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

Multipotential processed lipoaspirate (PLA) cells extracted from five human infrapatellar fat pads and embedded into fibrin glue nodules, were induced into the chondrogenic phenotype using chondrogenic media. The remaining cells were placed in osteogenic media and were transfected with an adenovirus carrying the cDNA for bone morphogenetic protein-2 (BMP-2). We evaluated the tissue-engineered cartilage and bone using in vitro techniques and by placing cells into the hind legs of five severe combined immunodeficient mice. After six weeks, radiological and histological analysis indicated that the PLA cells induced into the chondrogenic phenotype had the histological appearance of hyaline cartilage. Cells transfected with the BMP-2 gene media produced abundant bone, which was beginning to establish a marrow cavity. Tissue-engineered cartilage and bone from infrapatellar fat pads may prove to be useful for the treatment of osteochondral defects

Asymptomatic cyst-like cortical defects appearing after fractures in children have been occasionally reported. Typically, these defects appear during fracture consolidation, within the newly formed subperiosteal bone, proximal to the fracture line, do not enlarge, and progressively disappear. We have previously shown a fatty density on CT scan within the early cortical defect. We now present two additional cases in which early CT scans appeared to confirm that these transient cortical defects may consist of fat, and probably result from the inclusion of medullary fat within the subperiosteal haematoma

The cavities left after resection of bone bridges for partial closure of growth plates in children have commonly been filled with free fat grafts. Such cavities have been seen to elongate and thus enlarge during growth after the operation, but the fate of the grafts has been unknown. Similar cavities, made in the tibiae of growing pigs were filled with autogenous fat and studied by radiography for periods of up to 9 1/2 months. These cavities elongated in a manner similar to those in the clinical cases, and histological section showed them to be filled with living adipose tissue. The volume of this tissue had continuously increased in parallel with the growth in length of the bone. The fate of the grafts used in children may be similar to that seen experimentally

The operative technique and result of treatment of traumatic radio-ulnar synostosis in two patients are described. In both, the treatment was excision of the cross-union and interposition of a free non-vascularised fat transplant. The functional result was excellent, and there was no evidence of regrowth of the synostosis at two and three years respectively

We performed transoesophageal echocardiography on 24 patients during reamed intramedullary nailing of 17 tibial and seven femoral fractures. In 14 patients there was only minimal evidence of emboli passing through the heart, but in six copious showers of small emboli (< 10 mm maximum dimension) were observed. In four other patients, there were also multiple large emboli (> 10 mm maximum dimension). Three of these patients developed fat embolism syndrome postoperatively and one died. Earlier nailing was associated with smaller quantities of emboli

Aims. Rotator cuff muscle atrophy and fatty infiltration affect the clinical outcomes of rotator cuff tear patients. However, there is no effective treatment for fatty infiltration at this time. High-intensity interval training (HIIT) helps to activate beige adipose tissue. The goal of this study was to test the role of HIIT in improving muscle quality in a rotator cuff tear model via the β3 adrenergic receptor (β3AR). Methods. Three-month-old C57BL/6 J mice underwent a unilateral rotator cuff injury procedure. Mice were forced to run on a treadmill with the HIIT programme during the first to sixth weeks or seventh to 12th weeks after tendon tear surgery. To study the role of β3AR, SR59230A, a selective β3AR antagonist, was administered to mice ten minutes before each exercise through intraperitoneal injection. Supraspinatus muscle, interscapular brown fat, and inguinal subcutaneous white fat were harvested at the end of the 12th week after tendon tear and analyzed biomechanically, histologically, and biochemically. Results. Histological analysis of supraspinatus muscle showed that HIIT improved muscle atrophy, fatty infiltration, and contractile force compared to the no exercise group. In the HIIT groups, supraspinatus muscle, interscapular brown fat, and inguinal subcutaneous white fat showed increased expression of tyrosine hydroxylase and uncoupling protein 1, and upregulated the β3AR thermogenesis pathway. However, the effect of HIIT was not present in mice injected with SR59230A, suggesting that HIIT affected muscles via β3AR. Conclusion. HIIT improved supraspinatus muscle quality and function after rotator cuff tears by activating systemic sympathetic nerve fibre near adipocytes and β3AR. Cite this article: Bone Joint Res 2023;12(8):455–466

