Aims. The prevalence of scoliosis is not known in patients with idiopathic short stature, and the impact of treatment with recombinant human growth
Aims. The assessment of the potential pathological influence of Growth
There is a disparity in sport-related injuries between sexes, with females sustaining non-contact musculoskeletal injuries at a higher rate. Anterior cruciate ligament ruptures are between two and eight times more common than in males, and females also have a higher incidence of ankle sprains, patellofemoral pain, and bone stress injuries. The sequelae of such injuries can be devastating to an athlete, resulting in time out of sport, surgery, and the early onset of osteoarthritis. It is important to identify the causes of this disparity and introduce prevention programmes to reduce the incidence of these injuries. A natural difference reflects the effect of reproductive
Intermittently administered parathyroid
Aims. To examine the relationship of sex steroid
Aims. To develop an early implant instability murine model and explore the use of intermittent parathyroid
Impaction allograft is an established method of securing initial stability of an implant in arthroplasty. Subsequent bone integration can be prolonged, and the volume of allograft may not be maintained. Intermittent administration of parathyroid
Objectives. Mesenchymal stem cells (MSCs) are of growing interest in terms of bone regeneration. Most preclinical trials utilize bone-marrow-derived mesenchymal stem cells (bMSCs), although this is not without isolation and expansion difficulties. The aim of this study was: to compare the characteristics of bMSCs and adipose-derived mesenchymal stem cells (AdMSCs) from juvenile, adult, and ovarectomized (OVX) rats; and to assess the effect of human parathyroid
Aims. Osteoarthritis (OA) is prevalent among the elderly and incurable. Intra-articular parathyroid
Adrenomedullin is a peptide
Aims. Parathyroid
Abstract. Objectives. Current therapies for osteoporosis are limited to generalised antiresorptive or anabolic interventions, which do not target specific regions to improve skeletal health. Moreover, the adaptive changes of separate and combined pharmacological and biomechanical treatments in the ovariectomised (OVX) mouse tibia has not been studied yet. Therefore, this study combines micro- computed tomography (micro-CT) imaging and computational modelling to evaluate the efficacies of treatments in reducing bone loss. Methodology. In vivo micro-CT (10.4µm/voxel) images of the right tibiae of N=18 female OVX C57BL/6 mice were acquired at weeks 14, 16, 18, 20 and 22 of age for 3 groups: mechanical loading (ML), parathyroid
Introduction: Following an Australian study on the incidence of scoliosis in a population of short-statured children treated with human growth
Introduction: Retrospective reports of adverse events following growth
Introduction: Hip arthroplasty can present surgeons with difficult bone loss. Impacted allografting is a well-established way of initally securing implant stability. However subsequent bone integration and fusion can be prolonged. Also concerns relate on maintaining bone volume of allograft during integration. Intermittent administration of parathyroid
Introduction: Treatment of osteoarthritis by total joint replacement generally shows a high success rate; however challenges remain. Prostheses inserted without cement are popular worldwide. Insertion of uncemented implants is intended to be pressfit. Early bone growth on the implant is critical to long-term fixation. Parathyroid
Sex
In 65 mature Wistar rats a Kirschner wire was introduced into the medullary cavity of each femur. A closed transverse mid-shaft fracture of one femur was produced by a three-point bending technique. Subsequently the mechanical characteristics of the healing fracture, including the torque and angle of twist required to take the callus to its yield point and to ultimate failure, were compared with those for the opposite femur of each rat. Controls were killed in groups at two, three, four, five and seven weeks. Test animals were given bovine growth
1. A case is reported of a girl aged fifteen with growth
We have examined the deterioration of implant fixation after withdrawal of parathyroid
Aims: In order to assess the potential pathologic inßuence of any Parathyroid
In 15 consecutive patients with slipped capital femoral epiphysis we recorded height, weight and skeletal maturity. Sexual maturity was assessed clinically and biochemically, and Harris's hypothesis that there is an increased ratio of serum growth
Introduction: Parathyroid
The intermittent administration of parathyroid
A one-year-8-month-old girl who received radiotherapy and chemotheraphy after excision of embryonal rhabdomyosarcoma from left labium majus pudendi developed slipped capital femoral epiphysis (SCFE) over right hip when she was 9 years old. After mild limp had been noted for 6 months she was then referred to pediatric orthopedic surgeon and two Knowles pins were used to fix the slipping. The second case was a 17-year-old girl with Turner syndrome. SCFE developed during the growth
The changes in serum adjusted ionised calcium and parathyroid
Introduction: Since Albright first proposed the concept of diabetic osteopenia, many studies have investigated the levels of mineral bone density (BMD) and risk of osteoporosis. In this study we investigate the effect of exercise, alfacalcidol and parathyroid
Introduction. Recently, some case reports have been published, in which nonunions were successfully healed with parathyroid
Intermittent treatment with parathyroid
Introduction. Parathyroid
Since the approval of parathyroid
Improving periprosthetic bone is essential for implant fixation and reducing peri-implant fracture risk. This studied examined the individual and combined effects of iPTH and mechanical loading at the cellular, molecular, and tissue level for periprosthetic cancellous bone. Adult rabbits had a porous titanium implant inserted bilaterally on the cancellous bone beneath a mechanical loading device on the distal lateral femur. The right femur was loaded daily, the left femur received a sham loading device, and half of the rabbits received daily PTH. Periprosthetic bone was processed up to 28 days for qPCR, histology, and uCT analysis. We observed an increase in cellular and molecular markers of osteoblast activity and decrease in adipocytic markers for both treatments, with small additional effects in the combined group. Loading and iPTH led to a decrease and increase, respectively, in osteoclast number, acting through changes in RANKL/OPG expression. Changes in SOST and beta-catenin mRNA levels suggested an integral role for the Wnt pathway. We observed strong singular effects on BV/TV of both loading (1.53 fold) and iPTH (1.54 fold). Combined treatment showed a small additive effect on bone volume. In conclusion, loading and iPTH act through a pro-osteoblastic/anti-adipocytic response and through control of bone turnover via changes in the RANKL/OPG pathway. These changes led to a small additional, but not synergistic, increase in bone volume with the combined therapy.
