Changes in osteocyte density correspond with changes in osteoblast and osteoclast activity in an osteoporotic sheep model.

UNLABELLED: Histomorphometric assessment of trabecular bone in osteoporotic sheep showed that bone volume, osteoid surface area, bone formation rate, and osteocyte density were reduced. In contrast, eroded surface area and empty lacunae density were increased. Changes in osteocyte density correlated with changes in osteoblast and osteoclast activity. INTRODUCTION: Osteocytes contribute to the regulation of the activity of osteoclasts and osteoblasts that together control bone mass. Osteocytes therefore likely play a role in the loss of bone mass associated with osteoporosis. The purpose of this study was to investigate the relationships between osteocyte lacunar density and other bone histomorphometric parameters in the iliac crest (IC) and lumbar spine (LS) of osteoporotic sheep. METHODS: Osteoporosis was induced in ten mature ewes by an established protocol involving a combination of ovariectomy, dexamethasone injection, and low calcium diet for 6 months. Five ewes were used as controls. Post-mortem IC and LS biopsies were collected and processed for further histomorphometric assessment. RESULTS: Bone volume, osteoid surface, and bone formation rate in the IC and LS of osteoporotic sheep were reduced compared to those of the controls. In contrast, eroded surface area was increased in osteoporotic sheep. In the osteoporotic group, osteocyte density was reduced in the LS region and to a greater extent in the IC region. The empty osteocyte lacunae were increased 1.7-fold in LS and 2.1-fold in IC in the osteoporotic group. The osteocyte density correlated positively with markers of osteoblast activity and negatively with those of osteoclast activity. CONCLUSIONS: Depletion of osteocytes and an increase in the empty lacunae could be important factors contributing to bone loss in this model since they may adversely affect intercellular communication between osteoblasts and osteoclasts. The regional differences in histology suggest that there may be different pathological mechanisms operating at different anatomical sites.

Osteopenia in the maxillofacial area: a study in sheep.

UNLABELLED: Osteoporosis is a major public health problem worldwide. Its significance in the fields of traumatology and implantology of the maxillofacial area requires investigation. A large animal model was used to assess bone loss in the lumbar spine and mandible. INTRODUCTION: Osteoporosis is a prevalent disease characterized by low bone mass and microarchitectural deterioration of bone tissue. Osteoporosis-related fractures represent a major public health burden. The presence and relevance of osteoporosis in the maxillofacial area remain controversial. Research in humans is limited by difficulties in finding large homogenous study groups and, due to ethical considerations, numerous animal models have been used in osteoporosis research. The aim of this study was to assess a sheep model of generalized osteopenia for changes in the maxillofacial area. METHODS: Bone loss was induced in ten Merino sheep by ovariectomy, intramuscular administration of glucocorticoids, and a calcium-reduced diet. Five untreated animals served as controls. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry at the lumbar spine at baseline and after 1, 3, 6, 9, and 12 months. Lumbar and mandibular bone biopsies were obtained and analyzed with microcomputed tomography. RESULTS: Lumbar BMD decreased progressively in the intervention group and was most significantly low after 6 months (p < 0.001). Lumbar trabecular bone showed a significant decrease in bone volume (BV)/tissue volume (TV; p < 0.05) in the inducted group. Significant changes were found in both analyzed mandibular regions for BV/TV (p < 0.05). Regional variations were found for other parameters in the mandible. The cortical width was substantially reduced in the intervention group (p < 0.001). CONCLUSIONS: Microstructural changes occurring in sheep as a result of induction seem to have a generalized nature. This sheep model meets the criteria for further investigation in the maxillofacial area.

Iron content of eggs from hens given diets containing organic forms of iron, serine and methyl group donors, or phytoestogens.

1. This investigation included three experiments to determine whether the iron content of egg yolks could be enriched by supplementation of the laying diet with iron bound to organic compounds (Experiment 1), serine and methyl group donors methionine and choline (Experiment 2) or phytoestrogens (Experiment 3). 2. Hens at 34, 54 and 56 weeks of age were given experimental diets for 6, 4 and 4 weeks, respectively, in Experiments 1-3. Yolks from eggs laid over three successive days in the final week of feeding were pooled for each hen for analysis of iron by inductively coupled plasma mass spectrometry. 3. Iron concentration in egg yolk averaged 68-70, 66-71 and 62-69 microg/g in the respective experiments. 4. The addition of bloodmeal (1.22 mg Fe/egg) or phytoestrogens (1.25 mg Fe/egg) increased the total iron content of yolks by over 15% compared with the control diet (1.10 mg Fe/egg), and although this increase was not statistically significant it suggests that the iron content of eggs could be sufficiently manipulated to justify a nutritional claim of iron enrichment.

Validation of the sheep as a large animal model for the study of vertebral osteoporosis.

Rats have long been the animal of choice for research in the field of osteoporosis. In the search for a complementary large animal model the sheep appears useful but hitherto the extent of bone loss from the spine has failed to reach a level that is generally accepted as osteoporotic in humans. Osteoporosis was induced in ten sheep using ovariectomy, low calcium diet and steroid injection for 6 months. Bone samples of iliac crest (IC), lumbar spine (LS), and proximal femur (PF) from the osteoporotic sheep were compared with those from four normal sheep using densitometry, histomorphometry, biochemistry and basic mechanical testing. The differences were examined using an analysis of variance with Tukey-Kramer test. Overall, the bone mineral density at LS and PF decreased more than 25% after treatment. Trabecular bone volume decreased by 29.2, 33.4 and 42.6% in IC, LS and PF, respectively. The failure load of the LS in axial compression was reduced to 2,003 from 6,140 N. The extent of bone loss was sufficient to categorise these sheep as osteoporotic although the pattern of bone loss varied between sites. Reduced mechanical competence in LS confirmed the suitability of this model for evaluation of potential treatments for osteoporosis.