Aims. Intra-articular (IA) tumours around the knee are treated with extra-articular (EA) resection, which is associated with poor functional outcomes. We aim to evaluate the accuracy of MRI in predicting IA involvement around the knee. Methods. We identified 63 cases of high-grade sarcomas in or around the distal femur that underwent an EA resection from a prospectively maintained database (January 1996 to April 2020). Suspicion of IA disease was noted in 52 cases, six had IA pathological fracture, two had an effusion, two had prior surgical intervention (curettage/IA intervention), and one had an osseous metastasis in the proximal tibia. To ascertain validity, two musculoskeletal radiologists (R1, R2) reviewed the preoperative imaging (MRI) of 63 consecutive cases on two occasions six weeks apart. The radiological criteria for IA disease comprised evidence of tumour extension within the suprapatellar pouch, intercondylar notch, extension along medial/lateral retinaculum, and presence of IA fracture. The radiological predictions were then confirmed with the final histopathology of the resected specimens. Results. The resection histology revealed 23 cases (36.5%) showing IA disease involvement compared with 40 cases without (62%). The intraobserver variability of R1 was 0.85 (p < 0.001) compared to R2 with κ = 0.21 (p = 0.007). The interobserver variability was κ = 0.264 (p = 0.003). Knee effusion was found to be the most sensitive indicator of IA involvement, with a sensitivity of 91.3% but specificity of only 35%. However, when combined with a pathological fracture, this rose to 97.5% and 100% when disease was visible in Hoffa’s fat pad. Conclusion. MRI imaging can sometimes overestimate IA joint involvement and needs to be correlated with clinical signs. In the light of our findings, we would recommend EA resections when imaging shows effusion combined with either disease in Hoffa’s fat pad or retinaculum, or pathological fractures. Cite this article: Bone Joint J 2023;105-B(6):696–701

The June 2024 Research Roundup. 360. looks at: Do the associations of daily steps with mortality and incident cardiovascular disease differ by sedentary time levels?; Large-scale assessment of ChatGPT in benign and malignant bone tumours imaging report diagnosis and its potential for clinical applications; Long-term effects of diffuse idiopathic skeletal hyperostosis on physical function: a longitudinal analysis; Effect of intramuscular fat in the thigh muscles on muscle architecture and physical performance in the middle-aged females with knee osteoarthritis; Preoperative package of care for osteoarthritis an opportunity not to be missed?; Superiority of kinematic alignment over mechanical alignment in total knee arthroplasty during medium- to long-term follow-up: a meta-analysis and trial sequential analysis

Aims. Extracellular matrix (ECM) is a critical determinant of tissue mechanobiology, yet remains poorly characterized in joint tissues beyond cartilage in osteoarthritis (OA). This review aimed to define the composition and architecture of non-cartilage soft joint tissue structural ECM in human OA, and to compare the changes observed in humans with those seen in animal models of the disease. Methods. A systematic search strategy, devised using relevant matrix, tissue, and disease nomenclature, was run through the MEDLINE, Embase, and Scopus databases. Demographic, clinical, and biological data were extracted from eligible studies. Bias analysis was performed. Results. A total of 161 studies were included, which covered capsule, ligaments, meniscus, skeletal muscle, synovium, and tendon in both humans and animals, and fat pad and intervertebral disc in humans only. These studies covered a wide variety of ECM features, including individual ECM components (i.e. collagens, proteoglycans, and glycoproteins), ECM architecture (i.e. collagen fibre organization and diameter), and viscoelastic properties (i.e. elastic and compressive modulus). Some ECM changes, notably calcification and the loss of collagen fibre organization, have been extensively studied across osteoarthritic tissues. However, most ECM features were only studied by one or a few papers in each tissue. When comparisons were possible, the results from animal experiments largely concurred with those from human studies, although some findings were contradictory. Conclusion. Changes in ECM composition and architecture occur throughout non-cartilage soft tissues in the osteoarthritic joint, but most of these remain poorly defined due to the low number of studies and lack of healthy comparator groups. Cite this article: Bone Joint Res 2024;13(12):703–715

