Focal osteoporotic bone marrow defects of the jaws

Focal osteoporoticbonemarrow defectsof the jaws An analysis

of 197 new cases

Bruce F. Barker, D.D.S.,” Jerald L. Jensen, D.D.S., M.S.,** awd Pramis V. Howebl~, D.D.8, M.S.,*** Knnsas Pity, MO., Loqq Bench, Calif., rcwd Lomcr Lindn, Cdif. Osteoporotic bone marrow defects will usually present as asymptomatic radiolucencies which are located predominantly in the mandibular molar regions of middleaged women. Histologically, they are composed of either hematopoietic or, less commonly, fatty marrow. The majority of defects offer no ready explanation as to their pathogenesis; however, altered healing reactions or marrow hyperplasia may be the cause in a small number of cases. The defects often are radiographically similar to more ominous lesions, which must be ruled out.

F

ocal osteoporotic bone marrow defects (OPM1)) of the jaws usually appear as asymptomatic radiolucencies in the molar area of the mandible in middle-aged women. They are seldom considered in a clinical differential diagnosis. Histologically, they consist of hematopoietic or, less commonly, fatty marrow.‘? ‘a The pathogenesis is not known, but several suggested possibilities include (1) bone resorption secondary to marrow hyperplasia in response to an increased demand for b]()()(l (h&,‘, 5,7.“1) (2) persistent embryologic marrow remnants,‘, i and (3) altered regeneration of bony trabeculae in an area of previous trauma, local inflammation, or extraction.“, 20 Since only a small number of cases of OPMT) have been reported,7. 20 and because the pathogenesis is unknown, we thought it important to analyze a large series of casesand to further define these lesions, MATERIAL AND METHODS

The study was divided into two parts. All cases in the first part represent biopsies of radiographir defects of the jaws. In all cases, bone marrow was *Assistant Professor, Department of Oral Pathology, University of Missouri-Kansas City School of Dentistry. **Oral Pathologist, Veterans Administration Hospital, Long Beach, Calif. “““Professor of Dental Medicine, School of Dentistry, Loma Linda University.

404

Volume 38 Number 3

Table

Focal osteoporotic

bone marrow

defects of jaws

405

I. Incidence of marrow defects by age and sex

Age range 0 11 21 31 41 51 61 71

to to to to to to to to

(years) 10 20 30 40 50 60 70 so

*Age and/or

)

Males

Females 10 14 43 38 24 6 1

6 1: 8

sex not specified in remaining

Total

cases.

found to be responsible for the radiographic lesion. The majority of cases were retrieved from the files of a private oral pathology laboratory and included approximately 47,000 specimens, accessioned over a S-year period (mid-1957 to mid-1973). All diagnoses of OPMD were histologically confirmed on slides stained with hematoxylin and eosin. Cell-to-fat ratios (C:F) and myeloid-toerythroid ratios (M:E) were estimated independently by two of the authors and the results were compared. If significant differences in interpretation occurred, those slides were re-evaluated and a compromise was worked out. The relative number of megakaryocytes and the presence or absence of lymphoid follicles were recorded. Cases with insufficient material were excluded (Table IV). Histories and available radiographs were reviewed, and all clinical data were tabulated. Follow-up information was not available in the majority of cases. In the second part of the study, an attempt was made to evaluate the role of generalized bone marrow hyperplasia in the pathogenesis of OPMD. All marrow aspirations, sternal and iliac, performed at the Long Beach Veterans Administration Hospital over a one-year period were reviewed. Those caseswith significant marrow hyperplasia (C :F 70:30 or greater) were selected. Panorex radiographs of the jaws of thirty-six patients from this group were taken 1 month prior to the marrow aspiration. The radiographs were reviewed for the presence of possible OPMD. RESULTS Clinical features

