Osteomyelitis of the mandible in a patient with osteopetrosis

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in text, please cite in text or delete from list.: [CR37 CR42 CR43 CR44 CR45 CR46 CR47 CR48 CR49 CR50 CR51 CR52 CR53] {CR37} [37.] DO Lawoyin, JO Daramola, HA Ajagbe, (1988) {CR42} [42.] JJ Blum, M Hines, (1979) {CR43} [43.] F Suga, JR Lindsay, (1976) {CR44} [44.] CM Milroy, L Michaels, (1990) {CR45} [45.] MD Jones, ND Mulcahy, (1968) {CR46} [46.] M Hawke, AF Jahn, D Bailey, (1981) {CR47} [47.] EN Myers, S Stool, (1969) {CR48} [48.] H Hamersma, (1970) {CR49} [49.] CT Yarington Jr, PM Sprinkle, (1967) {CR50} [50.] ML Wong, TJ Balkany, J Reeves, BW Jafek, (1978) {CR51} [51.] A Baxter, (1971) {CR52} [52.] KO Paulose, S Al Khalifa, PK Shenoy, S Harris, RK Sharma, (1988)

Journal: 12663 Article: 196

{CR53} [53.] K Bjorvatn, O Gilhuus-Moe, D Aarskog, (1979)

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CASE REPORT1

2 Osteomyelitis of the Mandible in a Patient with Osteopetrosis.3 Case Report and Review of the Literature

4 Carlos Moreno Garcıa • Marıa Asuncion Pons Garcıa •

5 Raul Gonzalez Garcıa • Florencio Monje Gil

6 Received: 6 December 2009 / Accepted: 3 March 20117 ! Association of Oral and Maxillofacial Surgeons of India 2011

8 Abstract Osteopetrosis is a rare hereditary bone disorder

9 presenting with variable clinical features and is character-

10 ized by an increase in bone density and reduction of mar-

11 row spaces that result from a defect in the function of

12 osteoclasts and, consequently, a decrease in bone turnover.

13 This disease is generally divided into three types: severe

14 infantile malignant autosomal recessive, intermediate mild

15 autosomal recessive, and benign autosomal dominant. The

16 prognosis of the first two types is very poor and is char-

17 acterized by an early onset, usually within the first decade

18 of life, and early death. The benign-type is characterized by

19 a later onset and a longer life span. Ten percent of osteo-

20 petrosis cases develop osteomyelitis that usually involves

21 the mandible. The osteomyelitis is generally caused by

22 tooth extraction or pulpal necrosis. The leading cause of

23 the increased rate of infection is thought to be a lack of

24 adequate bone vasculature. Treatment of osteomyelitis

25 secondary to osteopetrosis is controversial. Treatment

26 regimens include high-dose systemic antibiotics coupled

27 with thorough debridement of necrotic bone and primary

28 closure of soft tissues, if possible. Hyperbaric oxygen has

29 been used for the treatment of chronic osteomyelitis.

30

31Introduction

32Osteopetrosis, also known as Albers-Schonberg disease,

33osteopetrosis generalisata [1] and marble bone disease

34[2, 3] was first described in 1904 by the German radiologist

35Albers-Schonberg [1, 4–6] as a bone disease with an

36increase in cortical bone mass at the expense of the med-

37ullary bone. In 1926, Karshner [7] introduced the term

38osteopetrosis to describe this disease [8]. It is a rare

39hereditary bone disorder [1, 6] presenting with variable

40clinical features and is characterized by an increase in bone

41density and reduction of marrow spaces that result from a

42defect in the function of osteoclasts [1, 4], and conse-

43quently, a decrease in bone turnover [6, 9]. It has been

44shown that the normal amount of osteoclasts are present,

45but that the cells are inactive or incompetent [8, 10].

46The disease represents a spectrum of clinical variants

47due to the heterogeneity of genetic defects resulting in

48osteoclast dysfunction. Classic osteopetrosis occurs in two

49varieties described as malignant and benign diseases [11].

