Osteomalacia

INTRODUCTION Vitamin D insufficiency in the context of neurodisability has been associated with an elevated risk of poor physical function, bone mineral density and fractures.Clinical experience indicates that the population in Greece generally exhibits lower levels of vitamin D compared to northern European populations. There is a lack of data in Greece concerning persons with neurological motor disorders, and globally, there are no established criteria for vitamin D recommendations. PURPOSE To assess vitamin D levels in populations with neurological disorders that result in motor disabilities to provide the epidemiological data necessary for the guidelines. The data from our study will establish a database for any future guidelines regarding vitamin D administration in neurological illnesses, which is now lacking. The major objective of the study is to determine vitamin D insufficiency in the neurological populations under investigation, while the secondary objective is to assess the impact of vitamin D supplementation on structural and functional parameters. METHOD The NeuroVitD trial will be a randomized, cluster-based, controlled intervention effectiveness trial of two years. Patient recruitment will occur from June 1, 2025, until June 1, 2027. A total of 120 individuals will participate, with 30 individuals designated as a control group. This includes strokes, spinal cord injuries, traumatic brain injuries, among others. Comprehensive epidemiological data, including demographic and anthropometric information, along with social habits such as sports participation and smoking, will be documented. Serum vitamin D levels, together with other biochemical markers, bone density, body composition, and metrics of strength, physical performance and speed, if applicable, will be assessed. The assessment will also include safety and tolerance to vitamin D. Bone density and body composition will be assessed using a DXA machine, strength will be evaluated with a hand dynamometer (utilization contingent upon condition), walking speed will be estimated with the appropriate test, physical performance with SPPB test and pain will be quantified using the proportional pain scale. Two measurements will be conducted for all parameters, at the commencement and conclusion of the study. New volunteers will be incorporated into the study for a duration of 2 years. The analysis of the results is anticipated in the second half of 2027. All individuals will be inpatients at the 2nd PMR Department at EKA Hospital and will adhere to the usual rehabilitation procedure tailored to their specific conditions. Individuals with low vitamin D levels (\<20 ng/ml) will be administered a vitamin D supplement, a medically warranted treatment. The control group will consist of individuals with neurological diseases and vitamin D levels exceeding 20 ng/ml. This study aimed to assess the effects of vitamin D supplementation at two distinct dosages. A treatment plan will be implemented, as applicable, consisting of either 50,000 I.U of vitamin D weekly for 8 weeks or 25,000 I.U of vitamin D for 4 weeks followed by 10,000 I.U of vitamin D drops weekly for an additional 4 weeks (totaling 8 weeks), with an evaluation of which group exhibits superior parameters. The dose that elicits the beneficial impact and is optimal for people with neurological impairment will be assessed. Furthermore, calcium, parathyroid hormone, and phosphorus will be assessed to examine the impact of vitamin D administration on additional biochemical markers. Exclusion criteria The subject is excluded if they: • are legally or mentally incapable of comprehending and consenting to participate in the study • have a history of or exhibit indicators of metabolic bone disease, including the following: Hypoparathyroidism, primary hyperparathyroidism, recent hyperthyroidism (within the last six months), Paget's disease of bone; no grade 3 or 4 pressure ulcers present; has undergone treatment with pharmacological agents influencing bone metabolism prior to the initial bone density assessment, including the following: Treatment with bisphosphonates in the year prior to the bone density assessment ; Administration of parathyroid hormone in the year prior to the research ; Administration of estrogens, selective estrogen receptor modulators (SERMs), tibolone, or anabolic steroids within the preceding six months. Thyroid drugs are permissible only if the dosage has remained consistent for the preceding six weeks and TSH levels are within the normal range. Corticosteroid medication exceeding 7.5 mg of prednisone orally per day for a duration exceeding one month within the past six months. Immunosuppressant therapy within the past year; Vitamin A therapy above 10,000 IU per day or Vitamin D exceeding 5,000 IU per day. Participants are prohibited from consuming additional vitamin D supplements exceeding 400 IU per day or traveling to regions with heightened sunshine exposure during the trial. RESULTS The findings will encompass vitamin D levels, bone density, body composition, strength, walking speed and pain. Additionally, the impact of vitamin D supplementation on various biochemical parameters will be analyzed, alongside gender and group comparisons. Correlations will be established based on participants' residential locations (urban or rural), the administration of vitamin D supplementation, seasonal variations, and associations with specific medications for neurological conditions. Statistical Analysis Our data will be presented using the number of patients (N), mean values (m.s.), and standard deviations for continuous variables, as well as frequencies (n) and percentages (%) for categorical variables. Comparisons of the absolute values of the variables between the two groups (controls vs. neurological lesions) will be conducted using Student's t-test or Welch test (if variances are uneven) and a one-way ANOVA model without repeated measures. For multiple comparisons between time points using pairwise multiple comparison analysis, the investigators will employ the Scheffé test. The General Linear Factorial model will be employed to analyze the factor differences on the measured parameters. Ultimately, the investigators will analyze the differences between the groups by correcting our findings for variables that may influence bone density (such as age and body mass index), employing the general linear factorial model; the tests will be two-sided with a significance threshold of p=0.05. The statistical analysis will utilize the SPSS (Statistical Package for the Social Sciences) software. The participants will engage in the study following written agreement from themselves or their legal representatives, after being thoroughly informed about the objectives and procedures of the research.

