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Musculoskeletal Health

Musculoskeletal Health

Current Projects

UC Davis Specialized Center of Research (SCOR) on Sex Differences

Researching sex differences in osteoarthritis, kyphosis, osteoporosis, and carpal tunnel syndrome

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Overview

SEX DIFFERENCES IN MUSCULOSKELETAL CONDITIONS ACROSS THE LIFESPAN

Overview:

UC Davis School of Medicine has been awarded a P50 Specialized Centers of Research (SCOR) on Sex Differences grant entitled “Sex Differences in Musculoskeletal Conditions across the Lifespan”.

The Objective

The objective of this proposal, entitled “Sex Differences in Musculoskeletal Conditions Across the Lifespan” (SDMSCAL), is to integrate cutting-edge basic science, epidemiologic, clinical studies and an intervention with an overarching goal of informing and transforming preventive efforts and clinical practice in diagnosis and treatment of these musculoskeletal conditions for both men and women and lead to improvements in women’s health.

The goals of the Center are as follows:

  1. Conduct critical, innovative, cutting edge, interdisciplinary and translational research to expel and characterize sex differences in musculoskeletal conditions over the lifespan.
  2. Translate research to the local and national medical communities.

The center has launching four related studies led by researchers at UC Davis and UC San Francisco. Expert investigators are conducting studies to explore four specific musculoskeletal syndromes that are known to differ by sex: 

Peak bone mass: Wei Yao, assistant professor of internal medicine, oversees a mechanistic study in progesterone receptors that are related to regulation or influence of peak bone mass.

Carpal tunnel syndrome: Jay Han, associate professor of physical medicine and rehabilitation, directs a prospective clinical cohort study using a novel diagnostic technology for diagnosing and treating carpal tunnel syndrome.

Osteoarthritis of the knee: Barton Wise, assistant professor of internal medicine, leads an epidemiologic imaging study to assess bone shape and its influence on the development, severity and prognosis of osteoarthritis of the knee. 

Kyphosis: Wendy Katzman, assistant clinical professor of physical medicine and rehabilitative science at UC San Francisco, leads a study team that will use a randomized clinical trial to examine exercise therapy outcomes in treating kyphosis.

The center at UC Davis is part of the Specialized Centers of Research on Sex and Gender Factors Affecting Women's Health, which was established in partnership with the NIH Office of Research on Women's Health. The specialized centers' program supports scientists who are associated with one or more major medical centers and conducting research that integrates basic, clinical and translational research. The UC Davis-led project is co-funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Faculty and Staff

DIRECTORS

Nancy E. Lane, M.D.
Director - SCOR
Co-Project Leader - SCOR Project 1
Project Leader - SCOR Project 3
Endowed Professor of Medicine and Rheumatology
Director: Musculoskeletal Diseases of Aging Research Group
Co-Director: Building Interdisciplinary Research Careers in Women's Health (BIRCWH)
Co-Director: Center for Translational Research in Osteoarthritis
UC Davis
nelane@ucdavis.edu

Heejung Bang, Ph.D.
co-Director - SCOR Core B
Associate Professor
Division of Biostatistics
Department of Public Health Sciences 
UC Davis
hbang@phs.ucdavis.edu 

Ellen Gold, Ph.D.
Co-Director – SCOR Core A
Co-Director  – SCOR Core B
Professor and Arline Rolkin Chair in Public Health Sciences
Chair, Department of Public Health Sciences
Chief, Division of Epidemiology
UC Davis
ebgold@ucdavis.edu

Barton Wise, M.D., M.Sc.
Associate Director – SCOR Core A
Co-Project Leader – SCOR Project 3
Assistant Professor, Medicine
Center for Musculoskeletal Health
UC Davis
blwise@ucdavis.edu

 

SCOR PROJECT TEAM

Colleen Anthonisen
Research Coordinator - SCOR Project 1
Department of Physical Medicine and Rehabilitation
UC Davis
canthonisen@ucdavis.edu

Jay Han, M.D., M.A.S.
Co-Project Leader - SCOR Project 2
Professor and Vice Chair
Dept. of Physical Medicine & Rehabilitation UC Irvine School of Medicine
jayjhan@uci.edu

Edward Hsiao, M.D., Ph.D.
Consultant – SCOR Project 1
Assistant Professor
Department of Endocrinology
UC San Francisco
edward.hsiao@ucsf.edu
http://cmb.ucsf.edu/cmb/edward-hsiao-md-phd
https://wiki.library.ucsf.edu/display/HsiaoLab/Home

Jeffrey Neil Katz, M.D., M.Sc.
Consultant – SCOR Project 2:
Associate Physician
Professor of Orthopedic Surgery
Brigham and Women’s Hospital
Department of Medicine
Rheumatology, Immunology
jnkatz@partners.org

Nanette Joyce, D.O., M.A.S.
Co-Project Leader - SCOR Project 2
Assistant Professor
Department of Physical Medicine and Rehabilitation (PM&R)
UC Davis
ncjoyce@ucdavis.edu

Wendy Katzman, P.T., D.P.T.Sc., O.C.S.
Project Leader - SCOR Project 4
Associate Professor
Department of PT & Rehabilitation Science
UC San Francisco
wendy.katzman@ucsfmedctr.org

Elizabeth Lincoln
Program Manager
Analyst IV, Supervisor
Center for Musculoskeltal Health
UC Davis
elincoln@ucdavis.edu

Roger Long, M.D.
Co-Investigator: SCOR Project 4
Associate Clinical Professor of Pediatrics
Pediatrics and Endocrinology
UC San Francisco
roger.long@ucsf.edu

John Lynch, Ph.D.
Co-Investigator: SCOR Project 3
OAI Coordinating Center
Director, MRI Quality Assurance
Dept of Epidemiology & Biostatistics
UC San Francisco
jlynch@psg.ucsf.edu

Felix Liu
Project 3: Imaging Assistant
OAI Coordinating Center
Department of Epidemiology
UC San Francisco
fliu@psg.ucsf.edu

Eduard Poltavskiy
Statistical programmer: SCOR Core B
Department of Public Health Sciences
UC Davis
eapoltavskiy@ucdavis.edu

Anne Schafer, M.D.
Co-Investigator: SCOR Project 4
Assistant Professor of Medicine
UC San Francisco and
San Francisco VA Medical Center
anne.schafer@ucsf.edu

Robert Szabo, M.D.
Co-Investigator: SCOR Project 2
Professor, Chief of Hand and Upper Extremity Service
UC Davis
robert.szabo@ucdmc.ucdavis.edu

Wei Yao, M.D.
Project Leader: SCOR Project 1
Associate Professor
Associate Director – Laboratory Core
Center for Musculoskeletal Health
UC Davis
yao@ucdavis.edu

Yuqing Zhang, D.Sc., M.P.H., M.B.
Project 3: Consultant
Professor of Medicine and Public Health
Boston University – School of Medicine
yuqing@bu.edu

Research

Four main studies are focused on musculoskeletal syndromes:

Project 1: Sex differences in progesterone receptor regulation of peak bone mass, Wei Yao, M.D., Project Leader

Project 2: Sex differences in carpal tunnel syndrome using person reported outcomes and high-resolution ultrasound, Jay J. Han, M.D., Co-Project Leader; Nanette C. Joyce, Co-Project Leader

Project 3: Sex differences in bone shape and knee osteoarthritis: the Osteoarthritis Initiative, Barton L. Wise, M.D., Project Leader

Project 4: Sex Differences in response to an exercise intervention for kyphosis, Wendy B. Katzman, P.T., D.P.T.Sc., O.C.S., Project Leader

 

PILOT STUDIES:

  • Estrogen modulation of mitochondrial calcium in heart failure via mitochondrial protein (TSPO), Saul Schaefer, M.D., Cardiovascular Medicine, SOM, UC Davis (sschaefer@ucdavis.edu)
  • Histopathology-based validation of imaging biomarkers of trapeziometacarpal Osteoarthritis of the thumb, Robert Boutin, M.D., Clinical Radiology, Department of Radiology, UC Davis (robert.boutin@ucdmc.ucdavis.edu
  • Investigating the molecular mechanisms of the progesterone receptor regulating bone formation in bone, Alex Zhong, Ph.D., Center for Musculoskeletal Health, SOM UC Davis (zazhong@ucdavis.edu)
  • Sex-specific Genetic effects in rheumatoid arthritis - PI: Damini Jawaheer, Ph.D., Children’s Hospital Oakland Research Institute (CHORI), California (djawaheer@chori.org)

 

Project 1: Sex differences in progesterone receptors regulation of peak bone mass.

