mandibular atrophy and metabolic bone loss

Mandibular atrophy and metabolic bone loss Histomorphometry of iliac crest biopsies in 74 patients

L. L. M. H. Habets 1, J. Bras 2 and J. P, R. van MerkesteyW 1Department of Oral and Maxillofacial Surgery, 2Department of Pathology, Academic Medical Centre at the University of Amsterdam, The Netherlands

L. L. M. H. Habets, J. Bras and J. P. R van Merkesteyn: Mandibular atrophy and metabolic bone loss. Histomorphometry o f iIiac crest biopsies in 74 patients. Int. J. Oral Maxillofac. Surg. 1988; 17: 325-329.

Abstract. Histomorphometry of iliac crest biopsies of 74 edentulous patients with severe atrophy of the mandible submitted for ridge augmentation, showed a mi- nority of the patients (14%) to have a significant decrease of trabecular bone volume, indicating osteoporosis. On the other hand, osteoid volume, osteoid seam thickness and active resorption surface, parameters for disturbances in mineralization, lack of calcium and hyperfunction of parathyroid glands, were significantly increased by 38%, 88% and 65% of the patients, respectively. These findings were more pronounced in the patients with radiological evidence of metabolic bone loss (38%, Gonion < 1). It may be concluded that metabolic bone loss, due to a lack of calcium and a subsequent hyperfunction of the parathyroid glands, plays a role in the etiology of severe atrophy of the edentulous mandible, which therefore might be prevented by supplementing with calcium with or without vitamin D.

Key words: mandible; atrophy; histomorphometry.

Accepted for publication 18 May 1988

Studies, based on radiological exami- nation, indicate a relation between mandibular atrophy and metabolic bone loss ~, s, 6, 9, 14, of which metabolic bone loss is defined as loss of bone due to alterations or disturbances in bone- mineral metabolism. ROSENQUIST et al? 4 found in all patients of a series of 12 edentulous female patients with severe mandibular atrophy and referred for vestibuloplasty of the mandible, a significant reduction of bone calcium mass in the radius, when compared with an age-matched control group of normal dentate persons. BAYS t~: WEINSTEIN 1 found in 4 of 10 consecutive edentulous patients, referred for osseous mandibular augmentation, a significantly decreased radial bone density. In a series of edentulous patients with severe atrophy of the mandible and submitted for ridge augmentation reported by BRAS et al?, 6 and HABETS et al. 9, 3 4 4 8 % of the patients, based on the cortical thickness at gonion 3, 4 had evidence of metabolic bone loss. In these patients, resorption of the augmented ridge was significantly faster than in patients without radiological indications of metabolic bone loss 6, 9.

Only 3, relatively small studies report on quantitative bone histology on unde-

calcified sections of iliac crest biopsies of edentulous patients, submitted for ridge augmentation 1, 8, ~0. In the study of FAZILI et al. 8, histomorphometrical findings of iliac crest biopsies of 6 edentulous female patients, are reported but not discussed. When compared to standard normal values reported in literature12,13, ~6, active resorption surface was elevated in 4 of the 6 patients (67%), whereas 2 of these 4 patients also showed an increase of osteoid volume. In the study of BAYS ~¢ WEINSTEIN 1, histomorphometry of iliac crest biopsies was done in 4 of l0 consecutive edentulous patients, who had radiological evidence of metabolic bone loss. Age and sex are not reported and the mean nor- real values used suggest a significant decrease of trabecular bone volume in 3 of the 4 patients. 2 of these 3 patients had a significant increase of osteoid volume and 1 had an increased osteoid seam thickness 1. These histological studies 1, 8 suggest an osteomalacia due to disturbances in mineralization (increase of osteoid volume and resorption surface) and an osteoporosis (decrease of trabecular bone volume).

