Sequential Therapy with Bisphosphonates and Strontium Ranelate

"A recent study provides evidence that prior bisphosphonate therapy results in blunting and delay of the BMD response to strontium ranelate. In a prospective study in postmenopausal women with osteoporosis, 56 bisphosphonate-naïve women and 52 women treated with an oral bisphosphonate for at least one year, who had stopped bisphosphonate therapy within the last month, were given strontium ranelate 2 g daily, together with calcium and vitamin D supplements. After 1 year of treatment, BMD in the lumbar spine had increased 5.6% in bisphophonate-naïve women and by 2.1% in women previously treated with bisphosphonates; at both 6 and 12 months the BMD increase in the former group was significantly less than in the latter. At the total hip there was no significant change in BMD at one year in the bisphophonate pretreated women compared to an increase of 3.4% in the treatment naïve group. In an extension of this study, it was shown that BMD in the spine in pretreated women increased in parallel with treatment naïve women from 6 months onwards, whereas some blunting of the BMD response at the hip was still observed after 2 years of treatment. The most likely mechanism to explain these effects is that bisphosphonates inhibit the uptake of strontium into bone because of suppression of bone turnover and the consequent reduction in newly formed bone."

"Osteoporosis: Diagnosis and Management," Dale W. Stovall (ed.), Wiley (Jul 15, 2013), 288 pages, Chapter 13, pages 202-203.

Long-Term Effect of Strontium Ranelate Treatment on BMD

http://onlinelibrary.wiley.com/doi/10.1359/JBMR.050810/full

In the SOTI trial, there were impressive BMD increases in the spine (12.7%) and total hip (8.6%). However, some caution is necessary in interpreting these results because much of this effect is caused by the higher atomic number of strontium (Z = 38) compared with calcium (Z = 20). When BMD is measured by DXA, strontium atoms in bone attenuate X-rays more strongly than calcium atoms. However, when the DXA scanner software calculates BMD from the measured X-ray transmission factors, the increased attenuation caused by bone strontium content (BSC) is interpreted as increased calcium content and will cause an artifactual increase in BMD. After the adjustment for BSC using Eq. 1, the measured BMD increase in the spine at 3 years of 12.7% was corrected to 6.8%.

The correction of the bone mineral content (BMD) changes found in the strontium ranelate trials for bone strontium content (BSC) was based on the following equation:

Adjusted BMD = Measured lumbar spine BMD /1+ 0.061 x BSC iliac crest % Eq. 1

“Although a commendable effort was made in the SOTI trial to correct the BMD data for the atomic number effect of strontium, there is clearly considerable uncertainty about the accuracy of the corrections made. This arises from the small number of subjects in whom iliac crest bone biopsy was performed and the reliance on animal data for the correction factor for inferring BSC in the spine.”

No human studies with strontium ranelate have yet reported how quickly bone strontium is washed out once treatment is stopped. However, on the basis of the ICRP strontium model, we can estimate the likely long-term retention. Figure 2 shows the results of calculations using the ICRP model to predict the long-term changes in BMD after 3 months, 1 year, and 3 years of treatment with strontium ranelate. The calculations make the following assumptions: (1) equal daily intake of strontium during the treatment period; (2) strontium intake ceases at the end of treatment; and (3) no true loss of bone is occurring. On the basis of the ICRP model, much of the strontium present in bone at the end of treatment is likely to still be there a decade later. If strontium ranelate treatment is given for >1 year, this long-term retention in bone is likely to have a significant effect on the interpretation of future BMD measurements.

Long-Term Effect of Strontium Ranelate Treatment on BMD - Blake - 2005 - Journal of Bone and...

onlinelibrary.wiley.com

Blake, G. M. and Fogelman, I. (2005), Long-Term Effect of Strontium Ranelate Treatment on BMD. J Bone Miner Res, 20: 1901–1904. doi:...