KLF transcription factors in bone diseases.

Krüppel-like factors (KLFs) are crucial in the development of bone disease. They are a family of zinc finger transcription factors that are unusual in containing three highly conserved zinc finger structural domains interacting with DNA. It has been discovered that it engages in various cell functions, including proliferation, apoptosis, autophagy, stemness, invasion and migration, and is crucial for the development of human tissues. In recent years, the role of KLFs in bone physiology and pathology has received adequate attention. In addition to regulating the normal growth and development of the musculoskeletal system, KLFs participate in the pathological process of the bones and joints and are intimately linked to several skeletal illnesses, such as osteoarthritis (OA), rheumatoid arthritis (RA), osteoporosis (OP) and osteosarcoma (OS). Consequently, targeting KLFs has emerged as a promising therapeutic approach for an array of bone disorders. In this review, we summarize the current literature on the importance of KLFs in the emergence and regulation of bone illnesses, with a particular emphasis on the pertinent mechanisms by which KLFs regulate skeletal diseases. We also discuss the need for KLFs-based medication-targeted treatment. These endeavours offer new perspectives on the use of KLFs in bone disorders and provide prognostic biomarkers, therapeutic targets and possible drug candidates for bone diseases.

Inhibition of receptor activator of nuclear factor kappa-B ligand-mediated osteoclast differentiation and bone resorption by Gryllus bimaculatus extract: An in vitro study.

Excessive bone-resorbing osteoclast activity during bone remodeling is a major feature of bone diseases, such as osteoporosis. Therefore, the inhibition of osteoclast formation and bone resorption can be an effective therapeutic target for various bone diseases. Gryllus biomaculatus (GB) has recently been approved as an alternative food source because of its high nutritional value and environmental sustainability. Traditionally, GB has been known to have various pharmacological properties, including antipyretic and blood pressure-lowering activity, and it has recently been reported to have various biological activities, including protective effects against inflammation, oxidative stress, insulin resistance, and alcohol-induced liver injury. However, the effect of GB on osteoclast differentiation and bone metabolism has not yet been demonstrated. In this study, we confirmed the inhibitory effect of GB extract (GBE) on the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation. To determine the effect of GBE on RANKL-induced osteoclast differentiation and function, we performed TRAP and F-actin staining, as well as a bone-resorbing assay. The intracellular mechanisms of GBE responsible for the regulation of osteoclastogenesis were revealed by Western blot analysis and quantitative real-time polymerase chain reaction. We investigated the relationship between GBE and expression of osteoclast-specific molecules to further elucidate the underlying mechanisms. It was found that GBE significantly suppressed osteoclastogenesis by decreasing the phosphorylation of Akt, p38, JNK, and ERK, as well as Btk-PLCγ2 signaling, in pathways involved in early osteoclastogenesis as well as through the subsequent suppression of c-Fos, NFATc1, and osteoclastogenesis-specific marker genes. Additionally, GBE inhibited the formation of F-actin ring-positive osteoclasts and bone resorption activity of mature osteoclasts. Our findings suggest that GBE is a potential functional food and therapeutic candidate for bone diseases involving osteoclasts.

Risk of fractures and use of bisphosphonates in adult patients with immune thrombocytopenia-A nationwide population-based study.

Corticosteroids remain the first-line treatment of immune thrombocytopenia (ITP), but increase the risk of osteoporosis and fractures. Bisphosphonates are used for the treatment of osteoporosis, but their usage among patients with ITP has not been systemically described. We investigated the risk of fractures and the use of bisphosphonates in adult patients with primary (pITP) and secondary ITP (sITP) compared with matched comparators in a nationwide registry-based cohort study. We identified 4030 patients with pITP (median age 60 years [IQR, 40-74]), 550 with sITP (median age 59 years [IQR, 43-74]) and 182 939 age-sex-matched general population comparators. All individuals were followed for incident fractures. Bisphosphonate use was estimated for calendar-years and in temporal relation to the ITP diagnosis. Adjusted cause-specific hazard ratio (csHR) for any fracture was 1.37 (95% confidence interval [CI] 1.23; 1.54) for pITP and 1.54 (1.17; 2.03) for sITP. The first-year csHR was 1.82 (1.39; 2.40) for pITP and 2.78 (1.58; 4.91) for sITP. Bisphosphonate use over calendar-years and in the early years following ITP diagnosis was higher among patients with ITP diagnosis compared with the general population. In conclusion, the risk of fractures and the use of bisphosphonates are higher in patients with ITP compared with the general population.

