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Biomedical subjects

N Miyakoshi

Publications and source records attributed to N Miyakoshi.

At least 19 recordsLinked to original sources

Ex vivo gene therapy with stromal cells transduced with a retroviral vector containing the BMP4 gene completely heals critical size calvarial defect in rats.

In order to develop a successful gene therapy system for the healing of bone defects, we developed a murine leukemia virus (MLV)-based retroviral system expressing the human bone morphogenetic protein (BMP) 4 transgene with high transduction efficiency. The bone formation potential of BMP4 transduced cells was tested by embedding 2.5 x 10(6) transduced stromal cells in a gelatin matrix that was then placed in a critical size defect in calvariae of syngenic rats. Gelatin matrix without cells or with untransduced stromal cells were the two control groups. The defect area was completely filled with new bone in experimental rats after 4 weeks, while limited bone formation occurred in either control group. Bone mineral density (BMD) of the defect in the gene therapy group was 67.8 +/- 5.7 mg/cm(2) (mean +/- s.d., n = 4), which was 119 +/- 10% of the control BMD of bone surrounding the defect (57.2 +/- 1.5 mg/cm(2)). In contrast, BMD of rats implanted with untransduced stromal cells was five-fold lower (13.8 +/- 7.4 mg/cm(2), P < 0.001). Time course studies revealed that there was a linear increase in BMD between 2-4 weeks after inoculation of the critical size defect with 2.5 x 10(6) implanted BMP4 cells. In conclusion, the retroviral-based BMP4 gene therapy system that we have developed has the potential for regeneration of large skeletal defects.

Animals↗

First total synthesis of (-)-ichthyothereol and its acetate.

The first and stereoselective total syntheses of (-)-ichthyothereol (1) and its acetate ((+)-2) were achieved by incorporation of the two chiral centers of diethyl L-tartrate. The starting diethyl L-tartrate was converted into trans-2-ethynyl-3-hydroxytetrahydropyran 14 in a stereoselective manner via the endo mode cyclization of the epoxy-alkyne derivative 12. The alcohol 12 was then transformed into (E)-iodoolefin derivative 15, which was exposed to a coupling reaction with 1-tributylstannyl-1,3,5-heptyne (19), derived from the corresponding 1-trimethylsilyl-1,3,5-heptyne (18), under Stille conditions to produce the all-carbon framework of the target natural products. Chemical modification of the coupled product 20 under conventional conditions completed the first total synthesis of (-)-ichthyothereol (1) and its acetate ((+)-2).

Alkynes↗

Evaluation of long-term sequential changes in bone mass and strength following withdrawal of incadronate disodium (YM175) in ovariectomized rats.

We evaluated the long-term effects of withdrawal of a newer third-generation bisphosphonate, incadronate disodium (YM175), on both cancellous and cortical bone mass and strength in ovariectomized (OVX) rats. One hundred and sixty female SD rats at 13 weeks of age were randomized into four groups: sham-operated, OVX, and low- and high- YM (0.01 or 0.1 mg/kg s.c., three times a week after OVX). After 4 weeks of treatment with vehicle or incadronate disodium, rats from each group (n = 8) were killed at 0 (baseline), 3, 6, 9, and 12 months after the withdrawal of YM175. Histomorphometric studies of the proximal tibia revealed a dose-dependent decrease in OVX-induced bone turnover; cancellous bone volume was significantly higher in the YM groups compared with the OVX control group up to 6 months after withdrawal at low dose and up to 12 months after withdrawal at high dose. The low-dose group showed little effect on tibial diaphyseal cortical bone volume and width, while the high-dose group preserved both cortical parameters 12 months after withdrawal. Mechanical testing of femurs revealed that both metaphyseal and diaphyseal strengths were significantly higher at high dose compared with the OVX group until 12 months after withdrawal. These observations demonstrated that high-dose incadronate disodium preserved both cancellous and cortical bone mass and strength in OVX rats for 12 months after withdrawal of the agent.

