Introduction. This study was to investigate the association of developmental dysplasia of the hip (DDH) and primary protrusion acetabuli (PPA) with Vitamin D receptor polymorphisms TaqI and FokI and oestrogen receptor polymorphisms Pvu II and XbaI. Methods. 45 patients with DDH and 20 patients with PPA were included in the study. Healthy controls (n=101) aged 18-60 years were recruited from the same geographical area. The control subjects had a normal acetabular morphology based on a recent pelvic radiograph performed for an unrelated cause. DNA was obtained from all the subjects from peripheral blood. Genotype frequencies were compared in the three groups. The relationship between the genotype and morphology of the hip joint, severity of the disease, age at onset of disease and gender were examined. Results. The oestrogen receptor XbaI wild-type genotype (XX, compared with Xx and xx combined) was more common in the DDH group (55.8%) than controls (37.9%), though this just failed to achieve statistical significance (p=0.053, odds ratio=2.1, 95% CI=0.9-4.6). In the DDH group, homozygosity for the mutant TaqI Vitamin D receptor t allele was associated with higher acetabular index (Mann-Whitney U-test, p= 0.03). Pvu II pp oestrogen receptor genotype was associated with low centre edge angle (p=0.07). Conclusion. This study suggests a possible correlation between gene polymorphism in the oestrogen and vitamin D receptors and susceptibility to, and severity of DDH. The TaqI vitamin D receptor polymorphisms may be associated with abnormal acetabular morphology leading to DDH while the XbaI oestrogen receptor XX genotype may be associated with increased risk of developing DDH. No such correlations were found in the group with PPA

Introduction: Evidence exists concerning the anti-oxidant properties of oestrogen in protecting neuronal cells from oxidative stress. The withdrawal of oestrogen after menopause is the major factor determining age related bone loss and apoptotic death of osteocytes. While oestrogen replacement demonstrates clear oestrogen receptor mediated benefits to bone cells little is known regarding oestrogens’ anti-oxidant effects in bone. Methods: Here we have used MLO-Y4 osteocyte-like cell line to determine whether oestrogen saving effects on osteocytes involves its activities as an anti-oxidant. MLO-Y4 cells were treated with physiological doses (10. −8. )M of either 17-beta E. 2. or the oestrogen receptor inactive stereoisomer 17-alpha E. 2. with or without the specific oestrogen receptor antagonist ICI 182,780 prior to the addition of 0.4milliM 30% (v/v) H. 2. O. 2. Cellular apoptosis was determined using morphological and biochemical criteria. Results: H. 2. O. 2. induced an increase in apoptosis of MLO-Y4 (14.3 ± 3 SD vs control 1.4 ± 0.9). Pre-treatment of the cells with 17-beta E. 2. significantly reduced H. 2. O. 2. induced apoptosis (2.4 ± 0.96). Pre-treatment of cells with 17-alpha E. 2. or ICI 182,780 also reduced oxidant induced apoptosis to 3.4 ± 1.5 SD and 7.0 ± 2.3 respectively. The cellular production of reactive oxygen species was determined using the free radical indicator 2′7′- dichlorodihydrofluorescein diacetate. H. 2. O. 2. induced increases in the number of ROS positive cells (34.6 ± 9.07 SD vs control 0.22 ± 0.39 SD). In contrast pre-treatment with both 17-beta E. 2. and 17-alpha E. 2. reduced the number of ROS positive cells associated with H. 2. O. 2. treatment (Fig 1). Conclusion: These data suggest that oestrogens ability to save osteocytes from oxidant induced death is independent of the oestrogen receptor and may be related to oestrogens known activity as an anti-oxidant. This raises the possibility that loss of osteocytes during oestrogen insufficiency may occur through a failure to suppress the activity of naturally occurring or disease associated production of oxidant molecules

