Aims. The aim of this study was to investigate the global and local impact of fat on bone in obesity by using the diet-induced obese (DIO) mouse model. Methods. In this study, we generated a diet-induced mouse model of obesity to conduct lipidomic and 3D imaging assessments of bone marrow fat, and evaluated the correlated bone adaptation indices and bone mechanical properties. Results. Our results indicated that bone mass was reduced and bone mechanical properties were impaired in DIO mice. Lipidomic sequencing and bioinformatic analysis identified 373 differential lipids, 176 of which were upregulated and 197 downregulated. Functional enrichment analysis revealed a significant downregulation of the pathways: fat digestion and absorption (ko04975) and lipolysis regulation in adipocytes (ko04923) in DIO mice, leading to local fat accumulation. The use of 3D imaging confirmed the increase in fat accumulation within the bone marrow cavity of obese mice. Conclusion. Our study sheds light on the intricate interplay between fat and bone, and provides a non-toxic and non-invasive method for measuring marrow adipose tissue. Cite this article: Bone Joint Res 2023;12(9):580–589

Aims. In the treatment of basal thumb osteoarthritis (OA), intra-articular autologous fat transplantation has become of great interest within recent years as a minimally invasive and effective alternative to surgical intervention with regard to pain reduction. This study aims to assess its long-term effectiveness. Methods. Patients diagnosed with stage one to three OA received a single intra-articular autologous fat transplantation. Fat tissue was harvested from the abdomen and injected into the trapeziometacarpal (TMC) joint under radiological guidance, followed by one week of immobilization. Patients with a minimum three-year post-procedure period were assessed for pain level (numerical rating scale), quality of life (Mental Health Quotient (MHQ)), the abbreviated version of the Disabilities of Arm, Shoulder and Hand questionnaire (QuickDASH)), and grip and pinch strength, as well as their overall impression of the treatment. Wilcoxon tests compared data from pre-intervention, and at one and three years post-intervention. Results. Out of 136 treated joints, the study involved 87 patients (37 patients were loss to follow-up, and 12 patients (9%) who underwent resection arthroplasty) with a median follow-up of 4.9 years (IQR 5.4 to 5.9). Pain, both at rest and during stress, significantly improved at one year and remained stable through three years. Sex, age, and stage of disease were not associated with postoperative pain levels. Patient-reported outcome measures for QuickDASH and MHQ improved up to at least three years post-treatment. Patients reported high satisfaction and willingness to recommend the procedure. Grip and pinch strength did not significantly change over time. Conclusion. The data show that autologous fat transfer has a longer-lasting effect in two-thirds of re-examined patients. If patients had an initial positive response, the pain-reducing effect lasted for at least three years. Therefore, this minimally invasive approach can offer a valuable treatment alternative for basal thumb OA

Fifty-five adults who had sustained a tibial fracture, or a femoral fracture, or both, were subjected to a double-blind randomised study to determine the efficacy of methylprednisolone in treating the fat embolism syndrome. This drug maintained arterial oxygen levels, stabilised or reduced the serum level of free fatty acids, and decreased the risk of the fat embolism syndrome in a statistically significant proportion of patients. Gurd's criteria for the diagnosis of the fat embolism syndrome were found inadequate. Other more sensitive criteria for early diagnosis and effective management were determined. There were no deaths or serious morbidity in our series

Objectives. Although many clinical and experimental investigations have shed light on muscle atrophy and intramuscular accumulation of fat after rotator cuff disruption, none have reported on their onset in the absence of muscle retraction. Methods. In 30 rabbits, we detached one supraspinatus (SSP) tendon and repaired it immediately, thus preventing muscle retraction. The animals were killed in groups of 10 at one, two and six weeks. Both shoulders of 15 non-operated rabbits served as controls. We measured the weight and volume of SSP muscles and quantified the cross-sectional area of intramuscular fat (i-fat) histologically. Results. There was significant loss of muscle weight and volume after one week (p = 0.004 and 0.003, respectively), and two weeks (both p < 0.001) in the experimental group; which recovered to control values after six weeks. I-fat accumulated one week after immediate repair, greater than in the control group and statistically significant at the mid-part of the muscle (mean 2.7% vs 1.5%, p = 0.008). I-fat continued to accumulate up to six weeks at all sites of the SSP muscle (all 3, p < 0.001). More fat accumulated closer to the musculotendinous junction than at the mid-part after two and six weeks (p = 0.012 and 0.019, respectively). Conclusion. Muscle atrophy and i-fat accumulation occur early after SSP tendon tear and immediate repair. While early repair benefitted muscle recovery, it did not prevent fat accumulation. SSP muscle retraction was not essential to the muscle alterations. The divergent evolution of muscle and fat points to different pathophysiologies. Cite this article: Bone Joint Res 2014;3:117–22

