Men's Osteoporosis Support Group

Atrial fibrillation, back pain and future fracture risk, teriparatide and biochemical markers, strontium ranelate, denosumab, vertebroplasty, and the relationship between fractures and mortality

Introduction. There are many studies this week relating to osteoporosis issues so I won't be discussing the various articles in as much detail as usual, instead leaving that up to you. I will give you the link to the PubMed abstract, as always, where you can get the information about how the study was conducted if you wish. I'll mainly highlight the purpose of the study, the conclusions and give my comments.

Menopause. 2009 Aug 12. [Epub ahead of print]. Osteoporosis treatment and atrial fibrillation: alendronate versus raloxifene. Huang WF and others. PMID: 19680161. This study compares the risk of various cardiac problems, including atrial fibrillation, in women taking raloxifene or alendronate (Fosamax) for osteoporosis. It is uncertain how much or if this study would apply to men also taking alendronate. But since the atrial fibrillation issue is still pending final determination, I wanted to add this study to the others posted here. If this study applies to men, here are the conclusions of importance: "Compared with raloxifene, alendronate did not increase the risk of AF (atrial fibrillation) and flutter in women with osteoporosis. Medical history contributed most to the development of AF or AMI in the women who received either raloxifene or alendronate."

Editor's comments: Here is a recent Update that will include links to any previous Updates on the atrial fibrillation question. This study is one more that shows no increased risk of atrial fibrillation from taking alendronate. So this is appearing to be increasingly a non-issue for those of us with osteoporosis who are taking a bisphosphonate unless future studies give conflicting results. I'll update the status if that happens.

Spine (Phila Pa 1976). 2009 Aug 15;34(18):1984-9. The relationship between back pain and future vertebral fracture in postmenopausal women. Kuroda T and others. PMID: 19680106. The authors were trying to find out if back pain was a predictor of a future fracture. They concluded that it was: "The data obtained in this study indicated that the back pain is significantly associated with osteoporosis and rheumatoid arthritis and that it can be useful predictor for future vertebral fracture risk in Japanese postmenopausal women in clinical settings."

Editor's comments. The study involved only Japanese women, but there is nothing to suggest the results wouldn't apply to all races, ethnicities and genders. These results are interesting to me since I had thoracic back pain for many years before I was finally diagnosed with osteoporosis and thoracic vertebral compression fractures. Many of the men that I hear from also have complained of back pain before being diagnosed with osteoporosis. So men (or women for that matter) who have any risk factors for, or thoughts that they might have osteoporosis, and who also have back pain, should not hesitate to have bone density testing done. The pain could indicate a current fracture or be an indicator of osteoporosis with the resultant increased risk of a future fracture.

Bone. 2009 Aug 10. [Epub ahead of print]. Rapid and Robust Response of Biochemical Markers of Bone Formation to Teriparatide Therapy. Glover SJ and other. PMID: 19679211. The purposes of this study were, "The aims of this study were to (1) describe changes in bone turnover markers during 28 days' treatment with teriparatide; (2) identify the earliest time point by which most subjects showed a biochemical response to teriparatide; (3) identify potential biomarkers of positive bone response; (4) describe changes in bone turnover markers 4 weeks after stopping teriparatide." The authors stated, "In conclusion, the bone formation markers PINP, PICP and OC show a rapid and robust increase in response to teriparatide which is noticeable during the first week of therapy. PINP is the most responsive marker. These findings have important implications for monitoring patients treated with teriparatide and may also inform the design of studies of new anabolic agents for osteoporosis."

Editor's comments. There are many references to biochemical markers of bone formation and resorption on this site, as well as to teriparatide, just do a FreeFind search to track them down. Since teriparatide, Forteo, is such a potent promoter of bone formation, one would expect rapid and dramatic increases in biochemical markers of bone formation, exactly what happened in this study. What was important is how quickly the changes occurred, almost 10% in the first two days, and over 110% by 28 days. These results show that there is no need to wait for a year or so to have bone density testing done to know how well the teriparatide is working. If base line and one-month biochemical markers of bone formation are done, you will know that quickly. If you aren't responding as expected, changes could be made rapidly, as needed. Also note how quickly the markers decreased after therapy stopped, thus indicating the need for follow up with another FDA approved osteoporosis medication when one stops taking teriparatide.

Bone. 2009 Aug 10. [Epub ahead of print]. Long-term treatment of postmenopausal osteoporosis with strontium ranelate: results at 8 years. Reginster JY and others. PMID: 19679207. This was an 8-year follow up study of women taking strontium ranelate for osteoporosis. The authors noted, "Conclusions. Long-term treatment with strontium ranelate 2g/day in postmenopausal osteoporotic women leads to continued increases in BMD at all sites. The data also provide some evidence for a sustained antifracture efficacy." [My emphasis]

Editor's comments. Strontium ranelate (SR) is not approved for treatment of osteoporosis in the United States or Canada to my knowledge, although it has been approved for use in Europe for several years. There are several Updates or articles on this site regarding its effectiveness, safety, etc., that you can check via FreeFind. I don't have access to the full article, making it harder to fully analyze the findings. It does appear, however, that the long-term antifracture effectiveness of SR is somewhat in doubt, at least according to these findings. That although it appears to continue to increase bone mineral density (BMD). Remember that BMD is far secondary in importance to fracture reduction.

