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Bone & Joint Open
Vol. 3, Issue 4 | Pages 340 - 347
22 Apr 2022
Winkler T Costa ML Ofir R Parolini O Geissler S Volk H Eder C

Aims

The aim of the HIPGEN consortium is to develop the first cell therapy product for hip fracture patients using PLacental-eXpanded (PLX-PAD) stromal cells.

Methods

HIPGEN is a multicentre, multinational, randomized, double-blind, placebo-controlled trial. A total of 240 patients aged 60 to 90 years with low-energy femoral neck fractures (FNF) will be allocated to two arms and receive an intramuscular injection of either 150 × 106 PLX-PAD cells or placebo into the medial gluteal muscle after direct lateral implantation of total or hemi hip arthroplasty. Patients will be followed for two years. The primary endpoint is the Short Physical Performance Battery (SPPB) at week 26. Secondary and exploratory endpoints include morphological parameters (lean body mass), functional parameters (abduction and handgrip strength, symmetry in gait, weightbearing), all-cause mortality rate and patient-reported outcome measures (Lower Limb Measure, EuroQol five-dimension questionnaire). Immunological biomarker and in vitro studies will be performed to analyze the PLX-PAD mechanism of action. A sample size of 240 subjects was calculated providing 88% power for the detection of a 1 SPPB point treatment effect for a two-sided test with an α level of 5%.


The Bone & Joint Journal
Vol. 104-B, Issue 8 | Pages 997 - 1008
1 Aug 2022

Aims

The aim of this study was to describe the management and associated outcomes of patients sustaining a femoral hip periprosthetic fracture (PPF) in the UK population.

Methods

This was a multicentre retrospective cohort study including adult patients who presented to 27 NHS hospitals with 539 new PPFs between 1 January 2018 and 31 December 2018. Data collected included: management strategy (operative and nonoperative), length of stay, discharge destination, and details of post-treatment outcomes (reoperation, readmission, and 30-day and 12-month mortality). Descriptive analysis by fracture type was performed, and predictors of PPF management and outcomes were assessed using mixed-effects logistic regression.


Bone & Joint Research
Vol. 11, Issue 7 | Pages 484 - 493
13 Jul 2022
Hayer S Niederreiter B Kalkgruber M Wanic K MaiĂźner J Smolen JS Aletaha D BlĂĽml S Redlich K

Aims

Insufficient treatment response in rheumatoid arthritis (RA) patients requires novel treatment strategies to halt disease progression. The potential benefit of combination of cytokine-inhibitors in RA is still unclear and needs further investigation. To explore the impact of combined deficiency of two major cytokines, namely interleukin (IL)-1 and IL-6, in this study double deficient mice for IL-1αβ and IL-6 were investigated in different tumour necrosis factor (TNF)-driven inflammatory bone disorders, namely peripheral arthritis and sacroiliitis, as well as systemic bone loss.

Methods

Disease course, histopathological features of arthritis, and micro-CT (µCT) bone analysis of local and systemic bone loss were assessed in 15-week-old IL1-/-IL6-/-hTNFtg in comparison to IL1-/-hTNFtg, IL6-/-hTNFtg, and hTNFtg mice. µCT bone analysis of single deficient and wild-type mice was also performed.


Bone & Joint Research
Vol. 11, Issue 10 | Pages 700 - 714
4 Oct 2022
Li J Cheung W Chow SK Ip M Leung SYS Wong RMY

Aims

Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models.

Methods

Literature research was performed on PubMed and Embase databases. Keywords used for search criteria were “bone AND biofilm”. Information on the species of the animal model, bacterial strain, evaluation of biofilm and bone infection, complications, key findings on observations, prevention, and treatment of biofilm were extracted.


Bone & Joint Research
Vol. 11, Issue 7 | Pages 465 - 476
13 Jul 2022
Li MCM Chow SK Wong RMY Chen B Cheng JCY Qin L Cheung W

Aims

There is an increasing concern of osteoporotic fractures in the ageing population. Low-magnitude high-frequency vibration (LMHFV) was shown to significantly enhance osteoporotic fracture healing through alteration of osteocyte lacuno-canalicular network (LCN). Dentin matrix protein 1 (DMP1) in osteocytes is known to be responsible for maintaining the LCN and mineralization. This study aimed to investigate the role of osteocyte-specific DMP1 during osteoporotic fracture healing augmented by LMHFV.