50Malignant osteopetrosis is transmitted as a mendelian-

51recessive trait and is diagnosed at birth or during early

52childhood. They had a generalized increase in bone density

53and myelofibrosis suffering from hepatosplenomegaly,

54anemia, thrombocytopenia, and neurologic manifestations

55like optic atrophy [12]. They usually die during the first

56years of age because of anemia or secondary infection [13].

57At the moment, allogenic hemopoietic stem cell trans-

58plantation is the only curative treatment of autosomal

59recessive osteopetrosis and should be offered as early as

60possible [12, 14].

61The benign variety of osteopetrosis is transmitted as a

62mendelian-dominant trait, develops later, and is diagnosed

63at third or fourth decade of life by means of a routine

64roentgenograms. There are two forms differentiated by

A1 C. M. Garcıa (&) ! R. G. Garcıa ! F. M. GilA2 Department of Oral and Maxillofacial Surgery-Head and NeckA3 Surgery, University Hospital Infanta Cristina, Badajoz, SpainA4 e-mail: [email protected]

A5 M. A. P. GarcıaA6 Department of Neurology, University Hospital Infanta Cristina,A7 Badajoz, Spain

123Journal : Large 12663 Dispatch : 10-3-2011 Pages : 6

Article No. : 196h LE h TYPESET

MS Code : MAOS-D-10-00003 h CP h DISK4 4

J. Maxillofac. Oral Surg.

DOI 10.1007/s12663-011-0196-y

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65 clinical and radiological signs. Autosomal dominant oste-

66 opetrosis (ADO) type I is characterized by a pronounced

67 and symmetrical osteosclerosis of the skull and an enlarged

68 thickness of the cranial vault [15]. Clinically, ADO type I

69 is the only type of osteopetrosis not associated with

70 increased fracture rate [16, 17]. Less sclerosis of the skull

71 was found in type II (Albers-Schoberg disease) and it was

72 more pronounced in the base. Clinical manifestations of

73 ADO type II are dominated by long-bone fractures, which

74 occur, with or without trauma, in 78% of the patients [18].

75 Other classic manifestations of ADO type II include hip

76 osteoarthritis, facial nerve palsy, and mandibular osteo-

77 myelitis [2, 12, 18].

78 An intermediate type described by Beighton et al. [19] is

79 more prevalent in practice. Tips and Lynch [20] reported

80 no racial or sexual predisposition. Malfunction of osteo-

81 clastic activity results in excessive formation of immature

82 bone, thickening of the cortical bones, and narrowing or

83 obliteration of the medullary cavities. It is believed that

84 osteoclasts fail to release the necessary lysosomal enzymes

85 for bone resorption into the extracellular space [21, 22].

86 Defects in different genes have been described that lead to

87 a phenotype with osteopetrosis. These defects include

88 mutations in the gene encoding carbonic anhydrase II, the

89 proton pump gene and the chloride channel gene. Recently,

90 the immune response has been incriminated in the patho-

91 genesis of various metabolic bone diseases, including

92 osteopetrosis.

93 Both cytotoxic T lymphocyte-associated antigen 4 and

94 programmed death-1, a newly identified immunoregulatory

95 receptor, have been shown to negatively regulate immune

96 responses, and to affect osteoclastogenesis and bone

97 remodelling [23, 24]. The clinical presentation and radio-

98 logical picture may vary according to the severity of the

99 disease.

100 Case Report

101 A 26 years old white male was referred to the Department

102 of Oral and Maxillofacial Surgery, University Hospital

103 Infanta Cristina of Badajoz, Spain for evaluation and

104 treatment of chronic abscess in the right side of the face.

105 The patient explained that the process started 6 months ago

106 after the extraction a molar of the mandible. Facial

107 examination revealed a infection of the mandible and a

108 wide abscess in the submandibular region of the right side

109 of the face with draining fistula. Intraoral examination

110 revealed extensively exposed necrotic bone with seques-

111 trum in the right mandibular molar area. Past medical

112 history revealed the diagnosis of ADO, with numerous

113 bone fractures. The patient was bearer of a hip joint

114 prosthesis (Figs. 1, 2).