Study 8123-001 is a Phase 1/2, multicenter, open-label, dose-escalation study to assess the safety, tolerability, PK and PD of KK8123, with an optional safety extension period. This study is comprised of a Screening Period followed by Part 1 and Part 2. The Screening Period will last up to 28 days (including obtaining informed consent). Part 1 is a Dose Escalation Period consisting of a nominal (planned) Treatment Period (all cohorts) and Observation Period of 32 to 44 weeks, and Part 2 is an optional Extension Period.

This randomised controlled dietary intervention study aims to recruit households/families of children, teens and adults, with 390 participants who will be randomised to receive vitamin D-fortified bread and advice to consume additional commercially available fortified foods (Treatment group) or identical unfortified bread and advice to consume additional commercially available fortified foods (Control group). The outcome of the study is to test whether increasing vitamin D intake through food (Treatment group) is sufficient to prevent wintertime vitamin D deficiency (measured using serum concentrations of 25-hydroxyvitamin D \<30 nmol/L) in comparison with the Control group. The target vitamin D intake for the treatment group in this study is \>20 μg/ day vitamin D. This will maintain serum concentrations of 25-hydroxyvitamin D (25(OH)D) (the biomarker of vitamin D status) \> 30 nmol/L, the clinical deficiency threshold to prevent metabolic bone disease, in over 90% of participants. At this vitamin D intake level, about 80% of participants will have a 25(OH)D concentration \> 50 nmol/L, the personal intake target in the US and EU.

Study Description: To evaluate participants with bone and mineral disorders at the NIH Clinical Center and obtain tissue and clinical specimens from outside institutions Objectives: Primary Objective: Provide a protocol within which participants with common and rare disorders of bone and mineral metabolism can be studied, evaluated and treated at NIH. Secondary Objectives: To obtain tissue and clinical specimens (including but not limited to blood, urine, nucleic acids, skin and bone) and data collected at outside institutions and the NIH Clinical Center from participants with various bone and mineral disorders. Tertiary/Exploratory Objective: Generate a pool of participants with bone and mineral disorders, from which research questions could arise and future clinical research studies may be generated. Endpoints: Primary Endpoint: Medical evaluation with clinical assessments performed at time points specific to each participant s diagnosis. Analysis of research and participant outcome data will be performed. Secondary Endpoint: Genetic and/or biochemical assessments of surgical waste material from the NIH Clinical Center or other medical facilities. Tertiary/Exploratory Endpoint: Development of a database containing information from enrolled participants with bone and mineral disorders and annotated specimens and data.

In this prospective observational sub-study, participants with pediatric-onset hypophosphatasia (HPP) (perinatal/infantile- or juvenile-onset) of any age will be followed for a minimum of 5 years at sites in the United States and potentially 1 or 2 other countries.

