Strontium ranelate in osteoporosis: new option soon?

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Rheumawire

Jan 29, 2004

Strontium ranelate in osteoporosis: new option soon?

Lyon, France - Strontium ranelate (Servier, Neuilly-sur-Seine, France),

a new drug for osteoporosis currently awaiting approval in Europe,

offers a novel approach with its 2-pronged activity of both increasing

bone formation and decreasing bone resorption. Clinical data from a

phase 3 trial, published this week in the New England Journal of

Medicine [1], establish its efficacy in reducing the risk of vertebral

fractures and also its role in the armamentarium of therapies for

osteoporosis, comments an accompanying editorial [2].

However, where exactly it will fit in among the existing therapies for

osteoporosis remains to be established, as more information about this

drug and how it works is needed, the editorialist, Dr Ghada El-Hajj

Fuleihan (American University of Beirut Medical Center, Lebanon), tells

rheumawire.

The results from this phase 3 study, known as the Spinal Osteoporosis

Therapeutic Intervention (SOTI) trial, were first presented at the World

Congress of Osteoporosis in May 2002 and were reported then on

rheumawire. Now, in the published report of the trial, the

investigators, led by Dr Pierre Meunier (Edouard Herriot Hospital, Lyon,

France), comment on how the results obtained with the new drug compare

with products already available for use in osteoporosis.

The SOTI trial involved 1649 postmenopausal women with osteoporosis and

at least one vertebral fracture and compared strontium ranelate (2 g

orally once daily) with placebo over a period of 3 years. The

intention-to-treat analysis was conducted in 1442 women for whom x-rays

were obtained after randomization.

Compared to placebo, strontium reduced the risk of new vertebral

fractures by 49% after 1 year and by 41% over the 3 years of the study.

This " seems similar " to the reductions that have been reported with

existing agents, the researchers comment, citing results from various

separate trials as follows: alendronate (47%), risedronate (49%),

raloxifene 60 mg (30%), and parathyroid hormone (65% after 21 months of

treatment).

The effect of the new drug on bone mineral density (BMD), which is

directly proportional to bone strength, also compares " favorably " with

existing agents, the researchers comment. In the SOTI trial, the

treatment effect after adjustment for the strontium content of bone was

an 8.1% increase in BMD at the lumbar spine at 3 years, while the

increases seen with other agents in separate trials have been 5.9% with

alendronate, 6.2% with risedronate, 2.6% with raloxifene, and 9% with

parathyroid hormone (20 µg at 21 months).

Adverse events reported by patients taking strontium were similar to

those seen in the placebo group, with diarrhea being the most frequent

(6.1% strontium vs 3.6% placebo, p=0.02). However, this effect

disappeared after the first 3 months, the researchers comment.

Compliance over the 3 years was also similar: 83% strontium vs 85%

placebo.

Meunier et al conclude that the SOTI results show that strontium

ranelate (2 g daily) " appears to reduce the risk of vertebral fractures

rapidly, effectively, and safely among postmenopausal women with

osteoporosis. "

A further trial of strontium (also at 2 g/day), involving more than 5000

elderly women, is assessing its efficacy in reducing the risk of

nonvertebral fractures. Known as the Treatment of Peripheral

Osteoporosis (TROPOS) trial, preliminary results from this study, also

reported in May 2002 [3], show a 16% reduction in the risk of peripheral

fractures (p=0.05) and a 41% reduction in the risk of hip fractures

(p=0.025).

Strontium offers a novel mechanism of action. Most agents used for

osteoporosis are antiresorptive products that prevent bone destruction

by reducing the rate of bone remodeling, as reflected by decreases in

both markers of bone resorption and markers of bone formation. In

contrast, the recently launched parathyroid-hormone product

(teriparatide, Forteo®, Lilly) increases both bone formation and bone

resorption. But this new strontium product increases bone formation

while reducing bone resorption.

" The changes in biochemical markers of bone resorption and formation

were most pronounced during the first 6 months of the study, " Meunier et

al write, but the dissociation between the two was evident throughout

the study. " The mechanism for the apparent dissociation between reduced

bone resorption and increased bone formation are not yet understood, but

they are probably different from the mechanisms of current treatment, "

they comment.

The accompanying editorial picks up on this point and suggests that

further study of the mechanism of action is needed, including detailed

investigations using bone histomorphometry. Thus far, it appears that

the effect of strontium on bone is complex and possibly dose- and

time-dependent, the editorialist adds.

Fuleihan tells rheumawire: " Although the mechanism of action of

strontium ranelate may be different from that of currently available

therapies, its efficacy in terms of vertebral fracture reduction is

comparable to that of antiresorptive drugs (eg, hormone therapy,

raloxifene, bisphosphonates) and a bit lower than that of bone-forming

drugs (parathyroid hormone). The study was not designed to address

nonvertebral fracture reduction; another parallel trial is being

conducted in over 5000 women and is designed to answer that question. As

with any new drug and pending additional information, its role among

other osteoporosis therapies, including its role as first-line therapy,

therefore remains to be established. "

Zosia Chustecka

Sources

1. Meunier PJ, Roux C, Seeman E, et al. The effects of strontium

ranelate on the risk of vertebral fracture in women with postmenopausal

osteoporosis. N Engl J Med 2004; 350:459-468.

2. Fuleihan GEH. Strontium ranelate - a novel therapy for osteoporosis

or a permutation of the same? N Engl J Med 2004; 350:504-506.

3. Reginster JY, Sawicki A, Devogelaer JP, et al. Strontium ranelate

reduces the risk of hip fracture in women with postmenopausal osteoporos

is. Osteoporos Int 2002; 13(Suppl 3):abstract S14.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org