Methods

A metaphyseal fracture was created in the distal femur of ovariectomy-induced osteoporotic Sprague Dawley rats. Rats were randomized to five different groups: 1) DMP1 knockdown (KD), 2) DMP1 KD + vibration (VT), 3) Scramble + VT, 4) VT, and 5) control (CT), where KD was performed by injection of short hairpin RNA (shRNA) into marrow cavity; vibration treatment was conducted at 35 Hz, 0.3 g; 20 minutes/day, five days/week). Assessments included radiography, micro-CT, dynamic histomorphometry and immunohistochemistry on DMP1, sclerostin, E11, and fibroblast growth factor 23 (FGF23). In vitro, murine long bone osteocyte-Y4 (MLO-Y4) osteocyte-like cells were randomized as in vivo groupings. DMP1 KD was performed by transfecting cells with shRNA plasmid. Assessments included immunocytochemistry on osteocyte-specific markers as above, and mineralized nodule staining.


Bone & Joint Research
Vol. 10, Issue 11 | Pages 734 - 741
1 Nov 2021
Cheng B Wen Y Yang X Cheng S Liu L Chu X Ye J Liang C Yao Y Jia Y Zhang F

Aims

Despite the interest in the association of gut microbiota with bone health, limited population-based studies of gut microbiota and bone mineral density (BMD) have been made. Our aim is to explore the possible association between gut microbiota and BMD.

Methods

A total of 3,321 independent loci of gut microbiota were used to calculate the individual polygenic risk score (PRS) for 114 gut microbiota-related traits. The individual genotype data were obtained from UK Biobank cohort. Linear regressions were then conducted to evaluate the possible association of gut microbiota with L1-L4 BMD (n = 4,070), total BMD (n = 4,056), and femur total BMD (n = 4,054), respectively. PLINK 2.0 was used to detect the single-nucleotide polymorphism (SNP) Ă— gut microbiota interaction effect on the risks of L1-L4 BMD, total BMD, and femur total BMD, respectively.


Bone & Joint 360
Vol. 10, Issue 6 | Pages 45 - 46
1 Dec 2021


Bone & Joint 360
Vol. 11, Issue 3 | Pages 14 - 17
1 Jun 2022


The Journal of Bone & Joint Surgery British Volume
Vol. 51-B, Issue 4 | Pages 719 - 735
1 Nov 1969
Ahuja M

1. A review of the literature on the normal variations in bone mass in a given population in relation to age, sex, nutritional and genetic background shows several lacunae in our knowledge. Consequently, the separation of milder degrees of osteoporosis is difficult and the definition of osteoporosis itself is uncertain. 2. This paper presents a necropsy study to determine variations in the bone mass that occur with age and sex in a normal Indian population in the Delhi area. Two hundred persons between nine months and seventy-six years of age who died by accident and with no evidence of chronic disease were studied. 3. The parameters of bone mass employed were : apparent bone density, ash per millilitre of bone, cortical thickness and visual grading of porosity of bone in macerated specimens. The first lumbar vertebra, the iliac crest, the fourth rib and the femoral shaft were the bones evaluated. 4. After an initial rise up to the third decade, the apparent bone density and ash per millilitre showed a progressive and significant decline with age in all the three trabecular bones: vertebra, iliac crest and rib. Although these values were in general lower in the females than in males at all ages, and the rate of decrease with age was faster in them than in males, it was only in the rib that a statistically significant difference between the sexes could be established with respect to decrease with age. 5. Decreases in apparent bone density and ash per millilitre of the vertebral bone with age were associated with an increase with age in the porosity as assessed by visual grading. 6. In the case of the femur no significant change was demonstrable with age in any of the parameters used in the present study. 7. From a comparison of the values for apparent density and ash per millilitre with grading of macerates and histological preparations, it is suggested that osteoporosis may be said to be present in this population if the apparent bone density is less than 020 and 046 in the vertebra and the iliac crest respectively or ifthe ash per millilitre is less than 0l2 in the vertebra. 8. The study has revealed that 44 per cent of persons studied in this sample over the age of fifty exhibit significant osteoporosis. It is considered possible that nutritional factors such as protein-calorie malnutrition may be responsible for this relatively high incidence


Bone & Joint Research
Vol. 3, Issue 7 | Pages 230 - 235
1 Jul 2014
van der Jagt OP van der Linden JC Waarsing JH Verhaar JAN Weinans H

