Calcium and hard tissue Flashcards
Calcium and hard tissue
- If it is in the Text and in the Notes it is Important. - probably review the slides for this one.
Bone is a
structural material
What is the Mineral Component of bone
Mineral Content Provides Stiffness and
Hardness to Bone and Teeth
Bone is Composed of: Collagen Hydroxyapatite (Ca10[PO4]6[OH]2) ¢ Bone is a Composite ¢ 50-60% of Hydroxyapatite Plates Fig 1-13 From Ten Cate’s Oral Histology, Sixth Edition
What is the Primary Protein Component of bone?
collagen
Enamel
¢ Matrix is Amelogenin ¢ Hydroxyapatite 90%
Dentin
¢ Matrix is Collagen (I) ¢ Hydroxyapatite 67%
WHY are bones a COMPOSITE STRUCTURE?
Composites can Combine Best of Two Materials
¢ Collagen is Tough but Not Strong
¢ Hydroxyapatite is Strong but Not Tough Not Tough = Brittle, like glass
¢ Mineralized Tissue is Both Strong and Tough
¢ Structural Integrity of Bone is Dependent on the Interaction of Collagen and Hydroxyapatite
SOME DIFFERENCES BETWEEN BONE AND TEETH
¢ Bone Has a Lower Mineral Content ¢ Bone is Maintained, Enamel is Not Maintained Bone Can Heal Enamel Cannot Heal – Can Remineralize Dentin Has a Limited Capacity to Heal ¢ Bone is Vascularized
PROCESS OF MINERALIZATION
Vesicles Containing a Saturated Solution of HA ¢ Initiates Crystallization and Rupture Vesicle
¢ Osteoblasts Excrete Matrix Proteins
¢ Pyrophosphate can Block Mineralization
¢ Alkaline Phosphatase Degrades Pyrophosphate
REMODELING CYCLE
¢ Bone is Dynamic Structure
¢ Constantly Building and Resorbing Bone
¢ Many Factors Will Influence Balance Serum Calcium
Hormones
Cytokines
CELLS INVOLVED IN REMODELING
§ Osteoblasts Build Bone
§ Osteoclasts Resorb Bone
§ Osteoblasts and Osteoclasts are from Different Lineages
How do the Remodeling Cycle and Serum Calcium Levels Affect one Another?
Decrease in bone mass = increase in serum Ca, and vice versa. Increase in serum Ca leads to bone synthesis, and the other end leads to bone resorption.
Promote Resorption
IL-1, IL-6 and TNF
Inhibit Resorption
Calcium
¢ Estrogens
¢ Calcitonin
¢ Tumor Growth Factor-β ¢ IL-17
Osteoblasts and Osteoclasts are from
Different Lineages
OSTEOCLAST ACTIVATION
Rank connects to RankL to break down, Osteoprogenerin to inhibit.
RankL leads to formation of:
Lysosomal Enzymes Collagenases Cathepsins
Acidic pH
BYPRODUCTS of osteoclasts
Calcium ¢ Collagen Peptides or Fragments ¢ Pyridinoline Crosslink Fragments ¢ Telopeptides NTX and CTX
Can Detect Byproducts in Serum and Urine
¢ Hydroxyproline
Osteoblast activation
cAMP Vitamin D TGF-β IGF-1 PDGF — RankL is attached for activation.
When activated forms: Collagen I, Alkaline Phosphatase, Osteocalcin, Fibronectin Bone Sialoprotein, Osteopontin
RankL
Osteoblast surface protein. Activates osteoclasts.
CALCIUM METABOLISM
Bone is a Calcium Store
¢ Hormonal Control of Calcium Homeostasis ¢ Vitamin D Plays an Important Role
DISTRIBUTION OF CALCIUM
99% of Calcium is contained in Mineralized
Tissue
¢ Remaining 1% is circulated in a Bound or Ionic Form
SERUM CALCIUM
¢ Ionized Calcium 50%
¢ Protein Bound Calcium 40% Bound to Albumin
¢ Citrate or Phosphate Bound Calcium 10%
MEASURING SERUM CALCIUM LEVELS
Most Tests Measure Total Calcium
¢ Ionic Calcium is Physiologically Active
¢ Ionic Levels not Affected by Albumin Bound Calcium
¢ Decrease in Albumin can be From Liver Disease, Malnutrition.