Summary

Osteoporosis is a major public health problem, with over 50% of Caucasian women and nearly 20% of Caucasian men at risk for an osteoporotic fracture in their lifetime (NIH Osteoporosis and Related Bone Diseases – National Resource Center). While some of the predictors of peak bone mass (PBM) include genetic predisposition and environmental factors, such as physical activity and diet, peak bone mass is also influenced by rapid changes in reproductive hormone levels for both genders, especially estrogen and progesterone during the accelerated growth period. Despite its well-studied effects in the reproductive system, progesterone’s effects on bone metabolism remain largely unknown. In our laboratory, mice whose nuclear progesterone receptors (PR) were rendered nonfunctional (PRKO) exhibited a rapid gain of bone mass (age 1-3 months) and greater peak bone mass but with a sex difference in magnitude of increase (3- fold higher PBM in females and +50% in males) in comparison to their wild type (WT) litter mates (Yao et al. 2009). Thus, the presence of progesterone nuclear receptors exerts inhibitory effects on bone formation during the period of rapid bone acquisition, and this inhibition is more profound in female mice. Based on our preliminary observations, we hypothesize that progesterone signaling inhibits bone formation during the rapid bone growth period such that peak bone mass is lower in females than in males. We further hypothesize that inhibition of progesterone signaling in osteoblasts during the period of rapid bone acquisition period accelerates achievement of peak bone mass, especially for females. To test our hypotheses, we propose the following specific aims:

Specific Aim 1: To investigate the direct effects of PR deletion on osteoblast and bone formation and compare these effects in female and male mice.

Specific Aim 2: To determine if the inhibition of PR in vivo will lead to an uncoupling of bone turnover, we will monitor bone architecture and bone turnover changes following these interventions to determine how these interventions affect peak bone mass acquisition and if the responses would be differ between the sexes.

Relevance

Osteoporosis is a major public health problem that currently affects 44 million Americans. Progesterone is known for its effects on the reproductive system, but its physiological roles in skeletal metabolism remains unclear. This study aims to clarify differences in peak bone mass acquisition between sexes with the overall goal of explaining sex differences in musculoskeletal diseases across the lifespan.

 

Project 2: Sex differences in carpal tunnel syndrome using person reported outcomes and high-resolution ultrasound.

Summary

Carpal tunnel syndrome (CTS) is the most frequently occurring peripheral nerve entrapment disorder (median nerve at the wrist) and is also one of the most prevalent modern-age upper limb musculoskeletal disorders. Despite its prevalence, the exact etiology and pathophysiology underlying CTS is unclear at this time. This project will address these gaps in knowledge and contribute to furthering our understanding of disease mechanism, and thereby improve the overall clinical care of patients with CTS by offering preventive measures or alternative therapeutic strategies. The proposed study is novel for the CTS field, and represents the largest natural history study incorporating the state-of-the-art high-resolution ultrasound (HRUS) and electrodiagnosis/electromyography (EDX) methodologies. We will follow a cohort of females and males with idiopathic CTS using a prospective natural history study design with 6 weeks of ‘standard-of-care’ conservative wrist splint treatment, and follow up for 12 months with the following aims. Aim 1: To determine and compare the baseline HRUS characteristics in females with and without idiopathic CTS (adjusted for age and BMI), and in males with and without idiopathic CTS (adjusted for age and BMI). Aim 2: To determine and compare by sex the ability of novel HRUS characteristics and patient-reported outcome measures in CTS to detect treatment effect changes between the pre- and post-treatment in men and women after 6 weeks of standard nocturnal neutral wrist splint treatment; and evaluate for correlation with other traditional measures of CTS severity and progression (as measured by hand diagram, sensibility testing, provocative maneuvers, and EDX parameters). Aim 3: To determine and compare the patient characteristics (age, sex, BMI, wrist anthropometrics, job-related risk factors), health-related quality of life measures, and clinical measures for CTS severity (physical measures, electrodiagnostic and sonographic parameters) in relation to short- and long-term outcomes in idiopathic CTS. 

Relevance

Establishment of standardized high-resolution ultrasound methodologies and determination of test capabilities in the diagnosis and monitoring of carpal tunnel syndrome will have important impact not only in health care of individuals with carpal tunnel syndrome but will also have far-reaching implications of reduced healthcare cost to society and increased economic productivity.

 

Project 3: Sex differences in bone shape and knee osteoarthritis: the Osteoarthritis Initiative.

Summary

Incidence and prevalence of either radiographic or symptomatic osteoarthritis (OA) are much higher in women than men; however, the underlying causes for this sex difference in OA remain unknown. Several potential explanations have been proposed for the sex difference in OA, including differences in estrogen level, physical activity, and laxity or alignment, but each has only moderate supporting evidence, and none fully explains the observed sex differences. Recently, several investigators have proposed that aspects of bone shape are associated with an increased risk of incident OA and with severity of OA, based on anthropometric measures, cross-sectional findings, or in one case statistical shape modeling done on 24 knees. Our group demonstrated that several specific proximal femoral shapes, assessed by Active Shape Modeling (ASM), were associated with incident radiographic hip OA in elderly women. Others have also reported that ASM-based knee shape is associated with severity of radiographic knee OA. It is postulated that changes in bone shape occur prior to cartilage damage in the joint. In the proposed study, we will take advantage of knee radiographs and magnetic resonance images (MRIs) collected annually for 5 years in the Osteoarthritis Initiative (OAI). We will measure femoral and tibial bone shape using an ASM method improved by our group. We will evaluate whether baseline bone shape is associated with incidence or progression of radiographic knee OA, pain and function and whether these associations differ by sex. We will apply group-based finite modeling methods to identify distinctive sub-groups that follow similar trajectories of bone shape change over time in women and men respectively and examine whether associations between various risk factors assessed at baseline (i.e., age, sex, body mass index, alignment, etc.) and membership of trajectories of bone shape differ by sex using a multinomial logistic regression model. Finally, we will evaluate the risk factors that determine sex-specific trajectories of bone shape change over time.

Relevance:

To our knowledge, no study has yet described the trajectories of changes in bone shape over time, examined how those trajectories differ by sex, or identified the risk factors that determine sex-specific trajectories of bone shape change over time. In the proposed study, we will take the advantage of knee radiographs and magnetic resonance images collected annually for 5 years in the Osteoarthritis Initiative.

 

Project 4: Gender response to exercise for hyperkyphosis.

Summary

Spinal deformity has an important and measurable impact on physical function and health-related quality of life (HRQoL), particularly in older adults. Deformity in the sagittal plane has the largest impact on clinical health status of older adults, increasing pain, and compromising gait speed, functional reach, balance, selfimage, and satisfaction with life in general. Hyperkyphosis is an important cause of sagittal plane malalignment and has been associated with poor health outcomes, including falls, fractures, activities of daily living (ADL) disability, and mortality. Higher prevalence of hyperkyphosis has been reported among females versus males, 28% versus 14%, respectively. Hyperkyphosis is accompanied by spinal muscle weakness17- 19 that may be modifiable with exercise. Sex differences in muscle strength may differentially affect the severity of hyperkyhosis and modify the response to exercise. Currently, there are few evidence-based treatments targeted to reduce hyperkyhosis and no proven exercise interventions that reduce hyperkyphosis and delay functional decline and disability. The primary hypothesis of project IV is that interventions that reduce hyperkyphosis by improving spinal muscle strength will also delay functional decline and disability, and could, therefore, have significant public health benefits. No study examining the impact of exercise to improve hyperkyphosis has determined whether treatment effects differ according to sex. This project proposes a paradigm where physical function can be improved in an exercise intervention targeted at reducing hyperkyphosis, which may reduce associated disability. Pilot work conducted by the project research team suggests that the approach is feasible and potentially effective. Project IV proposes a randomized controlled trial comparing a 12-week high-intensity spinal strengthening exercise intervention and home exercise practice to a control stretching intervention in community-dwelling males and females 55- 80 years old with hyperkyphosis. All primary and secondary outcomes will be compared between the exercise and the control group after 12-weeks. The long-term goal is to develop interventions to delayfunctional decline and physical disability in older males and females and to identify those who would most benefit from interventions.

Relevance:

Exercise interventions targeted at increasing function in older adults often neglect posture and spinal muscle weakness. No study examining the impact of exercise to improve hyperkyphosis has determined whether treatment effects differ according to sex. The aims of Project IV propose a paradigm where physical function can be improved in an exercise intervention targeted at reducing hyperkyphosis, which may reduce associated disability.