Animals↗

Evidence that IGF-binding protein-5 functions as a growth factor.

Recent studies support the concept that IGF-binding protein-5 (IGFBP-5) stimulates bone formation, at least in part, via IGF-independent mechanisms. To evaluate this hypothesis further, we evaluated in vitro and in vivo effects of IGFBP-5 on bone formation parameters using the IGF-I knockout (KO) mouse. Treatment of serum-free cultures of osteoblast clones derived from IGF-I KO mice with recombinant human IGFBP-5 increased both proliferation and alkaline phosphatase (ALP) activity in a dose-dependent manner, an effect comparable to that seen with IGF-I. IGF-II levels from media conditioned by osteoblasts derived from IGF-I KO mouse were below those detectable by RIA. To eliminate possible actions of IGF-II, if any was produced by osteoblasts derived from IGF-I knockout mice, the IGFBP-5 effect was studied in the presence of exogenously added IGFBP-4, a potent inhibitor of IGF-II actions in bone cells. Addition of IGFBP-4 blocked IGF-I- but not IGFBP-5-induced cell proliferation in osteoblasts derived from IGF-I knockout mice. Consistent with in vitro results, a single local injection of IGFBP-5 to the outer periosteum of the parietal bone of IGF-I KO mice increased ALP activity and osteocalcin levels of calvarial bone extracts. The magnitudes of IGFBP-5-induced increases in ALP and osteocalcin in parietal bone extracts of IGF-I KO mice were comparable to those seen in C3H mice. In contrast to IGFBP-5, local administration of IGFBP-4 had no significant effect on bone formation in C3H and IGF-I KO mice. These results provide the first direct evidence to our knowledge that IGFBP-5 functions as a growth factor that stimulates its actions in part via an IGF-independent mechanism.

Alkaline Phosphatase↗

Evidence that anabolic effects of PTH on bone require IGF-I in growing mice.

Although it has been established that PTH exerts potent anabolic effects on bone in animals and humans, the mechanism of PTH action on bone remains controversial. Based on the previous findings that PTH treatment increased production of IGF-I in bone cells and that PTH effects on bone cells in vitro were blocked by IGF-I-blocking antibodies, we proposed that IGF-I action is required for the stimulatory effects of PTH on bone formation. To test this hypothesis, we evaluated the effects of PTH on bone formation parameters in growing mice lacking functional IGF-I genes. Five-week-old IGF-I(-/-) mice and wild-type littermates were given daily sc injections of 160 microg/kg body weight of PTH (1-34) or vehicle for 10 d. In wild-type animals, PTH caused a significant increase in serum osteocalcin levels (113%), serum alkaline phosphatase activity (48%), and alkaline phosphatase activity in femoral bone extracts (>80%), compared with the vehicle-treated control group. In contrast, in IGF-I(-/-) mice, there was no significant effect of PTH on any bone formation parameters. PTH treatment increased total bone mineral density, as evaluated by peripheral quantitative computer tomography, at the distal metaphysis of the femur by 40% in wild-type mice, but it had no effect on bone mineral density in mice lacking functional IGF-I genes. In vitro studies using osteoblasts derived from control and IGF-I(-/-) mice revealed that PTH treatment increased cell number in osteoblasts derived from IGF-I knockout mice in the presence of exogenously added IGF-I but not without IGF-I. These data to our knowledge provide the first direct evidence that the anabolic effects of PTH on bone formation in vivo require IGF-I action in growing mice.

Animals↗

Systemic administration of insulin-like growth factor (IGF)-binding protein-4 (IGFBP-4) increases bone formation parameters in mice by increasing IGF bioavailability via an IGFBP-4 protease-dependent mechanism.

