Relationship Between Prepatellar Fat Thickness and Bone Mineral Density.

OBJECTIVE: To evaluate the relationship between bone mineral density (BMD) by measuring the prepatellar fat thickness with knee radiography and to gain a measurement method that has not been done before in the literature. STUDY DESIGN: Cross-sectional descriptive study. Place and Duration of the Study: Department of Physical Medicine and Rehabilitation, Training and Research Hospital, Sanliurfa, Turkiye, between January and June 2020. METHODOLOGY: Patients' age, body mass index (BMI) data, prepatellar fat thickness (mm), L1-L4 total, bone mineral density femoral neck, femur trochanter major, and femur total T scores were recorded. The relationships between these three groups (normal, osteopenia, osteoporosis) and between prepatellar fat tissue measurement were evaluated. One-way analysis of variance (ANOVA) and Post Hoc Tukey tests were used in the analysis. RESULTS:  A statistically significant difference was found in terms of trochanter major T score measurements (X2 = 20.435; p <0.001) and BMI (X2 = 66.535; p <0.001) measurements of prepatellar fat thickness measurement. A statistically significant difference was found between the three groups in terms of prepatellar fat thickness measurement, L1-4 T-score, femoral neck, and femur total values (p <0.001). CONCLUSION:  Prepatellar fat thickness in postmenopausal Turkish women was positively correlated with BMD; BMD increases as the prepatellar fat thickness increases. This explains that perapatellar fat thickness creates a mechanical load on the bones and causes an increase in BMD. KEY WORDS: Osteoporosis, Fat thickness, Bone mineral density.

Relationship between paraspinal muscle properties and bone mineral density based on QCT in patients with lumbar disc herniation.

OBJECTIVE: Increasing research suggests that paraspinal muscle fat infiltration may be a potential biological marker for the assessment of osteoporosis. Our aim was to investigate the relationship between lumbar paraspinal muscle properties on MRI and volumetric bone mineral density (vBMD) based on QCT in patients with lumbar disc herniation (LDH). METHODS: A total of 383 patients (aged 24-76 years, 193 females) with clinically and radiologically diagnosed LDH were enrolled in this retrospective study. The muscle cross-sectional area (CSA) and the proton density fat fraction (PDFF) were measured for the multifidus (MF), erector spinae (ES) and psoas major (PS) at the central level of L3/4, L4/5 and L5/S1 on lumbar MRI. QCT was used to measure the vBMD of two vertebral bodies at L1 and L2 levels. Patients were divided into three groups based on their vBMD values: normal bone density group (> 120 mg/cm3), osteopenia group (80 to 120 mg/cm3) and osteoporosis group (< 80 mg/cm3). The differences in paraspinal muscle properties among three vBMD groups were tested by one-way ANOVA with post hoc analysis. The relationships between paraspinal muscle properties and vBMD were analyzed using Pearson correlation coefficients. Furthermore, the association between vBMD and paraspinal muscle properties was further evaluated using multiple linear regression analysis, with age and sex also included as predictors. RESULTS: Among the 383 LDH patients, 191 had normal bone density, 129 had osteopenia and 63 had osteoporosis. In LDH patients, compared to normal and osteopenia group, paraspinal muscle PDFF was significantly greater in osteoporosis group, while paraspinal muscle CSA was lower (p < 0.001). After adjusting for age and sex, it was found that MF PDFF and PS CSA were found to be independent factors influencing vBMD (p < 0.05). CONCLUSION: In patients with LDH, paraspinal muscle properties measured by IDEAL-IQ sequence and lumbar MR scan were found to be related to vBMD. There was a correlation between the degree of paraspinal muscle PDFF and decreasing vBMD, as well as a decrease paraspinal muscle CSA with decreasing vBMD. These findings suggest that clinical management should consider offering tailored treatment options for patients with LDH based on these associations.

Proteomic Insights into Osteoporosis: Unraveling Diagnostic Markers of and Therapeutic Targets for the Metabolic Bone Disease.

