BONE RESEARCH OVERVIEW

At the Columbia University Irving Medical Center, the Early-Onset Osteoporosis Center (EOC) within the Metabolic Bone Diseases Program focuses research to identify and better understand the causes, risk factors, predictors of severity, natural history of and therapeutic options for rare forms of osteoporosis that affect young adults under the age of 50.

Research within the EOC is under the direction of Adi Cohen, MD, MHS, Professor of Medicine at CUMC, and Elizabeth Shane, MD, Professor Emerita of Medicine at CUMC, in the Division of Endocrinology, Department of Medicine at CUIMC.

We are actively recruiting patients for ongoing studies! We strongly encourage eligible participants to consider participating in our research program, as outlined below.

We are currently conducting studies of disease mechanisms, and treatment options, for idiopathic osteoporosis (IOP) in premenopausal women, and for pregnancy and lactation associated osteoporosis (PLO).


RESEARCH NEWS

• Our research on treatments for premenopausal osteoporosis was presented at the American Society for Bone and Mineral Research 2023 Annual Meeting and was featured in Medscape in October, 2023 .

• Our research on bone structure in premenopausal women with PLO was presented at the American Society for Bone and Mineral Research 2023 Annual Meeting. Congratulations to Sanchita Agarwal who presented this work and was honored with an ASBMR 2023 Fund for Research Young Investigator Award!


NOW RECRUITING!

Treatment Studies

Romosozumab (Evenity®) for Premenopausal Idiopathic Osteoporosis
Premenopausal women with idiopathic osteoporosis and a history of fracture (including those with PLO) may be eligible to participate.  Please see the attached FLYER for additional information. To discuss eligibility and study procedures please contact our RESEARCH OFFICE.

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This is a two-year open-label study of romosozumab (Evenity®) followed by denosumab (Prolia®). This is not a randomized trial - all participants will receive both active treatments. The principal investigators are Drs. Adi Cohen and Elizabeth Shane. This study has been approved by the Columbia University Institutional Review Board (IRB# AAAT1202) and is listed on ClinicalTrials.gov (NCT04800367).




Observational Studies

Pregnancy and Lactation Associated Osteoporosis Studies
Pregnancy and Lactation Associated Osteoporosis (PLO) is a rare condition in which young women sustain low trauma fractures during or soon after pregnancy, or during breastfeeding. Because PLO is rare, we know relatively little about its clinical features, causes, and prognosis. As medical researchers at CUIMC, we are very interested in studying the causes of and potential treatments for PLO. If you are eligible, we encourage you to consider participating in one or more different aspects of our research.


Bone Density Follow Up Study: Clinical Observational Study of Pregnancy and Lactation Associated Osteoporosis
Patients who choose to have clinical follow-up and/or medication treatment through the Metabolic Bone Diseases Program at CUIMC can contact the PATIENT CARE section of the EOC at CUIMC. For patients who elect this clinical care option, this study includes bone density testing every six months—in addition to usual clinical care—as well as specialized laboratory studies of bone metabolism.


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This study aims to better understand individual differences in medication response as well as natural history of PLO. The additional bone studies for those patients who are already receiving clinical care are funded by private research donations to our program. The principal investigator is Dr. Adi Cohen. This study has been approved by the Columbia University Institutional Review Board (IRB#AAAR9157).


ABOUT OUR RESEARCH

The Center’s tools of inquiry include advanced three-dimensional (3D) high resolution bone-imaging equipment and analysis techniques, evaluation of bone biopsy samples, laboratory investigation of bone cells, and analysis of patients’ DNA to learn about potential genetic etiologies of Early-Onset Osteoporosis

Normal and osteoporotic bone seen by high resolution peripheral QCT scanner (HR-pQCT of the Radius).

1. High resolution peripheral computed tomography (HR-pQCT):

This imaging technique provides a non-invasive method to visualize the microarchitecture of the radius and tibia bones.
Image analyses are conducted in collaboration with the laboratory of X. Edward Guo, PhD, Stanley Dicker Professor of Biomedical Engineering and Chair, Department of Biomedical Engineering, Columbia University.


2. Central quantitative computed tomography:
This imaging technique provides a non-invasive method to study the 3-dimensional structure of the spine and hip.

Image analyses are conducted in collaboration with Thomas Lang, PhD, Professor of Radiology and Biomedical Imaging, School of Medicine, UCSF.

 

Structural analyses (finite element analyses) of the central QCT images of the spine and hip
 

3. Bone biopsy studies:
Bone biopsy samples allow us to examine bone structure and remodeling as well as bone cell activity. Studies are conducted in collaboration with: David Dempster, PhD, Professor of Clinical Pathology at CUIMC, Stavroula Kousteni, PhD, Professor of Physiology & Cellular Biophysics at CUIMC, and Ralph Muller, PhD, Professor of Biomechanics and Head of the Laboratory for Bone Biomechanics, ETH Zurich.

