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Bone, a Masterpiece of Elastic Strength
When Harry Eastlack was 5 years old, he broke his left leg while out playing with his sister. The fracture failed to set properly, and soon his hip and knee had stiffened up as well. Examining the boy, doctors found ominous bony growths on the muscles of his thigh. Within a few years, bony deposits had spread throughout Harry’s body, infiltrating his chest, neck, back and buttocks. Surgeons tried to cut the excess bone away, only to watch it grow back thicker and more invasive than before.
By his mid-20s, his vertebrae had fused together, his torso been thrust rigidly forward and his back muscles replaced with solid bone. Finally, even his jaw locked up, and he died of pneumonia in 1973, just shy of his 40th birthday.
Mr. Eastlack had requested that his skeleton be preserved for scientific research, and today it can be seen at the Mutter Museum of the College of Physicians in Philadelphia  or rather, they can be seen. As the developmental biologist Armand Marie Leroi has observed in his book “Mutants,†Mr. Eastlack’s skeleton, with its “extra sheets, struts and pinnacles of bone,†amounts to “that of a 40-year-old man encased in another skeleton, but one that is inchoate and out of control.â€Â
Mr. Eastlack suffered from a rare and poorly understood congenital disease called fibrodysplasia ossificans progressiva, in which cuts, bruises and trauma to the body, no matter where they occur, end up being “repaired†by cells designed for building bone. Devastating as it is, the disorder reveals fundamental features of the astonishing connective tissue that is bone. For one thing, although bone may seem like stone, it is tirelessly, ambitiously alive. In many ways, bone is more animate than the muscles and fat draped over it or the quivering visceral organs it protectively encages. It certainly can be more attuned to its surroundings.
Researchers have discovered that an impressive raft of metabolic and reproductive hormones will activate bone tissue, often at doses much smaller than what is required to arouse the breast, gonads or other organs presumed to be a hormone’s principal target.
Among the most provocative revelations is that bone quickens to the touch of serotonin and oxytocin, signaling molecules more often associated with happy moods, friendship and cuddling together in a straw nest than with the integrity of the backbone.
“No organ is an island,†said Gerard Karsenty, a professor of genetics and development at the Columbia University Medical Center, “and the skeleton is connected functionally to many more organs than we had anticipated.â€Â
This week, Dr. Karsenty and other prominent names in the bone business will discuss their new research and gleefully clean out their closets at the Third New York Skeletal Biology and Medicine Conference, at the Mount Sinai School of Medicine.
The Eastlack case also reveals that healthy bone is disciplined bone, with a structure enviably organized at every scale yet probed, from the caliper calibrations of femurs and phalanges down to the nano dimensions of bone’s constituent atoms. “It’s all in the architecture,†said Robert O. Ritchie, a professor of materials science at the University of California, Berkeley, who studies bone.
Bone is built of two basic components: flexible fibers of collagen and brittle chains of the calcium-rich mineral hydroxyapatite. But those relatively simple ingredients, the springy and the salty, are woven together into such a complex cat’s cradle of interdigitating layers that the result is an engineering masterpiece of tensile, compressive and elastic strength. “We only wish we could mimic it,†Dr. Ritchie said.
Or at least mimic the signals that keep our 206 bones in line. Diseases of excess bone growth are rare, but bone degradation is an almost inevitable symptom of aging, and the severe form called osteoporosis is considered a major and mounting medical crisis. Unfortunately, said Dr. Mone Zaidi, a professor of medicine at Mount Sinai, “the armamentarium for osteoporosis is quite small compared to that for other age-related diseases like high blood pressure.â€Â
Behind the dissolution of bone with age is a system designed for the itinerant years of youth. The skeleton is a multipurpose organ, offering a ready source of calcium for an array of biochemical tasks, and housing the marrow where blood cells are born. Yet above all the skeleton allows us to locomote, which means it gets banged up and kicked around. Paradoxically, it copes with the abuse and resists breaking apart in a major way by microcracking constantly. “Bone microcracks, that’s what it does,†Dr. Ritchie said. “That’s how stresses are relieved.â€Â
Bone also has a crack repair team, in every sense of the word: osteoclast cells that dig around the cracks, using acids to wipe away the old matrix, and osteoblast cells that migrate in and secrete fresh spacklings of bone. “Bone remodeling is going on simultaneously in hundreds of locations a day,†Dr. Karsenty said. It’s our private MASH, he said, our ambulatory surgical unit that helps keep us on our feet.
But like all forms of health care, bone repair doesn’t come cheap, and maintaining skeletal integrity consumes maybe 40 percent of our average caloric budget. The costliness of the process could explain why the bone and gut appear to be hormonally synchronized, Dr. Karsenty said, controlled by a similar chemical vocabulary.
When bone needs more energy, it talks with the gut; if the gut is all spent, it’s time for osteoblast furlough. One candidate cross-link between the alimental and architectural is the hormone serotonin. Reporting last November in the journal Cell, Dr. Karsenty and his colleagues showed that if they slowed the release of serotonin from the gastrointestinal tract  which generates 95 percent of the body’s supply of the hormone, against 5 percent in the brain  they could prevent osteoporosis in mice, with no obvious side effects. And because the blood-brain barrier keeps the serotonin caches above and below the neck neatly compartmentalized, a similar approach might be tried in humans without inducing the sudden urge to reread “The Bell Jar.â€Â
Another potential frame-saver might be a variant of pitocin, the drug long used to induce uterine contractions and help speed up birth. This month in The Proceedings of the National Academy of Sciences, Dr. Zaidi and his colleagues showed that the hormone oxytocin stimulated bone building in mice. Pitocin is synthetic oxytocin. If our children won’t support us, maybe it’s time to give birth to ourselves.
