Osteosclerosis

Brain calcification is a common finding seen in various conditions including metabolic, neurological, developmental disorders, infectious diseases, trauma, toxic exposures, and also in normal aging. Researchers aim to better understand the clinical and genetic features of brain calcification by following a group of people with this condition over time. This observational study is designed to gather long-term information about brain calcification and its hereditary aspects. Participants include patients who have brain calcium deposits confirmed by CT scans, their relatives, and unrelated healthy individuals. The study involves observing and collecting data without any treatment intervention. The cohort will be followed for up to 20 years to monitor the occurrence and characteristics of hereditary brain calcification. During the study, participants will undergo assessments including CT scans to measure calcification levels and regular follow-ups to track changes. Researchers will record the incidence of hereditary brain calcification and gather clinical and genetic data. The study also involves obtaining informed consent and ensuring participants adhere to scheduled visits and procedures throughout the observation period.

Researchers are studying men with metastatic castration-sensitive prostate cancer to see if taking oral acetate can increase the amount of a gut bacterium called Akkermansia muciniphila. The trial aims to confirm this increase compared to standard care and to assess how well patients tolerate oral acetate. The study also explores whether higher levels of this bacterium relate to better metabolic health and bone strength. This is an early phase 1 clinical trial sponsored by Western University. Participants are randomly assigned to one of two groups. One group takes an apple cider vinegar caplet daily, containing 143 mg with 36% acetic acid, for three months. The other group receives standard care without supplementation. The study includes follow-up periods lasting up to six months to monitor changes and side effects. Throughout the study, stool samples will be collected at multiple time points to measure Akkermansia muciniphila levels. Researchers will also evaluate various metabolic markers such as blood sugar, cholesterol, and insulin resistance, plus bone health indicators. Side effects and tolerability will be checked after three months. Participants are monitored over six months to assess both primary and secondary outcomes related to metabolism and bone health.

Researchers are investigating the relationship between calcification characteristics seen on Computed Tomography Coronary Angiography (CTCA) and the outcomes of Percutaneous Coronary Intervention (PCI) in patients with chronic total occlusion (CTO) of the coronary artery. This observational study focuses on patients who underwent CTO PCI attempts and had CTCA scans at the study center within the last five years. The study aims to understand how calcification affects the success of PCI procedures and the use of calcium modification tools. The study involves reviewing medical records and imaging of patients who had both CTO PCI attempts and CTCA. Characteristics of calcification such as location, density measured in Hounsfield units, and quantity in the CTO will be analyzed and correlated with PCI success or failure. The study will also assess how calcium modification tools were used during PCI and their relationship to the severity of calcification. Statistical analyses will compare demographic and procedural data with calcification features and PCI outcomes. Participants will have their CTCA images and PCI reports reviewed retrospectively after providing consent through mailed forms. Researchers will analyze baseline patient data, calcification details, and procedural results. The main outcome measure is the correlation between calcification characteristics and PCI success or failure within 24 hours. Secondary measures include evaluating the role of calcium modifying tools relative to calcification severity. Participation involves no new treatment or intervention and is based on existing clinical data collected over the past five years.

Researchers are exploring the genetic causes of muscle diseases, especially those occurring alongside inherited bone disorders. This observational study aims to better understand how muscle and bone diseases that run in families affect tissue function and metabolism over time. The research uses a non-invasive technology called Diffuse Optical Spectroscopy to study these tissue changes. Diffuse Optical Spectroscopy is a quick and painless device developed at the University of California, Irvine. It measures concentrations of blood, water, and fats in tissues by shining infrared light on the skin using a probe placed on areas such as the calf, bicep, or head. The probe is held in place gently by hand or secured with medically approved wraps or tapes, leaving small marks on the skin to ensure consistent placement during repeated measurements. The technique involves no radiation and may include placing a detector directly on the skin in some cases. Participants will have the spectroscopy probe applied to specific body areas to gather data on tissue physiology. The study monitors muscle disease over a one-week period using these measurements. The process is safe, with no radiation exposure, and does not involve treatment but focuses on observation. Participation involves a series of painless measurements and may include family members with muscle or bone disorders. The total study duration and follow-up depend on individual circumstances.

