Bone Reports最新文献

Purpose

Radiofrequency echographic multi-spectrometry (REMS) is an ultrasound technology currently used for the densitometric evaluation of osteoporosis and has been validated against dual-energy X-ray absorptiometry. However, the use of REMS for bone densitometry in patients with severe motor and intellectual disabilities (SMID) remains to be reported. This study aimed to investigate whether REMS technology can be used for densitometric evaluation of osteoporosis in patients with SMID with hip dislocation and severe scoliosis.

Methods

Sixty-five patients with SMID, who resided in a long-term care facility and received comprehensive medical and rehabilitation care, underwent REMS scans of the femoral neck and/or lumbar spine. Data regarding anthropometric parameters (height and weight), bone mineral density (BMD), clinical diagnostic classification, physical ability, presence of scoliosis and hip dislocation, and frontal radiographs of both hip joints were obtained.

Results

We included 29 men and 34 women (mean age: 52.6 years). All patients underwent successful scanning at either the femoral neck (82.5 %) or lumbar spine (95.2 %). BMD measurements obtained using REMS revealed low values, with a mean BMD, T-score, and Z-score of 0.67 g/cm², −2.39 standard deviation (SD), and − 1.38 SD, respectively, at the femoral neck and 0.66 g/cm², −2.70 SD, and − 1.87 SD, respectively, at the lumbar spine. The average Cobb angle of the lumbar spine was 34.0°; furthermore, dislocation rates did not significantly differ between those with and without successful BMD measurements (p = 0.073). Lumbar BMD T-scores were significantly correlated with femoral neck BMD T-scores (p < 0.001, r = 0.530).

Conclusion

All patients with SMID were able to undergo measurements of either spinal or femoral neck BMD; furthermore, 77.7 % of the patients underwent measurements at both the lumbar spine and femur. Our data suggest that REMS is useful for measuring BMD in patients with SMID who are residing in institutions.

The Wnt signaling pathway is a key molecular process during fracture repair. Although much of what we now know about the role of this pathway in bone is derived from in vitro and animal studies, the same cannot be said about humans. As such, we hypothesized that Wnt signaling will also be a key process in humans during physiological fracture healing as well as in the development of a nonunion (hypertrophic and oligotrophic). We further hypothesized that the expression of Wnt-signaling pathway genes/proteins would exhibit a differential expression pattern between physiological fracture callus and the pathological nonunion tissues. We tested these two hypotheses by examining the mRNA levels of key Wnt-signaling related genes: ligands (WNT4, WNT10a), receptors (FZD4, LRP5, LRP6), inhibitors (DKK1, SOST) and modulators (CTNNB1 and PORCN). RNA sequencing from calluses as well as from the two nonunion tissue types, revealed that all of these genes were expressed at about the same level in these three tissue types. Further, spatial expression experiments identified the cells responsible of producing these proteins. Robust expression was detected in osteoblasts for the majority of these genes except SOST which displayed low expression, but in contrast, was mostly detected in osteocytes. Many of these genes were also expressed by callus chondrocytes as well. Taken together, these results confirm that Wnt signaling is indeed active during both human physiological fracture healing as well as in pathological nonunions.

We report here a rare case of an acute peripheral nerve compression by pseudotumoral calcinosis (PCT) at the right elbow in a patient with severe tertiary hyperaparathyroidism. This complication required urgent multidisciplinary management. Surgical decompression by PCT resection enabled rapid motor and sensory recovery.

We report a case of a patient with a de novo germline heterozygous truncating variant of CTNNB1 gene (c.2172del, p.Tyr724Ter) causing neurodevelopmental disorder with spastic diplegia and visual defects syndrome (NEDSDV) associated with a new clinical feature — severe pediatric-onset osteoporosis and multiple fractures. A functional effect of the identified variant was demonstrated using adipose-tissue derived primary mesenchymal stem cells, where we detected the alteration of CTNNB1mRNA and β-catenin protein levels using real-time PCR and Western blot analysis.

Bone loss is a well-known phenomenon in the older population leading to increased bone fracture risk, morbidity, and mortality. Supplementation of eggshell membrane (ESM) is evaluated due to its possible application to prevent bone loss and usage in osteoporosis therapy. The similar organic chemical composition of ESM and human bone is described in detail as both mainly consist of collagen type I, chondroitin sulfate, dermatan sulfate, hyaluronic acid and elastan. ESM and its components are reported to improve mineralization in bone tissue. In many studies ESM intake reduced pain in patients with joint disorders and reduced inflammatory processes. Additionally, ESM improved calcium uptake in human cells. These findings in comparison with a clinical pilot study reporting pain reduction in osteoporotic patients and increased osteoblast activity in in vitro assays support ESM to be a beneficial supplement for bone health. In this systematic review we combined chemical structure analysis with clinical studies to give a more comprehensive picture with novel explanations.

