NEWS RELEASE Environmental Toxicant Causes Osteoporosis by mikesanye


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                       Environmental Toxicant Causes Osteoporosis
               Common environmental contaminant found to cause “obesity of the bone”

Long Beach, Calif., January 13, 2011—Researchers have found that the powerful environmental toxicant
tributyltin (TBT) activates a master regulator of fat formation in the bone, which causes osteoporosis.
TBT is used commercially in wood preservatives, plastics, and pesticides. Results of the study were
presented at the 2011 Orthopaedic Research Society Annual Meeting in Long Beach, Calif.
         “Researchers have found that osteoporosis is caused when the bone marrow become s fatty,”
said study co-author Louis C. Gerstenfeld, PhD, Professor of Orthopaedic Surgery, Boston University
School of Medicine, Boston, Massachusetts.
         “There is growing recognition that a group of environmental contaminants are considered to be
environmental obesogens1” said co-author Jennifer Schlezinger, PhD, Associate Professor,
Environmental Health, Boston University School of Public Health. Her data suggests that these
environmental obesogens have the capacity to induce fat formation in bone.
         “Increases in environmental contaminants along with changes in diet may be leading to an
exacerbation of obesity in the bone,” Dr. Schlezinger said.
         With increased fat formation, less new bone is formed. As a consequence, the bone is weaker
and can become osteoporotic.
         Drs. Gerstenfeld and Schlezinger, along with several of their colleagues, conducted a study of
the environmental contaminant tributyltin (TBT) and its affect on bone marrow and on cortical and
trabecular bone.
        They compared those results to the peroxisome proliferator activated receptor γ (PPARγ)
agonist rosiglitazone, an anti-diabetic therapeutic, which causes fat formation in bone.
        The researchers tested the effects of TBT and rosiglitazone on laboratory animals (mice). They
established four test groups.
            1. No substance or sesame oil (control, n=12)
            2. Rosiglitazone (25 mg/kg, n=8)
            3. Low dose TBT (1 mg/kg, n=8)
            4. High dose TBT (10 mg/kg, n=10)
        The results of the study are as follows:
             In vitro, primary bone marrow cultures treated with rosiglitazone (10-100 nM)
                 stimulated adipocyte (fat cell) differentiation, while only the high dose of TBT (100 nM)
                 induced adipocyte differentiation

                Both rosiglitazone and TBT (100 nM) suppressed osteoblast (bone-forming cells)
              In vivo, significant effects were seen in the cortical compartment when treated with
                 rosiglitazone and the low dose of TBT
              High dose of TBT caused a reduction in cortical thickness, while low dose of TBT and
                 rosiglitazone had no effect
              Tissue mineral density was substantially reduced by treatment with rosiglitazone and
                 was reduced to a lesser degree by the high dose of TBT.
        The researchers also found that TBT had a significant effect on cortical bone, but no effect on
trabecular bone in the tibia. “During osteoporosis, much less cortical bone is lost than trabecular bone.
The loss of cortical bone usually contributes to a reduction in mechanical function at a much slower pace
than with trabecular bone loss. The effect of the toxicant on cortical bone loss therefore is quite
surprising and could be much more detrimental,” Dr. Gerstenfeld explained.
        This finding has potentially serious implications since the volume of cortical bone in the body
exceeds that of trabecular bone.
        “Our results suggest that TBT causes osteoporosis, probably by activating PPARγ, causing an
increase in adipocyte accumulation and a decrease in osteoblast formation,” the investigators stated.
        This research was supported by the National Institutes of Environmental Health Science and by
the Superfund Research Program.

    The ter m “environmental obesogen” was coined by Bruce Blumberg, PhD, of the University of California, Irvine

About the Orthopaedic Research Society (ORS):
The Orthopaedic Research Society (ORS) is the pre-eminent organization for the advancement of musculoskeletal
research. It seeks to transform the futur e through global multidisciplinary collaborations —focusing on the
complex challenges of orthopaedic trea tment. The ORS advances the global orthopaedic research agenda through
excellence in research, education, collaboration, communication and advocacy. The ORS Annual Meeting and
publication of the Journal of Orthopaedic Resea rch provide vital forums for the musculoskeletal community to
communicate the current state of orthopaedic research.

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