In the pubertal growth plate, sex hormones play important roles for the regulation of the proliferation, differentiation, maturation and programmed death of chondrocytes. Many studies have been reported on the regulation of oestrogen in long bone growth, however, some of the mechanisms have remained unclarified to date including its role for cell kinetics in the growth plate chondrocytes. The aim of this study was to clarify the effect of the deficiency of oestrogen on growth plate chondrocytes. We obtained the growth plates of femoral head from the normal and ovariectomized Japanese white rabbits at 10, 15, 20 and 25 weeks. Ovariectomy was performed at 8 weeks. The cell kinetics of chondrocytes as defined by the numbers of proliferating and programmed dying cells was investigated using immunohistological methods. The lengths of the femur were almost same both in the ovariectomised and normal rabbits. The height of the growth plate was larger in the former. The total number of chondrocytes in the ovariectomised rabbits was less than that of normal rabbits of the same age. Immunostaining of proliferating cell nucleous antigen (PCNA) showed a decrease number of proliferating chondrocytes and that of caspase-3 indicated a little increased number of apoptotic chondrocytes. Oestrogen regulates endochondral bone formation through several pathways. It directly binds oestrogen receptor alpha and beta, and the former accelerates longitudinal bone growth whereas the latter represses it. Another pathway is through the GH-IGF-I axis: it closely interacts with GH and IGF-I for the control of longitudinal bone growth. In addition, there might be other mediators including transforming growth factor-beta, other IGFs and still unknown paracrine or auto-crine factors as IHH PTHrP. Our study suggests that in the rabbit growth plate during puberty, oestrogen mainly acts through the GH-IGF-I axis since its defi-ciency declined the proliferating ability of chondrocytes, which led the decrease of the number of chondrocytes

Introduction: Retrospective reports of adverse events following growth hormone administration to short-statured children indicate that the incidence of scoliosis is elevated, largely due to the higher incidence of scoliosis in Turner/other syndromes within the group. The aims of this study are to analyse risk factors for scoliosis in these children. Methods: Data on 184 of 267 (65%) current and recent Australian children from the Australian OZGROW program was collected in 2001/2002 (from three Australian States). This included medical records (including past history of known scoliosis), growth charts, timing of growth hormone and oestrogen administration and the presence and severity of scoliosis from clinical examination. Growth hormone dosage was controlled by Australian Health Department guidelines. Standard oestrogen dosage was similar for all pubertal girls. The cohort was noted to comprise many varying syndromes, some of whom were pituitary hormone deficient. Potential risk factors for the development of scoliosis were statistically analysed. Results: Of 45 subjects with Turner Syndrome, 13 (30%) have idiopathic scoliosis and 2 have a hemi-vertebra. Of the other 139 subjects, 15 have scoliosis but 11 have syndromes which would normally be associated with scoliosis. Therefore, the incidence of idiopathic scoliosis in the remaining 128 subjects is 3.1% (4/128), which is within the normal population range. All 4 have mild scoliosis < 20 degrees. For the 139 subjects with idiopathic short stature or a specific syndrome, the age of commencement and total amount of growth hormone and/or oestrogen did not affect the degree of scoliosis. Discussion: Having Turner Syndrome was the only variable identified as a risk factor for having scoliosis (p< .001). The incidence of scoliosis in growth hormone treated Turner Syndrome subjects is much larger than previously reported (11–12%). 1,. 2. To the authors’ knowledge, this is the first report derived from non-retrospective data on the incidence of scoliosis in a growth hormone–treated Turner Syndrome population. This stimulated the next study looking at the incidence of scoliosis in growth hormone-treated and non-growth hormone-treated subjects with Turner Syndrome

