It took a while before Shelley Powers finally went to her doctor. She had experienced back pain before, but this felt different, and it had dragged on for months. She left that first visit none the wiser. X-rays showed nothing wrong. Her habits and environment hadn’t changed in any way that would explain it. But after a few more doctor visits and discussions about her family history, a possible explanation emerged: osteoporosis.
It seemed outlandish to be diagnosed with a disease associated with old age. This was 7 years ago when Powers was 53. She has always been thin, active, and ruddy with health. Her doctor sent her to a specialist to get a DXA test (dual X-ray absorptiometry), which measures the mineral density of bone by subtracting out the X-ray absorption due to soft tissue. Th e lower the density, the more fragile the bone. Sure enough, her bone density was far below the typical value. “That confirmed it,” says Powers. “And after that, I had to become very educated very quickly.”
The risks lying in her future were scary indeed. Osteoporosis changes the internal structure of bones, especially in the spongy matrix inside the ends of long bones, in the hips, and the spine. If left unchecked, large pores form in that matrix—hence the disease’s name—making bone so fragile it can shatter with the slightest impact. Th e killer is a hip fracture. A quarter of osteoporosis patients who suffer a hip fracture die within 6 months due to complications.
The disease caught Powers by surprise, and she is not alone. “Th e most important problem… is that the public, health professionals, and legislators do not recognize the extent of the problem,” says Robert Recker, director of the Osteoporosis Research Center at Creighton University in Omaha, Nebraska. “About 50 percent of all Caucasian women alive today will have a fracture due to osteoporosis before they die. Death rates from the fractures due to osteoporosis are greater than those from heart attacks, strokes, and breast cancer combined in women.” And yet, until relatively recently, the disease was off the public health radar.
Bones are more complicated than they seem. Th e soft marrow inside of bones is a factory for making new blood cells. The hard mineral part is a buff er that keeps the pH of blood stable. And most surprisingly, bones are constantly changing themselves. Th e skeleton seems like the only permanent structure in the adult body, but that is an illusion. At any given time, about a tenth of bone tissue is being broken down and built back up by teams of cells, and all of this is finely tuned by the endocrine system.
Calcium is the big player in this story. Everything from muscle contraction to neuronal signaling requires calcium ions to function. Th e vast majority of one’s calcium is locked up in hydroxyapatite, the crystals of calcium and phosphate that make bone hard. Th e remodeling cells are always poised on the surface of bones, waiting for molecular signals. When the concentration of calcium dissolved in the blood dips too low, cells called osteoclasts are triggered to break bone down to release minerals into the blood stream. Once blood calcium gets high enough, cells called osteoblasts are triggered. They grab calcium and phosphate from the bloodstream to rebuild bone.
In a healthy person, these negative feedback loops keep bone density and blood calcium levels steady. In osteoporosis, this homeostasis goes off kilter, causing bone to break down too quickly or rebuild too slowly.
This is what makes a cure for the disease so elusive, says Recker. “Its cause is complex, involving both genetic and environmental factors.” The ultimate problem, bone density, is controlled by a tangled endocrine circuit. The thyroid gland broadcasts a small polypeptide hormone called calcitonin that binds to osteoclast cells and slows down the rate of bone destruction. Balancing that signal, a gigantic polypeptide called parathyroid hormone (PTH) dials up the rate of bone breakdown. (To make matters more complex, the target of PTH is actually on the surface of the bone-building osteoblast cells, which then trigger their neighboring osteoclast cells with yet another signaling molecule.) Added to this are yet more layers of control, including the hormone estrogen, which decreases bone reabsorption and boosts bone formation. That is one reason why osteoporosis hits women around the same age as Powers. When estrogen levels plummet during menopause, a woman can start losing as much as 5 percent of her bone per year.
Once Powers was diagnosed, there was no question that she would need medication immediately. “I just had so many risk factors,” she says. She had a previous wrist fracture, she is petite—with thin bones to match—and has a family history of osteoporosis. “My father was diagnosed with it after he broke both hips and his spine.” Th e question was, which meds would work for her? Th e big guns in the osteoporosis pharmacy are the bisphosphonate drugs. The first to come on the market was Fosamax in the 1990s, and several others—Actonel, Boniva, Reclast—have followed. Bisphosphonates bind to bone and inhibit osteoclasts from breaking it down, but they can have nasty side effects. Th e drugs come as a pill that can cause ulcers in the esophagus. Th ere is also a question about whether the drugs change bone structure for the worse over the long term, making unusual fractures of the thigh bone more likely. And some nasty litigation is underway, with patients claiming that the drugs have caused a deterioration of the jaw bone only seen in workers at match factories.
Rather than bisphosphonates, Powers’ doctor started her on a relatively new drug called Forteo. It is actually a fragment of the PTH protein. Th ere are some worrying indications from rat studies that it can increase risk for bone cancers. Th e NIH has warned that it should be considered a drug of last resort. But Forteo is also the only osteoporosis medication that can directly stimulate the formation of new bone. And new bone is what Powers needed. So in spite of the risks, she started the daily injections.
She’s glad she did. “Th e pain was gone within a month,” she says. “I may have had microfractures in my lower lumbar.” The hormone could have reversed that crumbling. After 2 years of Forteo, she went on Fosamax. New treatments for osteoporosis are on the horizon. A bisphosphonate that does not upset the gastrointestinal tract is being developed by Mission Pharmacal. And a study recently demonstrated that a single dose of a bisphosphonate called zoledronic acid can dramatically decrease fracture risk—at least in rats.
But the most important prevention and treatment of osteoporosis is likely to remain the same: diet and exercise. “I’ve been completely off meds for 2 years now,” says Powers. She has a daily ritual of mineral water and yogurt for calcium and vitamin D, while Pilates and hiking in the California hills give her bones a healthy dose of stress.
In retrospect, Powers’ back ache was the best thing that could have happened to her. “One out of every two women and one out of every four men over 50 will be diagnosed with osteoporosis,” says Powers, and yet most will only find out after a severe fracture. She has become a board member of American Bone Health to help get the word out. “People need to get themselves screened. This disease is very preventable.”