6/2/2018 Bone, a Masterpiece of Elastic Strength - The New York Times

SCIENCE

Bone, a Masterpiece of Elastic Strength

Basics

By NATALIE ANGIER APRIL 27, 2009

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.”

4 Mr. Eastlack to
Subscribe suffered fromYork
The New a rare and poorly
Times. SEEunderstood
MY OPTIONS congenital disease
Subscriber login
ARTICLES
REMAINING
called fibrodysplasia ossificans progressiva, in which cuts, bruises and trauma to

https://www.nytimes.com/2009/04/28/science/28angi.html 1/4
6/2/2018 Bone, a Masterpiece of Elastic Strength - The New York Times

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.”

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.

https://www.nytimes.com/2009/04/28/science/28angi.html 2/4
6/2/2018 Bone, a Masterpiece of Elastic Strength - The New York Times

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.”

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.”

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 is thought to be very energetically demanding. 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

https://www.nytimes.com/2009/04/28/science/28angi.html 3/4
6/2/2018 Bone, a Masterpiece of Elastic Strength - The New York Times

compartmentalized, a similar approach might be tried in humans without

inducing the sudden urge to reread “The Bell Jar.”

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.

Correction: April 29, 2009

The Basics column on Tuesday, about bone formation, omitted the given name and
affiliation of a doctor who studies bone development. Dr. Mone Zaidi is a professor at
the Mount Sinai School of Medicine and the director of the Mount Sinai Bone
Program.

Correction: May 8, 2009

The Basics column on April 28, about bone formation, referred incorrectly to
continual bone repair in the body. The exact number of calories used in bone
remodeling on a daily basis has yet to be determined; bone repair does not “consume
maybe 40 percent of our average caloric budget.”
A version of this article appears in print on , on Page D1 of the New York edition with the headline:
Bone, a Masterpiece Of Elastic Strength.

© 2018 The New York Times Company

https://www.nytimes.com/2009/04/28/science/28angi.html 4/4