Introduction. Metabolic bone disease encompasses disorders of bone mineralization, abnormal matrix formation or deposition and alteration in osteoblastic and osteoclastic activity. In the paediatric cohort, patients with metabolic bone disease present with pain, fractures and deformities. The aim was to evaluate the use of lateral entry rigid intramedullary nailing in lower limbs in children and adolescents. Materials and Methods. Retrospective review was performed for an 11-year period. Lower limb rigid intramedullary nailing was performed in 27 patients with a total of 63 segments (57 femora, 6 tibiae). Majority of patients had underlying diagnoses of osteogenesis imperfecta or fibrous dysplasia (including McCune Albright disease). Mean age at surgery was 14 years. Indications for surgery included acute fractures, prophylactic stabilisation, previous nonunion and malunion, deformity correction and lengthening via distraction osteogenesis. Results. All fractures healed. Correction of deformity was successfully achieved in all segments. Delayed union occurred in 4 segments in 1 patient and was successfully treated with nail dynamization. Other complications included prominence, cortical penetrance and loosening of locking screws. One patient who had lengthening performed had nonunion and was managed with exchange nailing and adjunctive measures. Conclusions. Rigid intramedullary nailing is very effective in stabilisation and deformity correction of long bones in adolescent patients with pathological bone disease. The technique has low complication rates. We recommend the use of this technique in paediatric units with experience in managing metabolic bone conditions

We present the results of the surgical correction of lower-limb deformities caused by metabolic bone disease. Our series consisted of 17 patients with a diagnosis of hypophosphataemic rickets and two with renal osteodystrophy; their mean age was 25.6 years (14 to 57). In all, 43 lower-limb segments (27 femora and 16 tibiae) were osteotomised and the deformity corrected using a monolateral external fixator. The segment was then stabilised with locked intramedullary nailing. In addition, six femora in three patients were subsequently lengthened by distraction osteogenesis. The mean follow-up was 60 months (18 to 120). The frontal alignment parameters (the mechanical axis deviation, the lateral distal femoral angle and the medial proximal tibial angle) and the sagittal alignment parameters (the posterior distal femoral angle and the posterior proximal tibial angle) improved post-operatively. The external fixator was removed either at the end of surgery or at the end of the lengthening period, allowing for early mobilisation and weight-bearing. We encountered five problems and four obstacles in the programme of treatment. The use of intramedullary nails prevented recurrence of deformity and refracture

The aim of the study was to review the effectiveness of rigid IM nailing in stabilisation and deformity correction of lower limb long bones in adolescents with metabolic bone disease which to our knowledge has not been studied before. Medical records and radiographs were retrospectively reviewed looking at indications, deformity correction, number of osteotomies-if needed, bone healing, time to healing and incidence of complications. Between Aug 2010 and Mar 2015 fifteen patients (24 segments) had rigid IM nailing. Ten patients had Osteogenesis Imperfecta, four with McCune Albright syndrome and one with hypophosphatemic rickets. 22 femora and two tibiae were IM nailed. The mean age of the patients was 13.1 (9.6–16.75 years). Eleven out 24 segments were previously rodded. Eight segments were for acute fractures. 13 bones had significant deformities requiring corrective osteotomies. One patient had previous fracture non union. All patients were allowed to partial weight bear immediately postoperatively and were fully mobile six weeks following surgery. Mean follow up was 24 months (3–51 months) post-operatively. All deformities were corrected. All fractures and osteotomies radiologically united. Mean radiological union time was 5.5 months (6 weeks – 11 months). Patients with acute fractures had mean radiological union time of 4 months. Patients who had osteotomies had a mean radiological union time of 7.1 months. The patient with previous non union had BMP at the same time and radiologically healed in 10 months. Two patients had persistent bisphosphonate osteotomy lines but were asymptomatic. One patient had removal of a prominent distal locking screw and one had persistent Trendelenburg gait. Rigid intramedullary nailing is effective in stabilisation and deformity correction of long bones in adolescent patients with brittle bone disease. The technique has a low complication rate. We recommend the use of this technique in paediatric limb reconstruction in managing metabolic bone conditions