Radiomorphometric indices of the mandible as indicators of decreased bone mineral density and osteoporosis - meta-analysis and systematic review.

This review aims to evaluate the accuracy of various mandibular radiomorphometric indices in comparison with DEXA BMD measurements in the diagnosis of osteopenia and osteoporosis based on a meta-analysis of the sensitivity and specificity of the indices. PRISMA statement was followed. The materials for analysis were collected in August 2023 by searching three databases: PubMed Central, Web of Science, and Scopus. The selection of studies consisted of three selection stages, and 64 articles were finally obtained. Quality assessment was performed with the QUADAS-2 tool, and the general methodological quality of retrieved studies was low. Statistical analysis was performed based on 2 × 2 tables and estimated sensitivity and specificity were obtained using SROC curves. The most used indices were MCI, MCW and PMI. The best results in detecting reduced BMD obtained for MCW ≤ 3 mm, estimated sensitivity and specificity were 0.712 (95% CI, 0.477-0.870) and 0.804 (95% CI, 0.589-0.921), respectively. The most prone to the risk of bias is the MCI due to the examiner's subjectivism. Radiomorphometric indices of the mandible can be useful as a screening tool to identify patients with low BMD, but should not be used as a diagnostic method. Further research needs to focus on analysing the ability of the indices to detect osteoporosis and also in combination the indices with clinical parameters.

Current and Developing Pharmacologic Agents for Improving Skeletal Health in Adults with Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a genetic disorder characterized by increased bone fragility largely caused by defects in structure, synthesis, or post-translational processing of type I collagen. Drugs currently used to improve skeletal health in OI were initially developed to treat osteoporosis and clinical trials are ongoing to study their effectiveness in OI adults. Additionally, novel bone-protective agents are in preclinical studies and various phases of OI clinical trials. This review summarizes current knowledge on available pharmacologic agents and current drug trials involving OI participants. A PubMed online database search of all study types published in the English language using the terms "osteogenesis imperfecta," "OI," and "brittle bone disease" was performed in August 2022. Articles screened were restricted to adults. A ClinicalTrials.gov database search of all studies involving "osteogenesis imperfecta" was performed in August 2023. Although clinical trial data are limited, bisphosphonates and teriparatide may be useful in improving bone mineral density. As of yet, no clinical trials are available that adequately evaluate the usefulness of current therapies in reducing fracture risk. Several therapeutics, including teriparatide, setrusumab, anti-TGF-ß antibodies, and allogeneic stem cells, are being studied in clinical trials. Preclinical studies involving Dickkopf-1 antagonists present promising data in non-OI bone disease, and could be useful in OI. Research is ongoing to improve therapeutic options for adults with OI and clinical trials involving gene-editing may be possible in the coming decade.

Skeletal ciliopathy: pathogenesis and related signaling pathways.

Cilia are tiny organelles with conserved structures and components in eukaryotic cells. Ciliopathy is a set of diseases resulting from cilium dysfunction classified into first-order and second-order ciliopathy. With the advancement of clinical diagnosis and radiography, numerous skeletal phenotypes, including polydactyly, short limbs, short ribs, scoliosis, a narrow thorax, and numerous anomalies in bone and cartilage, have been discovered in ciliopathies. Mutation in genes encoding cilia core components or other cilia-related molecules have been found in skeletal ciliopathies. Meanwhile, various signaling pathways associated with cilia and skeleton development have been deemed to be significant for the occurrence and progression of diseases. Herein, we review the structure and key components of the cilium and summarize several skeletal ciliopathies with their presumable pathology. We also emphasize the signaling pathways involved in skeletal ciliopathies, which may assist in developing potential therapies for these diseases.

Selenoprotein W engages in overactive osteoclast differentiation in multiple myeloma.

