Aims

This study examined the relationship between obesity (OB) and osteoporosis (OP), aiming to identify shared genetic markers and molecular mechanisms to facilitate the development of therapies that target both conditions simultaneously.

Aims

This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation.

Dual plate constructs have become an increasingly common fixation technique for midshaft clavicle fractures and typically involve the use of mini-fragment plates. The goal of this technique is to reduce plate prominence and implant irritation, as these are common reasons for revision surgery. However, limited biomechanical data exist for these lower-profile constructs. The study aim was to compare dual mini-fragment orthogonal plating to traditional small-fragment clavicle plates for biomechanical non-inferiority and to determine if an optimal plate configuration could be identified, using a cadaveric model. Twenty-four cadaveric clavicles were randomized to one of six groups (n=4 per group), stratified by CT-based bone mineral content (BMC). The six different plating configurations compared were: pre-contoured superior or anterior fixation using a single 3.5-mm LC-DC plate, and four different dual-plating constructs utilizing 2.4-mm and 2.7-mm reconstruction or LC-DC plates. The clavicles were plated and then osteotomized to create an inferior butterfly fracture, which was then fixed with a single interfragmentary screw (OTA 15.2B). Axial, torsional, and bending (anterior and superior surface loading) stiffness were determined for each construct through non-destructive cyclic testing, using an MTS 858 Bionix materials testing system. This was followed by a load-to-failure test in three-point superior-surface bending. Kruskal-Wallace H and Mann-Whitney U were used to test for statistical significance. There were no significant differences in BMC (median 7.9 g, range 4.2-13.8 g) for the six groups (p=1.000). For axial stiffness, the two dual-plate constructs with a superior 2.4-mm and anterior 2.7-mm plate (either reconstruction or LC-DC) were significantly stiffer than the other four constructs (p=0.021). For both superior and anterior bending, the superior 2.4-mm and anterior 2.7-mm plate constructs were significantly stiffer when compared to the 3.5-mm superior plate (p=0.043). In addition, a 3.5-mm plate placed anterior was a stiffer construct than a superior 3.5-mm plate (p=0.043). No significant differences were found in torsional stiffness or load-to-failure between the different constructs. Dual plating using mini-fragment plates is biomechanically superior for fixation of midshaft clavicle fractures when compared to a single superior 3.5-mm plate and has similar biomechanical properties to a 3.5-mm plate placed anteriorly. With the exception of axial stiffness, no significant differences were found when different dual plating constructs were compared to each other. However, placing a 2.4-mm plate superiorly in combination with a 2.7-mm plate anteriorly might be the optimal construct, given the biomechanical superiority over the 3.5-mm plate placed superior

Aims

The preventive effects of bisphosphonates on articular cartilage in non-arthritic joints are unclear. This study aimed to investigate the effects of oral bisphosphonates on the rate of joint space narrowing in the non-arthritic hip.

Aims

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.

Aims. The association of auraptene (AUR), a 7-geranyloxycoumarin, on osteoporosis and its potential pathway was predicted by network pharmacology and confirmed in experimental osteoporotic mice. Methods. The network of AUR was constructed and a potential pathway predicted by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) terms enrichment. Female ovariectomized (OVX) Institute of Cancer Research mice were intraperitoneally injected with 0.01, 0.1, and 1 mM AUR for four weeks. The bone mineral density (BMD) level was measured by dual-energy X-ray absorptiometry. The bone microstructure was determined by histomorphological changes in the femora. In addition, biochemical analysis of the serum and assessment of the messenger RNA (mRNA) levels of osteoclastic markers were performed. Results. In total, 65.93% of the genes of the AUR network matched with osteoporosis-related genes. Osteoclast differentiation was predicted to be a potential pathway of AUR in osteoporosis. Based on the network pharmacology, the BMD and bone mineral content levels were significantly (p < 0.05) increased in the whole body, femur, tibia, and lumbar spine by AUR. AUR normalized the bone microstructure and the serum alkaline phosphatase (ALP), bone-specific alkaline phosphatase (bALP), osteocalcin, and calcium in comparison with the OVX group. In addition, AUR treatment reduced TRAP-positive osteoclasts and receptor activator of nuclear factor kappa-B ligand (RANKL). +. nuclear factor of activated T cells 1 (NFATc1). +. expression in the femoral body. Moreover, the expressions of initiators for osteoclastic resorption and bone matrix degradation were significantly (p < 0.05) regulated by AUR in the lumbar spine of the osteoporotic mice. Conclusion. AUR ameliorated bone loss by downregulating the RANKL/NFATc1 pathway, resulting in improvement of osteoporosis. In conclusion, AUR might be an ameliorative cure that alleviates bone loss in osteoporosis via inhibition of osteoclastic activity. Cite this article: Bone Joint Res 2022;11(5):304–316