One hundred ninety-seven casesmet the criteria for inclusion in the first part of the study. Of these cases, 140 occurred in females, 52 in males, in 5 casesthe patient’s sex was not specified. The age range was 7 years to 73 years, with more than half the patients being in the fourth and fifth decades. The average age was 41.8 years (Table I). The lesions were predominantly in Caucasians (170), with eleven in Negroes and one in a Mexican. In the remainder, race was not specified. The racial statistics undoubtedly reflect the predominant Caucasian clientele of the laboratory. The majority of OPMDs were located in the mandible (179), and most of these were in the molar area (138). None of the mandibular lesions were located anterior to the cuspids. Eighteen caseswere located in the maxilla, and eight of

406

Barker, Jensen, and Howell

Oral Surg. September, 1974

Fig. 1. A well-defined marrow defect with a thin, incomplete, sclerotic border. The defect is located in the edentulous third molar area of a 59-year-old woman. Histologic study revealed a mixture of fatty and hematopoietic marrow.

Fig. 8. Radiographs were taken because of a distal migration of a carious second premolar in a 33-year-old woman. Histologic study showed a moderately cellular focus of hematopoietic marrow, with no evidence of inflammation.

these known to involve the tuberosity. The exact locations were not specified in most remaining maxillary cases; however, one case was in the incisor area (Table II), The size of the defects, as determined from clinical descriptions and available radiographs, varied from 0.4 cm. to 3 cm., with the average being about 1.0 cm. in greatest dimension. Radiographic

features

Radiographic appearance varied from sharply defined radiolucencies with distinct sclerotic borders (Figs. 1 and 5) to extremely ill-defined areas with a moth-eaten appearance. Most commonly, these defects were poorly defined and had somewhat irregular borders (Fig. 3). Trabeculations were occasionally visible within the radiolucent areas, as were spotty calcified flecks. The “ladder effect,” frequently described in sickle-cell anemiaX8 was not present in any of our cases, including one case with proven sickle-cell anemia. The lamina dura of

Volume 38 Number 3

Fig. 3. A honeycombed or scalloped apex of a vital premolar in a 51.year-old

Table

marrow defect woman.

occurring in close association with the

II. Incidence of marrow defects by location site

Cases

Total

Mandibular first molar area Mandibular second molar area Mundibular third molar area Distal to mandibular third molar M;lltdil~Ulil~ IllOlCXTwgiotl ( NOS ) Mandibular nrernolar repion Kamus * Maxilla (NOS)’ Tubcrosity “One case occurred

in the incisor

area.

teeth adjacent to defects was uninvolved in the majority of cases; however, it was indistinct in a few cases and definitely absent in two cases. In ten cases the defects appeared as radiolucent areas surrounding or abutting on radiopaque, fibro-osseous lesions (Fig. 4). In four cases the OPMl)s represented rental radiolucencies in exostoses. Association

with

other

conditions

In fort,y-six cases (23 per cent) 0l’Ml)s were located in areas of previous extractions. The time interval between extraction and biopsy varied from 1 month to 30 years, with most more than 1 pear. The majority of lesions were asymptomatic. However, twent,v-six patients complained of pain in the area of the lesion. No particular significance cdan bc

408

Oral Surg. September, 1974

Barker, Jensen, and Howell

Fig. 4. This 27-year-old Negro woman had a smooth-bordered radiodensity of the posterior mandible, partially surrounded by a radiolucent zone. The diagnosis was osseous dysplasia with surrounding hone marrow defect. History revealed that teeth had been extracted 5 years previously. Histologically, the marrow was very cellular.

Fig. 5. A well-defined hematopoietic marrow impacted t.hird molar in a 24.yonr-old woman.

defect

associated

with the distal

aspect of an

attachecl to this finding, since the information available was not sufficient to rule out other possible causes of the pain. Twelve casts were associated with impacted teeth, with ten of these being mandibular third molars. l’ifteen cases were associated with bony or fibro-osseous lesions. Most (eight) were osseous dysplasia (also called periapical cemental dysplasia, gigantiform ccmentoma, cementoma, multiple enostosis, and sclerosing osteomyelitis). Four cases were locatetl in esostoses, two in enostoses, and one in association with fibrous dysplasia. Fourteen cases were situated adjacent to possihlr foci of inflammation. These conditions included nonvital t&h, retained root tips, previous fracture sites, chronic osteomyelitis, pcricoronitis, ant1 a pcriapical granuloma. Five patients were found to have systemic disease, while two additional patients had OPMDs adjacent to amcloblastomas (Table I II). A review of Panorcs radiographs of the thirty-six I~ong Beach Veterans