115A radiolucent, poorly demarcated image demonstrating

116evidence of sequestrum in the posterior right side of the

117mandible suggestive of a chronic osteomyelitis was

118observed in the panoramic radiograph (Fig. 3). An increase

119in bone density, with obliteration of the medullar spaces

120and loss of distinction between the cortex and medulla was

121present in the CT-scan. A hypodense image was observed

122in the posterior region of the right side of the mandible,

123showing destruction of the vestibular cortical suggestive of

124chronic osteomyelitis (Fig. 4).

125A biopsy was performed. The histopathology was

126reported as consistent with osteomyelitis. The treatment

Fig. 1 Past medical history revealed numerous bone fractures

Fig. 2 The patient was bearer of a hip joint prosthesis





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127 consisting in intravenous antibiotic therapy (clindamicyn),

128 debridement of the necrotic bone and sequestrum and

129 drainage of the abscess. He was submitted to a systemic

130 antibiotic regimen and daily irrigation of the osteomyelitis

131 region with iodine. Subsequently the patient maintained the

132 same antibiotic by oral administration for 10 days.

133 The chronic osteomyelitis remained unresolved for the

134 past 3 months and acute episodes are managed with anti-

135 biotic therapy (Co-amoxiclav, Metronidazole…). Hyper-

136 baric oxygen was used, with poor results. The condition

137 has maintained a chronic course for the last 12 months.

138 Discussion

139 The osteopetrosis are caused by a diminished activity of

140 osteoclasts, which results in defective remodelling of bone

141and increased bone density [12]. Osteopetrosis is generally

142divided into three types: severe infantile malignant auto-

143somal recessive, intermediate mild autosomal recessive,

144and benign autosomal dominant [3, 25]. The prognosis of

145the first two types is very poor and is characterized by an

146early onset, usually within the first decade of life, and early

147death. The benign-type is characterized by a later onset and

148a longer life span [3, 6].

149Dominant forms are more common [26]. Two subtypes

150of ADO are reported based on radiographical features [27].

151In type I (ADO I), there are generalized, diffuse osteo-

152sclerosis affecting mainly the cranial vault [27], due to

153mutation in the gene located in chromosome 11q12–13,

154precisely in the region where a high-bone-mass syndrome

155has been localised [28]. Type II (ADO II), the form orig-

156inally described in 1904 by Albers-Schonberg [29], is the

157most common form with an estimated prevalence of up to

1585.5/100,000. A gene residing in chromosome 16p13.3

159encoding the ClCN7 chloride channel [11], essential for the

160acidification of the extracellular resorption lacuna of

161osteoclast [30], is mainly defective in ADO II [31].

162There are three clinically distinct forms of autosomal

163recessive osteopetrosis (ARO) [32]. The most common

164ARO (also called the malignant type) [33], has severe

165manifestations, and presents in the infantile age group,

166presumably due to mutations either in the TCIRG1 gene

167which encode for the a3 subunit of the vacuolar H(?)-

168ATPase or in the ClCN7 gene encoding an osteoclast-

169specific chloride channel [34]. These patients have bone

170marrow compromise as a result of bone overgrowth in the

171marrow space. They usually die from anemia with con-

172gestive heart failure, or sepsis in their infancy or childhood.

173The increased susceptibility to severe infection is pre-

174sumably related to pancytopenia secondary to marrow

175space obliteration. The second ARO type with carbonic

176anhydrase II deficiency is associated with renal tubular

177acidosis and cerebral calcification, extramedullary hae-

178matopoiesis, hepatosplenomegaly and pancytopenia. The

179third recessive type is milder, presenting in childhood with

180variable orthopaedic and dental symptoms. They tend to

181have radiographical evidence of the disease, short stature,

182macrocephaly, increased upper segment/lower segment

183ratio, decreased arm span, mandibular prognathism, nerve

184compression, and a tendency for developing fractures and

185osteomyelitis. Of the 18 affected family members in 11

186families with this form reported so far, many children were

187asymptomatic with only radiographical disease. In many of

188these cases, there was parental consanguinity [31, 32].

