Thomas Weber

Overview:

Osteoporosis, with current studies that focus on advances in diagnosis and natural history of male and postmenopausal osteoporosis. The study on male osteoporosis include a collaborative study with outside investigators is examining the utility of lateral spine bone densitometry in identifying men with osteoporosis and low trauma fractures.

Hypophosphatemic disorders, including X-link hypophosphatemic rickets and tumor-induced osteomalacia. My ongoing research study, in collaboration with Dr. L Darryl Quarles at the University of Kansas, seeks to further confirm and extend our understanding of the role of FGF-23 in human disorders of phosphate homeostasis, including patients with chronic kidney disease. Pending studies include primary and sub-investigator directed Phase 1 / 2 first in human studies examining the effects of a monoclonal antibody and enzyme replacement therapy for X-linked hypophosphatemic rickets and hypophosphatasia, respectively.

Positions:

Professor of Medicine

Medicine, Endocrinology, Metabolism, and Nutrition
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1989

The University of Chicago

Medical Resident, Medicine

Yale University

Instructor, Medicine

Yale University

Fellow in Endocrinology, Medicine

Duke University

Grants:

Endocrinology and Metabolism Training Program

Administered By
Medicine, Endocrinology, Metabolism, and Nutrition
Awarded By
National Institutes of Health
Role
Mentor
Start Date
End Date

X-linked Hypophosphatemia Disease Monitoring Program (XLH-DMP) UX023-CL401

Administered By
Medicine, Endocrinology, Metabolism, and Nutrition
Awarded By
Ultragenyx Pharmaceutical
Role
Principal Investigator
Start Date
End Date

An integrated and diverse genomic medicine program for undiagnosed diseases

Administered By
Pediatrics, Medical Genetics
Awarded By
National Institutes of Health
Role
Collaborator
Start Date
End Date

Clinical indicators for early bone loss in Common Variable Immunodeficiency

Administered By
Medicine, Pulmonary, Allergy, and Critical Care Medicine
Awarded By
Immune Deficiency Foundation
Role
Collaborator
Start Date
End Date

A Phase 2b, Open-Label, Long-Term Extension Study to Evaluate the Safety and Pharmacodynamics of KRN23 in Adult Subjects with X-Linked Hypophosphatemia (XLH)

Administered By
School of Medicine
Awarded By
Ultragenyx Pharmaceutical
Role
Principal Investigator
Start Date
End Date

Publications:

Burosumab treatment in adults with X-linked hypophosphataemia: 96-week patient-reported outcomes and ambulatory function from a randomised phase 3 trial and open-label extension.

OBJECTIVES: To report the impact of burosumab on patient-reported outcomes (PROs) and ambulatory function in adults with X-linked hypophosphataemia (XLH) through 96 weeks. METHODS: Adults diagnosed with XLH were randomised 1:1 in a double-blinded trial to receive subcutaneous burosumab 1 mg/kg or placebo every 4 weeks for 24 weeks (NCT02526160). Thereafter, all subjects received burosumab every 4 weeks until week 96. PROs were measured using the Western Ontario and the McMaster Universities Osteoarthritis Index (WOMAC), Brief Pain Inventory-Short Form (BPI-SF) and Brief Fatigue Inventory (BFI), and ambulatory function was measured with the 6 min walk test (6MWT). RESULTS: Subjects (N=134) were randomised to burosumab (n=68) or placebo (n=66) for 24 weeks. At baseline, subjects experienced pain, stiffness, and impaired physical and ambulatory function. At week 24, subjects receiving burosumab achieved statistically significant improvement in some BPI-SF scores, BFI worst fatigue (average and greatest) and WOMAC stiffness. At week 48, all WOMAC and BPI-SF scores achieved statistically significant improvement, with some WOMAC and BFI scores achieving meaningful and significant change from baseline. At week 96, all WOMAC, BPI-SF and BFI achieved statistically significant improvement, with selected scores in all measures also achieving meaningful change. Improvement in 6MWT distance and percent predicted were statistically significant at all time points from 24 weeks. CONCLUSIONS: Adults with XLH have substantial burden of disease as assessed by PROs and 6MWT. Burosumab treatment improved phosphate homoeostasis and was associated with a steady and consistent improvement in PROs and ambulatory function. TRIAL REGISTRATION NUMBER: NCT02526160.
Authors
Briot, K; Portale, AA; Brandi, ML; Carpenter, TO; Cheong, HI; Cohen-Solal, M; Crowley, RK; Eastell, R; Imanishi, Y; Ing, S; Insogna, K; Ito, N; Jan de Beur, S; Javaid, MK; Kamenicky, P; Keen, R; Kubota, T; Lachmann, RH; Perwad, F; Pitukcheewanont, P; Ralston, SH; Takeuchi, Y; Tanaka, H; Weber, TJ; Yoo, H-W; Nixon, A; Nixon, M; Sun, W; Williams, A; Imel, EA
MLA Citation
URI
https://scholars.duke.edu/individual/pub1497368
PMID
34548383
Source
pubmed
Published In
Rmd Open
Volume
7
Published Date
DOI
10.1136/rmdopen-2021-001714