Osteoporosis (OP), a prevalent skeletal disorder characterized by compromised bone strength and increased susceptibility to fractures, poses a significant public health concern. This review aims to provide a comprehensive analysis of the current state of research in the field, focusing on the application of proteomic techniques to elucidate diagnostic markers and therapeutic targets for OP. The integration of cutting-edge proteomic technologies has enabled the identification and quantification of proteins associated with bone metabolism, leading to a deeper understanding of the molecular mechanisms underlying OP. In this review, we systematically examine recent advancements in proteomic studies related to OP, emphasizing the identification of potential biomarkers for OP diagnosis and the discovery of novel therapeutic targets. Additionally, we discuss the challenges and future directions in the field, highlighting the potential impact of proteomic research in transforming the landscape of OP diagnosis and treatment.

Development and internal validation of a clinical prediction model for osteopenia in Chinese middle-aged and elderly men: a prospective cohort study.

BACKGROUND: Early identification of patients at risk of osteopenia is an essential step in reducing the population at risk for fractures. We aimed to develop and validate a prediction model for osteopenia in Chinese middle-aged and elderly men that provides individualized risk estimates. METHODS: In this prospective cohort study, 1109 patients who attend regular physical examinations in the Second Medical Centre of Chinese PLA General Hospital were enrolled from 2015.03 to 2015.09. The baseline risk factors included dietary habits, exercise habits, medical histories and medication records. Osteopenia during follow-up were collected from Electronic Health Records (EHRs) and telephone interviews. Internal validation was conducted using bootstrapping to correct the optimism. The independent sample T-test analysis, Mann_Whitney U test, Chi-Square Test and multivariable Cox regression analysis were utilized to identify predictive factors for osteopenia in Chinese middle-aged and elderly men. A nomogram based on the seven variables was built for clinical use. Concordance index (C-index), receiver operating characteristic curve (ROC), decision curve analysis (DCA) and calibration curve were used to evaluate the efficiency of the nomogram. RESULTS: The risk factors included in the prediction model were bone mineral density at left femoral neck (LNBMD), hemoglobin (Hb), serum albumin (ALB), postprandial blood glucose (PBG), fatty liver disease (FLD), smoking and tea consumption. The C-index for the risk nomogram was 0.773 in the prediction model, which presented good refinement. The AUC of the risk nomogram at different time points ranged from 0.785 to 0.817, exhibiting good predictive ability and performance. In addition, the DCA showed that the nomogram had a good clinical application value. The nomogram calibration curve indicated that the prediction model was consistent. CONCLUSIONS: Our study provides a novel nomogram and a web calculator that can effectively predict the 7-year incidence risk of osteopenia in Chinese middle-aged and elderly men. It is convenient for clinicians to prevent fragility fractures in the male population.

Lower risk of low bone mineral density in high vitamin E level in older people: A cross-sectional study.

INTRODUCTION: Osteoporosis and osteopenia, together known as low bone mineral density (LBMD), are common problems in the elderly. LBMD may cause fragility fractures in the elderly. The relationship between Vitamin E and LBMD in old Americans is still unclear. In this study, we investigated the relationship between serum Vitamin E levels and LBMD in the elderly. METHODS: We utilized data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 and ultimately included 378 participants aged 50 to 79. Multivariable logistic or linear regression models were applied to examine the associations between serum Vitamin E levels and LBMD, total femur or lumbar spine BMD after adjusting for covariates. RESULTS: After adjusting for all covariates, higher serum Vitamin E levels reduced the risk of LBMD (OR 0.76; 95% CI 0.58-1.00) and were positively associated with total femur BMD (ß: 0.02; 95% CI: 0.01-0.03)， after adjusting for all covariates. In the subgroup analysis, for the BMI normal group (BMI<25), the serum Vitamin E levels were positively associated with the total femur (ß: 0.03; 95% CI: 0.01-0.05) and lumbar spine BMD (ß: 0.04; 95% CI: 0.01-0.07). In the BMI normal group, people with high serum Vitamin E levels have a lower incidence of LBMD (OR:0.43; 95% CI: 0.21-0.88). Though the P for interaction was larger than 0.05. CONCLUSION: This study found serum Vitamin E levels were negatively associated with LBMD in older Americans. Serum Vitamin E levels were positively associated with femur BMD in older Americans.

Surgical Considerations for Osteoporosis, Osteopenia, and Vitamin D Deficiency in Upper Extremity Surgery.

Fragility fractures as a result of osteoporosis, osteopenia, or vitamin D deficiency are some of the most common injuries encountered in orthopedics and require careful consideration when determining the appropriate management and treatment options. A thorough perioperative evaluation can identify causes of low bone mineral density allowing for initiation of appropriate therapy. Surgical treatment of these fractures can be difficult, and techniques should be employed to ensure stable fixation. It is important to understand the potential pitfalls associated with treatment of fragility fractures to prevent avoidable complications. Postoperative management is key to preventing future injuries in this unique patient population.