Focal osteoporotic bone marrow defects of jaws 409

Volume 38 Number 3

Table

III. Association of marrow defects with other conditions Associated

conditions

No. of oases

Previous extraction site History of pain Area of other surgery Impacted teeth Fibro-osseous lesions Osseous dysplasia Exostoses Enostoses Fibrous dysplasia Retained root tips Previous fracture sites Chronic osteomyelitis Pericoronitis Devital teeth Periapical granuloma Anemia (type unknown) Sickle-cell anemia Heart disease (NOS) Lymphoma Ameloblastoma

46 26 2 12 8 4 2 1 t 3 3 4 : 2 i 123

Total

Table

IV.

Incidence of marrow defects by cell: fat ratio and myeloid: erythroid

ratios Cell :fat

Myeloid:erythroid ratio

ratio

go-lOO:O-10 80-89 : 11-20 70-79:21-30 60-69 :31-40 50-59 :41-50 40-49 :51-60 30-39 : 61-70 20-29 : 71-80 lo-19 :81-90 o-9:91-100 reflect

: 8 4 22 58 51 21

;;; 4:l 3:l 2:l 1:l

Totals* *Totals estimation.

No. of cases

9:l 8:l 7:l

iii cases

omitted

because

158

Totals* marrow

was

judged

insufficient

for

accurate

Administration Hospital patients with generalized bone marrow hyperplasia associated with persistent anemias of various types failed to reveal a single OPMD. The age range in this group was 25 to 90 years, with the average being 62.3 years. There were thirty-three male and three female patients. Hemoglobin values ranged from 4.3 Gm./lOO ml. to 11.8 Cm./100 ml. with an average of 8.2 Gm./lOO ml. Histologic

examination

The majority of our cases exhibited a cellular hematopoietic bone marrow (Fig. 6)) with 111 having cell-to-fat ratios greater than 50 :50 ; in more than half of these, the ratio was 80:20 or greater. More than 100 cases exhibited an M:E ratio of 2 :1 or 3 :1 (Table IV). Megakaryocytes were identified in most

410

Barker, Jensen, and Howell

Oral Surg. September, 1974

Fig. 6. A very cellular hematopoietic marrow (95/5) taken from a radiolucency distal to an impacted third molar in a 29-year-old man. Fig. ‘7. A high-power photomicrograph demonstrating cells of myeloid, erythroid, and megakaryocytic series.

specimens (Fig. 7). Occasional small lymphoid aggregates were present in twenty-seven cases, and most of these were in lesions with hypercellular marrow. Bony trabeculae in pure OPMD (no associated fibro-osseous lesions) revealed no osteoblastic rimming or osteoclastic resorption. DISCUSSION In the two previously published series of OPMDs totaling thirty-five cases,7l 20 the majority occurred in the mandibular areas of middle-aged women. Our findings are confirmatory. We found ‘71 per cent of our cases in women, and 70 per cent of the defects were located in the posterior mandible. The percentage of our cases occurring in the maxilla was 9.1 per cent, which is lower than the previously reported figures of 23 per cent’ and 11 per cent.*O In addition, one of our cases occurred in the incisor area of the maxilla, a location not previously reported. Osteoporotic marrow defects are often confused with other lesions clinically