In the study by HABETS et al? °, histomorphometry of iliac crest biopsies in 11 edentulous patients revealed a sig-

nificant increase of osteoid volume, osteoid seam thickness and active resorption surface in 7 (64%), 10 (91%) and 10 (91%) patients, respectively, indicating a lack of calcium and release of calcium from the skeleton. This was supported by their endocrinological in- vestigations, that revealed a secondary hyperfunction of parathyroid glands in 8 of the 11 patients (73%) ~°.

In this study, the histomorphometric findings in iliac crest biopsies of 74 edentulous patients with a severe atrophy of the mandible and submitted for ridge augmentation, are reported and compared with radiological parameters for metabolic bone loss. The findings are discussed.

Material and methods

Between March 1983 and September 1986, 74 edentulous patients (11 men, 63 women) with a severe atrophy of the mandible were treated by a combined sandwich-visor osteotomy with interpositional and peripheral bone grafting. This series of 74 patients includes the 11 patients of an endocrinological, radiological and histomorphometrical study ~°.

On orthopantomograms (OPG) of these 74 patients, the cortial thickness at Gonion (Gonion-index) as a parameter for metabolic bone loss 3, 4 was measured with a digital mi-

326 H a b e t s et al.

crometer (Helios®). The OPG's were done on a Siemens ® OPG-2. A Gonion-index of less than 1 mm was interpreted as radiological evidence for metabolic bone loss 5, 6. 9. Based on the Gonion-index, female and male patients were divided into subgroups of patients with and without radiological evidence of metabolic bone loss.

Of these 74 patients, standard transiliac biopsies (2 cm inferior and posterior to the anterior superior iliac spine, diameter 0.6 cm) were taken during the operation. These iliac crest biopsies were fixed in BURKHARDT'S 7 fixative 7, longitudinally divided into 3 parts and embedded in methylmethacrylate without decalcification. Of each of these 3 embedded parts, sections of 5/~ thickness were cut, stained with Masson Goldner's trichrome stain and histomorphometrically analysed by semi-automatic methods (light microscope with extended drawing tube and digitizing tablet with microcomputer). Of each biopsy, a total of at least 60 (3 x 20) optical fields were measured at a magnification of 100 x (objective 10 x, ocular i0 x). The parameters used for histomorphometry were: (a) relative trabecular bone volume, expressed as a % of the spongy bone volume, as a parameter for osteoporosis; (b) relative osteoid surface, expressed as a % of the trabecular bone surface, as a parameter of osteoblast activity; (c) relative osteoid volume, expressed as a % of the trabecular bone volume, and the mean osteoid seam thickness, both as a parameter of osteoblast activity and disturbances in mineralization; (d) relative active resorption surface, histologically characterized by the presence of osteoclasts and expressed as a % of the trabecular bone surface, as a parameter for deficiency of cal-

Histomorphometry. 1983 March - 1986 Sept.

Women

Men

25 38

3 8

6 3

11

7 4

Fig. 1. Iliac crest biopsies in 74 edentulous patients with a severe atrophy of the mandible and submitted for ridge augmentation, subdivided in female and male patients with (Go< 1) and without (Go> 1) radiological evidence of metabolic bone loss.

cium and hyperfunction of the parathyroid glands.

The data obtained on the relative trabecular bone volume have been compared with normal values, reported by MELSEN et aD z, and are expressed as normal or decreased by more than once or twice the standard deviation. Data on the relative osteoid volume and osteoid surface have been compared with normal values, reported by MELSEN et a/J 2, and are expressed as normal or increased by more than once or twice the standard deviation. Data on the mean osteoid seam thickness have been compared with normal values, reported by SCHULZ & DEL- LING 16 and are expressed as normal or increased by more than once or twice the standard deviation. Data on the relative active resorption surface are considered as elevated, if larger than 1% of the trabecular bone surface 13 .

Differences between the 2'radiological subgroups of women (Gonion < I, Gordon > 1) and between the 2 radiological subgroups of men (Gonion < 1, Gonion _> 1) for the histomorphometrical parameters used were esti- mated with the Student-t test. As a level of significance, p < 0.05 was chosen.