Opportunistic prediction of osteoporosis in patients with degenerative lumbar diseases: a simplified T12 vertebral bone quality approach.

BACKGROUND: Osteoporosis is one of the risk factors for screw loosening after lumbar fusion. However, the probability of preoperative osteoporosis screening in patients with lumbar degenerative disease is low. Therefore, the aim of this study was to investigate whether a simplified vertebral bone quality (VBQ) score based on T12 T1-MRI could opportunistically predict osteoporosis in patients with degenerative lumbar spine diseases. METHODS: We retrospectively analyzed cases treated for lumbar degenerative diseases at a single institution between August 2021 and June 2022. The patients were divided into three groups by the lowest T-score: osteoporosis group, osteopenia group, and normal bone mineral density (BMD) group. The signal intensity based on the T12 vertebral body divided by the signal intensity of the cerebrospinal fluid was calculated to obtain the simplified VBQ score, as well as the CT-based T12HU value and the traditional L1-4VBQ score. Various statistical analyses were used to compare VBQ, HU and DEXA, and the optimal T12VBQ threshold for predicting osteoporosis was obtained by plotting the receiver operating curve (ROC) analysis. RESULTS: Total of 166 patients were included in this study. There was a statistically significant difference in T12VBQ scores between the three groups (p < 0.001). Pearson correlation showed that there was a moderate correlation between T12VBQ and T-score (r=-0.406, p < 0.001). The AUC value of T12VBQ, which distinguishes between normal and low BMD, was 0.756, and the optimal diagnostic threshold was 2.94. The AUC value of T12VBQ, which distinguishes osteoporosis from non-osteoporosis, was 0.634, and the optimal diagnostic threshold was 3.18. CONCLUSION: T12VBQ can be used as an effective opportunistic screening method for osteoporosis in patients with lumbar degenerative diseases. It can be used as a supplement to the evaluation of DEXA and preoperative evaluation. TRIAL REGISTRATION: retrospectively registered number:1502-009-644; retrospectively registered number date:27 oct 2022.

Three-Year Mortality of Older Hospitalized Patients with Osteosarcopenia: Data from the OsteoSys Study.

Osteosarcopenia, the concurrent presence of sarcopenia and osteopenia/osteoporosis, poses a significant health risk to older adults, yet its impact on clinical outcomes is not fully understood. The aim of this prospective, longitudinal multicentre study was to examine the impact of osteosarcopenia on 3-year mortality and unplanned hospitalizations among 572 older hospitalized patients (mean age 75.1 ± 10.8 years, 78% female). Sarcopenia and low bone mineral density (BMD) were evaluated using Dual Energy X-ray Absorptiometry and the European Working Group on Sarcopenia in Older People (EWGSOP2) and WHO criteria, respectively. Among participants, 76% had low BMD, 9% were sarcopenic, and 8% had osteosarcopenia. Individuals with osteosarcopenia experienced a significantly higher rate of mortality (46%, p < 001) and unplanned hospitalization (86%, p < 001) compared to those without this condition. Moreover, "healthy" subjects-those without sarcopenia or low BMD-showed markedly lower 3-year mortality (9%, p < 001) and less unplanned hospitalization (53%, p < 001). The presence of osteosarcopenia (p = 0.009) increased the 3-year mortality risk by 30% over sarcopenia alone and by 8% over low BMD alone, underscoring the severe health implications of concurrent muscle and bone deterioration. This study highlights the substantial impact of osteosarcopenia on mortality among older adults, emphasizing the need for targeted diagnostic and therapeutic strategies.

Prevalence of Musculoskeletal and Metabolic Disorders in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis.