Volume Number

38 3

and are rarely mentioned in a differential diagnosis. Crawford and Weathers7 noted such diagnoses as osteomyelitis, ameloblastoma, traumatic bone cyst, and fibrous dysplasia, with only two clinicians mentioning the possibility of an OPMD. A similar spectrum of diagnoses was notctl in our material, with OPMD rarely being considered. The radiographic appearance of these defects is not sufficiently characteristic to permit an exact diagnosis. However, a radiolucent lesion with either distinct or poorly defined irregular borders, located in the posterior mandible of a middle-aged woman, and not associated with a tooth, shoultl suggest an OPMD. A definite diagnosis requires microscopic examination of the tissue. This tissue is usually acquired by biopsy ; however, it seems reasonable that needle aspiration and cytologic examination would be equally diagnostic and much simpler in those lesions composed of active hematopoietic marrow. The pathogenesis of OPMD is unknown; however, three major hypotheses have been proposed. First, Box2 and Standish and Shafer?O proposed that these defects might be initiated by local stimuli and related to the vagaries of the healing reaction. Disuse atrophy resulting from loss of teeth was also mentioned as a possible contributing factor. Second, it has been proposed that the defects represent residual remnants of embryologic marrow persisting into adulthood.2, 7 The third postulate is that OPMD may be due to areas of marrow hyperplasia which occur in response to an increased demand for red blood cell production.?, 5, 7, 20 Only sixty of our 197 cases could be explained on the basis of vagaries of the healing reaction. Forty-six of these cases were in areas of previous extractions, and fourteen were associated with lesions which could be interpreted as causing low-grade inflammation (Table III). The theory that OPMDs represent remnants of marrow spaces persisting into adulthood could not be subjected to critical analysis in our material. However, if this theory were true, one might expect an equal incidence of OPMDs in adolescence and adulthood, which is not the case. Concerning the third hypothesis, it is well known that various hematologic disorders are associated with radiographic changes in bones and that these changes are a direct consequence of the marrow hyperplasia.“+ 9glo, 12-15,IT-l9 It is also known that foci of hematopoietic marrow persist into adulthood in certain areas of the j8ws.l’ 5, 7, I6 It thus seems reasonable to postulate that OPMD could be secondary to various hematologic disorders. Follow-up information and hematologic data at the time of biopsy were unavailable in most cases. One patient, however, was known to have anemia of undetermined etiology, another had a malignant lymphoma, and still another had sickle-cell anemia. Our study of thirty-six patients with significant generalized marrow hyperplasia associated with various persistent anemias failed to reveal a single case of OPMD. Also, in radiographic studies of the skull in patients with thalassemia6 and in patients with similar skull lesions found in association with iron-deficency anemia, sickle-cc11 anemia, polycythemia, and cyanotic congenital cardiac disease 3l 4, 9, lo, U-G 17-lDradiographic lesions which could be interpreted as OPMD weri not described. It therefore seems probable that although some OPMDs are

Oral Surg. September, 1974

due to marrow hyl)crplasias in response to increased demand for blood-cell production, the vast majority arc due to other causes. Stantlish and Shafer”’ noted that many of their hematopoietic dcfccts were in l)rtnlcllol)ausal MY~~VH,unclcr 50 years of age, and that those defects in older wome11 wcrc mainly fatty. 111this stutly of thirty-one fcmalc patients over 50 years of age, 2:) per cent of the clcfcets were primarily fatty, while the remainder (75 per cent) were cellular. In EWS of women under 50 years of age, 63 per cent were ecllular marrow defects and 13 per cent were fatty defects. Speculation that OPRlI) in l)rcincuopausal women is rclatcd to secondary marrow hyperplasia in rcsponsc to blood loss is not supl)ortcd by these data. Our fintliiigs suggest that OI’MI) may result from a variety of causes. Up to one thircl may bc csplaincd on the basis of an abnormal healing reaction, while a very small pcrccntagc could be explained on the basis of marrow hyperplasia associated with various hematologic disorders. The majority of cases, howcrcr, offer no ready explanation. It seems rcasona.ble to postulate that this latter group results from as yet unknown stimuli which induce localized marrow hyperplasia, with resultant bone resorption, which eventually becomes visible on radiographs. In a few of these, all that remains in the defect is fatty marrow. We wish to thank Drs. Albert M. Abrams and Raymond Melrose, California School of Dentistry, for providing several cases, including used in this article.