Aims. Disorders of bone integrity carry a high global disease burden, frequently requiring intervention, but there is a paucity of methods capable of noninvasive real-time assessment. Here we show that miniaturized handheld near-infrared spectroscopy (NIRS) scans, operated via a smartphone, can assess structural human bone properties in under three seconds. Methods. A hand-held NIR spectrometer was used to scan bone samples from 20 patients and predict: bone volume fraction (BV/TV); and trabecular (Tb) and cortical (Ct) thickness (Th), porosity (Po), and spacing (Sp). Results. NIRS scans on both the inner (trabecular) surface or outer (cortical) surface accurately identified variations in bone collagen, water, mineral, and fat content, which then accurately predicted bone volume fraction (BV/TV, inner R. 2. = 0.91, outer R. 2. = 0.83), thickness (Tb.Th, inner R. 2. = 0.9, outer R. 2. = 0.79), and cortical thickness (Ct.Th, inner and outer both R. 2. = 0.90). NIRS scans also had 100% classification accuracy in grading the quartile of bone thickness and quality. Conclusion. We believe this is a fundamental step forward in creating an instrument capable of intraoperative real-time use. Cite this article: Bone Jt Open 2023;4(4):250–261

Aims. Arthroscopic microfracture is a conventional form of treatment for patients with osteochondritis of the talus, involving an area of < 1.5 cm. 2. However, some patients have persistent pain and limitation of movement in the early postoperative period. No studies have investigated the combined treatment of microfracture and shortwave treatment in these patients. The aim of this prospective single-centre, randomized, double-blind, placebo-controlled trial was to compare the outcome in patients treated with arthroscopic microfracture combined with radial extracorporeal shockwave therapy (rESWT) and arthroscopic microfracture alone, in patients with ostechondritis of the talus. Methods. Patients were randomly enrolled into two groups. At three weeks postoperatively, the rESWT group was given shockwave treatment, once every other day, for five treatments. In the control group the head of the device which delivered the treatment had no energy output. The two groups were evaluated before surgery and at six weeks and three, six and 12 months postoperatively. The primary outcome measure was the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale. Secondary outcome measures included a visual analogue scale (VAS) score for pain and the area of bone marrow oedema of the talus as identified on sagittal fat suppression sequence MRI scans. Results. A total of 40 patients were enrolled and randomly divided into the two groups, with 20 in each. There was no statistically significant difference in the baseline characteristics of the groups. No complications, such as wound infection or neurovascular injury, were found during follow-up of 12 months. The mean AOFAS scores in the rESWT group were significantly higher than those in the control group at three, six, and 12 months postoperatively (p < 0.05). The mean VAS pain scores in the rESWT group were also significantly lower than those in the control group at these times (p < 0.05). The mean area of bone marrow oedema in the rESWT group was significantly smaller at six and 12 months than in the control group at these times (p < 0.05). Conclusion. Local shockwave therapy was safe and effective in patients with osteochondiritis of the talus who were treated with a combination of arthroscopic surgery and rESWT. Preliminary results showed that, compared with arthroscopic microfracture alone, those treated with arthroscopic microfracture combined with rESWT had better relief of pain at three months postoperatively and improved weightbearing and motor function of the ankle. Cite this article: Bone Joint J 2023;105-B(10):1108–1114

Aims. Adenosine, lidocaine, and Mg. 2+. (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery. Methods. Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed. Results. Despite comparable knee function, ALM-treated males had reduced systemic inflammation, synovial fluid angiogenic and pro-inflammatory mediators, synovitis, and fat pad fibrotic changes, compared to controls. Within the ACL graft, ALM-treated males had increased expression of tissue repair markers, decreased inflammation, increased collagen organization, and improved graft-bone healing. In contrast to males, females had no evidence of persistent systemic inflammation. Compared to controls, ALM-treated females had improved knee extension, gait biomechanics, and elevated synovial macrophage inflammatory protein-1 alpha (MIP-1α). Within the ACL graft, ALM-treated females had decreased inflammation, increased collagen organization, and improved graft-bone healing. In articular cartilage of ALM-treated animals, matrix metalloproteinase (MMP)-13 expression was blunted in males, while in females repair markers were increased. Conclusion. At 28 days, ALM therapy reduces inflammation, augments tissue repair patterns, and improves joint function in a sex-specific manner. The study supports transition to human safety trials. Cite this article: Bone Joint Res 2024;13(6):279–293

