Metabolic Bone Disorders Research Articles

Transition of care: toward tailored transition of adolescents with osteoporosis and metabolic bone diseases to adult care through an integrated, people-centered, disease-specific health services framework

BackgroundThe Egyptian Academy of Bone and Muscle Health in collaboration with the Egyptian College of Pediatric Rheumatology have identified two indicators to ensure optimum health outcomes among children: one is developmentally and nutritionally appropriate healthcare, and the second is the availability of an effective transition of care model from pediatric care to adult health services. Currently, there is no national guidelines on transition of care for children and adolescents with osteoporosis and metabolic bone disease. To close this gap, this work was carried out to develop the Egyptian guidelines for transition model of care.ResultsThe final recommendation included 12 specific domains. These included the following: targeted population, transition age, transition readiness, patient-targeted care, and disease-specific knowledge, patient education, and optimum model for the transition of care, transition referral, management approach, high quality of care, documentation, and recent service approaches as well as standards and quality indicators. All the overarching principles and most voters agreed with the 12 amended recommendations.ConclusionTransitional care is the term used to describe services that seek to bridge this care gap. Based on the best available data and professional judgment, these consensus-based recommendations guide ways to achieve optimal outcomes in transitional care for adolescents with osteoporosis and metabolic bone disorders. Though focussed on transition of care of bone and muscle health, this article can be the bases for transition services for children with other chronic conditions. This could be used as a blueprint for additional national or internationally healthcare transition policies.

Role of microRNA in Diabetic Osteoporosis.

Diabetic osteoporosis (DOP), a complication associated with diabetes mellitus (DM), is a metabolic bone disorder characterized by a reduction in bone mass per unit volume, impaired bone tissue microarchitecture, heightened bone fragility, and increased susceptibility to fractures. Individuals with diabetes exhibit a significantly greater incidence of osteoporosis and related fractures than those without diabetes. These fractures present a significant challenge in terms of the healing process and can result in severe consequences, including fatalities. MicroRNAs (miRNAs), a class of noncoding RNAs, play a pivotal role in numerous human diseases and are implicated in the pathogenesis of DOP. This review initially elucidates the essential role of miRNAs in the pathogenesis of DOP. Next, we emphasize the potential significance of miRNAs as valuable biomarkers for diagnosing DOP and predicting DOP-related fractures. Furthermore, we explore the involvement of miRNAs in managing DOP through various pathways, including conventional pharmaceutical interventions and exercise therapy. Importantly, miRNAs exhibit potential as targeted therapeutic agents for effectively treating DOP. Finally, we highlight the use of novel materials and exosomes for miRNA delivery, which has significant advantages in the treatment of DOP and overcomes the limitations associated with miRNA delivery.

A case study of hypophosphatasia: An underdiagnosed bone disorder characterized by low alkaline phosphatase.

Hypophosphatasia (HPP) is a rare genetic metabolic bone disorder that is underdiagnosed. Although there are many forms of this disease, based on age of onset, symptoms, and severity, HPP is characterized by low serum alkaline phosphatase levels, bone fractures, and dental complications. Diagnosis of HPP is made from clinical, laboratory, and radiologic findings. Genetic testing for an ALPL gene variant responsible for causing HPP confirms a molecular diagnosis. Distinguishing HPP from other more common bone disorders, such as osteoporosis, is important as the treatment for these diseases differs greatly. Although there is no known cure for HPP, treatment should be holistic and multidisciplinary.