Bone surface after double tetracycline labeling in order to study bone formation rate.

Within the bone biopsy samples, bone surfaces can be visualized and bone formation rate can be measured.

Osteoblastic cells growing in culture. Individual patient's cells have different morphology and growth rates.

Bone cells obtained from the bone biopsy samples, grown in culture in the laboratory of Stavroula Kousteni, PhD, CUIMC.

MicroCT analyses of bone biopsy samples, performed in the laboratory of Ralph Muller, PhD, ETH Zurich.

Healthy Bone

Osteoporotic Bone

4. Hormone and biochemistry studies:
In the Biomarkers Core Laboratory (BCL) at the Irving Institute for Clinical and Translational Research, we assess hormonal and biochemical characteristics of osteoporosis and biomarkers of medication response.

4. Genetic Studies:
We work in collaboration with the Institute for Genomic Medicine at Columbia University, under the direction of David Goldstein, PhD, to learn more about genetic causes of bone fragility in patients with early-onset osteoporosis.


FUNDED STUDIES

Our research program has received funding from the US Food and Drug Administration (FDA), the National Institutes of Health (NIH), industry sponsors, the Simon-Strauss Foundation and the Thomas L. Kempner, Jr. and Katheryn C. Patterson Foundation.


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The following investigations are ongoing at the EOC.

Principal Investigators: Drs. Elizabeth Shane and Adi Cohen

  1. Romosozumab for Premenopausal Idiopathic Osteoporosis
    The goal of this study is to characterize the effects of 24 months of treatment with romosozumab followed by denosumab on bone mass and remodeling in premenopausal women with idiopathic osteoporosis. This study has been approved by the Columbia University Institutional Review Board (IRB#AAAT1202)

  2. Pregnancy and Lactation Associated Osteoporosis: Bone Microstructure and Metabolism, Genotypic Characteristics, Natural History and Biomarkers of Disease Severity
    This study, funded by the FDA Office of Orphan Products Development through the Natural History Grants Program for rare diseases in 2017, aims to define the skeletal structure, bone metabolism, hormonal and genetic characteristics of women with PLO as an essential step toward the design of protocols to test targeted approaches to improve skeletal recovery and bone quality. This study has been approved by the Columbia University Institutional Review Board (IRB#AAAR0960).

  3. Personalized Investigation of Disease Mechanisms and Prediction of Medication Responsiveness in Women with Pregnancy and Lactation Associated Osteoporosis.
    This study, funded by a Precision Medicine Pilot Award from Columbia’s Irving Institute for Clinical and Translational Research in 2018, allows us to perform individual functional and genetic analyses of bone forming cells (primary osteoblasts) obtained from PLO patients’ bone biopsy samples. This study has been approved by the Columbia University Institutional Review Board (IRB#AAAR0960).


  4. Bone Density Follow Up Study: Clinical Observational Study of Pregnancy and Lactation Associated Osteoporosis
    For those patients who choose to have clinical follow up and/or medication treatment through the EOC at CUIMC, this study includes bone density testing every six months—in addition to usual clinical care—as well as specialized laboratory studies of bone metabolism. This study has been approved by the Columbia University Institutional Review Board (IRB#AAAR9157).


ONGOING RESEARCH WITH COMPLETED ENROLLMENT


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  1. Teriparatide for Idiopathic Osteoporosis in Premenopausal Women: A Phase 2 Study
    This study, funded by the FDA in 2010, is a randomized controlled trial of teriparatide for idiopathic osteoporosis. This study is closed to enrollment.
  2. Phase 2B Study of Denosumab to Prevent Bone Loss in Idiopathic Osteoporosis in Premenopausal Women Treated with Teriparatide
    This study, funded by the FDA in 2016, is an extension to the Phase 2 teriparatide study above, and is closed to enrollment. The goal of the study is to characterize the effects of denosumab on bone mass and remodeling in premenopausal women with idiopathic osteoporosis who have completed teriparatide.
  3. Bisphosphonates for Prevention of Post-Denosumab Bone Loss in Premenopausal Women with Idiopathic Osteoporosis
    This study, funded by Amgen, aims to determine whether transitioning to bisphosphonates prevents increases in bone remodeling and decreases in bone density in premenopausal women with idiopathic osteoporosis who have completed a course of teriparatide followed by one to three years of denosumab.
  4. IGF-1, bone turnover and response to teriparatide in premenopausal women with idiopathic osteoporosis.
    This project, funded by the NIH in 2013, investigates the contribution of insulin like growth factor 1 (IGF-1) resistance to the pathogenesis of premenopausal idiopathic osteoporosis and the response to teriparatide.


