Aims. To examine the relationship of
Traumatic acute or chronic tendon injuries are a wide clinical problem in modern society, resulting in important economic burden to the health system and poor quality of life in patients. Due to the low cellularity and vascularity of tendon tissue the repair process is slow and inefficient, resulting in mechanically, structurally, and functionally inferior tissue. Tissue engineering and regenerative medicine are promising alternatives to the natural healing process for tendon repair, especially in the reconstruction of large damaged tissues. The aim of TRITONE project is to develop a smart, bioactive implantable 3D printed scaffold, able to reproduce the structural and functional properties of human tendon, using FDA approved materials and starting from MSC and their precursor, MPC cell mixtures from human donors. Total cohort selected in the last 12 months was divided in group 1 (N=20) of subjects with tendon injury and group 2 (N=20) of healthy subject. Groups were profiled and age and gender matched. Inclusion criteria were age>18 years and presence of informed consent. Ongoing pregnancy, antihypertensive treatment, cardiovascular diseases, ongoing treatment with anti-aggregants, acetylsalicylic-acid or lithium and age<18 years were exclusion criteria. Firstly, we defined clinical, biological, nutritional life style and genetic profile of the cohort. The deficiency of certain nutrients and
Relating the results of our investigations to the knowledge hitherto acquired about the etiology of osteoporosis (which I have already referred to), I am inclined to interpret the pathogenesis of osteoporosis in the following way: 1) Primary osteoblastic deficiency: congenital (Lobstein); involutive (senile osteoporosis?); 2) Reduced osteoblastic activity from absence of trophic stimuli: (inactivity, ovarian agenesia, eunuchoidism, menopause); 3) Reduced osteoblastic activity from inhibitory stimuli: (cortisone, adrenocorticotrophic hormone (A.C.T.H.), stress, Cushing's disease, thyrotoxicosis); 4) Normal osteoblastic activity but insufficiency of constructive material: (malnutrition, disturbances of the digestive system, insufficiency of vitamin C, diabetes, thyrotoxicosis, cortisone, A.C.T.H., stress, Cushing's disease). Osteoporosis may therefore be the consequence either of a congenital osteoblastic deficiency, such as that found in cases of osteogenesis imperfecta, or of reduced osteoblastic activity due to absence of trophic stimuli such as mechanical stress and the
Objectives. Insufficient protein ingestion may affect muscle and bone mass, increasing the risk of osteoporotic fractures in the elderly, and especially in postmenopausal women. We evaluated how a low-protein diet affects bone parameters under gonadal hormone deficiency and the improvement led by hormone replacement therapy (HRT) with 17β-oestradiol. Methods. Female Wistar rats were divided into control (C), ovariectomized (OVX), and 17β-oestradiol-treated ovariectomized (OVX-HRT) groups, which were fed a control or an isocaloric low-protein diet (LP; 6.6% protein; seven animals per group). Morphometric, serum, and body composition parameters were assessed, as well as bone parameters, mechanical resistance, and mineralogy. Results. The results showed that protein restriction negatively affected body chemical composition and bone metabolism by the
Purpose: To investigate the effect of amifostine and dexrazoxane on bone mass of the vertebrae and femurs of doxorubicin treated male rats. Methods: Amifostine, Doxorubicin and Dexrazoxane were purchased from SMBD-Jewish General Hospital Pharmacy. Lactating Sprague Dawley dams with 14 male pups were purchased from Charles River Canada. At neonate day 10, rat pups were randomly divided into 4 groups of n=5. Pups were injected once intraperitoneally with either Phosphate Saline Buffer 1X (saline), or drugs, AMF (50 mg/kg), AMF + DOX (50 mg/kg +3 mg/ kg), or with AMF + DXR + DOX (50 mg/kg + 60 mg + 3 mg/kg, 20:1 DXR to DOX ratio). AMF and DXR were injected 30 minutes prior to the DOX injection. After injection, rat pups were returned to their mothers until weaning on neonate day 22. Rats were then sacrificed at day 38 (28 Post-Injection, PI). Bone mineral density (BMD) and micro computed tomography were analyzed. Results: Dissection of male pups days 1, 5 or 9 post-injection did not reveal any intestinal or organ damage. AMF treatment alone led to a slight but not significant increase in the right femoral, left femoral and lumbar vertebral BMDs. Similarly, AMF + DOX or AMF + DXR + DOX treated rats had no significant change in either femoral and vertebrae BMD. Conclusions: We recently showed that a single injection of DOX in young female rats is associated with low bone turnover resulting in vertebrae and femur bone growth deficits. However, no such a difference was detected when similarly treated males were examined. The role of