A clinical, radiological and histopathological study of femoral heads from 125 patients with fracture of the neck of the femur and from 30 cadavers was carried out to identify various risk factors. The findings showed that the Singh index was unreliable as a radiological indicator of the bone content of the femoral heads; that the bone content of the femoral head in patients sustaining a fracture of the femoral neck did not differ from that of the controls; that osteomalacia was not found in any of the heads examined; and that the distribution of trabecular microfractures did not support the hypothesis that fracture of the neck was the result of progressive fatigue. It was concluded that the single most important factor leading to fracture in this Australian population was injury caused by falls and that such injury was frequently associated with other disease processes.

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.

Aims. Osteoporosis (OP) is a metabolic bone disease, characterized by a decrease in bone mineral density (BMD). However, the research of regulatory variants has been limited for BMD. In this study, we aimed to explore novel regulatory genetic variants associated with BMD. Methods. We conducted an integrative analysis of BMD genome-wide association study (GWAS) and regulatory single nucleotide polymorphism (rSNP) annotation information. Firstly, the discovery GWAS dataset and replication GWAS dataset were integrated with rSNP annotation database to obtain BMD associated SNP regulatory elements and SNP regulatory element-target gene (E-G) pairs, respectively. Then, the common genes were further subjected to HumanNet v2 to explore the biological effects. Results. Through discovery and replication integrative analysis for BMD GWAS and rSNP annotation database, we identified 36 common BMD-associated genes for BMD irrespective of regulatory elements, such as FAM3C (p. discovery GWAS. = 1.21 × 10. -25. , p. replication GWAS. = 1.80 × 10. -12. ), CCDC170 (p. discovery GWAS. = 1.23 × 10. -11. , p. replication GWAS. = 3.22 × 10. -9. ), and SOX6 (p. discovery GWAS. = 4.41 × 10. -15. , p. replication GWAS. = 6.57 × 10. -14. ). Then, for the 36 common target genes, multiple gene ontology (GO) terms were detected for BMD such as positive regulation of cartilage development (p = 9.27 × 10. -3. ) and positive regulation of chondrocyte differentiation (p = 9.27 × 10. -3. ). Conclusion. We explored the potential roles of rSNP in the genetic mechanisms of BMD and identified multiple candidate genes. Our study results support the implication of regulatory genetic variants in the development of OP. Cite this article: Bone Joint Res 2023;12(2):147–154

Osteoporosis is a progressive, chronic disease of bone metabolism, characterized by decreased bone mass and mineral density, predisposing individuals to an increased risk of fractures. The use of animal models, which is the gold standard for the screening of anti-osteoporosis drugs, raises numerous ethical concerns and is highly debated because the composition and structure of animal bones is very different from human bones. In addition, there is currently a poor translation of pre-clinical efficacy in animal models to human trials, meaning that there is a need for an alternative method of screening and evaluating new therapeutics for metabolic bone disorders, in vitro. The aim of this project is to develop a 3D Bone-On-A-Chip that summarizes the spatial orientation and mutual influences of the key cellular components of bone tissue, in a citrate and hydroxyapatite-enriched 3D matrix, acting as a 3D model of osteoporosis. To this purpose, a polydimethylsiloxane microfluidic device was developed by CAD modelling, stereolithography and replica molding. The device is composed by two layers: (i) a bottom layer for a 3D culture of osteocytes embedded in an osteomimetic collagen-enriched matrigel matrix with citrate-doped hydroxyapatite nanocrystals, and (ii) a upper layer for a 2D perfused co-culture of osteoblasts and osteoclasts seeded on a microporous PET membrane. Cell vitality was evaluated via live/dead assay. Bone deposition and bone resorption was analysed respectively with ALP, Alizarin RED and TRACP staining. Osteocytes dendrite expression was evaluated via immunofluorescence. Subsequently, the model was validated as drug screening platform inducing osteocytes apoptosis and administrating standard anti-osteoporotic drugs. This device has the potential to substitute or minimize animal models in pre-clinical studies of osteoporosis, contributing to pave the way for a more precise and punctual personalized treatment

