The Early-Onset Osteoporosis Center

The Early-Onset Osteoporosis Center (EOC) within the Metabolic Bone Diseases Program in the Division of Endocrinology at Columbia University Irving Medical Center (CUIMC) conducts research in uncommon forms of osteoporosis that affect young adults. The EOC provides personalized clinical evaluation and treatment for adult patients who develop low bone density and/or have low trauma fractures early in life.

Some patients with Early-Onset Osteoporosis have an underlying medical condition or medication exposure that has had a negative impact on their skeleton. Other patients with early onset osteoporosis have known genetic causes that have affected bone development. Patients with no known condition or medication exposure causing bone fragility are said to have idiopathic osteoporosis.

The EOC uses state-of-the-art technologies to evaluate people with all types of early-onset osteoporosis, including advanced bone imaging analysis to assess bone quality and strength, detailed hormonal and metabolic studies to search for subtle hormonal causes of bone loss and fractures, analysis of bone biopsies to measure bone microstructure and assess the amount of bone tissue that is being broken down and formed, studies of bone cell growth and response to treatments. We also collaborate with experts in genetics to identify genetic causes of Early-Onset Osteoporosis. The Center’s research includes specialized studies of disease mechanisms and treatments for osteoporosis in premenopausal women, including those with osteoporosis associated with pregnancy and lactation.

The EOC was established through generous support from the Thomas L. Kempner Junior Family Foundation. Dr. Adi Cohen, MD, MHS, Associate Professor of Medicine directs the EOC. Dr. Elizabeth Shane, MD, Emerita Professor of Medicine in the Division of Endocrinology, Department of Medicine at CUIMC also participates in the EOC.

Research within the EOC

We are currently conducting research on causes and treatment options, for early onset osteoporosis, idiopathic osteoporosis (IOP) in premenopausal women, and for pregnancy and lactation associated osteoporosis (PLO). We are also conducting family studies of genetic etiologies of early onset osteoporosis.

We are actively recruiting patients for ongoing studies! We strongly encourage eligible participants to consider participating in our clinical and research programs.

Osteoporosis in Postmenopausal Women

Dr. Ethel Siris

One research area is the epidemiology of osteoporosis, including with risk factors for fracture, perceptions of risk, quality of life, mechanisms for risk prediction, etc. from a multinational cohort called GLOW, which is a longitudinal study of approximately 60,00 postmenopausal women from 723 primary care practices in 10 countries from North America, Europe and Australia. Another epidemiology study, NORA, that originally enrolled over 200,000 US postmenopausal women has also explored risk factors for fracture. 

Other areas of research focus on the effects of treatment adherence on fracture outcomes, and a series of ongoing studies regarding a new therapeutic agent for osteoporosis, denosumab, an inhibitor of RANK-ligand. 

Study of Women After Menopause who are Taking Medication and/or Receiving Counseling/Therapy for Depression 

 Drs. Marcella Walker and David Hellerstein

https://recruit.cumc.columbia.edu/studyinfopage/2490

As many as 1 in 3 women over the age of 50 will have bone fractures due to osteoporosis. Some studies suggest that depression and/or certain treatments for depression may further increase the risk of fracture. Whether this occurs, and if so, why, has not been clearly established. This is an understudied problem, but one that is important to clarify to improve bone health screening and treatment for older women.

Are you being treated for depression?

Columbia endocrinologist, Dr. Marcella Walker, MD, professor of medicine, in collaboration with David Hellerstein, MD, professor of clinical psychiatry and director of the Depression Evaluation Service, are conducting an NIH-funded study to assess bone health in postmenopausal women being treated for depression. Eligible participants who enroll will be evaluated at Columbia University Irving Medical Center four times over the course of 18 months, with dual energy x-ray absorptiometry (DXA) scans. DXA is the gold standard way to measure bone mineral density and to determine risk of fracture. Participants also receive repeat spine imaging, high resolution peripheral quantitative computed tomography (HRpQCT) scanning to assess bone microstructure, tests of muscle function and other non-invasive testing of skeletal health. Participants will receive tests at no cost and will get results of their bone testing as well as compensation. There is no treatment for depression in this study, and participants will continue to follow their treatment course for depression as specified by their provider. Click here to learn more.

What is osteoporosis and why is it important?