Several experimental models have been used to produce intravascular fat embolism. We have developed a simple technique to induce fat embolism using corn oil emulsified with distilled water to form fatty micelles. Fat embolism was produced by intravenous administration of these fatty micelles in anaesthetised rats, causing alveolar oedema, haemorrhage and increased lung weight. Histopathological examination revealed fatty droplets and fibrin thrombi in the lung, kidney and brain. The arteriolar lumen was filled with fatty deposits. Following fat embolism, hypoxia and hypercapnia occurred. The plasma phospholipase A. 2. , nitrate/nitrite, methylguidanidine and proinflammatory cytokines were significantly increased. Mass spectrometry showed that the main ingredient of corn oil was oleic acid. This simple technique may be applied as a new animal model for the investigation of the mechanisms involved in the fat embolism syndrome

Aims. The aim of this study was to assess whether it is possible to predict the mortality, and the extent and time of neurological recovery from the time of the onset of symptoms and MRI grade, in patients with the cerebral fat embolism syndrome (CFES). This has not previously been investigated. Methods. The study included 34 patients who were diagnosed with CFES following trauma between 2012 and 2018. The clinical diagnosis was confirmed and the severity graded by MRI. We investigated the rate of mortality, the time and extent of neurological recovery, the time between the injury and the onset of symptoms, the clinical severity of the condition, and the MRI grade. All patients were male with a mean age of 29.7 years (18 to 70). The mean follow-up was 4.15 years (2 to 8), with neurological recovery being assessed by the Glasgow Outcome Scale and the Mini-Mental State Examination. Results. In all, seven who had early-onset CFES (< 24 hours), and a severe Takahashi grade on MRI, died. There was a significant association between the time of onset of neurological signs and mortality (p = 0.035). Mortality was also significantly associated with a severe Takahashi grade (p < 0.001). Among the 27 surviving patients, 26 (96.3%) recovered completely. One (3.7%) had a cognitive deficit. The mean time to recovery was 4.7 weeks (2 to 13), with late recovery aftereight eight weeks being recorded in three patients. Conclusion. There was a significantly increased rate of mortality in patients with CFES who had an early onset of symptoms and a severe grade on MRI. Complete neurological recovery can be expected in most patients with CFES who survive. Cite this article: Bone Joint J 2022;104-B(1):142–149

1. Blood from forty-one healthy volunteers, seventy-one patients with fractures but without symptoms of fat embolism and seven patients with clinical evidence of fat embolism was examined microscopically for fat droplets and chemically for triglycerides. 2. Fat droplets, after Millipore filtration of the blood, were seen evenly distributed in all three groups. 3. There was no significant difference in triglyceride concentration between serum and filtrate in the three groups. 4. The results do not support the thesis that the Gurd test is a reliable aid in the diagnosis of fat embolism

Aims. Previous research has demonstrated increased early complication rates following total hip arthroplasty (THA) in obese patients, as defined by body mass index (BMI). Subcutaneous fat depth (FD) has been shown to be an independent risk factor for wound infection in cervical and lumbar spine surgery, as well as after abdominal laparotomy. The aim of this study was to investigate whether increased peritrochanteric FD was associated with an increased risk of complications in the first year following THA. Methods. We analyzed prospectively collected data on a consecutive series of 1,220 primary THAs from June 2013 until May 2018. The vertical soft tissue depth from the most prominent part of the greater trochanter to the skin was measured intraoperatively using a sterile ruler and recorded to the nearest millimetre. BMI was calculated at the patient’s preoperative assessment. All surgical complications occuring within the initial 12 months of follow-up were identified. Results. Females had a significantly greater FD at the greater trochanter in comparison to males (median 3.0 cm (interquartile range (IQR) 2.3 to 4.0) vs 2.0 cm (IQR 1.7 to 3.0); p < 0.001) despite equivalent BMI between sexes (male median BMI 30.0 kg/m. 2. (IQR 27.0 to 33.0); female median 29.0 kg/m. 2. (IQR 25.0 to 33.0)). FD showed a weak correlation with BMI (R² 0.41 males and R² 0.43 females). Patients with the greatest FD (upper quartile) were at no greater risk of complications compared with patients with the lowest FD (lower quartile); 7/311 (2.3%) vs 9/439 (2.1%); p = 0.820 . Conversely, patients with the highest BMI (≥ 40 kg/m. 2. ) had a significantly increased risk of complications compared with patients with lower BMI (< 40 kg/m. 2. ); 5/60 (8.3% vs 18/1,160 (1.6%), odds ratio (OR) 5.77 (95% confidence interval (CI) 2.1 to 16.1; p = 0.001)). Conclusion. We found no relationship between peritrochanteric FD and the risk of surgical complications following primary THA. Cite this article: Bone Joint J 2020;102-B(9):1146–1150