Advisory Boards

INTERNAL ADVISORY BOARD

Laurel A. Beckett, Ph.D.
Professor and Chief, Division of Biostatistics
Vice Chair of the Department of Public Health Sciences,
Biostatistics Unit
Department of Public Health Sciences
One shields Avenue
University of California
Davis, California 95616
530-754-6793
labeckett@ucdavis.edu

Nancy Byl , P.T., Ph.D., M.P.H., F.A.P.T.A.
Professor Emeritus
UC San Francisco School of Medicine Physical Therapy & Rehab Sciences
1675 Owens Street
San Francisco CA 94143
415-514-4816    
BylN@ptrehab.ucsf.edu

Diana L. Farmer, M.D.
Chair, Department of Surgery
UC Davis Children's Hospital
2315 Stockton Blvd.
Sacramento, CA 95617
916-734-3190
dlfarmer@ucdavis.edu

Sharmila Majumdar, Ph.D.
Vice Chair for Research, Professor, and
Director Musculoskeletal and Quantitative Imaging Research Group (MQIR),
Department of Radiology and Biomedical Imaging,  UC San Francisco
Professor Dept. of Orthopedic Surgery, UC San Francisco
Professor, Dept. of Bioengineering, UC Berkeley
Campus Box  2520
QB3 Building, 2nd Floor, Suite 203
1700 - 4th Street,
UC San Francisco
San Francisco, CA 94158
415-476-6830, 415-353-4534
Sharmila.Majumdar@ucsf.edu

Michael C. Nevitt, Ph.D., M.P.H.
Professor
PI, Osteoarthritis Initiative Coordinating Center
UC San Francisco
SF Coordinating Center
OAI Coordinating Center
Dept. of Epidemiology and Biostatistics
185 Berry Street
Lobby 5, Suite 5700
San Francisco, CA 94107
415-514-8048
mnevitt@psg.ucsf.edu

Robert A. Nissenson, Ph.D.
Professor of Medicine and Physiology
University of California, San Francisco
VA Medical Center
4150 Clement Street (111 N)
University of California
San Francisco, California 94121
415-750-2089
Robert.Nissenson@ucsf.edu

Eric Vittinghoff Ph.D.
Division of Biostatistics
Department of Epidemiology and Biostatistics
UC San Francisco
185 Berry St, Lobby 5, Suite 5700
San Francisco, CA 94107
415-514-8025
eric@biostat.ucsf.edu

 

EXTERNAL ADVISORY BOARD

Marc C. Hochberg, M.D., M.P.H.
CHAIR, SCOR EAB
Professor of Medicine and Epidemiology and Public Health
Head, Division of Rheumatology & Clinical Immunology
University of Maryland School of Medicine
10 S. Pine St., MSTF 8-34
Baltimore, MD 21201
410-706-6474
mhochber@medicine.umaryland.edu

Jeffrey Duryea Ph.D.
Associate Professor
Harvard Medical School Department of Radiology
Brigham and Women's Hospital
75 Francis St.
Boston, MA 02115
617-525-8251
jduryea@bwh.harvard.edu

Mark L. Johnson, Ph.D.
Professor and Chair
Department of Oral Biology
School of Dentistry
University Missouri, Kansas City
650 East 25th Street
Kansas city, MO   64108
816-235-2453
Johnsonmark@umkc.edu

Kathy M. Shipp, P.T., M.H.S., Ph.D, G.C.S.
Associate Professor
Division of Physical Therapy
Department of Community and Family Medicine
Senior Fellow, Center for the Study of Aging and Human Development
Duke University
DUMC Box 104002
Durham, NC  27708
919-681-1692
kathy.shipp@duke.edu

Outreach

COMMUNITY OUTREACH ACTIVITIES

Presentations to inform the community of sex differences in musculoskeletal diseases across the lifespan:

"Hyperkyphosis: Are we destined to stoop with aging? Translating research into clinical practice"
November 18, 2015, UCSD Endocrinology Grand Rounds, UCSD
Wendy Katzman, PT, DPTSc, OCS, Physical Therapy and Rehab Science, UCSF

Kyphosis and Exercise: What Have We Learned?
November 4, 2015, Ella Health
Wendy Katzman, PT, DPTSc, OCS, Physical Therapy and Rehab Science, UCSF

Research Overview Bone Targeted Delivery of MSCs to Augment Bone Formation
June 9, 2015, taping of Musculoskeletal Symposium/SOM Dean’s Office to be posted on UCDHS website for health system friends and donors
Wei Yao, MD, Center for Musculoskeletal Health, UC Davis

Osteoarthritis and Pain
May 18, 2015, Inter-Professional Interest Group on Aging, School of Medicine, UC Davis
Barton Wise, MD, MSc, Center for Musculoskeletal Health, UC Davis

Exercise Recommendations to Reduce Vertebral Fractures
May 15, 2015, National Osteoporosis Foundation Annual Meeting, Washington, DC
Wendy Katzman, PT, DPTSc, OCS, Physical Therapy and Rehab Science, UCSF

Research Overview Bone Targeted Delivery of MSCs to Augment Bone Formation
April 20, 2015, Center for Musculoskeletal Symposium/SOM Dean’s Office, UC Davis
Wei Yao, MD, Center for Musculoskeletal Health, UC Davis

Sex differences in Kyposis and response to treatments”
April 20, 2015, Center for Musculoskeletal Symposium/SOM Dean’s Office, UC Davis
Wendy Katzman, PT, DPTSc, OCS, Physical Therapy and Rehabilitation Science, UCSF

"Hyperkyphosis: Are we destined to stoop with aging? Translating research into clinical practice"
February 18, 2015, SCOR Science Exchange, UC Davis
Wendy Katzman, PT, DPTSc, OCS, Physical Therapy and Rehabilitation Science, UCSF

Osteoarthritis and Pain
February 10, 2015, UC Davis Pain Division’s Project ECHO Telementoring Lecture Series; broadcast via web to approximately 20 institutions with estimated 120 persons in attendance
Barton Wise, MD, MSc, Center for Musculoskeletal Health, UC Davis

"Age-Related Hyperkyphosis: Are We Destined to Stoop With Aging?”
February 7, 2015. American Physical Therapy Association Combined Sections Meeting, Indianapolis,Indiana
Wendy Katzman, PT, DPTSc, OCS, Physical Therapy and Rehabilitation Science, UCSF

"The Association of Knee Shape with Sex: The Osteoarthrtis Initiave
November 17, 2014, American College of Rheumatology 2014 Annual Meeting, Boston MA
Barton Wise, MD, MSc, Center for Musculoskeletal Health, UC Davis

"Osteoarthritis"
Lupus Foundation of Northern California Fall 2014 Lupus Treatment and Research Update
November 10, 2014
UC Davis Medical Center, Health and Technology (CHT) Building, Conf Room 1341
Nancy E. Lane, MD, UC Davis, Center for Musculoskeletal Health

“Inter-rater reliability of various commonly used median motor and sensory nerve conduction studies for evaluation of carpal tunnel syndrome
October 29, 2014, American Association of Neuromuscular & Electrodiagnostic Medicine 61st Annual Meeting, Savannah, GA
Bethany M. Lipa, Sarah E. Humbert, Eduard Poltavskiy, Heejung Bang, Colleen Anthonisen, Jay J. Han

Inter-rater reliability of the median motor nerve conduction study among electrodiagnosticians with varying levels of experience
October 29, 2014, American Association of Neuromuscular & Electrodiagnostic Medicine 61st Annual Meeting, Savannah, GA
Nathan Swain, Sarah E. Humbert, Bethany M. Lipa, Que H. Nguyen, Nanette Joyce, Jay J. Han

Effects of Sclerostin antibody on osteoblast and osteocyte viability/autophagy in mouse model of glucocorticoid-induced bone loss
September 14, 2014, American Society for Bone and Mineral Research Annual Meeting, Houston, Texas
Wei Yao, MD, Center for Musculoskeletal Health, UC Davis

Progesterone Receptor in Bone Cells Regulates Bone Mass Accrual
September 13, 2014, American Society for Bone and Mineral Research Annual Meeting, Houston, Texas
Wei Yao, MD, Center for Musculoskeletal Health, UC Davis

"Novel Approaches for the Prevention and Treatment of Inflammatory Bone Loss"
September 12, 2014, American Society for Bone and Mineral Research Annual Meeting, Houston, Texas
Nancy Lane, MD, Center for Musculoskeletal Health, UC Davis

Bone-specific progesterone receptor (PR) inhibition augments bone mass acquisition with sexual  dimorphism
August 3, 2014, International Bone & Mineral Society – 44th International Sun Valley Workshop: Musculoskeletal Biology
Alex Zhong, PhD, Center for Musculoskeletal Health, UC Davis

Bone-specific progesterone receptor (PR) inhibition augments bone mass acquisition with sexual dimorphism
August 3, 2014, International Bone & Mineral Society – 44th International Sun Valley Workshop: Musculoskeletal Biology (poster)
Alex Zhong, PhD, Center for Musculoskeletal Health, UC Davis

"Conditional knockout of progesterone receptor in the osteoprogenitor cells, but not in the mature osteoblasts, increases trabecular bone formation"
Plenary poster presentation, October 9th, 2015, American Society for Bone and Mineral Research meeting, Seattle, WA
Wei Yao, Center for Musculoskeletal Health, UC Davis

"Inactivation of the progesterone receptor in Mx1+ cells potentiates osteogenesis in vitro but not in vivo"
Poster presentation, October 12th, 2015, American Society for Bone and Mineral Research meeting, Seattle, WA
Wei Yao, Center for Musculoskeletal Health, UC Davis

"Bone targeted delivery of mesenchymal stem cells for fracture healing and sex difference"
Poster presentation,  October 11th, 2015, American Society for Bone and Mineral Research meeting, Seattle, WA
Wei Yao, Center for Musculoskeletal Health, UC Davis

 

 

 

 

 

"Sex Differences in Kyphosis and Response to Treatments"
August 1, 2014, AAOS/CORR/ORS/CMH-UCD/SWHR Musculoskeletal Sex Difference Throughout the Lifespan Research Symposium, Rosemont, Ill
Wendy Katzman, PT, DPTSc, OCS, Physical Therapy and Rehabilitation Science, UCSF

