Background. Reduced bone mineral density is recognised as a risk factor for hip fractures and fragility fractures in general. Vitamin D is important in maintaining healthy bone mineral levels and can therefore affect risk of hip fracture. We investigated the correlation between vitamin D levels and bone mineral density, as well as fracture type, in neck of femur fractures and also assessed the relationship of vitamin D and social deprivation. Method. We included all patients admitted to our department, with a neck of femur fracture over one year (October 2013 to October 2014). We analysed vitamin D levels for all patients during admission and compared these to bone mineral density scores, based on DEXA scan results; hip fracture type & comminution, based on admission radiographs; and levels of social deprivation, based on the patient's address. Results. In total 360 patients were admitted over the study period, with a neck of femur fracture, of which 298 had vitamin D assessed and 76 had DEXA scans. Of these cohorts, 71% were found to be vitamin D deficient and 7% had osteoporosis. No significant correlation was found between vitamin D scores and bone density, or with level of vitamin D deficiency and fracture type or comminution. A significant correlation was however identified, between low vitamin D levels and decreasing levels of social deprivation (R=0.11, p=0.04). Conclusion. No relationship was identified between vitamin D levels and hip fracture type, suggesting that vitamin D cannot be used to predict patients at risk of more comminuted fractures. Although no relationship was also identified for bone mineral density and vitamin D, this may be because the sample size of DEXA scans was relatively small. Interestingly the relationship between vitamin D and social deprivation was the reverse of what was expected and suggests that affluent individuals may be at greater risk of low vitamin D

Introduction. Osteonecrosis (ON) is a bone disease characterized by death of osteocytes and loss of associated hematopoietic elements usually occurring as focal lesions in weight bearing joints such as the hip. The pathophysiology of the disease is still unclear and osteonecrosis can be viewed as both a vascular and a bone disease. The number of mesenchymal stem cells (precursors of osteoblastic cells) has been shown to be depressed in patients with osteonecrosis. Also, the proliferation rate of the osteoblastic cells in the proximal femur may be depressed. These findings raised the possibility that osteonecrosis might be a disease of bone cells or bone metabolism. On this basis, we started this study to evaluate bone metabolism status among patients with osteonecrosis. Methods. In a prospective study, we evaluated 110 patients with osteonecrosis at the time of the diagnosis for vitamin D, parathormone, osteocalcin, and c-telopeptide measurements. DEXA was performed in all patients as well. We excluded from this study patients with sickle cell anemia (n=5), Gaucher disease (n=1), on hemodialysis (n=14), and who were already treated for osteoporosis (n=8). Results. There were 20 women and 90 men (mean age 47 ± 11 years). Twenty percent of the patients had unilateral osteonecrosis of the femoral head, 61 % of the patients had bilateral osteonecrosis, and 20 % had multifocal disease. Risk factors were corticosteroid and alcohol abuse. Vitamin D deficiency (<15 ng/ml) was found in 60 % of the patients and vitamin D insufficiency (15 to 30 ng/ml) was found in 15% of the patients. Secondary hyperparathyroidism (>55pg/ml) was present in only 7 patients. Patients with alcohol abuse had significantly lower vitamin D concentration than the other patients: 11.9 ± 8.7 vs. 20.8 ± 9.2 ng/ml (p=0.005). Among 90 samples, 45 showed an osteocalcin level below the normal range (<14 ng/ml). Most of the patients had a normal level of C-telopeptide. Patients with corticosteroid-associated osteonecrosis had significantly lower osteocalcin levels than others osteonecrotic patients: 14.1 ± 5.3 vs 22.7 ± 13.0 ng/ml (p=0.015). Bone mineral density measurements were obtained for 60 patients and showed a T-score < -1.5 at the lumbar site and < 1.8 at the hip. Conclusion. Patients with osteonecrosis have a high prevalence of vitamin D deficiency without secondary hyperparathyroidism. They also display a low bone turnover confirmed by low osteocalcin levels and normal levels of C-telopeptide. Osteonecrosis is also associated with severe osteopenia

We investigated the effect of vitamin D receptor gene (VDRG) polymorphism on the responsiveness to 1,25(OH). 2. D. 3. in human osteoblast-like cells. The cells were obtained from the femoral heads of 18 women with osteoarthritis of the hip. Three different restriction enzymes, BsmI, ApaI, and TaqI, were used to analyse the polymorphism. The genotypes of the 18 patients were bbAaTT (8), bbaaTT (6), BbAaTt (3), and BbAATt (1). Our findings showed that there were no differences according to the VDR genotype, but there was a statistically significant difference in the production of osteocalcin between BbAaTt and bbAaTT, and between BbAaTt and bbaaTT. Northern blot analysis of osteocalcin and VDR mRNA showed no significant differences among the three VDR genotypes. These findings suggest that VDR gene polymorphism affects the individual responsiveness of 1,25(OH). 2. D. 3.