1. A distinction must be made between the fat embolism syndrome, a clinical entity, and fat embolism demonstrated pathologically, which may be found after death following fracture with no prior evidence of the syndrome. 2. One hundred cases of the syndrome encountered over a period of four years have been studied in detail and the diagnostic criteria have been defined. These include one major feature, four minor features and fat macroglobulaemia. 3. Sixteen of the patients died–eight from severe pulmonary insufficiency of the syndrome, eight from other traumatic causes. 4. The prevention of shock is the best measure for prevention of the syndrome. The role of proteases in the production of shock and the place of protease inhibition in treatment of the syndrome are briefly discussed. 5. For the established case the aim of treatment is to ensure an adequate pressure of arterial oxygen

1. A diagnostic procedure is described which is specific for fat embolism. It allows identification of the pathological fat globules On a stained slide. 2. The amount of pathological fat can be estimated by comparing the serum triglyceride levels before and after filtration. 3. The method is simple, reproducible and inexpensive

1. Fat embolism occurs in a high percentage of all cases of injury and it is a relatively frequent complication of fractures of the long bones in civilian accidents as well as battle casualties. 2. The diagnosis can usually be established by the clinical features together with certain physical signs which must however be sought deliberately. 3. Important clinical features are the mental disturbance, alternation of coma with full consciousness, petechial haemorrhages in the conjunctiva and skin, and typical changes in the retina. 4. Evidence is still conflicting as to whether the fat arises by embolism from an injured bone, or by general metabolic disturbance. 5. The fat is harmful not so much by reason of mechanical obstruction of vessels as by erosion and rupture of the vessel wall clue to the liberation of fatty acids. 6. Preventive treatment appears to be of some value but no satisfactory specific treatment is yet available for the established case. 7. Ligation of the profunda vein has been tried in two patients, one of whom recovered and the other died

1. Reports of the lipaemia-clearing effect of heparin suggested that this drug might be of therapeutic value in fat embolism. 2. In an experimental trial with rats, heparin was found both to accelerate death and to increase the number of deaths after fat embolism. 3. It is accordingly concluded that a clinical trial of heparin in human fat embolism would not be warranted

The changes in a number of haemostatic factors after fractures of the tibia or femur were compared with those observed in patients with fat embolism complicating such fractures. After fractures uncomplicated by fat embolism there was a rise in the fibrinogen, α. 1. -antitrypsin and serum activation inhibitor. The plasminogen level and platelet count initially fell, but later increased to above the initial levels. Patients whose fractures were complicated by fat embolism had the same pattern of changes but quantitatively greater

Objectives. Previous genome-wide association studies (GWAS) have reported significant association of the single nucleotide polymorphism (SNP) rs8044769 in the fat mass and obesity-associated gene (FTO) with osteoarthritis (OA) risk in European populations. However, these findings have not been confirmed in Chinese populations. Methods. We systematically genotyped rs8044769 and evaluated the association between the genetic variants and OA risk in a case-controlled study including 196 OA cases and 442 controls in a northern Chinese population. Genotyping was performed using the Sequenom MassARRAY iPLEX platform. Results. We found that the variant T allele of rs8044769 showed no significant association of OA risk (p = 0.791), or association with body mass index (BMI) (pmeta = 0.786) in an additive genetic model. However, we detected a significant interaction between rs8044769 genotypes and BMI on OA risk (p = 0.037), as well as a borderline interaction between rs8044769 genotypes and age on OA risk (p = 0.062). Conclusions. Our findings indicate that rs8044769 in the FTO gene may not modify individual susceptibility to OA or increased BMI in the Chinese population. Further studies are warranted to validate and extend our findings. Cite this article: Prof L. Jiang. No association of the single nucleotide polymorphism rs8044769 in the fat mass and obesity-associated gene with knee osteoarthritis risk and body mass index: A population-based study in China. Bone Joint Res 2016;5:169–174. DOI: 10.1302/2046-3758.55.2000589

