Bone Reports最新文献

There is a wide spectrum of craniofacial bone disorders and dysplasias because embryological development of the craniofacial region is complex. Classification of craniofacial bone disorders and dysplasias is also complex because they exhibit complex clinical, pathological, and molecular heterogeneity. Most craniofacial disorders and dysplasias are rare but they present an array of phenotypes that functionally impact the orofacial complex. Management of craniofacial disorders is a multidisciplinary approach that involves the collaborative efforts of multiple professionals. This review provides an overview of the complexity of craniofacial disorders and dysplasias from molecular, clinical, and management perspectives.

Introduction

Fractures affect people's quality of life especially in the elders. One of the most important risk factors is osteoporosis. There are many screening tools to predict osteoporosis and fractures. We aimed to compare the predictive validity of three commonly used screening tools: fracture risk assessment tool (FRAX), osteoporosis self-assessment tool for Asians (OSTA) and one-minute osteoporosis risk test. Among them, OSTA and one-minute osteoporosis risk test were originally developed to predict osteoporosis risks and FRAX was to predict fracture risks.

Methods

This is an 11-year longitudinal study. We enrolled 708 senior people from health examinees in Taiwan in 2010. A standardized questionnaire and blood tests were provided. Annual telephone interview was conducted to assess the real fracture status. We calculated risk scores of FRAX, OSTA, and one-minute osteoporosis risk test and compared with real-world fracture records.

Results

The mean age of the participants were 74.9 (SD 6.4). There were 356 (50.3 %) men. From 2010 to 2020, a total of 105 (14.8 %) persons suffered from fractures. Compared to people without fractures, people with fractures had higher FRAX major osteoporotic fracture risk scores (14.0 % ± 7.6 % vs.11.3 % ± 5.7 %), higher hip fracture risk scores, and higher OSTA risk (5.9 % ± 1.4 % vs. 5.3 % ± 1.3 %). Cox regression analysis showed that hazard ratios for fracture of high FRAX risk was 1.53 (95 % confidence interval (CI) 1.05–2.21), and for high OSTA risk was 1.37 (95 % CI 1.04–1.82).

Conclusions

Only OSTA and FRAX scores were satisfactory in predicting 10-year fractures.

Objectives

Adjacent segment disc degeneration (ASDD) is one of the long-term sequelae of spinal fusion, which is more susceptible with osteoporosis. As an anti-osteoporosis drug, strontium ranelate (SR) has been reported to not only regulate bone metabolism but also cartilage matrix formation. However, it is not yet clear whether SR has a reversal or delaying effect on fusion-induced ASDD in a model of osteoporosis.

Materials and methods

Fifth three-month-old female Sprague-Dawley rats that underwent L4-L5 posterolateral lumbar fusion (PLF) with spinous-process wire fixation 4 weeks after bilateral ovariectomy (OVX) surgery. Animals were administered vehicle (V) or SR (900 mg/kg/d) orally for 12 weeks post-PLF as follows: Sham+V, OVX + V, PLF + V, OVX + PLF + V, and OVX + PLF + SR. Manual palpation and X-ray were used to evaluate the state of lumbar fusion. Adjacent-segment disc was assessed by histological (VG staining and Scoring), histomorphometry (Disc Height, MVD, Calcification rate and Vascular Bud rate), immunohistochemical (Col-II, Aggrecan, MMP-13, ADAMTS-4 and Caspase-3), and mRNA analysis (ColI, Col-II, Aggrecan, MMP-13 and ADAMTS-4). Adjacent L6 vertebrae microstructures were evaluated by microcomputed tomography.

Results

Manual palpation and radiographs showed clear evidence of the fused segment's immobility. After 12 weeks of PLF surgery, a fusion-induced ASDD model was established. Low bone mass caused by ovariectomy can significantly exacerbate ASDD progression. SR exerted a protective effect on adjacent segment intervertebral disc with the underlying mechanism possibly being associated with preserving bone mass to prevent spinal instability, maintaining the functional integrity of endplate vascular microstructure, and regulating matrix metabolism in the nucleus pulposus and annulus fibrosus.