To report the case of an asymptomatic simultaneous bilateral neck of femur fracture following vitamin D deficiency which was missed, misdiagnosed and treated for coexisting severe bilateral osteoarthritis knee. A male aged 62 years presented with severe osteoarthritis of both knee joints confining him to bed about eight weeks prior to presentation. The patient did not have any complaints pertaining to his hip joints/axial skeleton. Examination of the hip joints revealed only crepitus with absence of straight leg rising. Radiological survey showed bilateral displaced fracture neck of femur. He had elevated serum alkaline phosphatase; 119IU/L(N:39–117IU/L), decreased Serum 25 (OH) Vit D level;6.03ng/ml(N:7.6–75ng/ml), decreased spot urinary calcium;78mg/day(N:100–300mg/day) with normal serum calcium, phosphorus and highly raised parathormone levels;142.51pg/ml(N:12–72pg/ml). Tc-99 Bone scan showed increased radiotracer uptake in both the hip joints and knee joints. Bone Mineral Density was in favour of osteoporosis. Biopsy fromthe heads of both femurs also revealed osteoporosis. Bilateral staged total hip arthroplasty was done and he was put on Vitamin D replacement therapy. Patient was on regular monthly follow-up for intial one year and three monthly follow-up thereafter. At present with three year follow-up patient is community ambulant with a walking frame. Despite medical advice patient had denied total knee arthroplasty for osteoarthritis of his knee joints. Asymptomatic simultaneous bilateral neck of femur fracture is a rare injury and poses a diagnostic challenge to the treating orthopaedic surgeon with its bizarre clinical picture. Similar presentation of metabolic bone disease can be easily missed without a proper screening, keeping in mind a high index of suspicion for the above disorders. Besides proper clinical examination of both hip and knee joint should be performed in patients presenting with bilateral knee pain. A good functional outcome may be achieved with prompt surgical intervention and medical treatment

To determine the clinical efficacy of vitamin-D supplementation on pain intensity and functional disability in patients with chronic lower back pain.

This prospective cohort study was conducted from 20th March 2017 to 19th March 2019. The inclusion criteria were patients of CLBP aged between 15 to 55 years. Exclusion criteria included all the patients with Disc prolapse, Spinal stenosis, Any signs of neurological involvement, Metabolic bone disease (Hypo- or Hyperparathyroidism) and Chronic kidney disease/Chronic liver disease. Patients were supplemented with 50,000 IU of oral vitamin-D3 every week for 8 weeks (induction phase) and 50,000 IU of oral vitamin-D3 once monthly for 6 months (maintenance phase). Efficacy parameters included pain intensity and functional disability measured by VAS and modified Oswestry disability questionnaire (MODQ) scores at baseline, 2, 3 and 6 months post-supplementation. Vitamin-D3 levels were measured at baseline,2,3 and 6 months.

A total of 600 patients were included in the study. The mean age of patients was 44.2 ± 11.92 years. There were 337 (56.2%) male patients while 263 (43.8%) female patients. Baseline mean vitamin-D levels were 13.32 ± 6.10 ng/mL and increased to 37.18 ± 11.72 post supplementation (P < 0.0001). There was a significant decrease in the pain score after 2nd, 3rd& 6th months (61.7 ± 4.8, 45.2 ± 4.6 & 36.9 ± 7.9, respectively) than 81.2 ± 2.4 before supplementation (P < 0.001). The modified Oswestry disability score also showed significant improvement after 2nd, 3rd & 6th months (35.5, 30.2 & 25.8, respectively) as compared to baseline 46.4 (P < 0.001). About 418 (69.7%) patients attained normal levels after 6 months.