189In osteopetrosis, the determining factor for healing is the

190vascularity of the bone. Consequently, in such patients the

191healing process is slow, the outcome often unfavorable, and

192the bone becomes susceptible to infection [35]. Osteomy-

193elitis is a well-recognized complication of osteopetrosis

Fig. 3 Panoramic radiograph showing sclerosis of the jaws, greatdistortion in permanent teeth, hypercementosis and evidence of bonesequestrum on the posterior right side of the mandible

Fig. 4 CT showed a generalized increase in bone density and in theposterior region of the right side of the mandible was seen ahypodense image suggestive of abscess





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194 [2, 3, 36, 38, 39], and the general dental practitioner should

195 be aware that the reduced vascularity of bone and impaired

196 white cell function might lead to the development of oste-

197 omyelitis in patients with osteopetrosis. The most common

198 site of involvement is the mandible, and it is associated with

199 dental extractions or surgical exposure of the pathologic

200 bone [1, 6].

201 Patients with osteopetrosis frequently visit the dentists

202 for several complications like dental caries, delayed erup-

203 tion and early loss of teeth, enamel hypoplasia, malformed

204 roots and crowns, and thickening of the lamina dura; with

205 the most common problem being caries. Constriction of the

206 canals housing neurovascular bundles supplying the teeth

207 and jaws as well as obliteration of the marrow cavities and

208 dental pulp chambers, lead to bone necrosis and dental

209 caries [31], and ultimately develop osteomyelitis in 10% of

210 cases. Osteomyelitis may be potentially severe with a

211 protracted course due to the accompanying anemia and

212 neutropenia [31].

213 The change in bone structure is accompanied by a

214 marked tendency toward fragility, and fractures may be

215 sustained even in trivial accidents [35]. The pathologic

216 fractures in patients with osteopetrosis are likely the result

217 of structural weakness associated with poorly organized

218 bone and persistent accumulations of immature bone and

219 calcified cartilage. With progression of the disease, the

220 bones become increasingly sclerotic and opaque on radio-

221 graphs, the latter feature giving rise to the term ‘‘marble

222 bone’’ [4, 35]. The frontal and nasal bones may be dense

223 and somewhat enlarged, and the air sinuses may be

224 obscured [1, 35]. According to Bakeman et al. [3], osteo-

225 petrosis radiographically appears as an increased density of

226 the entire skeleton (e.g., ribs, pelvis, clavicle, femur, skull

227 base, and jaws). The long bones show increased cortical

228 thickening and decreased marrow space, and become club-

229 shaped. The pelvis and the scapula may show endobone

230 formations [3]. The presence of hypercementosis, involv-

231 ing different teeth, was also mentioned, was reported in the

232 literature only by Smith [6, 35].

233 The malignant form presents with devastating symptoms

234 early in childhood and rapid worsening of the condition,

235 resulting in a short lifespan, whereas the benign formmay be

236 diagnosed late in childhood with a variety of prominent

237 clinical features, such as frontal bossing, leonine facies,

238 malocclusion of teeth and hepatosplenomegaly [39]. Atyp-

239 ical features may include microcephaly and a normal upper

240 segment to lower segment ratio. A radiological skeletal

241 survey usually reveals increased bone density with poor

242 differentiation between the cortex and the medulla. The

243 defective remodelling process characteristic of osteopetrosis

244 has many clinical implications in the head and face regions.

245 Cranial imaging of autosomal recessive osteopetrosis shows

246 small optic canals, orbits and nasoethmoid complex. The

247paranasal sinuses are either poorly pneumatized, like the

248mastoid air cells, or show bud formation [40] Areas of

249condylar cartilage calcification may be seen [1]. These

250radiological characteristics of underdevelopment may sup-

251port the theory that delayed maturation is the primary mor-

252phological abnormality in osteopetrosis and that bone

253thickening is a secondary manifestation to reduced bone

254turnover. Of importance in the head and neck region is the

255stenosis and compression of the cranial foramina, resulting

256in multiple cranial palsies. The optic, olfactory, trigeminal,

257facial and cochlear nerves are most commonly affected.

