Interrelationship of Pulp and Systemic Disease

Fig 20-1 Evaluation of the presence of HIV in human dental pulp using in situ hybridization histochemistry. Dental pulp tissue from an HIV-positive patient was fixed, sectioned, and incubated with one of two biotinylated oligonucleotide probes complementary to a region of messenger RNA specific to HIV. Sections were incubated, washed, and developed. A positive signal is visible as a dark spot in the figure. (Reprinted from Glick et al'5 with permission.)

Several oral lesions have been shown to occur

in association with HIV-induced immunosuppres­

sion.9-11 The most strongly associated lesions in adult patients are mucosa! and include candidia­

sis (erythematous and pseudomembranous), hairy

leukoplakia, Kaposi sarcoma, non-Hodgkin lym­

phoma, and periodontal disease (linear gingival

erythema, necrotizing ulcerative gingivitis, and nec­

rotizing ulcerative periodontitis).12 For pediatric pa­

tients, the most strongly associated lesions are can­

didiasis (erythematous, pseudomembranous, and

angular cheilitis), herpes simplex infection, linear

gingival erythema, parotid enlargement, and recur­rent aphthous stomatitis (minor, major, and herpeti­form). The risk of developing these lesions is inverse­

ly related to the CD4+ counts. Thus, the presence of

oral lesions may serve as good clinical markers to

signal a loss in therapeutic efficacy of ART.13·14

Although HIV has been identified in dental

pulp15 and in periradicular lesions of pulpal origin,16

its direct contribution to pulpal disease remains

unknown (Fig 20-1 ). Studies to assess the caries risk in HIV-infected patients have yielded conflict­

ing results, and it is likely that numerous factors, such as the patient's immune status, dietary habits, medication profile, and salivary status, all contribute

to caries risk.17-19 The impaired immune response observed in patients with low CD4+ counts does not appear to be associated with an increase in endo­

dontic complications after root canal treatment,20·21 and three recent studies have confirmed that HIV­

infected patients respond well to and benefit from

indicated root canal therapy.22-24

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Herpesvirus infections

Herpesviruses are ubiquitous pathogens that have

the ability to establish latency in the infected host.25

There are eight identified human herpesviruses: her­

pes simplex virus 1 (HSV-1), herpes simplex virus 2

(HSV-2), varicella zoster virus (VZV), Epstein-Barr virus

(EBV), cytomegalovirus (CMV), human herpesvirus 6,

human herpesvirus 7, and human herpesvirus 8.26 Pri­

mary infections are often asymptomatic and typically

occur during childhood.

The pathophysiology of HSV-1 viral infection is

well established. During the primary infection, the

virus is transported via retrograde axonal transport

to regional sensory ganglia (typically the trigeminal

ganglia), where it establishes latency.27 During the

latent phase, the virus exists in a quiescent immuno­

logically shielded state. However, shedding of HSV

has been demonstrated in the saliva of asympto­

matic healthy adults. Although the clinical relevance of this finding remains to be determined, it reinforces

the need for strict adherence to infection-control

procedures in the dental office to minimize the risk

of occupational exposure.26

Clinically apparent recurrent infections are esti­

mated to occur in 15% to 40% of individuals har­

boring latent HSV-1.28 Well-documented triggers

associated with HSV recurrence include sunlight,

trauma, menstruation, fever, immunosuppression,

decompression of the trigeminal nerve, and irritation

by dental instruments. Three clinical forms of recur­

rence are recognized: (1) recurrent herpes labialis, (2) intraoral recurrence, and (3) recurrence mimicking

a primary infection. lntraoral recurrent lesions typi­

cally present as a focal clustering of vesicles affect­

ing the keratinized mucosa (gingiva or hard palate).

The vesicles quickly rupture and coalesce to form

the characteristic shallow erosion. The pain may be

so severe as to interfere with eating and speaking.

HSV-1 infection has been proposed as a potential etiologic factor of pulpal necrosis and should be

considered in the differential diagnosis of odontal­gia (see chapter 19). However, the overall impact of

HSV infection on pulpal disease remains unknown. In one study assessing 31 patients with an apical abscess or cellulitis of pulpal origin, HSV was detect­ed (using polymerase chain reaction) in only 1 of 31 specimens.29 In contrast, another study revealed the

presence of HSV in 15 of 50 necrotic pulps assessed by polymerase chain reaction.30

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Infectious Diseases

Fig 20-2 Periradicular radiographs of a patient 5 months after a herpes

zoster outbreak. Note the periradicular radiolucencies of the maxillary left

canine (a and b) and first and second premolars (c and d). (Reprinted from

Goon and Jacobsen38 with permission.)

The classic clinical presentation of a primary VZV infection is termed chickenpox. Similar to HSV, VZV establishes latency in neuronal ganglia (cranial nerve, dorsal root, and autonomic ganglia).31 Clinical VZV recurrence is called zoster (or shingles). Fac­

tors that predispose an individual to zoster include conditions of immunocompromise (eg, lymphoma,

Hodgkin disease, leukemia, or AIDS) and advanced

age.32 Zoster usually manifests a prodrome of mild

to moderate tingling, itching, burning, boring pain,

or numbness affecting the affected dermatome.33·34 Within 3 days, the characteristic erythematous papu­lar rash develops, which quickly progresses to ves­icles and pustules. Constitutional signs and symp­

toms of fever, chills, malaise, and headache may also

be present.

Resolution typically occurs within 3 weeks and

may lead to altered pigmentation or scarring of the

affected area. The most common complication of

zoster is postherpetic neuralgia, a condition charac­

terized by pain or hyperesthesia that persists after clinical resolution has occurred. An estimated 50% of patients over the age of 60 years who experience zoster are at risk for postherpetic neuralgia.

An estimated 13% of zoster cases involve the head and neck.34 Zoster of the maxillary or man­dibular branch may affect dentoalveolar structures such as the pulp and periodontal ligament, lead­ing to pulpal death, tooth exfoliation, internal root resorption, tooth neuralgia, and osteonecrosis34-37 (Fig 20-2). The degree to which zoster directly con-

d

tributes to pulpal disease is unknown, with only a

few case reports noted in the literature.38·39 Further confounding the issue, prodromal zoster pain not directly involving the dental pulp may mimic pain of pulpal origin.40

Recent reports have indicated that both CMV and EBV may play an important role in the etio­

pathogenesis of periapical pathoses.41-44 CMV estab­

lishes latency in monocytes and T lymphocytes, and

EBV establishes latency in B lymphocytes. Both virus­

es may upregulate the production of numerous pro­inflammatory cytokines such as interleukin 113, inter­leukin 6, and tumor necrosis factor a. These findings have led some to postulate that both CMV and EBV may contribute to the pathogenesis of periradicu­

lar pathosis, either as a result of direct infection or

through virus-induced immune system alteration.

Infection during fetal and childhood development

Maternal rubella (German measles) Maternal infection during pregnancy may directly affect the developing fetus, leading to changes that vary from inconsequential to severe enough to result in fetal death.45 Fortunately, it appears that the most commonly encountered maternal infections cause no significant harm to the developing fetus. The outcome of maternal infection depends largely on the infectious agent involved, the maternal immune

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Interrelationship of Pulp and Systemic Disease

Fig 20-3 Patient with rubella. Note the discoloration of the maxillary anterior teeth.

response, and the stage of fetal development when the infection occurred. Commonly reported orofa­cial defects attributed to maternal infection usually encompass structural defects such as cleft lip and

palate and various tooth malformations.

One of the more commonly cited examples of a

maternal infection that adversely affects tooth devel­

opment is rubella (German measles).46-49 Potential

effects on the developing teeth vary from none at

all to significant changes in terms of size, shape,

and color (Fig 20-3). In light of current vaccination

protocols, maternal rubella is now a rarely observed

phenomenon.

Childhood infections

Paralleling the effects of maternal infection on the

fetal tooth germ, infectious processes that occur

during childhood may adversely affect tooth devel­

opment. Once again, the high prevalence of child­

hood illnesses weighed against the actual low occur­

rence of tooth defects indicates that the overall risk is low. The actual etiopathologic mechanisms

leading to tooth germ damage are poorly under­stood and may involve direct injury to the develop­ing tooth by the infectious agent and/or metabolic changes (eg, fever or altered calcium metabolism) associated with the infection50·51 (Fig 20-4).

Clinical findings include quantitative defects (eg, pits, grooves, or partial or complete loss of enamel) and qualitative defects (eg, the presence of white

or discolored enamel with a smooth surface and normal thickness).52 Because enamel is continuously elaborated during tooth development, it may be

474

Fig 20-4 Enamel hypoplasia. Note the linear defect in enamel formation that may occur from any of the exan­thematous fevers (eg, rubella, measles, or chicken- pox). The position of the linear defect depends on the age of morphodif­ferentiation of the different permanent teeth at the time of the infection.

possible to crudely estimate the age at which the

infectious process occurred by the location of the linear defect on the enamel surface of the tooth.

Genetic and Developmental

Disorders

Taurodontism

Taurodontism is a developmental disturbance of

teeth that results in abnormally large pulp cham­

bers at the expense of root length.53-55 The cause

is unknown but likely involves aberration or failure

of epithelial root sheath differentiation.54 Both the

primary and permanent dentitions may be affected.

The overall prevalence of taurodontism is estimated

to be about 3%. Most cases occur as an isolated

trait, but the presence of taurodontism in associa­tion with several syndromes and diseases has been

reported56-76 (Box 20-1 ).

Taurodontism may affect one or more teeth; most cases involve molars and, to a lesser extent, premolars. The radiographic appearance is char­acteristic, revealing elongated pulp chambers and shortened roots.65·77-79 The altered pulp chamber and canal morphology of the taurodont may com­plicate the provision of endodontic therapy because identification of the canal may be compromised and affected teeth are more prone to manipulative frac­ture77·78 (Fig 20-5).

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Box 20_1 I Synd�omes a�d conditions

_ associated with taurodont1sm

Aarskog syndrome57 Apert syndrome58 CHARGE syndrome59 Down syndrome60 Ellis-van Creveld syndrome (chondroectodermal

dysplasia)61 Gorlin-Goltz syndrome (focal dermal hypoplasia)62 Glycogen storage disease type 11163 Kabuki syndrome58 Klinefelter (XXY) syndromess.54.5s

LADD syndrome66 Lowe syndrome67 McCune-Albright syndrome58 Menz microphthalmia syndromess Mohr syndromess Prader-Labhart-Willi syndrome68 Seckel syndrome69 Smith-Magenis syndrome 70 Thalassemia major 71 Tricho-dento-osseous syndrome72 Williams syndromess Wolf-Hirschhorn syndrome73.74 Triple-X syndrome (XXX); XXXX syndromessJs X-linked hypophosphatemic rickets (XLH)76

Dens in dente (dens invaginatus) and dens evaginatus

There are several examples of developmental dis­

orders of morphodifferentiation of teeth. Dens in

dente (dens invaginatus) and dens evaginatus are

two of the more common disorders of morphodiffer­

entiation that have pulpal implications. The reader

is encouraged to review oral pathology textbooks

for a complete discussion of other disorders of mor­

phodifferentiation (eg, gemination, fusion, concres­

cence, and dilacerations)_:>-s Dens in dente is a developmental disorder in

which a portion of the crown undergoes an invagina­tion prior to calcification. This is thought to involve

an infolding of the dental papilla during develop­

ment and may occur because of altered tissue pres­sures, trauma, infection, or localized discrepancies in cellular hyperplasia (eg, apically directed prolifera­tion of ameloblasts). Dens in dente is characterized by a deep infolding of enamel and dentin and often

involves maxillary lateral incisors80-83 (Fig 20-6). Teeth

Fig 20-5 Preop­erative radiograph of a taurodontic mandibu­lar right second molar. Note the relatively large pulp chamber and shortened roots with distal caries.

(Reprinted from Hayas­

hi77 with permission.)

Genetic and Developmental Disorders

Fig 20-6 Clinical presentation (a) and radiograph (b) of a dens in dente. (Courtesy of Dr Yoav Shiloah, San Antonio, TX.)

affected by dens in dente are classified into three

types: Type 1 is an enamel-lined, relatively minor

defect; type 2 is an enamel-lined blind sac that invades the root; and type 3 invades the root and has a secondary foramen. The prevalence has been

reported to be between 0.04% and 10.0%.80

There are several points of clinical significance in

the dens in dente tooth. First, there is an increased

risk of bacteria-induced pulpal necrosis, and prophy­

lactic placement of sealants may be indicated.80-84

Second, nonsurgical root canal treatment is difficult

because the anatomical complexity makes both tis­

sue debridement and complete obturation extreme­

ly challenging. Suggested treatment approaches include the use of ultrasonic files, calcium hydroxide dressings, and obturation with a thermoplasticized gutta-percha technique.

Dens evaginatus is a localized outgrowth of ameloblasts that appears clinically as a globule of enamel and may be reminiscent of an accessory cusp. The most commonly affected teeth are pre­

molars or molars. The prevalence is higher among Asians (about 15%) than among Caucasians.5 The

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Interrelationship of Pulp and Systemic Disease

Fig 20-7 Clinical and radiographic views of dens evagi­natus in an 11-year-old boy. (a) Clinical view of external anatomy. (b) Preoperative radiograph. Note the extensive periradicular radiolucency, complex root canal systems, and immature apex. The sinus tract is traced with a gutta-percha cone. (c) Postoperative view illustrating the use of Collatape (Sulzer Dental) and mineral trioxide aggregate (MTA) as an

internal barrier and final obturation with thermoplasticized gutta-percha. (Courtesy of Dr Neil Begley, Sequim, WA, and Dr William Schindler, San Antonio, TX.)

Fig 20-8 Type II DI in an 18-year-old man. Note the yellow-brown shade of the anterior teeth and the blue-gray shade of the posterior teeth. (Reprinted from Huber90 with permission.)

Fig 20-9 Periradicular radiographs of a patient with type I DI. (a) Preoperative radiograph. Note the reduced size of the pulp chamber, canal orifices, and canal systems in the first premolar as well as the presence of overextended gutta-percha and apical periodontitis. (b) One-year follow-up after root­end resection and MT A retrofill of the first premolar.

outgrowth is postulated to arise from proliferation

and elongation of a portion of the inner enamel epi­

thelium and associated dental papilla into the stel­

late reticulum of the developing enamel organ.85·86

The resultant extension contains enamel, dentin,

and pulp. The clinical significance of this disorder is

that the relatively narrow shelf of enamel, once pen­

etrated, often results in pulpal exposure (Fig 20-7).