The aim of our study was to evaluate if PTH is able to increase the trabecular density of osteoporotic bone at the site of an implant and whether the anabolic effect of PTH at this side is stronger then the effect of an osteoclast inhibitor like alendronate. 48 cement rod was inserted in the tibia of 48 female rats, of which 36 had been ovariectomized. The cement rods, which served as implants, were made of Palacos R bone cement. After implantation, the 36 ovariectomized rats were divided in 3 groups. One was injected subcutaneusly with PTH (1–34) at a dose of 60 g/kg BW. The second was injected with alendronate at a dose of 205 g/kg BW. The third with vehicle only. The remaining 12 sham operated rats were also injected with vehicle only. All injections were given three times a week and the rats were killed 2 weeks after implantation. The tibial segments around the hole of the rods were prepared histologically. Thus the surfaces which had been in contact with the rod appeared as straight lines and could be analyzed histomorphometricly. The trabecular density of the bone closest to the implant was measured. One femur of all animals was used for measurement by DEXA. There was a substantial increase in the trabecular density close to the rods with PTH treatment (Anova p=0.002). PTH lead to a trabecular density of 89%, where as the ovariectomized animals revealed a trabecular density of 58% and the sham operated control of 68%. No significant increase of implant related trabecular density could be found in the alendronate treated group. In this group a density of 72% was established. DEXA showed the expected differences in bone mineral content (Anova p=0.001). In this study, intermittent PTH treatment increased implant-related trabecular density in osteoporotic bone after 2 weeks. No such positive effect could be found with alendronate treatment at such a short period of time. We think the reason for this phenomenon could be the early onset of the anabolic PTH effect on regenerating bone, whereas alendronate is thought to only inhibit bone resorption, which might lead to a later effect. The early onset of PTH effects even in osteoporotic bone suggests that intermittent PTH treatment might lead to an increased micro-interlock between implant and bone and might therefore be considered as a possible drug to enhance incorporation of orthopedic implants.
Anterior cruciate ligament (ACL) injuries are among the most common and debilitating knee injuries in professional athletes with an incidence in females up to eight-times higher than their male counterparts. ACL injuries can be career-threatening and are associated with increased risk of developing knee osteoarthritis in future life. The increased risk of ACL injury in females has been attributed to various anatomical, developmental, neuromuscular, and
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
The April 2024 Research Roundup. 360. looks at: Prevalence and characteristics of benign cartilaginous tumours of the shoulder joint; Is total-body MRI useful as a screening tool to rule out malignant progression in patients with multiple osteochondromas?; Effects of vancomycin and tobramycin on compressive and tensile strengths of antibiotic bone cement: a biomechanical study; Biomarkers for early detection of Charcot arthropathy; Strong association between growth
Aims. Osteoporosis is common in total hip arthroplasty (THA) patients. It plays a substantial factor in the surgery’s outcome, and previous studies have revealed that pharmacological treatment for osteoporosis influences implant survival rate. The purpose of this study was to examine the prevalence of and treatment rates for osteoporosis prior to THA, and to explore differences in osteoporosis-related biomarkers between patients treated and untreated for osteoporosis. Methods. This single-centre retrospective study included 398 hip joints of patients who underwent THA. Using medical records, we examined preoperative bone mineral density measures of the hip and lumbar spine using dual energy X-ray absorptiometry (DXA) scans and the medications used to treat osteoporosis at the time of admission. We also assessed the following osteoporosis-related biomarkers: tartrate-resistant acid phosphatase 5b (TRACP-5b); total procollagen type 1 amino-terminal propeptide (total P1NP); intact parathyroid
The anterior cruciate ligament (ACL) is frequently injured in elite athletes, with females up to eight times more likely to suffer an ACL tear than males. Biomechanical and
Aims. A growing number of fractures progress to delayed or nonunion, causing significant morbidity and socioeconomic impact. Localized delivery of stem cells and subcutaneous parathyroid
Aims. Osteoarthritis (OA) is the most prevalent systemic musculoskeletal disorder, characterized by articular cartilage degeneration and subchondral bone (SCB) sclerosis. Here, we sought to examine the contribution of accelerated growth to OA development using a murine model of excessive longitudinal growth. Suppressor of cytokine signalling 2 (SOCS2) is a negative regulator of growth
Objectives. Osteoporosis has become an increasing concern for older people as it may potentially lead to osteoporotic fractures. This study is designed to assess the efficacy and safety of ten therapies for post-menopausal women using network meta-analysis. Methods. We conducted a systematic search in several databases, including PubMed and Embase. A random-effects model was employed and results were assessed by the odds ratio (OR) and corresponding 95% confidence intervals (CI). Furthermore, with respect to each outcome, each intervention was ranked according to the surface under the cumulative ranking curve (SUCRA) value. Results. With respect to preventing new vertebral fractures (NVF), all ten drugs outperformed placebo, and etidronate proved to be the most effective treatment (OR 0.24, 95% CI 0.14 to 0.39). In addition, zoledronic acid and parathyroid
