NEWS - Reports of severe pain with bisphosphonates

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Reports of severe pain with bisphosphonates

Rheumawire

Apr 19, 2005

Zosia Chustecka

Rockville, MD - US FDA officials have highlighted reports of severe bone,

joint, and muscle pain associated with the bisphosphonates alendronate

(Fosamax, Merck & Co) and risedronate (Actonel, Procter & Gamble, Aventis)

in a letter published in the Archives of Internal Medicine [1].

" Underreporting of pain is probably considerable because of its subjective

nature and because physicians may attribute pain to osteoporosis, " the

authors comment. Any serious or severe pain in bone, joint, and/or muscle

that is reported shortly after treatment with a bisphosphonate is started

should trigger a consideration for stopping the therapy, they add.

Most of the reports of severe pain have been associated with alendronate in

118 patients from the time it was first marketed in the US for osteoporosis

(September 1995) to November 2002. However, there have also been a few

reports with risedronate, a less widely used bisphosphonate, the FDA

officials comment: 6 reports in the period from its launch in September 1998

to June 2003. " The data suggest a class effect, " they add.

For alendronate, the FDA received serious-adverse-event (SAE) reports of

severe bone/joint or muscle pain in 112 women, 4 men, 1 adult of unknown

sex, and 1 child (age range 7-84 years, median 67 years). " Bones, joints,

and muscles throughout the body were affected. In some individuals, pain

began at 1 site and then migrated and became diffuse. It was often described

as 'severe,' 'extreme,' disabling,' or 'incapacitating.' Many patients were

unable to walk, climb stairs, or perform usual activities. Some became

bedridden and others required walkers, crutches, or wheelchairs. Many

underwent numerous diagnostic tests with mostly normal findings. "

For 96 patients with information on dose, alendronate was taken by the

majority at 10 mg/day (n=71, 74%); others took 5 mg/day (n=4, 4%), 20 to 25

mg/day (n=4, 4%), or the once-weekly formulation of 70 mg/week (n=17, 18%).

The median time to onset of pain from starting to take the drug was 14 days.

For 83 patients for whom there are further details, the pain stopped once

alendronate was discontinued in 55 patients (66%). Some patients experienced

immediate improvement, while the majority had a more gradual improvement.

Nine of these 83 patients (11%) reported pain once again when alendronate

was readministered.

The FDA officials comment that they reviewed clinical-trial data on both

alendronate and risedronate but found no meaningful differences between the

drugs and placebo for this adverse event. However, these differences

sometimes appear only in the marketplace experience, they comment.

New combo of once-weekly alendronate with vitamin D

A new combination product for osteoporosis has been approved in

the USan oral formulation for once-weekly administration containing

alendronate as well as vitamin D3 (cholecalciferol). Marketed as Fosamax

plus D, the new product contains 70-mg alendronate plus 2800-IU vitamin D3,

which represents 7 days' worth of the vitamin (recommended daily intake is

400-800 IU), the company says.

This product " will provide physicians with an important new

option " for women diagnosed with osteoporosis, says Dr Heaney

(Creighton University, Omaha, NE) in a press release. As well as the

" well-documented clinical benefit " of alendronate, it has the added

advantage of a weekly dose of vitamin D. " Many physicians and patients are

frequently unaware of the importance of vitamin D in bone health, " says

Heaney. " Given its effect on calcium absorption, vitamin D insufficiency is

an important medical concern for patients with osteoporosis, as it can lead

to bone loss and an increased risk of fracture. "

Source

1. Wysowski DK, Chang JT. Alendronate and risedronate:

reports of severe bone, joint, and muscle pain. Arch Int Med 2005;

165:346-347.

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Mayo Clinic in Rochester

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s Hopkins Medicine

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