"Do Women Recover as Well as Men after Knee Replacement?"
August 1, 2014, AAOS/CORR/ORS/CMH-UCD/SWHR Musculoskeletal Sex Difference Throughout the Lifespan Research Symposium, Rosemont, Ill
Barton Wise, MD, MSc, Center for Musculoskeletal Health, UC Davis

Progesterone nuclear receptor and peak bone mass
July 31, 2014, AAOS/CORR/ORS/CMH-UCD/SWHR Musculoskeletal Sex Difference Throughout the Lifespan Research Symposium, Rosemont, Ill
Wei Yao, MD, Center for Musculoskeletal Health, UC Davis

Inflammatory Arthritis: Why Does Sex Make a Difference?
July 31, 2014, AAOS/CORR/ORS/CMH-UCD/SWHR Musculoskeletal Sex Difference throughout the Lifespan Research Symposium, Rosemont, Ill
Nancy E. Lane, MD, Center for Musculoskeletal Health, UC Davis

Bone-specific progesterone receptor (PR) inhibition augments bone mass acquisition with sexual dimorphism
July 30, 2014, AAOS/CORR/ORS/CMH-UCD/SWHR Musculoskeletal Sex Difference Throughout the Lifespan Research Symposium, Rosemont, Ill (poster)
Alex Zhong, PhD, Center for Musculoskeletal Health, UC Davis

Teriparatide Alone and in Combination with Anti-Resorptives
July 24, 2014, 11th Annual Osteoporosis: New Insights in Research, Diagnosis and Clinical Care, UCSF, San Francisco, CA.
Anne Schafer, MD, UCSF and the San Francisco VA Medical Center

Bad to the Bones: Corticosteroids and Prevention of Corticosteroid-induced Osteoporosis
July 24, 2014, 11th Annual Osteoporosis: New Insights in Research, Diagnosis, and Clinical Care, UCSF San Francisco, CA
Nancy E. Lane, MD, Center for Musculoskeletal Health, UC Davis

"Kyphosis: Causes, Consequences, Treatment"
July 24, 2014, 11th Annual Osteoporosis: New Insights in Research, Diagnosis and Clinical Care, UCSF, San Francisco, CA.
Wendy Katzman, PT, DPTSc, OCS, Physical Therapy and Rehabilitation Science, UCSF

Take steps to improve posture
July 16, 2014, San Francisco Jewish Community Center
Wendy Katzman, PT, DPTSc, OCS, Physical Therapy and Rehabilitation Science, UCSF

"Post-EULAR Clinical Update"
July 16, 2014, Northern California Rheumatology Society, Sacramento, CA
Nancy Lane, MD, Center for Musculoskeletal Health, UC Davis; Yusuf Yazici, MD, NYU Langone Medl Ctr

"Background on aNGF Therapy and Results from the Placebo-Controlled Clinical Trials Including the Non-Serious Joint Related Adverse Events"
July 11, 2014, International Workshop on Osteoarthritis Imaging, Reykjavik, Iceland
Nancy E. Lane, MD, Center for Musculoskeletal Health, UC Davis

The association of knee shape with sex: the Osteoarthritis Initiative
July 9, 2014, International Workshop on Osteoarthritis Imaging, Reykavik, Iceland
Wise BL, Kritikos L, Liu F, Parimi N, Lynch JA, Zhang Y, Lane NE

Joint Effort on Osteoarthritis
May 27, 2014, Davis Orthopaedic Surgery Grand Rounds, UC Davis
Barton Wise, M.D., M.Sc. Center for Musculoskeletal Health, UC Davis

Osteoarthritis: Yesterday, Today and Tomorrow
May 21, 2014, Indian Health Services California Providers’ Best Practices and GPRA Measures Conference,  Sacramento, CA
Barton Wise, M.D., M.Sc. Center for Musculoskeletal Health, UC Davis

A new method of measuring frontal plane femoral shaft curvature provides preliminary data on an association between femoral shape, weight, and the difference between anatomic and mechanical alignment in knees with, or at risk of developing osteoarthritis
April 26, 2014, Osteoarthritis Research Society International (OARSI) World Congress, Paris, France
Wu D, Liu F, Lynch JA, Li X, Wise BL, Lane NE.

The Treatment of Osteoporosis and Rheumatoid Arthritis With a Little Help from Your Own Stem Cells"
April 16, 2014, Grand Rounds, Case Western Reserve University, Cleveland, OH
Nancy E. Lane, MD, Center for Musculoskeletal Health, UC Davis

The Art of Aging Gracefully Resource Fair – on Posture Screening
April 10, 2014, Jewish Community Center, San Francisco
Wendy Katzman, PT, DPTSc, OCS, Physical Therapy and Rehabilitation Science, UCSF

Healthy Bones Fight Fracture with Fitness
January 29, 2014, University of California Television (UCTV): http://www.youtube.com/watch?v=BixyHtp_fjI
Wendy Katzman, PT, DPTSc, OCS, Physical Therapy and Rehabilitation Science, UCSF

SCOR and Active Shape Modeling
November 14, 2013, UC Davis Biomedical Engineering group, University of California, Davis, CA.
Nancy E. Lane, MD and Barton Wise, M.D., M.Sc. Center for Musculoskeletal Health, UC Davis

"Vitamin D and Health"
October 28, 2013, American College of Rheumatology Annual Meeting, San Diego, CA
Nancy E. Lane, MD, Center for Musculoskeletal Health, UC Davis

"The Association of Proximal Tibia Shape with Sex: The Osteoarthritis Initiative” (Poster)
October 27, 2013 American College of Rheumatology Annual Conference, San Diego, CA,
Wise  BL, Liu F, Parimi N, Lynch JA, Zhang Y, Kritikos L, Lane NE.

"Effects of Inflammation in the Bone"
"FGF23: Emerging Concepts and Controversies"
October 4-7, 2013, American Society of Bone and Mineral Research Annual meeting, Baltimore, MD
Nancy E. Lane, MD, Center for Musculoskeletal Health, UC Davis

Directing MSCs to the Bone Surface to Form Bone with LLP2A-Ale
September 18, 2013, Stem Cell Research and Regenerative Medicine Retreat, UC Davis
Wei Yao, MD, Center for Musculoskeletal Health, UC Davis

Take steps to improve your posture"
September 16, 2013, Carlisle Retirement Home, San Francisco
Wendy Katzman, PT, DPTSc, OCS, Physical Therapy and Rehabilitation Science, UCSF

"Are HIV-infected women at greater risk for hyperkyphosis?"
September 13, 2013, Women’s HIV Study, University of California, San Francisco
Wendy Katzman, PT, DPTSc, OCS, Physical Therapy and Rehabilitation Science, UCSF

"Early Identification and Early Intervention in Osteoarthritis: From Tissue to Function"
August 28, 2013, SCOR Science Exchange, UC Davis
Deepak Kumar, PT, Ph.D., OCS, Musculoskeletal Research, UCSF

Investigating the mechanisms of progesterone receptor regulating bone formation in Bone”
August 3, 2014, 44th Sun Valley Workshop on Musculoskeletal Biology in Sun Valley, Idaho
Wei Yao, MD, Center for Musculoskeletal Health, UC Davis

Progesterone Receptor (PR) Regulates Bone Growth, in Bone?
July 10, 2013, Molecular Medicine and Biochemistry Research Meeting, UC Davis
 Alex Zhong, PhD, Center for Musculoskeletal Health, UC Davis

Effects of Glucocorticoid and Bone Material Properties"
May 17, 2013, AAOS/ORS Bone Quality and Fracture Prevention Research Symposium, Rosemont, Ill
Nancy E. Lane, MD, Center for Musculoskeletal Health, UC Davis

Bone Health
May 9, 2013, UC Davis TV (Health Education TV)
Wendy Katzman, PT, DPTSc, OCS, Physical Therapy and Rehabilitation Science, UCSF

Steps to improve your posture
May 6, 2013, Jewish Community Center of SF
Wendy Katzman, PT, DPTSc, OCS, Physical Therapy and Rehabilitation Science, UCSF

Causes, consequences and treatments for hyperkyphosis
May 4, 2013, UCSF/SFSU Graduation Program in Physical Therapy Research Symposium-Keynote speaker
Wendy Katzman, PT, DPTSc, OCS, Physical Therapy and Rehabilitation Science, UCSF

New option for Osteoporosis
April 10, 2013, China
Wei Yao, MD, Center for Musculoskeletal Health, UC Davis

Scintigraphic Tracking of Mesenchymal Stem Cells in the Equine Distal Limb
May 13, 2013, Musculoskeletal Stem Cell Symposium, Ctr for Musculoskeletal Health/Veterinary Med, UCD
Martin Vidal, BVSc, MS, PhD, DACVS, Surgical and Radiological Sciences, School of Vet Med, UC Davis