Results

Radiologically, a Gonion- index of lesss than 1 ram, indicating metabolic bone loss, was found in 28 of the 74 pat ients (38%), o f which 25 of the 63 women (40%) and 3 of the 8 men (38%) submitted for ridge augmentat ion (Fig. 1). For the 2 radiological subgroups o f women, (Gonion < 1, Gon ion > 1) and the 2 radiological subgroups of men (Gonion < 1, Gon ion > 1), the age and the histo- morphometr ica l findings, expressed as normal, decreased or increased by more than once or twice the s tandard devi- ation12, ]3, ~6, are summarized in Figs. 2-5.

Within these figures, the patients are arranged in h is tomorphometr ica l pat - terns. The findings are as follows.

Relative trabecular bone volume was decreased by more than twice the standard deviation, indicating osteoporosis , in:

3 o f the 25 women (12%) with a Gonion- index of less then 1 mm;

Pat,no.

132 185 177 188 11ss

74 137 117 121 171 142 186 161 124 175 166 159 140 144 147 156 118 125 184 130

Age group

==, ; •ml • • i Nil I mm | •ml • i mm) I toNi mm I mm mm I mm mm | mm I mm mm mm | mm mm 1 mm l mm m mm mm mm mm [] , m

Hls tomorphomet ry of l i lac crest

T r a b . O s t e o l d O s t e o l ¢ O s t e o l d A c t voh sur f . vol . seam res.

NNI ~ m

I

I )

I

I

I

I l N m

Fig. 2. The age and histomorphometric findings in the 25 women with a Gonion-index of less than 1 ram. The histomorphometric parameters are expressed as normal or as normal decreased, or increased with more than once or twice the standard deviation.

Mandibular atrophy 327

Pat .no. Age group

0 0 0 0 0

H-H-I-H 179

1-'g'2- E B I I 187 1 6 0

W 181 123 I. EB I 165 I • I

W 1 6 4

128 I •

I | ,

116 I 1 ~ ~se I I • 150 ~ 1 1 148 I ~ 1

I ~ 1 114 ~ 1 1 151 ~ 1 1 141 ~ 1 1

I ~ 1 145 I I • 133 I I • 157 I1 •

-P27-- I ~ l 163 • I 176 ~ 1 1 172 -- ~ ' - H ' - ~ 173

l-fT,,,,,,,~

His tomorphometry of lilac

Osteo ld Osteo ld Osteo ld sur f . vol . seam

- - - - - ~

K~",I

1

Trab. vol .

crest

Act . res.

<1>1

Fig. 3. The age and histomorphometrical findings in the 38 women with a Gonion-index of 1 mm or more. The histomorphometrical parameters are expressed as normal or as normal decreased, or increased, with more than twice once or the standard deviation.

5 of the 38 women (13%) with a Gonion- index of 1 mm or more;

1 of the 3 men (33%) with a Gonion- index of less than 1 mm;

1 of the 8 men (13%) with a Gonion- index of 1 m m or more~

Relative osteoid surface, a parameter for osteoblast activity, was normal in all patients.

Relative osteoid volume, a parameter for osteoblast activity and disturbances

in mineralization, was increased by more than twice the standard deviation in:

12 of the 25 women (48%) with a Gonion- index of less than 1 mm;

13 of the 38 women (34%) with a Gonion- index of 1 m m or more;


3 of the 8 men (38%) with a Gonion- index of 1 m m or more;

Mean osteoid seam thickness, a parameter for osteoblast activity and disturbances in mineralization, was increased by more than twice the standard diviation in:

21 o f the 25 women (84%) with a Gonion- index of less than 1 mm;

33 o f the 38 women (87%) with a Gonion- index of 1 mm or more;


8 of the 8 men (100%) with a Gonion- index of 1 mm or more;

An increase of active resorption surface, indicating a deficiency of calcium and a hyperfunction of the parathyroid glands, was found in:

15 of the 25 women (60%) with a Gonion- index of less than 1 mm;

23 o f the 38 women (61%) with a Gonion- index of 1 mm or more;