Discussion

Anti-osteoporosis medication SR treatments not only maintain bone mass and prevent fractures, but early intervention could also potentially delay degenerative conditions linked to osteoporosis. Taken together, our results suggested that SR might be a promising approach for the intervention of fusion-induced ASDD with osteoporosis.

Background

Proton pump inhibitors (PPIs) are among the most commonly prescribed medications worldwide for acid-related disorders. While their short-term efficacy and safety are well-established, concerns regarding their long-term effects on bone health have emerged. This umbrella review aimed to synthesize the available findings on the associations between PPI use and bone metabolism outcomes.

Methods

An electronic search was conducted using PubMed, Web of Science, Embase, and the Cochrane Database up to September 16, 2023. Systematic reviews and meta-analyses of randomized controlled trials (RCTs) and observational studies that evaluated the relationship between PPIs and bone metabolism outcomes were included. Data extraction, quality appraisal, and synthesis were performed in line with the Joanna Briggs Institute and PRISMA guidelines. The strength of the evidence was graded using the GRADE criteria. Statistical analysis was performed in R version 4.3.

Results

Out of 299 records, 27 studies met the inclusion criteria. The evidence indicated a statistically significant increased risk of fractures, notably hip, spine, and wrist fractures, in PPI users. PPI use was associated with changes in Bone Mineral Density (BMD) across various bones, though the clinical relevance of these changes remains uncertain. Furthermore, PPI-induced hypomagnesemia, which can influence bone health, was identified. A notable finding was the increased risk of dental implant failures in PPI users. However, the certainty of most of the evidence ranged from very low to low based on GRADE criteria.

Conclusion

The long-term use of PPIs may be associated with adverse bone health outcomes, including increased fracture risk, alterations in BMD, hypomagnesemia, and dental implant failure. While these findings highlight potential concerns for long-term PPI users, the current evidence's low certainty underscores the need for robust, high-quality research to clarify these associations.

Nowadays, there is an increasing prevalence of bone diseases and defects caused by trauma, cancers, infections, and degenerative and inflammatory conditions. The restoration of bone tissue lost due to trauma, fractures, or surgical removal resulting from locally invasive pathologies requires bone regeneration. As an alternative to conventional treatments, sustainable materials based on natural products, such as honeybee-derived products (honey, propolis, royal jelly, bee pollen, beeswax, and bee venom), could be considered. Honeybee-derived products, particularly honey, have long been recognized for their healing properties. There are a mixture of phytochemicals that offer bone protection through their antimicrobial, antioxidant, and anti-inflammatory properties. This review aims to summarize the current evidence regarding the effects of honeybee-derived products on bone regeneration. In conclusion, honey, propolis, royal jelly, beeswax, and bee venom can potentially serve as natural products for promoting bone health.

Bisphosphonates (BP) are anti-resorptive drugs that are widely used to prevent bone loss in osteoporosis. Since inhibition of bone resorption will cause a decrease in bone formation through a process called coupling, it is hypothesized that extended treatment protocols may impair bone healing. In this study, β-tri‑calcium-phosphate (βTCP) ceramics were inserted into critical-size long bone defects in estrogen-deficient mice under BP therapy. The study assessed the benefits of coating the ceramics with Bone Morphogenetic Protein-2 (BMP2) and an engineered BMP2 analogue (L51P) that inactivates BMP antagonists on the healing process, implant resorption, and bone formation.

Female NMRI mice (11–12 weeks of age) were ovariectomized (OVX) or sham operated. Eight weeks later, after the manifestation of ovariectomy-induced osteoporotic bone changes, BP therapy with Alendronate (ALN) was commenced. After another five weeks, a femoral critical-size defect was generated, rigidly fixed, and βTCP-cylinders loaded with 0.25 μg or 2.5 μg BMP2, 2.5 μg L51P, and 0.25 μg BMP2/2.5 μg L51P, respectively, were inserted. Unloaded βTCP-cylinders were used as controls. Femora were collected six and twelve weeks post-implantation.