Aims. Our aim was to investigate the prevalence of Propionibacterium (P.) acnes in the subcutaneous fat and capsule of patients undergoing shoulder surgery for frozen shoulder or instability. Patients and Methods. A total of 46 patients undergoing either an arthroscopic capsular release or stabilisation had biopsies taken from the subcutaneous fat and capsule of the shoulder at the time of surgery. These samples were sent for culture in enrichment, and also for Nucleic Acid Amplification testing. The prevalence of P. acnes and other microbes was recorded. Fisher's exact test of binary variables was used to calculate the association with significance set at p < 0.05. Assessment of influence of independent variables including a pre-operative glenohumeral injection, fat colonisation and gender, was undertaken using binary linear regression. Results. A total of 25 patients (53%) had P. acnes in one or more tissue samples and 35 (74%) had other bacterial species. The same microbe was found in the subcutaneous fat and the capsule in 13 patients (28%). There was no statistically significant association between the surgical pathology and capsular colonisation with P. acnes (p = 0.18) or mixed identified bacterial species (p = 0.77). Male gender was significantly associated with an increased capsular colonisation of P. acnes (odds ratio (OR) 12.38, 95% confidence interval (CI) 1.43 to 106.77, p = 0.02). A pre-operative glenohumeral injection was significantly associated with capsular P. acnes colonisation (OR 5.63, 95% CI 1.07 to 29.61, p = 0.04. Positive fat colonisation with P. acnes was significantly associated with capsular P. acnes (OR 363, 95% CI 20.90 to 6304.19, p < 0.01). Regression models pseudo R. 2. found fat colonisation with P. acnes to explain 70% of the variance of the model. Patients who had a pre-operative glenohumeral injection who were found intra-operatively to have fat colonisation with P. acnes had a statistically significant association with colonisation of their capsule with P. acnes (OR 165, 95% CI 13.51 to 2015.24, p < 0.01). Conclusion. These results show a statistically significant association between subcutaneous skin P. acnes culture and P. acnes capsular culture, especially when the patient has undergone a previous injection. The results refute the hypothesis that P. acnes causes frozen shoulder. Cite this article: Bone Joint J 2017;99-B:1067–72

Aims. Exosomes (exo) are involved in the progression of osteoarthritis (OA). This study aimed to investigate the function of dysfunctional chondrocyte-derived exo (DC-exo) on OA in rats and rat macrophages. Methods. Rat-derived chondrocytes were isolated, and DCs induced with interleukin (IL)-1β were used for exo isolation. Rats with OA (n = 36) or macrophages were treated with DC-exo or phosphate-buffered saline (PBS). Macrophage polarization and autophagy, and degradation and chondrocyte activity of cartilage tissues, were examined. RNA sequencing was used to detect genes differentially expressed in DC-exo, followed by RNA pull-down and ribonucleoprotein immunoprecipitation (RIP). Long non-coding RNA osteoarthritis non-coding transcript (OANCT) and phosphoinositide-3-kinase regulatory subunit 5 (PIK3R5) were depleted in DC-exo-treated macrophages and OA rats, in order to observe macrophage polarization and cartilage degradation. The PI3K/AKT/mammalian target of rapamycin (mTOR) pathway activity in cells and tissues was measured using western blot. Results. DC-exo inhibited macrophage autophagy (p = 0.002) and promoted M1 macrophage polarization (p = 0.002). DC-exo at 20 μg/ml induced collagen degradation (p < 0.001) and inflammatory cell infiltration (p = 0.023) in rats. OANCT was elevated in DC (p < 0.001) and in cartilage tissues of OA patients (p < 0.001), and positively correlated with patients’ Kellgren-Lawrence grade (p < 0.001). PIK3R5 was increased in DC-exo-treated cartilage tissues (p < 0.001), and OANCT bound to fat mass and obesity-associated protein (FTO) (p < 0.001). FTO bound to PIK3R5 (p < 0.001) to inhibit the stability of PIK3R5 messenger RNA (mRNA) (p < 0.001) and disrupt the PI3K/AKT/mTOR pathway (p < 0.001). Conclusion. Exosomal OANCT from DC could bind to FTO protein, thereby maintaining the mRNA stability of PIK3R5, further activating the PI3K/AKT/mTOR pathway to exacerbate OA. Cite this article: Bone Joint Res 2022;11(9):652–668