Aims. To investigate the effects of senescent osteocytes on bone homeostasis in the progress of age-related osteoporosis and explore the underlying mechanism. Methods. In a series of in vitro experiments, we used tert-Butyl hydroperoxide (TBHP) to induce senescence of MLO-Y4 cells successfully, and collected conditioned medium (CM) and senescent MLO-Y4 cell-derived exosomes, which were then applied to MC3T3-E1 cells, separately, to evaluate their effects on osteogenic differentiation. Furthermore, we identified differentially expressed microRNAs (miRNAs) between exosomes from senescent and normal MLO-Y4 cells by high-throughput RNA sequencing. Based on the key miRNAs that were discovered, the underlying mechanism by which senescent osteocytes regulate osteogenic differentiation was explored. Lastly, in the in vivo experiments, the effects of senescent MLO-Y4 cell-derived exosomes on age-related bone loss were evaluated in male SAMP6 mice, which excluded the effects of oestrogen, and the underlying mechanism was confirmed. Results. The CM and exosomes collected from senescent MLO-Y4 cells inhibited osteogenic differentiation of MC3T3-E1 cells. RNA sequencing detected significantly lower expression of miR-494-3p in senescent MLO-Y4 cell-derived exosomes compared with normal exosomes. The upregulation of exosomal miR-494-3p by miRNA mimics attenuated the effects of senescent MLO-Y4 cell-derived exosomes on osteogenic differentiation. Luciferase reporter assay demonstrated that miR-494-3p targeted phosphatase and tensin homolog (PTEN), which is a negative regulator of the phosphoinositide 3-kinase (PI3K)/AKT pathway. Overexpression of PTEN or inhibition of the PI3K/AKT pathway blocked the functions of exosomal miR-494-3p. In SAMP6 mice, senescent MLO-Y4 cell-derived exosomes accelerated bone loss, which was rescued by upregulation of exosomal miR-494-3p. Conclusion. Reduced expression of miR-494-3p in senescent osteocyte-derived exosomes inhibits osteogenic differentiation and accelerates age-related bone loss via PTEN/PI3K/AKT pathway. Cite this article: Bone Joint Res 2024;13(2):52–65

The purpose of this study was to evaluate whether epidural fibrosis formation around the spinal cord was affected by endogenous oestrogen deficient state after lumbar laminectomy in the rats. Thirty-six 12-month-old adult female Sprague-Dawley rats were used in this study. Bilaterally ooferectomy were done in 18 rats. Rats were divided into two groups: oophrectomised (oestrogen deficient) group and sham operated (oestrogen maintained) group. Three weeks after the ooferectomy each rat underwent complete bilaterally laminectomy at the L2 and L3 vertebral levels (two levels per rat). The rats were randomly divided into three equal groups (12 rats in each group). The rats were sacrificed at four, eight, and twelve weeks postoperatively and the lumbar spine excised en bloc, fixed and decalcified. Section stained with hematoxylin and eosin and Masson’s trichrome were used to evaluate epidural fibrosis, acute inflammatory cells, chronic inflammatory cells and vascular proliferation. Sections were analyzed by investigator blinded to the study and graded on a five-point grading system. Statistic were performed using Mann-Whitney U test when compare two variable and Kruskal-Wallis test when compare more than two variables. Compared with the oopherectomised group, the sham operated group showed decreased rate of epidural fibrosis and higher acute and chronic inflammatory cells response at four and eight weeks but this was no statistically significant (p> 0.05). The results of this study revealed that endogenous oestrogen may decrease epidural fibrosis formation after lumbar laminectomy in the rats

Aims: Hormone replacement therapy (HRT) reverses the menopausal decline in bone mineral density (BMD).We investigate if part of this response is through modulation of Interleukin-6 (IL-6) activity, which is known to be reduced by HRT. Methods: We have examined the association of the -174 G/C functional promoter polymorphism of the IL-6 gene with the BMD response to HRT (Prempak C: 0.625mg oestrogen per day and 0.15mg norgestrel). 65 women were genotyped for the IL-6 polymorphism, and differences in genotype related to changes in BMD over a one year follow up period. Results: Baseline BMD (0.75 g/cm. 2. ) was independent of IL-6 genotype. The rise in BMD with HRT (5% ± 3%, p < 0.00005 by paired t-test) was genotype-dependent, with BMD rising least amongst those of GG genotype (6% ± 3% for ≥1 C allele vs 4% ± 2% GG, p=0.03). In the HRT group, BMD rose most amongst those with the putatively ‘lowest IL-6’ genotype combination- namely ≥ 1 ACE I allele and ≥ 1 IL-6 C allele (n=14) (7% ± 3%), when compared with other genotype combinations (4% ± 2%) (n=16) (p=0.003). Conclusion: These are the first data to demonstrate an influence for IL-6 genotype in influencing response to oestrogen therapy, rather than its physiological withdrawal