Insulin-like growth factor (IGF)-binding protein-4 (IGFBP-4) is a potent inhibitor of IGF actions in vitro. However, we found that systemic administration of IGFBP-4 at pharmacological doses caused a significant increase in bone formation parameters in mice by a mechanism that may involve increased IGF bioavailability via proteolysis of IGFBP-4. To evaluate the hypothesis that proteolysis of IGFBP-4 is essential for the stimulatory effects of systemically administered IGFBP-4, we produced wild-type, protease-resistant, and IGFBP-4 proteolytic fragments and evaluated their effects using biochemical markers. Protease-resistant IGFBP-4 was more potent than wild-type IGFBP-4 in inhibiting IGF-I-induced mouse osteoblast cell proliferation in vitro and in inhibiting IGF-I-induced increase in alkaline phosphatase (ALP) activity in bone extract after local administration in vivo. Systemic administration of wild-type IGFBP-4, but not protease-resistant IGFBP-4, increased serum osteocalcin, serum ALP, and ALP in skeletal extracts in a dose-dependent manner, with a maximal effect of 40% (P < 0.05) at 1.25 nmol/mouse. Systemic administration of wild-type, but not protease-resistant, IGFBP-4 increased free IGF-I levels in serum in normal mice. IGF-I, but not wild-type IGFBP-4, increased bone formation parameters in IGF-I-deficient mice. This study demonstrates that systemic administration of IGFBP-4 increases bone formation parameters in mice by increasing IGF bioavailability in the circulation via an IGFBP-4 protease-dependent mechanism.

Alkaline Phosphatase↗

Postnatal and pubertal skeletal changes contribute predominantly to the differences in peak bone density between C3H/HeJ and C57BL/6J mice.

Previous studies have shown that 60-70% of variance in peak bone density is determined genetically. The higher the peak bone density, the less likely an individual is to eventually develop osteoporosis. Therefore, the amount of bone accrued during postnatal and pubertal growth is an important determining factor in the development of osteoporosis. We evaluated the contribution of skeletal changes before, during, and after puberty to the development of peak bone density in C3H/HeJ (C3H) and C57BL/6J (B6) mice. Volumetric bone density and geometric parameters at the middiaphysis of femora were measured by peripheral quantitative computed tomography (pQCT) from days 7 to 56. Additionally, biochemical markers of bone remodeling in serum and bone extracts were quantified. Both B6 and C3H mice showed similar body and femoral weights. B6 mice had greater middiaphyseal total bone area and thinner cortices than did C3H mice. Within strains, males had thicker cortices than did females. C3H mice accumulated more minerals throughout the study, with the most rapid accumulation occurring postnatally (days 7-23) and during pubertal maturation (days 23-31). C3H mice had higher volumetric bone density as early as day 7, compared with B6 mice. Higher serum insulin-like growth factor I (IGF-I) was present in C3H mice postnatally at day 7 and day 14. Until day 31, B6 male and female mice had significantly higher serum osteocalcin than C3H male and female mice, respectively. Alkaline phosphatase (ALP) was found to be significantly higher in the bone extract of C3H mice compared with B6 mice at day 14. These data are consistent with and support the hypothesis that the greater amount of bone accrued during postnatal and pubertal growth in C3H mice compared with B6 mice may be caused by increased cortical thickness, increased endosteal bone formation, and decreased endosteal bone resorption.

Animals↗

Long-term effects of withdrawal of bisphosphonate incadronate disodium (YM175) on bone mineral density, mass, structure, and turnover in the lumbar vertebrae of ovariectomized rats.