Introduction: Musculoskeletal disorders could be associated with metabolic disorders that are common after kidney transplantation, which could reduce the quality of life of patients. The aim of this study was to assess the prevalence of both musculoskeletal and metabolic disorders in kidney transplant patients. Methods: MEDLINE, CINAHL, Cochrane Library, EMBASE and Web of Science were searched from their inception up to June 2023. DerSimonian and Laird random-effects method was used to calculate pooled prevalence estimates and their 95% confidence intervals (CIs). Results: 21,879 kidney transplant recipients from 38 studies were analysed. The overall proportion of kidney transplant patients with musculoskeletal disorders was 27.2% (95% CI: 18.4-36.0), with low muscle strength (64.5%; 95% CI: 43.1-81.3) being the most common disorder. Otherwise, the overall proportion of kidney transplant patients with metabolic disorders was 37.6% (95% CI: 21.9-53.2), with hypovitaminosis D (81.8%; 95% CI: 67.2-90.8) being the most prevalent disorder. Conclusion: The most common musculoskeletal disorders were low muscle strength, femoral osteopenia, and low muscle mass. Hypovitaminosis D, hyperparathyroidism, and hyperuricemia were also the most common metabolic disorders. These disorders could be associated with poorer quality of life in kidney transplant recipients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier [CRD42023449171].

Age and sex are excellent predictors of bone complications in patients with type 2 diabetes with no history of osteoporotic fracture or treatment for osteoporosis.

OBJECTIVE: To identify patients with type 2 diabetes mellitus (T2DM) with no history of fracture or osteoporosis treatment who are at risk of bone complications through the assessment of bone quality and quantity. METHODS: Of the outpatients attending our clinic during 2021 to 2022, we retrospectively enrolled 137 (men/women: 85/52, median age: 65 years) consecutive patients aged ≥40 years who had T2DM but no history of fracture or osteoporosis treatment. The lumbar spine and femoral neck bone mineral density and the trabecular bone score were determined using dual-energy X-ray absorptiometry. Independent factors associated with bone disease were identified using logistic regression analysis, and odds ratios (ORs) were calculated. RESULTS: Age and female sex were significantly associated with high ORs for development of bone disease. The integrated risk of bone complications was nearly 40-fold higher in older (≥65 years) women than in younger (<65 years) men. This difference remained after adjustment for the duration of T2DM, body mass index, and HbA1c level. CONCLUSIONS: Older women have the highest risk of osteopenia and osteoporosis among patients with T2DM who have no history of fracture or osteoporosis treatment. These patients should undergo intensive monitoring for bone fragility from an early stage of their disease.

Cutaneous Calcified Mass of Foot in Pseudohypoparathyoidism: Case Report.

Soft tissue calcifications frequently appear on imaging studies, representing a prevalent but non-specific discovery, varying from a local reaction without clear cause to suggesting an underlying systemic condition. Because calcifications like these can arise from various causes, an accurate differential diagnosis is crucial. Differential diagnosis entails a methodical assessment of the patient, encompassing clinical presentation, medical history, radiological and pathological findings, and other pertinent factors. Through scrutiny of the patient's medical and trauma history, we can refine potential causes of calcification to vascular, metabolic, autoimmune, neoplastic, or traumatic origins. Furthermore, routine laboratory assessments, including serum levels of calcium, phosphorus, ionized calcium, vitamin D metabolites, and parathyroid hormone (PTH), aid in identifying metabolic etiologies. We describe a rare occurrence of osteoma cutis in a 15-year-old female patient with a history of pseudohypoparathyroidism (PHP) and Albright's hereditary osteodystrophy (AHO). The patient presented with a painful mass on the lateral side of her left foot. The diagnosis was based on medical history, laboratory tests, and imaging, leading to an excisional biopsy and complete pain relief post-surgery. Understanding such rare occurrences and related conditions is crucial for accurate diagnosis and management.

On the association between dietary oily fish intake and bone mineral density in frequent fish consumers of Amerindian ancestry. The three villages study.

