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Osteoporosis
the mandible or maxilla that has not healed over six to eight weeks, of post-menopausal osteoporosis in women who are at least five years
often occurring after oral surgery or a tooth extraction. About 95% of post-menopausal. It appears to have an analgesic effect that may
reported cases have been in cancer patients receiving prolonged high be clinically useful in the treatment of acute painful vertebral fractures.
27
doses of IV bisphosphonates. It is an extraordinarily rare event in patients
treated with bisphosphonates for osteoporosis, estimated to occur in Oestrogen
about 0.7 in 100,000 patient treatment years.
20
Zoledronate, given as an The WHI study showed that conjugated equine oestrogen (CEE) alone
28
annual 5mg IV infusion over 15 minutes, has been shown to reduce or in combination with a progestin
29
decreased the risk of vertebral and
vertebral, non-vertebral and hip fracture risk (annual meeting of the non-vertebral fractures in post-menopausal women not selected for high
American Society for Bone and Mineral Research, 15–19 September risk of fracture. Due to adverse events (increased risk of invasive breast
2006, Philadelphia, US). Approval of zoledronate for the treatment of cancer, heart attacks, stroke and venous thromboembolic events with
osteoporosis is pending at the time of writing. oestrogen–progestin; increased risk of stroke with oestrogen alone), both
arms of this study were ended prematurely. As a result, oestrogen is not
Selective Oestrogen Receptor Modulators recommended as a primary treatment for osteoporosis.
Raloxifene is a selective oestrogen modulator (SERM) that is approved for
the prevention and treatment of post-menopausal osteoporosis, with Trends and Investigational Agents
proven efficacy at increasing BMD and reducing the risk of vertebral There is a trend towards the use of injectable bisphosphonates and
fractures.
21
The Raloxifene Use for the The Heart (RUTH) trial in over longer dosing intervals than with currently available oral preparations,
10,000 post-menopausal women at risk of coronary heart disease (CHD) with the hope of improving on the poor patient compliance that has
showed no reduction in primary coronary events and an increase in the been reported with daily, weekly and monthly oral bisphosphonates.
31
risk of fatal stroke, although the overall death rates and total stroke rates Greater understanding of bone physiology at the molecular level has
were not increased.
22
The Study of Tamoxifen And Raloxifene (STAR) trial fostered the development of novel antiresorptive agents that target
in over 19,000 women at high risk of breast cancer demonstrated that specific cytokines (e.g. receptor activator of nuclear factor kB (RANK)
raloxifene was as effective as tamoxifen at reducing the risk of invasive ligand) or enzymes (e.g. cathepsin K). New delivery systems (such as
breast cancer with a lower risk of thromboembolic events.
23
Raloxifene oral calcitonin) may allow greater bioavailability and patient
should be considered as a treatment option to prevent bone loss, reduce acceptance compared with intranasal forms. New SERMs (e.g.
vertebral fracture risk and reduce the risk of invasive breast cancer in lasofoxifene, bazedoxifene and arzoxifene) and combinations of a
post-menopausal women who are not having difficulties with vasomotor SERM with oestrogen (e.g. bazedoxifene plus oestrogen) may offer
symptoms, not at high risk of stroke and not at high risk of improved therapeutic and safety profiles. Combinations (simultaneous,
thromboembolic events. sequential or cyclical) of antiresorptive and anabolic agents are being
investigated. The only large published head-to-head study comparing
Strontium Ranelate antiresorptive drugs with fractures as the primary end-point is the
Strontium ranelate is a compound that may have both antiresorptive Evista Alendronate Comparison (EVA) trial.
32
Unfortunately, the study
and anabolic properties. It is associated with large increases in BMD, in was terminated early due to slow enrollment, resulting in insufficient
part due to the incorporation of strontium, with an atomic weight that power to compare fracture risk between raloxifene and alendronate.
is heavier than calcium, into bone.
24
Strontium decreases the risk
of vertebral fractures
2
and non-vertebral fractures.
25
Summary
Clinicians now have a broad choice of antiresorptive agents for the
Salmon Calcitonin management of osteoporosis. When used appropriately, these drugs can
Synthetic salmon calcitonin given as an intranasal spray or by injection safely reduce fracture risk in patients at high risk of fracture. As experience
has an antiresorptive effect that is 40–50 times as great as human is gained with long-term use of antiresorptive drugs, better understanding
calcitonin. It is associated with a modest increase in spine BMD and a of how long to treat, when to consider a ‘drug holiday’ and how to
reduction in vertebral fracture risk,
26
and is approved for the treatment combine them with other therapeutic agents is beginning to emerge. ■
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96 EUROPEAN MUSCULOSKELETAL REVIEW 2007
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