Adipose tissue releases several bioactive peptides and
Breast cancer is generally managed surgically with adjuvant agents which include
The effect of high-fat diet and testosterone replacement therapy upon bone remodelling was investigated in orchiectomised male APOE-/- mice. Mice were split in to three groups: sham surgery + placebo treatment (control, n=9), orchiectomy plus placebo treatment (n=8) and orchiectomy plus testosterone treatment (n=10). Treatments were administered via intramuscular injection once a fortnight for 17 weeks before sacrifice at 25 weeks of age. Tibiae were scanned ex-vivo using µCT followed by post-analysis histology and immunohistochemistry. Previously presented µCT data demonstrated orchiectomised, placebo treated mice exhibited significantly reduced trabecular bone volume, number, thickness and BMD compared to control mice despite no significant differences in body weight. Trabecular parameters were rescued back to control levels in orchiectomised mice treated with testosterone. No significant differences were observed in the cortical bone. Assessment of TRAP stained FFPE sections revealed no significant differences in osteoclast or osteoblast number along the endocortical surface. IHC assessment of osteoprotegerin (OPG) expression in osteoblasts is to be quantified alongside markers of osteoclastogenesis including RANK and RANKL. Results support morphological analysis of cortical bone where no change in cortical bone volume or density between groups is in line with no significant change in osteoblast or osteoclast number and percentage across all three groups. Future work will include further IHC assessment of bone remodelling and adiposity, as well as utilisation of mechanical testing to establish the effects of observed morphological differences in bone upon mechanical properties. Additionally, the effects 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 sex
Re-rupture rates after rotator cuff repair remain high because of inadequate biological healing at the tendon-bone interface. Single-growth factor therapies to augment healing at the enthesis have so far yielded inconsistent results. An emerging approach is to combine multiple growth factors over a spatiotemporal distribution that mimics normal healing. We propose a novel combination treatment of insulin-like growth factor 1 (IGF-1), transforming growth factor β1 (TGF-β1) and parathyroid
Objectives. Ligaments which heal spontaneously have a healing process that
is similar to skin wound healing. Menopause impairs skin wound healing
and may likewise impair ligament healing. Our purpose in this study
was to investigate the effect of surgical menopause on ligament
healing in a rabbit medial collateral ligament model. Methods. Surgical menopause was induced with ovariohysterectomy surgery
in adult female rabbits. Ligament injury was created by making a
surgical gap in the midsubstance of the medial collateral ligament.
Ligaments were allowed to heal for six or 14 weeks in the presence
or absence of oestrogen before being compared with uninjured ligaments. Molecular
assessment examined the messenger ribonucleic acid levels for collagens,
proteoglycans, proteinases,
Introduction and Objective. The osteocyte, recognized as a major orchestrator of osteoblast and osteoclast activity, is the most important key player during bone remodeling processes. Imbalances that occur during bone remodeling, caused by
An increased prevalence of osteoarthritis (OA) in post-menopausal women has led to the suggestion that
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
Obese patients show a higher incidence of tendon-related pathologies. These patients present a low inflammatory systemic environment and a higher mechanical demand which can affect the tendons. In addition, inflammation might have a role in the progression of the disease as well as in the healing process. A systematic review was performed by searching PubMed, Embase and Cochrane Library databases. Inclusion criteria were studies of any level of evidence published in peer-reviewed journals reporting clinical or preclinical results. Evaluated data were extracted and critically analysed. PRISMA guidelines were applied, and risk of bias was assessed, as well as the methodological quality of the included studies. We excluded all the articles with high risk of bias and/or low quality after the assessment. Due to the high heterogeneity present among the studies, a metanalysis could not be done. Thus, a descriptive analysis was performed. After applying the previously described criteria, thirty articles were included, assessed as medium or high quality. We analysed the data of 50865 subjects, 6096 of which were obese (BMI over 30 accordingly to the WHO criteria). The overall risk of re-tear after surgery is about the 10% more than normal BMI subjects. The rupture risk fluctuates in the studies without showing a significant trend. Obese subjects have a higher risk to develop tendinopathy and a worse outcome after surgery as confirmed in several human studies. The obesity influence on tendon structure and mechanical properties may rely on the fat tissue endocrine proprieties and on
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