Regenerative Approach to Mandibular Bone Defects in Dogs Using rhBMP-2” 
May 13, 2013, Musculoskeletal Stem Cell Symposium, Ctr for Musculoskeletal Health/Veterinary Med, UCD
Boaz Arzi, DVM, DAVDC, Surgical and Radiological Sciences, School of Vet Med, UC Davis UC Davis

Clinical Application of Stem Cells in Horses
May 13, 2013, Musculoskeletal Stem Cell Symposium, Ctr for Musculoskeletal Health/Veterinary Med, UCD
Larry D. Galuppo, DVM, Dipl ACVS, Surgical and Radiological Sciences, School of Vet Med, UC Davis

Directing MSCs to the bone surface to form bone with LLP2A-Aln
May 13, 2013, Musculoskeletal Stem Cell Symposium, Ctr for Musculoskeletal Health/Veterinary Med, UCD
Nancy Lane, MD; Wei Yao, MD, Center for Musculoskeletal Health, UC Davis

Scaffold-mediated cues for instructing osteoprogenitor cells
May 13, 2013, Musculoskeletal Stem Cell Symposium, Ctr for Musculoskeletal Health/Veterinary Med, UCD
J. Kent Leach, Ph.D, Department of Biomedical Engineering, UC Davis

Bone Regeneration in Critical-Sized Calvarial Defect Model in Rats
May 13, 2013, Musculoskeletal Stem Cell Symposium, Ctr for Musculoskeletal Health/Veterinary Med, UCD
David Sahar, MD, Department of Surgery, UC Davis

Nanofibrous scaffolds and stem cells for tissue regeneration
May 13, 2013, Musculoskeletal Stem Cell Symposium, Ctr for Musculoskeletal Health/Veterinary Med, UCD
Aijun Wang, Ph.D, Department of Surgery, UC Davis

Enhanced retention of MSC after hypoxic pre-conditioning
May 13, 2013, Musculoskeletal Stem Cell Symposium, Ctr for Musculoskeletal Health/Veterinary Med, UCD
Fernando Fierro, Ph.D., Stem Cell Research Program, Dept. of Cell Biology and Human Anatomy,UC Davis

An update on Mesenchymal Stem Cell Therapies to treat osteoporosis
March 2013, Grand Rounds, Division of Rheumatology, UCLA
Nancy E. Lane, MD, Center for Musculoskeletal Health, UC Davis

An update on gout and arthritis
March 2013, Grand Rounds, UC Davis
Nancy E. Lane, MD, Center for Musculoskeletal Health, UC Davis

Osteoarthritis, Yesterday, Today and Tomorrow
February 23, 2013, Mini Medical School, University of California, Davis
Barton Wise, M.D., M.Sc. Center for Musculoskeletal Health, UC Davis

New option for Osteoporosis
February 9, 2013, Pathology, UC Davis
Wei Yao, MD, Center for Musculoskeletal Health, UC Davis

Work In Progress Seminar for BIRCWH/MCRTP/K12
December 18, 2012, University of California, Davis School of Medicine,
Barton Wise, M.D., M.Sc. Center for Musculoskeletal Health, UC Davis

Osteoarthritis: Yesterday, Today and Tomorrow
December 13, 2012, Grand Rounds, Dept. of Internal Medicine, UC Davis
Barton Wise, M.D., M.Sc. Center for Musculoskeletal Health, UC Davis

An update on Osteoporosis, diagnosis and therapy
December 2012, Family Practice Grand Rounds,
Nancy E. Lane, MD, Center for Musculoskeletal Health, UC Davis

No Weight Change After Knee Replacement: the Multicenter Osteoarthritis Study
December 3, 2012, Bay Area Clinical Research Symposium, San Francisco, CA
Barton Wise, M.D., M.Sc. Center for Musculoskeletal Health, UC Davis

Risk Factors for Knee Replacement in the MOST Cohort
November 28, 2012, Multicenter Osteoarthritis Study (MOST) Steering Committee and OSMB, Bethesda, MD. 
Barton Wise, M.D., M.Sc. Center for Musculoskeletal Health, UC Davis

Instrumental variables and Propensity Scores
November 2, 2012,Comparative Effectiveness Research class/discussion, CTSC, UC Davis
Barton Wise, M.D., M.Sc. Center for Musculoskeletal Health, UC Davis

Risk Factors for Knee Replacement in the MOST Cohort: Parity and Functional Impairment
October 31, 2012, Joint BIRCWH UCSF and UC Davis Research Seminar, UC Davis
Barton Wise, M.D., M.Sc. Center for Musculoskeletal Health, UC Davis

Osteoarthritis Epidemiology and Risk Factors
October 5, 2012, 43rd Annual Arthritis Foundation Rheumatology Symposium on Common Rheumatic Diseases: Osteoarthritis and Fibromyalgia, Via Christi Hospital System, Wichita, KS,
Barton Wise, M.D., M.Sc. Center for Musculoskeletal Health, UC Davis

New option for Osteoporosis
October 4, 2012,  American Society for Bone and Mineral Research 2012 Annual Meeting, Minneapolis, MN.
Wei Yao, MD, Center for Musculoskeletal Health, UC Davis

“Healthcare Economics and Single Payer Solutions
September 28, 2012, American Medical Students Association (AMSA), UC Davis
Barton Wise, M.D., M.Sc. Center for Musculoskeletal Health, UC Davis

Essential Rheumatologic Conditions
September 26, 2012, Second-year medical students, UC Davis School of Medicine
Barton Wise, M.D., M.Sc. Cen ter for Musculoskeletal Health, UC Davis

Publications

Project I: Sex differences in progesterone receptor regulation of peak bone mass

Zhong ZA, Sun W, Chen H, Lay YA, Lane NE, Yao W. Bone mass accrual changes in mouse models of targeted PR deletion in the osteoprogenitor cells. Manuscript Submitted.

Inactivation of PR in Prrx1+ osteoprogenitor cells resulted in higher trabecular bone mass and bone formation in both sexes.  Our resultes reveal PR in osteoprogenitor cells to be a potential target for bone mass augmentation.

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Dai W, Zhang H, Zhong Z, Jiang L, Chen H, Lay Y, Kot A, Ritchie R, Lane N, Yao W. β-Ecdysone Augments Peak Bone Mass in Mice of Both Sexes. Clin Orthop Relat Res. 2015 Aug;473(8):2495-2504. PMID: 25822452; PMCID: PMC4488193.
 
In this study, we found β-Ecdysone increased bone formation rate, suppressed bone resorption, and increased trabecular bone, cortical bone volume, and bone strength in both male and female mice. However, trabecular bone loss was completely prevented by β-Ecdysone in androgen deficient mice animals and partially prevented by β-Ecdysone in the estrogen-deficient mice.

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Dai W, Jiang L, Lay YA, Chen H, Jin G, Zhang H, Kot A, Ritchie RO, Lane NE, Yao W. Prevention of glucocorticoid induced bone changes with beta-ecdysone. Bone. Bone. 2015 May;74:48-57. PMID: 25585248;  PMCID: PMC4355031.
 
In this study, we found beta-ecdysone (βEcd), completely prevented the glucocorticoid (GC) -induced reduction in trabecular bone formation and bone strength and partially prevented the GC-induced reduction in cortical bone formation and bone strength via stimulating bone marrow stromal cells differentiation into osteoblast and maintaining the autophagy level in bone, which was otherwise suppressed by GC.

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Yao W, Lane NE. Targeted delivery of mesenchymal stem cells to the bone.  Bone. 2015 Jan;70:62-5. PMID: 25173607; PMCID: PMC4268265

We developed a hybrid compound, LLP2A-Ale in which LLP2A has high affinity for the α4β1 integrin on mesenchymal stem cells (MSCs) and alendronate that has high affinity for bone.  When LLP2A-Ale was injected into mice, the compound directed MSCs to both trabecular and cortical bone surfaces and increased bone mass and bone strength.  Additional studies are underway to further characterize this hybrid compound, LLP2A-Ale, and how it can be utilized for the treatment of bone loss resulting from hormone deficiency, aging, inflammation and to augment bone fracture healing. 

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Zhong, Z. A., Sun, W., Chen, H., Zhang, H., Lane, N. E., and Yao, W. Inactivation of the Progesterone Receptor in Mx1+ Cells Potentiates Osteogenesis in Calvaria but Not in Long Bone. PloS One. 2015 Oct 2;10(10). PMID: 26431032; PMCID: PMC4592269.

This report suggested that blocking progesterone signaling via PRs in calvarial Mx1+ cells promoted osteoblast differentiation in the calvaria.  Mx1+ was expressed by heterogeneous cells in bone marrow and did not differentiate into osteocyte during long bone development in vivo.  Selectively inactivating the PR gene in Mx1+ cells affected the membrane bone formation but did not affect peripheral skeletal homeostasis.

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Zhong ZA, Sun W, Chen H, Zhang H, Lay YA, Lane NE, Yao W. Optimizing tamoxifen-inducible Cre/loxp system to reduce tamoxifen effect on bone turnover in long bones of young mice. Bone. 2015 Dec;81:614-9. PMID: 26232373; PMCID: PMC4640982.
 