Vitamin-D supplementation in chronic lower back pain patients may lead to improvement in pain intensity and functional ability.

Fractures and related complications are a common challenge in the field of skeletal tissue engineering. Vitamin D and calcium are the only broadly available medications for fracture healing, while zinc has been recognized as a nutritional supplement for healthy bones. Here, we aimed to use polaprezinc, an anti-ulcer drug and a chelate form of zinc and L-carnosine, as a supplement for fracture healing. Polaprezinc induced upregulation of osteogenesis-related genes and enhanced the osteogenic potential of human bone marrow-derived mesenchymal stem cells and osteoclast differentiation potential of mouse bone marrow-derived monocytes. In mouse experimental models with bone fractures, oral administration of polaprezinc accelerated fracture healing and maintained a high number of both osteoblasts and osteoclasts in the fracture areas. Collectively, polaprezinc promotes the fracture healing process efficiently by enhancing the activity of both osteoblasts and osteoclasts. Therefore, we suggest that drug repositioning of polaprezinc would be helpful for patients with fractures

Extensive bone defects, caused by severe trauma or resection of large bone tumors, are difficult to treat. Regenerative medicine, including stem cell transplantation, may provide a novel solution for these intractable problems and improve the quality of life in affected patients. Adipose-derived stromal/stem cells (ASCs) have been extensively studied as cell sources for regenerative medicine due to their excellent proliferative capacity and the ability to obtain a large number of cells with minimal donor morbidity. However, the osteogenic potential of ASCs is lower than that of bone marrow-derived stromal/stem cells. To address this disadvantage, our group has employed various methods to enhance osteogenic differentiation of ASCs, including factors such as bone morphogenetic protein or Vitamin D, coculture with bone marrow stem cells, VEGF transfection, and gene transfer of Runx-2 and osterix. Recently, we mined a marker that can predict the osteogenic potential of ASC clones and also investigated the usefulness of the molecule as the enhancer of osteogenic differentiation of ASCs as well as its mechanism of action. Through RNA-seq gene analysis, we discovered that GSTT1 was the most distinguished gene marker between highly osteogenic and poorly osteogenic ASC clones. Knockdown of GSTT1 in high osteogenic ASCs by siGSTT1 treatment reduced mineralized matrix formation while GSTT1 overexpression by GSTT1 transfection or GSTT1 recombinant protein treatment enhanced osteogenic differentiation of low osteogenic ASCs. Metabolomic analysis confirmed significant changes of metabolites related to bone differentiation in ASCs transfected with GSTT1. A high total antioxidant capacity, low levels of cellular reactive oxygen species and increased GSH/GSSG ratios were also detected in GSTT1- transfected ASCs. GSTT1 can be a useful marker to screen the highly osteogenic ASC clones and also a therapeutic factor to enhance the osteogenic differentiation of poorly osteogenic ASC clones

