Periosteal appositional bone growth from age two to age seventy in man. A tetracycline evaluationкод для вставкиСкачать
Periosteal Appositional Bone Growth from Age Two to Age Seventy in Man A TETRACYCLINE EVALUATION ' BRUCE N. EPKER2 AND HAROLD M. FROST3 Orthopedic Research Lnboratory, Henry Ford Hospital, Detroit, Michigan ABSTRACT Periosteal appositional bone formation in human ribs was analyzed. Tetracycline labels deposited in uiuo reveal that in human ribs there can be continued apposition of periosteal bone after age 20, which decreases in amount with advancing age but is still present in the seventh decade. It has been tacitly assumed that periosteal osteoblastic activity and the concomitant periosteal apposition of new bone, which cause an increase in the outside diameter of a bone during its growth and development, ceases at or shortly after skeletal maturity, which occurs at about age 20 (Todd, '37; Krogman, '62; Tonna and Cronkite, '62). This concept has recently been challenged on the bases of studies of human ribs and femurs, in which increases in transverse dimensions were found to continue well past age 40 (Trotter et al., '60; Sedlin et al., '63; Smith and Walker, '64). It would be desirable to confirm these findings by some means which provides unequivocal and direct evidence that periosteal bone apposition does indeed continue after skeletal maturity, since this would (i) remove any doubt that sampling errors were present in these studies, and (ii) prove that periosteal bone formation remains active throughout life. Over 400 mineralized, complete crosssections of the middle third of the fifth, sixth or seventh rib from 92 metabolically normal individuals were studied (Frost, '58). The age ranged from 2 to 70 years, and the bones had been labeled in viuo on one or more occasions with a tetracycline antibiotic, which was usually given to treat infections. These ribs were selected for study on the bases that: (i) examination of mineralized cross sections with the fluorescence microscope showed one or more tetracycline labels to be present somewhere in the bone, showing that a tetracycline antibiotic had been given at some time prior to skeletal sampling, and (ii) the ANAT. REC.,154: 573-578. TABLE 1 T h e fourth column expresses as n per cent the fraction of the labeled subjects that hnd a circumferential lamellar (see footnote 6 , p . 5 7 5 ) tetracycline label. However, the size (i.e., circumference) o f labels i n older people was much less than i n children, so the per cent figures do not indicute absolute differencesi n the amount o f labeled bone, Age group Total number individuals Number of of labeled with a individuals periosteal label 0-9 10-19 12 5 11 20-29 30-39 40-49 50-59 60-69 20 20 13 7 15 14 12 4 2 5 92 52 Totals 4 P$gzt pe;',"b"a' 92 80 70 60 31 29 33 Mean56.4 individual was known to have had no serious metabolic disease or intrinsic bone disease prior to sampling. About three quarters of these cases were sampled at autopsy at the county medical examiner's office, causes of death including suicide, homicide, trauma, drowning and exposure. The remainder of the cases supplied rib at thoracotomy for nondebilitating lesions such as hiatus hernia, lung and mediastinal biopsy and repair of patent d u c t ~ s . ~ 1 Work supported b rants AM-04186 of National Institutes of HeaJth, et esda, Md., and Project 293, Henrv Ford HosDital. 2 Rksident, Department of Oral Surgery, Henry Ford Hospital, ,Detroit 2, Michigan. 3 Associate Orthopaedic Surgeon Department of Orthopaedic Surgery, Henry Ford Hbspital, Detroit 2, Michigan. 4 We are deeply indebted to the generosity of E. S. Zawadski, M.D. for the autopsy material and to R. Tabor, M.D., C. Lam, M.D. and T. Gehagen, M.D. for material obtained at thoracotomy. 3% 573 574 BRUCE N. EPKER AN D HAROLD M. FROST As reported in 1957 by Milch, Rall and Tobie, any of the tetracycline group of antibiotics will produce a permanent label or tissue marker at each place in the skeleton where new bone formation was active while the antibiotic was being administered (Milch et al., '57) see figure 1. In 44 of these cases the antibiotic was given at times known to us, and they proved to have been labeled an average of 46 months prior to sampling, the range being 0.1 to 10.5 years. While in the remaining 48 cases this information was not available, it is reasonable to assume that approximately similar figures apply to them. The 400 rib sections were studied by fluorescence microscopy to detect tetracycline labels in the subperiosteal circumferential lamellae, and when one or more such labels were present the fact was re- Fig. 1 The light bands are labels of tetracycline antibiotics as they appear under fluorescence microscopy. This is a rib cross-section from a nine-year-old child who had four separate labels incorporated in the cutaneous periosteal circumferential lamellae as it was drifting (to the right) during growth. Periosteum to the right, marrow cavity to the left ( 8 x ) . The bright, wavy line crossing the marrow space in the lower half :is a cotton fiber