Histological and micro-computer tomography (MicroCT) evaluation revealed that insertion of cylinders coated with 2.5 μg BMP2 accelerated fracture repair and induced significant bone formation compared to controls (unloaded cylinders or coated with 2.5 μg L51P, 0.25 μg BMP2) already six weeks post-implantation, independent of estrogen-deficiency and BP therapy. The simultaneous administration of BMP2 and L51P (0.25 μg BMP2/2.5 μg L51P) did not promote fracture healing six and twelve weeks post-implantation. Moreover, new bone formation within the critical-size defect was directly linked to the removal of the βTCP-implant in all experimental groups. No evidence was found that long-term therapy with ALN impaired the resorption of the implanted graft. However, osteoclast transcriptome signature was elevated in sham and OVX animals upon treatment with BP, with transcript levels being higher at six weeks than at twelve weeks post-surgery. Furthermore, the transcriptome profile of the developing repair tissue confirmed an accelerated repair process in animals treated with 2.5 μg BMP2 implants. L51P did not increase the bioefficacy of BMP2 in the applied defect model.

The present study provides evidence that continuous administration of BP does not inhibit implant resorption and does not alter the kinetics of the healing process of critical-size long bone defects. Furthermore, the BMP2 variant L51P did not enhance the bioefficacy of BMP2 when applied simultaneously to the femoral critical-size defect in sham and OVX mice.

Pentosidine (PEN) is an Advanced Glycation End-product (AGE) that is known to accumulate in bone collagen with aging and contribute to fracture risk. The PEN content in bone is correlated with serum PEN, making it an attractive, potential osteoporosis biomarker. We sought to develop a method for quantifying PEN in stored serum. After conducting a systematic narrative review of PEN quantification methodologies, we developed a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for quantifying total serum PEN. Our method is both sensitive and precise (LOD 2 nM, LOQ 5 nM, %CV < 6.5 % and recovery 91.2–100.7 %). Our method is also equivalent or better than other methods identified in our review. Additionally, LC-MS/MS avoids the pitfalls and limitations of using fluorescence as a means of detection and could be adapted to investigate a broad range of AGE compounds.

Background

Abnormalities of the hyoid bone are associated with impairment of oropharyngeal functions including feeding, swallowing, and breathing. Few studies have characterized anatomic abnormalities of the hyoid in patients with Robin sequence (RS), e.g. a less mineralized and voluminous hyoid. The purpose of this study was to compare normal hyoid bone morphology and hyoid bone morphology in children with isolated RS.

Methods

Three-dimensional (3D) reconstructions of the hyoid bone were obtained from CT-imaging of children with RS and unaffected controls. A 3D morphable model was constructed using Principal Component Analysis (PCA). Partial least squares – Discriminant Analysis (PLS-DA) and multivariate analysis of variance (MANOVA) were used to characterize and compare hyoid shape differences between patients with RS and an age-matched control group.

Results

The study included 23 subjects with RS (mean age 9.8 ± 10.3 months) and 46 age-matched control samples. A less voluminous hyoid was observed for the RS group with a larger lateral divergence of the greater horns compared to controls (MANOVA, p-value<0.001). The first shape variable from the PLS-DA model showed a significant correlation for the observed variance between the two groups (Spearman R = −0.56, p-value<0.001). The control samples and 151 CT-scans of subjects up to age 4 years were used to create a 3D morphable model of normal hyoid shape variation (n = 197, mean age 22.1 ± 13.1 months). For the normal 3D morphable model, a high degree of allometric shape variation was observed along the first principal component.

Conclusions

The 3D morphable models provide a comprehensive and quantitative description of variation in normal hyoid bone morphology, and allow detection of distinct differences between patients with isolated RS and controls.

Romosozumab (RSB) is a monoclonal antibody to sclerostin that is approved for post-menopausal osteoporosis at high fracture risk. It is administered as a monthly 210 mg subcutaneous injection for 12 months. We report the response to half the standard dose of RSB in an underweight patient with severe osteoporosis and primary biliary cholangitis (PBC). Using half dose RSB (approximately 3 mg/kg RSB), she demonstrated significant improvement in lumbar spine BMD, paralleling the results of phase III trials. This case highlights the effectiveness of RSB in a patient with concomitant PBC, in addition to its effectiveness at half the recommended dose in an underweight patient.