Abstract. Objectives. The aim of this study was to investigate whether mechanical loading induced by physical activity can reduce risk of sarcopenia in middle-aged adults. Methods. This was a longitudinal study based on a subset of UK Biobank data consisting of 1,918 participants (902 men and 1,016 women, mean age 56 years) who had no sarcopenia at baseline (assessed between 2006 and 2010). The participants were assessed again after 6 years at follow-up, and were categorized into no sarcopenia, probable sarcopenia, or sarcopenia according to the definition and algorithm developed in 2018 by European Working Group on Sarcopenia in Older People (EWGSOP). Physical activity was assessed at a time between baseline and follow-up using 7-day acceleration data obtained from wrist worn accelerometers. Raw acceleration data were then analysed to study the mechanical loading of physical activity at different intensities (i.e. very light, light, moderate-to-vigorous). Multinominal logistic regression was employed to examine the association between the incidence of sarcopenia and physical activity loading, between baseline and follow up, controlled for other factors at baseline including age, gender, BMI, smoking status, intake of alcohol, vitamin D and calcium, history of rheumatoid arthritis, osteoarthritis, secondary osteoporosis, and type 2 diabetes. Results. Among the 1918 participants with no sarcopenia at baseline, 230 (69 men and 161 women) developed probable sarcopenia and 37 (14 men and 23 women) developed sarcopenia at follow-up. Physical activity loading at moderate-to-vigorous intensity was higher in men (p<0.05), while women had higher physical activity loading at very light intensity (p<0.05). No significant difference was found in physical activity loading at light intensity between men and women (p>0.05). Logistic regression models showed that increase in physical activity loading at moderate-to-vigorous intensity significantly reduced the risk of sarcopenia (odds ratio = 0.368, p<0.05), but not probable sarcopenia (odds ratio = 0.974, p>0.05), while loading at light or very light activity intensity were not associated with the risk of sarcopenia or probable sarcopenia (p>0.05). Conclusion. Loading of physical activity at moderate-to-vigorous intensity could reduce risk of sarcopenia in middle-aged adults. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Osteochondrosis (OC) is a common joint disease that affects developing cartilage and subchondral bone in humans, and in multiple animal species including horses. It is an idiopathic localized joint disorder characterized by focal chondronecrosis and retention of growing cartilage that can lead to the formation of fissures, subchondral bone cysts or intra-articular fragments. OC is considered a complex multifactorial disease with chondrocyte biogenesis impairment mainly due to biochemical and genetic factors. Likewise, the molecular events involved in the OC are not fully understood. Moreover, the OC pathogenesis seems to be shared across species. In particular, equine OC and human juvenile OC share some symptoms, predilection sites and clinical presentation. In this study, by using the label-free mass spectrometry approach, proteome of chondrocytes isolated from equine OC fragments has been analysed in order to clarify some aspects of cell metabolism impairment occurring in OC. Equine chondrocytes isolated from 7 healthy articular cartilages (CTRL) and from 7 osteochondritic fragments (OC) (both obtained from metacarpo/metatarsophalangeal joints) were analysed. Proteins were extracted using urea and ammonium bicarbonate buffer, reduced, alkylated and digested with Trypsin/Lys-C Mix. Peptides were analysed using Q Exactive UHMR Hybrid Quadrupole-Orbitrap Mass Spectrometer (Thermo Scientific). All mass spectra of label-free samples analysed was set up to search against SwissProt human database (Homo sapiens) and SwissProt horse database (Equus caballus). One-way ANOVA was used for hypothesis testing. Proteins with a ≥1.5 fold change and with a FDR adjusted p value of ≤0.05 were defined as differentially expressed. Statistical analysis evidenced 41 proteins up-regulated in OC while 18 were down-regulated with respect to the CTRL. Functional analysis showed that up-regulated proteins in OC were related to extracellular matrix degradation, lysosome, apoptotic execution phase, unfolded protein response, hyaluronan and keratan sulfate degradation, oxidative stress response and negative regulation of BMP signalling pathway. The down-regulated proteins were associated with endochondral ossification, vitamin D in inflammatory disease, Wnt signalling pathway and ECM proteoglycans. Validation assays confirmed these findings. These findings may contribute to clarify the events determining the onset and progression of both equine and human OC. Imaging MS analysis of OC and healthy cartilage to analyse lipid and metabolomic changes occurring in OC cartilage is in progress

Mononuclear osteoclast precursors are present in the wear-particle-associated macrophage infiltrate found in the membrane surrounding loose implants. These cells are capable of differentiating into osteoclastic bone-resorbing cells when co-cultured with the rat osteoblast-like cell line, UMR 106, in the presence of 1,25(OH). 2. vitamin D. 3. In order to develop an in vitro model of osteoclast differentiation which more closely parallels the cellular microenvironment at the bone-implant interface in situ, we determined whether osteoblast-like human bone-derived cells were capable of supporting the differentiation of osteoclasts from arthroplasty-derived cells and analysed the humoral conditions required for this to occur. Long-term co-culture of arthroplasty-derived cells and human trabecular-bone-derived cells (HBDCs) resulted in the formation of numerous tartrate-resistant-acid-phosphatase (TRAP) and vitronectin-receptor (VNR)-positive multinucleated cells capable of extensive resorption of lacunar bone. The addition of 1,25(OH). 2. vitamin D. 3. was not required for the formation of osteoclasts and bone resorption. During the formation there was release of substantial levels of M-CSF and PGE. 2. Exogenous PGE. 2. (10. −8. to 10. −6. M) was found to stimulate strongly the resorption of osteoclastic bone. Our study has shown that HBDCs are capable of supporting the formation of osteoclasts from mononuclear phagocyte precursors present in the periprosthetic tissues surrounding a loose implant. The release of M-CSF and PGE. 2. by activated cells at the bone-implant interface may be important for the formation of osteoclasts at sites of pathological bone resorption associated with aseptic loosening