PUBLICATIONS

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  1. Kondapalli A, Kamanda-Kosseh M, Williams JM, Shiau S, Bucovsky M, Colon I, Shane E, Cohen A. Clinical characteristics of pregnancy and lactation associated osteoporosis: An online survey study. Osteoporosis International 2023 Aug; 34(8):1477-89.
  2. Agarwal S, Shiau S, Kamanda-Kosseh M, Bucovsky M, Kil N, Lappe JM, Stubby J, Recker RR, Guo XE, Shane E, Cohen A. Teriparatide followed by denosumab in premenopausal idiopathic osteoporosis: Bone microstructure and strength by HR-pQCT. J Bone Miner Res. 2023 Jan; 38(1): 35-47. 
  3. Agarwal S, Shane E, Lang T, Shiau S, Kamanda-Kosseh M, Bucovsky M, Lappe JM, Stubby J, Recker RR, Hu Y, Wang Z, Guo XE, Cohen A. Spine volumetric BMD and strength in premenopausal idiopathic osteoporosis: Effect of teriparatide followed by denosumab. J Clin Endocrinol Metab 2022 Jun; 107(7): e2690-e2701.
  4. Shane E, Shiau S, Recker RR, Lappe JM, Agarwal S, Kamanda-Kosseh M, Bucovsky M, Stubby J, Cohen A. Denosumab after teriparatide in premenopausal women with idiopathic osteoporosis. J Clin Endocrinol Metab 2022 Mar; 107(4): e1528-e1540.
  5. Goetz TG, Nair N, Shiau S, Recker RR, Lappe JM, Dempster DW, Zhou H, Zhao B, Guo X, Shen W, Nickolas TL, Kamanda-Kosseh M, Bucovsky M, Stubby J, Shane E, Cohen A. In premenopausal women with idiopathic osteoporosis, lower bone formation is associated with higher body fat and higher IGF-1. Osteoporosis International, 2022 Mar; 33(3): 659-672.
  6. Cohen A, Hostyk J, Baugh EH, Buchovecky CM, Aggarwal VS, Recker RR, Lappe JM, Dempster DW, Zhou H, Kamanda-Kosseh M, Bucovsky M, Stubby J, Goldstein DB, Shane E. Whole exome sequencing reveals potentially pathogenic variants in a small subset of premenopausal women with idiopathic osteoporosis. Bone 2022 Jan 154:116253.
  7. Cohen A, Shiau S, Nair N, Recker RR, Lappe JM, Dempster DW, Nickolas TL, Zhou H, Agarwal S, Kamanda-Kosseh M, Bucovsky M, Williams JM, McMahon DJ, Stubby J, Shane E. Effect of Teriparatide on Bone Remodeling and Density in Premenopausal Idiopathic Osteoporosis: A Phase II Trial. J Clin Endocrinol Metab 2020 Oct; 105(10).
  8. Cohen A, Kamanda-Kosseh M, Dempster DW, Zhou H, Muller R, Goff E, Colon I, Bucovsky M, Stubby J, Nickolas TL, Stein EM, Recker RR, Lappe JM, Shane E. Women with pregnancy and lactation associated osteoporosis (PLO) have low bone remodeling rates at the tissue level. J Bone Miner Res. 2019 Sep;34(9): 1552-1561.
  9. Cohen A, Kousteni S, Bisikirska B, Shah JG, Manavalan JS, Recker RR, Lappe J, Dempster DW, Zhou H, McMahon DJ, Bucovsky M, Kamanda-Kosseh M, Stubby J, Shane E. IGF-1 Receptor expression on circulating osteoblast progenitor cells predicts tissue-based bone formation rate and response to teriparatide in premenopausal women with idiopathic osteoporosis. J Bone Miner Res. 2017 June; 32(6):1267-1273.
  10. Cohen A, Kamanda-Kosseh M, Recker RR, Lappe JM, Dempster DW, Zhou H, Cremers S, Bucovsky M, Stubby J, Shane E. Bone density after teriparatide discontinuation in premenopausal idiopathic osteoporosis. J Clin Endocrinol Metab. 2015 Nov; 100(11):4208-14.
  11. Cohen A, Shen W, Dempster DW, Zhou H, Recker RR, Lappe JM, Kepley A, Kamada-Kosseh M, Bucovsky M, Stein E, Nickolas T, Shane E. Marrow adiposity assessed on transiliac crest biopsy samples correlates with noninvasive measurement of marrow adiposity by proton magnetic resonance spectroscopy (1H-MRS) at the spine but not the femur. Osteoporosis International 2015; 26(10):2471-8.