BACKGROUND: Patients with multiple myeloma exhibit malignant osteolytic bone disease due to excessive osteoclast formation and function. We recently identified that osteoclastogenic stimulator selenoprotein W (SELENOW) is upregulated via ERK signaling and downregulated via p38 signaling during receptor activator of nuclear factor (NF)-κΒ ligand (RANKL)-induced osteoclast differentiation. In the intrinsic physiological process, RANKL-induced downregulation of SELENOW maintains proper osteoclast differentiation; in contrast, forced overexpression of SELENOW leads to overactive osteoclast formation and function. METHODS AND RESULTS: We observed that SELENOW is highly expressed in multiple myeloma-derived peripheral blood mononuclear cells (PBMCs) and mature osteoclasts when compared to healthy controls. Also, the level of tumor necrosis factor alpha (TNFα), a pathological osteoclastogenic factor, is increased in the PBMCs and serum of patients with multiple myeloma. ERK activation by TNFα was more marked and sustained than that by RANKL, allowing SELENOW upregulation. Excessive expression of SELENOW in osteoclast progenitors and mature osteoclasts derived from multiple myeloma facilitated efficient nuclear translocation of osteoclastogenic transcription factors NF-κB and NFATc1, which are favorable for osteoclast formation. CONCLUSION: Our findings suggest a possibility that feedforward signaling of osteoclastogenic SELENOW by TNFα derived from multiple myeloma induces overactive osteoclast differentiation, leading to bone loss during multiple myeloma.

Osteocytes and Paget's Disease of Bone.

PURPOSE OF REVIEW: To describe the contributions of osteocytes to the lesions in Paget's disease, which are characterized by locally overactive bone resorption and formation. RECENT FINDINGS: Osteocytes, the most abundant cells in bone, are altered in Paget's disease lesions, displaying increased size, decreased canalicular length, incomplete differentiation, and less sclerostin expression compared to controls in both patients and mouse models. Pagetic lesions show increased senescent osteocytes that express RANK ligand, which drives osteoclastic bone resorption. Abnormal osteoclasts in Paget's disease secrete abundant IGF1, which enhances osteocyte senescence, contributing to lesion formation. Recent data suggest that osteocytes contribute to lesion formation in Paget's disease by responding to high local IGF1 released from abnormal osteoclasts. Here we describe the characteristics of osteocytes in Paget's disease and their role in bone lesion formation based on recent results with mouse models and supported by patient data.

Bone Health ECHO Case Report: Fractures and Hypercalcemia in a Patient with Stage 5 Chronic Kidney Disease.

Bone Health ECHO (Extension for Community Healthcare Outcomes) is a virtual community of practice with the aim of enhancing global capacity to deliver best practice skeletal healthcare. The prototype program, established at the University of New Mexico, has been meeting online weekly since 2015, focusing on presentation and discussion of patient cases. These discussions commonly cover issues that are relevant to a broad range of patients, thereby serving as a force multiplier to improve the care of many patients. This is a case report from Bone Health ECHO about a patient with stage 5 chronic kidney disease, hypercalcemia, and low bone density, and the discussion that followed.

Two Pathological Fractures in a Patient with Chronic Abnormalities in Serum Markers Following Two Liver Transplantations: A Case Report and Literature Review.

Bone disease is a common complication following liver transplantation, often overlooked in clinical practice. Clinical diagnosis of post-liver transplantation bone disease is challenging, and there have been few case report in the literature. This case report presents a patient who underwent two liver transplant surgeries, exhibited good daily activity, and did not display typical clinical symptoms such as fatigue, bone pain, or spinal deformities associated with prolonged sitting or standing. However, within the fifth year after the second liver transplant, the patient experienced two consecutive fractures. In March 2023, the patient underwent the first bone density test, which revealed osteoporosis. This case highlights the fact that severe fractures after liver transplantation may not necessarily be accompanied by typical symptoms of bone disease. Without timely examination and early prevention, serious consequences may arise. Therefore, this condition requires attention, proactive prevention, early detection, and timely treatment. Additionally, a retrospective analysis of the patient's previous laboratory data revealed persistent abnormalities in serum markers such as hypocalcemia and elevated alkaline phosphatase levels after liver transplantation, emphasizing the importance of monitoring these serum markers.

Role of fibroblast growth factor-23 as an early marker of metabolic bone disease of prematurity.