258Cummings et al. [41] reported the case of a six-month-old

259infant who was diagnosed with malignant autosomal

260recessive osteopetrosis and was found to have optic nerve

261pallor secondary to orbital fissure narrowing (seen on

262computed tomography of the brain) [24].

263Batra and Shah [54] reported a case of osteomyelitis of

264the mandible following tooth extraction in a 19-year-old

265woman with malignant osteopetrosis. This result was

266attributed to the poor bone vascularization and reduced local

267defences. Most teeth were unerupted and the paranasal

268sinuses were not aerated (as seen on computed tomographic

269evaluation of the facial bones). The initial clinical diagnosis

270was a draining gingivobuccal fistula; however, failure to

271respond to broad-spectrum antibiotics and the pathological

272description of the debrided bony fragments of the right

273maxilla shifted the diagnosis to chronic osteomyelitis. The

274chronicity of this infection has necessitated repeated surgi-

275cal intervention for further debridement of the necrotic tis-

276sues and infected bone [24].

277Ten percent of osteopetrosis cases develop osteomyelitis

278that usually involves the mandible. The osteomyelitis is

279generally caused by tooth extraction or pulpal necrosis. The

280leading cause of the increased rate of infection is thought to

281be a lack of adequate bone vasculature. Treatment of the

282infection is difficult because of the large amounts of poorly

283vascularized bone with gradual obliteration of the marrow

284space in the affected regions. Multiple draining fistulae and

285bony sequestrum are common clinical finding [8].

286Osteomyelitis of the maxilla is very rare, probably because

287of the thin cortical bone and rich collateral blood supply

288[12].

289Radiographically, the typical brugger jersey spineQ and

290endobones (bbone within a boneQ) were seen in the pelvis of

291the patients with ADO type II. These alterations are not

292present in ADO type I patients. On the other hand, radio-

293graphs in patients with ADO type I showed a pronounced

294sclerosis of the skull with an enlarged thickness of the cra-

295nial and facial walls positively correlated to age. The scle-

296rosis of the skull in type II was most striking at the base.

297Laboratory findings in ADO usually show the characteristic

298of a myelophthisic anemia due to the obliteration of hemo-

299poietic marrow cavities [2, 5, 24, 55].





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300 Important differential diagnoses considered are pykno-

301 dysostosis, metaphyseal dysplasia, diaphyseal sclerosis,

302 melorheostosis, osteopetrosis striata, osteopoikilosis,

303 Engelmann’s disease and infantile cortical sclerosis [31].

304 Treatment of osteomyelitis secondary to osteopetrosis is

305 controversial. Treatment regimens include high-dose sys-

306 temic antibiotics coupled with thorough debridement of

307 necrotic bone and primary closure of soft tissues, if possible

308 [2–4]. Hyperbaric oxygen (HBO) has been used for the

309 treatment of chronic osteomyelitis [3, 4]. Mechanisms of

310 HBO action in osteomyelitis include enhanced leucocytic

311 killing, osteoclastic resorption of the dead osteomyelitic

312 tissue, fibroblastic division, collagen production, neovas-

313 cularisation, and enhanced permeation of certain antibiotics

314 (aminoglycosides) across bacterial cell walls within the

315 necrotic tissue. As osteoclasts are 100 times more meta-

316 bolically active than osteocytes, its function is highly oxy-

317 gen dependant [31]. There are few reports demonstrating the

318 success of treatment; in many cases, the osteomyelitis

319 remains unresolved indefinitely [2, 12]. In a review of 57

320 cases of osteomyelitis resulting from osteopetrosis, most

321 cases were found to be chronic and resistant to treatment [2].

322 Unfortunately, there seems to be no definitive treatment for

323 osteopetrosis of the maxilla or mandible without complete

324 removal of the affected bone. In order to minimize such

325 problems, patients with osteopetrosis should be encouraged

326 to maintain good dental care and oral hygiene, because there

327 is a potential risk of promoting osteomyelitis if surgical

328 procedures are performed [6].