Reply to: Burosumab for Tumor-Induced Osteomalacia: not Enough of a Good Thing.

Authors
Jan de Beur, SM; Miller, PD; Weber, TJ; Peacock, M; Insogna, K; Kumar, R; Rauch, F; Luca, D; Cimms, T; Roberts, MS; Martin, JS; Carpenter, TO
MLA Citation
Jan de Beur, Suzanne M., et al. “Reply to: Burosumab for Tumor-Induced Osteomalacia: not Enough of a Good Thing.J Bone Miner Res, May 2021. Pubmed, doi:10.1002/jbmr.4317.
URI
https://scholars.duke.edu/individual/pub1483065
PMID
34030212
Source
pubmed
Published In
J Bone Miner Res
Published Date
DOI
10.1002/jbmr.4317

Diagnosis and Management of Tumor-induced Osteomalacia: Perspectives from Clinical Experience

Purpose: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome of abnormal phosphate and vitamin D metabolism caused by typically small endocrine tumors that secrete fibroblast growth factor 23 (FGF23). TIO is characterized clinically by progressive musculoskeletal pain, fatigue, proximal muscle weakness, and multiple fractures, leading to long-term disability. Misdiagnosis and delayed diagnosis are common because of the nonspecific symptoms, and several years may elapse before patients receive an accurate diagnosis and appropriate treatment. Thus, it is vital that awareness of the appropriate recognition and management of TIO is increased among healthcare professionals who may encounter patients with suspected TIO. Methods: A roundtable meeting was held on 10 January 2020 in Dallas, TX, USA, to gather perspectives on the diagnosis and treatment of TIO. The following topics were considered: clinical presentation, patient history, differential diagnosis, laboratory assessment, imaging, venous sampling, and treatment. Results: This report provides a summary of our collective experiences in the management of TIO. Main conclusions: Laboratory tests are mandatory to expedite TIO diagnosis and should include measurement of fasting serum phosphorus, renal phosphate reabsorption, serum 1,25-dihydroxyvitamin D, and serum FGF23 levels. Functional and anatomical imaging are essential to locate the FGF23-secreting tumor(s) causing TIO. Surgical resection is often a curative treatment when the tumor can be localized; however, better management of patients who cannot be operated on with targeted therapies is needed. Further efforts to increase awareness of TIO within the medical community, and education on recommended diagnostic and treatment pathways are required to improve the management of this debilitating disease.
Authors
Dahir, K; Zanchetta, MB; Stanciu, I; Robinson, C; Lee, JY; Dhaliwal, R; Charles, J; Civitelli, R; Roberts, MS; Krolczyk, S; Weber, T
MLA Citation
Dahir, K., et al. “Diagnosis and Management of Tumor-induced Osteomalacia: Perspectives from Clinical Experience.” Journal of the Endocrine Society, vol. 5, no. 9, Sept. 2021. Scopus, doi:10.1210/jendso/bvab099.
URI
https://scholars.duke.edu/individual/pub1494804
Source
scopus
Published In
Journal of the Endocrine Society
Volume
5
Published Date
DOI
10.1210/jendso/bvab099

Burosumab for the Treatment of Tumor-Induced Osteomalacia.