For tamoxifen-dependent Cre recombinase, also known as CreER recombinase, tamoxifen (TAM) is used to activate the Cre to generate time- and tissue-specific mouse mutants.  TAM is a potent CreER system inducer; however, TAM is also an active selective estrogen receptor modulator (SERM) that can influence bone homeostasis.  Our study reported that TAM treatment at 100 mg/kg/day x 4 days significantly affects bone homeostasis, resulting in an anabolic bone effect on trabecular bone in 1-month-old male mice.  However, a lower dose of TAM at 10 mg/kg/day x 4 days can yield similar Col1-CreERT2 induction efficacy with minimum effects on bone turnover in young male mice.

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Yao W, Dai W, Jiang L, Lay EY, Zhong Z, Ritchie RO, Li X, Ke H, Lane NE. Sclerostin-antibody treatment of glucocorticoid-induced osteoporosis maintained bone mass and strength. Osteoporosis Int. 2016 Jan;27:283-294. PMID: 26384674.

Glucocorticoids (GCs) inhibit bone formation by altering osteoblast and osteocyte cell activity and lifespan. High doses of GCs increase apoptosis of osteoblasts and osteocytes, while lower doses increase autophagy, a cell metabolic pathway that provides nutrients under stressful conditions, and can support cell survival.  Sclerostin is a Wnt inhibitor that reduces osteoblast function. A monoclonal antibody directed against sclerostin, Scl-Ab, prevented the GC-induced reduction in bone mass and bone strength; and this effect may partially be through the preservation of autophagy by Scl-Ab.  These data support the clinical studies with Scl-Ab to prevent and treat glucocorticoid-induced osteoporosis. 

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Project II: Sex differences in carpal tunnel syndrome using person reported outcomes and high-resolution ultrasound

Homer S, Anthonisen C, Poltavskiy E, Bang H, Szabo R, Han JJ. Assessment of Median Nerve to Carpal Tunnel Cross Sectional Areas in Healthy Controls and Individuals with Carpal Tunnel Syndrome. Manuscript in preparation.

This paper will examine the utility of median nerve cross sectional area to carpal tunnel cross sectional area ratio in individuals with CTS and healthy controls. This study will also examine this issue in males and females with CTS.

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Humbert SE, Lipa BM, Williams LM, Poltavskiy E, Bang H, Anthonisen C, Han JJ. Inter-rater Reliability of Median Nerve Conduction Studies for Carpal Tunnel Syndrome. Manuscript in preparation.
 
This study highlights the inter-rater reliability of commonly used MMS-NCS in the evaluation of CTS.  Overall, the results suggest that median motor onset-latency and CSI are highly stable and repeatable parameters across different examiners.

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Junck AD, Escobedo EM, Lipa BM, Cronan M, Anthonisen C, Poltavskiy E, Bang H, Han JJ. Reliability Assessment of Various Sonographic Techniques for Evaluating Carpal Tunnel Syndrome. J Ultrasound Med. 2015 Nov;34(11):2077-88. PMID: 26453123.

The study demonstrates the cross sectional area measurement locations with the highest and lowest intra- and inter-rater reliability as well as demonstrates that tracing of median nerve cross sectional area from captured images by different examiners does not contribute significantly to measurement variability.

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Swain NA, Lipa BM, Nguyen QH, Humbert SE, Joyce NC, Han JJ. Inter-rater Reliability of the Median Motor Nerve Conduction Study. Manuscript in preparation to submit to a PM&R journal.
 
The study demonstrates that the standard median motor nerve conduction study provides highly consistent performance and reliable measurements. Although both the latency and amplitude measurements showed high concordance between all electrodiagnosticians, the median motor distal latency showed especially high reliability, which is an important factor for electrodiagnostic criteria in CTS.

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Tran T, Williams L, Zafonte B, Netto A, Immerman I, Cronan M, Anthonisen C, Han J, Szabo R. Pre- and Post-Surgery Assessment of Carpal Tunnel Syndrome (CTS) Patients: Comparing CTSAQ and Neuro-QOL for Self-Assessment Outcomes and Characterizing Median Nerve Cross Sectional Area and Intra-Neural Blood Flow with High Resolution Ultrasound. Manuscript in preparation.

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Swain N, Humbert SE, Lipa BM, Nguyen QH, Joyce N, Jay J. Han. Inter-rater reliability of the median motor nerve conduction study among electrodiagnosticians with varying levels of experience. Abstract accepted.
 
The study demonstrates that the standard median motor nerve conduction study provides highly consistent performance and reliable measurements. Although both the latency and amplitude measurements showed high concordance between all electrodiagnosticians, the median motor distal latency showed especially high reliability, which is an important factor for electrodiagnostic criteria in CTS.

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Lipa BM, Humbert SE, Poltavskiy E, Bang E, Anthonisen C, Han JJ. Inter-rater reliability of various commonly used median motor and sensory nerve conduction studies for evaluation of carpal tunnel syndrome. Abstract accepted.
 
This study highlights the inter-rater reliability of commonly used MMS-NCS in the evaluation of CTS.  Overall, the results suggest that median motor onset-latency and CSI are highly stable and repeatable parameters across different examiners.

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Project III: Sex differences in bone shape and knee osteoarthritis: the Osteoarthritis Initiative

 

 

Wise BL, Liu F, Kritikos L, Lynch JA, Parimi N, Zhang Y, Lane NE.  The association of distal femur and proximal tibia shape with sex: the Osteoarthritis Initiative.  Manuscript accepted at Seminars in Arthritis and Rheumatism February 2016.

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Wise BL, Niu J, Liu F, Lynch JA, Zhang Y, Guermazi A, Felson DT, Kwoh K, Lane NE. The association of radiographic disease with lesions on MRI in lateral and medial compartment knee osteoarthritis: the Osteoarthritis Initiative. Manuscript submitted June 2015
 
The first comprehensive study on the relationship of radiographic disease with MRI lesions in lateral compartment knee osteoarthritis (which is much more common in women than in men) and comparing this with medial compartment knee osteoarthritis.

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Wise BL, Lynch J, Liu F, Parimi N, Kritikos L, Lane NE. Sex differences in knee bone shape: the Osteoarthritis Initiative. Abstract accepted.  Manuscript in preparation.

The shapes of the distal femur and proximal tibia that form the knee joint differ by sex in persons without knee OA as determined by analysis of Active Shape Modeling.

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D. Wu, B.L. Wise, N.E. Lane, F. Liu, J. Lynch.  Curvature of the femur as a measure of malalignment: the Osteoarthritis Initiative. Manuscript in preparation

Through this study, curvature has been shown to be an important parameter of femoral shape, specifically in the femoral shaft, and for knee alignment.

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Wise BL, Niu J, Felson DT, Hietpas J, Sadosky A, Torner J, Lewis CE, Nevitt M. Functional Impairment Is a Risk Factor for Knee Replacement in the Multicenter Osteoarthritis Study. Clin Orthop Relat Res. 2015 Aug;473(8)2505-13. PMID: 25754756. PMCID: PMC4488226.

 
This paper reports that functional impairment is a strong predictor of knee replacement surgery even after controlling for pain intensity, and it specifically breaks down the results by sex, with a trend towards greater effect in women at all levels of functional impairment.

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Wise BL, Kritikos L, Lynch JA, Liu F, Parimi P, Luker Tileston K, Nevitt N, Lane NE. Proximal Femur Shape Differs Between Subjects with Lateral and Medial Knee Osteoarthritis and Controls:  The Osteoarthritis Initiative.  Osteoarthritis and Cartilage. 2014 Dec;22(12):2067-73.  PMID:25194496. PMCID:PMC4252863  [Available on 2015/12/1].

Lateral compartment and medial compartment knee osteoarthritis are associated with different modes of hip shape variation. The identification of modes that define the shape of the proximal femur that are associated with ipsilateral lateral or medial compartment knee OA may lead to clinical intervention to improve the prognosis for each type of disease.

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Boissonneault A, Lynch JA, Wise BL, Segal NA, Gross KD, Murray DW, Nevitt MC, Pandit HG. Association of hip and pelvic geometry with tibiofemoral osteoarthritis: Multicenter Osteoarthritis Study (MOST).  Osteoarthritis and Cartilage. 2014 Aug;22(8):1129-35.  PMID: 24971867.  PMCID:PMC4195737.
 
Anatomical variations at the hip and pelvis are associated with compartment-specific knee OA and may help to explain sex differences in patterns of knee OA.

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Lane NE, Parimi N, Lui LY, Wise BL, Yao W, Lay YA, Cawthon PM, Orwoll E. Osteoporotic Fractures in Men (MrOS) Study Group. Association of Serum Uric Acid and Incident Nonspine Fractures in Elderly Men: The Osteoporotic Fractures in Men (MrOS) Study. J Bone Miner Res. 2014 Jul;29(7):1701-7. PubMed PMID: 24347506; PMCID: PMC4351860.

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Wise BL, Parimi N, Zhang Y, Cawthon PM, Barrett-Connor E, Ensrud KE, Lane NE, Osteoporotic Fractures in Men (MrOS) Group. Frailty and hip osteoarthritis in men in the MrOS cohort. J Gerontol A Biol Sci Med Sci. 2014 May;69(5):602-8. PMID: 24253535; PMCID: PMC3991147.