  12. Nishiyama KK, Cohen A, Young P, Wang J, Lappe JM, Guo XE, Dempster DW, Recker RR, Shane E. Teriparatide increases strength of the peripheral skeleton in premenopausal women with idiopathic osteoporosis: a pilot HR-pQCT study. J Clin Endocrinol Metab 2014; 99(7):2418-25.
  13. Cohen A, Dempster DW, Recker RR, Lappe JM, Zhou H, Zwahlen A, Muller R, Zhao B, Guo, X, Lang T, Saeed I, Liu XS, Gou XE, Cremers S, Rosen CJ, Stein EM, Nickolas TL, McMahon DJ, Young P, Shane E. Abdominal fat is associated with lower bone formation and inferior bone quality in healthy premenopausal women: a transiliac bone biopsy study. J Clin Endocrinol Metab. 2013; 98(6):2562-72.
  14. Cohen A, Stein EM, Recker RR, Lappe JM, Dempster DW, Zhou H, Cremers S, McMahon DJ, Nickolas TL, Muller R, Zwahlen A, Young P, Stubby J, Shane E, Teriparatide for idiopathic osteoporosis in premenopausal women: a pilot study. J Clin Endocrinol Metab. 2013; 98(5):1971-81.
  15. Shane E, Cohen A, Stein EM, McMahon DJ, Zhang C, Young P, Pandit K, Staron RB, Verna EC, Brown R, Restaino S, Mancini D. Zoledronic Acid versus alendronate for the prevention of bone loss after heart or liver transplantation. J Clin Endocrinol Metab. 2012; 97(12): 4481-90.
  16. Cohen A, Lang TF, McMahon DJ, Liu XS, Guo XE, Zhang C, Stein EM, Dempster DW, Young P, Saeed I, Lappe JM, Recker RR, Shane E. Central QCT reveals lower volumetric BMD and stiffness in premenopausal women with idiopathic osteoporosis, regardless of fracture history.J Clin Endocrinol Metab 2012;97(11):4244-52.
  17. Cohen A, Dempster DW, Stein EM, Nickolas TL, Zhou H, McMahon DJ, Muller R, Kohler T, Zwahlen A, Lappe JM, Young P, Recker RR, Shane E. Increased marrow adiposity in premenopausal women with idiopathic osteoporosis. J Clin Endocrinol Metab 2012; 97(8): 2782-91.
  18. Cohen A, Recker RR, Lappe J, Dempster DW, Cremers S, McMahon DJ, Stein EM, Fleischer J, Rosen CJ, Rogers H, Staron RB, LeMaster J, Shane E. Premenopausal women with idiopathic low trauma fractures and/or low bone mineral density. Osteoporosis International. 2012; 23(1): 171-82.
  19. Cohen A, Dempster D, Recker R, Stein EM, J L, Zhou H, Wirth AJ, van Lenthe GH, Kohler T, Zwahlen A, Muller R, Rosen CJ, Cremers S, Nickolas TL, DJ M, Rogers H, Staron RB, Lemaster J, Shane E.  Abnormal bone microarchitecture and evidence of osteoblast dysfunction in premenopausal women with idiopathic osteoporosis. J Clin Endocrinol Metab. 2011; 96(10): 3095-105.
  20. Liu XS, Cohen A, Shane E, Stein E, Rogers H, Kokolus SL, Yin PT, McMahon DJ, Lappe JM, Recker RR, Guo XE. Individual trabeculae segmentation (ITS)-based morphological analyses of high resolution peripheral quantitative computed tomography images detect abnormal trabecular plate and rod microarchitecture in premenopausal women with idiopathic osteoporosis. J Bone Mineral Res 2010; 25(7): 1496-1505.
  21. Cohen A, Liu XS, McMahon DJ, Rogers HF, LeMaster J, Recker RR, Lappe JM, Guo XE, Shane E. Bone microarchitecture and stiffness in premenopausal women with osteoporosis. J Clin Endocrinol Metab 2009; 94(11):4351-60.
  22. Cohen A, Fleischer J, Freeby MJ, McMahon DJ, Irani D, Shane E. Clinical characteristics and medication use among premenopausal women with osteoporosis and low BMD: the experience of an osteoporosis referral center. Journal of Women’s Health 2009; 18(1):79-84.
  23. Cohen A, Addonizio LJ, Lamour JM, Addesso V, Staron RB, Gao P, Shane E. Osteoporosis in adult survivors of adolescent cardiac transplantation may be related to hyperparathyroidism, mild renal insufficiency and increased bone turnover. Journal of Heart and Lung Transplantation 2005; 24:696-702.

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