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:

Associate 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

University of Chicago

Medical Resident, Medicine

Yale University

Instructor, Medicine

Yale University

Fellow in Endocrinology, Medicine

Duke University

Grants:

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

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

Clinical indicators for early bone loss in Common Variable Immunodeficiency

Administered By
Medicine, Pulmonary, Allergy, and Critical Care Medicine
Role
Collaborator
Start Date
End Date

UX023-CL203 Adult Extension Study

Administered By
Duke Clinical Research Institute
Role
Principal Investigator
Start Date
End Date

UX023-CL303 XLH Study

Administered By
Duke Clinical Research Institute
Role
Principal Investigator
Start Date
End Date

UX023T-CL201 TIO Study

Administered By
Duke Clinical Research Institute
Role
Principal Investigator
Start Date
End Date

Publications:

Impaired calcium sensing distinguishes primary hyperparathyroidism (PHPT) patients with low bone mineral density.

CONTEXT: A subset of PHPT patients exhibit a more severe disease phenotype characterized by bone loss, fractures, recurrent nephrolithiasis, and other dysfunctions, but the underlying reasons for this disparity in clinical presentation remain unknown. OBJECTIVE: We sought to identify new mechanistic indices that could inform more personalized management of PHPT. DESIGN: Pre-, peri-, and postoperative data and demographic, clinical, and pathological information from patients undergoing parathyroidectomy for PHPT were collected. Univariate and partial Spearman correlation was used to estimate the association of parathyroid tumor calcium sensing capacity with select variables. PATIENTS OR OTHER PARTICIPANTS: An unselected series of 237 patients aged >18years and undergoing parathyroidectomy for PHPT were enrolled. MAIN OUTCOME MEASURES: Calcium sensing capacity, expressed as the concentration required for half-maximal biochemical response (EC50), was evaluated in parathyroid tumors from an unselected series of 74 patients and assessed for association with clinical parameters. The hypothesis was that greater disease severity would be associated with attenuated calcium sensitivity and biochemically autonomous parathyroid tumor behavior. RESULTS: Parathyroid tumors segregated into two distinct groups of calcium responsiveness (EC50<3.0 and ≥3.0mM). The low EC50 group (n=27) demonstrated a mean calcium EC50 value of 2.49mM [95% confidence interval (CI): 2.43-2.54mM], consistent with reference normal activity. In contrast, the high EC50 group (n=47) displayed attenuated calcium sensitivity with a mean EC50 value of 3.48mM [95% CI: 3.41-3.55mM]. Retrospective analysis of the clinical registry data suggested that high calcium EC50 patients presented with a more significant preoperative bone mineral density (BMD) deficit with a t-score of -2.7, (95% CI: -3.4 to -1.9) versus 0.9, (95% CI: -2.1 to -0.4) in low EC50 patients (p<0.001). After adjusting for gender, age, BMI, 25 OH vitamin D level and preoperative iPTH, lowest t-score and calcium EC50 were inversely correlated, with a partial Spearman correlation coefficient of -0.35 (p=0.02). CONCLUSIONS: Impaired calcium sensing in parathyroid tumors is selectively observed in a subset of patients with more severe bone mineral density deficit. Assessment of parathyroid tumor biochemical behavior may be a useful predictor of disease severity as measured by bone mineral density in patients with PHPT.
Authors
Weber, TJ; Koh, J; Thomas, SM; Hogue, JA; Scheri, RP; Roman, SA; Sosa, JA
MLA Citation
Weber, Thomas J., et al. “Impaired calcium sensing distinguishes primary hyperparathyroidism (PHPT) patients with low bone mineral density..” Metabolism, vol. 74, Sept. 2017, pp. 22–31. Pubmed, doi:10.1016/j.metabol.2017.06.004.
URI
https://scholars.duke.edu/individual/pub1266055
PMID
28764845
Source
pubmed
Published In
Metabolism
Volume
74
Published Date
Start Page
22
End Page
31
DOI
10.1016/j.metabol.2017.06.004

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

Enzyme replacement therapy (ENB-0040) in hypophosphatasia improves functional outcome and decreases TNSALP substrates in adolescents and adults

Authors
Whyte⁎, MP; Greenberg, CR; Kishnani, P; Madson, K; Mhanni, A; Weber, TJ; Mack, K; Reeves, A; Plotkin, H; Kreher, NC; Landy, H
MLA Citation
Whyte⁎, M. P., et al. “Enzyme replacement therapy (ENB-0040) in hypophosphatasia improves functional outcome and decreases TNSALP substrates in adolescents and adults.” Bone, vol. 50, Elsevier BV, 2012, pp. S39–S39. Crossref, doi:10.1016/j.bone.2012.02.101.
URI
https://scholars.duke.edu/individual/pub922284
Source
crossref
Published In
Bone
Volume
50
Published Date
Start Page
S39
End Page
S39
DOI
10.1016/j.bone.2012.02.101

Osteoporosis in older women

Authors
Pham, AN; Colón-Emeric, CS; Weber, TJ
MLA Citation
Pham, A. N., et al. “Osteoporosis in older women.” Clinical Geriatrics, vol. 17, no. 10, Oct. 2009, pp. 20–28.
URI
https://scholars.duke.edu/individual/pub766039
Source
scopus
Published In
Clinical Geriatrics
Volume
17
Published Date
Start Page
20
End Page
28

Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men.

Transdermal testosterone (T) delivery represents an effective alternative to injectable androgens. We studied 163 hypogonadal men who applied 5, 7.5, or 10 g AndroGel (T gel) 1% CIII per day for up to 42 months. Efficacy data were presented in 123 subjects considered evaluable. Continuous AndroGel treatment normalized mean serum T and free T levels. Mean serum 5alpha-dihydrotestosterone concentrations and 5alpha-dihydrotestosterone/T ratio slightly increased, mean serum estradiol/T ratio doubled, and mean serum FSH and LH levels were suppressed by T replacement. Sexual function and mood parameters improved rapidly and were maintained throughout T treatment. Lean body mass increased (P = 0.0001) and fat mass decreased (P = 0.0001), and these changes were maintained with treatment but were not accompanied by significant increases in muscle strength. Increases in serum bone markers suggestive of increased bone formation were followed by gradual and progressive increases in bone mineral density more in the spine (P = 0.0001) than the hip (P = 0.0004). Mild local skin irritation occurred in 12 subjects, resulting in discontinuation in only one subject. Except for the anticipated increase in hematocrit and hemoglobin, there were no clinically significant changes in blood counts or biochemistry. In three subjects with elevated serum prostate-specific antigen, prostate biopsies showed cancer. We conclude that continued application of AndroGel resulted in beneficial effects similar to those with injectables and other transdermal preparations. This study was neither placebo controlled nor powered to determine the effects of T treatment on prostate cancer risk. Thus, monitoring for prostatic disease and assessment for erythrocytosis are strongly advised to reduce the risk of adverse events with T treatment of hypogonadal men.
Authors
Wang, C; Cunningham, G; Dobs, A; Iranmanesh, A; Matsumoto, AM; Snyder, PJ; Weber, T; Berman, N; Hull, L; Swerdloff, RS
MLA Citation
Wang, Christina, et al. “Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men..” J Clin Endocrinol Metab, vol. 89, no. 5, May 2004, pp. 2085–98. Pubmed, doi:10.1210/jc.2003-032006.
URI
https://scholars.duke.edu/individual/pub805271
PMID
15126525
Source
pubmed
Published In
The Journal of Clinical Endocrinology and Metabolism
Volume
89
Published Date
Start Page
2085
End Page
2098
DOI
10.1210/jc.2003-032006