N Engl J Med. 2009 Aug 11. [Epub ahead of print]. Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis. Cummings SR and others. PMID: 19671655. This study reports the 36-month results in women getting two denosumab injections annually for osteoporosis. The results showed that compared to placebo, there was a relative decrease in vertebral fractures of 68% , of hip fractures of 40%, and of nonvertebral fractures of 20%. The authors concluded, "Denosumab given subcutaneously twice yearly for 36 months was associated with a reduction in the risk of vertebral, nonvertebral, and hip fractures in women with osteoporosis."

Editor's comments. Use Freefind for the multiple articles on this site regarding denosumab. One recent Update found conflicting results regarding antifracture effectiveness when reviewing studies on denosumab. The Cummings and others study appears to side with the review showing denosumab was effective at fracture reduction, and it involved 7868 women, adding additional credence to the findings. Denosumab is not yet approved by the FDA for treatment of osteoporosis, although it recently won a vote of confidence from an FDA panel. The FDA is set to decide regarding final approval in October 2009.

N Engl J Med. 2009 Aug 6;361(6):569-79. A randomized trial of vertebroplasty for osteoporotic spinal fractures. Kallmes DF and others. PMID: 19657122. This and the next study compared vertebroplasty to placebo. "The primary outcomes were scores on the modified Roland-Morris Disability Questionnaire (RDQ) (on a scale of 0 to 23, with higher scores indicating greater disability) and patients' ratings of average pain intensity during the preceding 24 hours at 1 month (on a scale of 0 to 10, with higher scores indicating more severe pain)." The authors found no significant improvement in the outcomes between the placebo and test groups. They concluded, "Improvements in pain and pain-related disability associated with osteoporotic compression fractures in patients treated with vertebroplasty were similar to the improvements in a control group."

Editor's comments. Note that there was no difference in the comparison factors at one month, but at three months the test group's improvement approached statistical significance (64% vs. 48%, P=0.6), significance would be P=0.5. And the 3-month crossover rate in the control group was highly significantly greater than the placebo group (43% vs. 12%, P<0.001).

N Engl J Med. 2009 Aug 6;361(6):557-68. A randomized trial of vertebroplasty for painful osteoporotic vertebral fractures. Buchbinder R and others. PMID: 19657121. This is a similar study to the Kallmes and others study above. "The primary outcome was overall pain (on a scale of 0 to 10, with 10 being the maximum imaginable pain) at 3 months." The authors concluded, "We found no beneficial effect of vertebroplasty as compared with a sham procedure in patients with painful osteoporotic vertebral fractures, at 1 week or at 1, 3, or 6 months after treatment."

Editor's comment. There is a page on this Website devoted to vertebroplasty (percutaneous spinal vertebroplasty) and kyphoplasty. These results appear to question the effectiveness at relieving pain in the individuals with vertebral compression fractures who seek vertebroplasty treatment. It is unknown if the results will carry over to kyphoplasty as well. Until further research is done, individuals will have to go with their own judgment and that of the physician who wants to do the kyphoplasty in deciding whether to accept the therapy. Remember that kyphoplasty would have other potential benefits in that a balloon is used to increase the height of the vertebra before injecting cement. This would prevent decreases in height and other debilitations, such as, difficulty breather or sleeping that might result from the untreated fracture. Thus pain relief is not the only issue with kyphoplasty.

If not for the fact that so many placebo patients requested the crossover procedure in the Kallmes and others study, the results would be absolutely clear cut as to bringing vertebroplasty to a halt. Only time will tell if this one positive note regarding the procedure will lead to its continuation. For now it would behoove those referred for either vertebroplasty or kyphoplasty to be wary of the procedures and to get the best advice and information possible before having either procedure done.

CMAJ. 2009 Aug 4. [Epub ahead of print]. Relation between fractures and mortality: results from the Canadian Multicentre Osteoporosis Study. Ioannidis G and others. PMID: 19654194. This Canadian study of 7753 people (men and women) tested the effect of a fracture on mortality. The authors note, "Vertebral and hip fractures are associated with an increased risk of death. Interventions that reduce the incidence of these fractures need to be implemented to improve survival."

Editor's comments. These results are in agreement with several other studies that found increased risk of death in those who have a fracture, especially after diagnosis of osteoporosis. The bottom line is do whatever is required to prevent or treat osteoporosis, including exercise, proper diet, taking supplements of vitamin D and calcium, as needed, and FDA-approved osteoporosis medications. Ignoring this advice can be fatal.

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