Renowned endocrinologist Fuller Albright and colleagues discovered in the late 1920s that parathyroid hormone (PTH) — known to take calcium from bone — could be used to increase bone mass. But the findings were dismissed because they didn’t seem to make sense. It took decades before researchers revisited PTH as a possible osteoporosis therapy and rediscovered its power to reverse bone loss.
During the Rheumatology Research Foundation Oscar S. Gluck, MD Memorial Lecture: Parathyroid Hormone: Builder & Destroyer of Bone, endocrinologist Henry M. Kronenberg, MD, will update rheumatologists about current literature and discuss how its anabolic properties may help patients with inflammatory arthritis. The lecture, which honors Dr. Gluck’s significant contributions to bone research, goes from 7:30 – 8:30 am Tuesday in Room 25 A.
Dr. Kronenberg, Chief of the Endocrine Division at Massachusetts General Hospital, Boston, uses genetically manipulated mice to study PTH signaling and bone development.
“I’m particularly interested in the interaction of parathyroid hormone and bone,” Dr. Kronenberg said. “Some physicians may be unaware that PTH is a powerful therapy for osteoporosis. As a matter of fact, PTH 1-34 and analogous analogs are the only approved therapies we have for osteoporosis that actually increase bone formation. All the other therapies stop bone loss. PTH actually increases bone formation.
“Patients with rheumatoid arthritis, particularly rheumatoid arthritis treated with glucocorticoids, have a huge amount of associated osteoporosis. It’s important for rheumatologists to understand how PTH works to increase bone mass and to know that it’s available as a treatment option for their patients who develop osteoporosis.”
PTH, he said, is not an obvious therapy if you want to build bone.
“Parathyroid hormone was initially discovered as a hormone that takes calcium out of the bones and puts it into the blood stream,” Dr. Kronenberg said. “It raises blood calcium. And, in fact, when people have continually high levels of parathyroid hormone, they lose bone.”
Early experiments showed when patients were given PTH by once-daily subcutaneous injection — so the level of hormone is high for four or five hours and then plummets — it builds up instead of destroying bone.
“Initially, people didn’t believe it,” Dr. Kronenberg said. “It was eventually confirmed that PTH is a powerful method of bone formation. This raised questions. First, how does parathyroid hormone increase bone mass? And second, why would a hormone that is designed to take calcium out of the bone bother to increase bone in the first place? It sounds paradoxical.”
Dr. Kronenberg will attempt to answer both questions during his lecture.
“The first question is pretty clear,” he said. “There are multiple ways that PTH increases bone mass. One of the things we’ve shown recently is that it increases action on stem cells for bone cells. I’ll share some data on stem cells for bone and how parathyroid hormone affects those. I’ll also show some data that parathyroid hormone can wake up bone-lining cells. Activating bone-lining cells is a quick way to increase the number of bone-forming cells. So parathyroid hormone has both long-lasting effects through stem cells and short-acting effects through lining cells.”
Why a hormone that takes calcium out of bone would increase bone mass still isn’t understood in full detail, Dr. Kronenberg said.
“We know PTH takes calcium out of bone right away,” he said. “It happens within minutes. But when PTH builds bone, which in turn puts calcium into bone, it takes hours and days. I liken it to planning for retirement. Sometimes you need to spend some money, but you also need to invest and save some money because you’re going to need to spend it later as well.
“I theorize that if all we did was take calcium out of bone — if that was the main thing the parathyroid hormone did — the bone would be destroyed. I think it’s tactically wise that parathyroid takes calcium out quickly when needed to raise blood calcium for survival, but over time it slowly builds bone back up again for the next time.”
Dr. Kronenberg said he will share data that support his theory.