This is an open-label study to evaluate the effect of DensityTM, amorphous calcium carbonate (ACC), in postmenopausal women, compared to FREEDOM substudy. Subjects with a BMD T-score between -4.0 to -2.5 will be invited to enroll into this study. After signed ICF, eligible subject who meet NHI reimbursement criteria for use of denosumab will be assigned to A arm, and subject who does not meet NHI reimbursement criteria for use of denosumab, or who is no willing to receive denosumab treatment during study period, even meet NHI reimbursement criteria will be assigned to B arm. A total of 205 subjects will be enrolled into this study, in which 142 subjects in A arm and 63 subjects in B arm. In A arm, subject will receive 5 DensityTM tablets (equal to 1000 mg calcium element) daily with injections of 60 mg of ProliaTM (denosumab) every 6 months at study site, while in B arm, eligible subject will receive 5 DensityTM tablets (equal to 1000 mg calcium element) daily only. DensityTM tablets will be administered as follows: 5 tablets will be taken after meal. In addition, all subjects with a baseline 25-hydroxyvitamin D level of 12 to 20 ng/ml will be given 800 IU of vitamin D3 daily, while those with a baseline level above 20 ng/ml received 400 IU of vitamin D3, both administered after meal. The study will consist of 7 clinical visits. Subjects will come to the clinics at Visit 1 (screening visit, Month -1), Visit 2 (regimen start, Day 0 in Month 0), and Visit 3 to 7 (follow-up visits, Month 1, 6, 12, 18, 24). BMD assessment and blood drawing will be performed before study medication administration and at Month 1, 6, 12, and 24.

The overriding objectives of this study are: 1. Primary outcomes: 1. To confirm that administration of oral acetate increases the proportion of A. muciniphilia in the stool samples of patients with metastatic, castration-sensitive prostate cancer compared to a standard of care arm. 2. To confirm tolerability and assess for side effects of oral acetate supplementation. 2. Secondary outcomes: 1. To determine if increased counts of A. muciniphilia correlate with improved metabolic parameters and improved bone health.