Introduction: Large numbers of women are taking hormone replacement therapy (HRT) or an oestrogen containing contraceptive pill. They are being advised that these medications can increase their risk of developing deep vein thrombosis (DVT) and there has been considerable recent publicity. Aim: To determine the practice of New Zealand orthopaedic surgeons when women taking such medications present for major surgery. Method: A postal survey was sent to all New Zealand orthopaedic surgeons. The current practice was compared with recently revised national guidelines and manufacturers advice. Results: The response rate was 80% (118/148). There was wide variation in the beliefs surrounding the peri-operative use of both of these medications. Of the surgeons who replied, 44% indicated that they would routinely advise discontinuing the combined oral contraceptive pill peri-operatively for major surgery, 24% indicated that they would routinely advise discontinuing HRT peri-operatively. The mean duration that surgeons would discontinue the medication pre-operatively was 13 days for the contraceptive pill and nine days for HRT. The mean time for re-starting medication post-operatively was 18 days for the contraceptive pill and 13 days for HRT. Recently released New Zealand guidelines recommend that HRT should be stopped for at least 30 days prior to elective surgery and withheld for 90 days following surgery. Less than 3% of surgeons appeared to be routinely following this recommendation. Most manufacturers of combined oral contraceptive pills recommend stopping the medication for at least four weeks prior to elective surgery. Only 25% of surgeons routinely practice in accordance with these recommendations. Discussion: This survey demonstrated substantial differences between actual clinical practice, recently revised national guidelines and manufacturers’ advice. These differences need to be brought to the attention of surgeons and guideline producers alike. A review of international literature and recommendations revealed that these guidelines are very conservative and that strong evidence for them is lacking. Issues to be considered include the practicalities of implementing such recommendations; the associated risks of discontinuing medication; the presence of other risk factors; the type of surgery; the use of thromboprophylaxis and not least the wishes of the patient. The possible medico-legal implications are uncertain and caution in this area is advised

Introduction

Osteoporosis accounts for a major risk factor of fracture-associated disability or premature death in the elderly. Enhancement of bone anabolism for slowing osteoporosis is highly demanding. Exerkine fibronectin type III domain containing 5 (FNDC5) regulates energy metabolism, inflammation, and aging. This study was aimed to investigate whether Fndc5 signaling in osteoblasts changed estrogen deficiency-mediated bone loss or microarchitecture deterioration.

Abstract

Although effects of mechanical stimulation with high frequency, low magnitude vibrations on bone mass and bone mineral density in animal and clinical studies have been proven effective, its effects on fracture healing is less well described. 20 Sham and 20 ovarectomised (Ovx) Sprague Dawley rats at 22 weeks of age, had intra-medullary k-wire fixation followed by controlled mid-shaft fractures. The animals were divided into subgroups of 3 week Sham and Ovx treated and non-treated and 6 week Sham and Ovx treated and non-treated groups. The treated animals were vibrated for 20mins daily on a DMT (dynamic motion therapy) platform which had a frequency of 30hz, 8-micron vertical displacement and 3g force, the non treated animals allowed to move freely. Xrays, DEXA studies, micro computed tomography, Histological analysis and Mechanical studies performed at the end point. DMT treated animals had more bridging callus on radiographic and micro computed tomographic analysis compared to non-treated groups especially the OVX groups at 3 weeks compared to controls or Shams (using Image J software). DEXA studies showed increased bone mineral density and bone mineral content in the treated animals compared to the controls. Histological analysis showed increased callus and woven bone being laid down in the treated OVX groups. In the 6-week groups, the treated OVX groups had healed, remodelled fractures compared to the non-treated groups or Sham controls where the fracture gaps were still visible. Although significance was not achieved on mechanical analysis due to small sample size, in the OVX non-operated femora group that were treated with DMT there were indications that they were stronger than the control counterparts. High frequency low magnitude vibrations with the Juvent DMT device enhances fracture healing in oestrogen deficient models and this model could be used as a platform for clinical studies in future