Introduction and Aims: SHOX haploinsufficiency presents with Turner syndrome dysmorphic skeletal features – micrognathia (60%), cubitus valgus (47%), high-arched palate (25%) and Madelung deformity (7%). Idiopathic scoliosis is also present in 11% of Turner syndrome. This clinical observation and radiological study explores the possibility of SHOX haploinsufficiency expression in the scoliotic spine in Turner syndrome. Method: Turner syndrome presents a mesomelic short stature, thought to result from growth plate dysmorphism, presumably from SHOX gene haploinsufficiency. Forty-five Turner syndrome subjects on the Australian Growth
Purpose of the study: Determine the prevalence and course of spinal deformations in Willi-Prader syndrome and assess the effect of treatment with growth
Objectives. Oxidative stress plays a major role in the onset and progression of involutional osteoporosis. However, classical antioxidants fail to restore osteoblast function. Interestingly, the bone anabolism of parathyroid
Introduction Delayed puberty and delayed skeletal maturation have been implicated as risk factors for the progression of idiopathic scoliosis. Genetic defects (Turner syndrome) and hypothalamic- pituitary disorders are known causes of delayed puberty. Although it is recognized that the incidence of idiopathic scoliosis is elevated in Turner syndrome, human studies regarding the incidence/severity of scoliosis in children with suprasellar, hypothalamic region and pituitary tumours/ disorders is deficient. Methods A medical records search in five Australian states for suprasellar, hypothalamic region and pituitary tumours/disorders was performed. Identified patients underwent clinical or radiological evaluation for scoliosis. Pathology varied from suprasellar-hypothalamic region tumours, pan-hypopituitarism, pituitary tumours and growth
Introduction. Initial post-operative implant instability leads to impaired osseointegration, one of the most common reasons for aseptic loosening and revision surgery. In this study, we developed a novel murine model of implant instability and demonstrated the anabolic effect of immediate and delayed intermittent Parathyroid
Intermittent parathyroid
In osteoporosis treatment, current interventions, including pharmaceutical treatments and exercise protocols, suffer from challenges of guaranteed efficacy for patients and poor patient compliance. Moreover, bone loss continues to be a complicating factor for conditions such as spinal cord injury, prescribed bed-rest, and space flight. A low-cost treatment modality could improve patient compliance. Electrical stimulation has been shown to improve bone mass in animal models of disuse, but there have been no studies of the effects of electrical stimulation on bone in the context of bone loss under
Background and Objectives: It has been extensively discussed that there is a lowering effect of Replacement Therapy on lipids and lipoproteins. Recent hypotheses relate the lipids and osteoporosis. Thus, there is a possibility that
Nachemson (1996), drawing upon the theses of Sahlstrand (1977) and Lidström (1988), articulated the view there are more girls than boys with progressive AIS for the following reason. The maturation of postural mechanisms in the nervous system is complete about the same time in boys and girls. Girls enter their skeletal adolescent growth spurt with immature postural mechanisms – so that if they have a predisposition to develop a scoliosis curve, the spine deforms. In contrast boys enter their adolescent growth spurt with mature postural mechanisms so that they are protected from developing a scoliosis curve. There is evidence that postural sway improves with age in boys and girls until about 10 years of age after which it is similar between the sexes (Hirashawa 1973, Odenrick and Sandstedt 1984) findings which need further evaluation. We term Nachemson’s concept the neuro-ossesous timing of maturation (NOTOM) hypothesis. It may have an evolutionary basis through natural selection towards sexual and skeletal development during adolescence being earlier in girls and later in boys. The NOTOM hypothesis suggests a treatment to prevent progression of late-juvenile idiopathic scoliosis, early-AIS, and some secondary scolioses based on delaying the onset of puberty used therapeutically in girls with idiopathic precocious puberty (IPP, Grumbach and Styne 1998). The proposal is to administer a gonadorelin analogue which in the pituitary down-regulates the receptors to hypothalamic gonadotropin-releasing
1. The clinical features of hyperostosis cranii are briefly reviewed. In large series of cases the syndrome has been found to occur almost entirely in females. 2. In recent studies of dystrophia myotonica, it is apparent that hyperostosis cranii is one of the variable features of the disorder. This disease occurs equally among males and females and the hyperostosis cranii also is distributed equally among males and females. 3. Hyperostosis cranii also occurs in patients with Morgagni's syndrome, with acromegaly, and as "senile hyperostosis.". 4. The etiology of hyperostosis is still a matter for speculation. More recent studies have focused attention on the endocrine system, and it seems probable, in view of the sex distribution in dystrophia myotonica, that the key to the problem may be found in this disorder. 5. In dystrophia myotonica the characteristic skull changes are hyperostosis cranii, a small pituitary fossa, excessive sinus formation and prognathism. These are acromegaloid changes. Gonadal atrophy is a common feature and endocrine study suggests that the endocrine defect is primarily a failure of the androgenic function of the adrenals and the testes. 6. In rodents and in humans ablation of the gonads leads to overactivity of gonadotrophic cells and, at times, of somatotrophic cells. Sometimes pituitary tumours develop. 7. Acromegaloid features may occur in eunuchs, and it is likely that the acromegaloid changes in dystrophia myotonica are of the same order from overactivity of growth