There is a moderate to strong cross-sectional association of radiographic hip osteoarthritis (OA) and total hip replacement with frailty in older men.  We also found evidence of a longitudinal association between radiographic hip OA or radiographic hip OA and total hip replacement with subsequent increasing frailty status.

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Chaganti RK, Tolstykh I, Javaid MK, Neogi T, Torner J, Curtis J, Jacques P, Felson D, Lane NE, Nevitt MC. Multicenter Osteoarthritis Study Group (MOST). High plasma levels of vitamin C and E are associated with incident radiographic knee osteoarthritis. Osteoarthritis Cartilage. 2014 Feb;22(2):190-6. PMID: 24291351; PMCID: PMC3933364.

This study determined that high serum level of vitamin C was associated with an increase risk of developing knee osteoarthritis compared to individuals with lower vitamin C levels.  This was an unexpected finding and adds to the vibrant debate about vitamin supplementation and musculoskeletal tissue health.

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Chaudhari AJ, Leahy RM, Wise BL, Lane NE, Badawi RD, Joshi AA. Global point signature for shape analysis of carpal bones. Phys Med Biol. 2014 Feb 21;59(4):961-73. PMID: 24503490; PMCID: PMC3966902.

The authors demonstrated the utility of the global point signature-based bone shape representation for the comparison of carpal bones in healthy women and men. The analysis, albeit in a small population, was able to show statistically significant shape differences for carpal bones between the sexes, but not between the carpal bones of the right versus the left wrist in individuals of both sexes. The results indicate that there is value in the analysis of shape in addition to size for improving our understanding of bone morphology across populations.

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Nelson AE, Liu F, Lynch JA, Renner JB, Schwartz TA, Lane NE, Jordan JM. Association of incident symptomatic hip osteoarthritis with differences in hip shape by active shape modeling: the Johnston County Osteoarthritis Project. Arthritis Care Res (Hoboken) 2014 Jan;66(1):74-81. PMID: 23926053; PMCID: PMC3959908.

Morphologic variations at the proximal femur, assessed by Active Shape Modeling, were associated with baseline characteristics such as sex and race, and with incident hip osteoarthritis (OA) outcomes after 6 years of followup. Such shape variations may contribute to hip OA risk and provide another avenue of exploration to identify those at risk for this potentially debilitating condition.

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Wise B, Niu J, Zhang Y, Felson DT, Bradley L, Torner J, Nevitt M, Lane NE. The association of parity with osteoarthritis and knee replacement in the Multicenter Osteoarthritis Study.  Osteoarthritis Cartilage. 2013 Dec;21(12):1849-54. PMID: 24029601; PMCID: PMC3855897.

Parity in women at risk for osteoarthritis is associated with increasing risk for both incident radiographic osteoarthritis and knee replacement, particularly for those women with more than 4 children.

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Project IV: Sex differences in response to an exercise intervention for kyphosis Administrative Supplement: Does sex affect the epidemiology of kyphosis?

Katzman, WB, Vittinghoff, E, Kado, DM, Lane, NE, Ensrud, KE, Shipp, K. Thoracic kyphosis and rate of incident vertebral fractures: the Fracture Intervention Trial. In press, Osteoporos Int, 2016.

This investigation of older women from the Fracture Intervention Trial (FIT) found that greater kyphosis increased the rate of incident vertebral fractures, although we did not find an independent association of kyphosis on incident fracture, after adjustment for prevalent vertebral fracture. Excessive kyphosis may still be a clinical marker for prevalent vertebral fracture.

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Katzman WB, Harrison SL, Fink HA, Marshall LM, Orwoll E, Barrett-Connor E, Cawthon PM, Kado DM; for the Osteoporotic Fractures in Men (MrOS) Study Research Group. Physical function in older men with hyperkyphosis. J Gerontol A Biol Sci Med Sci. 2015 May;70(5):635-40. PMID:25431353; PMCID: PMC4400397.

This investigation of older men from the Osteoporosis in Men (MrOS) study found that hyperkyphosis,  an excessive curvature in the thoracic spine, affected 20% of the cohort. Hyperkyphosis was associated with impaired lower extremity physical function in these older men.

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Nardo, L, Lane, NE, Parimi, N, Cawthon, P, Fan, B, Shepherd, J, Cauley, J, Zucker-Levine, A, Murphy, R, Katzman, WB. Diffuse Idiopathic Skeletal Hyperostosis Association with Thoracic Spine Kyphosis: A Cross-sectional Study for the Health Aging and Body Composition Study. Spine. 2014. Spine (Phila Pa 1976). 2014 Nov 15;39(24). PubMed PMID: 25387143; PubMed Central PMCID: PMC4228693.

This investigation of older individuals from the Health Aging and Body Composition Study demonstrated that diffuse idiopathic skeletal hyperostosis (DISH) is associated with greater Cobb angle of kyphosis in the thoracic spine among older men and women, and this association is stronger within the black population.

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Kado DM, Miller-Martinez D, Lui LY, Cawthon P, Katzman WB, Hillier TA, Fink HA, Ensrud KE. Hyperkyphosis, Kyphosis Progression, and Risk of Non-Spine Fractures in Older Community Dwelling Women: The Study of Osteoporotic Fractures (SOF). J Bone Miner Res. 2014 Oct; 29(10):2210-6. PMID:24715607.  PMCID:PMC4177348.

We determined that greater kyphosis is associated with elevated non-spine fracture risk independent of traditional fracture risk factors in older women.

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Katzman WB, Miller-Martinez D, Marshall LM, Lane NE, Kado DM. Kyphosis and paraspinal muscle composition in older men: a cross-sectional study for the osteoporotic fractures in men (MrOS) research group. BMC Musculoskelet Disord. 2014 Jan; 16; 15-19. PMID: 24428860; PMCID: PMC4029749.

We investigated paraspinal muscle composition and its association with hyperkyphosis in older men. Hyperkyphosis was associated with low muscle volume in older men with BMI<30.

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Bansal S, Katzman WB, Giangregorio LM. Exercise for improving age-related hyperkyphotic posture: a systematic review.  Arch Phys Med Rehabil. 2014 Jan;95(1):129-40. PMID:23850611; PMCID: PMC3997126.

This systematic review evaluated previous research to determine if exercise can improve preexisting hyperkyphosis by decreasing the angle of thoracic kyphosis in adults aged ≥45 years. The scarcity and quality of available data did not permit a pooled estimate of the effect of exercise on hyperkyphotic posture; however, the positive effects observed in high-quality studies suggest some benefit and support the need for an adequately designed randomized controlled trial examining the effect of exercise on hyperkyphosis.

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Katzman WB, Miller-Martinez D, Marshall LM, Lane NE, Kado DM. Kyphosis and paraspinal muscle composition in older men: a cross-sectional study for the osteoporotic fractures in men (MrOS) research group. BMC Musculoskelet Disord. 2014 Jan 16;15:19.  PMID: 24428860; PMCID: PMC4029749.

Among men with BMI < 30 kg/m2, those in the lowest tertile of paraspinal muscle volume had greater adjusted mean kyphosis compared to the highest tertile. These results suggest that differences in body composition may potentially influence kyphosis in older men.

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Katzman WB, Huang MH, Lane NE, Ensrud KE, Kado DM. Kyphosis and Decline in Physical Function Over 15 Years in Older Community-Dwelling Women: The Study of Osteoporotic Fractures. J Gerontol A Biol Sci Med Sci. 2013 Aug;68(8):976-83. PMID: 23633167; PMCID: PMC3712361

In this investigation in older community-dwelling women from the Study of Osteoporotic Fractures, greater magnitude of kyphosis predicted worsening lower extremity function over 15 years. Early recognition and preventative measures against kyphosis progression may help preserve physical function over the long term.

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Kado DM, Huang MH, Karlamangla AS, Cawthon P, Katzman W, Hillier TA, Ensrud K, Cummings SR. Factors associated with kyphosis progression in older women: 15 years' experience in the study of osteoporotic fractures. J Bone Miner Res. 2013 Jan;28(1):179-87. PMID:22865329; PMCID: PMC3693545

Among 1196 women aged 65 years and older at baseline and followed over an average of 15 years, the mean increase in kyphosis was 7.1 degrees (SE = 0.25). Independent determinants of greater kyphosis progression were prevalent and incident vertebral fractures, low bone mineral density and concurrent bone density loss, low body weight, and concurrent weight loss. Thus, age-related kyphosis progression may be best prevented by slowing bone density loss and avoiding weight loss in older women.