The role of fibroblast growth factor 23 in the assessment of complications in chronic kidney disease

Secondary hyperparathyroidism is an early-stage complication of CKD (Chronic Kidney Disease). It is associated with disorders in bone metabolism, calcium deposition in vessels and organs, significantly increased risk of cardiovascular disease, and death. In recent years, an increasingly important role has been attributed to fibroblast growth factor (FGF 23) in regulating calcium/phosphate homeostasis, hyperparathyroidism, and its relation to vascular calcification, and left ventricular hypertrophy. This study conducted with 110 patients with varying degrees of renal insufficiency shows an increase in FGF23 and PTH when there is a decrease in glomerular filtration, a direct dependency between the levels of phosphate and PTH and FGF23, and a lack of such between calcium and PTH and FGF23. Of particular interest is the fact that patients treated with Calcitriol and Paricalcitol show a reduction in PTH levels, yet maintain high levels of FGF23. PTH serves as a marker for the rate of bone remodeling in patients, where elevated levels indicate renal bone disease. The analysis of FGF 23 is crucial in evaluating cardiovascular risk.

Acquired hypophosphatemic osteomalacia: case series from a Peruvian referral center (1999-2023).

Acquired hypophosphatemic osteomalacia (AHO) is a rare metabolic bone disorder characterized by hypophosphatemia and impaired bone mineralization. Tumor-induced osteomalacia (TIO) is the most common cause of AHO, caused by phosphaturic tumors that overproduce fibroblast growth factor 23 (FGF-23). To present the clinical characteristics, diagnostic challenges, and outcomes of seven cases of AHO in Peruvian patients between 1999 and 2023. A retrospective review of seven patients diagnosed with AHO was conducted. Clinical data, including diagnostic procedures, treatments, and outcomes, were collected. Seven cases of AHO were reviewed. In case one, osteomalacia did not improve despite supraphysiological doses of vitamin D (ergocalciferol/cholecalciferol), and no tumor was detected with available tests, resulting in the patient's death. Cases two and three involved tumors located in the right leg and right hemithorax, respectively, with symptom resolution following total resection. In cases four, five, and seven, exhaustive exams failed to locate tumors. Cases four, six, and seven showed elevated FGF-23 levels, while case five had inappropriately normal FGF-23 levels. Case seven was the first patient in Peru to receive burosumab treatment. In case six, a tumor in the head of the femur was identified, but the patient opted for nonsurgical management. The diagnosis of AHO is challenging, requiring a high index of clinical suspicion and biochemical confirmation. TIO is the most common cause of AHO, emphasizing the importance of locating the phosphaturic tumor. However, in some cases, the tumor remains elusive despite exhaustive diagnostic workups. This is particularly challenging in developing countries like Peru, where resources are limited.

Vitamin D Status in Supplemented Hemodialysis Patients

Introduction: Chronic kidney disease (CKD) causes decreased activity of the enzyme 1-alpha-hydroxylase and calcitriol deficiency with mineral and bone metabolism disorders or secondary hyperparathyroidism. Anticipation of the occurrence of these complications implies the systematic supplementation of all hemodialysis patients, with monitoring of biological parameters. It is in this context that this study was carried out, the general objective of which was to establish the profile of vitamin D concentration in hemodialysis and Ivorian public sector supplemented patients in Abidjan. Patients and Methods: In a cross-sectional study conducted from September to December 2022, we included 89 patients with end-stage CKD treated with hemodialysis at the CNPTIR in Cocody. The collection of epidemio-clinical data was done on the basis of a questionnaire on the one hand and the patients' medical records on the other. The vitamin D concentration was determined by the ELFA immunoassay method on mini Vidas (BIOMERIEUX). Results: The mean age of the patients was 45 ± 13 and 65.17% of them were men. 55.06% of the patients had been treated with dialysis for at least 5 years. 48.31% of the patients had regular supplementation treatment. Of the two types of vitamin D supplementation, 94.38% of the study population was supplemented with cholecalciferol compared to 18% for alfacalcidol with 12% of patients included, using both types. From a biological point of view, it appears that the average concentration of vitamin D in the patients was 26.9 ng/mL, and only 16% have a concentration of less than 20 mg/mL, corresponding to an deficiency vitamin D status. Conclusion: At the end of this cross-sectional study, it emerged that the average in adult hemodialysis subjects followed at the CNPTIR in Cocody had an insufficient vitamin D status. And 37% of the study population with normal vitamin D status. However, these results could be improved by better accessibility to the products, and regular compliance with supplementation.