University of Southern radiographs, that were

REFERENCES

5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17.

Box, H. K.: Red Bone marrow in Human Jaws, Canadian Dental Research Foundation, Bulletin No. 20, 1933, pp. 3-31. Box, H. K.: Bone Resorption in Red Marrow Hyperplasia in Human Jaws, Canadian Dental Research Foundation, Bulletin No. 21, July, 1936, pp. 3-27. Anemia Producing Britton, H. A., Ganby, J. P., and Kohler, C. M.: Iron Deficiency Evidence of Marrow Hyperplasia in the Calvarium, Pediatrics 25: 621-628, 1960. Anemia Burko, H., Mellins! H. Z., and Watso?, J.: Skull Changes in Iron Deficiency Simulating Congemtal Hemolytic Anemia, Am, J. Roentgenol. Radium Ther. Nucl. Med. 86: 447-452, 1961. Cahn, L. R.: Comment on Hematopoietic Marrow in the Jaws, ORAL SURG.7: 790, 1954. Caffey, J.: Cooley’s Anemia: Review of the Roentgenographic Findings in the Skeleton, Am. J. Roentgenol. Radium Ther. Nucl. Med. 78: 381-391, 1957. Crawford, B. E., and W.eathers, D. R.: Osteoporotic Marrow Defects of the Jaws, J. Oral Surg. 28: 600-603, 1970. Curtis, A. B. : Childhood Leukemias: Osseous Changes in Jaws on Panoramic Dental Radiographs, J. Am. Dent. Assoc. 83: 844-847, 1971. Dysktra, 0. II., and Halbertsma, T.: Polycythemia Vera in Childhood: Report of a Case With Changes in the Skull. Am. J. Dis. Child. 60: 907-916. 1940. Eng, L. : CYhronic Iron Defikiency Anemia With Bone Chanies Resembling Cooley’s Anemia, Acta Haematol. 19: 263-268, 1958. Jaffe, H. L.: Metabolic Degenerative, and Inflammatory Diseases of Bones and Joints, Philadelahia. 1972. Lea & Febieer. I). 44. Mariani,& M.,’ and Baseman, G. ? uber .” I skelett veraderungen bei kongenitalen, Beitr. Pathol. Anat. 126: 145, 1952. Moseley, J. E.: Bone Changes in Hematologic Disorders (Roentgen Aspects), New York, 1963, Grune & Stratton. Inc.. DD. 6-20. Mosiley, J. E.: Skull ‘Ghan&s in Chronic Iron Deficiency Anemia. Am. J. Roentgenol. Radium Ther. Nucl. Med. 85: 649-652, 1961. Nice, 0. M., Jr., Davies, M., and Wood, G. H.: Changes in Bone Associated With Cyanotic Congenital Cardiac Disease, Am. Heart J. 68: 25-31, 1964. Orban, B. J.: Orban’s Oral Histology and Embryology, ed. 7, St. Louis, 1972, The C. V. Mosby Company, p. 211. Powell, J. WV., h’eens, H. S., and Wenger, N. K.: The Skull Roentgenogram in Iron Defieiencv Anemia and in Secondarv Polveythemia. Am. J. Roenteenol. Radium Ther. ’ Nucl. Me”d. 95: 143-147, 1965. _ - ”

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18. Robinson, I. B., and Sarnat, B. G.: Roentgen Studies of the Maxillae and Mandible in Sickle-Cell Anemia, Radiology 58: 517-523, 1952. With Chronic Iron 19. Shahidi, N. T., and Diamond, L. K.: Skull Changes in Infants Deficiency Anemia, N. Engl. J. Med. 262: 137-139, 1960. 20. Standish, S. M., and Shafer, W. G.: Focal Osteoporotic Bone Marrow Defects of the Jaws, J. Oral Surg. 20: 123-128, 1962. Reprint requests to : Dr. Bruce F. Barker University of Missouri-Kansas School of Dentistry 650 E. 25th St. Kansas City, MO. 64108

City