Purpose

This study aimed to analyze the current medication treatment status for women with osteoporosis (OP) based on real-world prescription data from 2016 to 2021 in Chinese nine cities' tertiary Grade A hospital and systematically describe the medication treatment patterns in women with OP.

Methods

Prescription information for female OP patients in nine cities (Beijing, Shanghai, Guangzhou, Hangzhou, Tianjin, Zhengzhou, Chengdu, Shenyang, Harbin) was extracted from the Hospital Prescription Analysis Collaboration Project Database of the Hospital Pharmacy Professional Committee of the Chinese Pharmaceutical Association. Statistical analysis was conducted to evaluate demographic characteristics and medication treatment patterns.

Results

A total of 669,505 prescriptions for medication treatment of female OP patients were included in this study. The majority of patients were aged 60 to 99 years (69.79 %) followed by 50 to 59 years (18.81 %) and 40 to 49 years (6.69 %). Geographically, the highest concentration of patients was in North China (Beijing, Tianjin) (43.05 %) followed by East China (Shanghai, Hangzhou) (31.43 %). The top three prescribed medications were active vitamin D and its analogs (40.78 %), calcium supplements (32.51 %), and bisphosphonates (18.75 %). The prescription frequency of menopausal hormone therapy (MHT) was 0.31 %. The proportion of female OP patients receiving monotherapy and two drug combinations therapy is equivalent (about 37 %).

Conclusion

The diagnosis and treatment of female OP patients in China showed regional variations. The most commonly prescribed medications for this population were calcitriol, calcium carbonate with vitamin D3, and alendronate sodium with vitamin D3. The use of MHT was relatively limited.

Objective Isotretinoin, also known as 13-cis-retinoic acid, is an isomer of tretinoin, the oxidized form of Vitamin A. Orthodontic tooth movement (OTM) is the result of a cascade of inflammatory responses stimulated by a physical element that is the force generated by orthodontic appliances. Isotretinoin is mainly used among adolescents and young adults, and coincidentally it is this age group that also undergoes orthodontic treatment. Materials and Methods Fifty-five animals were used, and they were randomly divided into 11 groups, containing 5 animals in each group. Group 1: Control; Group 2: OTM for 7 days; Group 3: OTM for 14 days; Group 4: Treated with isotretinoin for 14 days with a dosage of 7.5 mg/kg/day; Group 5: Treated with isotretinoin for 14 days with a dosage of 1.0 mg/kg/day; Group 6: Treated with isotretinoin for 21 days with a dosage of 7.5 mg/kg/day; Group 7: Treated with isotretinoin for 21 days with a dosage of 1.0 mg/kg/day; Group 8: Treated with isotretinoin for 14 days with a dosage of 7.5 mg/kg/day and undergoing OTM for 7 days; Group 9: Treated with isotretinoin for 14 days with a dosage of 1.0 mg/kg/day and undergoing OTM for 7 days; Group 10: Treated with isotretinoin for 21 days with a dosage of 7.5 mg/kg/day and undergoing OTM for 14 days; Group 11: Treated with isotretinoin for 21 days with a dosage of 1.0 mg/kg/day and undergoing OTM for 14 days. In Groups 8, 9, 10 and 11, the animals were treated with isotretinoin for 7 days before OTM and maintained during the movement period in the respective groups.

Results There was a significant difference in microtomographic parameters, including Trabecular Volume (BV/TV), Trabecular Thickness (Tb.Th), Number of Trabeculae (Tb.N), and Trabecular Separation (Tb.Sp), between the groups. The group that received orthodontic force in conjunction with isotretinoin treatment at a dosage of 7.5 mg/kg/day exhibited lower tooth displacement over a period of 21 days and 14 days. Conclusion Isotretinoin caused a reduction in tooth displacement during OTM when administered at a dose of 7.5 mg/kg/day and isotretinoin did change the microtomographic parameters of treated animals.

Despite the dominant role of bone mass in osteoporotic fractures, aging bone tissue properties must be thoroughly understood to improve osteoporosis management. In this context, collagen content and integrity are considered important factors, although limited research has been conducted on the tensile behavior of demineralized compact bone in relation to its porosity and elastic properties in the native mineralized state. Therefore, this study aims (i) at examining the age-dependency of mineralized bone and collagen micromechanical properties; (ii) to test whether, and if so to which extent, collagen properties contribute to mineralized bone mechanical properties.