Unveiling the metabolic challenges in pulmonary arterial hypertension: Insights into thyroid, glycemic, lipid, and bone disorders

This study aimed to evaluate the prevalence of thyroid, glycemic, lipid and metabolic bone disorders among adult patients with pulmonary arterial hypertension (PAH). MethodsThis was an observational cross-sectional clinical study with patients with PAH, matched by sex and age with a control group without PAH. All individuals were enrolled into a clinical assessment, metabolic workup, thyroid ultrasound, and bone densitometry protocol. ResultsThe PAH group included 35 participants (34 females, 46 ± 15.5 years), and the control group, 40 (39 females, 41.8 ± 13.1 years). There was no difference in body mass index (BMI) between PAH and control group (27.5 ± 5.9 and 26.9 ± 4.3 kg/m2, respectively, p = 0.63; 95 % CI: −1.8, 2.94), neither in physical activity time per week (60.3 ± 103.3 and 98.9 ± 137.6, respectively, p = 0.17; 95 % CI: −95.23, 18.06). Although there was no difference in the prevalence of insulin resistance between the PAH (51.4 %) and the control group (47.5 %), p = 0.74, patients with PAH had a higher median of glycated hemoglobin (A1c) than the control group (6.1 % and 5.57 %, respectively, p = 0.006; 95 % CI: −0.14, 1.22). PAH group presented lower mean total cholesterol (170.46 ± 35.51 mg/dL) and median LDL-cholesterol [105 (83–129) mg/dL, median (P25–P75)] levels than the control group [192.1 ± 34.44 mg/dL, p = 0.009; 95 % CI = −37.76, 5.52 and 121.6 (97–145) mg/dL, p = 0.012; 95 % CI: −34.08, 0.77, respectively]. It was found a higher prevalence of hypothyroidism (22.9 %) in PAH group than in control group (2.5 %), p = 0.007. We found hyperparathyroidism (HPT) among 8 patients of PAH group (23 %), but none in the control group. Considering bone mineral density disorders, 12 patients from PAH group presented low bone mass, osteopenia, or osteoporosis (34 %), and 8 individuals in the control group (20 %), p = 0.032, which represented a 2.13 higher relative risk for those conditions for the former group. The patients with HPT presented a higher creatinine level (0.98 ± 0.12 mg/dL) than the PAH patients with normal parathyroid hormone (0.76 ± 0.14 mg/dL), p = 0.0004; 95 % CI: 0.12, 0.33. The PAH group also presented lower total hip (-0.15 ± 1.25) and femoral neck (−0.14 ± 1.07) bone mineral density (BMD) Z-scores than the control group (0.50 ± 1.13, p = 0.021; 95 % CI: −0.18, −0.027 and 0.35 ± 0.94, p = 0.038; 95 % CI: −0.16, −0.01, respectively). ConclusionIn this cohort, the findings of higher A1c levels, hypothyroidism prevalence, lower LDL and total cholesterol levels, and a higher prevalence of hyperparathyroidism, as well as lower total hip and femoral neck BMD Z-scores in the PAH group, compared to the control group and highlighting the dysregulation of various metabolic pathways in patients with HAP, suggesting the need for targeted interventions to enhance patient care. Additionally, they underscore the importance of gaining a deeper understanding of the mechanisms driving these changes and their potential pathophysiological connections to the disease.

Diagnostic and New Therapeutic Approaches to Two Challenging Pediatric Metabolic Bone Disorders: Hypophosphatasia and X-linked Hypophosphatemic Rickets.