Aims. Abnormal lipid metabolism is involved in the development of osteoarthritis (OA). Growth differentiation factor 11 (GDF11) is crucial in inhibiting the differentiation of bone marrow mesenchymal stem cells into adipocytes. However, whether GDF11 participates in the abnormal adipogenesis of chondrocytes in OA cartilage is still unclear. Methods. Six-week-old female mice were subjected to unilateral anterior crossbite (UAC) to induce OA in the temporomandibular joint (TMJ). Histochemical staining, immunohistochemical staining (IHC), and quantitative real-time polymerase chain reaction (qRT-PCR) were performed. Primary condylar chondrocytes of rats were stimulated with fluid flow shear stress (FFSS) and collected for oil red staining, immunofluorescence staining, qRT-PCR, and immunoprecipitation analysis. Results. Abnormal adipogenesis, characterized by increased expression of CCAAT/enhancer-binding protein α (CEBPα), fatty acid binding protein 4 (FABP4), Perilipin1, Adiponectin (AdipoQ), and peroxisome proliferator-activated receptor γ (PPARγ), was enhanced in the degenerative cartilage of TMJ OA in UAC mice, accompanied by decreased expression of GDF11. After FFSS stimulation, there were fat droplets in the cytoplasm of cultured cells with increased expression of PPARγ, CEBPα, FABP4, Perilipin1, and AdipoQ and decreased expression of GDF11. Exogenous GDF11 inhibited increased lipid droplets and expression of AdipoQ, CEBPα, and FABP4 induced by FFSS stimulation. GDF11 did not affect the change in PPARγ expression under FFSS, but promoted its post-translational modification by small ubiquitin-related modifier (SUMOylation). Local injection of GDF11 alleviated TMJ OA-related cartilage degeneration and abnormal adipogenesis in UAC mice. Conclusion. Abnormal adipogenesis of chondrocytes and decreased GDF11 expression were observed in degenerative cartilage of TMJ OA. GDF11 supplementation effectively inhibits the adipogenesis of chondrocytes and thus alleviates TMJ condylar cartilage degeneration. GDF11 may inhibit the abnormal adipogenesis of chondrocytes by affecting the SUMOylation of PPARγ. Cite this article: Bone Joint Res 2022;11(7):453–464

Aims. Hip fractures are a major cause of morbidity and mortality, and malnutrition is a crucial determinant of these outcomes. This meta-analysis aims to determine whether oral nutritional supplementation (ONS) improves postoperative outcomes in older patients with a hip fracture. Methods. A systematic literature search was conducted in August 2022. ONS was defined as high protein-based diet strategies containing (or not containing) carbohydrates, fat, vitamins, and minerals. Randomized trials documenting ONS in older patients with hip fracture (aged ≥ 50 years) were included. Two reviewers evaluated study eligibility, conducted data extraction, and assessed study quality. Results. There were 812 studies identified, of which 18 studies involving 1,522 patients met the inclusion criteria. The overall meta-analysis demonstrated that ONS was associated with significantly elevated albumin levels (weighted mean difference (WMD) 1.24 (95% confidence interval (CI) 0.95 to 1.53)), as well as a significant risk reduction in infective complications (odds ratio (OR) 0.54 (95% CI 0.39 to 0.76)), pressure ulcers (OR 0.54 (95% CI 0.33 to 0.88)), and total complications (OR 0.57 (95% CI 0.42 to 0.79)). Length of hospital stay (LOS) was also significantly reduced (WMD -2.36 (95% CI -4.14 to -0.58)), particularly in rehabilitation LOS (WMD -4.17 (95% CI -7.08 to -1.26)). There was a tendency towards a lower mortality risk (OR 0.93 (95% CI 0.62 to 1.4)) and readmission (OR 0.52 (95% CI 0.16 to 1.73)), although statistical significance was not achieved (p = 0.741 and p = 0.285, respectively). The overall compliance with ONS ranged from 64.7% to 100%, but no factors influencing compliance were identified. Conclusion. This meta-analysis is the first to quantitatively demonstrate that ONS could nearly halve the risk of infective complications, pressure ulcers, total complications, as well as improve serum albumin and reduce LOS. ONS should be a regular and integrated part of the perioperative care of these patients, especially given that the compliance with ONS is acceptable. Cite this article: Bone Joint J 2023;105-B(11):1149–1158

