). This deficiency in activated vitamin D results in decreased intestinal calcium absorption, hypocalcemia, and increased parathyroid gland activity. Excessiveparathyroid hormone(PTH) secretion attempts to correct the hypocalcemia by effecting an increase in bone resorption. Later in the courseof CKD, when the GFRdeclines to 20-25% of normal, compensatory mechanisms to enhance phosphateexcretion become inadequate, resulting in hyperphosphatemia, which further promotes hypocalcemia and increased PTH secretion
  28. 28. CLINICAL FEATURES:  Muscle weakness  Bone pain  Fractures with minor trauma  Rachitic changes  Varus and valgus deformities of long bone  Slipped capital femoralepiphysis RADIOGRAPHICFINDINGS Radiographs of the hands, wrists, and knees show subperiosteal resorption of bone with widening of the metaphyses. INVESTIGATIONS A. LABORATORY I. Blood test Sr no. Components Alteration 1. 25(OH)vitamin D Increased 2. 1,25(OH)vitamin D Normal 3. Serumcalcium decreased 4. SerumPhosphorus Increased 5. SerumParathyroid hormone Increased 6. SerumAlkaline phosphatase Increased 7. Blood urea nitrogen Increased 8. Blood creatinine(Jaffe’s reaction) Increased 9. Ionized calcium decreased
  29. 29. II. Urinetest Sr no. Components Alteration 1. Urine Calcium Increased 2. Urine Phosphate Decreased 3. Urine creatine increased III. Creatinine clearance Alteration: reduced B. RADIOGRAPHICINVESTIGATIONS 1. Bone X-rays- subperiostealboneresorption with wide metaphysis 2. Ultrasonic and CT Scan(renaldisorder) C. OTHER TESTS 1. Bone density test 2. Bone biopsy TREATMENT: -Patients with low 25(OH)D (25-hydroxy-vitamin D) levels should be treated with ergocalciferol. -Patients with a normal 25(OH)D levelbutelevated PTH level should be treated with 0.01-0.05 µg/kg/24 hr of calcitriol OSTEOMALACIA(ADULT RICKETS) The term is derived fromGreek "osteon" =bone; and "malakia" = softness. The bones are softened due to insufficientmineralization after epiphyseal fusion. Affects flat bones and diaphysis of long bones. Most commonly seen in postmenopausal women.
  30. 30. MORPHOLOGY: -In adults, the lack of vitamin D deranges the normal bone remodeling that occurs throughoutlife. -The newly formed osteoid matrix laid down by osteoblasts is inadequately mineralized, thus producing the excess of persistentosteoid that is characteristic of osteomalacia. ETIOLOGY:  Dietary deficiency  Poor endogenous synthesis  Steatorrhea(failureto absorb fat)  Conditioned deficiency CLINICAL FEATURES GENERAL:  Contours of bone not affected  Bone is weak, vulnerable to gross fractures or microfractures mostlikely to affect vertebral border and femoral necks  Vague bony pain  Muscular weakness  Pelvic deformity in affected multiparous females  Waddling gait  Difficulty climbing stairs ORAL MANIFESTATIONS:  Vague bony pain  Muscular weakness  Pseudofractures
  31. 31. RADIOGRAPHICFINDINGS:  Normal bony contour  Psedofractures seen(Looser’s zone) Looser’s zone-radiolucentlines that occur wherelarge arteries are in contact with underlying skeletal elements, it is thought that arterial pulsations lead to radiolucencies. INVESTIGATIONS: A. LABORATORY I. Blood test Sr no. Components Alteration 1. 25(OH)vitamin D decreased 2. 1,25(OH)vitamin D Normal or low 3. Serumcalcium Normal 4. SerumPhosphorus decreased 5. SerumParathyroid hormone Increased 6. SerumAlkaline phosphatase Increased 7. Blood urea nitrogen Increased 8. Blood creatinine(Jaffe’s reaction) Increased 9. Ionized calcium Normal II. Urinetest Sr no. Components Alteration 1. Urine Calcium decreased 2. Urine Phosphate increased 3. Urine creatine Increased in renal disorder
  32. 32. III. Creatinine clearance Alteration: reduced in renal disorder B. RADIOGRAPHICINVESTIGATIONS 1. Bone X-rays 2. Ultrasonic and CT Scan(renaldisorder) C. OTHER TESTS 1. Bone density test 3. Bone biopsy- increasein thickness and extent of osteoid seam HYPERVITAMINOSIS: The recommended upper limits for long term vitamin D intake are: Children <1year-1000IU Older children, adults-2000IU ETIOLOGY: -Long-termhigh intake, mostcases are secondary to misuseof prescribed or over- the-counter vitamin D supplements -Overfortification of milk, -contamination of table sugar, and -inadvertent useof vitamin D supplements as cooking oil. NOTE: Vitamin D intoxication is never secondary to excessiveexposureto sunlight, probably because ultraviolet irradiation can transformvitamin D3 and its precursor into inactive metabolites
  33. 33. PATHOGENESIS: Although vitamin D increases intestinal absorption of calcium, the dominant mechanismof the hypercalcemia is excessive bone resorption. CLINICAL MANIFESTATIONS: The signs and symptoms of vitamin D intoxication are secondary to hypercalcemia.  GI manifestations -nausea, -vomiting, -poor feeding, -constipation, -abdominal pain, and -pancreatitis.  cardiac findings -hypertension, -decreased Q-T interval, and -arrhythmias.  The central nervous system -lethargy, -hypotonia, - confusion, -disorientation, - depression, -psychosis, -hallucinations, and -coma.