The diagnosis and management of metabolic bone disease among children can be challenging. This difficulty could be due to many factors, including limited awareness of these rare conditions, the complex pathophysiology of calcium and phosphate homeostasis, the overlapping phenotype with more common disorders (such as rickets), and the lack of specific treatments for these rare disorders. As a result, affected individuals could experience delayed diagnosis or misdiagnosis, leading to improper management. In this review, we describe the challenges facing diagnostic and therapeutic approaches to two metabolic bone disorders (MBD) among children: hypophosphatasia (HPP) and X-linked hypophosphatemia (XLH). We focus on explaining the pathophysiological processes that conceptually underpin novel therapeutic approaches, as well as these conditions' clinical or radiological similarity to nutritional rickets. Particularly in areas with limited sun exposure and among patients not supplementing vitamin D, nutritional rickets are still more common than HPP and XLH, and pediatricians and primary physicians frequently encounter this disorder in their practices. More recently, our understanding of these disorders has significantly improved, leading to the development of novel therapies. Asfotas alfa, a recombinant, human- tissue, nonspecific alkaline phosphatase, improved the survival of patients with HPP. Burosumab, a human monoclonal anti-FGF23 antibody, was recently approved as a specific therapy for XLH. We also highlight the current evidence on these two specific therapies' safety and effectiveness, though long-term data are still needed. Both HPP and XLH are multisystemic disorders that should be managed by multidisciplinary teams. Finally, recognizing these conditions in early stages will enable affected children and young adults to benefit from newly introduced, specific therapies.

The Biphasic Activity of Auricularia Auricula-Judae Extract on Bone Homeostasis Through Inhibition of Osteoclastogenesis and Modulation of Osteogenic Activity.

Osteoporosis arises from the disturbance of bone homeostasis, a process regulated by osteoblasts and osteoclasts. The treatment and prevention of bone metabolic disorders resulting from an imbalance in bone homeostasis require the use of agents that effectively promote both bone formation and anti-resorptive effects. Therefore, an investigation was carried out to determine the potential of the edible mushroom Auricularia auricula-judae in modulating bone remodeling by inhibiting RANKL-induced osteoclastogenesis and enhancing BMP-2-stimulated osteoblast differentiation. Moreover, this study assessed the mode of action of the Auricularia auricula-judae extracts. The staining of tartrate-resistant acid phosphatase (TRAP), a marker for osteoclast activity, demonstrated that Auricularia auricula-judae water extract (AAJWE) inhibited the formation of multinucleated osteoclasts while exhibiting no cytotoxic effects. The study demonstrated that AAJWE reduced RANKL-induced osteoclast differentiation by inhibiting c-Fos/NFATc1 through the inhibition of ERK and JNK phosphorylation during the RANKL-induced osteoclast differentiation. Moreover, AAJWE exhibited a dose-dependent induction of ALP expression in the presence of BMP-2 during osteoblast differentiation. The AAJWE strengthened BMP-2-induced osteogenesis through the activation of Runx2 and Smad phosphorylation. Therefore, AAJWE emerges as a promising candidate for both prevention and therapy owing to its biphasic effect, which aids in the preservation of bone homeostasis.

Development of Minodronic Acid-Loaded Dissolving Microneedles for Enhanced Osteoporosis Therapy: Influence of Drug Loading on the Bioavailability of Minodronic Acid.

Osteoporosis is a metabolic bone disorder with impaired bone microstructure and increased bone fractures, seriously affecting the quality of life of patients. Among various bisphosphonates prescribed for managing osteoporosis, minodronic acid (MA) is the most potent inhibitor of bone context resorption. However, oral MA tablet is the only commercialized dosage form that has extremely low bioavailability, severe adverse reactions, and poor patient compliance. To tackle these issues, we developed MA-loaded dissolving microneedles (MA-MNs) with significantly improved bioavailability for osteoporosis therapy. We investigated the influence of drug loading on the physicochemical properties, transdermal permeation behavior, and pharmacokinetics of MA-MNs. The drug loading of MA-MNs exerted almost no effect on their morphology, mechanical property, and skin insertion ability, but it compromised the transdermal permeability and bioavailability of MA-MNs. Compared with oral MA, MA-MNs with the lowest drug loading (224.9μg/patch) showed a 9-fold and 25.8-fold increase in peak concentration and bioavailability, respectively. This may be ascribed to the reason that the increased drug loading can generate higher burst release, higher drug residual rate, and drug supersaturation effect in skin tissues, eventually limiting drug absorption into the systemic circulation. Moreover, MA-MNs prolonged the half-life of MA and provided more steady plasma drug concentrations than intravenously injected MA, which helps to reduce dosing frequency and side effects. Therefore, dissolving MNs with optimized drug loading provides a promising alternative for bisphosphonate drug delivery.