Trauma is a leading cause of morbidity and mortality in low middle income countries with road traffic accident as a common mechanism of trauma. Femur and tibia shaft fractures are common with a burden of 5% and 20% respectively. For proper fracture healing and treatment, vitamin D supplements are prescribed in routine practice. Vitamin D can cause confusion, polyuria, thirst, anorexia, vomiting, constipation, nausea, arrhythmias, seizures, potentiate cardiac drugs, renal failure, tissue calcium deposit, bone demineralization, muscle/bone pain, allergy, weakness, metallic taste, weight loss, chest pain, dyspnea. In developing countries, most patients skip supplements due to the unaffordability, toxicity, and inaccessibility of slums. Considering the vitamin D cost and toxicity, alternative effective, safe, and affordable treatment is a prerequisite. Prunus dulcis (sweet almonds) is a dietary item which contains essential bone micronutrients that contribute in bone health for structural strength and proper functioning. evidence shows enormous health benefits of almonds According to one study, 60 grams of Prunus dulcis (almonds) reduced osteoclast formation and calcium release, indicating a positive effect on bone health. In another study, Prunus dulcis extract accelerated tibial bone fracture healing in rabbits, which is another evidence for potential benefits of Prunus dulcis on bone healing and health. In continuation to this, other health benefits are also reported. Prunus dulcis (almond) are consumed as a dietary item but it may occasionally cause allergy and if consumed in higher amount (\~11 grams/day), can cause toxicity Based on the available facts, the current trial question is whether addition of Prunus dulcis (almonds) in the diet is safe, assists fracture healing, and improve vitamin D levels in blood in the femur and tibia shaft fractures compared to routine vitamin D supplement? It is hypothesized that compared to routine vitamin D3, Prunus dulcis (almonds) non-inferiorly improves fracture callus index with raise in vitamin D3 level in blood in femur and tibia shaft fracture patients. The clinical trial aims to evaluate and compare the safety and effect of Prunus dulcis (almonds) on callus formation and callus bridging in femur and tibia shaft fractures and improvement in vitamin D level in blood up to 13 weeks compared to routine vitamin D supplements. This might assist orthopaedic surgeons in optimizing bone healing through almonds in patients arriving with fracture injuries as an alternative dietary bone nutritive source. Primary Objectives: 3\. To compare tibia and femur shaft fracture callus index (mm) and callus bridging (The Radiological Union Score for Tibial fractures-RUST) on x-rays at 4 and 13 weeks herewith group 1 suffering vitamin D insufficiency (arm A versus arm B) and group 2 suffering vitamin D deficiency (arm B versus arm C) treated as cross-over with oral 5 grams/day whole almonds and 200,000IU/week vitamin D3. 4\. To compare the incidence of adverse events between almonds and vitamin D3 treatments in all trial arms up to 13 weeks follow-up. Secondary Objectives: 3\. To compare the average almonds and vitamin D3 treatment cost. 4. To compare within group blood vitamin D levels (ng/mL) at baseline and post-treatment at 4 and 13 weeks. Methods: Number of participants: 136 Study design: Single-center, open-labeled, crossover (1:1 for each group), non-inferiority randomized controlled trial. Study Duration: 24 months Study procedures: After Institutional and Ethical Review Committee approvals, patient eligibility is assessed by the designated trained researcher in in-patient and outpatient orthopaedic units. Consent administration process: Informed written consent (English and Urdu) administration as per Good Clinical Practice Guidelines (GCP) guidelines. Clinical trial method is explained to patients. Patients are allowed to read the consent form and ask questions. A signed consent copy is provided to each subject. Patient Screening: Eligibility criteria: assessment. Sampling Method: Non-probability, consecutive sampling Randomization: Patients (N=136) are divided into two groups. Group 1 (vitamin D insufficiency, blood vitamin D level 21-29 ng/mL) and Group 2 (vitamin D deficiency, blood vitamin D level ≤20 ng/mL). Within two weeks of screening, patients are randomly allocated into a total of three arms. III. Group 1 (N=14): Arm A (n=7) = 5±0.5 grams/day of whole almonds for 4 weeks, followed by 7 days washout period and initiating cross-over treatment by oral vitamin D3 200,000 units/week for 8 weeks. Arm B (n=7) = Oral vitamin D3 200,000 units/week for 8 weeks, followed by 7 days washout period and initiating cross-over treatment by 5±0.5 grams/day of whole almonds for 4 weeks IV. Group 2 (N=122): Arm B (n=61) = Oral vitamin D3 200,000 units/week for 8 weeks, followed by 7 days washout period and initiating cross-over treatment by 5±0.5 grams/day of whole almonds for 4 weeks. Arm C (n=61) = Oral vitamin D3 200,000 units/week together with 5±0.5 grams/day whole almonds for 4 weeks, followed by 7 days washout period and initiating cross-over treatment by oral vitamin D3 200,000 units/week for 8 weeks. Patient follow-ups and Data Collection: Patients are followed at 4 weeks±1 week and 13 weeks±1 week follow-up visits after treatment. In order to reduce bias, researchers were trained on data collection form and GCP guidelines prior to data collection. In case of lost to follow-up, patients are contacted by telephone to gather necessary information. Assessments: Fracture site routine X-rays and RUST score for bone fracture healing are assessed by treating surgeon/investigator(s) at follow-ups. The research study does not seem to have any potential health hazard as vitamin D is routinely prescribed, and almonds are consumed as a dietary item. Complying with all regulatory standards and as per International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) guidelines, study subjects experiencing any adverse event (AE)/serious adverse event (SAE) will be provided optimum care at earliest. Principal Investigator is responsible for sending reports to the reporting bodies (Ethical Review Committee, Sponsor etc.) as required. Investigational product handling: The investigational products is regularly purchased from the Purchase Department of the Hospital, weighted, packaged, and properly labelled by the designated researcher and stored at the secure dry hygienic place. The product is dispensed to the patient by the designated researcher. The daily diary is provided to the patients for compliance and investigational product intake. The returns of used packs/products are collected at follow-ups. Data management: Data is managed at the Department of Surgery. Randomization list is generated. Data is kept secure in cabinets with a lock and key and a password-protected system with controlled data access. Fifteen percent of the data is double-checked/validated by the Principal Investigator. Data will be archived and stored for 15 years or longer after study completion. Statistical Consideration: The Statistical Package for Social Sciences (SPSS) version 19.0 will be used to analyze data. Quantitative variables (age, callus index, vitamin D3 level, etc.) will be expressed as mean±SD or median (IQR) as appropriate and qualitative variables (gender, type of fracture, etc.) as frequencies (percentages). Data will be analyzed by intention to treat analysis. Investigational product related AEs/SAEs will be assessed by incidence and stratification. Per group between arms comparisons for the mean difference of callus index, RUST scores, and vitamin D3 level will be analyzed by mixed ANOVA and within arms follow-up observation by repeated measures ANOVA/Freidman test and generalized estimating equation (GEE). Femur and tibia fractures within each arm will be compared for callus index and vitamin D levels by independent student t-test/Mann Whitney U test (as appropriate). The p-value less than 0.05 will be considered statistically significant with a confidence interval of 95%. Multiple regression will be used to assess the association between covariates like age, gender, fracture type, etc., and a numeric outcome like callus index, vitamin D3 level, etc. The percentage of lost to follow-ups will also be assessed. Withdrawals: Patients can withdraw from the study at any time without losing any of his/her patient rights. Study Close-out: Study close-out process will be of one to two-month duration.