329 Management of osteopetrosis has to be individualised

330 because of the wide spectrum of clinical symptoms and

331 complications. Medical management of osteopetrosis

332 revolves around modulation of the osteoclasts, either to

333 stimulate the remaining host osteoclasts or to provide an

334 alternative source of the same. Restriction of calcium

335 intake [56], high-dose calcitriol therapy, steroids, para-

336 thyroid hormone and recombinant human interferon

337 gamma-1b, have all been attempted to stimulate the host

338 osteoclasts with variable success rate.

339 Use of a microvascularized osseous free flap may be

340 favorable but may be precluded because of absence of a

341 suitable donor site in these patients [12].

342 Palliative treatment, including nerve decompression and

343 debridement, seems to be the best course of action. The

344 best treatment appears to be preventive management with

345 routine dental care. Teeth should be endodontically treated,

346 if possible, rather than extracted, because periosteal strip-

347 ping of bone may predispose asymptomatic bone to

348 become necrotic and to sequester. Any debridement should

349 be as conservative as possible, removing only grossly

350 necrotic bone through limited flap dissections. Because the

351 disease process is systemic, there is often no clear delin-

352 eation between affected and unaffected bone [9].

353Recently, bone marrow transplantation has been suc-

354cessfully used in the treatment of malignant osteopetrosis,

355offering hope to those so afflicted; [6, 57] it has been

356curative in a significant percentage of patients but an

357acceptable donor can be found in only about 40% [31].

358

359References

3601. Elster AD, Theros EG, Key LL et al (1992) Cranial imaging in361autosomal recessive osteopetrosis. Part I. Facial bones and362calvarium. Radiology 183:129–1353632. Barry CP, Ryan CD (2003) Osteomyelitis of the maxilla sec-364ondary to osteopetrosis: report of a case. Oral Surg Oral Med Oral365Pathol Oral Radiol Endod 95:12–153663. Bakeman RJ, Abdelsayed RA, Sutley SH et al (1998) Osteope-367trosis:a review of the literature and report of a case complicated368by osteomyelitis of the mandible. J Oral Maxillofac Surg 56:3691209–12133704. Juggins KJ, Walton GM, Patel M (2001) Osteomyelitis compli-371cating osteopetrosis e a case report. Dent Update 28:509–5113725. Steiner M, Gould AR, Means WR (1983) Osteomyelitis of373mandible associated with osteopetrosis. J Oral Maxillofac Surg37441:395–4053756. Portela MA, Santana E, Jorge WA, Paraiso M (2006) Osteomy-376elitis of the mandible associated with autosomal dominant oste-377opetrosis: a case report. Oral Surg Oral Med Oral Pathol Oral378Radiol Endod 102:94–983797. Karshner RG (1926) Osteopetrosis. AJR 16:405–4193808. Long RG, Ziccardi V (2001) Osteopetrosis of the maxilla. Oral381Surg Oral Med Oral Pathol Oral Radiol Endod 91:139–1403829. Battaglia MA, Drigo P, Laverda AM et al (1991) Osteomielite e383osteopetrosis infantile. Descrizione di un caso. Minerva Stomatol38440:125–12738510. Shapiro F, Glimcher MJ, Holtrop ME, Tashjian AH, Brickley-386Parsons D, Kenzora JE (1980) Human osteopetrosis: a histolog-387ical, ultrastructural, and biochemical study. J Bone Joint Surg38862:384–39938911. Benichou OD, Cleiren E, Gram J et al (2001) Mapping of auto-390somal dominant osteopetrosis Type II (Albers-Schfnberg disease)391to chromosome 16p13.3. Am J Hum Genet 69:647–65439212. Junquera L, Rodrıguez-Recio C, Villarreal P, Garcıa-Consuegra393L (2005) Autosomal dominant osteopetrosis and maxilloman-394dibular osteomielitis. Am J Otolaryngol Head Neck Med Surg39526:275–27839613. Stocks RM, Wang WC, Thompson JW et al (1998) Malignant397infantile osteopetrosis. Arch Otolaryngol Head Neck Surg398124:684–68939914. Driessen GJ, Gerritsen EJ, Fischer A et al (2003) Long-term400outcome of haematopoietic stem cell transplantation in autosomal401recessive osteopetrosis: an EBMT report. Bone Marrow Trans-402plant 32:657–66340315. Bollerslev J, Grontved A, Andersen PE Jr (1988) Autosomal404dominant osteopetrosis: an otoneurological investigation of the405two radiological types. Laryngoscope 98:411–41340616. Bollerslev J, Andersen PE Jr (1988) Radiological, biochemical407and hereditary evidence of two types of autosomal dominant408osteopetrosis. Bone 9:7–1340917. Van Hul E, Gram J, Bollerslev J et al (2002) Localization of the410gene causing autosomal dominant osteopetrosis type I to chro-411mosome 11q12–13. J Bone Miner Res 17:1111–111741218. Benichou OD, Laredo JD, de Vernejoul MC (2000) Type II413autosomal dominant osteopetrosis (Albers-Schfnberg disease):