A Review of Celiac Disease and Its Implications on Fertility and Pregnancy.

Celiac disease is a systemic autoimmune disorder triggered by dietary gluten ingestion. The classic clinical presentation is characterized by diarrhea with malabsorption and weight loss; however, the spectrum of possible initial symptoms is broad. Affected individuals may be asymptomatic or may suffer from extraintestinal manifestations that can include metabolic bone disorders, thyroid dysfunction, neurologic manifestations, amenorrhea, or impaired fertility. Several studies have demonstrated an association between celiac disease and infertility and worsened pregnancy outcomes. Numerous possible mechanisms through which celiac disease could be associated with women's fertility have been proposed in the literature.

In-silico analysis predicts disruption of normal angiogenesis as a causative factor in osteoporosis pathogenesis

Angiogenesis-osteogenesis coupling is critical for proper functioning and maintaining the health of bones. Any disruption in this coupling, associated with aging and disease, might lead to loss of bone mass. Osteoporosis (OP) is a debilitating bone metabolic disorder that affects the microarchitecture of bones, gradually leading to fracture. Computational analysis revealed that normal angiogenesis is disrupted during the progression of OP, especially postmenopausal osteoporosis (PMOP). The genes associated with OP and PMOP were retrieved from the DisGeNET database. Hub gene analysis and molecular pathway enrichment were performed via the Cytoscape plugins STRING, MCODE, CytoHubba, ClueGO and the web-based tool Enrichr. Twenty-eight (28) hub genes were identified, eight of which were transcription factors (HIF1A, JUN, TP53, ESR1, MYC, PPARG, RUNX2 and SOX9). Analysis of SNPs associated with hub genes via the gnomAD, I-Mutant2.0, MUpro, ConSurf and COACH servers revealed the substitution F201L in IL6 as the most deleterious. The IL6 protein was modeled in the SWISS-MODEL server and the substitution was analyzed via the YASARA FoldX plugin. A positive ΔΔG (1.936) of the F201L mutant indicates that the mutated structure is less stable than the wild-type structure is. Thirteen hub genes, including IL6 and the enriched molecular pathways were found to be profoundly involved in angiogenesis/endothelial function and immune signaling. Mechanical loading of bones through weight-bearing exercises can activate osteoblasts via mechanotransduction leading to increased bone formation. The present study suggests proper mechanical loading of bone as a preventive strategy for PMOP, by which angiogenesis and the immune status of the bone can be maintained. This in silico analysis could be used to understand the molecular etiology of OP and to develop novel therapeutic approaches.