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 sex steroid
Nachemson [2] drawing upon the theses of Sahlstrand [3] and Lidström [4] articulated the view there are more girls than boys with progressive AIS for the following reason. The maturation of postural mechanisms in the nervous system is complete about the same time in boys and girls. Girls enter their skeletal adolescent growth spurt with immature postural mechanisms – so if they have a predisposition to develop a scoliosis curve, the spine deforms. In contrast, boys enter their adolescent growth spurt with mature postural mechanisms so they are protected from developing a scoliosis curve. We term Nachemson’s concept the neuro-osseous timing of maturation (NOTOM) hypothesis [1,5] The earlier sexual and skeletal maturation of girls may have an evolutionary basis through natural selection. Curve progression in AIS is associated with acceleration of the adolescent growth spurt [6]. Postural sway involves proprioceptive, vestibular and visual input to the central nervous system. In normal children there is a significant reduction in postural sway amplitude between six to nine years and 10–14 years [7,8]. In 1071 normal children aged 6–14 years postural sway is more stable in girls from 6–9 years and over 10 years there is no sex effect [9]; all these findings fit the Nachemson concept. But in view of a subsequent report on 64 normal children aged 3–17 years showing the change with age is limited to boys [10] the age and sex effect of postural sway in healthy children needs further evaluation. In AIS children stabilometry findings are conflicting and observed greater postural sway may be secondary to the curve. In the siblings of scoliotics Lidström et al [11] concluded that postural aberration is a factor in the aetiology of AIS. Conclusion: The NOTOM hypothesis suggests a treatment to prevent progression of late-juvenile idiopathic scoliosis, early-AIS, and some secondary scolioses. It is based on delaying the onset of the adolescent growth spurt and puberty as used therapeutically in children with idiopathic precocious puberty (IPP)[12]. The proposal is to administer a gonadorelin analogue which in the pituitary down-regulates receptors to hypothalamic gonadotropin-releasing
Background: Relatively little is known about the risk factors for carpal tunnel syndrome (CTS) in the community. Previous studies have generally assessed smaller numbers of patients in specialist clinics, or in particular occupations. Therefore, we have performed a case-control study using the West Midlands General Practice Research Database. Methods: Our cases were all patients with a recorded diagnosis of CTS; four controls per case were individually matched by age, sex and general practice. Information on constitutional,
Breast cancer survivors have known risk factors that might influence the results of total hip arthroplasty (THA) or total knee arthroplasty (TKA). This study evaluated clinical outcomes of patients with breast cancer history after primary THA and TKA. Our total joint registry identified patients with breast cancer history undergoing primary THA (n = 423) and TKA (n = 540). Patients were matched 1:1 based upon age, sex, BMI, procedure (hip or knee), and surgical year to non-breast cancer controls. Mortality, implant survival, and complications were assessed via Kaplan-Meier methods. Clinical outcomes were evaluated via Harris Hip Scores (HHSs) or Knee Society Scores (KSSs). Mean follow-up was six years (2 to 15).Aims
Methods
This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA. Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization.Aims
Methods
The presentation of musculoskeletal disease differs in men and women, and recognition of the differences between men and women's burden of disease and response to treatment is critical to optimizing care. In this presentation, I will discuss the expanding evidence in the literature that examine the role of sex and gender in musculoskeletal disease, including how its examination increases the innovations and contributions, as well as expands the knowledge about musculoskeletal disease, conditions, and injury in a broad sense. We will discuss the role that structural anatomy differences,
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
Adolescent idiopathic scoliosis (AIS), defined by an age at presentation of 11 to 18 years, has a prevalence of 0.47% and accounts for approximately 90% of all cases of idiopathic scoliosis. Despite decades of research, the exact aetiology of AIS remains unknown. It is becoming evident that it is the result of a complex interplay of genetic, internal, and environmental factors. It has been hypothesized that genetic variants act as the initial trigger that allow epigenetic factors to propagate AIS, which could also explain the wide phenotypic variation in the presentation of the disorder. A better understanding of the underlying aetiological mechanisms could help to establish the diagnosis earlier and allow a more accurate prediction of deformity progression. This, in turn, would prompt imaging and therapeutic intervention at the appropriate time, thereby achieving the best clinical outcome for this group of patients. Cite this article:
This study examined whether systemic administration of melatonin would have different effects on osseointegration in ovariectomized (OVX) rats, depending on whether this was administered during the day or night. In this study, a titanium rod was implanted in the medullary cavity of one femoral metaphysis in OVX rats, and then the rats were randomly divided into four groups: Sham group (Sham, n = 10), OVX rat group (OVX, n = 10), melatonin day treatment group (OVX + MD, n = 10), and melatonin night treatment group (OVX + MN, n = 10). The OVX + MD and OVX + MN rats were treated with 30 mg/kg/day melatonin at 9 am and 9 pm, respectively, for 12 weeks. At the end of the research, the rats were killed to obtain bilateral femora and blood samples for evaluation.Aims
Methods
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 sex
Summary. Arginine supplementation is helpful in treatment of osteoporosis. Introduction. Nitric oxide (NO) is a short-lived free radical involved in several biological processes as a bioregulator and as a second messenger. It inhibits osteoclastic bone resorption in vitro and regulates bone remodeling. Zolendronic acid has been established as a treatment for post menopausal osteoporosis. Study was done to compare the efficacy of Nitic oxide donor (L-arginine) with that of Zolendronic acid for the treatment of osteoporosis. Method. The study was not designed to compare these two drugs against a placebo, because the beneficial effects of Zolendronic acid in treatment of osteoporosis are well established. Institutional Review Board approvals were obtained. One hundred patients of osteoporosis having T score of −2.5 or more, were randomised to receive L-arginine) or Zolendronic acid. All patients received 1.0 g of calcium and 400 IU of vitamin D supplementation per day. In addition Group I patients received L-arginine (2 gm.) per day while Group II patients received zoledronic acid 5 mg i.v. over 15 min. Patient were followed at regular intervals clinically, by biochemical investigations and at one year for DEXA scan. Results. Patients in both groups improved clinically and bio-chemically over one year period. T score on DEXA scan at one year showed improvement in bone density. Average pretreatment T score was −3.65 in group I and −3.52 in group II. At one year followup average T score was −2.9 in group I and −2.6 in group II. Difference was not statistically significant. Discussion. Oral administration of L-arginine in pharmacological doses induces growth
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 sex steroid
Desmoid tumours are a rare fibroblastic proliferation of monoclonal origin, arising in deep soft-tissues. Histologically, they are characterized by locally aggressive behaviour and an inability to metastasize, and clinically by a heterogeneous and unpredictable course. Desmoid tumours can occur in any anatomical site, but commonly arise in the limbs. Despite their benign nature, they can be extremely disabling and sometimes life-threatening, causing severe pain and functional limitations. Their surgical management is complex and challenging, due to uncertainties surrounding the biological and clinical behaviour, rarity, and limited available literature. Resection has been the first-line approach for patients with a desmoid tumour but, during the last few decades, a shift towards a more conservative approach has occurred, with an initial ‘wait and see’ policy. Many medical and regional forms of treatment are also available for the management of this condition, and others have recently emerged with promising results. However, many areas of controversy remain, and further studies and global collaboration are needed to obtain prospective and randomized data, in order to develop an appropriate shared stepwise approach. Cite this article:
Healthy bone metabolism is a tightly coupled dynamic process that relies on a balance between bone resorption (catabolism) by osteoclasts and bone formation (anabolism) by osteoblasts. Traditionally, tissue-engineering approaches for non-union fracture repair employ local anabolic therapeutic delivery strategies that target mesenchymal stem cells (MSCs) and osteoblasts to induce bone formation, however, the challenge of healing non-union defects depends on the cause of defect e.g. trauma or disease, and targeting bone formation alone is often not sufficient. Our research focuses on utilising both anabolic therapeutics, including recombinant human bone morphogenic protein (rhBMP) −2 and parathyroid
Background. Acromegaly, which stems from high level of serum growth
1. Breech malposition and
This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms. We analyzed microarray data from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA), machine learning, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify common genetic factors between POMP and sarcopenia. Further validation was done via differential gene expression in a new cohort. Single-cell analysis identified high expression cell subsets, with mononuclear macrophages in osteoporosis and muscle stem cells in sarcopenia, among others. A competitive endogenous RNA network suggested regulatory elements for these genes.Aims
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The June 2024 Children’s orthopaedics Roundup360 looks at: Proximal femoral unicameral bone cysts: is ESIN the answer?; Hybrid-mesh casts in the conservative management of paediatric supracondylar humeral fractures: a randomized controlled trial; Rate and risk factors for contralateral slippage in adolescents treated for slipped capital femoral epiphysis; CRP predicts the need to escalate care after initial debridement for musculoskeletal infection; Genu valgum in paediatric patients presenting with patellofemoral instability; Nusinersen therapy changed the natural course of spinal muscular atrophy type 1: what about spine and hip?; The necessity of ulnar nerve exploration and translocation in open reduction of medial humeral epicondyle fractures in children.
