bisphosphonates and postmenopausal osteoporosis

This is strictly not nutrition but the concepts are very relevant to nutrition and important slowly evolving disease conditions.
Black et al looked at the use of Once yearly infusions of zoledronic acid for the treatment of postmenopansal osteoporosis. N Engl Med. 2007:356:1809-22
Oral bisphosphonates help prevent fractures in postmenopausal women, but they can be inconvenient to take and many women stop their treatment. These authors wanted to test whether a more convenient yearly infusion of intravenous zoledronic acid would also reduce the risk of fractures.
7765 postmenopausal women with osteoporosis took part in a randomised, double blind trial, sponsored by the manufacturers of zoledronic acid. Participants were given three infusions of zoledronic acid (5 mg) or a placebo at yearly intervals. They were followed up for 12 months after their last infusion. The authors looked for vertebral fractures in yearly spinal radiographs. Other fractures, including hip, were reported by participants and confirmed by radiographs. The authors monitored participants bone mineral density using dual energy x ray absorptiometry and used serum markers to monitor bone turnover.
Zoledronic acid is a third-generation bisphosphonate. .Analogues of pyrophosphate. the bisphosphonates bind to calcium hvdroxyapatite in the skeleton blocking calcium release. They inhibit osteoclast formation and osteoblast proliferation and induce osteoclast apoptosis. These agents also block skeletal calcium release induced by various factors released by tumours Both zoledronic acid and pamidronatc have been shown to have direct anti tumour effects in vitro, Zoledronic acid induces cell apoptosis and inhibits proliferation in human breast, prostate. and myeloma cell lines. ( Dunham D Journal of Pharmacy Society of Wisconsin Jan/Feb 2003, – 9-13)
3.3% (92/2822) of the women given zoledronic acid had a vertebral fracture, a reduction of 70% compared with the 10.9% (310/2853) of those given placebo Zoledronic acid also significantly reduced the risk of hip fracture (1.4% v 2.5%, ), all non-vertebral fractures, all clinical fractures, and clinical vertebral fractures. It also significantly increased women’s bone mineral density at the hip, lumbar spine, and femoral neck compared with placebo (by 6%, 6.7%, and 5.1%) and reduced bone turnover.
The down side is that an infusion of zoledronic acid was associated with a higher incidence of fever, myalgia, flu-like symptoms, headache, and arthralgia. It was also associated with a higher risk of serious atrial fibrillation (5% v 1.3%,), but no long term renal toxicity. One woman in each group developed osteonecrosis of the jaw, a rare side effect of intravenous bisphosphonates given in high doses to patients with cancer.
A single yearly infusion of 5 mg zoledronic acid helped prevent important osteoporotic fractures in this vulnerable population of postmenopausal women. The excess of atrial fibrillation is a worry and needs further investigation. Some women might find a yearly infusion easier and more convenient than regular oral drugs, and it’s possible the two routes are equally effective.
Reported in the BMJ 7th July 2007 p 36
It seems extraordinary that an annual infusion at a dose of 5 mg can have such a sustained effect.

Martin Eastwood
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