3 o f the 3 men (100%) with a Gonion- index of less than 1 mm;

6 of the 8 men (75%) with a Gonion- index of 1 m m or more;

For the 2 radiological subgroups of women (Gonion < 1, Gonion _> 1). and the 2 subgroups of men (Gonion < 1, Gonion _> 1), the range, mean, standard deviation and the median of the histo- morphometr ica l parameters used, are summarized in Tables l, 2. In the subgroups o f women and men with radiological evidence o f metabolic bone loss, relative osteoid volume, relative osteoid surface and relative active resorption surface tended to be more pronounced. However, these findings were statistically not significant

Discussion

In the subgroups of women with and without radiological evidence of metabolic bone loss (Figs. 2, 3), only a min- ority o f the patients, 12 and 13% respectively, revealed a significant decrease of trabecular bone volume, indicating osteoporosis. However, most of these oste- oporotic femals, also showed an increase of osteoid volume, osteoid seam thickness and active resorption surface, which was also found in a larger number of the other female patients.

The osteoid volume and the mean osteoid seam thickness were significantly increased in 48% and 84%, respectively, of the women with radiological evidence of metabolic bone loss (Fig. 2)

328 H a b e t s et al.

Age group Pat .no Histol

0 0 0 0 0

Trab . vol .

Fig. 4. The age and histomorphometrical findings in 3 men with a Goion-index of less than 1 rnm. The histomorphometrical parameters are expressed as normal or as normal decreased, or increased, with more than once or twice the standard deviation.

0 0 0 0 0

178 153 119 139 120 126 152 167

am n n a n minim

I N I I N i

N i l I mn

• "aN l

Fig. 5. The age and histomorphometrical findings in 8 men with a Gonion-index of 1 mm or more. The histomorphometrical parameters are expressed as normal or as normal decreased, or increased, with more than once or twice the standard deviation.

Table 1. Iliac crest histomorphometry in 25 women with (Fig. 2., Gonion < 1) and 38 women without (Fig. 3., Gonion >_ 1) indications of metabolic bone loss

Gonion < 1, 25 women Gonion _> 1, 38 women range median mean + sd range median mean +sd

Trab. volume 12.4-53.1% 23.7 25.1 + 8.24 12.540.2% 23.6 24.4_+ 6.76 Ost. surface 0.0-17.4% 7.4 7.63-4.46 0.7-15.9% 5.2 6.3_+4.05 Ost. volume 0.0-8.1% 2.3 2.63-1.81 0.1-5.8% 1.9 2.13-1.40 Ost. thickn. 0.0--61.9/~m 32.1 33.0+ 12.5 13.5-59.4/~m 34.4 33.83- 10.6 Res. surface 0.0-8.4% 1.4 2.0 3-1.99 0.2-0.6% 1.2 1.6 3-1.30

Table 2. Iliac crest histomorphometry in 3 men with (Fig. 4., Gonion < 1) and 8 without (Fig. 5., Gonion >_ 1) indications of metabolic bone loss

Gonion < 1, 3 men Gonion _> 1, 8 men range median mean_+ sd range median mean__+ sd

Trab. volume 16.6-27.7% 21.0 21.83-4.56 19.4-30.2% 23.6 24.3+_4.00 Ost. surface 3.5-12.1% 7.4 7.7__+3.52 1.2-14.6% 4.5 6.63-4.67 Ost. volume 1.2-5.9% 3.8 3.6_+ 1 . 9 2 0.3-6.3% 2.4 2.73-2.06 Ost. thickn. 34.4-42.3 #m 41.0 39.23- 3.51 28.4-61.5 ¢tm 33.2 38.1 -t- 11.8 Res. surface 1.6-2.9% 1.6 2.0+0.61 0.0M.I% 1.9 2.0+ 1.25

and in 34% and 87%, respectively, o f women without radiological evidence o f metabolic bone loss (Fig. 3). Since the osteoid surface, a parameter for osteoblast activity, was normal in all patients, the increase of osteoid volume and the mean osteoid seam thickness can be interpreted as a disturbance in mineralization, most probably due to a lack o f calcium. This is supported by the increase o f active resorption surface a (parameter for calcium deficiency and hyperfunction o f the parathyroid glands) in 60% of the women with and 61% of the women without radiological evidence of metabolic bone loss. These histological parameters for a disturbance in mineralization and lack o f calcium seemed to b e m o r e pronounced in the subgroup of women with radiological evidence of metabolic bone loss than in the subgroup of women without radiological evidence of metabolic bone loss (Table 1). However, the figures found were statistically not significant.