Low-energy fractures in children are a common cause of morbidity and may reflect underlying skeletal fragility. Emerging evidence suggests that hypovitaminosis D, obesity, and abnormal bone metabolism play important roles in fracture risk. However, the combined effect of these factors remains insufficiently studied, particularly in pediatric populations. This study is designed as a prospective case-control investigation to explore the relationship between vitamin D status, bone metabolic markers, and obesity in children presenting with trauma. Children aged 3-15 years with low-energy trauma will be recruited and divided into two groups: those with radiologically confirmed fractures (cases) and those with similar trauma but without fractures (controls). Baseline assessments include anthropometric measurements, dietary calcium intake through a food-frequency questionnaire, and laboratory evaluation of bone metabolism. Blood samples will be obtained within 7 days of the trauma and processed under standardized conditions to measure 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), alkaline phosphatase (ALP), calcium, and phosphate. Samples are collected non-fasting and stored on ice to minimize variability in PTH measurement. The primary outcome is the association of fracture occurrence with serum alkaline phosphatase (ALP) levels. Secondary outcomes include serum calcium, 25OHD concentration, a composite bone risk score, and body mass index (BMI) percentile. Outcomes are analyzed using descriptive statistics, group comparisons, and logistic regression to identify independent predictors of fracture risk. The study aims to provide novel insights into the multifactorial etiology of pediatric fractures. By integrating metabolic, nutritional, and anthropometric data, the project seeks to establish a more comprehensive risk profile that can guide preventive strategies and inform clinical practice in pediatric bone health.

Cohort: All coronary CTO patients who underwent a PCI attempt and also underwent CTCA at our centre in the last 5 years. Method of identifying and consenting patients: Screening of our local database to identify suitable patients who fulfil the inclusion/exclusion criteria. These patients will be telephoned and the consent form and participant information sheet will be maile dot them along with a self addressed stamped envelope.On receipt of the consent form, we will countersign it and return a copy to the patient. Consented patients' images and reports of the CTCA and CTO PCI will be reviewed. Characteristics of calcification in the CTO on the CTCA will be evaluated including site, density and quantity of calcification. This will be correlated with CTO PCI outcomes of success and failure. Also this will be correlated with use of calcium modification tools for the CTO PCI. * Baseline and demographic as well as procedural data will be compared with CTO PCI outcomes and presence/characteristics of calcification. * Characteristics of calcification in the CTO assessed will include: site, density in Hounsfield units and quantity. * Site of calcification (proximal, body or distal) will be correlated with the CTO PCI outcome by chi square analysis. * Calcium density (in Hounsfield Units) on the CTCA will be correlated with successful versus failed CTO PCI by ROC curve analysis. * Quantity of calcification will be assessed as a percentage of the cross section of the CTO body (as \<50%, 50-75% and 75-100%) and correlated with CTO PCI success by contingency analysis. * Use of calcium modification tools will be correlated with CTO PCI outcome (success or failure) and density of calcification on CTCA (ROC curve and ANOVA). * Categorical variables will be compared by the chi square or Fisher's test and continuous variables will be compared by the Mann Whitney U test. In addition, based on CTO PCI outcome of success or failure, patients will be compared for demographics and procedural variables. * Categorical variables will be presented as percentage and compared with the chi square or Fisher's test * Continuous variables will be presented as median (range) and compared with student's t-test or Mann Whitney test.