Tumor-induced osteomalacia (TIO) is caused by phosphaturic mesenchymal tumors producing fibroblast growth factor 23 (FGF23) and is characterized by impaired phosphate metabolism, skeletal health, and quality of life. UX023T-CL201 is an ongoing, open-label, phase 2 study investigating the safety and efficacy of burosumab, a fully human monoclonal antibody that inhibits FGF23, in adults with TIO or cutaneous skeletal hypophosphatemia syndrome (CSHS). Key endpoints were changes in serum phosphorus and osteomalacia assessed by transiliac bone biopsies at week 48. This report focuses on 14 patients with TIO, excluding two diagnosed with X-linked hypophosphatemia post-enrollment and one with CSHS. Serum phosphorus increased from baseline (0.52 mmol/L) and was maintained after dose titration from week 22 (0.91 mmol/L) to week 144 (0.82 mmol/L, p < 0.0001). Most measures of osteomalacia were improved at week 48: osteoid volume/bone, osteoid thickness, and mineralization lag time decreased; osteoid surface/bone surface showed no change. Of 249 fractures/pseudofractures detected across 14 patients at baseline, 33% were fully healed and 13% were partially healed at week 144. Patients reported a reduction in pain and fatigue and an increase in physical health. Two patients discontinued: one to treat an adverse event (AE) of neoplasm progression and one failed to meet dosing criteria (receiving minimal burosumab). Sixteen serious AEs occurred in seven patients, and there was one death; all serious AEs were considered unrelated to treatment. Nine patients had 16 treatment-related AEs; all were mild to moderate in severity. In adults with TIO, burosumab exhibited an acceptable safety profile and was associated with improvements in phosphate metabolism and osteomalacia. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research..
Authors
Jan de Beur, SM; Miller, PD; Weber, TJ; Peacock, M; Insogna, K; Kumar, R; Rauch, F; Luca, D; Cimms, T; Roberts, MS; San Martin, J; Carpenter, TO
MLA Citation
Jan de Beur, Suzanne M., et al. “Burosumab for the Treatment of Tumor-Induced Osteomalacia.J Bone Miner Res, vol. 36, no. 4, Apr. 2021, pp. 627–35. Pubmed, doi:10.1002/jbmr.4233.
URI
https://scholars.duke.edu/individual/pub1470037
PMID
33338281
Source
pubmed
Published In
J Bone Miner Res
Volume
36
Published Date
Start Page
627
End Page
635
DOI
10.1002/jbmr.4233

FRACTURE AND SURGICAL BURDEN IN PEDIATRIC AND ADULT PATIENTS WITH HYPOPHOSPHATASIA: RESULTS FROM PATIENT-REPORTED OUTCOME SURVEYS

Authors
Weber, TJ; Sawyer, EK; Moseley, S; OdrIjin, T; Kishnani, PS
MLA Citation
Weber, T. J., et al. “FRACTURE AND SURGICAL BURDEN IN PEDIATRIC AND ADULT PATIENTS WITH HYPOPHOSPHATASIA: RESULTS FROM PATIENT-REPORTED OUTCOME SURVEYS.” Osteoporosis International, vol. 26, SPRINGER LONDON LTD, 2015, pp. S90–91.
URI
https://scholars.duke.edu/individual/pub1131018
Source
wos
Published In
Osteoporosis International : a Journal Established as Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa
Volume
26
Published Date
Start Page
S90
End Page
S91