Alendronate (Fosamax) for bone disease in patients with Gaucher Disease

Gauchers News Contents

Dr Gregory Grabowski is a Professor of Paediatrics, Molecular Genetics, Biochemistry and Microbiology at the University of Cincinatti. He, together with Dr Richard Wenstrup, have completed a trial using the bisphosphonate drug Alendronate (Fosamax) on patients with Gaucher disease. He gave the following results at the US Gaucher Conference on 11 October 2003 and a paper was published in the journal Blood on 1 September 2004.

Dr Grabowski described the trial involving adult patients with Gaucher disease to see if their bones improved by taking Fosamax which is a bisphosphonate drug taken by mouth. He gave the following results:


Dr Grabowski recommended that the drug should be given in addition to enzyme replacement therapy for the treatment of adults with Gaucher disease who have decreased bone density.

A 70mg pill should be taken once a week in a single dose as other trials have shown that the drug at a dose of 70mg taken once a week is as effective as 10mg taken once a day and that a 10mg pill is as effective as a 40mg pill taken once a day. Merck, the company which makes Fosamax, is now only producing the 70mg pill to be taken once a week .

The drug should not be given to pregnant women as it may cause abnormal bone in foetuses.


Dr Grabowski said that it is not known what effect Fosamax would have on children with Gaucher disease but the safety of the drug has been established in children with other diseases.

Care should be taken to do no harm: however a 17½ year old with Gaucher disease has been given the drug and her bone density increased considerably.

Dr Grabowski and his lead investigator Dr Wenstrup plan to carry out a placebo double-blind trial on children to establish safety and has started the recruitment of patients aged between 6 and 18 years who have been on enzyme replacement therapy for at least 18 months.

The first part of the trial will last for 18 months. The children will be evaluated every six months with 46 taking the drug and another 46 taking a placebo. They will continue to take enzyme therapy. The second part of the trial will be an open label study.

A summary of the paper in the journal Blood is given below:

Blood, 1 September 2004, Vol. 104, No. 5, pp. 1253-1257. Prepublished online as a Blood First Edition Paper on March 9, 2004; DOI 10.1182/blood-2003-11-3854.

Gaucher Disease: alendronate disodium improves bone mineral density in adults receiving enzyme therapy.

Richard J Wenstrup, Laurie Bailey, Gregory A Grabowski, Jay Moskovitz, Alan E Oestreich, Wei Wu, and Shumei Sun Division of Human Genetics, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH, USA Clinical Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA Department of Community Health, Wright State University School of Medicine, Kettering, OH, USA

Symptomatic patients with Gaucher disease are treated with injectable forms of the human enzyme. Treatment results in significant decreases in lipid storage in liver, spleen, and bone marrow, but the generalized osteopenia and focal bone lesions present in many adult patients are refractory to treatment. A double blind, two-arm placebo controlled trial of alendronate (40 mg/day) was performed in adults with GD who had been treated with enzyme for at least 24 months.

Primary therapeutic endpoints were improvements in:

  1. bone mineral density (BMD) and content (BMC) at the lumbar spine and
  2. focal lesions in X-rays of long bones assessed by a blinded reviewer.

Thirty-four patients with GD type 1 (18-50 yrs.) receiving enzyme therapy were randomized. After 18 months, BMD at the lumbar spine was 0.068 ± 0.21 and 0.015 ±0.034 for alendronate and placebo groups respectively (p= 0.001).

Long bone X-rays showed no change in focal lesions or bone deformities in any subject in either arm. Alendronate is a useful adjunctive therapy in combination with ERT for the treatment of GD related osteopenia in adults, but it cannot be expected to improve focal lesions.

Gauchers News Contents

Source: Gauchers News April 2003; updated October 2004.
© Copyright Gauchers Association 2003, 2004