Researchers are evaluating BoneMRI, a new 3D MRI technique developed by MRIGuidance BV, which creates CT-like images to visualize bone structure and morphology in the spine. This study aims to validate BoneMRI's accuracy in showing spinal bone details, focusing on how well it measures radiodensity and 3D shape across different hospital scanners and MRI machines. The goal is to improve diagnosis and treatment planning while reducing exposure to ionizing radiation. The study involves patients who are referred for both MRI and CT scans of the spine due to suspected bone-related spine disorders. Participants will have an additional MRI sequence taken using BoneMRI technology, alongside their routine scans. This prospective multi-center study expects to include 50 patients per center over 36 to 48 months. BoneMRI images will be compared to standard CT images to assess accuracy and reliability across various MRI configurations. During the study, participants will undergo routine clinical MRI and CT scans as part of their standard care, with the extra BoneMRI sequence added for research purposes. Researchers will measure how accurately BoneMRI reconstructs tissue radiodensity and 3D spinal morphology. There are no additional risks since BoneMRI images are not used in patient care decisions. The study may help reduce future patients' radiation exposure if BoneMRI proves accurate enough to replace some CT scans.

Researchers are collecting biological and clinical data from patients with progressive bone, calcium, and growth plate diseases. The goal is to better understand the biological processes behind these conditions and to identify factors that predict disease progression and potential new treatment targets. This observational study is sponsored by University Hospital, Toulouse, and focuses on patients of all ages up to 99 years old with these pathologies. Participants will undergo regular clinical monitoring, including blood and urine tests. In cases where surgery is part of the treatment, surgical residues may also be collected and preserved. These biological samples and clinical data will be gathered over an average period of 5 years to build a comprehensive collection for ongoing research. Throughout the study, patients will have clinical and biological evaluations to provide data for research. The main measure is the building of this biological and clinical collection from day 0 through study completion. Researchers will also look for markers that may indicate disease progression based on new insights gained from the data. Participants will be monitored regularly as part of their routine care, and the study may last up to 5 years or more.

Osteoporosis and obesity are highly prevalent and disabling chronic diseases. Osteoporosis is a disease of low bone mass, which predisposes people to bone fragility and increased risk of bone fractures. Obesity is a disease characterized by excess body fat levels, which predisposes people to diabetes, heart disease, stroke, hypertension, cancer, sleep apnea, osteoarthritis, and gallbladder disease. An essential component to research on the prevention and treatment of osteoporosis and obesity is a valid method for monitoring body fat levels and bone mineral density. Dual energy X-ray absorptiometry (DXA) is a method for analyzing bone mineral density and body composition, particularly bone mineral content, fat mass and lean mass in children and adults. DXA scanners use an X-ray tube to produce radiation, which is then filtered into low- and high-energy beams. These beams of radiation are emitted from beneath a table that the supine human body is lying on. The arm, which passes above the person, detects the attenuation of the radiation for each pixel the body occupies. Based on known attenuation levels of different human tissues, the imaging software provides information on the composition of each pixel of the body. These pixels are then summed to provide information on: total body bone mineral content, total bone mineral density, fat mass, and lean mass. The DXA can also assess regional body composition (e.g. trunk fat), which is of importance in evaluating health effects of body fatness patterns. Using standard protocols, bone mineral content and density can be assessed in areas of the body indicating high risk of fractures (e.g. hip and lumbar spine) or areas that are likely to be responsive to dietary or physical activity manipulations (e.g. lumbar spine and radius). Peripheral quantitative computed tomography (pQCT) is a 3-dimensional imaging technique that goes beyond the 2-dimensional imaging of DXA to assess both true volumetric bone density and bone geometry, the two key components of bone strength. Additionally, it can divide bone into its component parts, i.e. separately assessing bone density and bone geometry of cortical and trabecular bone. As such, the measurements obtained from pQCT provides a more complete picture of what may be occurring within bone tissue that contributes to either bone gain or bone loss, depending on the population and question of interest. pQCT assesses parameters of bone strength at the radius (forearm) and tibia (lower leg). A vital component of any clinical and research program is precision testing, which assesses the reproducibility of DXA and pQCT measurements within an individual technician and/or between multiple technicians. This study was designed to address our facility's needs and ethical requirement to complete precision testing. This precision testing is a necessary component of verifying the feasibility and validity of the method, as well as cross-calibrating DXA scanners in our multi-site studies. We are completing this testing with the two DXA scanners, the GE Lunar iDXA and the Hologic Horizon W DXA, as well as with the Stratec XCT 3000 pQCT. A vital component of any clinical and research program is precision testing, which assesses the reproducibility of DXA measurements within an individual technician and/or between multiple technicians. As alluded to above, the validity of bone and soft tissue measurements by DXA and pQCT is related to the skill of the technician in: 1) properly positioning the person before scanning and 2) properly analyzing the scan images afterward. Both of these components are subjective, requiring experience and feedback to improve technique. From an ethical standpoint, a level of technician competency is important in ensuring that both research volunteers and the technician are not exposed to radiation without the benefit of acceptable scan results. From a clinical and research standpoint, understanding the inherent variability in testing is an important component in planning and executing research studies having bone or body fat outcomes. As described the Conference of Radiation Control Program Directors, Inc. (CRCPD), and as established by the International Society of Bone Densitometry (ISCD), measurement of precision is a key component for assessing: 1. The smallest change (least significant change, LSC) in bone density that is biologically significant 2. The time interval between measurements necessary to detect changes. Precision testing requires that multiple scans be completed on individuals representative of the primary target population of interest, sometimes within a fairly short period of time. This exposure of additional radiation to a select group of individuals has created controversy about whether precision testing is necessary and ethical. The CRCPD and ISCD has fully supported precision testing, and recommended that it be a routine practice in all DXA sites. The CRCPD states that, "Some states without understanding the need for precision testing have prohibited the measurement despite low radiation doses and limited numbers of repeat densitometry determinations. Their major concern, of course, is the apparent unnecessary radiation to a few, select patients. To address the benefit versus risk issue, those exposed to the additional, small amount of radiation (equal to approximately an additional 6-12 hours of background radiation) are providing a benefit to themselves and all others by validating the results of bone mineral density (BMD) exams for that facility. Without precision testing, the BMD study is of no value resulting in thousands of patients being exposed to unnecessary radiation."

