Paget's Disease of Bone

Researchers are evaluating the combination of Disitamab Vedotin and Toripalimab to treat advanced HER2-positive extramammary Paget disease of the scrotum. This phase II clinical trial aims to determine if this combination reduces tumor size and delays disease progression, while also studying the safety and medical problems that may occur during treatment. Participants will receive intravenous infusions of Disitamab Vedotin at 2mg/kg and Toripalimab at 3mg/kg every 3 weeks. Treatment continues until the disease progresses, intolerable side effects occur, or other specified reasons arise. The study includes regular clinical tumor imaging and lesion measurements during treatment. Participants visit the clinic every 3 weeks for checkups and tests, including assessments of tumor response using RECIST criteria. The main outcome measured is the objective response rate every 6 weeks for up to 24 weeks. Secondary outcomes include progression-free survival and adverse events monitored over an average of 2 years. Follow-up continues until disease progression, withdrawal, loss to follow-up, or death.

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 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 studying families affected by inherited inclusion body myopathy (IBM), Paget disease of bone (PDB), and frontotemporal dementia (FTD), conditions linked to changes in the VCP gene. The goal is to understand how mutations in this gene lead to muscle, bone, and cognitive problems seen in IBMPFD. This observational study involves adults with personal or family histories of these conditions or related muscle and bone disorders. Participants provide biological samples like blood and urine, share family and medical histories, and complete questionnaires about their health. Some participants may be invited to visit the University of California, Irvine, for a two-day program including local procedures such as MRI and bone scans. Travel is only required for those selected for additional testing. Throughout the study, samples are coded to protect participant privacy. The research team collects data to better understand the disease's impact on muscle, bone, and brain function. Participation involves sharing medical information and possibly undergoing imaging tests during the study period, which continues through December 2030.

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."

This research aims to compare new bone growth after sinus floor elevation surgery in patients needing dental implants. The study focuses on whether making multiple small holes (perforations) in the cortical bone layer of the sinus floor before placing augmenting material improves bone formation. The trial involves 12 patients who require sinus floor elevation on both sides of the mouth, allowing direct comparison within each patient. Participants will undergo a lateral window sinus floor elevation on both sides. One side will follow the standard procedure by filling the sinus with augmentation material without perforation. The other side will have several perforations made in the cortical bone layer before the augmentation material is inserted to enhance blood supply to the graft. Both sides will then heal for 4 to 6 months before dental implants are placed. During implant placement, a bone biopsy will be taken from the treated areas to assess new bone formation through histological analysis. The study includes randomized assignment of sides and double-blinding to ensure unbiased results. Participants will be monitored throughout the healing period, with the main outcome measured at 4 to 6 months after surgery to compare bone growth between the two procedures.

This research aims to better understand Extramammary Paget's Disease (EMPD), focusing on women with vulvar or perianal Paget's disease. The study will collect tissue samples and swabs to explore the microorganisms (microbiome) living on or near affected skin areas. Researchers want to learn more about treatment outcomes and disease characteristics in this specific group. Participants will be identified during visits to the Dermatology or Gynecologic Surgery departments at Mayo Clinic. They will undergo cultures of skin, rectum, and vagina to analyze the microbiome. Women will follow a care pathway including dermatology consultations, preoperative genital sensory testing, and possibly Moh's micrographic surgery or excisional procedures by gynecologic surgery. Samples such as swabs, urine, and tissue will be collected before interventions for further analysis. During the study, participants will complete various sexual health and quality of life questionnaires. They will be monitored for outcomes including long-term survival over 25 years. The study collects data through physical exams, questionnaires, tissue sampling, and clinical follow-up. This observational registry aims to gather comprehensive information on EMPD in women, supporting better understanding and care.

Researchers are evaluating Ivonescimab, a PD-1/VEGF bispecific antibody, for the treatment of multiple advanced rare tumors. This phase II, multi-cohort, and multi-center study includes 20 different tumor types such as Paget's disease of the scrotum, metastatic paraganglioma, sarcomas, renal carcinomas, prostate cancer, and tumors with brain metastases. The study aims to assess if Ivonescimab improves the objective response rate and prolongs survival, as well as to monitor safety and quality of life during treatment. Participants receive Ivonescimab at a dose of 20mg/kg given by intravenous infusion every 21 days. Treatment continues until disease progression, unacceptable toxicity, or for a maximum of two years. Imaging evaluations are conducted every 9 weeks during the first year and every 12 weeks afterward. Dose delays up to 12 weeks are allowed under specific conditions, but dose reductions are not permitted. Participants undergo a screening period within 28 days before starting treatment. Safety follow-up visits occur 30 days after the last dose, including physical exams and lab tests. Afterward, survival follow-up is done every 3 months for up to one year through visits or phone calls. Researchers track tumor response, progression-free survival, overall survival, quality of life, and record any adverse events throughout the study.