History of The Mount Sinai Bone Program
Created in 1999, The Mount Sinai Bone Program has achieved international prominence by making seminal discoveries on how the vertebrate skeleton is modeled and remodeled in health and disease. The basic and translational studies have used cutting-edge approaches to examine many facets of bone physiology, including regulation of the skeleton by hormones, enzymes, autocoids, second messengers, and transcriptional regulators. By studying the pathophysiology of bone and mineral disorders, studies have helped unmask actionable therapeutic targets. This Program has been funded by the National Institutes of Health and multiple other funding agencies since its inception. With research laboratories based at Icahn School of Medicine at Mount Sinai, the Program has also provided clinical care for patients with osteoporosis, metabolic bone diseases, and rare bone disorders.
Early Research Contributions
Landmark discoveries by members of The Mount Sinai Bone Program include the first description of calcium sensing in the osteoclast, the cell that removed old bone, as a primary physiologic mechanism for the control of excessive bone removal. The group also discovered that nitric oxide regulates bone remodeling, an observation that has led to the testing of nitric oxide donors for use in human osteoporosis. In 2003, they established, for the first time, the existence of a pituitary-bone axis, which has revolutionized the way we view endocrine physiology. In this new arm of skeletal regulation, the pituitary hormones TSH, ACTH, FSH, oxytocin and vasopressin, previously thought solely to stimulate single targets, bypass these organs to affect the skeleton directly. These studies implicate pituitary hormones in the pathophysiology of osteoporosis, shifting the paradigm from our traditional, one–disease–one–hormone hypothesis to a multifaceted pathophysiology with enormous future therapeutic implications. The group has also delineated the effects of genetic diseases, including Gaucher Disease and Congenital Adrenal Hyperplasia, on the skeleton, and probed the pathophysiology of osteoporosis resulting from aging, the menopause, thyroid disease, pregnancy and lactation, hyponatremia, smoking, and organ transplantation. In addition, the group has also focused on the role of the nervous system and muscle in skeletal regulation, mechanisms that regulate cartilage homoeostasis, the crossover of anti-cancer and anti-osteoporosis drugs, and the use of stem cells to promote skeletal regeneration.
Recent Research Highlights
- Zaidi Group
Aside from providing the first evidence for a pituitary–bone axis (Cell, 2003, 2006), in two recent papers published in Nature, the Zaidi group found that genetic or pharmacological inhibition of FSH not only increases bone mass, but also reduces body fat and prevents neurodegeneration. In essence, this laid a firm foundation for a single anti-FSH agent to treat osteoporosis, obesity, and Alzheimer’s disease that affect millions of men and women worldwide. This corpus of work was selected by Nature Medicine as one of eight “Notable Advances” in biomedicine for 2017 and was editorialized in the New York Times. The Zaidi group have now developed a novel humanized FSH-blocking antibody, which is undergoing preclinical testing.
- Yuen and Kim Group
The Yuen and Kim groups collaboratively showed that inhibitors of the enzyme phosphodiesterase 5A (PED5A)—drugs used for erectile dysfunction—are potent stimulators of bone formation and can potentially be repurposed for osteoporosis.
- Ginzburg Group
The Ginzburg group discovered that erythroferrone (ERFE), a molecule that regulates hepcidin and iron metabolism, regulates bone formation by binding to bone morphogenetic proteins. These studies focus on the role of ERFE in the pathophysiology of bone loss in β-thalassemia.