PURPOSE: Metabolic bone disease of prematurity (MBDP) remains a significant cause of morbidity in extremely premature newborns. In high-risk patients, suspected diagnosis and subsequent treatment modifications, with limitations in terms of sensitivity and specificity, rely on low phosphorus levels and/or high levels of alkaline phosphatase (ALP). We investigated the potential of fibroblast growth factor-23 (FGF23) as an early marker for MBDP when measured at 3-4 weeks of life in at-risk patients. METHODS: A single-center prospective observational non-interventional study including preterm newborns of both sexes, with a gestational age of less than 32 weeks and/or a birth weight of less than 1500 g. In the standard biochemical screening for MBDP performed between 3 and 4 weeks of life within a nutritional profile, the determination of FGF23 was included along with other clinical and metabolic studies. The study was conducted at Marqués de Valdecilla University Hospital in Santander, Spain, from April 2020 to March 2021. Participants provided informed consent. Biochemical analyses were conducted using various platforms, and follow-up evaluations were performed at the discretion of neonatologists. Patients at high risk for MBDP received modifications in treatment accordingly. The sample was descriptively analyzed, presenting measures of central tendency and dispersion for continuous variables, and absolute numbers/percentages for categorical ones. Tests used included t-tests, Mann‒Whitney U tests, chi-square tests, logistic regressions, Pearson correlation, and ROC curve analysis (IBM SPSS Statistics version 19). Significance level: P < 0.05. RESULTS: In the study involving 25 at-risk premature newborns, it was found that 20% (n = 5) were diagnosed with MBDP. Three of these patients (60%) were identified as high-risk based on standard biochemical evaluation at 3-4 weeks of age, while the other two patients (40%) were diagnosed in subsequent weeks. However, in all 5 patients, measurement of FGF23 levels would allow for early identification and optimization of treatment before other markers become altered. Low levels of FGF23 at 3-4 weeks, even with normal phosphorus and ALP levels, indicate the need for modifications in nutritional supplementation. CONCLUSIONS: MBDP remains a significant concern in extremely premature newborns. Current diagnostic methods rely on limited biochemical markers. Early detection of low FGF23 levels enables timely interventions, potentially averting demineralization.

Continuous versus intermittent bolus infusion of calcium in preterm infants receiving total parenteral nutrition: a randomized blind clinical trial.

BACKGROUND: Premature neonates need adequate nutritional support to provide sufficient essential nutrients for optimal growth. Calcium (Ca) is one of the important nutrients in parental nutrition support of premature infants. This study aimed to compare the effect of continuous and intermittent bolus infusion of Ca on the incidence of metabolic bone disease (MBD) in preterm infants. METHODS: This randomized double-blind clinical trial was conducted on ninety preterm infants in the NICU of Al-Zahra Hospital in Tabriz, Iran. The preterm infants were randomly allocated to either a continuous infusion group (received 4-5 ml/kg/day of Ca gluconate 10% by PN solution in a 24-h period) or an intermittent bolus administration group (received 1-2 ml/kg/day Ca gluconate 10% three to four times per day). Serial serum levels of Ca, phosphorous, alkaline phosphatase (ALP), vitamin D and parathyroid hormone (PTH) were assessed on the 7th day, 30th day and 45th day of life. RESULTS: A total of 78 infants completed the study. The serum ALP level on the 45th day after birth was 753.28 ± 304.59 IU/L and 988.2 ± 341.3 IU/L in the continuous infusion and intermittent bolus administration groups, respectively (P < 0.05). MBD in preterm infants with ALP levels above 900 IU/L on the 45th day of life was significantly lower in the continuous infusion group than in the intermittent bolus administration group (p < 0.05). The mean serum levels of calcium, phosphorus, vitamin D and PTH in 45-day-old infants were not significantly different between the two groups. CONCLUSION: The MBD in preterm infants who received continuous infusion of Ca was lower than that in preterm infants who received intermittent bolus administration of Ca. TRIAL REGISTRATION: The Iranian Registry of Clinical Trials ( http://www.irct.ir ) with the identification No. IRCT20210913052466N1.

Effect of early preventive supplementation with calcium and phosphorus on metabolic bone disease in premature infants.