Sclerostin (SOST) is an endogenous inhibitor of Wnt/β-catenin signalling pathway to impair osteogenic differentiation and bone anabolism. SOST immunotherapy like monoclonal antibody has been observed to control bone remodeling and regeneration. This study is aimed to develop a SOST vaccine and test its protective effects on estrogen deficiency-induced bone loss in mice. Gene sequences coded SOST peptide putative targeting Wnt co-receptor LRP5 were cloned and constructed into vectors expressing Fc fragment to produced SOST-Fc fusion protein. Mice were subcutaneously injected SOST-Fc to boost anti-SOST antibody. Bone mineral density, microstructure, and mechanical property were quantified using μCT scanning and material testing system. Serum bone formation and resorption markers and anti-SOST levels were measured using ELISA. SOST-Fc injections significantly increased serum anti-SOST antibody levels but reduced serum SOST concentrations. SOST-Fc vaccination significantly reduced estrogen deficiency-induced serum bone resorption markers CTX-1 increased serum bone formation marker osteocalcin. Of note, it significantly alleviated the severity of estrogen-induced loss of bone mineral density, trabecular morphometric properties, and biomechanical forces of bone tissue. Mechanistically, SOSF-Fc vaccination attenuated trabecular loss histopathology and restored immunostaining of Wnt pathway like Wnt3a, β-catenin, and TCF4 in bone tissue along with increased serum osteoclast inhibitor OPG levels but decreased serum osteoclast enhancer RANKL concentrations. Taken together, SOST-Fc vaccination boosts anti-SOST antibody to neutralize SOST and mitigates the estrogen deficiency-induced bone mass and microstructure deterioration through preserving Wnt signalling. This study highlights an innovative remedial potential of SOST vaccine for preventing osteoporosis.

Background

MicroRNAs are non-coding small RNAs that reportedly regulate mRNA targets or protein translation of various tissues in physiological and pathological contexts. This study was undertaken to characterise the contributions of microRNA-29a (miR-29a) to the progression of estrogen deficiency-mediated excessive osteoclast resorption and bone loss.

The expression of the mechanosensor, integrin αvβ3, is reduced in osteoporotic bone cells compared to controls. MLO-Y4 osteocytes experience altered mechanotransduction under estrogen deficiency and it is unknown whether this is associated with defective αvβ3 expression or signalling. The objectives of this study are to (1) investigate αvβ3 expression and spatial organisation in osteocytes during estrogen deficiency, and (2) establish whether altered responses of osteocytes under estrogen deficiency correlate to defective αvβ3 expression and functionality. MLO-Y4 cells were cultured as follows: Ctrl (no added estradiol), E+ (10nM 17β-estradiol for 5 days), and Ew (10nM 17β-estradiol for 3 days and withdrawal for 2 days). Cells were cultured with/without 0.5µM IntegriSense750 (αvβ3 antagonist). Laminar oscillatory fluid flow of 1Pa at 0.5Hz was applied for 1hr. αvβ3 content was quantified using an ELISA. The location and quantity of αvβ3 and focal-adhesions was determined by immunocytochemistry. Estrogen withdrawal under static conditions led to lower cell and focal-adhesion area (p<0.05), compared to E+ cells. Fluid flow led to higher αvβ3 content (p<0.05) in all groups, compared to static counterparts, with αvβ3 blocking altering this response. Fluid flow on Ew cells had the highest αvβ3 levels (p<0.05), but αvβ3 did not localise at focal-adhesions sites. Cell morphologies were similar after treatment with the αvβ3 antagonist to the Ew group. These results suggest there are fewer functional focal-adhesion sites at which αvβ3 integrins localise to facilitate mechanotransduction. To further understand these results, we are analysing osteocyte mechanotransduction by quantifying PGE2 and gene expression (COX-2, RANKL, OPG, SOST).