The New york Times
When Harry Eastlack was 5 years old, he broke his left leg while out playing with his sister. The fracture failed to set properly, and soon his hip and knee had stiffened up as well. Examining the boy, doctors found ominous bony growths on the muscles of his thigh. Within a few years, bony deposits had spread throughout Harry’s body, infiltrating his chest, neck, back and buttocks. Surgeons tried to cut the excess bone away, only to watch it grow back thicker and more invasive than before.
By his mid-20s, his vertebrae had fused together, his torso been thrust rigidly forward and his back muscles replaced with solid bone. Finally, even his jaw locked up, and he died of pneumonia in 1973, just shy of his 40th birthday.
Mr. Eastlack had requested that his skeleton be preserved for scientific research, and today it can be seen at the Mutter Museum of the College of Physicians in Philadelphia  or rather, they can be seen. As the developmental biologist Armand Marie Leroi has observed in his book “Mutants,†Mr. Eastlack’s skeleton, with its “extra sheets, struts and pinnacles of bone,†amounts to “that of a 40-year-old man encased in another skeleton, but one that is inchoate and out of control.â€Â
Mr. Eastlack suffered from a rare and poorly understood congenital disease called fibrodysplasia ossificans progressiva, in which cuts, bruises and trauma to the body, no matter where they occur, end up being “repaired†by cells designed for building bone. Devastating as it is, the disorder reveals fundamental features of the astonishing connective tissue that is bone. For one thing, although bone may seem like stone, it is tirelessly, ambitiously alive. In many ways, bone is more animate than the muscles and fat draped over it or the quivering visceral organs it protectively encages. It certainly can be more attuned to its surroundings.
Researchers have discovered that an impressive raft of metabolic and reproductive hormones will activate bone tissue, often at doses much smaller than what is required to arouse the breast, gonads or other organs presumed to be a hormone’s principal target.
Among the most provocative revelations is that bone quickens to the touch of serotonin and oxytocin, signaling molecules more often associated with happy moods, friendship and cuddling together in a straw nest than with the integrity of the backbone.
“No organ is an island,†said Gerard Karsenty, a professor of genetics and development at the Columbia University Medical Center, “and the skeleton is connected functionally to many more organs than we had anticipated.â€Â
This week, Dr. Karsenty and other prominent names in the bone business will discuss their new research and gleefully clean out their closets at the Third New York Skeletal Biology and Medicine Conference, at the Mount Sinai School of Medicine.
The Eastlack case also reveals that healthy bone is disciplined bone, with a structure enviably organized at every scale yet probed, from the caliper calibrations of femurs and phalanges down to the nano dimensions of bone’s constituent atoms. “It’s all in the architecture,†said Robert O. Ritchie, a professor of materials science at the University of California, Berkeley, who studies bone.
Bone is built of two basic components: flexible fibers of collagen and brittle chains of the calcium-rich mineral hydroxyapatite. But those relatively simple ingredients, the springy and the salty, are woven together into such a complex cat’s cradle of interdigitating layers that the result is an engineering masterpiece of tensile, compressive and elastic strength. “We only wish we could mimic it,†Dr. Ritchie said.
Or at least mimic the signals that keep our 206 bones in line. Diseases of excess bone growth are rare, but bone degradation is an almost inevitable symptom of aging, and the severe form called osteoporosis is considered a major and mounting medical crisis. Unfortunately, said Dr. Mone Zaidi, a professor of medicine at Mount Sinai, “the armamentarium for osteoporosis is quite small compared to that for other age-related diseases like high blood pressure.â€Â
Behind the dissolution of bone with age is a system designed for the itinerant years of youth. The skeleton is a multipurpose organ, offering a ready source of calcium for an array of biochemical tasks, and housing the marrow where blood cells are born. Yet above all the skeleton allows us to locomote, which means it gets banged up and kicked around. Paradoxically, it copes with the abuse and resists breaking apart in a major way by microcracking constantly. “Bone microcracks, that’s what it does,†Dr. Ritchie said. “That’s how stresses are relieved.â€Â
Bone also has a crack repair team, in every sense of the word: osteoclast cells that dig around the cracks, using acids to wipe away the old matrix, and osteoblast cells that migrate in and secrete fresh spacklings of bone. “Bone remodeling is going on simultaneously in hundreds of locations a day,†Dr. Karsenty said. It’s our private MASH, he said, our ambulatory surgical unit that helps keep us on our feet.
But like all forms of health care, bone repair doesn’t come cheap, and maintaining skeletal integrity consumes maybe 40 percent of our average caloric budget. The costliness of the process could explain why the bone and gut appear to be hormonally synchronized, Dr. Karsenty said, controlled by a similar chemical vocabulary.
When bone needs more energy, it talks with the gut; if the gut is all spent, it’s time for osteoblast furlough. One candidate cross-link between the alimental and architectural is the hormone serotonin. Reporting last November in the journal Cell, Dr. Karsenty and his colleagues showed that if they slowed the release of serotonin from the gastrointestinal tract  which generates 95 percent of the body’s supply of the hormone, against 5 percent in the brain  they could prevent osteoporosis in mice, with no obvious side effects. And because the blood-brain barrier keeps the serotonin caches above and below the neck neatly compartmentalized, a similar approach might be tried in humans without inducing the sudden urge to reread “The Bell Jar.â€Â
Another potential frame-saver might be a variant of pitocin, the drug long used to induce uterine contractions and help speed up birth. This month in The Proceedings of the National Academy of Sciences, Dr. Zaidi and his colleagues showed that the hormone oxytocin stimulated bone building in mice. Pitocin is synthetic oxytocin. If our children won’t support us, maybe it’s time to give birth to ourselves.
The New york Times