Aims

Assessment of bone mineral density (BMD) with dual-energy X-ray absorptiometry (DXA) is a well-established clinical technique, but it is not available in the acute trauma setting. Thus, it cannot provide a preoperative estimation of BMD to help guide the technique of fracture fixation. Alternative methods that have been suggested for assessing BMD include: 1) cortical measures, such as cortical ratios and combined cortical scores; and 2) aluminium grading systems from preoperative digital radiographs. However, limited research has been performed in this area to validate the different methods. The aim of this study was to investigate the evaluation of BMD from digital radiographs by comparing various methods against DXA scanning.

Segmental bone transport (SBT) using an external fixator is currently a standard treatment for large-diameter bone defects at the donor site with low morbidity. However, long-term application of the device is needed for bone healing. In addition, patients who received SBT treatment sometimes fail to show bone repair and union at the docking site, and require secondary surgery. The objective of this study was to investigate whether a single injection of recombinant human bone morphogenetic protein 2 (rhBMP-2)-loaded artificial collagen-like peptide gel (rhBMP-2/ACG) accelerates consolidation and bone union at the docking site in a mouse SBT model. Six-month-old C57BL/6J mice were reconstructed by SBT with external fixator that has transport unit, and a 2.0-mm bone defect was created in the right femur. Mice were divided randomly into four treatment groups with eight mice in each group, Group CONT (immobile control), Group 0.2mm/d, Group 1.0mm/d, and Group BMP-2. Mice in Group 0.2mm/d and 1.0mm/d, bone segment was moved 0.2 mm per day for 10 days and 1.0 mm per day for 2 days, respectively. Mice in Group BMP-2 received an injection of 2.0 μg of rhBMP-2 dissolved in ACG into the bone defect site immediately after the defect-creating surgery and the bone segment was moved 1.0 mm/day for 2 days. All animals were sacrificed at eight weeks after surgery. Consolidation at bone defect site and bone union at docking site were evaluated radiologically and histologically. At the bone defect site, seven of eight mice in Group 0.2mm/d and two of eight mice in Group 1.0mm/d showed bone union. In contrast, all mice in Group CONT showed non-union at the bone defect site. At the docking site, four of eight mice in Group 0.2 mm/d and three of eight mice in Group 1.0 mm/d showed non-union. Meanwhile, all mice in Group BMP-2 showed bone union at the bone defect and docking sites. Bone volume and bone mineral content were significantly higher in Group 0.2mm/d and Group BMP-2 than in Group CONT. HE staining of tissue from Group 0.2mm/d and Group BMP-2 showed large amounts of longitudinal trabecular bone and regenerative new bone at eight weeks after surgery at the bone defect site. Meanwhile, in Group CONT and Group 1.0mm/d, maturation of regenerative bone at the bone defect site was poor. Differences between groups were analyzed using one-way ANOVA and a subsequent Bonferroni's post-hoc comparisons test. P < 0.05 was considered significant. rhBMP-2/ACG combined with SBT may be effective for enhancing bone healing in large bone defects without the need for secondary procedures

Bone is a dynamic tissue with a quarter of the trabecular and a fifth of the cortical bone being replaced continuously each year in a complex process that continues throughout an individual’s lifetime. Bone has an important role in homeostasis of minerals with non-stoichiometric hydroxyapatite bone mineral forming the inorganic phase of bone. Due to its crystal structure and chemistry, hydroxyapatite (HA) and related apatites have a remarkable ability to bind molecules. This review article describes the accretion of trace elements in bone mineral giving a historical perspective. Implanted HA particles of synthetic origin have proved to be an efficient recruiting moiety for systemically circulating drugs which can locally biomodulate the material and lead to a therapeutic effect. Bone mineral and apatite however also act as a waste dump for trace elements and drugs, which significantly affects the environment and human health.