In the subgroups of male patients, a similar pattern was found (Figs. 4 and 5, Table 2). The low number o f male patients did not permit a further analysis.

F r o m these findings, it may be concluded that metabolic bone loss, histologically not characterized as osteoporosis, but as a disturbance in mineralization and increased resorption, plays a role in the etiology of mandibular atrophy. This disturbance in mineralization and increased resorption can be explained by a relative shortage o f calcium and subsequent hyperfunction of the parathyroid glands.

This is supported by our endocrinological studies 1°, that showed a secondary hyperfunction of the parathyroid glands in 8 of 11 edentulous patients submitted for ridge augmentat ion I°. The findings of KROOK et al. ~1, who found in animals with nutrional secondary hyperparathy- roidism, the first signs of bone loss in the jaws, especially the mandible, also support this hypothesis.

The reason for a relative shortage o f calcium might be a dietary one. Surveys of the diet of Nor th-Americans have demonstrated that 33% of women between the ages o f 18 and 74 years did not intake the recommended quantities of calcium, whereas only 25% of women older than 35 years were shown to have adequate calcium intakes1< A factor equally important to the absolute calcium intake is the calcium-phoshorus ratio. This ratio should be approximate-

Mandibular atrophy 329

ly 1:1. The N o r t h - A m e r i c a n diet, however, usually conta ins an excess of phosphorus. Due to an excess of diet-phosphorus and the subsequent increase of serum phospha t e , serum calcium is low- ered, ul t imately result ing in secondary hyper func t ion of the pa ra thy ro id glands 2, 1~

In a diet analyses of 14 endetulous pat ients with min imal residual ridge loss of the mand ib l e and 30 edentulous patients with severe residual ridge loss of the mandib le , WICAL & SWOOPE ~7 found in the group o f pat ients with a severe residual ridge loss, a significant decrease of calcium a n d phosphorus in take wi th a significant decrease of the calc ium/ phosphorus rat io, due to a relative increase of p h o s p h o r u s 17.

WICAL 8~ BRUSSEE 18 also noted, in a group of pa t i en t s receiving calcium and v i tamin D2 daily for at least 1 year fol- lowing teeth extract ion, a significant re- duct ion in a lveolar bone resorp t ion when c o m p a r e d to identical pat ients receiving a p lacebo TM.

It may therefore be concluded tha t metabol ic b o n e loss, due to a relative lack of calc ium and a subsequent hyper- funct ion of the pa ra thyro id glands, plays a role in the etiology of a t rophy of the eden tu lous mandible . I t may be prevented by a daily supplement of calcium with or w i thou t v i tamin D.

References

1. Bays, R. A., & Weinstein, R. S.: Systemic bone disease in patients with mandibular atrophy. J. Oral Maxillofac. Surg. 1982: 40: 270-272.

2. Baxter, J. C.: Relationship of osteoporosis to excessive residual ridge resorption. J. Prosthet. Dent. 1981: 46:123 t25.

3. Bras, J., Ooij, C. R van., Abraham-In- pijn, L., Kusen, G. J. & Wilmink, J. M.: Radiographic interpretation of the mandibular angular cortex. A diagnostic tool in metabolic bone loss. Part I. Normal state. Oral. Surg. Oral. Med, Oral Pathol. 1982: 53: 541-545.