Dentinogenesis imperfecta

Dentinogenesis imperfecta (DI) can occur either as

an isolated finding or in association with osteogene­

sis imperfecta.87-93 Three types of DI are recognized.

DI type I is associated with osteogenesis imperfecta

and likely represents the dental manifestation of the underlying type I collagen defect. DI types II and Ill

are attributed to mutations affecting the dentin sia­lophosphoprotein (OSPP') gene.87·92·94 DSPP encodes two tooth matrix proteins (dentin sialoprotein and

dentin phosphoprotein) that are involved with den­

tinogenesis.92·%-97 Recent studies have demonstrated that DI types II and Ill occur as a consequence of altered dentin sialoprotein and phosphoprotein pro­duction.89·91·96 DI type II is considered to be the most

476

common dental genetic disease in humans, affecting

an estimated 1 in 6,000 to 8,000 people.87·92

The clinical findings of all types of DI are similar

and characteristic. The teeth manifest an amber­

brown to blue-gray hue, an opalescent sheen, crack­ing or loss of enamel, and attrition8B-91·98 (Fig 20-8).

Radiographic findings for DI types I and II include a

bulbous crown structure, cervical constriction, short

roots, and obliteration of the pulp chamber (Fig 20-9).

For DI type Ill, the radiographic features are similar,

except that the pulp chambers appear normal or

enlarged (shell teeth), and periradicular radiolucen­

cies are frequently present. The notable clinical

similarities between DI types II and Ill, along with a

similar condition called dentin dysplasia type II, has prompted some to speculate that these disorders

represent phenotypic variations of a single disor­

der.91·94 Both the primary and permanent dentitions

may be affected. The altered tooth structure associated with DI may

compromise the success of endodontic therapy.99 Pulpal obliteration may compromise access, canal

identification, and chemomechanical debridement. The presence of extensive shelling may increase the risk of spontaneous or manipulative enamel frac­ture. The altered, and at times difficult to identify,

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Genetic and Developmental Disorders

II ftjtjtjfJ•lm Proven genes for amelogenesis imperfecta*

Gene Inheritance pattern Phenotypic findings

Amelogenin (AMELXJ

Enamelin (ENAM)

X-linked

Autosomal dominant

Distinctive vertical banding pattern on enamel of affected females

Hypoplastic (thin) enamel

Mild pitting

Horizontal lines in the affected enamel. especially in the cervical third

Distal-less homeobox

3 (OLX3)t Autosomal dominant Enamel hypoplasia

Taurodontism

Enamelysin (MMP20) Autosomal recessive Pigmented agar-brown discoloration

Rough, mottled enamel

Enamel fracturing

Kallikrein 4 (KLK4) Autosomal recessive

Decreased radiopacity of enamel

Pigmented yellow-brown discoloration

Hot/cold sensitivity

Chewing sensitivity

Enamel fracturing

Decreased radiopacity of enamel

*Data from Ng and Messer. 101

'Phenotype considered a variation of the trichodento-osseous syndrome.

root canals may compromise the success of surgical

endodontic treatment.

Amelogenesis imperfecta

Amelogenesis imperfecta (Al) comprises a hetero­

genous group of heritable developmental disorders that affect both the primary and permanent denti­tions in the absence of a generalized syndrome.100-105

Al is estimated to occur in 1:14,000 patients in the United States, and autosomal-dominant, autosomal­recessive, and X-linked patterns of inheritance have been described.102 To date, four confirmed genes

for Al have been described, but others remain to be identified and mapped101 (Table 20-1). A univer­

sally accepted nosology to describe the phenotypic

diversity of Al does not exist, but most cases are clinically described as either hypoplastic, hypocalci­fied, or hypomatured.101·102·106

In addition to the universal enamel impairment observed in Al, other anomalies, such as delayed or failed eruption, crown resorption, and pulp calcifica­tion, have been reported.107 However, the extreme phenotypic diversity observed in Al compromises comparative studies, of which there are few. In one study of 22 patients from nine unrelated families with various forms of Al, the presence of crown resorption (41%), delayed eruption (27%), and pulp

calcifications (14%) was significantly greater than that observed in controls.107 The presence of pulp calci­fication was highly associated with the autosomal­recessive hypoplastic form of Al.

Although the patient with Al may present sig­

nificant restorative and esthetic challenges for the

dental practitioner, there is no Al-specific reason to

withhold indicated endodontic therapy.

Osteoclastic diseases

Osteoclasts, which are essential for normal tooth

eruption, are highly specialized cells derived from hematopoietic cell precursors in the bone mar­

row and peripheral blood.10a-112 Osteoclast forma­

tion requires the presence of two essential factors

found in bone marrow stromal cells and osteoblasts: macrophage colony-stimulating factor and receptor activator of nuclear factor KB ligand (RANKL).109·113·114 Binding of RANKL with the osteoclastic recep­tor activator of nuclear factor KB (RANK) leads to increased nuclear factor KB (NFKB) signaling and upregulation of genes required for osteoclast differ­entiation and activity. Another defined modulator in the RANK/RANKL system is osteoprotegerin (OPG), which is a soluble decoy receptor that competes with RANK for the RAN KL binding site.

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Interrelationship of Pulp and Systemic Disease

It appears that most processes affecting bone

resorption and tooth eruption act through mod­ulation of the balance of RANKL and OPG108-112

for RANK. Disease states that result in reduced

osteoclastic activity (eg, osteopetrosis, cleidocranial

dysplasia, and pyknodysostosis) commonly exhibit

phenotypic delay or failure of tooth eruption, while

disease states that result in increased osteoclastic

activity (eg, Paget disease of bone [PDB] and juve­

nile Paget disease) manifest accelerated tooth loss.

Paget disease of bone (osteitis deformans) PDB is a heterogenous, focal, progressive bone dis­

ease characterized by active bone turnover.114·115 The

risk of developing PDB increases with age, affect­

ing an estimated 1 % of individuals over the age of

40 years in the United States.116 Men are at slightly

greater risk than women. In addition to a genetic

predisposition, other yet to be defined environ­

mental factors likely contribute to the disease pro­

cess.111.118

Mutations affecting the sequestosome 1 gene are

found in up to 50% and 30% of patients with familial

and sporadic cases of PDB, respectively.119 Sequesto­

some 1 (also known as p62) is an important scaffold

protein in the NFKB pathway. In terms of environ­

mental factors, some have proposed that a latent

paramyxoviral infection (eg, measles, canine distem­per virus, or respiratory syncytial virus) contributes to

PDB, but this issue remains unresolved.113·118·120 PDB may affect one (monostotic) or a few (poly­

ostoti c) bones, and most cases are asympto­

matic and discovered incidentally.116·118.121 The

most commonly affected sites include the pelvis,

skull, vertebra, femur, and tibia. Affected bones

usually manifest an initial osteolytic phase, followed

by a mixed osteolytic/osteosclerotic phase, which

ultimately progresses to a disorganized osteoscle­rotic phase. In reality, all three arbitrary phases of

PDB may exist concurrently. Common clinical signs

and symptoms include osseous distortion or expan­

sion and mild to moderate, deep, aching bone pain. Elevated serum total alkaline phosphatase levels are

reflective of the increased bone activity and charac­teristic for the disease. While osteosarcoma is a rare

complication of PDB, most cases of adult osteosar­coma occur in patients with PDB.113

Skull involvement is estimated to occur in about 27% of patients and may result in hearing loss and vestibular problems in up to 89% of those affected.122 It is postulated that, in addition to direct auditory

478

nerve impingement, the disease may adversely alter

the bone density, mass, and structure of the auditory complex to contribute to hearing compromise.

Numerous dental abnormalities, such as malocclu­

sion, hypercementosis, tooth mobility, root resorp­

tion, pulp calcification, osteomyelitis, poorly fitting

prostheses, and excessive postsurgical bleeding,

have been associated with PDB.122·123 However, these

findings are largely based on anecdotal case reports,

and their true prevalence is unknown. In a cross­

sectional survey of 292 patients with PDB, 93% of

those with maxillomandibular involvement related having dental problems, compared to only 10% of

those with skull or other distant bone involvement.122

However, compared to controls, the patients with

dental problems reported no significant difference in

edentulism, tooth movement, change in bite, change

in denture fit, periodontal disease, or need for endo­dontic treatments. Many of the dental changes asso­ciated with PDB are likely explained by the dynamic

nature of the disease. During the osteolytic phase,

tooth mobility, shifting, and increased postsurgical

bleeding may occur. More mature pagetoid changes

affecting the jaws may manifest as malocclusion and/

or deformity and result in an increased risk of osteo­

myelitis.

Potential radiographic changes associated with

PDB reflect the brisk osteoclastic and osteoblastic

nature of the disease.121·124 The characteristic lytic

sign of PDB affecting the skull is osteoporosis cir­

cumscripta, whereas the characteristic sclerotic sign

is the cotton wool appearance. An overall mosaic

of lytic and sclerotic findings is frequently noted.

Potential radiographic findings of PDB involving

the jaws include hypercementosis, thickening of the

periodontal ligament space, root resorption, and

pulpal obliteration.123·125-129

Hypercementosis has been reported to occur frequently in PDB, and its presence is considered highly suggestive of PDB.123·126·127 Large amounts of cementum may be deposited in the apical two­

thirds of the roots, giving the tooth the appear­ance of a baseball bat (Fig 20-10). The cementum

may appear to be fused with the adjacent sclerotic bone130 (Fig 20-11), resulting in ankylosis.128 In such a

scenario, the involved teeth will be abnormally firm.

Lytic activity around an involved tooth may affect the lamina dura to produce a widened periodontal ligament space. In contrast to primary or secondary hyperparathyroidism, which manifests generalized thickening of the periodontal ligament space, in

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Genetic and Developmental Disorders

Fig 20-10 Ground section of a maxil­lary second premolar showing the extensive hypercementosis associated with Paget dis­ease.

Fig 20-11 Characteristic intraoral radiographic features of Paget disease. Note the variable appearance of the canal space, periodontal ligament space, and lamina dura. (a) Areas of radiolucency. (b) Isolated sclerosis. (c) Iso­lated sclerosis and distal root resorption of the maxillary second molar. (d) Isolated sclerosis and hypercementosis of the second premolar. (Reprinted from Barnett and Elfenbein130 with permission.)

PDB the widening is restricted to involved teeth. An additional lytic change that may occur is root resorp­tion, which may clinically manifest as mobility. Paral­leling the concurrent mixed lytic and sclerotic pro­cesses affecting the bone, lytic changes may affect some teeth while other teeth may demonstrate hypercementosis.

The potential for pagetoid changes to affect the pulp has been proposed, but few reports addressing the issue exist.125•128•129 In one case report evaluat­ing a mandibular third molar, internal resorption of the dentin, direct apposition of cellular hard tissue partially occluding the coronal pulp, and dystrophic calcification in the radicular region of the pulp were noted. The overall mosaic pattern observed was similar to that typically observed in the bone and cementum.125 These potential radiographic findings may interfere with endodontists' ability to establish a proper working length, prompting some to rec­ommend the use of an apex locator to establish the canal length.123

Disturbances of vitamin D metabolism

The primary regulator of calcium homeostasis and subsequent bone and dentin mineralization in the body is bioactive vitamin D {1a,25-dihydroxyvitamin 03).131-133 Numerous rachitic conditions relating to specific alterations in vitamin D metabolism have been identified. Both vitamin D-dependent rickets type I (VDDRI) and vitamin D-dependent rickets type II (VDDRll) are rare recessive disorders, while X-linked hypophosphatemic rickets (XLH) is passed as an X-linked dominant trait. The phenotypic pre­sentations of all three forms of rickets have much in common, but subtle variations do exist.

Vitamin D-dependent rickets type 1 VDDRI manifests as deficient 1-a-hydroxylase pro­duction, and the responsible mutation has been mapped to chromosome 12.131 1-a-hydroxylase is a member of the cytochrome P450 superfamily of enzymes and is required for normal vitamin D acti­vation. It acts on the circulating vitamin D precur­sor 25-hydroxyvitamin D

3 to form bioactive vitamin

D.132•134 Originally believed to be restricted to the kid­ney, 1-a-hydroxylase expression and activity occur at several extrarenal sites, including skin, lymph nodes, colon, pancreas, brain, endothelial cells, and bone.

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Interrelationship of Pulp and Systemic Disease

Prominent clinical features of VDDRI include stunted growth, skeletal abnormalities, genu val­gum, rachitic rosary, open fontanels, pathologic fractures, muscle weakness, and convulsions. Com­mon laboratory findings include hypocalcemia, hypophosphatemia, elevated parathyroid hormone, high alkaline phosphatase, normal levels of vitamin D precursors, and low levels of bioactive vitamin D. A single case report of the dental findings in a patient with VDDRI noted the presence of enamel hypoplasia, large quadrangular pulp chambers, and short roots.133 The administration of physiologic lev­els of bioactive vitamin D (1a,25-dihydroxyvitamin D3) is the treatment of choice. Such therapy bypass­es the deficient enzyme, thereby fostering normal development.

Vitamin D-dependent rickets type II Mutational abnormalities mapped to chromosome 12 underlie VDDRll.131 In this scenario, the vitamin D receptor is adversely affected, resulting in end­organ resistance to vitamin D modulation. The resul­tant defective intestinal calcium absorption leads to hypocalcemia and rickets. Laboratory findings include hypocalcemia, elevated parathyroid hor­mone levels, and hypophosphatemia. Vitamin D precursor levels are normal, and bioactive vitamin D levels are elevated. The elevated levels of bioactive vitamin D help to distinguish VDDRI from VDDRll.131

The clinical findings of VDDRll are often severe and usually apparent within a few months of birth.131 The clinical phenotype is similar to that for VDDRI. However, a fairly characteristic feature of VDDRll is sparse body hair, or a/opecia universa/is, the pres­ence of which appears to correlate well with disease severity. Medical therapy is limited and consists of calcium infusion and the administration of pharma­cologic levels of precursor and bioactive vitamin D. Because neither of these approaches addresses the receptor deficiency, results have been mixed.

Only a single report is available in the English literature addressing the dental findings associated with VDDRll.135 The authors reported on the dental findings in three children with VDDRll. Two of the three children, both girls, exhibited no evidence of enamel hypoplasia but did manifest enlarged pulp chambers and thin dentin. Both responded well to medical therapy and experienced normal root canal and pulp chamber development. The other child, a boy, presented with a more severe phenotypic presentation of VDDRI I than the two

480

girls. On initial examination, an abscessed primary maxillary first molar was noted, and his teeth also exhibited enlarged pulp chambers and thin dentin. The abscessed tooth was extracted and submitted for histologic assessment. The histologic findings showed abundant interglobular dentin and a lack of a predental layer. This child did not respond to medical therapy, and the dental defects persisted.