An experimental study performed in 16 mongrel dogs is presented, which shows that when venous stasis is combined with the local injection of non-esterified fatty acid an intense thrombosis results. This response is not produced by venous stasis alone, nor by the combination of venous stasis and triacylglycerol. Histologically it is quite different from the response produced by an inert intraluminal foreign body. It does resemble venous thrombosis described experimentally and in patients. The clinical relevance of these findings is that during accidental or operative trauma to a long bone, fat is commonly forced into the local venous circulation. If this event is combined with venous stasis or a tourniquet is used, then the circumstances of this experiment are reproduced. It is suggested that the venous thrombosis which commonly complicates long-bone injury or operation is in part caused by the thrombogenic nature of the introduced fat

An episode of hypotension is common during cemented joint replacement, and has been associated with circulatory collapse and sudden death. We studied the mechanism of hypotension in two groups of six dogs after simulated bilateral cemented arthroplasty. In one group, with no lavage, the insertion of cement and prosthesis was followed by severe hypotension, elevated pulmonary artery pressure, decreased systemic vascular resistance and a 21% reduction in cardiac output. In the other group, pulsatile intramedullary lavage was performed before the simulated arthroplasties. Hypotension was less, and although systemic vascular resistance decreased, the cardiac output did not change. The severity of the hypotension, the decrease in cardiac output and an increase in prostaglandin metabolites were related to the magnitude of pulmonary fat embolism. Pulsatile lavage prevents much of this fat embolism, and hence the decrease in cardiac output. The relatively mild hypotension after lavage was secondary to transient vasodilation, which may accentuate the hypotension caused by the decreased cardiac output due to a large embolic fat load. We make recommendations for the prevention and management of hypotension during cemented arthroplasty

1. Three cases of acute peptic ulceration are reported after cerebral fat embolism complicating skeletal injuries. In two instances death occurred after perforation of an ulcer, and in the third intestinal haemorrhage led to death. 2. Although intracranial lesions and peptic ulceration have been reported on many occasions, so far as we know cerebral fat embolism as a cause has not been previously recognised. 3. The possible pathogenesis is discussed

1. Three patients are reported in whom a sudden acute internal derangement of the knee was caused by torsion of a pedunculated portion of the infrapatellar fat pad. 2. The symptoms and signs are described. 3. The pathological changes and the pathogenesis are discussed

We examined the roles of methylmethacrylate (MMA) monomer and cementing technique in the formation, and haemodynamic outcome, of pulmonary fat emboli. The preparation of the femoral canal and the cementing technique were studied in four groups of adult dogs as follows: control (no preparation); lavage; cement pressurisation; and cement pressurisation after lavage. We measured the intramedullary pressure, pulmonary artery pressure (PAP), pulmonary capillary wedge pressure and bilateral femoral vein levels of triglyceride, cholesterol and MMA monomer at rest and after reaming, lavage, and cementing. Femoral vein triglyceride and cholesterol levels did not vary significantly from resting levels despite significant elevations in intramedullary pressure with reaming, lavage and cementing (p = 0.001). PAP was seen to rise significantly with reaming (p = 0.0038), lavage (p = 0.0031), cementing (p = 0.0024) and cementing after lavage (p = 0.0028) while the pulmonary capillary wedge pressure remained unchanged. MMA monomer was detected in femoral vein samples when cement pressurisation was used. Intramedullary lavage before cementing had no significant effect on the MMA level. Haemodynamic evidence of pulmonary embolism was noted with reaming and intramedullary canal preparation, irrespective of the presence of MMA monomer. We found no relationship between MMA monomer level and intramedullary pressure, PAP or pulmonary capillary wedge pressure. Our findings suggest that the presence of MMA monomer in femoral venous blood has no effect on the formation of fat emboli or their pulmonary haemodynamic outcome during cemented hip arthroplasty

Twenty young men with displaced fractures of one or more long bones in the lower limb, but with no evidence of cranial, thoracic or abdominal injury, were studied prospectively. Although all the patients became hypoxaemic, the six who developed signs of respiratory distress (Group 1) were found to have a significantly lower arterial oxygen tension and a significantly higher rate of urinary urea excretion than the remaining 14 patients whose pulmonary function appeared to be clinically normal (Group 2). Circulating fat macroglobules were identified in three cases, only one of whom was in Group 1, and hence the tests for fat embolism were not of prognostic value. Although an immunodeficient state is considered to contribute to the pulmonary insufficiency which occurs after major trauma, convincing evidence of a lymphocyte-suppressive agent was found in only one patient