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[Frontiers in Bioscience 3, c17-26, April 16, 1998] Reprints PubMed CAVEAT LECTOR |
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IN SEARCH OF AN ANIMAL MODEL FOR POSTMENOPAUSAL DISEASES E. A. Thorndike and A. S. Turner Department of Clinical Sciences, Colorado State University, Ft.Collins ,CO 80523 Received 9/25/97 Accepted 4/10/98 7. ORAL BONE LOSS Oral bone loss affects up to 94% of the elderly population (presently about 30 million); it is likely to increase in the future as the number of elderly increases (53). There is an intense interest to show correlation between systemic osteoporosis (specifically the hip and spine) and bone loss of the mandible and maxilla (54). Some studies have shown that bone density of the mandible is diminished in post-menopausal women suffering from osteoporosis when compared to controls (53). Others have shown that oral bone loss of the maxilla and mandible associated with osteoporosis of the hip and spine, as well as atrophy of the residual ridges after tooth loss, occurs frequently and inhibits prosthetic rehabilitation (53). The relationship between osteoporosis and oral bone loss is poorly understood. A large animal model exhibiting bone loss of the maxofacial region along with systemic osteoporosis would greatly clarify this relationship. To date, however, there has been little to no development of a model that could be used to study both of these diseases. The non-human primate has always been a promising model with obvious anatomical and physiological similarities, along with similar endocrine and sex steroid metabolism (55), but the disadvantages outlined in table 1 have restricted the use of primates. 7.1 The Use of Sheep to Study Oral Bone Loss Changes observed in mandibular bone at various stages of development in sheep have been studied (56). It was suggested that the sheep may be a model for human eduntulism. We have studied mandibular bone loss in OVX sheep using DXA (57). Skeletally mature ewes (4-5 years old; same breed and housing; n = 42) were divided into four groups: sham treated, OVX, OVX plus one estradiol (E2) implant (OVXE) and OVX plus two E2 implants (OVX2E). After 12 months, bone mineral density (BMD) of 4 regions of interest of excised mandibles (ROI: R1, R2, R3, and R4) was measured with DXA. Two scans of each bone were obtained and a mean BMD of each ROI was determined. Biopsies of both cortical and trabecular bone were obtained from the angles of randomly selected left mandible, four from OVX and four from sham, for histomorphometry. The BMD at all 4 ROI was lower in the OVX group than in the sham, OVXE or OVX2E groups. The mean BMD of the OVX group versus all others was lower but was not statistically significant (p = 0.26). (The means of BMD of all regions combined are shown in figure 5.) Cancellous bone volume was 24% and 36% in the OVX and sham groups respectively. The number of active remodeling sites (cuboidal osteoblasts) was 3.63 and 1.38 in the OVX and sham groups. Only modest changes in mandibular bone density was demonstrated after a year of estrogen deficiency. Although these changes did not reach statistical significance, larger numbers of animals or longer periods of follow-up will be needed to determine if the sheep can be used as a model for oral bone loss. ![]() Figure 5. Mean (+S.E.) of BMD of 4 regions of interest in the mandible in Sham, OVX, OVXE and OVX2E groups. This study, based on DXA and histomorphometry of the mandible, provided some evidence that systemic bone loss in OVX ewes may be accompanied by oral bone loss. Further, there was evidence that the prophylactic effect of estrogen occurred with oral bone loss as well as with osteoporosis. This supported the epidemiological data from one population of older women in a California retirement community, where estrogen users had retained more natural teeth than the non-users (58). Others have demonstrated that ERT had a positive affect on bone mass in the mandible and lumbar spine (59). The OVX ewe may be a useful large animal model in the study of mandibular bone loss and its manifestations. Although associations have been made between the extent of reduction of the residual ridges and osteoporosis in people, the sheep model may allow more controlled study of the effects of osteoporosis on bone remodeling following tooth loss and on the rate of success of dental implants and bone substitute materials in osteoporotic sites. The sheep model may also be useful in the study of therapeutic agents (e.g. estrogen analogs) and their protection against oral bone loss. Compared to laboratory animals, the sheep is particularly attractive to those studying the osseous responses to loaded implants and fixtures. The size of the ovine mandible allows implants of a more realistic size and loading to be used with better appreciation of the response to the tissues surrounding the implants. |