Osteoporosis or “porous bone” is a silent medical condition, common in women after menopause, which causes bone loss and weakening of the bone’s structure (Figure 1). It increases the risk for fractures or broken bones. Because the condition has no symptoms, people may not know they are at risk unless their bone mineral density is measured by DXA. While most fractures tend to be painful and may cause a temporary reduction in normal activities, the consequences of some types of fractures may be more lasting. Hip fractures can permanently reduce independence. For example, some people who sustain hip fractures remain dependent on assisted walking devices like canes or walkers or need help from family members to perform activities that they could perform themselves previously. Hip fractures sometimes even shorten one’s life due to complications that arise after fractures such as blood clots or pneumonia. Spine fractures can cause a permanent bending of the spine or a “dowager’s hump”. If an individual has already had a fracture related to osteoporosis, their risk of future fracture is high.

How might depression and its treatment be linked to bone health?

It is not entirely clear.  A number of studies have found a link between depression and bone health. Some indicate lower bone mineral density, accelerated bone loss or an increased risk of fractures among those who are depressed compared to those who are not. The mechanisms that underlie this relationship are still not known. Two neurotransmitters, serotonin and norepinephrine, are thought to contribute to regulating bone mass under normal circumstances.

With depression, these transmitters may become dysregulated and accelerate bone loss. Also, depression and psychological stress may increase cortisol (the body’s stress hormone), which can also lead to bone loss. Beyond that, depression may cause weight loss, reduced physical activity or other behaviors that are detrimental to bone health. Some studies indicate an increased risk for falls among those with depression. It is also possible that individuals with depression are more likely to have other medical conditions or take medications that negatively impact bone health compared to those who are not depressed. Finally, some types of antidepressants may increase the risk of bone loss – this is the subject of our study.

Do antidepressants affect bone?  

Antidepressants are one of the most commonly prescribed type of drugs. Recent estimates suggest that more than 1 in 8 adults in the United States take antidepressants, a number which has increased during the Pandemic. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants because they are safe and effective. Some studies have linked SSRIs to accelerated bone loss and greater risk of fracture. How this may happen is unclear. Changes in serotonin signaling that normally regulates skeletal health may occur when SSRIs are used. We hypothesize that with chronic use, this may reduce bone formation, leading to an imbalance between bone breakdown and bone build up. Some other types of antidepressants may have similar effects. There is not enough evidence in humans, however, to know if this is the case - our study is investigating this mechanism.

What should I do if I have depression and am concerned about my bone health?

It is important for individuals being treated for depression to continue their depression treatment as prescribed by their health care provider. We do not recommend that individuals stop antidepressants due to concerns about skeletal health. If you are worried, talk to your physician.  He or she may recommend a DXA scan to evaluate your bone health and gauge your risk of fracture. DXA is a painless and non-invasive test similar to an x-ray. There are effective medications to prevent and treat osteoporosis. Depending on your results and risk, you may be a candidate.  Healthy behaviors can also positively influence bone health and slow bone loss. These include ensuring adequate dietary calcium and vitamin D, weight-bearing exercise, limiting alcohol, and stopping smoking.

 We hope that results from this study will provide important information needed to better inform screening and treatment recommendations for assessing bone health in women with depression.

Bariatric Surgery

Drs. Emily Stein and Shonni Silverberg

This prospective study evaluates changes in vitamin D, markers of bone turnover, bone density and microarchitecture for two years following bariatric surgery. Patients undergoing Roux-en-Y gastric bypass, and gastric banding are enrolled. Microarchitectural changes are evaluated using high resolution peripheral computed tomography. This study will help demonstrate the changes in microstructure underlying the previously reported losses in bone density after weight loss surgery. The findings will help to elucidate whether these bone density losses are adaptations to unloading of the skeleton with weight loss or whether they represent pathology and increased risk of fracture. 

Paget's Disease of Bone

Dr. Ethel Siris 

We have been studying the genetics of Paget’s disease, in collaboration with Prof. Jacques Brown’s laboratory in Quebec, funded by a grant from the Evelyn S. Nef Foundation. We have collected data on over 70 patients with Paget’s disease from our practice in the Metabolic Bone Diseases Unit, including extensive demographic information (ethnicity, family history of Paget’s disease) as well as sites of skeletal involvement, and analyzing samples of blood for a series of candidate genes for this disease. 

Bone biopsy samples allow us to examine bone structure, bone formation processes and bone cell activity. Within the bone biopsy samples, bone surfaces can be visualized and bone formation rate can be measured.

Bone cells obtained from the bone biopsy samples are grown in culture in the laboratory of Stavroula Kousteni, PhD, Professor of Physiology & Cellular Biophysics at CUIMC, bone cells obtained from bone biopsy samples can be grown in culture to investigate study their growth and functional characteristics.