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414 clinical and radiological manifestations in 42 patients. Bone415 26:87–93416 19. Beighton P, Horan F, Hamersma H (1977) A review of the os-417 teopetroses. Postgrad Med J 53:507–516418 20. Tips RL, Lynch HT (1962) Malignant congenital osteopetrosis419 resulting from a consanguineous marriage. Acta Paediatr 51:420 585–588421 21. Marks SC Jr (1973) Pathogenesis of osteopetrosis in the rat:422 reduced bone resorption due to reduced osteoclast function. Am J423 Anat 138:165–189424 22. Schofield BH, Levin LS, Doty SB (1974) Ultrastructure and425 lysosomal histochemistry of ia rat osteoclasts. Calcif Tissue Res426 14:153–160427 23. Nagahama K, Aoki K, Nonaka K et al (2004) The deficiency of428 immunoregulatory receptor PD-1 causes mild osteopetrosis. Bone429 35:1059–1068430 24. Hamdan A, Nabulsi M, Farhat F, Haidar R, Fuleihan N (2006)431 When bone becomes marble: head and neck manifestations of432 osteopetrosis. Paediatr Child Health 11(1):37–40433 25. Shaff MI, Mathis JM (1982) Osteomyelitis of the mandible. an434 initial feature in late-onset osteopetrosis. Arch Otolaryngol 108:435 120–121436 26. Bollerslev J (1989) Autosomal dominant osteopetrosis: bone437 metabolism and epidemiological, clinical, and hormonal aspects.438 Endocr Rev 10:45–67439 27. Bollerslev J, Andersen PE Jr (1988) Radiological, biochemical440 and hereditary evidence of two types of autosomal dominant441 osteopetrosis. Bone 91:7–13442 28. Van Hul E, Mathysen D, Bollerslev J, Gram J, Van Hul W (2000)443 Autosomal dominant osteopetrosis type I is genetically linked to444 the same region on human chromosome 11 as the high bone mass445 phenotype. J Bone Miner Res 15(suppl 11):S260446 29. Albers-Schonberg HE (1904) Rontgenbilder einer seltenen447 Knockenerkrankung. Munch Med Wochenschr 51:365–368448 German449 30. Kornak U, Kasper D, Bosl MR et al (2001) Loss of the ClC-7450 chloride channel leads to osteopetrosis in mice and man. Cell451 104:205–215452 31. Chattopadhyay P, Kundu AK, Saha AK, Karthak RO (2008)453 Mandibular osteomyelitis and multiple skeletal complications in454 Albers-Schonberg disease. Singapore Med J 49(9):e229–e233455 32. Kahler SG, Burns JA, Aylsworth AS (1984) A mild autosomal456 recessive form of osteopetrosis. Am J Med Genet 17:461–464457 33. Gerritsen EJ, Vossen JM, van Loo IH et al (1994) Autosomal458 recessive osteopetrosis: variability of findings at diagnosis and459 during the natural course. Pediatrics 93:247–253460 34. Sly WS, Hewett-Emmett D, Whyte MP, Yu YSL, Tashian RE461 (1983) Carbonic anhydrase II deficiency identified as the primary462 defect in the autosomal recessive syndrome of osteopetrosis with463 renal tubular acidosis and cerebral calcification. Proc Natl Acad464 Sci USA 80:2752–2756465 35. Smith NH (1966) Albers-Schonberg disease (osteopetrosis). Oral466 Surg Oral Med Oral Pathol 22:699–710