X-linked hypophosphatemic rickets The most prevalent form of rickets is caused by mutations affecting the PHEX gene (phosphate­regulating gene with homology of endopep­tidases that maps to the X chromosome) and is termed X-linked hypophosphatemia.136 The muta­tion responsible for XLH has been mapped to Xp22.2-p22.1, and the incidence is estimated at 1 in 20,000 persons.70·136-138 Patients with XLH experience impaired 1-a-hydroxylase activity, reduced phos­phate resorption in the kidney and intestine, hypo­phosphatemia, and hyperphosphaturia. The current medical treatment of choice is the prompt institution of supplemental vitamin D and phosphate therapy.

The main clinical features include severe bony deformities, impaired growth, short stature, frontal bossing, craniotabes, and a square-shaped head. The dental findings affect both the primary and per­manent dentitions and include enlarged pulp cham­bers, enlarged pulp horns, hypocalcified and inter­globular dentin, short roots, taurodontism, poorly defined lamina dura, and hypoplastic alveolar ridg­es70·133·138 (Figs 20-12 and 20-13). The severity of the clinical and radiographic dental lesions is influenced by the patient's age, the type of teeth (prenatal or postnatal odontogenesis), and whether the patient was undergoing therapy prior to the time of exami­nation.

The finding of prominent pulp horns extending up to the dentinoenamel junction in both denti­tions is regarded by some as pathognomonic for XLH.137·139 These abnormalities place the XLH patient at risk for spontaneous dental abscesses, which occur frequently and often without any evidence of preexisting trauma or caries.70·137·138·140·141 It is likely that attrition of the enamel allows bacterial entry into the dentinal tubules and pulp.70·142·143 Although endodontic treatment is clearly [ndicated in many instances, the underlying structural defects associ­ated with XLH may compromise the clinician's ability to obtain an adequate obturation seal.

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Fig 20-12 (a and b) Bitewing radio­graphs of a patient with XLH rickets. Note the enlarged pulp chambers, large root canal systems, and pulp horns that extend to the dentinoenamel junction. (Reprinted from Bender and Naidorf139 with permis­sion.)

Genetic and Developmental Disorders

Fig 20-13 Ground section of a premolar from a patient with XLH rickets. The high risk of pulpal necrosis and subsequent periradicular lesions is readily apparent. The pulp horn defect appears as a tubular cleft covered only by a thin layer of hypoplastic enamel, showing the exten­sion of the pulp horn to the dentinoenamel junction. Note the appearance of hypoplastic enamel and interglobular dentin. (Courtesy of Dr C. J. Witkop).

Hemoglobinopathies

Hemoglobinopathies are a group of hereditary

blood disorders that affect hemoglobin. The two

most commonly cited diseases of this group are

thalassemia and sickle cell anemia (SCA).

Thalassemia Thalassemia refers to a group of clinically hetero­

genous and common hemolytic anemias involving

reduced or absent hemoglobin production.63·144·145

Most cases are inherited in an autosomal-recessive

pattern, and an estimated 1.67% of the worldwide

population carries a thalassemia trait.145 Thalasse­

mias vary in severity and are classified as homozy­

gous (major), heterozygous (minor}, or compound

heterozygous (intermedia). The most serious type of thalassemia is the major form of 13-thalassemia, also

known as Cooley anemia.145·146

Hemoglobin consists of four protein subunits, typically two subunits called a-globin and two subunits called {3-globin. The HBB gene provides

instructions for making 13-globin. Over 200 point mutations affecting the gene have been discovered, which helps account for the variability in 13-globin­chain synthesis reduction.145•147 In 13-thalassemia, two 13-globin genes that carry a severe mutation are present. The imbalance between normal a-globin

production and reduced 13-globin production results in severe anemia, an ineffective compensatory eryth­

ropoiesis, and iron overload. The compensatory

erythropoiesis often leads to a 15- to 30-fold expan­

sion of the bone marrow.63•147 Iron overload under­

lies most of the other characteristic manifestations,

including hepatosplenomegaly, skeletal changes, growth retardation, increased susceptibility to infec­tion, endocrine dysfunction, and cardiac failure.

Medical management is multidisciplinary and

centered on lifelong regular transfusions and

chelation therapy. The primary cause of death in

13-thalassemia is cardiac failure, usually during early

adulthood, because of iron overload.145

Orofacial manifestations of 13-thalassemia are

frequently observed and generally a consequence

of the extensive marrow space expansion. A char­acteristic "rodent" or "chipmunk" facies may be

observed because of the presence of maxillary pro­trusion and expansion, bossing of the skull, hyper­

telorism, and prominent cheek bones.63·146·148 Mal­occlusion is commonly observed, typically marked

by overbite, flaring, increased overjet, and spac­ing of the teeth. Delayed dental development has been reported, as has a higher prevalence of tau­rodontism. Radiographically, the jaws have been

described as osteoporotic with coarse trabecula­tion 146 (Fig 20-14).

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Interrelationship of Pulp and Systemic Disease

Fig 20-14 Periradicular radio­

graph from a patient with thalas­

semia.

Sickle cell anemia

Fig 20-15 Periradicular radio­

graph from a patient with sickle cell

anemia.

SCA represents the most common form of a

group of sickling disorders that affect hemo­globin.149 It is a recessive disorder estimated to affect 1 in 500 African Americans. Approximately 13% of African Americans are heterozygous carriers of the

SCA trait. SCA is caused by a single point muta­

tion at the sixth codon, which leads to the substi­tution of valine for glutamic acid in the 13 chain of

hemoglobin.150 When deoxygenated, affected hemo­

globin undergoes polymerization, which causes the red blood cell to change into the characteristic sickle

shape.151 For those individuals with SCA, more than

70% of circulating hemoglobin is affected, whereas for those with SCA trait, less than 45% of circulating

hemoglobin is affected.151 The sickle red cell is more fragile than a healthy

red cell and cannot deform as it attempts to move through the capillaries. As a consequence, the affect­ed red cell life span is reduced from the normal 120 days to a range of 10 to 30 days, and compensatory marrow hyperplasia is characteristic (Fig 20-15). The disruption of blood flows leads to vascular occlu­sions, hemorrhages, infarctions, and ischemic necrosis affecting a variety of body tissues and organs.149·151

Clinical manifestations of SCA include chronic hemolytic anemia, pallor, increased susceptibility to

482

infection, and specific end-organ damage (eg, reti­

nopathy, nephropathy, leg ulcers, and osteomyelitis of long bones and the mandible).149 Characteristic

painful episodic vaso-occlusive crises (sickle cell

crises) occur in the abdomen, joints, muscles, and

bones. These crises may be precipitated by dehy­dration, acidosis, strenuous exercise, trauma, pulmo­

nary disease, or a prior vaso-occlusive event. There is no cure for SCA Medical management

is multidisciplinary and targeted to relieve pain,

prevent infection, prevent end-organ damage, and control complications if they occur.150 Heterozygous carriers generally do not manifest significant clinical disease.

Head and neck manifestations of SCA, such as

marrow hyperplasia, osteoporosis, bone infarction,

osteonecrosis, and osteomyelitis, are observed in

79% to 100% of SCA patients.151 The risk that osteo­

myelitis will affect the jaws of patients with SCA is 200 times that found in healthy controls.152 Radio­paque lesions, commonly observed in the posterior body of the mandible, are believed to represent a sclerotic response to a prior osseous infarction.151

A spectrum of neuropathic manifestations may

occur as a consequence of vaso-occlusive events.

Examples include asymptomatic pulpal necrosis,

symptomatic pulpitis without evident radiographic involvement, vague jaw pain or paresthesia, and referred odontalgia.151·153-155 When feasible, endo­dontic treatment is preferred over extraction to

reduce the risk of osteomyelitis. All dental care

should be performed in close consultation with the

managing physician. If surgery is necessary, surgical

manipulation and trauma should be minimized.156

Other inherited disorders affecting the oral cavity

Gaucher disease Gaucher disease, the most commonly occurring

lysosomal storage disorder, is a recessively inher­ited deficiency of the enzyme acid-13-glucosidase.157·158

Acid-13-glucosidase breaks down the glycolipid glu­cocerebroside to yield glucose and ceramide. Insuf­ficient enzyme availability leads to accumulation of glycolipid throughout the reticuloendothelial system, particularly in macrophages. Gaucher disease is clas­sically divided into three types, based on the presence or absence and rate of progression of neurologic manifestations.158·159 Type I Gaucher disease is the

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Fig 20-16 Radiographic presentation of Gaucher disease. (a and b) Uniform bilat­

eral periapical radiolucency of the mandibular second premolars and first molars. (c) Twenty-year follow-up revealing evidence of periapical root resorption on the second

premolar and first molar. The resorption only occurs in the apical portion of the

roots. (d) Twenty-year follow-up of the contralateral side reveals less periapical root

resorption. (Reprinted from Bender and Bender163 with permission.)

Genetic and Developmental Disorders

II m�CEJ•Ell Dental observations in 11 patients with Gaucher disease (type 1)

Mandibular Maxillary Sclerotic Hemorrhagic Radiologic root radiolucency radiolucency Osteopenia changes Biopsy diathesis resorption

+ + + +

+ + +

+ + + + +

+ 0 + + +

+ + + +

+ 0 + + 0

+ 0 + + 0 +

+ 0 + 0 + +

+ 0 + +a +a

+ + + + + 0 +b

+ 0 + 0 + 0 0

+, present;-, absent; 0, not mentioned; +a, autopsy; +b, histologic resorption. (Reprinted from Bender and Bender'" with permission.)

most frequently occurring genetic disorder affecting Ashkenazi Jews, among whom the carrier rate is about 1 in 15.158 Most patients with Gaucher disease respond well to the administration of recombinant acid­�-glucosidase (enzyme replacement therapy).15s.159

The clinical manifestations of Gaucher disease vary greatly, ranging from death in utero to inconsequen­tial. Common signs and symptoms include hepato­splenomegaly, thrombocytopenia, and anemia. Skeletal manifestations affect an estimated 75% of patients and include osteopenia, lytic lesions, path­ologic fracture, deformity, chronic and acute bone pain, bone infarcts, and osteonecrosis.157·160·161 An Erlenmeyer flask-like appearance of the distal head

of the femur is considered a pathognomonic sign for Gaucher disease.161•162

In a small survey, radiographic involvement of the jaws, consisting of enlarged marrow spaces, cortical thinning, endosteal scalloping, external root resorp­tion, or radiolucencies of the jaws, were noted in 25 of 28 patients studied.162 Involvement of the mandibular body and the premolar and first molar region of the mandible has also been noted163 (Fig 20-16). Bender and Bender163 reported on the dynamic nature of Gaucher disease, following 11 affected patients over a period of 13 to 60 years (Table 20-2). They noted lesion enlargement and temporary bone regenera­tion that occurred after local curettage, tooth extrac-

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Interrelationship of Pulp and Systemic Disease

II @tjtfJ•f 111 Other inherited disorders affecting the oral cavity

Mode of Disease

Fabry disease166·167

Oculocerebrorenal syndrome (Lowe syndrome)67.16s.169

Cyclic neutropenia 110-173

Papi I Ion-Lefevre syndrome174-177

Chediak-Higashi syndrome 11s-1so

22q11.2 deletion syndrome (DiGeorge syndrome)181

Primary oxalosis type 11s2-1s4

inheritance

X-linked recessive

X-linked recessive

AD

AR

AR

AD

AR

AD, autosomal dominant; AR, autosomal recessive.

Pathogenesis

Deficiency of lysosomal enzyme a-galactosidase

Deficient phosphatidylinositol 4,5-bisphosphate-5-phosphatase

Cyclic production of white blood cells (21-day periodicity)

Defective cathepsin C activity

Defective intracellular protein traffick­ing to and from the lysosome

Deletion of approximately 30 genes on chromosome 22

Deficiency of alanine-glyoxylate aminotransferase

Other disorders

Clinical manifestations

Acroparesthesias, angiokeratomas, hypohidrosis, corneal opacity, hearing loss, malocclusion, diastemas, mucous retention cysts

Hydrophthalmos, cataracts, mental retardation, renal tubular dysfunction, large pulp chambers, dysplastic dentin, periodontal disease

Increased susceptibility to infection, progressive periodontal disease, oral ulcerations

Palmoplantar hyperkeratosis, severe early-onset periodontitis leading to early tooth loss

Severe immunologic defects, reduced pigmentation, mild bleeding tendency, progressive neurologic dysfunction

Cardiovascular defects, craniofacial anomalies, ear defects, immunologic problems, parathyroid abnormalities, kidney abnormalities

Progressive nephrolithiasis/ nephrocalcinosis and eventual renal failure, extrarenal calcium deposits, slate-gray teeth, odontalgia, pulpal calcifications, root resorption

tion in proximity to the lesion, or long-bone fracture.

These changes were eventually replaced by further

lytic destruction. While extraosseous extension of

Gaucher lesions is considered rare, reports of extraos­

seous extension into masseter muscle and sphenoid

sinuses have been published.160·161·164

Numerous other uncommon or rare inherited disor­

ders may manifest involvement of the oral cavity. A

selected few are summarized in Table 20-3.74·16b--184

Aside from the previously mentioned exter­

nal root resorption, specific dental and gingival

changes associated with Gaucher disease appear

to be minimal.162 However, these patients should be

closely followed and should undergo regular radio­

graphic assessment to monitor osseous involvement because they may be at increased risk for develop­

ing osteomyelitis or pathologic fracture.165 Many

of these patients undergo splenectomy as part of

their disease management, which may increase their

risk of infection. Finally, the commonly observed

thrombocytopenia places the patient with Gaucher

disease at risk for increased postsurgical bleeding.162

484

I Endocrine Disorders

Diabetes mellitus

Diabetes mellitus is a serious endocrine disorder

characterized by an absolute or relative insulin insuf­

ficiency or target resistance to insulin activity. In the United States, an estimated 25.8 million indi­viduals have diabetes, and an estimated 7.0 million

are undiagnosed.185 Patients with poorly controlled

diabetes manifest chronic hyperglycemia and are at

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increased risk for myriad complications, including infection.186-189 The five classic complications of dia­betes are (1) retinopathy, (2) nephropathy, (3) neu­ropathy, (4) macrovascular disease, and (5) impaired wound healing.187,189-191

Hyperglycemia leads to the creation and accu­

mulation of advanced glycation end-products

(AGEs), which are believed to contribute directly to the etiopathogenesis of diabetes.187·189·191-196 AGEs impair normal homeostatic collagen turnover, lead­ing to the accumulation of a more mature, less soluble collagen in the vessel wall; subsequent ves­sel wall thickening and reduction in lumen size; and a decrease in tissue perfusion.187·189·195 AGE-altered collagen is also more prone to bind with low-density

lipoprotein to form atheromas, which contribute to

large vessel disease.187 At the immunologic level, hyperglycemia results in impaired chemotaxis, adherence, and phagocytosis of polymorphonuclear leukocytes.187 AGE interaction with monocytes and macrophages results in the creation of a proinflam­matory phenotype.187,191,193.197

While it is axiomatic that adequate medical con­trol of diabetes is essential to the maintenance of oral health, the impact of poor oral health (eg, peri­odontitis or periradicular abscess) on the control

and progression of diabetes must be understood.