¢ Need a Correction Factor to Determine Total Calcium Levels
HORMONAL CONTROL OF CALCIUM
¢ Parathyroid Hormone is the Primary Regulator
of Calcium Levels
¢ 84 Amino acid Protein Synthesized by the Parathyroid Gland
¢ Triggers an Increase in Serum Calcium
¢ Production is Stimulated by Low Plasma Calcium
CALCIUM SENSING RECEPTORS
¢ Found on Several Cell Types
¢ Parathyroid Gland: Parathyroid Hormone
¢ Thyroid C-Cells: Calcitonin
¢ Kidney Tubules: Regulates Calcium Excretion
OTHER HORMONES THAT REGULATE CALCIUM
Calcitonin inhibits Bone Resorption
¢ 32 Amino acid Protein Produced by C-Cells
¢ Other Hormones: Thyroid Hormone
Estrogen and Testosterone
Insulin Like Growth Factors (IGF-1 and IGF-2)
ABSORBED AND EXCRETED CALCIUM
Calcium is Absorbed in the Small Intestine Active Transport Regulated by Vitamin D
Transport Based on Relative Serum/Gut Levels
¢ Calcium is Excreted in Urine and Feces
Kidneys are Regulated by PTH
Large Intestine Levels Governed by Small Intestine
VITAMIN D
Vitamin D plays and Important Role in Calcium
Regulation
¢ Increases Serum Calcium
¢ Vitamin D increases Gut Adsorption of Calcium
¢ Vitamin D increase Bone Adsorption
VITAMIN D SYNTHESIS
Precursor Synthesized in Skin
¢ Stored in Liver
¢ Converted to Active Form in the Kidney ¢ 1α hydroxylase is Point of Regulation
1α-HYDROXYLASE STIMULATION
Parathyroid Hormone ¢ Low Calcium
¢ Low Vitamin D
¢ Calcitonin
1α-HYDROXYLASE INHIBITION
Low Parathyroid Hormone
¢ High Serum Calcium
¢ High Vitamin D
¢ 24-Hydroxylase can Inactivate Liver Precursor 25-hydroxycholecalciferol
Calcium is Important for:
Clotting, Muscle Contraction, Cardiovascular Function
Serum Calcium Levels Trigger
Production of
Regulatory Hormones
DISORDERS OF CALCIUM AND BONE
Hypercalcemia
¢ Hypocalcemia
¢ Metabolic Disorders of The Bone
HYPERCALCEMIA – EXCESS CALCIUM
Common Causes ¢ Primary Hyperparathyroidism ¢ Malignant Disease ¢ Iatrogenic Vitamin D Uncommon Causes ¢ Thyrotoxicosis ¢ Multiple Myeloma ¢ Sarcoidosis ¢ Renal Failure ¢ Drug Induced Lithium Thiazide Diuretics ¢ Familial Hypocalciuric Hypercalcemia
HYPERPARATHYROIDISM (HPT)
Increase in Production of Parathyroid Hormone
¢ Diagnosed By ‘bone, stones and abdominal groans
¢ 80-85% are caused by an Adenoma
¢ Occurs in 1-500 to 1-1000 in Population
¢ Intact Parathyroid Hormone is an indication of HPT
EFFECT ON BONE - HPT
HPT increases Bone remodeling
¢ Results in Osteopenia
¢ Six Months After Surgery Most but not all Bone Density back to Normal
HYPERCALCEMIA ASSOCIATED WITH MALIGNANCY (HCM)
Primary Cause of Hypercalcemia from Parathyroid Hormone-Related Protein (PTHrP)
¢ PTHrP has Sequence Homology with PTH
Hypophosphatemia, Phosphaturia, Increased Renal
Calcium Resorption, Osteoclast Activation
¢ PTHrP Produced by Tumors
¢ Common Tumors: Breast, Lung, Kidney other Solid Tumors
¢ Less Common Tumors: Hematologic, Gastrointestinal, Head and Neck
HCM FROM BONE TUMOR OR METASASES
¢ Locally Active
¢ Alters RANKL/Osteoprogenerin (OPG) Balance
¢ Produces Cytokines and Growth Factors
SYMPTOMS AND TREATMENT 0 HCM
Dehydration ¢ Vomiting ¢ Reduced Renal Perfusion ¢ Treatment with Bisphosphonates ¢ Bisphosphonates Inhibit Osteoclast Activity
SIDE EFFECTS OF BISPHOSPHONATES
Drug against hypercalcemia:
Inhibit Remodeling ¢ Osteonecrosis in ¢ Slow Fracture Healing ¢ Brittle Bones ¢ Long Half-Time are Incorporated in Bone Mandible ¢ Typified by Oral Lesions
VITAMIN D - Hypercalcemia
Vitamin D is the Third Leading Cause of
Hypercalcemia
¢ Normally Obvious Cause