46736. Gupta DS, Gupta MK, Borle RM (1986) Osteomyelitis of the468mandible in marble bone disease. Int J Oral Maxillofac Surg46915:201–20547037. Lawoyin DO, Daramola JO, Ajagbe HA et al (1988) Osteomy-471elitis of the mandible associated with osteopetrosis: report a case.472Br J Oral Maxillofac Surg 26:330–33547338. Hinds EC (1970) Non-inflammatory bone disease. J Oral Surg47428:27–3847539. ShahAM,BobyKF,Karande SC,LahiriKR, JainMK(1996)Three476sibs with mild variety of osteopetrosis. J PostgradMed 42:123–12547740. Bartynski WS, Barnes PD, Wallman JK (1989) Cranial CT of478autosomal recessive osteopetrosis. AJNR Am J Neuroradiol 10:479543–55048041. Cummings TJ, Proia AD (2004) Optic nerve compression in481infantile malignant autosomal recessive osteopetrosis. J Pediatr482Ophthalmol Strabismus 41:241–24448342. Blum JJ, Hines M (1979) Biophysics of flagellar motility. Q Rev484Biophys 12:103–18048543. Suga F, Lindsay JR (1976) Temporal bone histopathology of486osteopetrosis. Ann Otol Rhinol Laryngol 85:15–2448744. Milroy CM,Michaels L (1990) Temporal bone pathology of adult-488type osteopetrosis. Arch Otolaryngol Head Neck Surg 116:79–8448945. Jones MD, Mulcahy ND (1968) Osteopathia striata, osteopetrosis,490and impaired hearing:a case report. Arch Otolaryngol 87:491116–11849246. Hawke M, Jahn AF, Bailey D (1981) Osteopetrosis of the tem-493poral bone. Arch Otolaryngol 107:278–28249447. Myers EN, Stool S (1969) The temporal bone in osteopetrosis.495Arch Otolaryngol 89:460–46949648. Hamersma H (1970) Osteopetrosis (marble bone disease) of the497temporal bone. Laryngoscope 80:1518–153949849. Yarington CT Jr, Sprinkle PM (1967) Facial palsy in osteope-499trosis. Relief by endotemporal decompression. JAMA 202:54950050. Wong ML, Balkany TJ, Reeves J, Jafek BW (1978) Head and501neck manifestations of malignant osteopetrosis. Otolaryngology50286:585–59450351. Baxter A (1971) Dehiscence of the fallopian canal. An anatom-504ical study. J Laryngol Otol 85:587–59450552. Paulose KO, Al Khalifa S, Shenoy PK, Harris S, Sharma RK506(1988) Osteopetrosis (marble bone disease)—agenesis of para-507nasal sinuses. J Laryngol Otol 102:1047–105150853. Bjorvatn K, Gilhuus-Moe O, Aarskog D (1979) Oral aspects of509osteopetrosis. Scand J Dent Res 87:245–25251054. Batra P, Shah N (2004) Recalcitrant osteomyelitis following511tooth extraction in a case of malignant osteopetrosis. Int Dent J51254:418–42351355. Brockstedt H, Bollerslev J, Melsen F, Mosekilde L (1996) Cor-514tical bone remodeling in autosomal dominant osteopetrosis: a515study of two different phenotypes. Bone 18:67–7251656. Miyamoto RT, House WF (1980) Neurologic manifestations of517the osteopetrosis. Arch Otolaryngol 106:210–21451857. Benecke JE (1993) Facial nerve dysfunction in osteopetrosis.519Laryngoscope 103:494–497

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Osteomyelitis of the mandible in a patient with osteopetrosis

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