RADIATION CAUSES BONE LOSS

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BlankRADIATION CAUSES BONE LOSS

The scientific world has been shaken by a report from Clemson University that a

single therapeutic dose of radiation can cause appreciable bone loss. Senior

author Ted Bateman, PhD, a professor of bioengineering, and his South Carolina

colleagues showed that when mice were given a dose of just two Gy (two gray, a

radiation dosage formerly designated as 200 rads), between 29 and 39 percent of

their interior bone mass was destroyed.

It did not particularly matter which kind of radiation the mice were exposed to.

Gamma rays, protons, high-speed carbon and iron nuclei all had a similar and

markedly destructive effect. Dr. Bateman and his colleagues reached these

figures by creating 3D computer scans of the spongy interior of the bones and

then calculating how much bone mass these irradiated mice had lost compared to a

control group.

" We were surprised at how large the difference in bone mass was, " Dr. Bateman

told the weekly magazine, New Scientist (Barry 2006).

Two Gy of radiation is similar to a single therapeutic dose of radiation given

to human cancer patients, while a full course of therapeutic radiation typically

delivers as much as 70 or even 80 Gy. It had previously been known that patients

receiving therapeutic radiation suffered some bone loss and were put at a

greater risk of fractures. But until now it was unknown that just a single dose

of radiation could trigger such severe bone loss. This news is doubly disturbing

since chemotherapy (often now given with radiation as part of a one-two punch)

can also independently cause bone loss. The cumulative effects of radiation and

chemotherapy delivered to the same patient may therefore be significantly more

damaging.

The Clemson scientists demonstrated what they called " profound changes in

trabecular architecture. " (The term " trabecular " describes the microscopic bony

latticework that characterizes the interior of skeletal bones. The trabecular

pattern of bony tissue is what gives bones their structural strength.)

Significant losses in bone volume were observed for the four types of radiation

that were studied: gamma (volume down 29 percent), proton (down 35 percent),

carbon (down 39 percent), and iron (down 34 percent). Several measurements of

bone health, including trabecular connectivity, density, thickness, spacing, and

number were also adversely affected.

" These data have clear implications for clinical radiotherapy, " the Clemson

scientists said, " in that bone loss in an animal model has been demonstrated at

low doses " (ibid.)

Dr. Bateman agreed, however, that making a direct extrapolation of these

findings to humans could be difficult. The bones of the mice in the experiment

were still growing, making them more susceptible to radiation damage. (This is

also the case in young human patients.) Although the Clemson findings have

caused a stir particularly in space research circles, NASA's chief radiation

health officer, Dr. Cucinotta, pointed out that the gamma ray dose in

these mouse experiments was 40 times greater than space station astronauts would

experience over a period of months, and 2 to 4 times what astronauts on a Mars

mission would encounter. However, astronauts are also exposed to high-energy and

iron nuclei in addition to gamma radiation.

Bone Death: A Long History

It has been known for quite some time that radiation could cause " serious and

permanent injuries " to growing bones as well as localized but incapacitating

diseases (Fajardo 2001: 365). In fact, the real surprise in the latest study was

that relatively small doses caused such a significant amount of damage.

The basic concept of 'bone death' was probably known to the ancient Greek

physician, Hippocrates. Necrosis of the bone (i.e., osteonecrosis) was fully

described as early as 1794. In 1903, just a few years after the 1895 discovery

of X-rays, the German surgeon Georg Clemens Perthes (1869-1927) exposed one wing

of a day-old chicken to X-rays. Just 12 days later he noted that growth of the

irradiated wing was retarded and that the feathers were abnormally formed. In

1905, two French scientists, ph Recamier and Louis Mathieu Tribondeau

(1872-1918), described similar growth retardation in kittens.

In the intervening decades, various tumors, especially sarcomas, were found with

increased frequency in patients who had undergone irradiation. Ewing, MD

(1866-1943), the celebrated American pathologist (after whom the bone tumor

called 'Ewing's sarcoma' is named), was extremely interested in the reactions of

bones to radiation. He was impressed by the ability of radiation to shrink the

size of bone tumors and, along with surgery and Coley's toxins (a fever-causing,

mixed bacterial vaccine), to effect prolonged remissions in some cases (Ewing

1940:370). He described three patients who had been irradiated for bone cancers

and whose irradiated bones then became brittle and easily fractured. Ewing also

observed thickening in the outer layer (known as the cortical plate) of bone at

the expense of the marrow cavity and noted the increased susceptibility of

irradiated bones to infection (Fajardo 2001).