Renal Osteodystrophy is a type of metabolic bone disease characterized by bone mineralization deficiency due to electrolyte and endocrine abnormalities. Patients with chronic kidney disease (CKD) are more likely to experience falls and fractures due to renal osteodystrophy and the high prevalence of risk factors for falls. Treatment involves medical management to resolve the etiology of the underlying renal condition, as well as management (and prevention) of pathological fractures. A 66-year-old female patient, with severe osteoporosis and chronic kidney disease undergoing haemodialysis, has presented with multiple fractures along the years. She was submitted to bilateral proximal femoral nailing as fracture treatment on the left and prophylactically due to pathological bone injury on the right, followed by revision of the left nail with a longer one after varus angulation and fracture distal to the nail extremity. Meanwhile, the patient suffered a pathological fracture of the radial and cubital diaphysis and was submitted to conservative treatment with cast, with consolidation of the fracture. Posteriorly, she re-fractured these bones after a fall and repeated the conservative treatment. Clinical management: There is a multidisciplinary approach to manage the chronic illness of the patient, including medical management to resolve the etiology and consequences of her chronic kidney disease, pain control, conservative or surgical fracture management and prevention of falls. The incidence of chronic renal disease is increasing and the patients with this condition live longer than previously and are more physically active. Thus, patients may experience trauma as a direct result of increased physical activity in a setting of weakened pathologic bone. Their quality of life is primarily limited by musculoskeletal problems, such as bone pain, muscle weakness, growth retardation, and skeletal deformity. A multidisciplinary approach is required to treat these patients, controlling their chronic diseases, managing fractures and preventing falls

Metabolic bone diseases, such as osteoporosis and osteopetrosis, result from an imbalanced bone remodeling process. In vitro bone models are often used to investigate either bone formation or resorption independently, while in vivo, these processes are coupled. Combining these processes in a co-culture is challenging as it requires finding the right medium components to stimulate each cell type involved without interfering with the other cell type's differentiation. Furthermore, differentiation stimulating factors often comprise growth factors in supraphysiological concentrations, which can overshadow the cell-mediated crosstalk and coupling. To address these challenges, we aimed to recreate the physiological bone remodeling process, which follows a specific sequence of events starting with cell activation and bone resorption by osteoclasts, reversal, followed by bone formation by osteoblasts. We used a mineralized silk fibroin scaffold as a bone-mimetic template, inspired by bone's extracellular matrix composition and organization. Our model supported osteoclastic resorption and osteoblastic mineralization in the specific sequence that represents physiological bone remodeling. We also demonstrated how culture variables, such as different cell ratios, base media, and the use of osteogenic/osteoclast supplements, and the application of mechanical load, can be adjusted to represent either a high bone turnover system or a self-regulating system. The latter system did not require the addition of osteoclastic and osteogenic differentiation factors for remodeling, therefore avoiding growth factor use. Our in vitro model for bone remodeling has the potential to reduce animal experiments and advance in vitro drug development for bone remodeling pathologies like osteoporosis. By recreating the physiological bone remodeling cycle, we can investigate cell-cell and cell-matrix interactions, which are essential for understanding bone physiology and pathology. Furthermore, by tuning the culture variables, we can investigate bone remodeling under various conditions, potentially providing insights into the mechanisms underlying different bone disorders

