A distinct “bone” division at Washington University

With the merger of Barnes and Jewish Hospitals in 1993, the division relinquished its endocrine function to the “sister” Endocrine Division at the former Barnes Hospital, and became the current Division of Bone and Mineral Diseases, thus completing the transformation into a unit entirely focused on skeletal disorders. Since then, our division has remained an independent unit within the Department of Medicine at Washington University School of Medicine in St. Louis, a unique entity in academic medicine.

During the 1990s, the Division of Bone and Mineral Diseases continued to grow its research and clinical programs around a new generation of faculty who, as their predecessors, later became prominent investigators and leaders in the bone and mineral scientific community.

Among them, Roberto Pacifici, MD, made the initial, seminal observations that inflammatory cytokines play central roles in post-menopausal osteoporosis and estrogen-dependent bone loss, and his contributions were instrumental in opening a new avenue of investigation that is now known as osteoimmunology. Roberto Civitelli, MD, demonstrated the biologic importance of direct cell-cell interactions via gap and adherens junctions in regulating osteoblast differentiation and function, thus opening a new direction of research that has expanded into other disciplines, including mechanotransduction and stem cell biology. Pacifici functioned as Interim Chief (1999-2001), and later became the Chief of the Division of Endocrinology and Metabolism at Emory University. Roberto Civitelli, MD, was named the Sydney M. and Stella H. Shoenberg Professor of Medicine in 2003, and was appointed chief of the division in February 2010.

The Bone Health Program established

The last decade of the 20th century was also a fertile period for clinical research, as novel therapeutic options for treating osteoporosis and other metabolic bone disorders were introduced. Hinging on its leadership position in the field, the Division of Bone and Mineral Diseases led the way in testing and applying new diagnostic methods and therapies for improved patient care.

As an outgrowth of Avioli’s consulting with NASA on the effect of zero-gravity on bone loss in astronauts, division faculty pioneered the development and application of non-invasive methods for measuring bone mineral density using isotope-based absorptiometers, as well as of biochemical markers of bone turnover.

With the transition to X-ray based densitometers, the division was among the first centers nationally to be equipped with state-of-the-art diagnostic tools for the diagnosis of osteoporosis, thus paving the way for the establishment of a specialized clinical practice program, the Bone Health Program in the early 1990s. The Bone Health Program would thrive for the next two decades and to this date it remains an internationally recognized center of excellence for diagnosis and treatment of osteoporosis and other metabolic bone diseases.

Major contributors to new treatments for osteoporosis

While the clinical practice was growing, so was the division involvement in clinical research. In the early 1990s, Avioli established a research study unit, which at the peak of its operations was able to manage up to a dozen industry-sponsored clinical trials (and more than 4500 encounters per annum) testing safety and efficacy of new drugs for osteoporosis. In the best tradition of Avioli’s philosophy, this clinical research unit also offered resources and knowledge for development of investigator-driven clinical research projects, fostering internal growth and facilitating interdisciplinary research projects.

Through such collaborative efforts several important discoveries were made; for example, that the prevalence of celiac disease in subjects with osteoporosis is about 10-fold higher than in the general population; and that estrogen replacement therapy as well as calcium and vitamin D supplementation lead to improved alveolar bone mass and dental health.

Within this environment, Reina Armamento-Villareal, MD, one of the latest trainees, observed that key polymorphic genetic variants of estrogen metabolizing enzymes impact on bone mass acquisition, and on the response to aromatase inhibitors in patients with breast cancer. Armamento-Villareal moved on to directing a bone metabolism clinic at the University of New Mexico, in Albuquerque; and more recently, joined the faculty of Baylor College of Medicine, Houston, TX.