Objectives. Metabolic syndrome and low-grade systemic inflammation are associated with knee osteoarthritis (OA), but the relationships between these factors and OA in other synovial joints are unclear. The aim of this study was to determine if a high-fat/high-sucrose (HFS) diet results in OA-like joint damage in the shoulders, knees, and hips of rats after induction of obesity, and to identify potential joint-specific risks for OA-like changes. Methods. A total of 16 male Sprague-Dawley rats were allocated to either the diet-induced obesity group (DIO, 40% fat, 45% sucrose, n = 9) or a chow control diet (n = 7) for 12 weeks. At sacrifice, histological assessments of the shoulder, hip, and knee joints were performed. Serum inflammatory mediators and body composition were also evaluated. The total Mankin score for each animal was assessed by adding together the individual Modified Mankin scores across all three joints. Linear regression modelling was conducted to evaluate predictive relationships between serum mediators and total joint damage. Results. The HFS diet, in the absence of trauma, resulted in increased joint damage in the shoulder and knee joints of rats. Hip joint damage, however, was not significantly affected by DIO, consistent with findings in human studies. The total Mankin score was increased in DIO animals compared with the chow group, and was associated with percentage of body fat. Positive significant predictive relationships for total Mankin score were found between body fat and two serum mediators (interleukin 1 alpha (IL-1α) and vascular endothelial growth factor (VEGF)). Conclusion. Systemic inflammatory alterations from DIO in this model system may result in a higher risk for development of knee, shoulder, and multi-joint damage with a HFS diet. Cite this article: K. H. Collins, D. A. Hart, R. A. Seerattan, R. A. Reimer, W. Herzog. High-fat/high-sucrose diet-induced obesity results in joint-specific development of osteoarthritis-like degeneration in a rat model. Bone Joint Res 2018;7:274–281. DOI: 10.1302/2046-3758.74.BJR-2017-0201.R2

Aims. The aim of this study was to describe a quantitative 3D CT method to measure rotator cuff muscle volume, atrophy, and balance in healthy controls and in three pathological shoulder cohorts. Methods. In all, 102 CT scans were included in the analysis: 46 healthy, 21 cuff tear arthropathy (CTA), 18 irreparable rotator cuff tear (IRCT), and 17 primary osteoarthritis (OA). The four rotator cuff muscles were manually segmented and their volume, including intramuscular fat, was calculated. The normalized volume (NV) of each muscle was calculated by dividing muscle volume to the patient’s scapular bone volume. Muscle volume and percentage of muscle atrophy were compared between muscles and between cohorts. Results. Rotator cuff muscle volume was significantly decreased in patients with OA, CTA, and IRCT compared to healthy patients (p < 0.0001). Atrophy was comparable for all muscles between CTA, IRCT, and OA patients, except for the supraspinatus, which was significantly more atrophied in CTA and IRCT (p = 0.002). In healthy shoulders, the anterior cuff represented 45% of the entire cuff, while the posterior cuff represented 40%. A similar partition between anterior and posterior cuff was also found in both CTA and IRCT patients. However, in OA patients, the relative volume of the anterior (42%) and posterior cuff (45%) were similar. Conclusion. This study shows that rotator cuff muscle volume is significantly decreased in patients with OA, CTA, or IRCT compared to healthy patients, but that only minimal differences can be observed between the different pathological groups. This suggests that the influence of rotator cuff muscle volume and atrophy (including intramuscular fat) as an independent factor of outcome may be overestimated. Cite this article: Bone Jt Open 2021;2(7):552–561