Craniometaphyseal Dysplasia (CMD) is a rare bone disorder primarily affecting the bones of the head and long bones, characterized by progressive bone growth in the face and head and widening of the ends of long bones. This research aims to identify genetic changes and regulatory elements that cause CMD, study blood and tissue samples from patients, and understand the biological processes behind the disorder. The long-term goal is to find ways to slow down abnormal bone growth in people with CMD. The study does not involve treatments but focuses on observing participants with CMD and their family members to gather genetic and molecular information. Blood and tissue samples are collected to analyze genetic mutations and cellular mechanisms related to CMD. The study includes affected individuals and unaffected family members to help distinguish CMD from related bone disorders. Participants will provide samples and undergo evaluations to help identify genetic causes of CMD. Researchers will analyze these samples to understand how CMD develops and progresses. The primary outcome measure is the identification of genetic elements responsible for CMD. Participation involves ongoing observation without treatment, and the study began in 2009 with plans extending through 2030.

Diseases affecting bone due to aging, such as osteoporosis and osteoarthritis, lead to reduced bone mass, strength, and joint health. Current non-surgical treatments mainly involve drugs that do not change the disease and often cause side effects. This research aims to better understand how bone cells work and affect bone health to find new treatment targets. The study will collect bone samples from patients undergoing various orthopedic surgeries to analyze bone biology, genetics, and environmental factors. Participants include patients having elective or urgent orthopedic surgeries like joint replacements, fracture repairs, or osteotomies. Bone tissue removed during surgery will be collected for analysis within four hours. Blood samples and questionnaires will also be collected shortly after surgery. The study uses advanced single-cell techniques to explore bone cell diversity and applies machine learning to analyze how genetic differences impact bone structure and quality. During the study, participants will provide surgical bone waste and blood samples within hours of their procedure. They will complete questionnaires within one week after surgery. Researchers will monitor bone and blood samples to identify molecular and genetic factors that influence bone health. The study plans to run over the next ten years, generating detailed data to help develop new therapies for bone diseases associated with aging.

Researchers are studying rare skeletal disorders, which include many conditions affecting the bones that are not well understood and often lack specific treatments. The goal is to better understand the causes and progression of these disorders over time by collecting clinical and genetic data. This observational clinical and laboratory study allows participants to contribute remotely or in person, supporting a comprehensive evaluation of skeletal disorders, including known and unknown genetic causes. Participants include individuals with known or suspected skeletal disorders involving phosphate metabolism, skeletal overgrowth, or those with pregnancies affected by skeletal findings, as well as their healthy family members. The study collects medical records, blood, saliva, urine, and tissue samples for genetic testing and research. Those aged 2 years and older may have imaging scans like X-rays. Participants visiting the clinic may undergo physical exams, biopsies, photographs, and hospital stays for additional tests. Some samples may be used to create stem cells for research. Participants will be involved indefinitely, with ongoing data collection and evaluations. Researchers will review medical history, perform genetic tests, imaging, and laboratory studies, and monitor changes over time using photos and clinical observations. The primary outcome is to identify genetic causes and genotype-phenotype links, while secondary outcomes include describing the natural history of these disorders. This long-term study is designed to deepen understanding and support future research in skeletal disorders.