OBJECTIVE: The objective was to study the effect of early preventive calcium and phosphorus supplementation on metabolic bone disease in preterm infants. METHODS: A retrospective analysis of 234 preterm infants with a gestational age < 32 weeks or birth weight < 1500 g who were hospitalized in the Neonatology Department of the Second Hospital of Shandong University from 01.2018 to 12.2020 was conducted. One hundred thirty-two premature infants hospitalized from 01.2018 to 06.2019 did not receive prophylactic calcium and phosphorus supplementation in the early postnatal period. These infants received calcium or phosphorus supplementation at the time of hypocalcaemia or hypophosphatemia diagnosis. One hundred two premature infants hospitalized from 07.2019 to 12.2020 received early preventive calcium and phosphorus supplementation after birth. The levels of serum calcium and phosphorus, alkaline phosphatase, 25-hydroxyvitamin D, calcitonin, and parathyroid hormone at different time points and growth indicators at six months of age were compared between the two groups of infants. The number of cases of metabolic bone disease and fracture between the two groups was compared. RESULTS: 1) A total of 12 infants (5.13%) among the 234 preterm infants were diagnosed with metabolic bone disease, including 2 (1.96%) in the prophylactic supplementation group and 10 (7.58%) in the nonprophylactic supplementation group. Fractures occurred in 3 premature infants (25.0%) with metabolic bone disease, all of whom were in the group that did not receive prophylactic supplementation. 2) There was no significant difference in serum calcium and calcitonin levels between the two groups. The levels of serum phosphorus and 25 hydroxyvitamin D in the prophylactic supplementation group were higher than those in the nonprophylactic supplementation group (P < 0.05). In comparison, alkaline phosphatase and parathyroid hormone levels were lower in the prophylactic supplementation group than in the nonprophylactic supplementation group (P < 0.05). Preterm infants in the prophylactic supplementation group had higher weight, length, head circumference, and bone density values than those in the nonprophylactic supplementation group (P < 0.05). CONCLUSION: Preventive supplementation with calcium and phosphorus after birth can effectively improve calcium and phosphorus metabolism, and reduce the incidence of metabolic bone disease and fractures in premature infants. This can be further publicized and used clinically.

Nonfamilial cherubism in a 6-month-old infant: a case report.

BACKGROUND: Cherubism is known as a very rare autosomal dominant familial disorder of childhood caused by a mutation in the SH3BP2 gene on 4p16.3. It has not yet been observed at birth and is usually diagnosed in children aged 2-7. Here, we present a non-hereditary case of cherubism at a very early age. CASE PRESENTATION: A 6-month-old girl presented with bilateral progressive jaw enlargement. On physical examination, bilateral asymmetrical jaw enlargement, predominantly on the left side, and some enlarged, non-tender, mobile submandibular lymph nodes were detected. No other abnormality was observed. Further investigations with radiology suggested cherubism and Burkitt's lymphoma as differential diagnoses. Later on, histopathologic evaluations were suggestive of cherubism. No surgical interventions were indicated, and the child is on regular follow-ups. CONCLUSION: Non-hereditary Cherubism, despite scarcity, can present in children below two years of age, even as early as the beginning of primary dentition. Accurate and swift diagnosis is essential to avert physical and psychological complications. Our case report shows the importance of keeping cherubism in mind as a differential diagnosis of bone disease, even in children under a year old, and the value of interdisciplinary collaboration in dealing with rare genetic disorders.

European survey showed wide variations in diagnostic procedures and management strategies for metabolic bone disease of prematurity in 22 countries.

AIM: The aim of this study was to evaluate the clinical relevance, diagnostic procedures and treatment strategies for metabolic bone disease in preterm infants across Europe. METHODS: An e-survey was distributed by email to 545 neonatal units in 38 European countries between July and October 2021. The protocol was based on the Checklist for Reporting Results of Internet E-Surveys. RESULTS: In total, 76 neonatal units (14%) from 22 European countries (58%) completed the e-survey. In the 12 months prior to the survey, 29% of 76 units reported at least one symptomatic case of fracture associated with metabolic bone disease of prematurity, and 18% of 76 units reported at least one case of craniofacial deformity. Most centres followed local guidelines for diagnosis (77% of 73 units) and treatment (63% of 72 units). Alkaline phosphatase was the blood marker most used for treatment indication (81% of 72 units), and phosphate supplementation was the treatment most used (82% of 71 units). CONCLUSION: Metabolic bone disease of prematurity remains clinically relevant. Wide variations in diagnostic procedures and management strategies were observed in European neonatal units. Evidence-based consensus guidelines appear urgently needed to reduce the number of symptomatic cases.

