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Flashcards in Calcium and hard tissue Deck (60):
1

Calcium and hard tissue

1. If it is in the Text and in the Notes it is Important. - probably review the slides for this one.

2

Bone is a

structural material

3

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

4

What is the Primary Protein Component of bone?

collagen

5

Enamel

¢ Matrix is Amelogenin ¢ Hydroxyapatite 90%

6

Dentin

¢ Matrix is Collagen (I) ¢ Hydroxyapatite 67%

7

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

8

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

9

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

10

REMODELING CYCLE

¢ Bone is Dynamic Structure
¢ Constantly Building and Resorbing Bone
¢ Many Factors Will Influence Balance — Serum Calcium
— Hormones
— Cytokines

11

CELLS INVOLVED IN REMODELING

§ Osteoblasts Build Bone
§ Osteoclasts Resorb Bone
§ Osteoblasts and Osteoclasts are from Different Lineages

12

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.

13

Promote Resorption

IL-1, IL-6 and TNF

14

Inhibit Resorption

Calcium
¢ Estrogens
¢ Calcitonin
¢ Tumor Growth Factor-β ¢ IL-17

15

Osteoblasts and Osteoclasts are from

Different Lineages

16

OSTEOCLAST ACTIVATION

Rank connects to RankL to break down, Osteoprogenerin to inhibit.

RankL leads to formation of:
Lysosomal Enzymes Collagenases Cathepsins
Acidic pH

17

BYPRODUCTS of osteoclasts

Calcium
¢ Collagen Peptides or Fragments
¢ Pyridinoline Crosslink
Fragments ¢ Telopeptides NTX and
CTX

Can Detect Byproducts in Serum and Urine
¢ Hydroxyproline

18

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

19

RankL

Osteoblast surface protein. Activates osteoclasts.

20

CALCIUM METABOLISM

Bone is a Calcium Store
¢ Hormonal Control of Calcium Homeostasis ¢ Vitamin D Plays an Important Role

21

DISTRIBUTION OF CALCIUM

99% of Calcium is contained in Mineralized
Tissue
¢ Remaining 1% is circulated in a Bound or Ionic Form

22

SERUM CALCIUM

¢ Ionized Calcium 50%
¢ Protein Bound Calcium 40% — Bound to Albumin
¢ Citrate or Phosphate Bound Calcium 10%

23

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

24

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

25

CALCIUM SENSING RECEPTORS

¢ Found on Several Cell Types
¢ Parathyroid Gland: Parathyroid Hormone
¢ Thyroid C-Cells: Calcitonin
¢ Kidney Tubules: Regulates Calcium Excretion

26

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)

27

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

28

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

29

VITAMIN D SYNTHESIS

Precursor Synthesized in Skin
¢ Stored in Liver
¢ Converted to Active Form in the Kidney ¢ 1α hydroxylase is Point of Regulation

30

1α-HYDROXYLASE STIMULATION

Parathyroid Hormone ¢ Low Calcium
¢ Low Vitamin D
¢ Calcitonin

31

1α-HYDROXYLASE INHIBITION

Low Parathyroid Hormone
¢ High Serum Calcium
¢ High Vitamin D
¢ 24-Hydroxylase can Inactivate Liver Precursor 25-hydroxycholecalciferol

32

Calcium is Important for:

Clotting, Muscle Contraction, Cardiovascular Function

33

Serum Calcium Levels Trigger

Production of
Regulatory Hormones

34

DISORDERS OF CALCIUM AND BONE

Hypercalcemia
¢ Hypocalcemia
¢ Metabolic Disorders of The Bone

35

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

36

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

37

EFFECT ON BONE - HPT

HPT increases Bone remodeling
¢ Results in Osteopenia
¢ Six Months After Surgery Most but not all Bone Density back to Normal

38

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

39

HCM FROM BONE TUMOR OR METASASES

¢ Locally Active
¢ Alters RANKL/Osteoprogenerin (OPG) Balance
¢ Produces Cytokines and Growth Factors

40

SYMPTOMS AND TREATMENT 0 HCM

Dehydration
¢ Vomiting
¢ Reduced Renal Perfusion
¢ Treatment with Bisphosphonates
¢ Bisphosphonates Inhibit Osteoclast Activity

41

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

42

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

43

HYPOCALCEMIA

Drop in Serum Albumin (Adjusted Calcium
Levels)
¢ Changes in Ionized Calcium from pH Change

44

SYMPTOMS OF HYPOCALCEMIA

Neuromuscular Irritability ¢ Chveostek’s Sign
¢ Trousseau’s Sign
¢ Numbness
¢ Tingling ¢ Cramps ¢ Tetany ¢ Seizures

45

HYPOPARATHYROIDISM - cause

Usually a Result of a Damaged Parathroid Gland — Surgery
— Tumor
— Thyroid Disease
— Parathroid Disease

46

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

47

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

48

METABOLIC BONE DISEASE

Osteoporosis
¢ Paget’s Disease ¢ Osteomalacia

49

OSTEOMALACIA

Defects in Hydroxyapatite Formation ¢ Due to Vitamin D Deficiency
¢ Rickets

50

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

51

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

52

OSTEOPOROSIS

Loss of Mineral Density with Age – Peak Density
at 30
¢ Increase Risk of Fracture
¢ Relative Rates of Bone Synthesis and Resorption Change

53

TREATMENTS FOR OSTEOPOROSIS

Estrogen (Hormone Replacement Therapy) ¢ Bisphosphonates
¢ Calcitonin
¢ PTH(1-34 Amino Acid Sequence)

54

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

55

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

56

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

57

Unloading of Bone Result in a

Decrease of Bone Synthesis while Maintaining Same Level of Bone Degradation.
¢ Serum Calcium Levels Increase.
¢ Decrease in PTH

58

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

59

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.

60

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.