7336 Decades In The Dark: The Long Road To Diagnosing And Treating Hypophosphatasia

Abstract Disclosure: V.A. Mendpara: None. G. Madrigal Loria: None. L.Z. Khan: None. Background: Hypophosphatasia (HPP) is a rare bone disorder that results from deficient activity of the tissue non-specific isoenzyme alkaline phosphatase (ALP).[1] This case highlights a patient whose diagnosis of this treatable genetic condition was significantly delayed for almost two decades, despite receiving care at a prominent academic institution. The patient's persistently low ALP levels in routine lab tests were overlooked by multiple clinicians, leading to a delay in her care and eventual treatment. Case presentation: A 61-year-old Caucasian woman presented at the endocrinology clinic with complaints of severe fatigue, generalized pain, multiple childhood fractures, and ongoing dental issues. The rheumatology clinic to which she was referred for polyarthralgia diagnosed her with Hypophosphatasia (HPP) after noting chronically low alkaline phosphatase (ALP) levels from her previous charts ranging from 15 to 24 U/L (normal range: 34 to 123 U/L) over two decades. Her serum calcium, parathyroid hormone (PTH), and 25-hydroxy vitamin D levels were within normal ranges. A DEXA scan revealed normal bone density, effectively ruling out osteoporosis. Further investigation showed elevated Vitamin B6 levels at 219.6 nmol/L (normal range: 20.0 to 125.0 nmol/L), raising suspicion for HPP. The patient's family history provided additional insight, with her mother having a history of short stature and fractures and her son experiencing premature tooth loss at the age of 2. A genetic evaluation identified a heterozygous pathogenic variant in the ALPL gene (c.881A>C, p.Asp294Ala), confirming the diagnosis of autosomal dominant HPP. Initiating treatment with Asfotase alfa, a medication targeting HPP, resulted in a marked improvement in the patient's symptoms. Discussion: This case shows the diagnostic complexities of HPP, stressing the significance of actively screening for this condition via ALP levels in routine laboratory testing or during osteoporosis evaluations. The diagnostic process is critical to distinguish HPP from primary osteoporosis, as treatment and potential risks differ significantly. Inadvertent use of bisphosphonates can worsen hypomineralization and lead to atypical femoral fractures in HPP patients. Asfotase alfa enzyme replacement therapy, available since 2015, offers a targeted approach by replacing the enzyme defect, thereby mitigating symptoms. Heightened awareness among healthcare providers of HPP in adults holds the potential to enhance diagnosis rates and facilitate improved treatment outcomes for this highly treatable condition.[1] Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, Eighth Edition. ASBMR. Presentation: 6/2/2024

Targeting osteoblastic 11β-HSD1 to combat high-fat diet-induced bone loss and obesity

Excessive glucocorticoid (GC) action is linked to various metabolic disorders. Recent findings suggest that disrupting skeletal GC signaling prevents bone loss and alleviates metabolic disorders in high-fat diet (HFD)-fed obese mice, underpinning the neglected contribution of skeletal GC action to obesity and related bone loss. Here, we show that the elevated expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), the enzyme driving local GC activation, and GC signaling in osteoblasts, are associated with bone loss and obesity in HFD-fed male mice. Osteoblast-specific 11β-HSD1 knockout male mice exhibit resistance to HFD-induced bone loss and metabolic disorders. Mechanistically, elevated 11β-HSD1 restrains glucose uptake and osteogenic activity in osteoblast. Pharmacologically inhibiting osteoblastic 11β-HSD1 by using bone-targeted 11β-HSD1 inhibitor markedly promotes bone formation, ameliorates glucose handling and mitigated obesity in HFD-fed male mice. Taken together, our study demonstrates that osteoblastic 11β-HSD1 directly contributes to HFD-induced bone loss, glucose handling impairment and obesity.

Herbal medicine Ninjinyoeito inhibits RANKL-induced osteoclast differentiation and bone resorption activity by regulating NF-κB and MAPK pathway