Cite this article: Bone Joint Res 2020;9(10):709–718.

Osteoporosis (OP) is a chronic metabolic bone disease characterized by the decrease of bone tissue per unit volume under the combined action of genetic and environmental factors, which leads to the decrease of bone strength, makes the bone brittle, and raises the possibility of bone fracture. However, the exact mechanism that determines the progression of OP remains to be underlined. There are hundreds of trillions of symbiotic bacteria living in the human gut, which have a mutually beneficial symbiotic relationship with the human body that helps to maintain human health. With the development of modern high-throughput sequencing (HTS) platforms, there has been growing evidence that the gut microbiome may play an important role in the programming of bone metabolism. In the present review, we discuss the potential mechanisms of the gut microbiome in the development of OP, such as alterations of bone metabolism, bone mineral absorption, and immune regulation. The potential of gut microbiome-targeted strategies in the prevention and treatment of OP was also evaluated.

Cite this article: Bone Joint Res 2020;9(8):524–530.

A balanced inflammatory response is important for successful fracture healing. The response of osteoporotic fracture healing is deranged and an altered inflammatory response can be one underlying cause. The objectives of this review were to compare the inflammatory responses between normal and osteoporotic fractures and to examine the potential effects on different healing outcomes. A systematic literature search was conducted with relevant keywords in PubMed, Embase, and Web of Science independently. Original preclinical studies and clinical studies involving the investigation of inflammatory response in fracture healing in ovariectomized (OVX) animals or osteoporotic/elderly patients with available full text and written in English were included. In total, 14 articles were selected. Various inflammatory factors were reported; of those tumour necrosis factor-α (TNF-α) and interleukin (IL)-6 are two commonly studied markers. Preclinical studies showed that OVX animals generally demonstrated higher systemic inflammatory response and poorer healing outcomes compared to normal controls (SHAM). However, it is inconclusive if the local inflammatory response is higher or lower in OVX animals. As for clinical studies, they mainly examine the temporal changes of the inflammatory stage or perform comparison between osteoporotic/fragility fracture patients and normal subjects without fracture. Our review of these studies emphasizes the lack of understanding that inflammation plays in the altered fracture healing response of osteoporotic/elderly patients. Taken together, it is clear that additional studies, preclinical and clinical, are required to dissect the regulatory role of inflammatory response in osteoporotic fracture healing.

Cite this article: Bone Joint Res 2020;9(7):368–385.

Aims

Idiopathic scoliosis is the most common spinal deformity in adolescents and children. The aetiology of the disease remains unknown. Previous studies have shown a lower bone mineral density in individuals with idiopathic scoliosis, which may contribute to the causation. The aim of the present study was to compare bone health in adolescents with idiopathic scoliosis with controls.

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.

Objectives

MicroRNAs (miRNAs) have been reported as key regulators of bone formation, signalling, and repair. Fracture healing is a proliferative physiological process where the body facilitates the repair of a bone fracture. The aim of our study was to explore the effects of microRNA-186 (miR-186) on fracture healing through the bone morphogenetic protein (BMP) signalling pathway by binding to Smad family member 6 (SMAD6) in a mouse model of femoral fracture.

Objectives

Experimental studies indicate that non-steroidal anti-inflammatory drugs (NSAIDs) may have negative effects on fracture healing. This study aimed to assess the effect of immediate and delayed short-term administration of clinically relevant parecoxib doses and timing on fracture healing using an established animal fracture model.