4. Bras, J., Ooij, C. R van., Abraham-In- pijn, L. Wilmink, J. M. & Kusen, G. J.: Radiographic interpretation of the mandibular angular cortex. A diagnostic tool in metabolic bone loss. Part II. Renal ostcodystrofy. Oral Surg. Oral Med. Oral Pathol. 1982: 53: 647-650.

5. Bras, J., Ooij, C. R van, Duns, J. Y., Wansink, H. M., Driesen, R. M. & Ak- ker, H. P van den: Mandibular atrophy and metabolic bone loss. A radiologic analysis of 126 edentulous patients. Int. J. Oral Surg. 1983: 12: 309-313.

6. Bras, J., Ooij, C. R Van & Akker, H. R van den: Mandibular atrophy and metabolic bone loss. Mandibular ridge augmentation by combined sandwich-visor osteotomy and resorption related to metabolic bone state. Int. J. Oral Surg. 1985: 14: 16-21.

7. Burkhardt, R. (ed.).: Farbatlas der klini- schen Histopathologie yon Knochenmark und Knochen. Berlin, Heidelberg, New York: Springer-Verlag, 1970: p. 7.

8. Fazili, M., Overvest-Eerdmans, G. R, Van, Vernooy, A. M., Visser, W. J. & Waas, M. A. J. van: Follow-up investiga- tion of reconstruction of the alveolar pro- cess in the atrophic mandible. Int. J. Oral Surg. 1978: 7: 400404.

9. Habets, L. L. M. H., Bras, J., Akker, H. R van den, Borgmeyer-Hoelen, A. M. M. J. & Ooij, C. R van: Mandibular atrophy and metabolic bone loss. Mandibular ridge augmentation by combined sandwich-visor osteotomy and resorption related to metabolic bone state. A 5 year follow-up. Int. J. Oral. MaxiIlofac. Surg. 1987: 16: 540-547.

10. Habets, L. L. M. H., Bras, J., Borgmeyer- Hoelen, A. M. M. J.: Mandibular atro-

phy and metabolic bone loss. Endocrin- ology, radiology and histomorphometry. Int. J. Oral Maxillofac. Surg. 1988: 17: 208-211.

11. Krook L., Whalen, J. R, Lesser, G. V. & Berens, D. L.: Experimental studies on osteoporosis. Meth. Achiev. exp. Pathol. 1975: 7: 72-108.

12. Melsen, F., Melsen, B., Moskilde, L. Bergmann, S.: Histomorphometric analysis of normal bone from the iliac crest. Acta Pathol. Microbiol Scand. 1978: 86: 70-8 I.

13. Rasmussen, H. & Bordier, P. (eds.): The physiological and cellular basis of metabolic disease. Baltimore: Williams and Wilkins, 1974, pp. 57-70.

14. Rosenquist, J. B., Baylink, D. J. & Berger, J. S.: Alveolar atrophy and decreased skeletal mass of the radius. Int. J. Oral Surg. 1978: 7: 479481.

15. Schachtele, C. F., Rosamond, W. D. & Harlander, S. K.: Diet and aging: Current concerns related of oral health. Gerodon- tics 1985: 1: 117-124.

16. Schulz, A. & Delling, G.: Age related changes of new bone formation. Determi- nation of histomorphometric parameters of the iliac crest trabecular bone. In: Ja- woreski, Z. F. G. (ed.): Proceedings of the 1st Workshop on Bone Morphometry. Ottawa: University of Ottawa Press, 1976: pp. 189-190.

17. Wical, J. C. & Swoope, C. C.: Studies of residual ridge resorption. Part II. The relationship of dietary calcium and phosphorus to residual ridge resorption. J. Prosthet. Dent. 1974: 32: 13-22.

18. Wical, J. C. & Brussee, R: Effects of a calcium and vitamin D supplement on alveolar ridge resorption in immediate denture patients. J. Prosthet. Dent 1979: 41: 4-11.

Address: J. Bras Academic Medical Centre at the University of

Amsterdam Deparment of Pathology, H2 Meibergdreef 9, 1105 A Z Amsterdam The Netherlands

mandibular atrophy and metabolic bone loss

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