Aims. Loosening of the tibial component after total knee arthroplasty (TKA) is a common indication for revision. Increasing the strength of the initial tibial implant/cement interface is desirable. There is little information about the surgical techniques that lead to the highest strength. We investigated the effects of eight variables on the strength of the initial tibial baseplate/cement interface. Materials and Methods. A total of 48 tibial trays were cemented into acrylic holders using cement from two manufacturers, at three different times (early, normal, and late) using two techniques: cementing the tibial plateau or the plateau and the keel; and involving two conditions of contamination with marrow fat (at the metal/cement and cement/cement interfaces). Push-out tests were performed with load continuously recorded. Results. Compared with normal conditions, early cementing increased the mean strength of the interface when using the two cements, Simplex and Palacos, by 48% and 72%, respectively. Late cementing reduced the strength by 47% and 73%, respectively. Cementing the keel increased the mean strength by 153% and 147%, respectively, for the two cements. Contamination of the metal/cement interface with fat reduced the mean strength by 99% and 94% for the two cements but adding cement to the underside of the tibial tray prior to insertion resulted in the mean strength being lowered by only 65% and 43%, respectively. Conclusion. In order to maximize the strength of the tibial tray/cement interface, cement should be applied to the component soon after mixing, contamination of the interface should be avoided, and the keel and the plateau should be cemented

Aims. Resection of the proximal humerus for the primary malignant bone tumour sometimes requires en bloc resection of the deltoid. However, there is no information in the literature which helps a surgeon decide whether to preserve the deltoid or not. The aim of this study was to determine whether retaining the deltoid at the time of resection would increase the rate of local recurrence. We also sought to identify the variables that persuade expert surgeons to choose a deltoid sparing rather than deltoid resecting procedure. Patients and Methods. We reviewed 45 patients who had undergone resection of a primary malignant tumour of the proximal humerus. There were 29 in the deltoid sparing group and 16 in the deltoid resecting group. Imaging studies were reviewed to assess tumour extension and soft-tissue involvement. The presence of a fat rim separating the tumour from the deltoid on MRI was particularly noted. The cumulative probability of local recurrence was calculated in a competing risk scenario. Results. There was no significant difference (adjusted p = 0.89) in the cumulative probability of local recurrence between the deltoid sparing (7%, 95% confidence interval (CI) 1 to 20) and the deltoid resecting group (26%, 95% CI 8 to 50). Patients were more likely to be selected for a deltoid sparing procedure if they presented with a small tumour (p = 0.0064) with less bone involvement (p = 0.032) and a continuous fat rim on MRI (p = 0.002) and if the axillary nerve could be identified (p = 0.037). Conclusion. A deltoid sparing procedure can provide good local control after resection of the proximal humerus for a primary malignant bone tumour. A smaller tumour, the presence of a continuous fat rim and the identification of the axillary nerve on pre-operative MRI will persuade surgeons to opt for a deltoid resecting procedure. Cite this article: Bone Joint J 2017;99-B:1244–9

Aims. To examine the relationship of sex steroid hormones with osteopenia in a nationally representative sample of men in the USA. Methods. Data on bone mineral density (BMD), serum sex hormones, dairy consumption, smoking status, and body composition were available for 806 adult male participants of the cross-sectional National Health and Nutrition Examination Survey (NHANES, 1999-2004). We estimated associations between quartiles of total and estimated free oestradiol (E2) and testosterone (T) and osteopenia (defined as 1 to 2.5 SD below the mean BMD for healthy 20- to 29-year-old men) by applying sampling weights and using multivariate-adjusted logistic regression. We then estimated the association between serum hormone concentrations and osteopenia by percentage of body fat, frequency of dairy intake, cigarette smoking status, age, and race/ethnicity. Results. Men in the lowest quartile of total E2 concentrations (< 21.52 pg/ml) had greater odds of osteopenia compared with men in the highest quartile (odds ratio (OR) 2.29, 95% confidence interval (CI) 1.11 to 4.73; p-trend = 0.030). Total and free T were not associated with osteopenia. Low total E2 concentrations were associated with greater odds of osteopenia among non-daily dairy consumers (p-trend = 0.046), current or former smokers (p-trend = 0.032), and younger men (p-trend = 0.031). No differences were observed by race/ethnicity and obesity. Conclusion. In this nationally representative study of the USA, men with lower total E2 were more likely to have osteopenia, which was particularly evident among younger men, men with less-than-daily dairy consumption, and current or former smokers. Cite this article:Bone Joint Res. 2020;9(3):139–145