This study was designed to develop a model for predicting bone mineral density (BMD) loss of the femur after total hip arthroplasty (THA) using artificial intelligence (AI), and to identify factors that influence the prediction. Additionally, we virtually examined the efficacy of administration of bisphosphonate for cases with severe BMD loss based on the predictive model. The study included 538 joints that underwent primary THA. The patients were divided into groups using unsupervised time series clustering for five-year BMD loss of Gruen zone 7 postoperatively, and a machine-learning model to predict the BMD loss was developed. Additionally, the predictor for BMD loss was extracted using SHapley Additive exPlanations (SHAP). The patient-specific efficacy of bisphosphonate, which is the most important categorical predictor for BMD loss, was examined by calculating the change in predictive probability when hypothetically switching between the inclusion and exclusion of bisphosphonate.Aims
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Background. Though less common than in females, osteoporosis and osteoporosis-related fractures are not uncommon in males. Our primary objectives were (1) to compare the rates of osteoporosis and osteopenia in adult Brazilian males versus females, 55 years old and over and presenting for bone mineral densitometry (BMD); and (2) to compare males and females as to past osteoporosis screening and management. Methods. From our clinic population, we prospectively surveyed 343 males and 493 females, all at least 55 years of age, who had presented for BMD testing, to identify baseline demographic and clinical characteristics; risk factors for osteoporosis and osteoporotic fractures; overall osteoporosis and 10-year fracture risk; and evidence of prior assessment for and/or management/prevention of osteoporosis. Final osteoporosis risk was determined using the results of BMD testing and the FRAX® tool. Gender comparisons were performed using Pearson 2 analysis for nominal and ordinal variables, Student's t-tests for normally-distributed continuous variables, and Mann-Whitney U tests for non-normally-distributed continuous variables, with all tests 2-tailed and p=0.05 set as the threshold for statistical significance. Binary logistic regression was performed to identify predictors of prior
This study aimed, through bioinformatics analysis, to identify the potential diagnostic markers of osteoarthritis, and analyze the role of immune infiltration in synovial tissue. The gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by R software. Functional enrichment analyses were performed and protein-protein interaction networks (PPI) were constructed. Then the hub genes were screened. Biomarkers with high value for the diagnosis of early osteoarthritis (OA) were validated by GEO datasets. Finally, the CIBERSORT algorithm was used to evaluate the immune infiltration between early-stage OA and end-stage OA, and the correlation between the diagnostic marker and infiltrating immune cells was analyzed.Aims
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Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and subchondral bone sclerosis. Pathological changes in cartilage and subchondral bone are the main processes in OA. In recent decades, many studies have demonstrated that activin-like kinase 3 (ALK3), a bone morphogenetic protein receptor, is essential for cartilage formation, osteogenesis, and postnatal skeletal development. Although the role of bone morphogenetic protein (BMP) signalling in articular cartilage and bone has been extensively studied, many new discoveries have been made in recent years around ALK3 targets in articular cartilage, subchondral bone, and the interaction between the two, broadening the original knowledge of the relationship between ALK3 and OA. In this review, we focus on the roles of ALK3 in OA, including cartilage and subchondral bone and related cells. It may be helpful to seek more efficient drugs or treatments for OA based on ALK3 signalling in future.
Several artificial bone grafts have been developed but fail to achieve anticipated osteogenesis due to their insufficient neovascularization capacity and periosteum support. This study aimed to develop a vascularized bone-periosteum construct (VBPC) to provide better angiogenesis and osteogenesis for bone regeneration. A total of 24 male New Zealand white rabbits were divided into four groups according to the experimental materials. Allogenic adipose-derived mesenchymal stem cells (AMSCs) were cultured and seeded evenly in the collagen/chitosan sheet to form cell sheet as periosteum. Simultaneously, allogenic AMSCs were seeded onto alginate beads and were cultured to differentiate to endothelial-like cells to form vascularized bone construct (VBC). The cell sheet was wrapped onto VBC to create a vascularized bone-periosteum construct (VBPC). Four different experimental materials – acellular construct, VBC, non-vascularized bone-periosteum construct, and VBPC – were then implanted in bilateral L4-L5 intertransverse space. At 12 weeks post-surgery, the bone-forming capacities were determined by CT, biomechanical testing, histology, and immunohistochemistry staining analyses.Aims
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Introduction: Aggressive fibromatosis is a benign but locally aggressive process. It arises from musculo-aponeurotic tissues, and invades locally without respect for tissue planes, surrounding vessels and nerves, which makes treatment of local recurrences difficult. Aims: Our aim is to review our experience in the management of aggressive fibromatosis, focussing on the cases of multiple recurrences, as well as to evaluate the need for disabling surgery. Material and methods: We present the series of 33 patients (15 male and 18 female) diagnosed of aggressive fibromatosis treated between 1993 and 2003; the follow-up period was no less than two years. The locations were shoulder girdle (8), lower extremity (8), upper extremity (6), gluteus (5), paravertebral (4) and thorax (2). There were 6 cases with 3 or more episodes of local recurrences; in these cases, depending on location and size, and considering high surgical morbidity, associations of radiotherapy, chemotherapy and