Objectives. Electromagnetic fields (EMF) are widely used in musculoskeletal disorders. There are indications that EMF might also be effective in the treatment of osteoporosis. To justify clinical follow-up experiments, we examined the effects of EMF on bone micro-architectural changes in osteoporotic and healthy rats. Moreover, we tested the effects of EMF on fracture healing. Methods. EMF (20 Gauss) was examined in rats (aged 20 weeks), which underwent an ovariectomy (OVX; n = 8) or sham-ovariectomy (sham-OVX; n = 8). As a putative positive control, all rats received bilateral fibular osteotomies to examine the effects on fracture healing. Treatment was applied to one proximal lower leg (three hours a day, five days a week); the lower leg was not treated and served as a control. Bone architectural changes of the proximal tibia and bone formation around the osteotomy were evaluated using in vivo microCT scans at start of treatment and after three and six weeks. Results. In both OVX and sham-OVX groups, EMF did not result in cancellous or cortical bone changes during follow-up. Moreover, EMF did not affect the amount of mineralised callus volume around the fibular osteotomy. Conclusions. In this study we were unable to reproduce the strong beneficial findings reported by others. This might indicate that EMF treatment is very sensitive to the specific set-up, which would be a serious hindrance for clinical use. No evidence was found that EMF treatment can influence bone mass for the benefit of osteoporotic patients. Cite this article: Bone Joint Res 2014;3:230–5


The Bone & Joint Journal
Vol. 97-B, Issue 1 | Pages 89 - 93
1 Jan 2015
Maier GS Seeger JB Horas K Roth KE Kurth AA Maus U

Hypovitaminosis D has been identified as a common risk factor for fragility fractures and poor fracture healing. Epidemiological data on vitamin D deficiency have been gathered in various populations, but the association between vertebral fragility fractures and hypovitaminosis D, especially in males, remains unclear. The purpose of this study was to evaluate serum levels of 25-hydroxyvitamin D (25-OH D) in patients presenting with vertebral fragility fractures and to determine whether patients with a vertebral fracture were at greater risk of hypovitaminosis D than a control population. Furthermore, we studied the seasonal variations in the serum vitamin D levels of tested patients in order to clarify the relationship between other known risk factors for osteoporosis and vitamin D levels. We measured the serum 25-OH D levels of 246 patients admitted with vertebral fractures (105 men, 141 female, mean age 69 years, . sd. 8.5), and in 392 orthopaedic patients with back pain and no fractures (219 men, 173 female, mean age 63 years, . sd. 11) to evaluate the prevalence of vitamin D insufficiency. Statistical analysis found a significant difference in vitamin D levels between patients with vertebral fragility fracture and the control group (p = 0.036). In addition, there was a significant main effect of the tested variables: obesity (p < 0.001), nicotine abuse (p = 0.002) and diabetes mellitus (p < 0.001). No statistical difference was found between vitamin D levels and gender (p = 0.34). Vitamin D insufficiency was shown to be a risk factor for vertebral fragility fractures in both men and women. Cite this article: Bone Joint J 2015;97-B:89–93


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 10 | Pages 1313 - 1320
1 Oct 2012
Middleton RG Shabani F Uzoigwe CE AS Moqsith M Venkatesan M

Osteoporosis is common and the health and financial cost of fragility fractures is considerable. The burden of cardiovascular disease has been reduced dramatically by identifying and targeting those most at risk. A similar approach is potentially possible in the context of fragility fractures. The World Health Organization created and endorsed the use of FRAX, a fracture risk assessment tool, which uses selected risk factors to calculate a quantitative, patient-specific, ten-year risk of sustaining a fragility fracture. Treatment can thus be based on this as well as on measured bone mineral density. It may also be used to determine at-risk individuals, who should undergo bone densitometry. FRAX has been incorporated into the national osteoporosis guidelines of countries in the Americas, Europe, the Far East and Australasia. The United Kingdom National Institute for Health and Clinical Excellence also advocates its use in their guidance on the assessment of the risk of fragility fracture, and it may become an important tool to combat the health challenges posed by fragility fractures


Bone & Joint 360
Vol. 1, Issue 3 | Pages 30 - 33
1 Jun 2012

The June 2012 Research Roundup. 360. looks at: platelet-rich plasma; ageing, bone and mesenchymal stem cells; cytokines and the herniated intervertebral disc; ulcerative colitis, Crohn’s disease and anti-inflammatories; the effect of NSAIDs on bone healing; osteoporosis of the fractured hip; herbal medicine and recovery after acute muscle injury; and ultrasound and the time to fracture union


The Journal of Bone & Joint Surgery British Volume
Vol. 74-B, Issue 1 | Pages 67 - 73
1 Jan 1992
Kwong L Jasty M Mulroy R Maloney W Bragdon C Harris W

The radiographic and histological features of radiolucent areas at the cement-bone interface were correlated in 15 specimens retrieved at post-mortem from patients who had undergone cemented total hip arthroplasty, two weeks to 15 years prior to death. All but one of the components were securely fixed, as demonstrated by direct measurements of micromotion. Extensive radiolucencies were present in all but one case. In 11 of the 14 specimens with radiolucencies, histological examination showed that the radiolucent areas represented regions of osteoporosis and bone remodelling. The remodelling changes were characterised by osteoporosis, cancellisation and thinning of the endosteal cortex, and osteopenia of the trabecular bone. In two specimens the appearance of radiolucency was found to be due to fibrous tissue at the cement-bone interface and in one specimen there was a mixed picture of osteolysis and fibrosis. The study demonstrates that radiolucent lines can occur with well-fixed components and that they may commonly represent osteoporosis rather than the presence of a fibrous membrane at the cement-bone interface