This study was designed to evaluate the long-term effects of incadronate disodium (YM175) after its withdrawal on cancellous bone mass in ovariectomized (OVX) rats. Thirteen-week-old female SD rats were randomized into four groups: sham-operated, OVX, low-YM, and high-YM (0.01 mg/kg or 0.1 mg/kg subcutaneously [sc], three times a week after OVX) groups. After 4 weeks of treatment with vehicle or YM175, rats from each group were killed at time points of 0 (baseline), 3, 6, 9, and 12 months after withdrawal of the agent. Bone mineral density (BMD) of the lumbar vertebrae was measured by dual-energy X-ray absorptiometry (DXA). Bone volume (BV/TV), trabecular number and trabecular separation (Tb.N and Tb.Sp), eroded surface (ES/BS), osteoclast number and osteoclast surface (N.Oc/BS and Oc.S/BS), osteoid surface (OS/BS), and bone formation rate (BFR/BS) were measured as histomorphometric parameters of the fifth lumbar vertebra. BMD, BV/TV, Tb.N, and Tb.Sp in YM175-treated groups were maintained at the same level as in the sham group until 12 months after withdrawal in the high-YM group and until 3 months after withdrawal in the low-YM group. YM175 decreased both bone formative and resorptive parameters in histomorphometry. Serum bone-specific alkaline phosphatase (ALP) and urinary deoxypyridinoline at both doses of YM175 also showed a suppressive effect of this agent on bone turnover. These results indicate that YM175, after withdrawal, still maintains bone volume dose dependently by depressing bone resorption and formation in OVX rats. Intermittent YM175 treatment with a long interval may be sufficient to maintain the bone volume and structure in OVX rats.

Aging↗

Restoring effect of human parathyroid hormone (1-34) on trabecular connectivity in ovariectomized rats.

The purpose of this study was to determine if the loss of the trabecular connectivities can be recovered by human parathyroid hormone-(1-34) therapy in ovariectomized (OVX) rats. Seven-month old female Wistar rats underwent ovariectomy or sham-operation at the beginning of the experiment. All sham operated groups (sham groups) were sacrificed after 0 (initial-BL group), 4, 8, 12, and 16 weeks, and one-third of the OVX rats were sacrificed as the baseline controls (OVX-BL groups) at 4, 8, and 12 weeks after OVX. Four weeks PTH or its vehicle treatment for residual OVX rats was started at 4, 8, or 12 weeks after OVX (OVX+PTH groups, OVX+vehicle groups). h-PTH (6.0 microg/kg) was injected subcutaneously six times a week for 4 weeks for each group. Their proximal right tibiae were processed for undecalcified Villanueva bone staining sections for bone histomorphometry. Furthermore, changes in trabecular connectivities were determined by node-strut analysis. h-PTH completely restored OVX-induced cancellous bone loss by stimulating bone formation. In node-strut analysis, node number in the OVX-BL-4, -8, and -12 groups was decreased to 53%, 49% and 44% of the initial-BL value respectively, and that in the OVX-4, -8, -12 + PTH groups recovered to 80%, 66%, 56% of the initial-BL value respectively. However, they were lower than those in their corresponding sham groups. The findings of this study suggested that decreased trabecular connectivity by OVX was recovered by intermittent h-PTH administration. However, delayed treatment blunted the restoration of trabecular connectivity.

Animals↗

Differential protein profile in the ear-punched tissue of regeneration and non-regeneration strains of mice: a novel approach to explore the candidate genes for soft-tissue regeneration.

Wound repair/regeneration is a genetically controlled, complex process. In order to identify candidate genes regulating fast wound repair/regeneration in soft-tissue, the temporal protein profile of the soft-tissue healing process was analyzed in the ear-punched tissue of regeneration strain MRL/MpJ-Fas(lpr) (MRL) mice and non-regeneration strain C57BL/6J(B6) mice using surface-enhanced laser desorption and ionization (SELDI) ProteinChip technology. Five candidate proteins were identified in which responses of MRL to the ear punch were 2-4-fold different compared to that of B6. Their corresponding genes were predicted using an antigen-antibody assay validated mass-based approach. Most of the predicted genes are known to play a role or are likely to play a role in the wound repair/regeneration. Of the five candidate proteins, the amount of the 23560 Da protein in the ear-punched tissue was significantly correlated with the rate of ear healing in six representative strains of mice, making it a good candidate for fast wound repair/regeneration. We speculate that the increased concentration of the 23560 Da protein in the wound tissue could stimulate the expression of various growth-promoting proteins and consequently speed up the wound repair/regeneration processes. Here, we have shown that examination of protein expression profile using SELDI technology, coupled with database search, is an alternative approach to search for candidate genes for wound repair/regeneration. This novel approach can be implemented in a variety of biological applications.