ObjectivesOsteoporosis is a systemic bone metabolism disorder characterized by decreased bone mass and strength. Osteoclasts (OCs) are giant multinucleated cells that regulate bone homeostasis by degrading bone matrix. Excessive OC differentiation and activity can lead to serious bone metabolic disorders including osteoporosis. Current treatments, including antiresorptive drugs, exert considerable adverse effects, including jaw osteonecrosis. Herbal medicines, such as Ninjinyoeito (NYT), may also offer efficacy, but with fewer adverse effects. In this study, we investigated NYT's effects on osteoclastogenesis. MethodsTartrate-resistant acid phosphatase (TRAP) staining and bone resorption assays were performed to examine NYT's effects on OC differentiation and function. OC-related gene expression at mRNA and protein levels was investigated to confirm NYT's inhibitory action against osteoclastogenesis. We also demonstrated involvement of signaling pathways mediated by IκBα and mitogen-activated protein kinases (MAPK) [extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38] and showed nuclear translocation of nuclear factor of activated T-cell cytoplasmic 1 (NFATc1) and nuclear factor kappa B (NF-κB) p65 during osteoclastogenesis. ResultsTRAP staining and bone resorption assays confirmed that NYT significantly inhibited OC differentiation and function. Western blot and RT-PCR results showed that NYT ameliorated osteoclastogenesis by suppressing mRNA and protein level expression of OC-related genes. Moreover, blots and immunocytochemistry (ICC) data clarified that NYT abrogates signaling pathways mediated by IκBα and MAPK (ERK, JNK, p38), and demonstrated nuclear translocation of NFATc1 and NF-κB p65 during OC differentiation. ConclusionsThese findings suggest NYT is an alternative therapeutic candidate for treating osteoporosis.

Bone Marrow and Metabolic Bone Disease.

The bone marrow represents one of the largest organs in the body, with a relevant metabolic role that continues to be investigated. Numerous studies have focused on marrow adipose tissue (MAT). Evidence indicates that the bone marrow adipocytes do not only work as storage tissue but also consist of endocrine and paracrine cells, with the potential to contribute to local and systemic metabolism. MAT plays a role in bone health through its interaction with the other components of bone. Many metabolic disorders (osteoporosis, obesity, diabetes) have a complex and still not well-established or understood relationship with bone health. This article surveys the literature on the relationship of bone marrow and metabolic disorders, and how it is being studied using imaging techniques, with a special focus on bone health.

Computationally derived endosteal strain and strain gradients correlate with increased bone formation in an axially loaded murine tibia model

Osteoporosis is a common metabolic bone disorder characterized by low bone mass and microstructural degradation of bone tissue due to a derailed bone remodeling process. A deeper understanding of the mechanobiological phenomena that modulate the bone remodeling response to mechanical loading in a healthy bone is crucial to develop treatments. Rodent models have provided invaluable insight into the mechanobiological mechanisms regulating bone adaptation in response to dynamic mechanic stimuli. This study sheds light on these aspects by means of assessing the mechanical environment of the cortical and cancellous tissue to in vivo dynamic compressive loading within the mouse tibia using microCT-based finite element model in combination with diaphyseal strain gauge measures. Additionally, this work describes the relation between the mid-diaphyseal strains and strain gradients from the finite element analysis and bone formation measures from time-lapse in vivo tibial loading with a fluorochrome-derived histomorphometry analysis. The mouse tibial loading model demonstrated that cancellous strains were lower than those in the midshaft cortical bone. Sensitivity analyses demonstrated that the material property of cortical bone was the most significant model parameter. The computationally-modeled strains and strain gradients correlated significantly to the histologically-measured bone formation thickness at the mid-diaphyseal cross-section of the mouse tibia.

Bone-A-Fide Breakthrough: Machine Learning Cracks the Code on Osteoporosis Treatment Using the Irish Hip Fracture Database