A two- to three-times greater rate of periodon­tal disease has been observed in individuals with

diabetes. This is understandable, given the fact that the typical area of the susceptible periodon­tium is roughly the size of the palm.198 Such a large inflammatory burden may negatively impact glu­cose control in the diabetic patient and confer an increased risk of developing diabetes-related com­plications.188-191,194, 197-199

Although there are few studies addressing the

relationship between diabetes and pulpal disease, logical points of intersection to consider would include diabetes-induced microvascular, neuropathic, and inflammatory changes. It appears that diabetic patients in need of endodontic treatment are more likely to present with larger periradicular lesions, har­bor more virulent pathogens, experience periopera­tive symptoms, and experience a higher incidence of

therapeutic failure than control patients.186·200-205 The increased risk of infection and potential poor

wound healing observed in the diabetic patient has led some to advocate the administration of antimi­crobial prophylaxis prior to dental treatment, partic­ularly in the individual with poorly controlled diabe-

Endocrine Disorders

tes.206 However, there have been no studies directly addressing the issue, and the overall complexity of diabetes would seem to confound any attempted study. It is clear that any infection, including pulp­al disease, in the diabetic patient must be man­

aged promptly and aggressively. As a rule, diabetic patients under good disease control can be gener­

ally regarded as normal patients, whereas patients who are either suspected of having diabetes or

whose diabetes seems under poor control should be referred for medical evaluation prior to the delivery of dental care. Medical consultation is further rec­ommended for any anticipated dental treatment, such as extensive surgery, that can adversely impact the patient's glucose control.

Adrenal dysfunction

Cortisol, a naturally occurring glucocorticoid of the adrenocortex, and the catecholamine epinephrine are the primary modulators of the stress response.207-210 Cortisol stimulates peripheral fat and protein catab­olism to serve as substrates for the hepatic produc­tion of glucose.211 Well-established anti-inflammatory and immunomodulatory effects of cortisol include preventing leukocyte migration from the circulation

into the extravascular space, reducing the accumula­tion of monocytes and granulocytes at inflammatory sites, and suppressing the production of numerous cytokines and other proinflammatory mediators. Cortisol also acts in a permissive role to allow other hormones such as catecholamines and angiotensin II to modulate cardiac contractility, vascular tone, and blood pressure.212-214 Finally, cortisol provides nega­tive feedback to the hypothalamus and the anterior

pituitary gland (hypothalamic-pituitary-adrenal [HPA]

axis) in regulating corticotropin-releasing hormone

and adrenocorticotropin-releasing hormone.207·210·215 Conditions of insufficient cortisol production,

regardless of the etiology, are termed Addison dis­ease. 216 Most cases of glucocorticoid deficiency develop insidiously, presenting with nonspecific signs and symptoms such as lethargy, anorexia, nausea, weight loss, and hypoglycemia. These

patients are typically prescribed empirical replace­ment glucocorticoid therapy.217 Conditions of endogenous cortisol excess are termed Cushing syndrome.211·218·219 However, the most frequent cause of glucocorticoid excess is iatrogenic. The clinical findings of cortisol excess correspond directly to the

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Interrelationship of Pulp and Systemic Disease

severity and duration of glucocorticoid excess and

include truncal obesity, violaceous striae of the skin,

buffalo hump, facial fullness (moon facies), facial

plethora, acne, hirsutism, easy bruising, muscle wast­

ing, and myopathy.

There are no disease-specific oral manifestations

of Addison disease. Some individuals manifest a

patchy brown (bronzing) pigmentation of the face

(with superimposed areas of vitiligo}, the buccal

mucosa, the tongue, and, less frequently, the lips

and gingivae. Head and neck manifestations of

Cushing syndrome include facial plethora, moon

face, hirsutism, and acne. Affected children may

exhibit delayed or arrested dental development

paralleling the overall growth retardation that may

occur with glucocorticoid excess.220·221 Chronic expo­

sure to excess glucocorticoid appears to stimulate odontoblast-like cells within the dental pulp, result­

ing in narrowing of the dental pulp chamber or com­

plete pulpal obliteration222-224 (Fig 20-17).

Patients with Addison disease are inherently

unable to produce sufficient levels of adrenocorti­

cotropic hormone or cortisol to meet physiologic

demand. Similarly, chronic exogenous glucocorticoid

exposure can suppress the HPA axis, and therefore

patients on chronic glucocorticoid therapy may not

be able to produce sufficient levels of adrenocorti­

cotropic hormone and cortisol to meet physiologic

demand.211·225--227 The concern in clinical practice is

that, for either situation, an overwhelming stressor

(surgery, sepsis, or fever) may precipitate an Addi­sonian crisis (adrenal insufficiency with hypotension

and shock).22&-230 Accordingly, supplemental gluco­

corticoids ("stress dose" steroids) are recommend­

ed perioperatively for patients with documented or

presumed HPA axis suppression when they are to

undergo a stressful medical procedure. Fortunately,

486

-

.. ..... -

Fig 20-17 Comparison of predentin thickness in teeth collected from a healthy patient (a) and a patient who was chronically treated with gluco­

corticoids, suffering from renal failure, and under­going dialysis (b). The predentin is about four times wider in the healthy patient than it is in the chronically ill patient (hematoxylin-eosin stain). (Reprinted from Wysocki et al224 with permission.)

it appears that the risk of an Addisonian crisis dur­

ing an outpatient dental procedure is low or very

low.217·23° Consequently, patients need only to take

their usual daily glucocorticoid dose on the day of

the procedure. If moderate or major surgical stress is

anticipated under general anesthesia and the patient

has documented or presumed HPA axis suppression,

then appropriate stress doses of perioperative ste­

roids are indicated.

I Cancer

There are few reports of malignancies affecting the

dental pulp. The risk that a primary malignancy will

arise from pulpal tissue appears to be extremely

remote.231 In reviewing the dental literature pub­

lished over a 100-year span (1870 to 1970), Stanley129

reported fewer than 20 case reports of pulpal cancer.

Furthermore, if a primary pulpal malignancy were to

develop, the enclosed nature of the pulp chamber

increases the likelihood that the tumor growth will adversely interrupt the pulpal vascular network, result­

ing in self-strangulation. A more likely, albeit still rare,

scenario occurs when the pulp or periradicular area is

infiltrated by a hematologic malignancy or is the tar­

get of a solid tumor metastasis.232-251

Regardless of the specific malignancy involved,

the presenting signs and symptoms are often non­specific and mimic routine inflammatory pulpal or

periodontal disease.235•237•238·243·244 Thus, the pres­

ence of findings such as odontalgia, percussion

sensitivity, periradicular radiolucencies, and gingival

inflammation and swelling often raise little suspicion.

However, the presence of more worrisome findings,

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such as altered sensation (eg, anesthesia or par­esthesia), asymmetric widening of the periodontal

ligament space, loss or thinning of the lamina dura,

and moth-eaten or ill- defined radiolucencies, war­

rant increased suspicion (Fig 20-18). Finally, a prior

history of malignant disease, especially of the breast,

lung, adrenal glands, kidney, prostate, thyroid, and

colon, should raise the clinician's suspicion of a

malignancy even more.252,253

Therapeutic interventions to treat cancer may

adversely affect structures of the head and neck,

including the dental pulp.254-261 Probably the most

frequently incurred therapy-induced damage affect­ing adult patients occurs as a consequence of head

and neck irradiation therapy. Potential signs and

symptoms associated with head and neck irradiation

include mucositis, irreversible salivary gland impair­

ment, taste aberration, radiation caries, and osteo­

radionecrosis.256 While developed teeth appear to

be fairly resistant to the effects of irradiation, it has been suggested that radiation-induced collagen

damage within the dental pulp results in impaired odontoblastic metabolism, which in turn contributes to poor dentinal hydration.261 It has been further

suggested that impaired dentin homeostasis con­

tributes to the increased caries risk observed in the

postirradiation patient.

Dental infection and dental trauma (eg, extrac­

tion or apical surgery) increase the risk for develop­

ment of osteoradionecrosis. As a consequence,

endodontic treatment is the preferred alternative to extraction in managing problematic teeth in the

patient who has undergone head and neck irradia­

tion.256·258·262 Fortunately, the success of conservative

endodontic treatment in managing previously irradi­

ated teeth appears to be on par with that of treat­

ment in control teeth.258

lnterventional chemotherapy and radiation thera­

pies may adversely affect craniofacial development

in the growing child.255-257·261·262 In principle, any ther­apy that may directly kill odontogenic cells, inhibit

their metabolism, or block or alter signaling and cell

communication may result in aberrant tooth develop­

ment.255 Resultant abnormalities include hypodontia, root stunting, microdontia, enlarged pulp chambers,

and retention of primary teeth. The observed abnor­

malities reflect the stage of dental development during which the interventional therapy was prescribed. From

an endodontic perspective, therapeutic success may be compromised by the aberrant tooth development.

References

Fig 20-18 (a and b) Periradicular radiographs of a 13-year-old patient with acute monocytic leukemia. Note the uniform widening of the periodontal liga­ment space.

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195. Miley DD, Terezhalmy GT. The patient with diabetes mellitus: Etiology, epidemiology, principles of medical management, oral disease burden, and principles of dental management. Quintessence Int 2005;36:779-795.

196. Sampathkumar R, Balasubramanyam M, Rema M, Premanand C, Mohan V. A novel advanced glycation index and its association with diabetes and microangiopathy. Metabolism 2005;54: 1002-1007.

197. Grossi SG, Skrepcinski FB, Decaro T, Zambon JJ, Cummins D, Genco RJ. Response to periodontal therapy in diabetics and smokers. J Periodontol 1996;67: 1094-1102.

198. Mealey BL, Rose LF. Diabetes mellitus and inflammatory periodontal dis­eases. Curr Opin Endocrinol Diabetes Obes 2008; 15: 135-141.

199. Chandu A, Macisaac RJ, Smith AC, Bach LA. Diabetic ketoacidosis sec­ondary to dento-alveolar infection. Int J Oral Maxillofac Surg 2002;31: 57-59.

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232. Ahmad S, Roberts GJ, Lucas VS, Barrett AW, Harkness W. Metastatic infiltration of the dental pulp by medulloblastoma. J Oral Pathol Med 2002;31 :244-245.

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234. Bavitz JB, Patterson OW, Sorensen S. Non-Hodgkin's lymphoma disguised as odontogenic pain. J Am Dent Assoc 1992; 123:99-100.

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236. Heng C, Heng J. Implications of malignant lymphoma on a periapical man­dibular lesion. Gen Dent 1995;43:454-458.

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238. Kanas R, Jensen J, DeBoom G. Painful, nonhealing tooth extraction socket. J Am Dent Assoc 1986; 113:441-442.

239. Keyes GG, Balaban FS, Lattanzi DA. Periradicular lymphoma: Differen­tiation from inflammation. Oral Surg Oral Med Oral Pathol 1988;66:

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241. Levi PA Jr, Kim OM, Harsfield SL, Jacobson ER. Squamous cell carci­noma presenting as an endodontic-periodontic lesion. J Periodontol 2005;76: 1798-1804.

242. Maygarden S, Askin F, Burkes E, McMillan C, Sanders J. Isolated extra­medullary relapse of acute myelogenous leukemia in a tooth. Mod Pathol 1989;2:59-62.

243. Morgan L. Infiltrate of chronic lymphocytic leukemia appearing as a peri­apical radiolucent lesion. J Endod 1995;21 :475-478.

244. Peterson D, Gerad H, Williams L. An unusual instance of leukemic infil­trate. Diagnosis and management of periapical tooth involvement. Cancer 1983;51: 1716-1719.

245. Pruckmayer M, Glaser C, Marosi C, Leitha T. Mandibular pain as the lead­ing clinical symptom for metastatic disease: Nine cases and review of the literature. Ann Oncol 1998;9:559-564.

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246. Selden H, Mannhoff D, Hatges N, Michel R. Metastatic carcinoma to the mandible that mimicked pulpal/periodontal disease. J Endod 1998;24:267-270.

247. Shankar S. Dental pulp metastases and pan-osseous mandibular involve­ment with mammary adenocarcinoma. Br J Oral Maxillofac Surg 1984;22:455-461.

248. Svoboda W, Aaron G, Albano E. North American Burkitt's lymphoma pre­senting with intraoral symptoms. Pediatr Dent 1991;13:52-58.

249. Thompson 10, Phillips VM, Kalan M. Metastatic squamous cell carcinoma manifesting as a periapical lesion. J Dent Assoc S Afr 1992;47:481-483.

250. Todd H, Langeland K. Pulpal destruction of neoplastic etiology. J Endod 1987; 13:299-301.

251. Tsui S, Wong M, Lam W. Burkitt's lymphoma presenting as mandibular swelling-Report of a case and review of publications. Br J Oral Maxillofac Surg 2000;38:8-11.

252. D'Silva NJ, Summerlin DJ, Cordell KG, et al. Metastatic tumors in the jaws: A retrospective study of 114 cases. J Am Dent Assoc 2006; 137: 1667-1672.

253. Kuttan NA, Flemming DK, Dane JN, Ang DB. Metastatic lesion of the anterior mandible with an occult primary: A case report. Spec Care Dentist 2006;26:76-80.

254. Dahlliif G. Craniofacial growth in children treated for malignant disease. Acta Odontol Scand 1998;56:378-382.

255. Hiiltta P, Hovi L, Saarinen-Pihkala UM, Peltola J, Alaluusua S. Disturbed root development of permanent teeth after pediatric stem cell transplantation. Dental root development after SCT. Cancer 2005; 103: 1484-1493.

256. Huber MA, Terezhalmy GT. The head and neck radiation oncology patient. Quintessence Int 2003;34:693-717.

257. Kaste SC, Hopkins KP, Jones D, Crom D, Greenwald CA, Santana VM. Dental abnormalities in children treated for acute lymphoblastic leukemia. Leukemia 1997;11:792-796.

