Exciting New Developments in Osteoporosis Treatment
This report was reviewed for medical and scientific accuracy by Michael Divon, MD , Director of OB/GYN, Lenox Hill Hospital, New York.
Medicinal versions of a naturally occurring hormone stirred considerable excitement among doctors attending the World Congress on Osteoporosis held June 13-18 at Navy Pier in Chicago, Illinois. Researchers say that for the first time, a cure for osteoporosis appears to be in sight.
Affecting about ten million Americans, 80 percent of them women, osteoporosis is a crippling bone disease that primarily occurs as a result of inadequate calcium intake from childhood, leaving bones brittle and subject to fractures-commonly of the spine, hip, and forearm.
The condition is most prevalent in women after menopause, when ovarian production of the bone-protective hormone estrogen drops off sharply, and it continues to increase in severity with age. As the body's ability to retain and use calcium to form new bone declines through time, a thinning process known as bone resorption takes place in which old bone is dissolved by the body faster than new bone can be formed to replace it. Untreated, this process can ultimately lead to fractures caused by a simple fall-commonly involving the hip and forearm-or by merely lifting a bag of groceries, causing a vertebra to collapse. In severe cases, vertebrae spontaneously collapse under the body's own weight, leading to spinal deformities such as the so-called "dowager's hump."
Until now, physicians have treated osteoporosis with a number of agents designed to slow bone resorption and preserve patients' bone mass. Hormone replacement therapy (HRT) with estrogen and bisphosphonates (bone specific agents such as alendronate [Fosamax®] and risedronate [Actonel™]), and calcium and Vitamin D supplements, used alone and in combination, all work this way to greater or lesser degrees, which is why they are referred to as "anti resorptive agents." They preserve bone strength by slowing the removal of calcium from the skeleton. But what researchers have been working hard to find is a "formative agent," a drug capable of helping the body form new bone, thereby restoring a neutral or positive bone balance that will return weakened osteoporotic bone to normal strength and density, thus preventing or at least significantly reducing the risk for fractures.
It now appears they have found one. Clinical trials presented at the World Congress on Osteoporosis 2000 convincingly showed daily injections of hPTH 1-34 (PTH) could build strong new bone in women with osteoporosis and reduce their risk of spinal fracture by up to 80 percent when taken in combination with estrogen and calcium/vitamin D supplements.
PTH is a medicinal form of parathyroid hormone, which is produced by four small glands that surround the thyroid gland in the neck. The hormone's job is to maintain a calcium balance in the body, which is necessary not just to form bone but to regulate various other cellular processes as well. If calcium levels are low, for instance, the hormone tells the bones to dissolve calcium into the blood to maintain functions of other organs, such as the heart and brain. But PTH also puts calcium back into bone by telling the kidneys to retain any calcium they encounter, and it stimulates Vitamin D production, which tells the intestines to extract more calcium from food.
Importantly, it also tells bone cells to use calcium to make more bone, which gave researchers the idea that combining PTH with estrogen would provide a one- two punch against osteoporosis. On the one hand, they reasoned, estrogen would preserve what bone remained, while PTH would potentiate calcium uptake from food and supplements, while encouraging bone cells to grow new bone.
So far, the strategy appears to be working. According to Dr. Jeri Nieves, an Epidemiologist and Director of Bone Density Testing at Helen Hayes Hospital in West Haverstraw, NY, "We believe PTH has taken us further towards a cure for osteoporosis. Anti resorptive agents reduce fractures by 50 percent, which is very helpful, but there is obviously room for improvement. We believe our study demonstrates PTH is an exciting next step in the treatment of osteoporosis."
Dr. Nieves was referring to a three-year trial of 52 patients that showed PTH added new bone to a four percent increase in bone mass that the women had already achieved taking estrogen replacement therapy alone for 12 months. "When they took PTH in addition to estrogen," she added, "the spine bone density went up another 13 percent, the hip increased 4.5 percent and the total body bone density increased by 3.5 percent. Further, when we followed these patients for another year after they stopped taking PTH, it was clear they retained the new bone."
A dramatic decrease in fractures was seen in study participants, she added. In the study, 27 patients received PTH with estrogen, while 25 were given estrogen alone. When researchers compared the two groups after three years, only two spinal fractures occurred in the combined therapy group, compared to 12 in patients receiving estrogen alone. "If we can reproduce these findings in subsequent studies that show this agent increases bone mass throughout the skeletal system, it will be a wonderful advance in preventing fractures due to osteoporosis," Dr. Nieves said.
In a similar study reported at the Chicago meeting by Dr. Bruce Roe, a Professor of Medicine at the University of Manitoba in Canada, 74 women received calcium and Vitamin D supplements as needed (daily calcium intake was maintained at 1500 mg per day) with either PTH plus HRT, or placebo over a two-year period. When researchers compared the two groups, those receiving PTH increased their spinal bone density by 12 percent within six months and 29 percent after two years. "The results at six months were the equivalent of what we see with anti resorptive drugs alone after two years," Dr. Roe said, "and the results at 24 months were triple what we see with any other therapy-that's an extremely significant improvement if you are trying to prevent fractures of the vertebrae."
Further, large bone density increases were also noted in the hip and forearm, he added, the main sites doctors focus on in measuring how well patients are responding to therapy. "With these early results, we are beginning to think a cure for osteoporosis is possible," Dr. Roe said. "By the end of our study, 65 percent of the women who had osteoporosis had regained normal bone density, whereas no change occurred to those taking placebo."
Researchers are now trying to sort out if PTH can be used as a stand-alone therapy or should be combined with HRT or bone specific agents, Dr. Nieves added. Still in the developmental stage, PTH has not yet gone before the FDA for approval. "It may turn out this therapy is best used in a select group of patients who have responded to HRT or bisphosphonates, but are still in a high fracture risk category," she pointed out.
The one drawback to the therapy at present is that it requires a daily injection by needle, which some patients may be reluctant to do, but work is already underway to investigate pill or patch forms of delivery, making the therapy more acceptable to a much wider patient population, Dr. Nieves concluded.