Objectives. Osteoporosis is a systemic bone metabolic disease, which often occurs among the elderly. Angelica polysaccharide (AP) is the main component of angelica sinensis, and is widely used for treating various diseases. However, the effects of AP on osteoporosis have not been investigated. This study aimed to uncover the functions of AP in mesenchymal stem cell (MSC) proliferation and osteoblast differentiation. Methods. MSCs were treated with different concentrations of AP, and then cell viability, Cyclin D1 protein level, and the osteogenic markers of runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP-2) were examined by Cell Counting Kit-8 (CCK-8) and western blot assays, respectively. The effect of AP on the main signalling pathways of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Wnt/β-catenin was determined by western blot. Following this, si-H19#1 and si-H19#2 were transfected into MSCs, and the effects of H19 on cell proliferation and osteoblast differentiation in MSCs were studied. Finally, in vivo experimentation explored bone mineral density, bone mineral content, and the ash weight and dry weight of femoral bone. Results. The results revealed that AP significantly promoted cell viability, upregulated cyclin D1 and increased RUNX2, OCN, ALP, and BMP-2 protein levels in MSCs. Moreover, we found that AP notably activated PI3K/AKT and Wnt/β-catenin signalling pathways in MSCs. Additionally, the relative expression level of H19 was upregulated by AP in a dose-dependent manner. The promoting effects of AP on cell proliferation and osteoblast differentiation were reversed by H19 knockdown. Moreover, in vivo experimentation further confirmed the promoting effect of AP on bone formation. Conclusion. These data indicate that AP could promote MSC proliferation and osteoblast differentiation by regulating H19. Cite this article: X. Xie, M. Liu, Q. Meng. Angelica polysaccharide promotes proliferation and osteoblast differentiation of mesenchymal stem cells by regulation of long non-coding RNA H19: An animal study. Bone Joint Res 2019;8:323–332. DOI: 10.1302/2046-3758.87.BJR-2018-0223.R2

PEMF is currently approved by the FDA for adjunctive treatment of lumbar/cervical spine fusion and for treatment of long-bone non-unions. Soft tissues are a potential new therapeutic application for PEMF due to pre-clinical studies showing a reduction of inflammatory markers following PEMF exposure. The aim was therefore to investigate the structural/functional effects of PEMFs on tendon-to-bone and tendon-to-tendon healing in a rotator-cuff (RC) and Achilles tendon (AT) repair model, respectively. RC study: Adult male rats (n=280), underwent bi-lateral supraspinatus tendon transections with immediate repair followed by cage activity until sacrifice (4, 8, and 16 weeks). Non-controls received PEMF for 1, 3, or 6 hours daily. AT study: Male rats underwent acute, complete transection and repair of the Achilles tendon (FULL, n=144) or full thickness, partial width injury (PART, n=160) followed by immobilization for 1 week. Sacrifice was at 1, 3, and 6 weeks. Outcome measures included passive joint mechanics, gait analysis, biomechanical assessments, histological analysis of the repair site and mCT (humerus) assessment (FULL only). RC study: Significant increases in modulus, stiffness, bone mineral content and improved collagen organization was observed for the PEMF groups. No differences in joint mechanics and ambulation were observed. AT study: A decrease in stiffness and limb-loading rate was observed for the PEMF groups for the FULL groups, whereas an increase in stiffness with no change in range-of-motion was seen for the PART groups. The combined studies show that PEMF can be effective for soft tissue repair but is dependent on the location of application

Stress shielding has been a well-recognised problem with uncemented femoral components resulting in proximal bone loss and dysfunction, but less attention has been paid to the preservation of acetabular bone stock. Uncemented acetabular components often demonstrate reduced bone density on plain radiographs in the mid-portion of the cup (zone 2), which may be due to the rigidity of the outer shell. This study compares the change in bone density around three different cups with varying moduli of elasticity at a minimum of 2 years. Our hypothesis was that less rigid cups would be associated with improved bone density and less stress shielding. This prospective randomised controlled trial compared the bone mineral content (BMC) adjacent to three different cups with marked differences in stiffness. Cup A was an all titanium shell, cup B was a titanium coated all polyethylene implant and cup C was a tantalum backed shell. All articulations used a 32mm ceramic femoral head. Cup B used polyethylene modified by treatment with vitamin E whereas cups A and C used a liner made of irradiated cross linked polyethylene. Five regions of interest (ROI) were established adjacent to the cup, regions 2, 3 and 4 where similar to the DeLee and Charnley regions 1, 2 and 3. Bone density was measured using IDXA preoperatively, postoperatively, 6 months, 1 and 2 years and compared for each ROI and implant. Precision measurements showed significant reliability. All areas showed a reduction in BMC following insertion of the acetabular cup. Bone loss was less in ROI 1 and 4 in the area of rim fit for all cups and the maximal bone loss was seen in ROI 2 and 3 at the dome of the cup. The more elastic cup (Cup B) produced the least bone loss in this area (p<0.05). Cup C produced the largest bone loss at ROI 2 (40%) which continued increasing at 2 years. Cup stiffness is related to bone loss adjacent to the acetabulum, presumably due to a similar process of stress shielding as seen in the femur. All cups produced similar changes at the periphery of the cup but the more elastic cup retained bone density beneath the cup which continued past 2 years. This improvement in bone quality is likely to be associated with better acetabular bone stock into the future and more reliable long term cup fixation