From January 2003 a long term follow-up project started for adult patients treated in our Centre for cancer in pediatric age, to evaluate late effects of therapy. For all patients a personalized follow-up was scheduled (time, function-tests, etc). We analyzed 24 cases of bone tumors: 14 osteosarcoma (OS) and 10 Ewing’s sarcoma (ES). Median age at diagnosis was 13 years (range 11–18) for OS patients, 11.6 years (range 6–18) for ES; 50% males in both groups. All patients were treated according current CNR/ISG-protocols: all OS cases underwent surgery; in 5/10 ES patients local treatment was surgery, in 5/10 radiotherapy; 7/24 received hematopoietic stem cells transplantation (HSCT). Median age at evaluation is respectively 26.5 years (range 18.7–34) and 23.5 (range 21.6–32); median follow-up is 13 years (range 6–22) and 13.7 (range 6.7–22.3). Cardiovascular function is normal in all OS cases; 3/10 ES patients developed asymptomatic ejection fraction reduction, currently not treated. One OS patient underwent bilateral thoracotomy and HSCT for multiple metastases at diagnosis and had a mild lung function alteration. One OS patient developed mild chronic kidney disease, one ES nephrolithiasis. Liver function is normal in all cases. Height velocity and final height are normal in 10/14 OS and 9/10 ES patients; in remaining 5/24 no growth
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 sex
Low-energy distal radius fractures (DRFs) are the most common upper arm fractures correlated with bone fragility. Vitamin D deficiency is an important risk factor associated with DRFs. However, the relationship between DRF severity and vitamin D deficiency is not elucidated. Therefore, this study aimed to identify the correlation between DRF severity and serum 25-hydroxyvitamin-D level, which is an indicator of vitamin D deficiency. This multicentre retrospective observational study enrolled 122 female patients aged over 45 years with DRFs with extension deformity. DRF severity was assessed by three independent examiners using 3D CT. Moreover, it was categorized based on the AO classification, and the degree of articular and volar cortex comminution was evaluated. Articular comminution was defined as an articular fragment involving three or more fragments, and volar cortex comminution as a fracture in the volar cortex of the distal fragment. Serum 25-hydroxyvitamin-D level, bone metabolic markers, and bone mineral density (BMD) at the lumbar spine, hip, and wrist were evaluated six months after injury. According to DRF severity, serum 25-hydroxyvitamin-D level, parameters correlated with bone metabolism, and BMD was compared.Aims
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Slipped capital femoral epiphysis may be associated with hypothyroidism and other endocrinopathies. Routine screening for such abnormalities is unlikely to be cost-effective since the overall incidence of these disorders, in association with slipped capital femoral epiphysis, is low. The identification of a presenting characteristic which would predict the chance of an associated endocrinopathy would allow only selected children to be screened. Our aim was to determine if certain characteristics were useful as a screen for patients with an underlying endocrinopathy who presented with slipped capital femoral epiphysis. Between January 1988 and December 1996 we recorded gender, age, height, unilateral or bilateral involvement and an associated diagnosis of endocrinopathy for all patients who were treated for slipped capital femoral epiphysis. Of 166 such patients 13 (7.8%) had an endocrinopathy. Height was the only useful screening characteristic, although bilateral involvement was more likely in those with an endocrinopathy. Most (90.9%) of this latter group were below the tenth percentile for height compared with only 5.4% in those who did not have an endocrinopathy (p <
0.005). The sensitivity and negative predictive value of detecting an underlying endocrinopathy in a patient presenting with a slipped capital femoral epiphysis and short stature (tenth percentile or less) were 90.2% and 98.6%, respectively. Patients who are on or below the tenth percentile for height at the time of presentation should be screened for a possible endocrine abnormality using measurement of thyroid-stimulating
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Introduction Men will account for 30% of hip fractures in the next decade and men have a higher mortality after hip fracture than women. Men with osteoporosis often have secondary aetiological conditions. Our aim was to prospectively define secondary causes of osteoporosis in a group of men presenting with hip fracture. Methods Forty-two men presenting with hip fracture were prospectively recruited and compared with 19 male controls that had primary hip arthroplasty for osteoarthritis. Bone mineral density (BMD) was measured by DEXA of unaffected hip and spine. Secondary causes of osteoporosis were identified from history and by biochemical and
Background: We have recently observed that many of our sarcoma patients presented also with thyroid disorders. Literature data are almost unavailable on this topic. Materials and Methods: Retrospective analysis of files of patients with sarcoma and clinically overt thyroid disorders. Results: Out of 375 patients with soft tissue sarcomas (STS) and 235 with bone sarcoma (BS) including small blue round cell tumors (SBRC), 28 patients (4.6%) had an associated significant thyroid disorder. The types of sarcoma were mainly liposarcoma followed by malignant fibrous histiocytoma, leiomyosarcoma and bone sarcoma. The primary sites were mainly limb and trunk. The interval between the diagnosis of the thyroid disorder and the sarcoma varied between {−14} years (thyroid first) and {+16.5} years (thyroid later) with a median of {−0.2} years. Thyroid disorders included goiter, thyroiditis and carcinoma. Conclusions: There are basic-science and clinical evidences to a possible common pathway that leads to the association between overt thyroid disorders and sarcomas of bone or soft tissues. Oncogene erbA activity is related to thyroid receptors to T3 and to development of sarcoma. Cross talk of the sarcoma oncogene and the erbA might contribute to the development of sarcoma. The thyroid
Avascular femoral head necrosis in the context of gymnastics is a rare but serious complication, appearing similar to Perthes’ disease but occurring later during adolescence. Based on 3D CT animations, we propose repetitive impact between the main supplying vessels on the posterolateral femoral neck and the posterior acetabular wall in hyperextension and external rotation as a possible cause of direct vascular damage, and subsequent femoral head necrosis in three adolescent female gymnasts we are reporting on. Outcome of hip-preserving head reduction osteotomy combined with periacetabular osteotomy was good in one and moderate in the other up to three years after surgery; based on the pronounced hip destruction, the third received initially a total hip arthroplasty.Aims
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