258. Lilly JP, Cox D, Arcuri M, Krell KV. An evaluation of root canal treatment in patients who have received irradiation to the mandible and maxilla. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;86:224-226.

259. Minicucci EM, Lopes LF, Crocci AJ. Dental abnormalities in children after chemotherapy treatment for acute lymphoid leukemia. Leuk Res 2003;27:45-50.

260. Oguz A, Cetiner S, Karadeniz C, Alpaslan G, Alpaslan C, Pinarli G. Long­term effects of chemotherapy on orodental structures in children with non­Hodgkin's lymphoma. Eur J Oral Sci 2004; 112:8-11.

261. Springer IN, Niehoff P, Warnke PH, et al. Radiation caries-Radiogenic destruction of dental collagen. Oral Oncol 2005;41 :723-728.

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Page numbers followed by "f" denote figures; "t" tables; and "b" boxes

A A fibers, 135--137, 148, 150f, 434 Aj3 fibers, 136--137 Acetaminophen, 193-195, 200 Acid etching

description of, 48, 340 illustration of, 49f microcirculatory effects, 126 reactionary dentin stimulated by, 38

Actinomyces species, 214, 220, 234, 37 6f Adaptive immune responses, 285-287 Adaptive immunity, 329 Addison disease, 485--486 AO fibers, 137, 167, 177-178 Adhesion molecules, 247-248, 250 Adhesion restorations, 323, 344 Adhesive dentistry, 323 Adhesive luting cements, 323 Adhesive resin systems, 312-313 Adhesives, 312-313

chronologic classification of, 337 etch-and-rinse, 336 self-etching, 336

Adrenal dysfunction, 485--486 Advanced glycation end-products, 485 Afferent nerve fibers, 147 Aging

biologic changes associated with, 431-436 blood vessels affected by, 432-434 cellular behavior affected by, 432 degenerative processes induced by, 431 dentinal sensitivity and, 177 dentinogenesis changes, 431, 438-440 disease versus, 422 intratubular and intertubular dentin formation

secondary to, 440 odontoblast changes secondary to, 427, 429-

430 oral health during, 421 overview of, 421 oxidative stress theory of, 423-424 process of, 421-425 pulp capping considerations, 441-442 pulp testing responses to evaluate effects of,

436-437 pulpal changes secondary to, 425-442 pulpodentin complex changes secondary to,

334,427,440-442 radiographic signs of, 441 root canal revascularization using blood clotting

affected by, 101 senescence and, 421-423 sensory nerves affected by, 434-436 telomeres, 423-425, 431

Airborne particle abrasion, 367-368 Allergy-induced sinusitis, 455 Allodynia, 449

central mechanisms of, 171-173, 172b characteristics of, 169t, 169-170 definition of, 169

Index

peripheral mechanisms of, 170b, 170--171 Allogeneic bone marrow transplantation, 93-94 Allogeneic stem cells, 95 a-Adrenergic receptors, 118f Amalgam, 344 Ameloblasts, 4, 17f Amelogenesis imperfecta, 477, 477t Amelogenins, 316 Anemia

Cooley, 481 sickle cell, 464, 481-482, 482f

Antigen I/Ii, 221 Antigen-presenting cells, 80, 269-270 Antigen-presenting dendritic cells, 277-278 Anti-inflammatory cytokines, 268-269 Antimicrobial agents, 208 Apical foramen, 101, 375, 3811 Apical periodontitis

definition of, 206, 222, 278 external root resorption and, 404-405 periapical responses, 277-282 persistence of, 232f pulpal responses, 277-278 radiograph of, 206f symptomatic, 231 treatment of, 234-235

Apoptosis, 33, 311 Arachidonic acid metabolites, 250--252, 254-

255, 290--291 Archaea, 231 Argon laser, 359 Arterioles, 109-110, 11 Of, 1211, 127f Arteriovenous anastomosis

shunts, 111 Y-shaped, 112f

Atypical odontalgia, 461-462 Autologous stem cells, 94-95, 104 Avulsion, 386 Axon degeneration, 147

B B cells, 80, 279, 283b Bacteria

antibacterial agents, 221 beneficial types of, 214 in biofilm

community lifesty le of, 207-208 intercommunication among, 208-209 quorum sensing, 208-209

cariogenic, 213-215, 216t coaggregation of, 210 endodontic infections, 222 endodontic-periodontal diseases caused by,

377-378 fluoride effects on metabolism by, 222 Gram-negative, 227b Gram-positive, 227b microleakage of, 303, 343 mutans streptococci, 213-214 nutrients for, 230 primary intraradicular infections caused by,

226--228, 227b proteolytic, 377

pulpal healing affected by, 302-303 Streptococcus mutans, 214

Bacterial sinusitis, 455 Basement membrane, 73 Bay cysts, 3811, 381-382 Bead implantation assays, 6, 6f Bell stage, of tooth development, 3f, 4 j3-Adrenergic receptors, 119 Bifidobacterium species, 215 Bioactive molecule-containing materials, 315--

317 Biofilm, plaque

antimicrobial resistance of, 208 bacteria in. See Bacteria, in biofilm. caries formation secondary to, 211-212. See

also Caries. characteristics of, 207 definition of, 206--207 disease enhancement, 208 endodontic-periodontal infections caused by,

379 extracellular matrix formation, 207 formation of, 209f, 209-210 illustration of, 207f infectious, 379 microcolonies in, 207

Bleaching intracoronal, 410 lasers for, 367

Blood clotting, for root canal revascularization, 100--101, 102t

Blood vessels aging effects on, 432-434 arterioles, 109-110, 11 Of, 1211, 127f capillaries, 110--111 venules, 111

Bonding. See Dentin bonding. Bone morphogenetic proteins

BMP-4, 11 calcitonin gene-related peptide effects, 63 enamel knots and, 14 expression of, 111 function of, 77, 97t odontoblast differentiation, 355 source of, 97t tooth development role of, 10--11, 11 f

Bone sialoprotein, 18, 18t, 20, 211, 74 Bradykinin, 123, 256 Bud stage, of tooth development, 2, 3f

c C fibers, 135--137, 148-150, 434 Calcific metamorphosis, 314 Calcitonin gene-related peptide, 63, 70, 121-

123, 136, 139,243-247,434,436 Calcium hydroxide, 305

antimicrobial properties of, 308-309 caustic actions of, 308 dentin adhesives vs, 312-313 dentinal bridges created using, 308-310, 314 description of, 71, 308 mineral trioxide aggregate vs, 314 outcomes of, 310

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Index

pulp inflammatory responses caused by, 315 reactionary dentin deposition affected by, 342 reparative dentin formation, 308 resin-modified glass ionomers vs, 312 zinc oxide-eugenol vs, 318

Calcospherites, 31, 31f, 48 Cancer. 486-487 Candida albicans, 378 Cannabinoid receptors, 164 Cap stage, of tooth development, 2-3, 3f Capillaries, 11�111 Capillary filtration, 114 Capillary network, 111 Capsaicin, 122, 149, 245, 462 Carbohydrates, 213, 220 Caries

antibacterial control for. 22�221 bacteria associated with, 213--215, 216t, 22�

221, 224 categories of, 211-212 cavitation caused by, 217f characteristics of, 325--328 childhood, 215, 343 deep, 217f, 332f definition of, 211 dendritic cells' response to, 85 dentinal, 216f, 216t, 216-218, 326, 327f-328f description of, 205 diagnosis of. 218f, 218--219 diet and, 218, 220 ecological plaque hypothesis of, 212-213,

213f economic burden of, 206 enamel, 211 etiology of, 212-215, 317 fluoride for. 221-222 global prevalence of, 205--206 hand instruments used to remove, 318 immunocompetent cells' response to, 85--86 nonspecific plaque hypothesis of, 212 nursing, 215 occlusal, 216t, 307f, 330f, 332f pathogenesis of, 212 prevalence of, 205 prevention of, 22�222 primary, 212, 325 progression of, 327 progressive, 206f pulp exposure caused by, 224, 224f pulpal responses to, 331 radiographs of, 218, 218f recurrent, 211-212, 218-219 remaining, 212 root, 211, 216t saliva and, 218, 220 secondary, 211, 325 sequelae of, 205 smooth surface, 216t specific plaque hypothesis of, 212 treatment of, 219-220, 326 vaccine for. 221 white-spot lesion presentation of, 211, 211 f zone of destruction, 216, 217f

Carious dentin, 324 Cavity preparation

dentin permeability effects, 61-62 heat production during

causes of, 335 inflammation secondary to, 170

immunocompetent cells' response to, 84-85 mechanical stimuli during, 353--355 odontoblast disruptions caused by, 75, 341 pulpal injury caused by, 334--335 tertiary dentinogenesis effects, 35 thermal stimuli during, 349-353

CD4' T cells, 279 CD8' T cells, 279 Cell adhesion molecules, 248

494

Cell-rich layer of Hiihl, 28, 41 Cell-rich zone, 68 Cementoblasts, 282, 398 Cementodentin junction, 405 Cementoenamel junction, 56, 353 Cementum, 58, 398--399 Central sensitization, 171-173 Cervical loop, 4 C-factor. 338--339 Charcot-Leyden crystals, 383, 384f Chediak-Higashi syndrome, 484t Chemoattractants

in leukocyte adhesion, 250 transforming growth factor-[31, 41

Chemokines, 269, 282, 287 Chickenpox, 473 Childhood caries, 215, 343 Chlorhexidine gluconate, 221, 319 Cholesterol crystals, 382, 382f Chronic paroxysmal hemicrania, 457 Chronic periapical lesions, 281 Circulatory system. See Microcirculatory system,

of pulp. Clotting system, 257-259 Cluster headache, 457-458 co2 lasers, 361-362 Coaggregation, 210 Cocci, 227b, 229 Cold stimuli, for pulpal vitality testing, 179-180 Collagen

age-related changes in, 427-428 basement membrane expression of, 14-15 biosynthesis of. 71-72 characteristics of, 67 chemical composition of, 70 definition of, 70, 76 degradation of, 71 dentin types of, 16 intraluminal, SH odontoblast synthesis of, 29 in pulp, 7�71 reverse transcriptase-polymerase chain reaction

amplification of, 9f structure of, 70 type I, 70 type II, 70 type Ill, 70 type V, 70 type VI, 70

Collagen fibrils, 31, 7�71, 71f Colony-stimulating factor. 97t Connective tissue

definition of, 67 extracellular matrix, 67 function of, 67

Continuous capillary, 111 Convergence theory, 176-177, 448--449 Cooley anemia, 481 Core-binding factor a1, 12, 13f, 432 Coronal leakage, 384-385 Coronal pulp, 71f Coronal restoration, 385 Corticosteroids, 195 Crown fracture, 304, 385 Crown-root fracture, 385--386 Cushing syndrome, 485-486 Cusp

fracture of, 385 morphogenesis of, 14, 15f

Cyclic neutropenia, 484t Cyclo-oxygenases

arachidonic acid metabolites synthesized by, 25�251

inhibitors of, 194 Cyclophosphamide, 283--284 Cysteine cathepsins, 318, 326 Cysts, 381f, 381-382 Cytokines

anti-inflammatory, 268--269 functional studies of, 292-293 inflammatory role of, 263 osteoclast activity inhibited by, 292 proinflammatory, 264-268, 265f, 287-289,

291-293 secretion of, 263

Cytomegalovirus, 231, 379 Cytotoxic T cells, 79, 278

D Deafferentation, 461-462 Decorin, 18t 72, 73f Deep caries, 217f Defensins, 270 Demineralization

description of, 212 fluoride effects on, 221-222

Dendritic cells, 82-84, 83f, 279-280, 283b, 400 Dens evaginatus, 475-476 Dens in dente (dens invaginatus), 475f, 475-476 Dental epithelium, 4 Dental follicle, 2, 4 Dental follicle progenitor cells, 95 Dental plaque. See Plaque. Dental pulp constructs, 98--100, 99f, 102t Dentin. See also Pulpodentin complex.

acid etching of, 48, 49f apical, 59-60 axial, 56 caries-affected, 325--326, 327f-328f carious, 324, 328 characteristics of, 52-53, 53t, 62 coefficients of thermal expansion, 350 collagen types in, 16 composition of, 52, 52t, 335 definition of, 48 depth-related changes in structure of, 5�52 exposure of, 62 formation of, 16 grinding of, effect on pulpal blood flow, 125f hereditary opalescent, 476 intertubular. 32, 49, 440 intratubular. 49, 440 laser effects, 361 mantle, 31, 48, 53t mineralization of, 16, 3�31 morphology of, 48--50 nerve endings in, 136f neuronal desensitivity, 187-190 noxious substance permeation in, �2 periluminal, 49 peritubular. 32, 32f. 49, 52, 438 permeability

cavity preparations effect, 61-62 cementum effects, 58--59 dentinal thickness and, 56f depth, 54 description of, 69 factors that affect, 56, 69 illustration of, 55f importance of, 441 noxious substances, �2 pulpal blood flow effects, 61 restorative procedures effect, 61-62 smear layer effects, 57-59 tubular occlusion, 328 types of, 54 uniformity of, 55, 58

physical characteristics of, 52-53, 53t porosity of, 54-55 primary, 27, 28f, 48 reactionary

cavity etching stimulation of, 38 cellular signaling of, 38 definition of, 34, 78, 324 deposition areas for, 334 ethylenediaminetetraacetic acid effects, 38

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production of, 333 remaining dentinal thickness effects, 37-38 restorative materials effect on formation of,

342-343 remaining thickness, 37-38, 325, 334--335 remodeling of, 30 reparative, 34, 78, 308, 324 resorption of, 411 root

impermeability of, 58 mechanics of, 53-54 permeability of, 56f, 56-60

sclerotic description of, 327 illustration of, 32f permeability of, 56

secondary, 27, 33-34, 48--49, 78, 430, 433, 438--439

secretory model of, 29-30, 32-33 softness of, 52 tensile strength of, 52-53 tertiary, 27, 34--35, 49, 49f, 78, 317, 324 thermal properties of, 335, 349, 350t thickness of, 49, 325 trauma-induced exposure of, 224 water content of, 51-52

Dentin adhesives, 312-313 Dentin bonding

glass ionomers for, 312, 337-338 history of, 335 limitations of, 338-340 polymerization shrinkage concerns, 338 pulp affected by, 340--341 resin-based materials for, 335-337, 336f resin-modified glass ionomers for, 312, 338

