Good vibrations and strong bones? Jens Jordan
288:555-556, 2005. doi:10.1152/ajpregu.00799.2004
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The American Journal of Physiology - Regulatory, Integrative and Comparative Physiology illuminate normal or abnormal regulation and integration of physiological mechanisms at all levels of biological organization, ranging from molecules to humans, including clinical investigations. It is published 12 times a year (monthly) by the American Physiological Society, 9650 Rockville Pike, Bethesda MD 20814-3991. Copyright 2005 by the American Physiological Society. Am J Physiol Regul Integr Comp Physiol 288: R555–R556, 2005;doi:10.1152/ajpregu.00799.2004. Editorial Focus Jens Jordan Franz-Volhard Clinical Research Center, Charite´, Campus Buch and HELIOS Klinikum, Berlin, Germany
THE HUMAN PHYSIOLOGY of bone perfusion has been neglected.
bone vascular function. In this study (1), oophorectomy in-
The issue may be explained in part by technical difficulties in
creased the responsiveness of isolated vascular rings from
assessing bone blood flow in vivo. Currently available tech-
small bone arteries to norepinephrine and to endothelin. How-
niques may be rather expensive, and the access of interested
ever, whether vascular damage to the bone vasculature ex-
scientists to these techniques may be limited. Another possible
plains the association between osteoporosis and cardiovascular
explanation for the neglect is the fact that the integration
between cardiovascular and bone research fails because each
Interestingly, treatment of some cardiovascular risk factors
research area is narrowly focused on its own organ or tissue
appears to have a beneficial effect on osteoporosis. For exam-
system. This state of affairs is unfortunate given the potentially
ple, smoking cessation leads to an improvement in markers of
important interactions between the cardiovascular system and
bone turnover within a 6-wk period (5). Lipid-lowering therapy
bone. Indeed, bone and vascular disease frequently coexist in
increases bone mineral density (3). Thiazide diuretics appear to
the same patients. Osteoporosis risk is increased in patients
lower the bone fracture rate (7). Moreover, beta blockers
with atherosclerosis and vice versa. The correlation is probably
appear to do the same (6). Finally, estrogen replacement
explained in part by a common underlying mechanism rather
therapy improves bone density and endothelial function in
than a spurious association. Bone perfusion may be such a
If bone perfusion has an important effect on bone density, could
Perfusion appears to be matched to the metabolic demands
an increase in bone perfusion also increase bone density? How
of the bone. For example, increased bone turnover and inflam-
can bone blood flow be increased? In this issue of the American
mation are associated with an increased blood flow. Blood flow
Journal of Physiology-Regulatory, Integrative and Comparative
decreases as bone turnover normalizes or the inflammation has
Physiology, Stewart et al. (9) reviewed the literature on bone
resolved. Failure of the vasculature to respond to metabolic
perfusion and bone mass. The few available publications seem to
needs of the bone might predispose to bone disease. Alterations
suggest that increased venous pressure and increased perfusion
in vascular function and in intraosseous angiogenesis may be
tend to increase bone mass. They reasoned that an increase in leg
contributory. Several studies suggest a correlation between
and, perhaps, bone perfusion may contribute to the recently
bone perfusion and bone density. Studies used different meth-
described increase in bone mass with whole body vibration (10). To address this issue, they assessed changes in leg hemodynamics
odologies and are, therefore, difficult to compare. In one study
and fluid shifts using strain-gauge and impedance plethysmogra-
(8), magnetic resonance imaging was used to obtain an indirect
phy before and during whole body vibration. The vibration was
measure of bone marrow perfusion at the level of the lumbar
elicited by placing the subjects on a vibrating platform. Whole
spine. Bone marrow perfusion was correlated with bone min-
body vibration increased blood flow to the lower body while
eral density in postmenopausal but not in premenopausal
subjects were in the supine position. Furthermore, the intervention
women. In another study (2), decreased bone marrow perfusion
reversed the decrease in leg blood flow in the upright position.
was associated with progression of collapse of fractured ver-
Finally, leg vibration shifted the microvascular filtration relation
tebra in patients with osteoporosis.
to higher pressures, both in the supine and in the upright position.
Perhaps “bone vascular disease” contributes to osteoporosis.
The shift is probably explained by improved lymphatic drainage.
One might further speculate that interventions that improve
Thus whole body vibration substantially altered leg hemody-
bone vascular function may have a beneficial effect on bone
structure. The anatomic structure of blood small blood vessels
The study by Stewart et al. (9) necessarily has some limita-
within the bone is similar to the structure of blood vessels in
tions. The authors did not measure bone perfusion directly. It
other tissues. These vessels may be susceptible to the same
is difficult to know whether the change in leg blood flow is
genetic and environmental risk factors.
associated with a change in bone perfusion. I would suggest
If bone vascular disease and, thus, alterations in perfusion
comparing “cheap” leg blood flow measurements with “costly”
were a cause of excessive bone loss, atherosclerosis risk factors
more direct measurements of bone blood flow in future studies.
should also increase the risk for osteoporosis. Indeed, smoking,
It would be tremendously helpful to have inexpensive methods
diabetes mellitus, elevated low-density lipoprotein cholesterol,
that could be used to obtain hemodynamic measurements that
reduced high-density lipoprotein cholesterol, and hyperhomo-
are relevant for bone hemodynamics. Furthermore, the authors
cystinemia are associated with increased cardiovascular risk
did not provide data linking changes in hemodynamics and
and reduced bone mineral density(4). Both the risk for cardio-
bone turnover. Perhaps more questions were raised than an-
vascular disease and the risk for osteoporosis increase sharply
swered. Nevertheless, the study is of importance because it
after menopause. A study in rabbits suggests that experimental
may generate interest in studying the interaction between bone
“postmenopause” through oophorectomy leads to changes in
and the cardiovascular system. Promising clinical and epide-miological data linking vascular disease and osteoporosisought to be supported by solid physiological work. Equally
Address for reprint requests and other correspondence: J. Jordan, Franz-
important, the study suggests that even in the era of molecular
Volhard Clinical Research Center, Haus 129, Charite´-Campus Buch, Wiltberg-str. 50, 13125 Berlin, Germany (E-mail: jordan@fvk.charite-buch.de).
medicine, a simple and “old-fashioned” physiological method
0363-6119/05 $8.00 Copyright 2005 the American Physiological Society
Editorial Focus
is still useful to raise new scientific hypotheses. A final ques-
5. Oncken C, Prestwood K, Cooney JL, Unson C, Fall P, Kulldorff M,
tion for those who will not be interested in bones: Do good
and Raisz LG. Effects of smoking cessation or reduction on hormone profiles and bone turnover in postmenopausal women. Nicotine Tob Res 4:
vibrations add to angiogenesis elsewhere?
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Genes and Immunity (1999) 1 , 3–19 1999 Stockton Press All rights reserved 1466-4879/99 $15.00 http://www.stockton-press.co.uk REVIEW Cytokine gene polymorphism in human disease: on-line databases J Bidwell1, L Keen1, G Gallagher2, R Kimberly3, T Huizinga4, MF McDermott5, J Oksenberg6,J McNicholl7, F Pociot8, C Hardt9 and S D’Alfonso101 Department of Pathology and Microbiology, Univer