embedded in the mountant. PERIOSTEAL BONE GROWTH 575 Fig. 2 Rib cross-section (166 x ) from a 37-year-old female. The India ink markers separate two tetracycline labels incorporated in the periosteal circumferential lamellae. corded. Therefore, while all of the cases in this study had some tetracycline labeled bone, not all of them had labels deposited in the subperiosteal circumferential lamellae.5*6The data are shown in table 1. RESULTS Ninety-two per cent of the children under age ten who had received tetracycline had a label in the subperiosteal lamellae, usually on the cutaneous cortex (see fig. 1). With increasing age, there was a significant decline in the per cent of labeled people who had periosteal labels, the level being 33% in the seventh decade. We also observed that the size (i.e., circumference), of labels in older people was much less than in children, so the figures in table 1 do not indicate absolute differences in the amount of labeled bone between young and old (see figs. 2, 3). DISCUSSION It has generally been assumed that after skeletal maturation periosteal osteogenic activity was active only in pathological states or/and in fracture healing, i.e., that after skeletal maturity bones do not get bigger. In this regard, it has been suggested that with increasing age bone cells respond with less vigor (Tonna and Cronkite, '62). But recent studies of periosteal remodeling, bone surface drift, and of age related changes in bone mass, volume and cross-sectional area, have suggested that the periosteal bone surface remains active and in positive bone balance (i.e., in sum, continually adds bone so that the periosteal envelope continues to enlarge) throughout life (Trotter et al., '60; Sedlin et al., '63; Smith and Walker, '64; Epker and Frost, '65). If this were so, tetracycline labels should be incorporated into periosteal circumferential lamellae in adults as well as in children. This study shows that this is the case. 5 Labeled: had been given a tetracycline antibiotic. Label: tetracycline that had been deposited in newly forming bone. 6 Circumferential lamellae are the layers of new lamellar bone deposited immediately under the penosteum. This specifically excludes Haversian systems, and thus any tetracycline labels i n Haversian systems. 576 BRUCE N . EPKER A N D HAROLD M. FROST Fig. 3 Rib Cross section (166 X ) from 66-year-old male. The light band to the right is a tetracycline label incorporated i n the periosteal circumferential lamellae. We found that: (i) new periosteal bone apposition occurs throughout life, and (ii) with increasing age, a decreasing fraction of the labeled cases revealed circumferential lamellar labeling. The rapidly growing child, as compared to the adult, demonstrates significantly more sites of new periosteal bone apposition. However, even those persons aged 60 to 70 show some evidence of such appositional growth. At no age were 100% of the periosteal surfaces labeled. This could mean one of two things: (i) periosteal bone formation is normally intermittent, so that at some moment a label will not be deposited; (ii) or periosteal bone formation had stopped permanently in those individuals who lacked a periosteal label. It is unreasonable to assume that (ii) is true in children, which implies that (i) is the correct interpret ation. Most of the labels at all ages had been covered over by 5 to 30 CI of new unlabeled periosteal circumferential lamellae bone (see figs. 2, 3 ) . This must have been added after the time of labeling but before skeletal sampling. Since Auneomycin, the first tetracyline antibiotic was first marketed in 1950, there can be no doubt that all labeled patients older than age 35 received their label after skeletal maturity. These findings are coiiclusive evidence that human periosteal bone apposition can continue after skeletal m,aturity. LITERATURE CITED Epker, B. N., and H. M. Frost 1965 A histological study of remodeling at the periosteal, haversian canal, cortical endosteal, and trabecular endosteal surfaces in human ribs. Anat. Rec., 152: 129-136. Frost, H. M. 1958 Preparation of thin, undecalcified bone sections by rapid manual method. Stain Technol., 33: 272-276. Krogman, W. M. 1962 The Human Skeleton in Forensic Medicine. Charle's C Thomas, Springfield, Ill., p. 227. Milch, R. A ,, D. P. Rall and J. E. Tobie 1957 Bone localization of the tetracyclines. J. Nat. Cancer Inst., 19: 87-93. PERIOSTEAL BONE GROWTH Sedlin, E. D., A. R. Villanueva and H. M. Frost 1963 Variations in cross section area of rib cortex with bone. Gerontology, 18: 9-13. Smith, R., and R. Walker 1964 Femoral expansion i n aging women: implications for osteoporosis and fractors. Science, 145: 156-157. Todd, T. W. 1937 Atlas of Skeletal Maturation (Hand). Mosby, St. Louis. 577 Tonna, E. A., and E. P. Cronkite 1962 Changes in the skeletal cell proliferative response to trauma concomitant with aging. J. Bone and Joint Surg., 44A: 1557-1568. Trotter, M., G. E. Broman and R. R. Peterson 1960 Densities of bones of white and negro skeletons. J. Bone and Joint Surg., 42A: 50-58.