The most famous instance of radiation damaging bones, however, occurred in the

first decades of the 20th century. Industrial engineers learned that by adding a

small amount of radium to a zinc sulfide solution (at a ratio of 1:30,000) they

could create a luminescent paint that glowed in the dark. This seemed to be a

harmless product. Around the time of World War I, approximately 2,000 young

women in New Jersey were employed painting the dials of clocks and watches with

luminous paint. In order to create fine brush tips for this detailed work they

would frequently lick the tip of the brushes. Over the years, these women either

ingested radium itself or breathed in radon gas in sufficient quantities to

cause serious medical problems for many of them. A New York dentist, Theodore

Blum, DDS, was the first to observe an unusual number of jaw-bone injuries in

these unfortunate dial painters, a condition he called 'radium jaw.'

The medical examiner of Essex County, NJ, at the time, on Marland, MD,

then became alarmed and launched a thorough investigation. He found severe

anemia in most of these women. At autopsy, many of these women had necrosis of

the bones, especially the mandible (lower jaw). Marland also recounted how the

damaged bone marrow, excised osteosarcomas (cancers) of their bones, or even

organs removed at autopsy literally glowed in the dark (Fajardo 2001: 366).

These women were so radioactive that, even after death, their bodily organs

would fog photographic film!

The most incredible part of this saga is that despite the fact that the danger

of luminous paint was well established in the 1920s, it was not until nearly 20

years later - in the run-up to World War II - that action was finally taken to

bar the use of radium in watch dial paint (Caufield 1989). It was a most

shameful episode in public health, but it did make the general public aware that

radiation could seriously damage bones and organs.

What is the Tolerance Dose?

Medical dictionaries define a 'tolerance dose' as the largest quantity of a

substance or treatment that an organism can endure without exhibiting

unfavorable or injurious effects. The tolerance dose of radiation to the bones

has traditionally been set quite a bit higher than is implied by the recent

Clemson article. There are many variables, but generally speaking when the dose

is from 70 to 80 Gy the incidence of osteoradionecrosis (bone death caused by

radiation) is in the range of 14-22 percent. It is 4 percent when the dose is

under 70 Gy. The tolerance dose for the adult human femur (thigh bone) is said

to be 38 to 43 Gy.

In the 1950s, Bonfiglio, MD, of the University of Iowa, found a 1.2 to

1.9 percent increase in the incidence of fractures of the femur after pelvic

irradiation for cancer (Fajardo 2001:373). Among patients who still have their

teeth, the bone necrosis rate caused by radiation is 24 percent. Among those

lacking teeth the rate is less - 14 percent. In studies involving patients who

still had teeth, this bony necrosis developed on average 10 months after

completion of radiation therapy. In those without teeth, it occurred on average

22 months later.

As noted above, if the bone is growing (as in the Clemson experiment) the

tissues are ultra-sensitive to radiation. Clinical observations suggest a

tolerance range of 15-30 Gy for growing bones.

In conclusion, exposing bone to radiation can result in four major types of

complications: necrosis (a type of cell death), fractures, severe alterations in

bone growth, and radiation-induced cancers. The topic of radiation-induced

cancers in particular has not received the attention it deserves. Radiation

itself is called a " complete carcinogen, " in that it can cause the four phases

of cancer's formation: (a) initiation, ( promotion, © progression and (d)

metastatic activity of transformed cells. While radiation-induced tumors of bone

are not common, they do occur, as the case of the radium-dial painters

dramatically showed.

Fajardo, MD, who recently retired as a professor of pathology at Stanford

University, California, has documented many such cases. " Irradiation from both

external and internal sources is associated with an increased risk of

osteosarcoma, " or bone cancer, he wrote in his classic textbook, Radiation

Pathology (Fajardo 2001:128). The minimum latency period for radium-caused

tumors is 3.5 years with a peak time of about 8 years, although cases were

documented as long as 25 years after initial exposure. Children who receive

radiation for cancers (other than those of bony origin) are at particular risk

if their growing bones receive large doses of radiation.

Although the danger of therapeutic radiation always seems to come as a surprise

to the general public, most of the risks of radiation to the bone were

recognized soon after Roentgen discovered X-rays. Yet, astonishingly, in the

21st century some patients receiving radiation are still not told about the full

extent or true likelihood of the harmful side effects of radiation therapy.

--Ralph W. Moss, Ph.D.

References:

Barry, . Space radiation scare for astronauts. New Scientist, July 22,

2006, p. 14.

Caufield, C. Multiple Exposures: Chronicles of the Radiation Age. NY: Harper &

Row, 1989, pp. 29-40. An excellent account for the general public.

Fajardo LF, Berthrong M, , RE. Radiation Pathology. Oxford: Oxford

University Press, 2001. Outstanding medical textbook.

Hamilton SA, Pecaut MJ, Gridley DS, et al. A murine model for bone loss from

therapeutic and space-relevant sources of radiation. J Appl Physiol. 2006 Jun 8;

[Epub ahead of print]

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