1. The syndrome of osteoporosis is reviewed and its various causes are mentioned. Osteoporosis in youngish patients without any demonstrable cause is referred to as "idiopathic." The scant literature on this condition is reviewed. Its clinical, radiological, biochemical and histological features are considered. 2. A series of thirty-eight cases is analysed, and illustrative case histories are described. The peculiarities of the disease as it is seen in women are discussed, particularly the relationship to pregnancy and lactation, which appear to act as precipitating factors, rather than being primarily causative. 3. The differential diagnosis is discussed. Osteogenesis imperfecta may not always be easy to distinguish; since it is really a "congenital osteoporosis" this is hardly surprising. 4. The following possible etiological factors are propounded (apart from pregnancy): nutritional, occupational, lack of
Cartilage-bone interactions play a critical role in joint diseases and the osteochondral junction has been identified as a locus of osteoarthritis development. However, it is challenging to study osteochondral (OC) interaction in vitro, since cartilage and bone require very different environments. We developed a new medium-to-high throughput osteochondral microphysiological system bioreactor to culture biphasic native or engineered constructs and that can be used to study any musculoskeletal tissue interfaces. We developed engineered constructs from hMSCs on a porous polymeric matrix with a gradient in pore size to assess the supportive effect of the local topology on cartilaginous and osseous differentiation. Furthermore, we developed a triphasic, vascualized osteochondral constructs based on porous polycaprolactone and methacrylated gelatin scaffolds to study the specific effects of vasculature on cartilage and bone. We also cultured native OC tissues from postmenopausal women, exposing either cartilage or bone to
Four cases of slipped upper femoral epiphyses in patients with intracranial tumours causing hypopituitarism and chiasmal compression are presented. Detailed endocrine studies in three cases showed severe deficiencies of growth hormone as well as of gonadotrophin and
Transcription factor nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of chronic inflammatory diseases in all organ systems. Despite its importance, NF-κB targeted drug therapy to mitigate chronic inflammation has had limited success in preclinical studies. We hypothesized that sex differences affect the response to NF-κB treatment during chronic inflammation in bone. This study investigated the therapeutic effects of NF-κB decoy oligodeoxynucleotides (ODN) during chronic inflammation in male and female mice. We used a murine model of chronic inflammation induced by continuous intramedullary delivery of lipopolysaccharide-contaminated polyethylene particles (cPE) using an osmotic pump. Specimens were evaluated using micro-CT and histomorphometric analyses. Sex-specific osteogenic and osteoclastic differentiation potentials were also investigated in vitro, including alkaline phosphatase, Alizarin Red, tartrate-resistant acid phosphatase staining, and gene expression using reverse transcription polymerase chain reaction (RT-PCR).Aims
Methods
Aims. The assessment of the potential pathological influence of Growth Hormone (hGH), Testosterone, Estradiol, Follicle Stimulating Hormone (FSH) and Luteinizing Hormone in the development of SCFE and the re-evaluation of the Harris theory (increased quotient of hGH/
In the pubertal growth plate,
Porcine and fish by-products in particular are rich sources for collagen, which is the main component of the extracellular matrix (ECM). Although there are studies investigating different collagen derived from various tissue sources for the purpose of creating biomaterials, the comparison of biophysical, biochemical and biological properties of type II collagen isolated from cartilaginous tissues has yet to be assessed. In addition, it has been shown from previous studies that