Animals↗

Outcome of one-level posterior lumbar interbody fusion for spondylolisthesis and postoperative intervertebral disc degeneration adjacent to the fusion.

STUDY DESIGN: Review of the clinical and radiologic records of patients who underwent one-level posterior lumbar interbody fusion (PLIF) at L4-L5. OBJECTIVE: To determine whether adjacent intervertebral disc degeneration after PLIF affects the clinical results, and whether preoperative caudal disc (L5-S1) degeneration affects postoperative clinical results. SUMMARY OF BACKGROUND DATA: There is little reliable information in the literature regarding clinical results and adjacent disc degeneration after PLIF. METHODS: Forty-five patients who underwent L4-L5 PLIF for spondylolisthesis with more than 5 years of postoperative observation were included in this study. PLIF was performed in conjunction with posterior instrumentation. The posterior lumbar intervertebral grafting was performed using both autograft and a ceramic spacer. Intervertebral disc heights at L2-L3, L3-L4, and L5-S1 were measured before and after surgery. The patients were divided into two groups based on the presence or absence of the preoperative L5-S1 narrowing. Correlation between clinical status evaluated by the recovery rate of the Japanese Orthopedic Association (JOA) score and disc heights were determined. RESULTS: All intervertebral disc heights adjacent to the fusion decreased after surgery (P < 0.05). However, no significant correlation was seen between clinical results estimated by the recovery rate and postoperative disc narrowing. There was also no significant difference in clinical results between patients with or without preoperative L5-S1 narrowing. CONCLUSIONS: There is no evidence from the results that postoperative narrowing of the adjacent disc and preoperative narrowing of the L5-S1 disc affects the clinical outcome of L4-L5 PLIF.

Adult↗

Histomorphometric evaluation of the recovering effect of human parathyroid hormone (1-34) on bone structure and turnover in streptozotocin-induced diabetic rats.

The purpose of this study was to determine whether human parathyroid hormone (h-PTH) enhances trabecular bone mass and connectivities that were reduced by streptozotocin (STZ)-induced diabetes in rats. Seven-month-old female Wistar rats were injected with STZ or its vehicle intraperitoneally. All vehicle-injected normal controls were sacrificed 0, 4, 6, 8, 12, 14, and 16 weeks after injection, and one-third of the STZ-injected rats were sacrificed as the baseline controls 4, 6, and 8 weeks after the injection. Eight-week h-PTH (6. 0 microg/kg, 6 times a week) or its vehicle treatment by subcutaneous injection for residual diabetic rats was started 4, 6, or 8 weeks after the STZ injection. The rats' proximal right tibiae were processed for undecalcified Villanueva bone staining sections for bone histomorphometry. Furthermore, changes in trabecular connectivities were determined by node-strut analysis. The decreased cancellous bone volume (BV/TV) and turnover in diabetic rats were recovered in all PTH-treated groups. In node-strut analysis, the node-related parameters (N.Nd/TV, NdNd/TV) were significantly increased by PTH when it was administered 4 weeks after STZ injection but were not increased when administration was started after 6 weeks. The results indicated that PTH enhanced bone turnover and bone mass but not trabecular connectivity in the late stage of diabetes in rats. Early treatment of osteoporosis is important in preventing fractures caused by decreased bone strength resulting from decreased trabecular connectivity.

Analysis of Variance↗

Insufficiency fractures of the distal tibiae.

We describe two patients with uncommon types of insufficiency fractures that occurred at the distal tibiae. In case 1, a 71-year-old man with secondary osteoporosis due to hypogonadism fracture of his left distal tibia was overlooked because initial radiographs had seemed normal. However, bone scintigram obtained 2 months prior to the onset of fracture had already demonstrated abnormally high uptake at the site. In case 2, a 62-year-old woman with postmenopausal osteoporosis sustained an insufficiency fracture of the left distal tibia. Good clinical results were obtained with nonsurgical treatment. Based on the clinical course of case 1, we believe that bone scintigrams may be useful not only for the early diagnosis of insufficiency fracture but also for predicting such fractures.