Bone & Joint 360
Vol. 11, Issue 2 | Pages 34 - 37
1 Apr 2022


The Journal of Bone & Joint Surgery British Volume
Vol. 54-B, Issue 2 | Pages 277 - 298
1 May 1972
Brenton DP Dow CJ James JIP Hay RL Wynne-Davies R

1. Skeletal and other clinical features in twenty-three patients with homocystinuria have been compared with those in sixteen patients with Marfan's syndrome. 2. The two diseases are clinically similar but florid arachnodactyly and scoliosis are commoner in Marfan's syndrome, whereas widening of epiphyses and metaphyses of long bones is a distinctive feature of homocystinuria. 3. Patients with homocystinuria frequently have osteoporosis at a young age with a high incidence of vertebral involvement including biconcavity and flattening. Patients with Marfan's syndrome do not have osteoporosis and may have excessively tall vertebrae. 4. Mental retardation and thrombosis are common in homocystinuria and uncommon in Marfan's syndrome. 5. Homocystinuria is most probably inherited as an autosomal recessive and Marfan's syndrome as an autosomal dominant. 6. The two diseases should be differentiated because of the thrombotic risk in homocystinuria, and also because in this disease there is a possibility of treating the biochemical defect. 7. Although patients with homocystinuria may present to the orthopaedic surgeon with osteoporosis, severe genu valgum or scoliosis, the disease is an uncommon cause of these defects


Bone & Joint Research
Vol. 11, Issue 4 | Pages 214 - 225
20 Apr 2022
Hao X Zhang J Shang X Sun K Zhou J Liu J Chi R Xu T

Aims

Post-traumatic osteoarthritis (PTOA) is a subset of osteoarthritis (OA). The gut microbiome is shown to be involved in OA. However, the effect of exercise on gut microbiome in PTOA remains elusive.

Methods

A total of 18 eight-week Sprague-Dawley rats were assigned into three groups: Sham/sedentary (Sham/Sed), PTOA/sedentary (PTOA/Sed), and PTOA/treadmill-walking (PTOA/TW). PTOA model was induced by transection of the anterior cruciate ligament (ACLT) and the destabilization of the medial meniscus (DMM). Treadmill-walking (15 m/min, 30 min/d, five days/week for eight weeks) was employed in the PTOA/TW group. The response of cartilage, subchondral bone, serology, and gut microbiome and their correlations were assessed.


Bone & Joint 360
Vol. 10, Issue 4 | Pages 45 - 47
1 Aug 2021


Bone & Joint 360
Vol. 1, Issue 5 | Pages 26 - 28
1 Oct 2012

The October 2012 Oncology Roundup. 360. looks at: the causes of primary bone tumours; adjuvant chemotherapy in the longer term; vascularised fibular grafts to salvage massive femoral allografts; a new look at old risks; reconstruction with excised irradiated bone; predicting chemosensitivity in osteosarcoma ; and chemotherapy, osteoporosis and the risk of fracture


The Journal of Bone & Joint Surgery British Volume
Vol. 50-B, Issue 1 | Pages 2 - 13
1 Feb 1968
Solomon L

1. Senile osteoporosis is one of the common causes of morbidity in old people. Its distribution in European and American populations has been deduced from epidemiological studies of its major complications, such as fractures of the vertebrae and the femoral neck. Although there has been some evidence that different population groups differ in their susceptibility to this condition, no demographic study of its prevalence in the white and Bantu races has previously been made. 2. The present paper describes an epidemiological study of femoral neck fractures in the Bantu population of Johannesburg, covering the years 1957-63. The cases were analysed by age and sex, the type of trauma and the level of the fracture. The number of fractures was related to the population at risk; the fracture incidence was expressed both as an age-specific rate and as a standardised rate and compared with fracture rates in European populations. It was found that the fracture rate in the elderly Bantu is less than one-tenth of that in Western European populations, and that males and females are affected equally. It was concluded that senile or post-menopausal osteoporosis is much less pronounced in the Bantu than in white populations. 3. The relationship of these findings to endocrine changes, calcium balance and racial factors is discussed. It is suggested that senile osteoporosis is not caused by a simple calcium deficiency but may be related to an imbalance between calcium intake, absorption and excretion, or a failure of the complex mechanism which normally controls this balance. Whatever the immediate cause, however, race plays an important part in determining the onset and distribution of the condition