1. Individuals who are normal and not osteoporotic seem to show retention of cortical bone at successive decades of life in proportion to the total lean body-mass. In patients with osteoporosis the weight of the skeleton decreases at a rate exceeding the physiological rate of atrophy of muscle, tendon and bone tissue that occurs with the time-dependent process of ageing. 2. Six patients representing the typical forms of osteoporosis commonly found in orthopaedic practice were investigated intensively over a period of three years and compared with individuals in whom there was no osteoporosis by studies of metabolic balance, Sr85 osteograms, and tetracycline deposition. 3. Studies of metabolic balance in patients with osteoporosis showed normal or negative calcium balances, but an equilibrium for the metabolism of nitrogen and phosphorus. Increased intake of calcium in the diet produced retention of calcium but not sufficient phosphorus, nitrogen or gain in weight to prove that the patient had made new bone and healed the osteoporosis. 4. Radio-isotope osteograms showed high, normal or low rates of change of uptake of Sr85 and the accretion rate was calculated to be normal or low in individuals with osteoporosis. High uptake of tetracycline by a small mass of bone tissue and by a relatively small percentage of the total number of osteons suggested that in an adult human being the calcium reserve in the skeleton is enormous. Thirty to 50 per cent of the total bone mass was sufficient to turn over 0·5 to 1·0 gramme, the amount of calcium utilised in twenty-four hours by the human adult. This was accomplished by structural or old bone throughout the entire skeleton, and by labile or newer bone located in approximately 10 per cent of the total number of Haversian cylinders or osteons. 5. Some of the unclosed or half-closed osteons were hyperactive in osteoporotic bones. In the process of remodelling of cortical bone a significant quantity of bone tissue was incompletely restored and there were, presumably as a result, intermittently large or small negative calcium balances. Osteoporosis may have been the cause, rather than the result, of the negative calcium balance. 6. The experimental and clinical literature of the past ten years, and studies on patients described in this critical review, were interpreted to indicate that prolonged calcium deficiency, castration, hyperadrenal corticoidism or a sedentary life may precipitate, accentuate and accelerate osteoporosis in individuals who are genetically predisposed to develop it. Sometimes high calcium intake or
The case histories of these Black Notley patients show that no serious harmful effects have been caused by pregnancies going to full term. Most of the patients had normal confinements; Caesarian sections were few and were usually done for obstetric reasons, not for fear of reactivation of the disease. This experience bears out a remark made to me by Marcel Galland. When asked if Caesarian sections were required for women who became pregnant after treatment at Berck for skeletal tuberculosis, he replied: "Jarnais! Tout passe!". Two patients in the series had artificial abortions, and one aborted spontaneously. Two of these three patients did not do as well as other patients whose pregnancies went to full term. Quite another question is whether the onset of skeletal tuberculosis sooii after pregnancy may be attributed to the pregnancy. In a group of women of child-bearing age, it would be difficult to distinguish between post hoc and propter hoc in considering this question. One patient of this series, H. Q. (Case 25), was admitted eight months pregnant with active tuberculosis of the knee; but pain in the joint had started fifteen months before admission, and the onset of disease no doubt preceded the pregnancy. Some of the patients admitted to Black Notley were mothers of young children hut there is no note of any pregnancy having preceded the onset of tuberculosis by a short interval. The follow-up reports of the married patients compare favourably with those of the unmarried. Further, it may be argued that pregnancy increases resistance to tuberculosis. Such a belief was current from the time of Hippocrates until the middle of the nineteenth century, and clinical evidence can be quoted in favour of such a view. In America, Lyman (1943) followed up 1,818 women who had been treated for tuberculosis in a sanatorium; many had married despite medical advice to the contrary. Lyman found that the late results of treatment were four times as good in the married patients as in the single women. Lyman says, "When we consider that the married group established this record in spite of the fact that 192 out of 315 gave histories of pregnancies (averaging 2·25 children each), it is clear that some factor not yet accounted for has exerted a profound influence in their cases.". I have speculated elsewhere as to what this factor may be (Wilkinson 1949). But it seems clear that increased sterol circulation in the body is associated with increased reticulo-endothelial activity (Fraser 1935). Thus reticulo-endothelial proliferation has been observed in the lesions of lupus following the administration of calciferol (Dowling, Gauvain and Macrae 1948). An increase of blood cholesterol is found during pregnancy. The