Aged↗

Effects of dietary calcium depletion and repletion on dynamic determinants of tibial bone volume in two inbred strains of mice.

As an adjunct to our efforts to identify the genes that determine peak bone density, we examined phenotypic differences between two inbred strains of mice, C3H/HeJ (C3H) and C57BL/6J (B6), which are of similar size but differ with respect to peak bone density (e.g., C3H mice have 53% higher femoral bone density than B6 mice). The current studies were intended to compare the skeletal responses of C3H and B6 mice to 2 weeks of dietary calcium (Ca) depletion, followed by 2 weeks of Ca repletion. Initial studies showed that: (a) femur dry weight decreased during Ca depletion in both C3H and B6 mice (by 25% and 19%, respectively, p < 0.001) and most of this loss was recovered during Ca repletion; and (b) serum alkaline phosphatase (ALP) activity increased during Ca depletion, in both strains of mice (p < 0.001), and returned to normal after Ca repletion. Histological analyses of ground cross sections prepared at the tibiofibular junction showed that Ca-depletion increased medullary area in both C3H and B6 mice (indicating endosteal bone loss, p < 0.01), with reversal during Ca repletion. There were no effects of Ca depletion or repletion on periosteal bone growth. Endosteal bone forming surface and endosteal mineral apposition decreased during Ca depletion and increased during repletion in both C3H and B6 mice (p < 0.05). Net bone formation decreased during Ca depletion in C3H mice, but not B6 mice (p < 0.01), and was normal during Ca repletion in both strains. Endosteal bone resorbing surface and net bone resorption increased during Ca depletion and decreased during repletion in both strains (p < 0.01). A supplemental study (of Ca depletion without repletion) confirmed the effects of Ca depletion on femoral dry weight and serum ALP activity (p < 0.001 for each). This supplemental study also showed that Ca deficiency increased serum parathyroid hormone (PTH) (p < 0.05) and decreased (tibial) cortical bone area and cortical mineral content (p < 0.05 to p < 0.001) in both strains of mice. Together, these data demonstrate that the skeletal responses to Ca depletion and repletion are, qualitatively, similar in C3H and B6 mice.

Alkaline Phosphatase↗

Development and evaluation of C-telopeptide enzyme-linked immunoassay for measurement of bone resorption in mouse serum.

The mouse is increasingly being used as an animal model for the study of skeletal phenotypes in humans, mainly because of the ease of genetic manipulation. Biochemical markers of bone metabolism provide a valuable parameter for the assessment of skeletal metabolism. In the mouse model, assays for bone formation have been available for a long time; however, little is known about bone resorption markers. The present study describes the development of a serum C-telopeptide enzyme-linked immunoassay (ELISA), which measures degradation products of type I collagen that are generated by osteoclastic bone resorption. The C-telopeptide ELISA uses affinity-purified antibodies generated against human sequence DFSFLPQPPQEKAHDGGR. The epitope involves an amino acid sequence, which is identical in the mouse and human C-terminal peptide of type I collagen (alpha1 chain). Sensitivity of the ELISA used was <0.1 ng/mL. The average intra- (n = 10) and interassay (n = 8) coefficient of variation for two controls was <12%. The average dilution and spike recovery rates were 98% and 97%, respectively. Application of the ELISA to measure C-telopeptide in 3-4-week postovariectomized (ovx) C57BL/6J (B6) mice (n = 9 or 10) showed a 45% higher C-telopeptide concentration than the sham-operated mice. Treatment of ovx mice with estradiol (400 microg/kg body weight) or alendronate (1.0 mg/kg body weight) resulted in a 20%-50% decrease in C-telopeptide levels compared to the vehicle-treated ovx group. In addition, B6 mice fed a calcium-deficient diet (0.01% calcium) showed a 50% higher C-telopeptide concentration compared to the B6 mice receiving a normal diet (0.6% calcium). In conclusion, the C-telopeptide ELISA exhibited acceptable analytical performance and sufficient discriminatory power to show expected directional changes in the rate of bone resorption following ovariectomy, ovx plus estradiol or alendronate treatment, and administration of a calcium-deficient diet. Therefore, the ELISA developed in this study could be used for measuring bone resorption in the mouse model.