Two cylindrical cortical bone samples from fresh frozen human anatomic donor material were extracted from 80 proximal diaphyseal sections from a cohort of 24 female and 19 male donors (57 to 96 years at death). One sample per section was tested in uniaxial tension under hydrated conditions. First, the native sample was tested elastically (0.25 % strain), and after demineralization, up to failure. Morphology and composition of the second specimen was assessed using micro-computed tomography, Raman spectroscopy, and gravimetric methods. Simple and multiple linear regression were employed to relate morphological, compositional, and mechanical variables with age and sex.

Macro-tensile properties revealed that only elastic modulus of native samples was age dependent whereas apparent elastic modulus was sex dependent (p < 0.01). Compositional and morphological analysis detected a weak but significant age and sex dependency of relative mineral weight (r = −0.24, p < 0.05) and collagen disorder ratio (I_∼1670/I_∼1640, r = 0.25, p < 0.05) and a strong sex dependency of bone volume fraction while generally showing consistent results in mineral content assessment. Young's modulus of demineralized bone was significantly related to tissue mineral density and Young's modulus of native bone.

The results indicate that mechanical properties of the organic phase, that include collagen and non-collagenous proteins, are independent of donor age. The observed reduction in relative mineral weight and corresponding overall stiffer response of the collagen network may be caused by a reduced number of mineral-collagen connections and a lack of extrafibrillar and intrafibrillar mineralization that induces a loss of waviness and a collagen fiber pre-stretch.

As international incidence of diabetes and diabetes-driven comorbidities such as chronic kidney disease (CKD) continue to climb, interventions are needed that address the high-risk skeletal fragility of what is a complex disease state. Romosozumab (Romo) is an FDA-approved sclerostin inhibitor that has been shown to increase bone mineral density and decrease fracture rates in osteoporotic patients with mild to severe CKD, but its effect on diabetes-weakened bone is unknown. We aimed to test Romo's performance in a model of combined diabetes and CKD. 6-week old male C57BL/6 mice were randomly divided into control (CON) and disease model (STZ-Ad) groups, using a previously established streptozotocin- and adenine-diet-induced model. After 16 weeks of disease induction, both CON and STZ-Ad groups were subdivided into two treatment groups and given weekly subcutaneous injections of 100 μL vehicle (phosphorus buffered saline, PBS) or 10 mg/kg Romo. Mice were euthanized after 4 weeks of treatment via cardiac exsanguination and cervical dislocation. Hindlimb bones and L4 vertebrae were cleaned of soft tissue, wrapped in PBS-soaked gauze and stored at 20C. Right tibiae, femora, and L4s were scanned via microcomputed tomography; tibiae were then tested to failure in 4-pt bending while L4s were compression tested. Romo treatment significantly increased cortical and trabecular bone mass in both STZ-Ad and CON animals. These morphological improvements created corresponding increases in cortical bending strength and trabecular compression strength, with STZ-Ad treated mice surpassing vehicle CON mice in all trabecular mechanics measures. These results suggest that Romo retains its efficacy at increasing bone mass and strength in diabetic kidney disease.

Introduction

Tumor-induced osteomalacia (TIO), is a rare acquired paraneoplastic syndrome characterized by defective bone mineralization, caused by the overproduction of fibroblast growth factor 23 (FGF23) by a tumor.

Material and methods

We conducted a systematic review to identify all case reports of TIO, focusing on those associated with mesenchymal tumors. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) consensus, and we included patients with a diagnosis of TIO and histological confirmation of phosphaturic mesenchymal tumors or resolution of the condition after treatment of the tumor. Bibliographical searches were carried out until December 2023 in the Cochrane Library, Medline and Embase, as well as congress abstracts online.

Results

We identified 769 articles with 1979 cases reported. Most patients were adults, with a higher incidence on men. Disease duration before diagnosis is a mean of 4.8 years. Most tumors were histologically classified as PMT. Lower limbs were the predominant location. Hypophosphatemia was present in 99.8 % of patients. The FGF23 was elevated at diagnosis in 95.5 %. Resection of the tumor was the treatment of choice in most of patients. After resection, there was a clinical improvement in 97.6 % of cases, and serum phosphorus and FGF23 levels returned to normal ranges in 91.5 % and 81.4 % of the patients, respectively.

Conclusion

TIO is usually misdiagnosed with rheumatological or musculoskeletal disorders. The diagnosis should be suspected in patients with hypophosphatemic osteomalacia, and the measurement of serum FGF23 can be useful for diagnosis and management.