Pycnodysostosis: Characteristics of teeth, mouth and jaws.

OBJECTIVES: To describe the clinical and radiographic oro-dental characteristics of patients with pycnodysostosis (PDO). MATERIALS & METHODS: A short interview and clinical examination of seven patients with PDO were performed as well as assessment of the temporomandibular joints and masticatory muscles using the diagnostic criteria for temporomandibular disorders, DC-TMD form. A full set of records were taken including photos and intraoral scan. Finally, existing cone beam computed tomography (CBCT) images and radiographs were also studied. RESULTS: All patients presented with bimaxillary micrognathia, five had a convex profile, and two had a straight profile. In addition, posterior open bite, Angle Class III molar relation with accompanying anterior crossbite and a grooved median palate were common findings. No patient showed symptoms of temporomandibular disorder (TMD) apart from some clicking. Finally, the main radiographic findings were the obtuse mandibular angle, the frontal bossing, the elongation of the coronoid/condylar process and the presence of hypercementosis with obliterated pulp chambers. CONCLUSION: The examined patients with PDO were characterized by dental crowding, malocclusion (anterior crossbite, posterior open bite), hypercementosis, obliterated pulp chambers and deviations in mandibular morphology. In conclusion, patients with PDO have a specific need for dental and orthodontic monitoring with focus on crowding and posterior open bite. The patients will benefit from a long-term orthodontic plan including extractions.

Associations of cumulative voriconazole dose, treatment duration, and alkaline phosphatase with voriconazole-induced periostitis.

OBJECTIVE: To investigate the associations of cumulative voriconazole dose, treatment duration, and alkaline phosphatase with voriconazole-induced periostitis. MATERIALS AND METHODS: One hundred and thirty-one patients with voriconazole use were identified using a clinical informatics tool. Health record data including age, sex, immune status, alkaline phosphatase, voriconazole levels, voriconazole dose, frequency, and treatment duration were collected. Imaging studies during the duration of treatment were reviewed by two radiology trainees and imaging features of voriconazole-induced periostitis were confirmed by a board-certified musculoskeletal radiologist. The length, location in the body, location in the bone, type, and morphology of periostitis lesions were recorded. Incident voriconazole-induced periostitis was defined as new periostitis on imaging after 28 days or more of voriconazole treatment in the absence of an alternative diagnosis. Univariate Firth's logistic regression models were performed using cumulative voriconazole dose, treatment duration, and average ALP as predictors and incident VIP as the outcome. RESULTS: There were nine patients with voriconazole-induced periostitis and 122 patients without voriconazole-induced periostitis. The most common lesion location in the body was the ribs (37%) and morphology was solid (44%). A 31.5-g increase in cumulative voriconazole dose was associated with 8% higher odds of incident periostitis. Increased treatment duration (63 days) and higher average alkaline phosphatase (50 IU/L) were associated with 7% higher odds of periostitis and 34% higher odds of periostitis, respectively. CONCLUSION: Increased cumulative voriconazole dose, treatment duration, and average alkaline phosphatase were associated with higher odds of voriconazole-induced periostitis.

Nutritional and Inflammatory Aspects of Low Parathyroid Hormone in Maintenance Hemodialysis Patients-A Longitudinal Study.