The aims of this meta-analysis were to assess: 1) the prevalence of coronavirus disease 2019 (COVID-19) in hip fracture patients; 2) the associated mortality rate and risk associated with COVID-19; 3) the patient demographics associated with COVID-19; 4) time of diagnosis; and 5) length of follow-up after diagnosis of COVID-19. Searches of PubMed, Medline, and Google Scholar were performed in October 2020 in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. Search terms included “hip”, “fracture”, and “COVID-19”. The criteria for inclusion were published clinical articles reporting the mortality rate associated with COVID-19 in hip fracture patients. In total, 53 articles were identified and following full text screening 28 articles satisfied the inclusion criteria.Aims
Methods
Up to 10% of fractures result in undesirable outcomes, for which female sex is a risk factor. Cellular sex differences have been implicated in these different healing processes. Better understanding of the mechanisms underlying bone healing and sex differences in this process is key to improved clinical outcomes. This study utilized a macrophage–mesenchymal stem cell (MSC) coculture system to determine: 1) the precise timing of proinflammatory (M1) to anti-inflammatory (M2) macrophage transition for optimal bone formation; and 2) how such immunomodulation was affected by male A primary murine macrophage-MSC coculture system was used to demonstrate the optimal transition time from M1 to M2 (polarized from M1 with interleukin (IL)-4) macrophages to maximize matrix mineralization in male and female MSCs. Outcome variables included Alizarin Red staining, alkaline phosphatase (ALP) activity, and osteocalcin protein secretion.Objectives
Methods
The osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) balance is of the utmost importance in fracture healing. The aim of this study was therefore to investigate the impact of nonosteogenic factors on OPG and RANKL levels. Serum obtained from 51 patients with long bone fractures was collected over 48 weeks. The OPG and serum sRANKL (soluble RANKL) concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Smoking habit, diabetes, and alcohol consumption were recorded.Objectives
Methods
The aim of this study was to explore risk factors for complications associated with dural tear (DT), including the types of DT, and the intra- and postoperative management of DT. Between 2012 and 2017, 12 171 patients with degenerative lumbar diseases underwent primary lumbar spine surgery. We investigated five categories of potential predictors: patient factors (sex, age, body mass index, and primary disease), surgical factors (surgical procedures, operative time, and estimated blood loss), types of DT (inaccessible for suturing/clipping and the presence of cauda equina/nerve root herniation), repair techniques (suturing, clipping, fibrin glue, polyethylene glycol (PEG) hydrogel, and polyglycolic acid sheet), and postoperative management (drainage duration). Postoperative complications were evaluated in terms of dural leak, prolonged bed rest, headache, nausea/vomiting, delayed wound healing, postoperative neurological deficit, surgical site infection (SSI), and reoperation for DT. We performed multivariable regression analyses to evaluate the predictors of postoperative complications associated with DT.Aims
Patients and Methods
Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass and deterioration of bone microarchitecture, which results in increased bone fragility and fracture risk. Casein kinase 2-interacting protein-1 (CKIP-1) is a protein that plays an important role in regulation of bone formation. The effect of CKIP-1 on bone formation is mainly mediated through negative regulation of the bone morphogenetic protein pathway. In addition, CKIP-1 has an important role in the progression of osteoporosis. This review provides a summary of the recent studies on the role of CKIP-1 in osteoporosis development and treatment.