Reports addressing the effects of oily fish intake on bone health are inconsistent. This study shows that consumption of ≥ 5.2 oily fish servings/week (728 g) is associated with lower prevalence of osteopenia/osteoporosis in elderly women of Amerindian ancestry. Results suggest a beneficial effect of oily fish intake in this population. OBJECTIVES: Oily fish is a major dietary source of omega-3 polyunsaturated fatty acids and other nutrients that may have a positive effect on bone health. However, this association is inconsistent and seems to be more evident in certain ethnic groups. We aimed to assess the association between oily fish intake and bone mineral density (BMD) in frequent fish consumers of Amerindian ancestry living in rural Ecuador. METHODS: This study included 399 individuals aged ≥ 60 years living in three neighboring rural villages of coastal Ecuador. Dietary oily fish intake was quantified systematically using validated surveys and BMD was determined by dual-energy x-ray absorptiometry. Ordinal logistic regression models, adjusted for demographics and cardiovascular risk factors, were fitted to assess the independent association between oily fish intake and bone health. RESULTS: Participants had a mean age of 68.8 ± 6.8 years, and 58% were women. The mean intake of oily fish was 8.5 ± 4.7 servings/week, with 308 (77%) reporting high fish intake (≥ 5.2 servings/week [728 g]). Ninety-four (24%) participants had normal BMD T-scores, 149 (37%) had osteopenia, and 156 (39%) had osteoporosis. Ordinal logistic regression models showed no association between high fish intake and bone health in the total population. When men and women were analyzed separately, the association became significant for women only in both unadjusted (OR: 2.52; 95% C.I.: 1.22 - 5.23) and fully-adjusted models (OR: 2.23; 95% C.I.: 1.03 - 4.81). CONCLUSION: Consumption of ≥ 5.2 oily fish servings/week is associated with lower prevalence of osteopenia and osteoporosis in elderly women of Amerindian ancestry.

Incidence of metabolic bone disease in neonates under 32 gestational weeks at the Hospital Universitario de Santander in Colombia. / Incidencia de enfermedad metabólica ósea en neonatos con menos de 32 semanas de gestación en el Hospital Universitario de Santander en Colombia

INTRODUCTION: Metabolic bone disease of premature infants is a rare complication characterized by a lower mineral content in bone tissue. OBJECTIVE: To establish the incidence of metabolic bone disease in premature infants and to determine associated risk factors. MATERIALS AND METHOD: We conducted a descriptive prospective cohort study for one year in all newborns under 32 gestational weeks, or 1,500 g, at the Hospital Universitario de Santander to determine the incidence of metabolic bone disease. We collected demographic data and prenatal histories of the selected patients, and later, we measured serum alkaline phosphatase and serum phosphorus at the third week of birth, having as reference values for diagnosis less than 5.6 mg/dl for the first one and more than 500 UI/L for the second one. We applied statistical tools for data analysis, such as average proportions, dispersion, distribution and association measures, and binomial regression. RESULTS: From a total of 58 patients, 7 had a diagnosis of metabolic bone disease, with an incidence of 12%. The weight was reported as an independent variable for the development of the disease, being significant in children under 1,160 g, as well as prolonged parenteral nutrition for more than 24 days. When performing the multivariate analysis, low weight and short time of parenteral nutrition appeared as risk factors; in the same way, maternal age below 22 years is associated with a higher relative risk, even more than a newborn weight inferior to 1,160 g. CONCLUSION: Establishing an early intervention in patients with metabolic bone disease enhancing risk factors, such as low weight and prolonged parenteral nutrition, is critical to prevent severe complications.

Introducción. La enfermedad metabólica ósea de neonatos prematuros es una complicación poco común que se caracteriza por una disminución del contenido mineral en el hueso. Objetivo. Establecer la incidencia de la enfermedad metabólica ósea en neonatos prematuros y los factores de riesgo asociados. Materiales y métodos. Durante un año, se realizó un estudio prospectivo de cohorte, descriptivo, con todos los neonatos nacidos con menos de 32 semanas de gestación o un peso menor de 1.500 g en el Hospital Universitario de Santander. Se recolectaron datos demográficos y antecedentes prenatales de los pacientes seleccionados. A la tercera semana de nacimiento, se midieron la fosfatasa alcalina y el fósforo sérico, tomando como valores de referencia diagnóstica aquellos inferiores a 5,6 mg/dl para el primero y aquellos mayores de 500 UI/L para la segunda. Para el análisis de la información, se emplearon herramientas estadísticas, como proporciones de promedios, medidas de dispersión, distribución y asociación, y regresión binomial. Resultados. De un total de 58 pacientes, 7 tuvieron diagnóstico de enfermedad metabólica ósea, con una incidencia del 12 %. De las variables estudiadas, el peso se reportó como una variable independiente para el desarrollo de la enfermedad, significativa en aquellos neonatos con peso menor de 1.160 g, al igual que la nutrición parenteral prolongada por más de 24 días. Al hacer el análisis multivariado, La edad materna menor de 22 años representó un riesgo relativo mayor, en comparación con un peso inferior a 1.160 g. Conclusión. Se estableció la importancia de una intervención temprana en pacientes con factores de riesgo para enfermedad metabólica ósea, como bajo peso (menor de 1.160 g) y nutrición parenteral prolongada (mayor de 24 días), con el fin de prevenir complicaciones graves.