BACKGROUND: Low serum parathyroid hormone (PTH) is an accepted marker for adynamic bone disease which is characterized by increased morbidity and mortality in maintenance hemodialysis (MHD) patients. In light of the known cross-sectional associations between PTH and malnutrition-inflammation syndrome, we aimed to examine the longitudinal associations between PTH with changes in nutritional and inflammatory parameters and clinical outcomes in MHD patients with low PTH. METHODS: This historical prospective and longitudinal study analyzed a clinical database at a single hemodialysis center, containing the medical records of 459 MHD patients (mean age of 71.4 ± 12.9 years old, 171 women), treated between the years 2007-2020. Bone turnover, nutritional and inflammatory marker levels were recorded at 0, 6, 12, 18, 24, 30, and 36 months followed by a median of 24 additional months of clinical observations. According to previous use of vitamin D analogs and/or calcium-sensing receptor agonists, the study participants were divided into treatment-related and disease-related groups. A linear mixed effects model was adjusted for baseline demographics and clinical parameters. RESULTS: Of 459 MHD patients, 81 (17.6%) had PTH lower than 150pg/mL. Among them, 30 patients had treatment-related and 51 had disease-related low PTH. At baseline, MHD patients with treatment-related low PTH had a higher rate of diabetes compared to the disease-related group. In a linear mixed effects model, increased PTH over time was associated with decreased levels of alkaline phosphatase and C-reactive protein and with increased hemoglobin and albumin, but not the geriatric nutritional risk index at 3-year follow-up. The survival rate did not differ between the groups, with the risk of hospitalizations due to fractures being higher (HR: 4.04 with 95% CI: 1.51-10.8) in the disease-related group. Statistical significance of this association was abolished after adding C-reactive protein or alkaline phosphatase to the multivariate models. CONCLUSIONS: Low serum PTH in MHD patients behaves differently depending on its cause, with a higher risk of fractures in the disease-related group. This association is dependent on inflammation. Our results should be verified in larger epidemiological studies.

Targeting the Role of PRME in Regulating Bone Remodelling During Postmenopausal Osteoporosis.

Kariavattom Campus Postmenopausal osteoporosis (PMO) is an old age disorder associated with estrogen deficiency, which reduces bone mass and makes bones more prone to fracture. The present study was proposed to evaluate the invivo osteogenic efficiency of Pterospermum rubiginosum methanolic bark extract (PRME) in the PMO model. Molecular docking studies on transcription factor NFATC1 showed excellent interactions with phytochemical ligands with the lowest binding energies. Female Sprague Dawley (SD) rats (n=24) were divided into four groups, (n=6 each) sham control (Group I) and osteoporotic control (Group II) groups treated with saline, PRME (50 mg/kg/day) and alendronate (10 mg/kg/day) treated with Group III and Group IV (n=6) respectively. The serum tartrate-resistant acid phosphatase 5b and cathepsin-K also exhibited a significant rise after PRME treatment 12.33±2.30 mU/ml and 427.68±46.97 pg/ml, respectively. DEXA results exhibited a remarkable increase in total bone mineral content and density values in PRME-treated animals (0.175±0.002 g/cm2) and (7.95±0.23 g) when compared to osteoporotic control (0.163±0.004 g/cm2) and (6.83±0.34 g). Long-term toxicity study revealed that PRME is non-toxic, up to 100 mg/kg bodyweight for 6 months. Our findings suggest PRME protects osteoporotic SD rats from PMO damage resulting from estrogen deficiency by regulating bone remodelling markers and upregulating BMD indices.

Comparing long and intermediate-length plates for metastatic bone disease of the proximal humerus: A retrospective analysis.

AIMS: Managing proximal humerus pathologic fractures requires strategic planning to ensure optimal patient outcomes. Traditionally, fixation of the humerus using long devices has been considered the standard of care, but emerging evidence has challenged this approach. This study aimed to compare long plates (LPs) and intermediate-length plates (IPs) in this clinical context. METHODS: Forty-four patients with proximal humerus metastatic bone disease were retrospectively studied from 2013 to 2019, with 11 (25%) receiving long plates (LPs) and 33 (75%) intermediate-length plates (IPs). Outcomes included tumor progression, reoperation rates, postoperative anemia, blood loss, operation time, and hospitalization duration. Tumor progression was classified into three categories, with Type III progression (new metastatic lesions in the distal humerus) theoretically benefiting most from whole bone stabilization. RESULTS: Tumor progression occurred in three patients (7%), all of them was in IPs. No revision surgery was needed to address these tumor progressions, including one type III progression which occurred 34 months postoperatively after IP surgery. IP were associated with a reduced operation time compared with LP (median, 1.5 h [IQR, 1.2-1.9] vs. 2.4 [IQR, 1.7-2.5]; p = 0.004). No differences were found for the other perioperative outcomes. CONCLUSIONS: Our findings reveal a low incidence of tumor progression and low reoperation rates in both groups. The shortened operative time associated with IP use suggests its particular suitability for patients with limited life expectancy. Further research is needed to elucidate the ideal prosthesis length that best balances the risks and benefits when addressing proximal humerus metastatic disease.