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Aims. This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation. Methods. In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload. Results. Utilizing an OVX rat model, we observed significant alterations in bone mass and osseointegration due to VIT administration in aged rats with iron overload. The observed effects were concomitant with reductions in bone metabolism, oxidative stress, and inflammation. To elucidate whether these effects are associated with osteoclast and osteoblast activity, we conducted in vitro experiments using MC3T3-E1 cells and RAW264.7 cells. Our findings indicate that iron accumulation suppressed the activity of MC3T3-E1 while enhancing RAW264.7 function. Furthermore, iron overload significantly decreased oxidative stress levels; however, these detrimental effects can be mitigated by VIT treatment. Conclusion. Collectively, our data provide compelling evidence that VIT has the potential to reverse the deleterious consequences of iron overload on osseointegration and bone mass during ageing. Cite this article: Bone Joint Res 2024;13(9):427–440


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_I | Pages - 82
1 Mar 2002
Schnaid E Schnitzler C Sweet M
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We studied the histomorphometry of the trabecular bone of 19 black men and 15 black women over the age of 60 years who had sustained fractured neck of femur (FNF) as a result of minor trauma. The findings were correlated with indicators of iron overload (ferritin and vitamin C). A striking feature was the presence of iron granules in the bone marrow of 16 of the men and nine of the women, together with fibrosis. Present in large numbers, the granules were quantitated. There were significantly more iron granules in the men than in the women (p =0.05). Ferritin levels were higher in those patients with large numbers of granules than in those with few or no granules. There was no clear correlation with the indicators, bone formation or resorption. We concluded that iron overload is a strong aetiological factor in black male FNF patients. In postmenopausal female FNF patients, the possible aetiological role of iron overload is complicated by hormone deficiency


The Journal of Bone & Joint Surgery British Volume
Vol. 82-B, Issue 6 | Pages 872 - 875
1 Aug 2000
Schnaid E MacPhail AP Sweet MBE

We explored the role of iron overload, deficiency of vitamin C and alcohol abuse in the aetiology of cervical and intertrochanteric fractures of the neck of the femur as a result of minor trauma. We studied prospectively 72 patients (45 men, 27 women). Levels of serum iron markers, vitamin C and alcohol markers were measured. Consumption of alcohol was estimated using questionnaires. The findings were compared with those of an age- and gender-matched control group. The mean age of the men was 59.5 years and of the women 66.9 years, with a male predominance. In the men, iron overload, as shown by high levels of serum ferritin (p < 0.001) and deficiency of vitamin C (p < 0.03), as well as abuse of both Western and the traditional type of alcohol, appear to be important aetiological factors. In women, alcohol abuse was also common, but iron markers and levels of vitamin C did not differ significantly from the control group


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_II | Pages 134 - 134
1 Feb 2003
Lunn JV Gallagher P Crowe J Boucher-Hayes D Murray P
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Aseptic loosening of implants following hip arthroplasty is a cause of significant patient morbidity. We genotyped 99 revision hip arthroplasty patients and 116 primary hip arthroplasty patients for the C282Y and the H63D mutations, which cause Haemochromatosis. Haemochromatosis is an inherited condition leading to excessive iron absorption and deposition in the body. All patients at the time of their primary hip arthroplasty were diagnosed as having osteoarthritis. We identified 9 of the 99 revision arthroplasty patients as being homozygous for the C282Y mutation. The time to revision in this group was significantly lower (p< 0.005) when compared to the remaining 90 patients in the group (mean 8.7 years vs 14.8 years). Analysis of variables such as patient age and sex and also type of prosthesis, place of surgery and operating surgeon had no confounding influence. We hypothesise that undiagnosed iron overload in the patients homozygous for the C282Y mutation is likely to cause premature failure of their primary hip arthroplasty


Aims

Astragalus polysaccharide (APS) participates in various processes, such as the enhancement of immunity and inhibition of tumours. APS can affect osteoporosis (OP) by regulating the osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs). This study was designed to elucidate the mechanism of APS in hBMSC proliferation and osteoblast differentiation.

Methods

Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were performed to determine the expression of microRNA (miR)-760 and ankyrin repeat and FYVE domain containing 1 (ANKFY1) in OP tissues and hBMSCs. Cell viability was measured using the Cell Counting Kit-8 assay. The expression of cyclin D1 and osteogenic marker genes (osteocalcin (OCN), alkaline phosphatase (ALP), and runt-related transcription factor 2 (RUNX2)) was evaluated using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Mineral deposits were detected through Alizarin Red S staining. In addition, Western blotting was performed to detect the ANKFY1 protein levels following the regulation of miR-760. The relationship between miR-760 and ANKFY1 was determined using a luciferase reporter assay.


Bone & Joint Open
Vol. 2, Issue 12 | Pages 1062 - 1066
1 Dec 2021
Krasin E Gold A Morgan S Warschawski Y

Aims

Hereditary haemochromatosis is a genetic disorder that is caused by several known mutations in the human homeostatic iron regulator protein (HFE) gene. Abnormal accumulation of iron causes a joint disease that resembles osteoarthritis (OA), but appears at a relatively younger age and is accompanied by cirrhosis, diabetes, and injury to other organs. Increased serum transferrin saturation and ferritin levels are known markers of haemochromatosis with high positive predictive values.

Methods

We have retrospectively analyzed the iron studies of a cohort of 2,035 patients undergoing knee joint arthroplasty due to OA.


The Bone & Joint Journal
Vol. 101-B, Issue 5 | Pages 540 - 546
1 May 2019
Juneau D Grammatopoulos G Alzahrani A Thornhill R Inacio JR Dick A Vogel KI Dobransky J Beaulé PE Dwivedi G

Aims

Cardiac magnetic resonance (CMR) was used to assess whether cardiac function or tissue composition was affected in patients with well-functioning metal-on-metal hip resurfacing arthroplasties (MoMHRA) when compared with a group of controls, and to assess if metal ion levels correlated with any of the functional or structural parameters studied.

Patients and Methods

In all, 30 participants with no significant cardiac history were enrolled: 20 patients with well-functioning MoMHRA at mean follow-up of 8.3 years post-procedure (ten unilateral, ten bilateral; 17 men, three women) and a case-matched control group of ten non-MoM total hip arthroplasty patients (six men, four women). The mean age of the whole cohort (study group and controls) at the time of surgery was 50.6 years (41.0 to 64.0). Serum levels of cobalt and chromium were measured, and all patients underwent CMR imaging, including cine, T2* measurements, T1 and T2 mapping, late gadolinium enhancement, and strain measurements.