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Upcoming Events

Current and Emerging Strategies for Osteoporosis Diagnosis and Treatment”
April 21, 2016, Grand Rounds, Internal Medicine, UC Davis
Nancy E. Lane, MD, UC Davis, Center for Musculoskeletal Health

SCOR Hosted Events

"What Effect is really being measured? Challenges in studying risk factors for disease sequelae"
February 16, 2016, Biostatistis Seminar Series, UC Davis
Yuqing Zhang, MD, DSc, Schools of Medicine and Public Health, Boston University

"What Effect is Really Being Measured? Challenges in Studying Risk Factors for Disease Recurrence or Progression"
February 16, 2016, SCOR Scientific Exchange, UC Davis
Yuqing Zhang, MD, DSc, Schools of Medicine and Public Health, Boston University

Leaders in Integrative Muscloskeletal Biology(LIMB) (Journal Club)
December 8, 2015, UC Davis
Damian Genetos, Department of Anatomy, Physiology and Cell Biology, UC Davis

Leaders in Integrative Muscloskeletal Biology(LIMB) (Journal Club)
November 10, 2015, UC Davis
Damian Genetos, Department of Anatomy, Physiology and Cell Biology, UC Davis

"Dissociation of pain and swelling in murine arthritis"
October 21, 2015, SCOR Science Exchange, UC Davis
Maripat Corr, MD, Rheumatology Section, Department of Medicine, UCSD

Leaders in Integrative Muscloskeletal Biology(LIMB) (Journal Club)
July 8,, 2015, UC Davis
Damian Genetos, Department of Anatomy, Physiology and Cell Biology, UC Davis

"Exercise Mimetics to Improve Muscule Bioenertetics, Muscle Growth & Regeneration, and Fat and Clucose Metabolism in Muscle Diseases"
May 19, 2015 SCOR Scientific Exchange, UC Davis
Craig McDonald, MD, Department of Physical Medicine & Rehabilitation, UC Davis

"Effects of Gastric Bypass Surgery on Calcium Metabolism and the Skeleton"
April 23, 2015, Internal Medicine Grand Rounds (SCOR Scientific Exchange), UC Davis
Anne Schafer, MD, Department of Medicine, UCSF and San Francisco VA Medical Center

"Anabolic Therapy for Osteoporosis, Alone and in Combination with Antiresorptive Therapy"
April 23, 2015, Endocrinology Clinical Conference (SCOR Scientific Exchange), UC Davis 
Anne Schafer, MD, Department of Medicine, UCSF and San Francisco VA Medical Center

Leaders in Integrative Muscloskeletal Biology(LIMB) (Journal Club)
April 15, 2015, UC Davis
Damian Genetos, Department of Anatomy, Physiology and Cell Biology, UC Davis

Leaders in Integrative Muscloskeletal Biology(LIMB) (Journal Club)
March 12, 2015, UC Davis
Damian Genetos, Department of Anatomy, Physiology and Cell Biology, UC Davis

"Hyperkyphosis: Are we destined to stoop with aging? Translating research into clinical practice"
February 18, 2015, SCOR Science Exchange, UC Davis
Wendy Katzman, PT, DPTSc, OCS, Physical Therapy and Rehabilitation Science, UCSF

"The Role of Wnt Signaling in Skeletal Development and Disease"
January 20, 2015, SCOR Science Exchange, UC Davis
Bart Williams, PhD, Center for Cancer and Cell Biology, Laboratory of Cell Signaling and Carcinogenesis, Van Andel Institute

"The Continuum of Knee Osteoarthritis: Biomechanical and Morphological Considerations"
December 9, 2014, SCOR Scientific Exchange, UC Davis
Toran D. MacLeod, PT, PhD, Biomechanics Laborator, Dept. of Physical Therapy, California State University, Sac.

"Are Osteoclasts a Master Regulator of Bone Remodeling?"
June 18, 2014, SCOR Scientific Exchange, UC Davis
Merry Jo Oursler, Ph.D. Mayo Clinic

"Complexities of Osteoblast Signaling in Skeletal Homeostasis and Repair"
May 7, 2014, SCOR Scientific Exchange, UC Davis
Robert A. Nissenson, PhD, Medicine and Physiology, UCSF Research Career Scientist at VA Medical Center, SF

"Integrating TGF-b and Wnt signaling in the skeleton"
April 9, 2014, SCOR Scientific Exchange, UC Davis
Damian Genetos, PhD, Department of Anatomy, Physiology and Cell Biology Vet Med, UC Davis

"Protein citrullination: A link between innate and adaptive immunity"
January 13, 2014, SCOR Scientific Exchange, UC Davis
Jeremy Sokolove, MD, Staff Physician at VA Palo Alto Health Care System and Instructor of Medicine at Stanford University School of Medicine

"Relationship between soluble OSCAR and erosion, a preliminary study"
September 30, 2013, SCOR Scientific Exchange, UC Davis
Tania Crotti, PhD, Bone and Joint Research Laboratory, SOM, University of Adelaide

"Using Tissue Engineering to Understand Gender Differences in ACL Rupture"
September 24, 2013, SCOR Scientific Exchange, UC Davis
Keith Baar, PhD, Department of Physiology and Membrane Biology, UC Davis

"Early Identification and Early Intervention in Osteoarthritis: From Tissue to Function"
August 28, 2013, SCOR Scientific Exchange
Deepak Kumar, PT, PhD, OCS, UCSF

Scintigraphic Tracking of Mesenchymal Stem Cells in the Equine Distal Limb
May 13, 2013, Musculoskeletal Stem Cell Symposium, Ctr for Musculoskeletal Health/Veterinary Med, UCD
Martin Vidal, BVSc, MS, PhD, DACVS, Surgical and Radiological Sciences, School of Vet Med, UC Davis

Regenerative Approach to Mandibular Bone Defects in Dogs Using rhBMP-2” 
May 13, 2013, Musculoskeletal Stem Cell Symposium, Ctr for Musculoskeletal Health/Veterinary Med, UCD
Boaz Arzi, DVM, DAVDC, Surgical and Radiological Sciences, School of Vet Med, UC Davis UC Davis

Clinical Application of Stem Cells in Horses
May 13, 2013, Musculoskeletal Stem Cell Symposium, Ctr for Musculoskeletal Health/Veterinary Med, UCD
Larry D. Galuppo, DVM, Dipl ACVS, Surgical and Radiological Sciences, School of Vet Med, UC Davis

Directing MSCs to the bone surface to form bone with LLP2A-Aln
May 13, 2013, Musculoskeletal Stem Cell Symposium, Ctr for Musculoskeletal Health/Veterinary Med, UCD
Nancy Lane, MD; Wei Yao, MD, Center for Musculoskeletal Health, UC Davis

Scaffold-mediated cues for instructing osteoprogenitor cells
May 13, 2013, Musculoskeletal Stem Cell Symposium, Ctr for Musculoskeletal Health/Veterinary Med, UCD
J. Kent Leach, Ph.D, Department of Biomedical Engineering, UC Davis

Bone Regeneration in Critical-Sized Calvarial Defect Model in Rats
May 13, 2013, Musculoskeletal Stem Cell Symposium, Ctr for Musculoskeletal Health/Veterinary Med, UCD
David Sahar, MD, Department of Surgery, UC Davis

Nanofibrous scaffolds and stem cells for tissue regeneration
May 13, 2013, Musculoskeletal Stem Cell Symposium, Ctr for Musculoskeletal Health/Veterinary Med, UCD
Aijun Wang, Ph.D, Department of Surgery, UC Davis

Enhanced retention of MSC after hypoxic pre-conditioning
May 13, 2013, Musculoskeletal Stem Cell Symposium, Ctr for Musculoskeletal Health/Veterinary Med, UCD
Fernando Fierro, Ph.D., Stem Cell Research Program, Dept. of Cell Biology and Human Anatomy,UC Davis

"Connexin43 and bone adaptation to load"
April 23, 2013, SCOR Scientific Exchange
Henry Donahue, PhD, Penn State University  

Become a Participant

There are 2 on-going clinical trials conducted on UC Davis SCOR projects.

Project 2: Sex differences in carpal tunnel syndrome using person reported outcomes and high-resolution ultrasound

Jay J. Han, M.D., Project Leader

The primary objective of this study is to determine whether improvement in ultrasonographic measures correlates with symptomatic improvement after 6 weeks of wrist splint use.

There are 2 study visits 6 weeks apart and one follow-up questionnaire via US mail or phone after 3 months. Controls have a one-time visit. All study visits will occur at UCD Medical Center in Sacramento, CA. Compensation will be provided.

To find out if you are eligible for this study, cal 916 734-4307.

 

Project 4: Sex Differences in response to an exercise intervention for kyphosis
Wendy B. Katzman, P.T., D.P.T.Sc., O.C.S., Project Leader

The purpose of this study is to learn about the effects of specific spinal muscle strengthening exercises on kyphosis. We will also investigate the differences in the effects of exercise between men and women.

•    Exercise groups meet for one-hour, twice a week for 3 months.
•    Groups will meet at the UC San Francisco Osher Center
•    Participants who completed the SCOR study will receive a $50 gift card.

To find out if you are eligible for this study, call 415-514-6776.

Email: CMHClinicalTrials@ucdmc.ucdavis.edu

Contact Us

UC Davis Center for Musculoskeletal Health
4625 2nd Ave., Suite 2000
Sacramento CA 95817
Telephone: 916-734-4534
Fax: 916-734-4773