Dentin chips, 99, 304--305 Dentin dysplasia, 476 Dentin matrix

composition of, 17-18 growth factors in, 36 lateral branches of, 30, 30f odontoblast-like cell differentiation induced

by, 41 remodeling of, 29-30 secondary, 34 vesicle, 31f

Dentin matrix protein 1, 18, 18t, 20, 21f, 430 Dentin phosphoproteins, 18-19, 29 Dentin sialophosphoprotein, 8, 17-19, 310, 476 Dentin sialoprotein, 18, 74, 76, 476 Dentinal bridge

calcium hydroxide for creating, 308-310 defects, 43 formation of, 43, 71 vital pulp therapy and, 306-307

Dentinal caries, 216f, 216t, 216-218 Dentinal fluid, 52f, 55f

description of, SO flow

evaporative, 352 sensitivity management by reduction of,

186-187 pain perception secondary to movement of,

177 Dentinal sensitivity

age and, 177 characteristics of, 177-178 desensitizing agents for

fluoride-containing medications, 189 guanethidine, 189-190 potassium-containing dentrifices, 188-189,

188t-189t strontium chloride solutions, 189

diagnosis of, 190--191 hydrodynamic theory of, 177-178 inflammation effects, 178 lasers for, 365-367 management of, 185-190

mechanisms of, 177-178 neuronal desensitivity, 187-190 neurophysiology of, 151-152 overview of, 185-186 prevalence of, 185-186 risk factors, 185

Dentinal tubules aging changes, 441 anatomy of, 223 bacteria in, 51f caries infections in, 317 cocci in, 229f convergence of, 49 density of, 51t, 54--56, 57f, 60, 324 diameter of, 51t exposed,373-374,374f innervation of, 177 microleakage, 60 permeability

description of, 50, 54 sensitivity management by reductions in,

186-187 scanning electron micrograph of, 223f sclerosis effects, 319, 331 shape of, 30, 31f, 31-32

Dentinoenamel junction, 48-50, 216 Dentinogenesis

aging effects on, 431, 438-440 definition of, 430 glycosaminoglycans' role in, 72 primary, 31-33, 430 reactionary

biologic processes, 35f-36f, 35-37 definition of, 35, 331, 333 factors that affect, 37-38 histomorphometric findings, 37-38 odontoblast upregulation during, 35-37 restorative materials that cause, 35-36

reparative biologic processes during, 35f collagen fibrils in, 72 definition of, 333 dentin bridge formation vs, 43 description of, 38 fibrodentin matrix secreted before, 39 histologic findings, 38, 39f matrices secreted during, 38, 39f-40f odontoblast-like cell differentiation, 41-43 progenitor cell recruitment in, 40-41 tertiary dentinogenesis and, 39

secondary, 33-34 tertiary

cavity preparation materials that affect, 35-36 description of, 34--35 transforming growth factor-j31 's role in, 36

Dentinogenesis imperfecta, 16, 17f, 476f, 476-477

Dentrifices, 188-189, 188t-189t Developmental malformations, 387 Diabetes mellitus, 484-485 Digastric muscle, 454f DiGeorge syndrome, 285-286, 484t Direct pulp capping, 340 Discontinuous capillary, 111 Diversity of microbiota, 226 DNA chips, 22 Dysfunctional pain, 175

E Ecological plaque hypothesis, 212-213, 213f Ectomesenchyme, 2 EDTA-soluble dentin matrix protein preparation,

342 Eicosanoids. See Arachidonic acid metabolites. Elderly, 421 Embryonic stem cells, 93-94 Enamel caries, 211 Enamel cracks, 224

Index

Enamel fracture, 385 Enamel knots, 14, 15f Enamel matrix derivative, 316 Endocrine disorders

diabetes mellitus, 484-485 glucocorticoid excess, 485-486

Endodontic disease periodontal disease and, 389-392, 389f-392f primary, 388, 392

Endodontic infections archaea, 231 characteristics of, 225b description of, 222 extraradicular, 234 fungi that cause, 231 microbiota associated with, 226-228, 227b,

228f, 230--232 pathogenesis of, 222-224 persistent, 225b persistent intraradicular, 225b, 232-234 primary intraradicular

characteristics of, 225b, 226 description of, 225-226 geographic influences, 228-229 microbiota associated with, 226-228, 227b, 228f,

230 routes of, 223f secondary intraradicular, 225b, 232-234 treatment of, 234--235, 406 types of, 225-234 viruses that cause, 231-232

Endodontic therapy microcirculatory system effects, 126 pain continuance after

description of, 173-174 local anesthetics for, 195-196 management strategies for, 199-200 nonsteroidal anti-inflammatory drugs for, 193-

194, 199-200 Endodontic-periodontal diseases

anatomical relationships, 373-375 contributing factors

avulsion, 386 coronal leakage, 384 crown fracture, 385 crown-root fracture, 385-386 developmental malformations, 387 enamel fracture, 385 luxation, 386 perforation, 386-387 poor endodontic treatment, 384 root fracture, 386, 390 trauma, 385-386

differential diagnosis of, 388-392 etiology of

bacteria, 377-378 Charcot-Leyden crystals, 383, 384f cholesterol crystals, 382, 382f foreign bodies, 380, 380f-381f fungi, 376f, 378 infectious biofilms, 379 live pathogens, 375-379 nonliving pathogens, 380--383 Rushton hyaline bodies, 383, 383f Russell bodies, 382f, 382-383 viruses, 379

overview of, 37 3 portals of exit, 374--375 prognosis for, 392-393

Endogenous opioid peptides, 164 Endothelin 1, 123, 243 Endothelin receptor A, 243 Endothelin receptor B, 243 Enterococcus faecalis, 233 Eosinophils, 283b Epidermal growth factor, 97t Episodic neuropathic pain, 458 Epithelial rests of Malassez, 380

495

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Index

Epitheliated granuloma, 380 Epstein-Barr virus, 231-232, 379, 473 Erupting teeth, 142 Er:YAG lasers, 362-36S Etch-and-rinse adhesives, 336 Etchants, 36 Etching. See Acid etching. Ethylenediaminetetraacetic acid, 36, 38, 103,

342, 361 Evaporative fluid flow, 3S2 Evolutionary theory, 422 Excimer lasers, 36S Excitatory amino acids, 162, 16S External root resorption. See Root resorption,

external. Extracellular matrix

basement membrane, 73 collagen. See Collagen . dentin, 9, 440 fibronectin, 73--74 growth factors in, 42 laser capture microdissection studies of, 9 odontoblast secretion modulated by, 33 plaque biofilm formation of, 207 tooth morphogenesis role of, 14--1 S

Extrusive luxation, 386

F Fabry disease, 484t Fenestrated capillary, 111 Fermentable carbohydrates, 213, 220 Fibrillar proteins, 67 Fibrinogen, 2S7, 3S4 Fibroblast(s)

connective tissue remodeling, 79 definition of, 78 functions of, 67 illustration of, 78f interleukin-1 effects, 264 mitotic activity of, 78 morphology of, 78 substance P effects, 70

Fibroblast growth factors, 10--11, 14, 97t Fibrodentin, 39 Fibronectin, 73f. 73-74 Fibronectin-binding protein, 333 Fluorescent antibody cell sorting, 96 Fluoride

caries prevention using, 221-222 dentinal sensitivity managed using, 189

Foreign bodies, 380, 380f-381f FOXP3+CD2S+ cells, 280 Fractures, 385--386 Free radicals, 423--424 Fungi, 231, 376f, 378 Fusobacterium species, 217

G G proteins, 14S Gap junctions, 7 6, 136f Gaucher disease, 482-484, 483f, 483t Gene regulation, 422 Genetic and developmental disorders

amelogenesis imperfecta, 477 dens in dente, 47Sf, 475-476 dentinogenesis imperfecta, 16, 17f, 476f, 47&--

477 Gaucher disease, 482-484, 483f, 483t hemoglobinopathies, 481-482 hypophosphatemic rickets, 479-481, 481f sickle cell anemia, 481-482, 482f taurodontism, 474, 47Sf thalassemia, 481, 482f

German measles, 473--47 4 Glass ionomers

conventional, 337, 337f description of, 312 resin-modified, 312, 338

Glia, 16S

496

Glial-derived neurotrophic factor, 137 Glossopharyngeal neuralgia, 4S9-460 G lucocorticoid excess, 48S-486 Glucocorticoids, 19S Glycosaminoglycans, 4, 67, 72 Golgi complex, 74--7S, 434 G-protein-coupled receptors, 14S Gram-negative bacteria, 227b Gram-positive bacteria, 227b Granulocyte colony-stimulating factor, 284 Granulocyte-macrophage colony-stimulating factor,

287 Growth factors

angiogenic, 36 definition of, 10, 77, 97 in dentin matrix, 36 function of, 97t insulin-like, 36 odontoblast-like cell differentiation induced

by, 42 orthodontic therapy effects, 127 regenerative medicine use of, 9&--98 types of, 97t

Growth-associated protein-43, 137 Guanethidine, 189-190 Gutta-percha, 3S&--3S8

H Hageman factor, 2S7 Hartwig's epithelial root sheath, 397 Hayflick phenomenon, 423 Headache

cluster, 4S7-4S8 migraine, 4SS-4S7

Healing bacteria effects on, 302-303 with cementum, 402 osseous replacement for, 402-403, 403f

Heat shock proteins, 33S, 432 Helper T cells, 79, 278, 280, 291-292 Hemoglobinopathies, 481-482 Hemorrhage control, 305--306 Hereditary opalescent dentin, 476 Herpes zoster, 460 Herpesvirus, 379, 472-473, 473f Heterotypic assays, Sf Histamine, 123, 242 Homeostatic regeneration, 91 Homotypic assays, Sf Horizontal gene transfer, 208 Hot stimuli, for pulpal vitality testing, 179 Human immunodeficiency virus, 286, 379, 471-

472 Humeral immunity, 281-282 Hydroxyapatite crystals

carbonated, 221 characteristics of, SO formation of, 29 nucleation of, 31

Hyperalgesia, 148 central mechanisms of, 171-173, 172b characteristics of, 169t, 169-170 definition of, 169 peripheral mechanisms of, 170b, 170--171

Hyperesthesia, 460 Hyperglycemia, 48S Hyperparathyroidism, 478-479 Hypersensitivity. See Dentinal sensitivity. Hypoesthesia, 460 Hypophosphatemic rickets, 479-481, 481f

Ibuprofen, 193-194 Immune responses

adaptive, 285--287 innate, 283-28S periapical, 277-282

Immunity, 277 lmmunocompetent cells

caries-induced response, 85--86 cavity preparation and restoration effects,

84--8S dendritic cells, 82--84 lymphocytes, 79--81 macrophages, 81--82

Immunodeficiencies description of, 283 innate responses, 283--28S specific responses, 285--287

lmmunoglobulins, 270, 281, 426 Indirect pulp capping, 317-319 Infection. See also Endodontic infections.

in childhood development, 473--474 cytochemical responses to, 139-14S in fetal development, 473--474 intraradicular. See lntraradicular infections. structural responses to, 139-14S

Inflammation dentinal sensitivity caused by, 178 heat-induced, 170--171 humeral immunity in, 281-282 management of, 403 mediators of. See Inflammatory mediators. microcirculatory system effects, 127-128 neuropeptides' role in, 243--247 prostaglandins' role in, 2S1 resident cells in, 282 response to, 16&--167 restorative materials and procedures that

cause, 343f root resorption induced by, 401-402

Inflammatory cyst, 381f Inflammatory mediators

arachidonic acid metabolites, 2S0--2S2, 2S4--2SS, 290--291

chemokines, 269 cytokines, 263--264, 26&--269. See alsoCytokines. defensins, 270 description of. 127-128, 241 drugs that block, 192-19S function of, 241 histamine, 123, 242 immunoglobulins, 270 maresins, 2SS microcirculatory system effects, 127-128 nerve functions affected by, 171-172 neuropeptides, 243--247, 3S4 nitric oxide, 261t, 261-262, 3SS nociceptors sensitized by, 160 nucleotide-binding oligomerization domains,

267-268 odontoblast production of, 242 oxygen-derived free radicals, 262-263 periapical, 287-293 plasma proteases

clotting system, 2S7-2S9 complement system, 2S&--2S7 fibrinolytic systems, 2S7-2S9 kinin system, 2S6 lysosomal enzymes, 260--261 matrix metalloproteinases, 260--261 protease inhibitors, 261

platelet-activating factor, 2S6 protectins, 2SS regulatory mechanisms, 168--169 resolvins, 2SS root resorption, 399 serotonin, 242-243

Inflammatory pain characteristics of, 16&--177 nonsteroidal anti-inflammatory drugs for,

193-- 194, 199-200 Injury-induced regeneration, 91 Innate immunity

adaptive immunity and, transition between, 329

deficiencies in, 283-28S description of, 277

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toll-like receptors, 266--267 Innervation

agents involved in, 138t axonal transport, 134, 135f developing teeth, 142 erupting teeth, 142 neuropeptide-rich fibers, 134 overview of, 133-137 parasympathetic, 138 peptidergic, 143-145 primary teeth, 142 pulpal, 141, 1411 sensory neurons, 134f, 134-135, 434 sympathetic, 138

lntegrins, 77, 250, 397 lntercellular cell adhesion molecules, 248, 250 lnterleukin-1, 264, 289 Interleukin- la, 288 lnterleukin-1 f3, 287-289 lnterleukin-2, 268 lnterleukin-6, 268-269, 287-288, 399 lnterleukin-8, 287 lnterleukin-11, 288, 399-400 Internal root resorption. See Root resorption, internal. lnterneurons, 162-163 Interstitial pressure

microvascular exchange effects on, 114-116 pulpal, 115--116

Interstitial space, 114 lntertubular dentin, 32, 49, 440 lntracanal irrigants, 100, 235 lntracoronal bleaching, 410 lntraligamentary injections, of local anesthetics,

198 lntraluminal collagen, 511 lntraradicular infections

persistent, 225b, 232-234 primary

characteristics of, 225b, 226 description of, 225--226 geographic influences, 228-229 microbiota associated with, 226-228, 227b,

228f, 230 secondary,225b,232-234

lntratubular dentin, 49, 440 Ion channels, 145--147 Irreversible pulpitis, 450-451 lrrigants, 100, 235

J Junctional epithelium, 134-135

K Kallikrein, 123 Kinin system, 256 Kininogens, 256 Knockout mice, for tooth development studies,