Abstract Background Osteoporosis is a metabolic bone disorder characterised by decreased bone mineral density and mass. Due to its asymptomatic nature, it often remains undiagnosed and untreated until a fracture occurs. Traditionally, treatment decisions for osteoporosis are based on clinical appropriateness while balancing the treatment's risks and benefits. Machine learning (ML) is revolutionising healthcare domains through pattern recognition of previously “unseen” observations. Presently, its application in osteoporosis is limited to early diagnosis. More research is needed to examine its role in guiding osteoporosis treatment. This study aims to identify new predictive attributes for osteoporosis treatment using ML techniques on data from the Irish Hip Fracture Database (IHFD). Methods Datasets from January to March 2023 in University Hospital Waterford were sourced from the IHFD. Osteoporosis treatment decisions were obtained from discharge letters. Preliminary data cleaning was performed in Excel with zero-variance and near-zero predictor. Attributes excluded. The dataset was entered into the WEKA 3.8.6 environment for ML processing. Results The initial dataset containing 141 instances and 32 attributes was refined using the Correlation Feature Selection and Ranker Search Method, identifying key osteoporosis treatment predictors. The highest correlation attributes are pre-fracture total score, pre-fracture indoor score, and age. Moderately positive correlations are discharge destination, pre-fracture outdoor and shopping score, ASA grade, Length-of-stay, admission code, Admission 4AT score, Frailty scale, and fracture type. The implemented J48 Tree ML-trained model revealed Correctly Classified Instances and Incorrectly Classified Instances of 98.24% and 1.7%, respectively, indicating a high prediction accuracy rate. Conclusion This study demonstrates the potential of ML in enhancing osteoporosis treatment decision-making by leveraging datasets from the IHFD. Integrating ML algorithms with traditional approaches can provide a comprehensive, nuanced and personal approach to osteoporosis treatment and patient care. The study opens avenues for future research in applying big data and advanced analytics in healthcare, underscoring the evolving landscape of medical decision-making.

Elevations of N-Terminal Mid-Fragment of Osteocalcin and Cystatin C Levels are Associated with Disorders of Glycolipid Metabolism and Abnormal Bone Metabolism in Patients with Type 2 Diabetes Mellitus Complicated with Osteoporosis.

Type 2 diabetes mellitus (T2DM) patients always develop osteoporosis (OP). We examined correlations of N-terminal mid-fragment of osteocalcin (N-MID) and cystatin C (Cys C) levels with glycolipid metabolism, bone metabolism markers, and bone mineral density (BMD) in elderly T2DM-OP patients. Grouping was performed as per whether T2DM patients developed OP (OP group) or not (N-OP group). N-MID and Cys C were measured using enzyme-linked immunosorbent assay, with correlations with glycolipid metabolism, bone metabolism indicators, and BMD analyzed using Pearson's correlation coefficient. Elderly T2DM-OP patients showed elevated disease duration, age, body mass index, glycated hemoglobin (HbA1c), Homer's insulin resistance (HOMA-IR), total cholesterol (TC), beta-carboxy-terminal crosslinked telopeptide of type 1 collagen (β-CTX), tartrate-resistant acid phosphatase 5b (TRACP-5b), N-MID and Cys C levels, and reduced high-density lipoprotein cholesterol (HDL-C), bone alkaline phosphatase (B-ALP), aminoterminal propeptide of type I procollagen (PINP), carboxyterminal propeptide of type I procollagen (PICP), BMD, and calcium supplementation. N-MID and Cys C were positively correlated with HbA1c, HOMA-IR, TC, β-CTX, and TRACP-5b and negatively with HDL-C, B-ALP, PINP, PICP, and BMD in elderly T2DM-OP patients. Conclusively, the abnormal elevations of serum N-MID and Cys C were associated with glycolipid metabolism disorder, abnormal bone metabolism, and decreased BMD in elderly T2DM-OP patients.

Treatment of glucocorticoid-induced osteoporosis with concurrent denosumab and romosozumab: a case report.

Osteoporosis is a metabolic bone disorder for which treatment options include antiresorptive therapies (e.g., bisphosphonates, denosumab); anabolics (e.g., teriparatide, abaloparatide); and dual mechanisms (e.g., romosozumab). Management of osteoporosis with concurrent antiresorptive and anabolic agents may be superior to monotherapy, as demonstrated in the DATA trial with the combination of denosumab and teriparatide. However, there is limited experience with the combination of denosumab and romosozumab, which may be an alternative antiresorptive/anabolic regimen for individuals who are not candidates for PTH receptor agonists. In this case, we present a young man with glucocorticoid-induced osteoporosis who could not tolerate a daily injectable anabolic and who experienced improvement in bone mineral density with concurrent denosumab and off-label romosozumab administration.