3D cell culture studies more accurately represent the complex in vivo mechanical environment of human bone and are, thus, superior to 2D studies when testing the efficacy of osteoporosis therapies. As such, the objective of this study was to use a 3D model to investigate the effect of sclerostin antibodies. Sclerostin is a protein, which inhibits osteoblasts and is downregulated under mechanical stimulation. It is not yet known how expression of sclerostin mediates the site-specific and temporal changes in mineralisation. To address this, we developed a 3D cellular niche of MC3T3 osteoblasts encapsulated within gelatin and applied mechanical loading to the constructs using a custom-designed compression bioreactor system (0.5% strain at 0.5 Hz, 1 hr/day) (VizStim) under continuous perfusion of cell culture media. Osteoblasts were pretreated with estrogen for 14 days, followed by estrogen withdrawal (EW) to simulate postmenopausal conditions. 3D constructs were successfully fabricated and actin staining revealed the formation of dendritic cells under both static and stimulated conditions indicative of osteocyte-like cells. Under static conditions, estrogen treatment enhanced production of calcium by osteoblasts when compared to the same cells cultured under estrogen deficient conditions. Overall, preliminary results propose a link between mechanical stimulation, estrogen deficiency and mineral production by osteoblasts. Ongoing studies are comparing the static and stimulated groups after a longer culture period of 21 days using sclerostin antibodies. This research aims to deliver further understanding of the mechanical regulation of bone formation, and will inform novel approaches for regeneration of bone tissue and treatment of osteoporosis.

Aims

Deciphering the genetic relationships between major depressive disorder (MDD) and osteoarthritis (OA) may facilitate an understanding of their biological mechanisms, as well as inform more effective treatment regimens. We aim to investigate the mechanisms underlying relationships between MDD and OA in the context of common genetic variations.

Osteoporosis has long been associated with weak bones but recent studies have shown that bone tissue mineral becomes more heterogeneous and the expression of mechanosensors are altered during estrogen deficiency in an animal model of osteoporosis. However, whether these changes occur as a primary response to estrogen deficiency is unknown. In this study we investigate whether matrix production and mineralisation by mechanically-stimulated osteoblasts are impaired as a direct consequence of estrogen depletion. Osteoblast-like MC3T3-E1 cells were cultured for 14 days with 10⁻⁸M of 17β-estradiol and subsequently cultured with osteogenic media only, or supplemented with estrogen or an estrogen antagonist (Fulvestrant, 10⁻⁷M). Physiological shear stress (1Pa) was applied using an orbital shaker (290rpm, 40min/day), which allows long-term culture and induces oscillatory flow on cells. Osteoblasts phenotype, extracellular matrix (ECM), mineralisation and mechanosensors were tracked by qRT-PCR (Runx2, Col1a1, Col1a2, Cox2, Bglap2, FN1), by biochemical assays (ALP activity, DNA and calcium content), by immunostaining (integrin α_v, BSP2, fibronectin) and by labelling with calcein the calcium. The results of this study demonstrate that after 7 days, estrogen depleted cells had less integrin α_v mechanosensors compared to those that received continuous estrogen treatment. By 14 days the ECM formation (calcium, fibronectin) by osteoblasts was altered under estrogen depletion, when compared to cells that were cultured continuously with estrogen. This study provides evidence of changes in osteoblast behaviour under estrogen depletion, which might explain the alteration in tissue mineral content and the decrease of integrins observed previously in ovariectomized rats in vivo.