¢ Also Measure Levels Vitamin D3, Vitamin D2 and 1,25(OH)2D3
HYPOCALCEMIA
Drop in Serum Albumin (Adjusted Calcium
Levels)
¢ Changes in Ionized Calcium from pH Change
SYMPTOMS OF HYPOCALCEMIA
Neuromuscular Irritability ¢ Chveostek’s Sign
¢ Trousseau’s Sign
¢ Numbness
¢ Tingling ¢ Cramps ¢ Tetany ¢ Seizures
HYPOPARATHYROIDISM - cause
Usually a Result of a Damaged Parathroid Gland Surgery
Tumor
Thyroid Disease
Parathroid Disease
PTH RESISTANCE
¢ Increase in PTH ¢ Hypomagnesemia ¢ End Organ Resistance ¢ Need Magnesium for to PTH PTH to Bind to ¢ Usually Genetic Defect G-protein Secretory Granules
ABNORMAL METABOLISM OF VITAMIN D
Vitamin D Deficiency
Reduced Exposure to Sunlight Poor Dietary Intake
Malabsorption
¢ Tissue Resistance to Vitamin D
¢ Also a Result of Clinical Conditions Liver Disease
Renal Failure
METABOLIC BONE DISEASE
Osteoporosis
¢ Paget’s Disease ¢ Osteomalacia
OSTEOMALACIA
Defects in Hydroxyapatite Formation ¢ Due to Vitamin D Deficiency
¢ Rickets
RICKETS
Noted During the Industrial Revolution ¢ Lack of Sunlight Because of Pollution and Narrow Alley’s ¢ Inhibited Vitamin D Metabolism ¢ Bone and Muscle Weakness ¢ Skeletal Deformity – Large Head, Spinal Curvature ¢ Cod Liver Oil
Rickets diagnoses
Rickets can be Difficult to Diagnose from
Skeletons
Bone Remodels
Only Sever Cases are Obvious
¢ Dentin Would have ‘Gaps’ Due to Rickets
Interglobular Dentin
Observed in Animals and Some Human Cases of Vitamin D Deficiency
Dentin Does Not Remodel
¢ Examine Skeletal Remains vs. Healthy Adults
OSTEOPOROSIS
Loss of Mineral Density with Age – Peak Density
at 30
¢ Increase Risk of Fracture
¢ Relative Rates of Bone Synthesis and Resorption Change
TREATMENTS FOR OSTEOPOROSIS
Estrogen (Hormone Replacement Therapy) ¢ Bisphosphonates
¢ Calcitonin
¢ PTH(1-34 Amino Acid Sequence)
PAGET’S DISEASE
Large Numerous multinucleate Osteoclasts ¢ Large Number of Osteoblasts ¢ Increase in Alkaline Phosphatase ¢ Large Misshapen Bones ¢ Less Dense, Brittle ¢ High Serum Content of Hydroxyproline, Pyridinolines and Telopeptides
Paget’s Disease cause/treatment
Cause is Unknown Genetic? Early Childhood Viral Infection? ¢ Most Common in Europe, Australia and New Zeeland ¢ Some are Asymptomatic ¢ Treatments: Bisphosphonates Calcitonin
SPACE TRAVEL
Microgravity is known to have a profound effect
on Bone Density and Calcium Metabolism
¢ 1% Bone Mass is Lost Per Month of Space Travel
¢ Roughly the same as bed rest or 1 Year of Osteoporosis
¢ Mission to Mars Could Result in 50% Bone Mass Loss
Unloading of Bone Result in a
Decrease of Bone Synthesis while Maintaining Same Level of Bone Degradation.
¢ Serum Calcium Levels Increase.
¢ Decrease in PTH
CONSEQUENCES of being in space
Gut absorption of Calcium is Decreased
¢ Increase in Serum Calcium does not Result in New Bone Formation
¢ Body is Metabolizing Bone as its Primary Calcium Source Rather than the Diet
EXTENSIVE EXERCISE AND BONE LOSS
For Competitive Cyclists Bone Density Decrease
was observed after nine months of training
¢ Even after a three month rest period the Bone Density did not Return.
POTENTIAL REASONS for bone loss from exercise
(1) an increase in PTH, possibly consequent to a decrease in serum calcium during exercise as a result of excess dermal calcium loss
¢ (2) insufficient energy availability during periods of heavy training and competing
¢ (3) suppression of sex hormones
¢ (4) an increase in stress hormones and pro-
inflammatory cytokines
¢ (5) self-imposed restriction on weight bearing activities in favor of cycling.