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

Olecranon fractures are common injuries representing roughly 5% of pediatric elbow fractures. The traditional surgical management is open reduction and internal fixation with a tension band technique where the pins are buried under the skin and tamped into the triceps. We have used a modification of this technique, where the pins have been left out of the skin to be removed in clinic. The purpose of the current study is to compare the outcomes of surgically treated olecranon fractures using a tension-band technique with buried k-wires (PINS IN) versus percutaneous k-wires (PINS OUT). We performed a retrospective chart review on all pediatric patients (18 years of age or less) with olecranon fractures that were surgically treated at a pediatric academic center between 2015 to present. Fractures were identified using ICD-10 codes and manually identified for those with an isolated olecranon fracture. Patients were excluded if they had polytrauma, metabolic bone disease, were treated non-op or if a non-tension band technique was used (ex: plate/screws). Patients were then divided into 2 groups, olecranon fractures using a tension-band technique with buried k-wires (PINS IN) and with percutaneous k-wires (PINS OUT). In the PINS OUT group, the k-wires were removed in clinic at the surgeon's discretion once adequate fracture healing was identified. The 2 groups were then compared for demographics, time to mobilization, fracture healing, complications and return to OR. A total of 35 patients met inclusion criteria. There were 28 patients in the PINS IN group with an average age of 12.8 years, of which 82% male and 43% fractured their right olecranon. There were 7 patients in the PINS OUT group with an average age of 12.6 years, of which 57% were male and 43% fractured their right olecranon. All patients in both groups were treated with open reduction internal fixation with a tension band-technique. In the PINS IN group, 64% were treated with 2.0 k-wires and various materials for the tension band (82% suture, 18% cerclage wire). In the PINS OUT group, 71% were treated with 2.0 k-wires and all were treated with sutures for the tension band. The PINS IN group were faster to mobilize (3.4 weeks (range 2-5 weeks) vs 5 weeks (range 4-7 weeks) p=0.01) but had a significantly higher complications rate compared to the PINS OUT group (6 vs 0, p =0.0001) and a significantly higher return to OR (71% vs 0%, p=0.0001), mainly for hardware irritation or limited range of motion. All fractures healed in both groups within 7 weeks. Pediatric olecranon fractures treated with a suture tension-band technique and k-wires left percutaneously is a safe and alternative technique compared to the traditional buried k-wires technique. The PINS OUT technique, although needing longer immobilization, could lead to less complications and decreased return to the OR due to irritation and limited ROM

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

Cigarette smoking has a negative impact on the skeletal system by reducing bone mass and increasing the risk of fractures through its direct or indirect effects on bone remodeling. Recent evidence shows that smoking causes an imbalance in bone turnover, making bone vulnerable to osteoporosis and fragility fractures. In addition, cigarette smoking is known to have deleterious effects on fracture healing, as a positive correlation has been shown between the daily number of cigarettes smoked and years of exposure to smoking, although the underlying mechanisms are not fully understood. Smoking is also known to cause several medical and surgical complications responsible for longer hospital stays and a consequent increase in resource consumption. Smoking cessation is, therefore, highly advisable to prevent the onset of metabolic bone disease. However, some of the consequences appear to continue for decades. Based on this evidence, the aim of our work was to assess the impact of smoking on the skeletal system, particularly bone fractures, and to identify the pathophysiological mechanisms responsible for the impairment of fracture healing. Because smoking represents a major public health problem, understanding the association between cigarette smoking and the occurrence of bone disease is necessary in order to identify potential new targets for intervention

Objectives. This study aims to evaluate if micro-CT can work as a method for the 3D assessment and analysis of cancellous bone by comparing micro-CT with undecalcified histological sections in OVX rats. Methods. The mandible and tibia of sham, ovariectomised (OVX) and zoledronate-injected ovariectomised (OVX-ZOL) rats were assessed morphometrically. Specimens were scanned by micro-CT. Undecalcified histological sections were manufactured from the specimen scanned by micro-CT and stained with haematoxylin and eosin. Bivariate linear regressions and one-way analysis of variance were undertaken for statistics using SPSS 16.0.1 software. Results. There were highly significant correlations between undecalcified histological sections and micro-CT for all parameters (bone volume density (BV/TV), bone surface density (BS/BV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp))in the mandible and tibia. Bone histomorphometric parameters analysed by both methods exhibited significant differences among sham, OVX, and OVX-ZOL groups. There were significant correlations between mandible and tibia in BV/TV, BS/BV, and Tb.Sp. Conclusions. Micro-CT is a complementary tool to histological sections in basic research that could improve our understanding of bone histomorphometry. The mandible can be used as an effective site to assess bone morphometry of OVX or metabolic bone disease rat models. Cite this article: H. Liu, W. Li, Y. S. Liu, Y. S. Zhou. Bone micro-architectural analysis of mandible and tibia in ovariectomised rats: A quantitative structural comparison between undecalcified histological sections and micro-CT. Bone Joint Res 2016;5:253–262