Use of data-independent acquisition mass spectrometry to identify an objective serum indicator of the need for osteoporotic therapeutic intervention.

Osteoporosis is characterized by weakened bone microstructure and loss of bone mass. Current diagnostic criteria for osteoporosis are based on the T-score, which is a measure of bone mineral density. However, osteoporotic fragility fractures can occur regardless of the T-score, underscoring the need for additional criteria for the early detection of patients at fracture risk. To identify indicators of reduced bone strength, we performed serum proteomic analysis using data-independent acquisition mass spectrometry with serum samples from two patient groups, one with osteoporosis but no fractures and the other with osteopenia and fragility fractures. Collective evaluation of the results identified six serum proteins that changed to a similar extent in both patient groups compared with controls. Of these, extracellular matrix protein 1 (ECM1), which contributes to bone formation, showed the most significant increase in serum levels in both patient groups. An ELISA-based assay suggested that ECM1 could serve as a serum indicator of the need for therapeutic intervention; however, further prospective studies with a larger sample size are necessary to confirm these results. The present findings may contribute to the provision of early and appropriate therapeutic strategies for patients at risk of osteoporotic fractures. SIGNIFICANCE: This study aimed to identify objective serum indicators of the need for therapeutic intervention in individuals at risk of osteoporotic fracture. Comprehensive proteome analyses of serum collected from patients with osteoporosis but no fractures, patients with osteopenia and fragility fractures, and controls were performed by data-independent acquisition mass spectrometry. Collective evaluation of the proteome analysis data and ELISA-based assays identified serum ECM1 as a potential objective marker of the risk of fragility fractures in patients with osteoporosis or osteopenia. The findings are an important step toward the development of appropriate bone health management methods to improve well-being and maintain quality of life.

Osteoporosis and depression in perimenopausal women: From clinical association to genetic causality.

BACKGROUND: Osteoporosis and major depressive disorder (MDD) represent two significant health challenges globally, particularly among perimenopausal women. This study utilizes NHANES data and Mendelian randomization (MR) analysis to explore the link between them, aiming to provide a basis for intervention strategies for this group. METHODS: The study analyzed NHANES 2007-2018 data using weighted logistic regression in R software to evaluate the link between MDD and osteoporosis risk. Then, a two-sample MR analysis with GWAS summary statistics was performed, mainly using the IVW method. Additional validation included MR Egger, Weighted Median, Mode, and MR-PRESSO methods. RESULTS: The research analysis indicated a significant link between MDD and the risk of osteopenia/osteoporosis. Our analysis revealed a significant positive relationship between MDD and both femoral neck osteoporosis (OR = 6.942 [95 % CI, 1.692-28.485]) and trochanteric osteoporosis (OR = 4.140 [95 % CI, 1.699-10.089]). In analyses related to osteopenia, a significant positive correlation was observed between MDD and both total femoral osteopenia (OR = 3.309 [95 % CI, 1.577-6.942]) and trochanteric osteopenia (OR = 2.467 [95 % CI, 1.004-6.062]). Furthermore, in the MR analysis, genetically predicted MDD was causally associated with an increased risk of osteoporosis via the IVW method (P = 0.013). LIMITATIONS: Our study was limited by potential selection bias due to excluding subjects with missing data, and its applicability was primarily to European and American populations. CONCLUSION: Integrating NHANES and MR analyses, a robust correlation between MDD and osteoporosis was identified, emphasizing the significance of addressing this comorbidity within clinical practice and meriting further investigation.

Plasma serotonin precursors and metabolite are correlated with bone mineral density and bone turnover markers in patients with postmenopausal osteoporosis.