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 hormone and insulin like growth factor-1 responses and stimulates nitric oxide synthesis. Growth hormone and insulin like growth factor-1 are important mediator of bone turnover and osteoblastic bone formation. While nitric oxide is potent inhibitor of osteoclastic bone resorption because of this dual effect on physiological regulator of bone remodeling. L-arginine could potentially increase bone formation over bone resorption and consequently increase bone mass. Oral supplementation of L-arginine may be novel strategy in prevention and treatment of osteoporosis

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.

Cite this article: X. Peng, X. Wu, J. Zhang, G. Zhang, G. Li, X. Pan. The role of CKIP-1 in osteoporosis development and treatment. Bone Joint Res 2018;7:173–178. DOI: 10.1302/2046-3758.72.BJR-2017-0172.R1.

Objectives

In order to screen the altered gene expression profile in peripheral blood mononuclear cells of patients with osteoporosis, we performed an integrated analysis of the online microarray studies of osteoporosis.

Objectives

Degenerative disc disease (DDD) and osteoarthritis (OA) are relatively frequent causes of disability amongst the elderly; they constitute serious socioeconomic costs and significantly impair quality of life. Previous studies to date have found that aggrecan variable number of tandem repeats (VNTR) contributes both to DDD and OA. However, current data are not consistent across studies. The purpose of this study was to evaluate systematically the relationship between aggrecan VNTR, and DDD and/or OA.

Objectives

To assess the sensitivity and specificity of self-reported osteoporosis compared with dual energy X-ray absorptiometry (DXA) defined osteoporosis, and to describe medication use among participants with the condition.

Objectives

To determine the pattern of mutations of the WISP3 gene in clinically identified progressive pseudorheumatoid dysplasia (PPD) in an Indian population.

Objectives

This study aims to assess the correlation of CT-based structural rigidity analysis with mechanically determined axial rigidity in normal and metabolically diseased rat bone.

Conventional non-steroidal anti-inflammatory drugs (NSAIDs) and newer specific cyclo-oxygenase-2 (cox-2) inhibitors are commonly used in musculoskeletal trauma and orthopaedic surgery to reduce the inflammatory response and pain. These drugs have been reported to impair bone metabolism. In reconstruction of the anterior cruciate ligament the hamstring tendons are mainly used as the graft of choice, and a prerequisite for good results is healing of the tendons in the bone tunnel. Many of these patients are routinely given NSAIDs or cox-2 inhibitors, although no studies have elucidated the effects of these drugs on tendon healing in the bone tunnel.

In our study 60 female Wistar rats were randomly allocated into three groups of 20. One received parecoxib, one indometacin and one acted as a control. In all the rats the tendo-Achillis was released proximally from the calf muscles. It was then pulled through a drill hole in the distal tibia and sutured anteriorly. The rats were given parecoxib, indometacin or saline intraperitoneally twice daily for seven days. After 14 days the tendon/bone-tunnel interface was subjected to mechanical testing.

Significantly lower maximum pull-out strength (p < 0.001), energy absorption (p < 0.001) and stiffness (p = 0.035) were found in rats given parecoxib and indometacin compared with the control group, most pronounced with parecoxib.

The haematoma occurring at the site of a fracture is known to play an important role in bone healing. We have recently shown the presence of progenitor cells in human fracture haematoma and demonstrated that they have the capacity for multilineage mesenchymal differentiation. There have been many studies which have shown that low-intensity pulsed ultrasound (LIPUS) stimulates the differentiation of a variety of cells, but none has investigated the effects of LIPUS on cells derived from human fracture tissue including human fracture haematoma-derived progenitor cells (HCs). In this in vitro study, we investigated the effects of LIPUS on the osteogenic activity of HCs. Alkaline phosphatase activity, osteocalcin secretion, the expression of osteoblast-related genes and the mineralisation of HCs were shown to be significantly higher when LIPUS had been applied but without a change in the proliferation of the HCs. These findings provide evidence in favour of the use of LIPUS in the treatment of fractures.