Objectives. Osteoporosis and osteomalacia lead to increased fracture risk. Previous studies documented dysregulated osteoblast and osteoclast activity, leading to a high-turnover phenotype, reduced bone mass and low bone mineral content. Osteocytes, the most abundant bone cell type, are involved in bone metabolism by enabling cell to cell interaction. Osteocytes presence and viability are crucial for bone tissue homeostasis and mechanical integrity. Osseo-integration and implant degradation are the main problems in developing biomaterials for systemically diseased bone. This study examines osteocyte localisation, morphology and on the implant surface and at the implant bone interface. Furthermore, the study investigates ECM proteins regulation correlated to osteocytes and mechanical competence in an ovariectomised rat model with a critical size metaphyseal defect. Methodology. After induction of osteoporosis, 60 female Sprague-Dawley rats were randomised into five groups: SrCPC (n=15), CPC (n=15), ScB30 (n=15), ScB30Sr20 (n=15) and empty defect (n=15). The left femur of all animals underwent a 4mm wedge-shaped metaphyseal osteotomy that was internally fixed with a T-shaped plate. The defect was then either filled with the above mentioned implants or left empty. After six weeks, histomorphometric analysis showed a statistically significant increase in bone formation at the tissue-implant interface in the SrCPC group compared to the other groups (p<0.01). Osteocyte morphology and networks were detected using silver and staining. ECM proteins were investigated through immunohistochemistry. Cellular populations were tested using enzyme histochemistry. Mineralisation was assessed using time of flight secondary ion mass spectrometry (TOF-SIMS). Statistical analysis was performed using Mann Whitney U test with Bonferroni correction. Results. In the SrCPC and compared to other test groups, osteocytes presence and morphology was enhanced. An increased osteocytic activity was also seen in ScB30Sr20 when compared to SCB30 alone. Local osteomalatic lesions characterised by the presence of excessive unmineralised osteoid as revealed by the VKVG staining in the intact bone was also seen. A regular pattern of osteocytes distribution reflecting a better bone maturation was also seen in case of the Sr substituted cements. Whereas in case of the ScB30 degenerated osteocytes with a comparatively irregular arrangement were seen. Nonetheless, ECM proteins indicating discrepant bone turnover (RANKL, OPG, BMP2, OCN; ASMA) were noticed to increase within these regions and were accompanied by the presence of apoptotic osteocytes. Interestingly, osteocytes were also localised near the blood vessels within the newly formed woven bone. On the other hand, osteocytes allocation at implant bone interface and on the implant surface were qualitatively better in the Sr substituted groups when compared to the other test groups. Furthermore, this correlates with healing enhancement and implant retention results obtained from the histomorphometry (BV/TV and Osteoclasts count). The first qualitative results of the sclerostin visualisation showed a lower expression in the Sr supplemented biomaterials compared to the Sr free ones. Conclusion. Osteoblasts, osteoclast and osteocytes are the key players to bone metabolism through production and mineralisation of ECM or resorption. The current study indicates the importance in therapeutically targeting osteocytes to regulate bone metabolism in osteoporotic/osteomalatic bone. Sr inhibits osteoclast activity which is important for implant degradation. However, in osteoporotic bone osteoclasts inhibition is crucial to enhance the healing. Our data suggest that osteocytes allocation at the bone implant interface and on the implant surface is aiding in implant degradation through osteocytes dependent resorption. Currently, discrepancies in mechanosensitivity, proliferation and fibrotic tissue formation are being investigated together with several anchorage proteins to quench further effects of osteocyte presence at the implant bone interface