Objective . Dunkin Hartley guinea pigs, a commonly used animal model of osteoarthritis, were used to determine if high frequency ultrasound can ensure intra-articular injections are accurately positioned in the knee joint. Methods. A high-resolution small animal ultrasound system with a 40 MHz transducer was used for image-guided injections. A total of 36 guinea pigs were anaesthetised with isoflurane and placed on a heated stage. Sterile needles were inserted directly into the knee joint medially, while the transducer was placed on the lateral surface, allowing the femur, tibia and fat pad to be visualised in the images. B-mode cine loops were acquired during 100 µl. We assessed our ability to visualise 1) important anatomical landmarks, 2) the needle and 3) anatomical changes due to the injection. . Results. From the ultrasound images, we were able to visualise clearly the movement of anatomical landmarks in 75% of the injections. The majority of these showed separation of the fat pad (67.1%), suggesting the injections were correctly delivered in the joint space. We also observed dorsal joint expansion (23%) and patellar tendon movement (10%) in a smaller subset of injections. Conclusion. The results demonstrate that this image-guided technique can be used to visualise the location of an intra-articular injection in the joints of guinea pigs. Future studies using an ultrasound-guided approach could help improve the injection accuracy in a variety of anatomical locations and animal models, in the hope of developing anti-arthritic therapies. Cite this article: Bone Joint Res 2015;4:1–5

Aims. In the context of tendon degenerative disorders, the need for innovative conservative treatments that can improve the intrinsic healing potential of tendon tissue is progressively increasing. In this study, the role of pulsed electromagnetic fields (PEMFs) in improving the tendon healing process was evaluated in a rat model of collagenase-induced Achilles tendinopathy. Methods. A total of 68 Sprague Dawley rats received a single injection of type I collagenase in Achilles tendons to induce the tendinopathy and then were daily exposed to PEMFs (1.5 mT and 75 Hz) for up to 14 days - starting 1, 7, or 15 days after the injection - to identify the best treatment option with respect to the phase of the disease. Then, 7 and 14 days of PEMF exposure were compared to identify the most effective protocol. Results. The daily exposure to PEMFs generally provided an improvement in the fibre organization, a decrease in cell density, vascularity, and fat deposition, and a restoration of the physiological cell morphology compared to untreated tendons. These improvements were more evident when the tendons were exposed to PEMFs during the mid-acute phase of the pathology (7 days after induction) rather than during the early (1 day after induction) or the late acute phase (15 days after induction). Moreover, the exposure to PEMFs for 14 days during the mid-acute phase was more effective than for 7 days. Conclusion. PEMFs exerted a positive role in the tendon healing process, thus representing a promising conservative treatment for tendinopathy, although further investigations regarding the clinical evaluation are needed. Cite this article: Bone Joint Res 2020;9(9):613–622

Objectives. This study aimed to assess the effect of age and osteoporosis on the proliferative and differentiating capacity of bone-marrow-derived mesenchymal stem cells (MSCs) in female rats. We also discuss the role of these factors on expression and migration of cells along the C-X-C chemokine receptor type 4 (CXCR-4) / stromal derived factor 1 (SDF-1) axis. Methods. Mesenchymal stem cells were harvested from the femora of young, adult, and osteopenic Wistar rats. Cluster of differentiation (CD) marker and CXCR-4 expression was measured using flow cytometry. Cellular proliferation was measured using Alamar Blue, osteogenic differentiation was measured using alkaline phosphatase expression and alizarin red production, and adipogenic differentiation was measured using Oil red O. Cells were incubated in Boyden chambers to quantify their migration towards SDF-1. Data was analyzed using a Student’s t-test, where p-values < 0.05 were considered significant. Results. CD marker expression and proliferation of the MSCs from the three groups was not significantly different. The young MSCs demonstrated significantly increased differentiation into bone and fat and superior migration towards SDF-1. The migration of SDF-1 doubled with young rats compared with the adult rats (p = 0.023) and it was four times higher when compared with cells isolated from ovariectomized (OVX) osteopenic rats (p = 0.013). Conclusion. Young rat MSCs are significantly more responsive to osteogenic differentiation, and, contrary to other studies, also demonstrated increased adipogenic differentiation compared with cells from adult and ostopenic rats. Young-rat-derived cells also showed superior migration towards SDF-1 compared with MSCs from OVX and adult control rats. Cite this article: A. Sanghani-Kerai, L. Osagie-Clouard, G. Blunn, M. Coathup. The influence of age and osteoporosis on bone marrow stem cells from rats. Bone Joint Res 2018;7:289–297. DOI: 10.1302/2046-3758.74.BJR-2017-0302.R1