Osteoporosis Treatment -- Without Estrogen
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A class of drugs called bisphosphonates has become the new mainstay
treatment for postmenopausal women diagnosed with osteoporosis in the
post-hormone-replacement era. Taking just one pill a week, or even one
a month, may prevent, slow or stop the breakdown and progress of this
bone-thinning condition, according to the May issue of Mayo Clinic
Women's HealthSource.

Newswise - A class of drugs called bisphosphonates has become the new
mainstay treatment for postmenopausal women diagnosed with
osteoporosis in the post-hormone-replacement era. Taking just one pill
a week, or even one a month, may prevent, slow or stop the breakdown
and progress of this bone-thinning condition, according to the May
issue of Mayo Clinic Women's HealthSource.

An estimated 10 million Americans, mostly women, have osteoporosis,
where bones become weak and highly prone to fractures. Millions more
have low bone density (osteopenia), which can increase the risk of
fractures.

Bone -- a living tissue -- is constantly remodeling, with old bone
breaking down and new bone replacing it. Bisphosphonates work by
slowing the breakdown and reabsorption of old bone, an ongoing process
that accelerates as estrogen levels fall during the first few years
after menopause. By slowing the process, bisphosphonates help preserve
bone density and reduce the risk of fractures.

Estrogen once was commonly prescribed to reduce bone loss. But when
the landmark Women's Health Initiative Study, released in 2002, showed
that long-term estrogen use increased the risk of breast cancer, heart
attacks, strokes and blood clots, hormone therapy fell out of favor.

Bisphosphonates have filled the void and perform as well as estrogen
in preventing bone loss. Bisphosphonates available to treat
osteoporosis include alendronate (Fosamax), ibandronate (Boniva) and
risedronate (Actonel).

Patients should talk with a doctor about the best ways to prevent and
treat osteoporosis. Bisphosphonates have potential side effects, most
commonly heartburn and abdominal pain caused by irritation of the
esophagus or stomach. Even when taking medications, patients should
take steps to protect bones, including consuming adequate calcium and
vitamin D; engaging in regular weight-bearing exercise such as walking
and weight training; and avoiding smoking and excessive use of
alcohol.

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Bisphosphonates

Bisphosphonates are a family of drugs used to prevent and treat
osteoporosis. There are three bisphosphonates currently approved for
use in Canada: alendronate (Fosamax ®), etidronate (Didrocal ®) and
risedronate (Actonel ®).

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<<snip>>
Bisphosphonates have antioxidant properties as iron chelators
<<snip>>

Antioxidant effect of bisphosphonates and simvastatin on chondrocyte
lipid peroxidation.
Dombrecht EJ, De Tollenaere CB, Aerts K, Cos P, Schuerwegh AJ, Bridts
CH, Van Offel JF, Ebo DG, Stevens WJ, De Clerck LS
Biochem Biophys Res Commun. 2006 Jul 28;

The objective of this study was to evaluate the effect of
bisphosphonates (BPs) and simvastatin on chondrocyte lipid
peroxidation. For this purpose, a flow cytometrical method using
C11-BODIPY(581/591) was developed to detect hydroperoxide-induced
lipid
peroxidation in chondrocytes. Tertiary butylhydroperoxide (t-BHP)
induced a time and concentration dependent increase in chondrocyte
lipid peroxidation. Addition of a Fe(2+)/EDTA complex to t-BHP or
hydrogen peroxide (H(2)O(2)) clearly enhanced lipid peroxidation. The
lipophilic simvastatin demonstrated a small inhibition in the
chondrocyte lipid peroxidation. None of three tested BPs (clodronate,
pamidronate, and risedronate) had an effect on chondrocyte lipid
peroxidation induced by t-BHP. However, when Fe(2+)/EDTA complex was
added to t-BHP or H(2)O(2), BPs inhibited the lipid peroxidation
process varying from 25% to 58%. This study demonstrates that BPs
have
antioxidant properties as iron chelators, thereby inhibiting the
chondrocyte lipid peroxidation. These findings add evidence to the
therapeutic potential of bisphosphonates and statins in rheumatoid
arthritis.

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Age-associated Iron Accumulation in Bone: Implications for
Postmenopausal Osteoporosis and a New Target for Prevention and
Treatment by Chelation.
Liu G, Men P, Kenner GH, Miller SC
Biometals. 2006 May 11;

Iron accumulation in tissues is believed to be a characteristic of
aged

humans and a risk factor for some chronic diseases. However, it is
not
known whether age-associated iron accumulation is part of the
pathogenesis of postmenopausal osteoporosis that affects
approximately
one out three women worldwide. Here, we confirmed that this
accumulation of iron was associated with osteopenia in ovariectomized
(OVX) rats (a model of peri- and postmenopausal osteoporosis due to
estrogen deficiency). To further investigate whether the increased
iron

level plays a causal role in the onset of bone loss, we treated OVX
rats with an orally active and bone targeted chelator that prevented
iron accumulation in their skeletal tissues. The results showed that
this treatment mitigated the loss of bone mass and the deterioration
of

bone micro-architecture. We also found that one possible mechanism of
the protective action of iron chelation was to significantly reduce
bone resorption. Thus, these findings provide a novel target and a
potentially useful therapeutic strategy for the prevention and
treatment of postmenopausal osteoporosis and perhaps other age-
related
diseases.

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