  34. 34.  renal system - polyuria, -dehydration, -hypernatremia -acute renal failure, -nephrolithiasis, and -nephrocalcinosis, Deaths are usually associated with arrhythmias or dehydration. INVESTIGATIONS: A. LABORATORY I. Blood test Sr no. Components Alteration 1. 25(OH)vitamin D INcreased 2. 1,25(OH)vitamin D Normal or low 3. Serumcalcium Increased 4. SerumPhosphorus increased 5. SerumParathyroid hormone decreased 9. Ionized calcium increased II. Urinetest Sr no. Components Alteration 1. Urine Calcium increased 2. Urine Phosphate decreased
  35. 35. B. RADIOGRAPHICINVESTIGATIONS 1. Bone X-rays 2. Ultrasonic and CT Scan(renaldisorder) -nephrocalcinosis C. OTHER TESTS 1. Bone density test 2. Bone biopsy 3. Blood pressure-increased 4. ECG-decreased Q-T interval -arrythmias Note: Surprisingly, levels of 1,25-D areusually normal. This may be due to downregulation of renal 1α-hydroxylaseby the combination of low PTH, hyperphosphatemia, and a direct effect of 1,25-D. Thereis evidence indicating that the level of free 1,25-D may behigh, owing to displacement from vitamin D– binding proteins by 25-D. TREATMENT: -Focuses on control of hypercalcemia. -Many patients with hypercalcemia are dehydrated as a resultof polyuria from nephrogenic diabetes insipidus, poor oralintake, and vomiting. -Rehydration lowers the serumcalcium level via dilution and corrects prerenal azotemia. -The resultant increased urine output increases urinary calcium excretion. -Urinary calcium excretion is also increased by high urinary sodiumexcretion. -The mainstay of the initial treatment is aggressivetherapy with normal saline, often in conjunction with a loop diuretic to further increase calcium excretion. -Normal saline, with or without a loop diuretic, is often adequate for treating mild or moderate hypercalcemia. -More significanthypercalcemia usually requires other therapies. -Glucocorticoids decreaseintestinal absorption of calcium by blocking the action of 1,25-D. Thereis also a decreasein the levels of 25-D and 1,25-D. Theusual dosageof prednisoneis 1-2 mg/kg/24 hr. -Calcitonin, which lowers calcium by inhibiting bone resorption, is a useful adjunct, but its effect is usually not dramatic.
  36. 36. -There is an excellent responseto intravenous or oralbisphosphonates in vitamin D intoxication. -Bisphosphonates inhibitbone resorption through their effects on osteoclasts. -Hemodialysis using a low or 0 dialysatecalcium can rapidly lower serum calcium in patients with severe hypercalcemia that is refractory to other measures. -Along with controlling hypercalcemia, it is imperative to eliminate the sourceof excess vitamin D.
  37. 37. REFERENCES 1. Robbins and Cotran Basis of Pathology, 8th edition,Kumar Abbas Fausto Aster. Page no.802-809 2. Textbook of biochemistry for medical students, 6th edition,DMVasudevan, page no.384-387,411-420 3. Harpers illustrated biochemistry,26th edition,RobertMurray, DarylGranner, Peter Mayes, Victor Rodwell 4. Textbook of medical physiology,11th edition, Guyton and Hall,page no.978- 986 5. Nelsons Textbook of pediatrics,19th edition 6. Harrisons principleof internal medicine, 17th edition 7. Medlineplus medical encyclopedia 8. Synopses (newsletter of the Australian and Newzealand society of pediatric dentistry,October 2009,issue43)

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