7-8, 12 Korff fibers, 68, 71, 73

L Lactobacilli, 214 Lamina phase, of tooth development, 2, 3f Laser(s)

argon, 359 co,, 361-362 dentinal injury caused by, 361-362 dentinal sensitivity treated with, 365--367 description of, 358-359 Er:YAG, 362-365 excimer, 365 Nd:YAG, 359, 365--366 pulpal responses, 359-361 root canal use, 361 ruby, 361 schematic diagram of, 359f soft tissue uses of, 367 tooth bleaching use of, 367

types of, 358-359 wavelengths of, 359f

Laser capture microdissection, 9 Laser Doppler flowmetry, 127-128 Lateral luxation, 386 Lateral periodontitis, 406 Leukemia, 487f Leukocyte adhesion

chemotactic factors involved in, 250 margination, 247 molecules involved in, 247-248, 250

Leukocyte adhesion deficiency-1, 250, 283 Leukocyte adhesion deficiency-2, 248, 283 Leukotrienes

B., 311 description of, 252

L-form bacteria, 378 Lidocaine, 196-197 Linear coefficient of thermal expansion, 350--351 Lipopolysaccharides, 217, 267, 281 Lipoteichoic acid, 264, 269, 282, 329 Lipoxins, 252, 254-255, 255 Lipoxygenase, 252, 254-255 Local anesthetics

circulatory effects, 124-125 intraligamentary injections of, 198 intraosseous administration of, 197-198 pain block using, 450 pain localization using, 177 pain management using, 195--198 speed of injection, 197

Lowe syndrome, 484t Luxation, 386 Lymphatic vessels, 112-114 Lymphocytes. See B cells; T cells. Lysosomal enzymes, 260--261

M Macrophages, 811, 81-82, 287-288 Magnetic resonance imaging, 104 Major histocompatibility complex molecules, 80--

84, 83f, 269-270, 354 Mantle dentin, 31, 48, 53t Maresins, 255 Margination, 247 Masseter muscle, 454f Maternal rubella, 473-474 Matrix metalloproteinases

aging effects on, 425 collagen degradation by, 339 definition of, 30, 326 dentin remodeling, 261 extracellular matrix degradation caused by, 261 inhibitors of, 339-340 odontoblast expression by, 30 odontoblast synthesis of, 76-77 source of, 326 tooth morphogenesis role of, 15

Mechanoreceptors, 135 Medial pterygoid muscle, 454f Medullary dorsal horn, 160f, 162 Membrane attack complex, 256 Membrane receptors, 145--147 Mesenchymal cells, undifferentiated, 68, 79 Mesenchyme, dental

enamel knot formation regulated by, 14 molecules that affect, 10

Metarterioles, 110 Microarrays, 22, 22f Microbiota

definition of, 226 diversity of, 226 ecology of, 230--231 in endodontically treated teeth, 233-234 primary intraradicular infections caused by,

226-228, 227b, 228f, 230 Microcirculatory system, of pulp. See also Pulpal

blood flow. arterioles, 109-110, 1101, 1211, 127f

capillaries, 110--111 description of, 109 diagnostic uses of, 128 endodontic therapy effects, 126 inflammatory mediators effect, 127-128 local anesthetics effect, 124-125 lymphatic vessels, 112-114 microcirculation, 114-115 orthodontic therapy effects, 126-127 orthognathic surgery effects, 127 restorative procedures effect, 125--126 schematic diagram of, 11 Of transcapillary exchange, 114-115 venules, 111

Microcomputed tomography, 431 Microsurgery, 437f Migraine, 455-457

Index

Mineral trioxide aggregate, 307, 313-315, 315f Mitochondrial DNA, 423 Mitochondrial respiratory system, 423 Moire interferometry, 350 Monocytes, 283b Multiple sclerosis, 465 Mutans streptococci, 213-214 Myelin, 146, 146f Myofascial pain, 452-454

N Naloxone, 164-165 Natural killer T cells, 280 Nd:YAG laser, 359, 365--366 Nerve degeneration, 147 Nerve fibers

Af3, 136-137 activation of, 1511 A8, 137 antigen-presenting cells and, 270 chemical signaling, 138 cytochemical features of, 137 immunochemistry of, 140f inflammation effects, 171-172 odontoblasts and, 177 patterns of, 140f pulpal interactions with, 139 sprouting of, 141, 171, 243 types of, 136-137

Nerve growth factor, 97t, 136-137, 434 Neuritic pain, 460-461 Neurokinin A, 143, 243 Neurons, 164 Neuropathic pain

continuous, 460-462 definition of, 458 description of, 174-175, 175f episodic, 458

Neuropeptide Y, 119, 1201, 143, 243, 245--246, 354 Neuropeptides, 122f, 143, 243-247, 354, 434 Neuropulpal interactions

agents involved in, 138b schematic diagram of, 134f

Neutrophils, 262, 283b Niches, 93 Nitric oxide, 261t, 261-262, 355 Nociceptors

central sensitization activated by, 172 drugs that block release or actions of inflammatory

mediators, 192-195 interneurons effect, 163, 163f neurophysiology of, 147-153 sensitization of, 170 signal transmission pathways, 160--166

Nodes of Ranvier, 146 Noncollagenous proteins, 18, 18t Nonodontogenic pain

atypical odontalgia, 461-462 cardiac origin of, 462-463 causes of, 451-453 clinical features of, 452b cluster headache, 457-458

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Index

deafferentation origin of, 461-462 glossopharyngeal neuralgia, 459-460 migraine, 455-457 myofascial pain, 452-454 psychogenic origin, 463--464 systemic disorders that cause, 464-465 trigeminal autonomic cephalgia, 457-458 trigeminal neuralgia, 458-459 zoster, 473

Nonspecific plaque hypothesis, 212 Nonsteroidal anti-inflammatory drugs, 193-194,

199-200 Notch signaling, 41, 310, 432 Nucleotide-binding oligomerization domains,

267-268 Nucleus caudalis, 162-164 Nursing caries, 215

0 Occlusal adjustment, for pain management, 191 Occlusal caries, 216t, 307f, 330f, 332f Oculocerebrorenal syndrome, 484t Odontalgia

atypical, 461-462 diagnosis of, 190-191 incidence of, 185, 447

Odontoblast age-related changes in, 426, 429-430 calcium transport system, 30 cavity preparation effects on, 341 cell body of, 74-75 characteristics of, 68 collagen synthesis, 29 cultures for studying, 6, 9 death of, 43 definition of, 4, 47, 76 differentiation of

bone morphogenetic proteins, 355 collagen fibers in, 71 core-binding factor a 1 's role in, 12, 14 fibronectin effects, 73 morphologic changes, 15-16 signaling interactions that influence, 10-15 steps involved in, 15 studies of, 9 terminal events in, 16f, 73

fibronectin effects on, 73 functions of, 76-78, 138, 355 glycosaminoglycans effect, 72 Golgi complex, 74-75 illustration of, 6f, 48f inflammatory mediators produced by, 242 injury response of, 77-78 innate immunity functions of, 77 integrins secreted by, 77 junctions of, 75-76, 136f life cycle of, 399f matrix metalloproteinase synthesis by, 76-77 mitochondria of, 75 morphology of, 15-16, 28, 68, 430 nerve fibers and, 177 osteoclast vs, 400 phenotype of, 28--29 predentin secretion by, 16f progenitor cells for, 40-41 pulp and, relationship between, 28--29 restorative materials effect on, 341-342 secondary, 78 secretory behavior of, 29f, 29-31, 33, 76-77 sensory fibers and, interactions between, 138 structure of, 74-76 synthesis functions of, 76-77 toll-like receptor 4, 102 tooth sensation role of, 138 type I collagen in, 17f ultrastructural appearance of, 28f

Odontoblast layer characteristics of, 68--69

498

definition of, 111 illustration of, 68f

Odontoblast process, 47, 75, 75f, 440 Odontoblastoid cells, 96 Odontocytes, 431 Odontogenesis. See Tooth development. Odontogenic pain, 191-199, 447, 451b. See also

Pain. Odontogenic toothache, 449b, 450f, 451 Oligonucleotide arrays, 22 Opioids, 196 Opsonization, 270 Orthodontics, 126-127 Orthognathic surgery, 126-127 Osseous replacement, 402-403, 403f Osteitis deform ans. See Paget disease of bone. Osteocalcin, 18t Osteoclast(s), 477

calcified tissue resorption by, 400 extracellular protein binding, 397 mediators that affect functioning of, 399 odontoblast vs, 400

Osteoclast-activating factor, 288 Osteoclastic diseases, 477-478 Osteoimmunology, 400 Osteonectin, 18t, 74 Osteopontin, 18, 18t, 21, 211, 401 Osteoprotegerin, 398, 477-478 Oxidative stress, 423--424 Oxygen-derived free radicals, 262-263

p Paget disease of bone, 415, 478-479, 4791 Pain

classification systems for, 452 diagnostic approach, 190-191, 465 dysfunctional, 175 endogenous analgesic system activated by,

165 incidence of, 159, 185 inflammatory. See Inflammatory pain. local anesthetic blocking of, 450 myofascial, 452-454 neuritic, 460-461 neuropathic

continuous, 460-462 definition of, 458 description of, 174-175, 175f episodic, 458

nonodontogenic. See Nonodontogenic pain. nonpharmacologic treatment of, 191-192 odontogenic, 191-199, 447, 451b perception of

drugs that block, 198--199 mechanisms, 159-160, 164-166

postendodontic therapy, 173-174 prostaglandins' role in, 251-252 pulpal vitality testing to diagnosis, 178--180 referred, 176-177, 447-448, 448f-4491 site of, 449-451 source of, 449-451 transmission of

drugs that block, 195-198 physiologic mechanisms, 160-166

treatment of corticosteroids, 195 cyclo-oxygenase inhibitors, 194 glucocorticoids, 195 nonpharmacologic, 191-192 nonsteroidal anti-inflammatory drugs, 193-

194, 199-200 pharmacologic, 192-199 strategies for, 199-200

Papillon-Lefevre syndrome, 484t Parasympathetic nerves

pulpal blood flow regulated by, 120-121 tooth innervation by, 138

Peptidergic innervation, 143-145 Peptidoglycans, 264

Periapical bone loss, 288--289 Periapical immune responses, 277-282 Periapical inflammation

humeral immunity in, 281-282 mediators of, 287-293 resident cells in, 282

Periapical lesions chronic, 281 definition of, 277 description of, 281 illustration of, 376f, 380f, 384f immune cells in, 278--281

Periapical replacement resorption, 404 Periluminal dentin, 49 Periodontal disease

endodontic disease and, 389-392, 3891-392f. See also Endodontic-periodontal diseases.

primary, 388, 3891-390f, 393 Periodontal ligament-derived stem cells, 7, 7f Periodontitis

apical. See Apical periodontitis. lateral, 406 progressive, 390

Peritubular dentin, 32, 32f, 48, 52, 440 Permeability

capillary, 127 dentin. See Dentin, permeability.

Phospholipids, 2511 Pink tooth, 412 Plaque

accumulation of, 206f acid production by, 214 beneficial bacteria in, 214 biofilm. See Biofilm, plaque. definition of, 206 developmental stages of, 209-210 mechanical removal of, 220

Plasma cells, 283b Plasma exudate, 305-306 Plasma proteases

clotting system, 257-259 complement system, 256-257 fibrinolytic systems, 257-259 kinin system, 256 lysosomal enzymes, 260-261 matrix metalloproteinases, 260-261 protease inhibitors, 261

Plasticity embryonic stem cells, 93 trigeminal ganglion, 140-141

Platelet-activating factor, 256 Platelet-derived growth factor, 97t Platelet-endothelial cell adhesion molecule, 248 Polymerization shrinkage, 338--339, 341 Polymorphonuclear neutrophils, 278--279, 285 Porcine enamel matrix, 316 Porphyromonas species, 217 Postherpetic neuralgia, 473 Postnatal stem cells, 93-94, 98 Potassium-containing dentrifices, 188t, 188--189 Predentin, 16f, 47-48, 48f, 71-72, 411-412, 433,

486f Prekallikrein, 256 Pressure resorption, 403--404 Pre-trigeminal neuralgia, 458 Prevotella species, 217 Primary caries, 212 Primary dentinogenesis, 31-33, 430 Primary endodontic disease, 388, 392 Primary hyperparathyroidism, 478-479 Primary oxalosis type I, 484t Primary periodontal disease, 388, 3891-390!, 393 Primary teeth, 142 Progenitor cells

chemoattractants, 41 definition of, 92 dental follicle, 95 description of, 310 mesenchymal cells, 40

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regenerative medicine use of, 92-95 in reparative dentinogenesis, 40--41

Progressive periodontitis, 390 Proinflammatory cytokines, 264-268, 265f, 287-289,

291-293 Projection neurons, 163-164 Prostaglandins

description of, 123, 168, 251-252, 290 E2, 282

Prosthetic procedures, 125--126 Protease inhibitors, 15, 261 Protectins, 255 Protein kinases, 164 Proteoglycans

bacterial penetration prevented by, 73 definition of, 67 in extracellular matrix, 18t hydrophilicity of, 72 structure of, 72

Proteolytic bacteria, 377 Pulp

adhesion molecules in, 247-248, 250 age-related changes in, 425--442 biology of, 21-22 blood vessels of, 432-434 caries-induced exposure of, 224, 224f cellular arrangement of, 68f, 68--69 circulatory system of. See Microcirculatory system. clonal lines for studying, 6 collagen types in, 70-71 coronal, 711, 429f crown fracture involving, 385 dendritic cells of, 82-84 dentin bonding effects on, 340-341 edema of. 305 elasticity of, 71 exposure of, 302f, 303-305 features of, 68--69 innervation of, 141, 1411 low-compliance environment of, 69 mineralization of, 437 necrosis of, 404-405 nerve fibers of. See Nerve fibers. odontoblasts of. See Odontoblast. radicular, 429f recession of, 33 responses of, 277-278 revascularization of. 407 root resorption role of. 401-402 sensory innervation of. 70 size reductions in, 438 structural organization of, 68--69 sympathetic nervous system innervation of, 118 testing responses of, for aging evaluations,

436-437 tissue engineering of, 103 vascular responses of, 242 vasculature of. See Microcirculatory system. vitality of. See Vital pulp.

