Update on strontium ranelate
Summary of various studies' effectiveness concerning fracture reduction. See Therapie. 2003 Sep-Oct;58(5):415-20 by Meunier PJ, PMID: 14682189. This is an interesting article because it discusses the various fracture reduction rates of not only strontium ranelate (SR), which is in stage III clinical trials, as well as the therapies that have been approved for treating osteoporosis. A summary of the results: 10-mg/day of alendronate (Fosamax) reduces vertebral fractures by 48%, 5-mg/day of risedronate (Actonel) reduces vertebral fractures by 49% and 41% in two separate studies, human parathyroid (Forteo) reduces risk of vertebral fractures by 65% and SR reduced vertebral fracture risk by 41% in a 3-year trial. The SR is not approved for treatment of osteoporosis yet, but appears to be headed that way if results continue as they have been going. As can be seen, the fracture reduction rate of SR is definitely similar to that of the current crop of approved medications. Below are additional studies to further describe this new medication.
Pharmacological profile of SR. See: Osteoporos Int. 2003;14 Suppl 3:S9-12. by Marie PJ, PMID: 12730801. SR has both an effect on bone formation and bone resorption making it unique within the group of medications mentioned above. The additional importance of its mechanism of action is that it increases bone mineral density (BMD) without affecting the quality of bone mineralization. These combined effects have been demonstrated in normal rats, normal adult monkeys, ovariectomized rats and by in-vitro studies. The authors conclude, "Altogether, these pharmacologic results suggest that SR optimizes bone metabolism by decreasing bone resorption and promoting bone formation, which may be of potential value in the treatment of osteoporosis."
Strontium ranelate as a new paradigm in osteoporosis treatment. See Drugs Today (Barc). 2003 Feb;39(2):89-101, Reginster JY, Deroisy R and Jupsin I, PMID: 12698204. This article summarizes the method of action of SR, the various preclinical studies done on it and the clinical trials that have been done so far, including stage II and III trials. These determined that 2 g is the dose required to get adequate results and that this dosage appears safe with adverse effects equal to the placebo group in the studies done so far. The authors conclude, "All these results imply that strontium ranelate is a new, effective and safe treatment for vertebral and nonvertebral osteoporosis, with a unique mode of action.
SR at the microscopic level. See: Osteoporos Int. 2003;14 Suppl 3:S19-24, Boivin G, Meunier PJ, PMID: 12730799. This study describes the microscopic findings of the various animal and human studies done to date on SR via X-ray microanalysis, X-ray diffraction and computerized quantitative contact microradiography. They found that SR was taken up into compact and cancellous bone in a dose-dependent manner with higher content in the newer than older bone. There was almost a two-fold decrease in SR content in animals killed 6 or 10 weeks after SR withdrawal, indicating it is not locked into the bone long term as are the bisphosphonates. There was essentially no detectable alteration of the degree of bone mineralization nor a major modification of bone mineral at the crystal level in the long-term treatment groups. The authors conclude, "This emphasizes the value, as antiosteoporotic treatment, of SR, which is safe at the bone mineral level.
Two- and three-year clinical trials in postmenopausal women. The PREVOS trial evaluated the ability of SR to prevent early postmenopausal women from losing BMD with 40 participants in the trial and placebo groups. The dosages tested were 125-, 550- and 1-g/day for the two-year trial. After 24 months only the 1-g/day SR dosage showed significantly increased BMD compared to placebo, with annual adjusted increases in BMD of +0.66% in SR vs. -.05% in the placebo group. There was also a statistically significant increase in bone alkaline phosphatase (a marker of increased bone turnover) at all time points in the study while there was no effect on markers of bone resorption. Additionally, SR was tolerated the same as placebo. See: Osteoporos Int. 2002 Dec;13(12):925-31. Reginster JY and others, PMID: 12459934. A recent study on postmenopausal women taking 2-g/day of SR has shown a significant reduction in fracture risk during the 3-year study. See: N Engl J Med. 2004 Jan 29;350(5):459-68, Meunier PJ and others, PMID: 14749454. The 14.4% and 8.3% increase in spinal and femoral neck BMD, respectively, appears right in line with results from other approved osteoporosis medications. The 41% decrease in new vertebral fractures over the three years also is similar to the results with other approved medications.
Influence of strontium on bone mineral density when measured by dual-energy X-ray absorptiometry (DXA). Thanks to a visitor to the Website who pointed out that this study also applies concerning SR. See: J Clin Densitom 1999 Winter;2(4):371-9, Nielsen SP and others, PMID: 10677790. In summary, this laboratory study was done to see if the higher radiographic density of strontium compared to calcium would be significant when comparing DXA results on individuals who had ingested SR. The authors note that an adjustment factor (10% overestimation for 1 mol/mol% Sr) will need to be used for all presently available types of instrument and acquisition modes. So, if and when SR is approved for treatment of osteoporosis, DXA results will need to be adjusted to get a proper comparison to standards that have been developed before SR was used.
Summary. These results appear quite positive for SR and we can expect it to be added to the list of approved osteoporosis medications in the not too distance future barring any unforeseen circumstances. As always, postmenopausal women were the study group in trial so far so men will have to take this medication as an off-label usage if and when it is approved. It remains to be shown if there are any benefits in the use of SR compared to the bisphosphonates, which would appear to be their main competition. The one thing that is obvious immediately is that a single weekly dose of the bisphosphonates is effective whereas daily dosing is required for SR. The SR short half-life in bone might be a plus or a minus depending upon your outlook when compared to the extremely long (approximately 10-year) half-life of the bisphosphonates. Time will tell how well SR stacks up against the other medications for the treatment of osteoporosis.