Objectives. Osteoporosis is a metabolic disease resulting in progressive loss of bone mass as measured by bone mineral density (BMD). Physical exercise has a positive effect on increasing or maintaining BMD in postmenopausal women. The contribution of exercise to the regulation of osteogenesis in osteoblasts remains unclear. We therefore investigated the effect of exercise on osteoblasts in ovariectomized mice. Methods. We compared the activity of differentially expressed genes of osteoblasts in ovariectomized mice that undertook exercise (OVX+T) with those that did not (OVX), using microarray and bioinformatics. Results. Many inflammatory pathways were significantly downregulated in the osteoblasts after exercise. Meanwhile, IBSP and SLc13A5 gene expressions were upregulated in the OVX+T group. Furthermore, in in vitro assay, IBSP and SLc13A5 mRNAs were also upregulated during the osteogenic differentiation of MC3T3-E1 and 7F2 cells. Conclusion. These findings suggest that exercise may not only reduce the inflammatory environment in ovariectomized mice, indirectly suppressing the overactivated osteoclasts, but may also directly activate osteogenesis-related genes in osteoblasts. Exercise may thus prevent the bone loss caused by oestrogen deficiency through mediating the imbalance between the bone resorptive activity of osteoclasts and the bone formation activity of osteoblasts. Cite this article: W-B. Hsu, W-H. Hsu, J-S. Hung, W-J. Shen, R. W-W. Hsu. Transcriptome analysis of osteoblasts in an ovariectomized mouse model in response to physical exercise. Bone Joint Res 2018;7:601–608. DOI: 10.1302/2046-3758.711.BJR-2018-0075.R2

Purpose of the study: Oestrogen depletion leads to osteoclastic hyperactivity and subsequent postmenopausal osteoporosis. Little is known about interactions with bone absorption induced by wear particles from joint bearings. The purpose of this study was to evaluate bone response to polyethylene (PE) particles in a mouse model of oestrogen deficiency. Material and methods: Particles of PE were implanted in the calvaria of seven non-ovariectomised mice and in seven ovariectomised mice (OVX). Fourteen mice were operated on without implantation of the particles (7 non-OVX and 7 OVX, control groups). The mice were sacrificed at two weeks. The crania were studied under a microscanner and histologically without decalcification. Results: The microscanner showed that particles of PE induced a significant decrease in bone thickness in non-OVX mice (p=0.04), while the thickness remained unchanged in OVX mice who had received the particles (p=0.40). After implantation of the PE particles, the number of osteoclasts per mm of bone perimeter was 2.84±1.6 in the non-OVX mice and 1.74±1.3 in OVX mice (p=0.004). Compared with controls, the mean loss of bone was 12±10% in the non-OVX mice versus 4.7±0.9%in the OVX mice (p=0.004). Discussion: The volume of osteolysis induced by PE particles was smaller in OVX mice compared with non-OVX mice. Conclusion: These results suggest that a deficit in oestrogens has a protective effect against bone adsorption induced by PE particles

Objectives. Ligaments which heal spontaneously have a healing process that is similar to skin wound healing. Menopause impairs skin wound healing and may likewise impair ligament healing. Our purpose in this study was to investigate the effect of surgical menopause on ligament healing in a rabbit medial collateral ligament model. Methods. Surgical menopause was induced with ovariohysterectomy surgery in adult female rabbits. Ligament injury was created by making a surgical gap in the midsubstance of the medial collateral ligament. Ligaments were allowed to heal for six or 14 weeks in the presence or absence of oestrogen before being compared with uninjured ligaments. Molecular assessment examined the messenger ribonucleic acid levels for collagens, proteoglycans, proteinases, hormone receptors, growth factors and inflammatory mediators. Mechanical assessments examined ligament laxity, total creep strain and failure stress. Results. Surgical menopause in normal medial collateral ligaments initiated molecular changes in all the categories evaluated. In early healing medial collateral ligaments, surgical menopause resulted in downregulation of specific collagens, proteinases and inflammatory mediators at 6 weeks of healing, and proteoglycans, growth factors and hormone receptors at 14 weeks of healing. Surgical menopause did not produce mechanical changes in normal or early healing medial collateral ligaments. With or without surgical menopause, healing ligaments exhibited increased total creep strain and decreased failure stress compared with uninjured ligaments. Conclusions. Surgical menopause did not affect the mechanical properties of normal or early healing medial collateral ligaments in a rabbit model. The results in this preclinical model suggest that menopause may result in no further impairment to the ligament healing process. . Cite this article: Bone Joint Res 2015;4:38–44