Pulp capping adhesive systems for, 312-313 in aging tissue, 441-442 dentin bridge formation as indication of, 43 dentinal bridge effects on, 306-307 direct, 340 exposure duration effects on, 303 hemorrhage control before, 305--306 indirect, 317-319 materials for

calcium hydroxide. See Calcium hydroxide. dentin adhesives, 312-313 description of, 305--306, 311 experimental bioactive molecule-containing

materials, 315--317 glass ionomers, 312 mineral trioxide aggregate, 313-315, 315f zinc oxide-eugenol, 318

microbial leakage effects on, 310

Pulp core, 69 Pulp proper, 69 Pulp space infection

description of, 404 external root resorption caused by, 404-408 prevention of. 407 treatment of, 407-408

Pulp stem cells description of, 95--96 pulp constructs created from, 98-100, 99f, 102t smear layer attachment of, 102, 103f

Pulp stones, 437-438 Pulpal blood flow

bacterial effects, 127-128 calculation of, 114 dentin grinding effects on, 125f histamine effects, 242 inflammatory mediators effect, 69 measurement of, 116-117 neuropeptides' effect on, 122f prosthetic procedures' effect on, 125--126 regulatory mechanisms of

a-adrenergic receptors, 118f endocrine factors, 123 metabolism, 117-118 neuronal, 118-123 neurotransmitters, 122 paracrine factors, 123 parasympathetic nerves, 120-121 peptidergic afferent fibers, 121-123 schematic diagram of, 115f, 117f sympathetic nerves, 118-120 trigeminal sensory nerves, 126

restorative procedures' effect on, 125-126 sensory nerve denervation effects on, 1211 stimulation of, 61

Pulpal infection. See also Endodontic infections. caries. See Caries. protective immunity against, 282-287

Pulpal injury. See also Tooth injury. cavity preparation as cause of, 334-335 description of, 77-78 healing after, 302-303 microleakage, 343 pulp capping for. See Pulp capping. reasons for, 301 root resorption caused by, 402-403 signaling molecules contributing to, 43f

Pulpal interstitial pressure, 115--116 Pulpal nerves

degeneration of, 147 sensory functions of, 148-150, 152-153

Pulpitis immune cells in, 277-278 management of, 190-199 opioids for, 198 pain caused by, 147, 190-199 silent, 147

Pulpodentin complex. See also Dentin; Pulp. age-related changes in, 427, 440--442 caries

defense responses to, 329-331, 330f-3311 description of. 325 injury responses to, 328-329 responses to, 328-333

characteristics of, 69-70, 223 defense responses by, 329-331, 330f-3311 definition of, 1 functions of, 91 injury response

to caries, 328-329 cavity preparation, 334 description of, 77-78 neuroanatomical responses, 141 signaling molecules contributing to, 43f stimuli that cause, 139 summary of, 344-345

permeability of, 324-325

repair capacity of, 334 structure of, 47-48, 48f, 324-325

Pulse oximetry, 128

Q Ouorum sensing, 208-209

R Radiographs

aging, 441 apical periodontitis, 206f caries, 218, 218f

Index

external root resorption, 413, 414f, 415 internal root resorption, 412-413, 412f, 415

Raman spectroscopy, 431 RANKL, 282, 398, 401, 477-478 Reactionary dentin

cavity etching stimulation of, 38 cellular signaling of, 38 definition of, 34, 78 deposition areas for, 334 ethylenediaminetetraacetic acid effects, 38 production of, 333 remaining dentinal thickness effects, 37-38 restorative materials' effect on formation of, 342-

343 Reactionary dentinogenesis

biologic processes, 35f-36f, 35--37 definition of, 35, 331, 333 factors that affect, 37-38 histomorphometric findings, 37-38 odontoblast upregulation during, 35--37 restorative materials that cause, 35--36

Reactive oxygen species, 423 Receptor activator of nuclear factor Kf3 ligand. See

RAN KL. Recombinant human bone morphogenetic proteins,

91, 310 Recombinant human insulin-like growth factor 1,

97-98 Recurrent caries, 211-212, 218-219 Referred pain, 176-177, 447-448, 448f-449f Regeneration

definition of, 92 history of, 91 homeostatic, 91 injury-induced, 91

Regenerative endodontics challenges associated with, 104b delivery improvements for, 103-104 dental pulp constructs for, 98-100, 99f, 102t objectives of, 92 outcome measurements, 104 postnatal stem cells for, 98-99, 99f, 102t research priorities for, 102-104 root canal revascularization using blood clotting,

100-101, 102t Regenerative medicine

foundations of, 92-98 growth factors, 96-98 history of, 91 progenitor cells, 92-95 stem cells. See Stem cells.

Regulatory T cells, 278, 280, 291 Remaining caries, 212 Remaining dentinal thickness, 37-38, 325, 334-335,

355 Remineralization

description of, 212 fluoride effects on, 222

Renal dystrophy, 415 Reparative dentin, 34, 78, 308 Reparative dentinogenesis

biologic processes during, 35f collagen fibrils in, 72 definition of, 333 dentin bridge formation vs, 43 description of, 38 fibrodentin matrix secreted before, 39

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Index

histologic findings, 39f matrices secreted during, 38, 39f-40f odontoblast-like cell differentiation, 41-43 progenitor cell recruitment in, 40--41 tertiary dentinogenesis and, 39

Reparative tertiary dentinogenesis, 316 Replicative senescence, 423 Resident cells, 282 Resin-based materials, 335-337, 336f-337f Resin-modified glass ionomers, 312, 338 Resolvins, 255 Restorative dentistry, 323 Restorative materials and procedures

bacterial microleakage, 303, 343 calcium hydroxide . See Calcium hydroxide. dentin permeability effects, 61-62 inflammation caused by, 343f microcirculatory effect, 125-126 mineral trioxide aggregate, 313--315, 31 Sf odontoblast survival affected by, 341-342 physical properties of, 349-351 reactionary dentin formation affected by, 342-

343 specific heat of, 349-350 tertiary dentinogenesis effects, 35-36 thermal conductivity of, 349 thermal diffusivity of, 350 tooth-colored, 344 toxicity of, 303 zinc oxide-eugenol, 318

Revascularization of root canals using blood clotting, 100-101, 102t

Reverse transcriptase-polymerase chain react­ion, 9f

Rickets hypophosphatemic, 479-481, 4811 vitamin D-dependent, 479-480

Root canals accessory, 37 4 disinfection of, 102 filling stage of, bacteria present at, 232-233 infections of. See Endodontic infections. laser therapy of, 361 lateral, 374 pulp stem cell attachment to, 103f revascularization of, using blood clotting,

100-101, 102t sodium hypochlorite-irrigated, 57f

Root caries, 211, 216t Root dentin

impermeability of, 58 mechanics of, 53--54 permeability of, 56f, 56-60

Root fracture, 386, 390 Root perforation, 386--387 Root resorption

cervical, 408 external

apical periodontitis and, 404-405 description of, 402 diagnostic features of, 413, 414b, 415 diffuse injury, 402-403 lateral periodontitis with, 406 localized injury, 402 pressure-induced, 403-404 pulp space infection, 404-408 radiographic findings, 413, 414f, 415 sulcular infection, 408-410 vitality testing, 415

histologic appearance of, 399f inflammation-induced, 401-402 inflammatory mediators involved in, 399 internal

characteristics of, 411 clinical manifestations of, 412 description of, 411 diagnostic features of, 413, 414b, 415 etiology of, 4111, 411-412 histologic appearance of, 411 f, 412

500

pink tooth, 412, 415 radiographic findings, 412-413, 412f, 415 treatment of, 412-413 vitality testing, 415

mechanisms of, 397-401 misdiagnoses, 415 Paget disease of bone and, 415. See a/so

Paget disease of bone. pulpal role in, 401-402 renal dystrophy and, 415 requirements for, 401 resistance to, 397-398 subepithelial inflammatory, 408-410, 415 systemic causes of, 415-416

Rubella, 473-474, 474f Ruby lasers, 361 Ruffini mechanoreceptors, 135 Rushton hyaline bodies, 383, 383f Russell bodies, 382f, 382-383

s Saliva, 218, 220, 222 Scaffolds,99-100, 102 Sclerotic dentin

description of, 327 illustration of, 32f permeability of, 56

Secondary caries, 211 Secondary dentin, 27, 33--34, 48-49, 78, 430, 433,

439,440 Selectins, 248 Self-etching adhesives, 336 Senescence,421-423 Sensitivity. See Dentinal sensitivity. Sensory fibers

injury responses of, 139 odontoblast and, interactions between, 138

Sensory neurons, 134f, 134-135, 434 Serotonin, 242-243 Severe combined immunodeficiency, 285-286 Shingles, 473 Sickle cell anemia, 464, 481-482, 482f Silent pulpitis, 147 Single-bottle adhesive systems, 336 Sinus headache, 454 Sinusitis, 455, 460 Small integrin-binding ligand, N-linked glyco­

protein family, 18 Smear layers

creation of, 57, 335 description of, 57 illustration of, 58f permeability effects, 58 pulp stem cell attachment to, 102, 103f removal of, 103, 341 treatment of, 58

Smear plugs, 57 Smooth surface caries, 216t Sodium channels, 146 Sodium hypochlorite, 235 Somatoform pain disorder, 464 Specific plaque hypothesis, 212 Spirochetes, 378 Starling forces, 114-115, 116 Stellate reticulum, 4 Stem cells, 41

advantages of, 94-95 allogeneic, 95 from apical papilla, 95 autologous, 94-95, 104 definition of, 92 developmental stages of, 94f differentiation of, 7 embryonic, 93--94 from human exfoliated deciduous teeth, 7,

7f, 95 isolation and identification of, 96 niches of, 93 osteogenic induction of, 7f

overview of, 91-92 periodontal ligament-derived, 7, 7f postnatal, 93--94, 98 "-

protein expression by, 96 pulp. See Pulp stem cells. source-based classification of, 94 tooth-derived, 6-7, 7f umbilical cord, 94 xenogeneic, 95

Sternocleidomastoid muscle, 454f Stratum intermedium, 4 Streptococcus mutans, 214 Subepithelial inflammatory root resorption,

408-410,415 Subluxation, 386 Substance P, 70, 121-123, 243--247, 334 Sulcular infection, 408-410 Suppressor T cells, 291 Sympathetic nerves

pulpal blood flow regulated by, 118-120 tooth innervation by, 119f, 138

Systemic disorders

T

herpesvirus infections, 472-473, 473f human immunodeficiency virus, 471-472 nonodontogenic pain caused by, 464-465 Paget disease, 478-479, 479f rubella, 473-474, 474f

T cells, 283b caries-induced response, 85-86 CD4+, 279 CDS+, 279 cytotoxic, 278 description of, 79-80 helper, 278, 280, 291 illustration of, 80f mechanism of activation, 80 natural killer, 280 regulatory, 278, 280, 291 suppressor, 291

Taurodontism, 474, 475b, 475f Telomeres, 423-425, 431 Temporalis muscle, 454f Temporomandibular dysfunction, 453-454 Terminal arteriole, 110 Terminal capillary network, 68 Tertiary dentin, 27, 34-35, 49, 49f, 78, 317, 324 Tertiary dentinogenesis

cavity preparation materials that affect, 35-36

description of, 34-35 reparative, 316 transforming growth factor-fl1 's role in, 36

T halassemia, 481, 482f T hermal allodynia, 449 T hermal stimuli

cavity preparation, 349-353 laser treatment, 358-366

Thromboxanes, 251-252 Tight-junction capillary, 111 Tissue development stages, 94f T issue engineering

definition of, 92 pulp, 103 scaffolds for, 99-100

Toll-like receptors, 77, 102, 266f-267f, 266-267, 282, 287-288, 329

Tooth bleaching, 367 Tooth development

description of, 1-2 enamel knots, 14 epithelial-mesenchymalsignalinginteractions

during, 10f experimental systems for

description of, 4 knockout mice, 7-8 laser capture microdissection, 9 tooth organ culture systems, 4-6, Sf

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transgenic mice, 7--8 general features of, 2 stages of, 2-4, 3f

Tooth injury. See also Pulpal injury. axonal degeneration secondary to, 147 classification of, 139 cytochemical responses to, 139-145 delayed neural reactions to, 141 human teeth studies of, 141-142 ion channels, 145--147 membrane receptors, 145--147 stimuli that cause, 139 structural responses to, 139-145 trigeminal nerve and ganglion plasticity, 140-141

Tooth organ culture systems, 4--6, Sf Toothache, odontogenic, 449b, 450f, 451 Tooth-colored restorative materials, 344 Tooth-derived stem cell lines, 6--7, 7f Tooth-signaling molecules, 1 Transcapillary exchange, 114-115 Transcription factors

core-binding factor a 1, 12, 13f definition of, 10 function of, 10

Transdentinal permeability, SSf Transforming growth factor-a, 97t Transforming growth factor-fl, 97t Transforming growth factor-[l 1, 430

chemotactic role of, 41 etchants that solubilize, 36 inflammatory role of, 269 odontoblast secretion, 33 odontoblast-like cell differentiation induced by,

41-42, 42f production of, 293 reactionary dentinogenesis role of, 36 receptors, 38

transgenic mice studies of, 8 Transgenic mice

development of, 7-8 tooth development studies using, 7f, 7--8

Transient receptor potential ion channels, 145 Transient receptor potential vanilloid 1, 462 Transmigration, 248 Transmitted-light photoplethysmography, 128 Trauma

dentin exposure caused by, 224 endodontic-periodontal diseases secondary to,

385--386 Trephination, 191-192 Treponema species, 378 Trigeminal autonomic cephalgia, 457-458 Trigeminal ganglion

dental nerve cell bodies, 137f plasticity of, 140-141

Trigeminal neuralgia, 458-459 Trigeminal sensory neurons, 162 Trigeminovascular system, 455 Trigger points, 452 True combined endodontic-periodontal disease,

391f-392f, 391-392 Tubular sclerosis, 219 Tumor necrosis factor, 264, 284 Tunnel defects, 43

u Ultrasound, 333 Umbilical cord stem cells, 94 Undifferentiated mesenchymal cells, 68, 79

v Vascular cell adhesion molecule, 248 Vascular endothelial growth factor, 329 Vasoactive intestinal peptide, 120-121, 143, 243

Vasoactive neuropeptides, 329 Vasoconstrictors, 124 Veil/one/la species, 214 Venular network, 111 Venules, 111 Viruses, 231-232, 379 Vital pulp

Index

external root resorption prevented by main­tenance of, 407

testing of description of, 178-180 root resorption diagnosis, 415

Vital pulp therapy. See also Pulp capping. dentin adhesives for, 312-313 dentinal bridge effects, 306-307 description of, 301 mineral trioxide aggregate for, 313-315, 31 Sf resin-modified glass ionomers for, 312

Vitamin D metabolism disorders, 479-481 Vitamin D-dependent rickets, 479-480 Voltage-gated ion channels, 145

w Wide dynamic range projection neurons, 164

x Xenogeneic stem cells, 95 X-linked hypophosphatemic rickets, 479-481, 4811

z Zinc oxide-eugenol, 318 Zone of destruction, 216, 217f Zone of Hohl, 96 Zone of Weil, 68, 113 Zoster, 473, 473f

501

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