Alendronate↗

Anterior decompression with single segmental spinal interbody fusion for lumbar burst fracture.

STUDY DESIGN: The clinical and radiologic records for seven patients with lumbar burst fracture who underwent anterior decompression with single segmental interbody fusion were reviewed. OBJECTIVE: To determine the clinical results obtained with this method and its influence on the intervertebral disc degeneration inferior to the fusion. SUMMARY OF BACKGROUND DATA: Some patients with Denis' type B fracture can tolerate one-segment anterior fusion. However, there is no reliable information in the literature regarding the juxtafusional disc degeneration after one-segment fusion. METHODS: Seven patients with type B lumbar burst fractures, including four with cleavage fracture of the lower endplate, underwent anterior single segmental fusion; three patients underwent surgery with no instrumentation, and four underwent surgery with Kaneda instrumentation. The mean follow-up period lasted 85 months. The kyphosis angle and inferior intervertebral disc height adjacent to the fusion were measured before and after surgery. Pain and working status were evaluated using the scales proposed by Denis et al. RESULTS: Significant correction loss was obtained 1 year after surgery in the patients in whom no instrumentation was used (7.3 +/- 0.6 degrees), compared with the correction loss in patients whose surgery included the use of instrumentation (0.3 +/- 0.5 degree; P = 0.00001). No further correction losses were seen in either group at the final follow-up examination. No marked reduction in disc height was observed in any patient, including the four patients with cleavage fracture of the lower endplate. All patients returned to their previous occupation; five patients were rated as P1 (no pain) and W1 (returned to heavy labor), and two patients were rated as P2 (minimal pain) and W2 (return to heavy labor with lifting restrictions) at the final follow-up examination. CONCLUSIONS: There was slight correction loss within 1 year when no instrumentation was used, but this deformity did not affect the clinical results. The results provided no evidence that cleavage fracture of the lower endplate accelerates degeneration of the adjacent intervertebral disc.

Adolescent↗

Histomorphometric evaluation of the effects of ovariectomy on bone turnover in rat caudal vertebrae.

The purpose of this study was to learn whether caudal vertebrae can be used to evaluate the effects of ovariectomy (OVX) in rats. Seven-month-old female Wistar rats were divided into two groups: the OVX group and the untreated control group. All rats were killed at 8 weeks and their 4th lumbar (L4), 1st caudal (C1), 3rd caudal (C3), and 5th caudal (C5) vertebrae were processed undecalcified and sectioned with Villanueva bone stain for quantitative bone histomorphometry. Both length of vertebral bodies and the cancellous tissue area in C1 were similar in size to L4 but significantly bigger than C3 and C5. Within the groups, cancellous bone volume (BV/TV) and trabecular thickness in both groups gradually increased in caudal vertebrae in relation to the distal direction. Between the groups, OVX rats exhibited a significantly lower BV/TV relative to control rats at L4 and C1, however, no significant difference were seen at C3 and C5. Bone formation-related parameters such as osteoid and mineralizing surface, and eroded surface were higher in the OVX group than in the control group in caudal as well as in lumbar vertebrae. By quantitative analysis of bone marrow composition, yellow marrow volume in C3 and C5 was significantly higher than that in L4 and C1, in both groups. Our results suggest that C1 is similar to L4 in size, bone turnover, and bone marrow composition. However, further experiments are needed to evaluate the possibility that C1 vertebra could be used as an alternative site for histomorphometric evaluation of bone changes in OVX rats.

Animals↗