BACKGROUND: Serotonin (5-HT) precursors regulate bone remodeling. This study aims to investigate the correlation of plasma 5-HT precursors and metabolite with bone mineral density (BMD) and bone turnover markers in postmenopausal osteoporosis (PMOP) patients. METHODS: The age, body mass index (BMI), and years since menopause (YSM) were documented for 348 postmenopausal women in normal/osteopenia/osteoporosis (OP) groups, with lumbar spine and femoral neck BMD measured. Serum bone turnover markers (PINP/ß-CTX) and plasma 5-HT, 5-HT precursors (Trp/5-HTP) and metabolite (5-HIAA) were measured by ELISA. OP patients were allocated to high/low expression groups following ROC analysis of 5-HT/Trp/5-HTP/5-HIAA. The relationship of plasma 5-HT/Trp/5-HTP/5-HIAA, BMD, and bone turnover markers with PMOP was analyzed using logistic regression analysis. The correlation of plasma 5-HT/Trp/5-HTP/5-HIAA with BMD and bone turnover markers was analyzed using Pearson's correlation analysis, followed by logistic regression analysis of the relationship between plasma 5-HT/Trp/5-HTP/5-HIAA and BMD, bone turnover markers and PMOP. RESULTS: BMI, YSM, BMD and PINP, and ß-CTX levels differed among groups. Levels of plasma 5-HT precursors/metabolite were increased in OP patients. Individuals with high 5-HT precursors/metabolite levels had low BMD and high PINP/ß-CTX levels. The 5-HT precursors/metabolite negatively-correlated with BMD and positively-correlated with PINP/ß-CTX. BMI, YSM, BMD, and PINP/ß-CTX/Trp/5-HTP/5-HT related to PMOP and were independent risk factors for OP. CONCLUSION: Plasma 5-HT precursors and metabolite negatively-correlate with BMD and positively-correlate with PINP/ß-CTX in PMOP patients. Peripheral 5-HT precursors and metabolite level may be a new direction of treatment of PMOP and bone metabolism-related disorders.

The role of echinacoside-based cross-linker nanoparticles in the treatment of osteoporosis.

Background: Current drugs for treating osteoporosis may lead to toxic side effects. Echinacoside (ECH) is a natural small molecule drug. This study examined and compared the therapeutic effects of cross-linker (CL)-ECH and ECH-free nanoparticles on osteoporosis. Methods: Echinocandin-based CL-ECH nanoparticles were prepared, and the nanoparticle size and drug loading were optimized and characterized by adjusting the ratio. The antioxidant effect of CL-ECH nanoparticles on bone marrow-derived macrophages (BMDMs) was analyzed using flow cytometry, immunofluorescence staining and quantitative real-time polymerase chain reaction (qRT-PCR). Bone marrow stromal cells (BMSCs)-based detection of bone-producing effects was conducted using alkaline phosphatase (ALP), Alizarin Red S (ARS) and qRT-PCR. TRAP, phalloidin staining, and qRT-PCR was performed to detect osteogenesis-inhibiting effect on BMDMs. CL-ECH nanoparticles were applied to treat an ovariectomized (OVX) mouse model at low doses. Results: Compared to ECH, CL-ECH nanoparticles suppressed oxidative stress in BMDMs by promoting NRF-2 nuclear translocation, which inhibited the production of both reactive oxygen species (ROS) and osteoclast production through downregulating NF-κB expression, with limited effect on the osteogenesis of BMSCs. In vivo studies showed that low-dose CL-ECH nanoparticles markedly improved bone trabecular loss compared to ECH administration in the treatment of osteoporosis. Conclusions: The current discoveries provided a solid theoretical foundation for the development of a new generation of anti-bone resorption drugs and antiosteoporosis drugs.

Bone loss after discontinuation of denosumab: the devil is in the details.

A 47-year-old postmenopausal woman with osteoporosis was treated with denosumab, which was discontinued due to side effects. She was therefore transitioned to a yearly intravenous infusion of zoledronic acid. An increase in bone turnover markers together with bone loss at the lumbar spine was observed before the second infusion, suggesting an overshooting of bone resorption due to denosumab discontinuation. On physical examination, the patient was restless and reported having lost about 10 kg since the last visit. A solitary left inferior thyroid nodule was noted on neck palpation. Circulating thyroid hormone levels were elevated, with suppressed thyroid-stimulating hormone. A thyroid scan showed increased uptake in the left inferior nodule with suppression of the remainder of the thyroid gland. A diagnosis of hyperthyroidism due to toxic adenoma was made. The patient was treated with radioactive iodine ablation, with consequent complete normalization of thyroid function. She continued yearly treatment with zoledronic acid. She remained clinically well with no further fractures. Bone turnover markers were appropriately suppressed and bone mineral density increased in the spine and hip. This case illustrates how the overshooting phenomenon following denosumab discontinuation may be compounded by the development of secondary conditions, which can result in suboptimal response to antiresorptive osteoporosis medications.