Wait 30 or 60 minutes after taking bisphosphonates?
The original studies with alendronate (Fosamax) used a two-hour time period before participants were allowed to eat after taking the medication on an empty stomach. Later this wait was reduced to 30 minutes with participants still achieving clinically significant increases in bone mineral density (BMD) with the shorter wait period. In the Read Newsletters I have always suggested waiting longer than one-half hour if it isn't too inconvenient since early research showed a 40% improvement in the absorption of Fosamax with the two-hour wait compared to the one-half hour wait. Up to now, I'm not aware of any studies that actually compared the effectiveness in a controlled clinical trial using different waiting periods but with the same dose of a bisphosphonate. That has changed with the publication of a new study by Tanko LB and others, PMID: 12689686. The authors used ibandronate as the the bisphosphonate in their study. This is a late-generation bisphosphonate that is more potent than Fosamax, but that is structurally similar and with the same mechanism of action as Fosamax and other bisphosphonates. The authors found for every variable tested that the 60-minute wait period was more effective than the 30-minute wait. They stated, "In conclusion, if reducing the post-dose fasting interval, dose-increase compensation would likely be required to maintain efficacy of oral ibandronate treatment." The truth is that even the 30-minute wait periods produced fairly good increases in BMD considering that the study only went for 48 weeks. However, the improvement in BMD with the added one-half hour wait was pretty impressive, too. Although these results can't be applied directly to those of us taking Fosamax or Actonel, I think it is safe to assume there will be increased absorption over the longer waiting period, and a greater chance of increased BMD with that method, too. So, as I've said previously, the one-half hour wait is certainly a minimum period to wait before eating. But, if it isn't a big problem, waiting longer--up to the full two hours if possible--will probably improve your BMD over the long haul. Since most of us are taking bisphosphonates only once weekly, this longer waiting period is not as much of an inconvenience as when we took it on a daily basis.
Effect of discontinuing bisphosphonates
This is an interesting study that involved individuals who had taken alendronate (ALN) for one year to treat osteoporosis caused by high doses of glucocorticoid (GC) therapy. For some reason, some of the people did not continue with alendronate therapy after the one-year study even though they were still on the corticosteroids. See PMID: 12687554, Emkey R and others. This afforded the authors a chance to see what the effect of discontinuing the alendronate was on participants' BMD. They found, "Substantial loss of BMD in the lumbar spine and hip was seen in patients who discontinued treatment with ALN but who continued to take >6 mg/day of GCs. However, patients receiving GCs who remained on the ALN regimen appeared to benefit from continued ALN treatment, since BMD was maintained in this latter group." The bottom line here is that the laws of cause and effect are still functional. If your osteoporosis cause isn't treated and "cured," you must continue with osteoporosis therapy for life. Perhaps some day there will be a maintenance dose of medications that will be a lower dose than required for treatment and that will retain but not increase BMD. Until that time, people must stay on the full dosage regimen of their proven osteoporosis medication to avoid regressing and risking a return to osteoporosis with the risk of fractures from the weakened bones.
Transdermal estradiol to treat men with advanced prostate cancer
This is a very interesting study, probably with implications for men and women. It shows that the transdermal route of estradiol (estrogen) is safer than the oral route in men with advanced prostate cancer due to a decrease in cardiovascular risk. There is considerable evidence that transdermal estradiol is the safest form of estrogen for women undergoing HRT, too. And this decreased safety factor with oral estrogens may explain much of the negative results currently noted in the news with HRT that uses estrogen derived from horses and that uses a non-natural form of progestin (Prempro). See my discussion of HRT for details on this. In this study by Ockrim JL and others, PMID: 12686820, a total of 20 patients received transdermal estradiol that increased serum estradiol to 1,000 pmol/l. This in turn increased serum testosterone to normal levels within 3 weeks and showed biochemical evidence of disease regression. Only two patients had problems and the remaining patients had significant increases in BMD after 15 months with functional and symptomatic quality of life improvement also noted. The authors conclude, "Transdermal estradiol therapy prevented andropause symptoms, improved quality of life scores and increased bone density. Transdermal estradiol costs a tenth of current therapy cost, with the potential for considerable economic savings over conventional hormone therapies." This study would appear to have extremely important implications for men with advanced prostate cancer. A treatment that slows or stops tumor growth, prevents osteoporosis, and improves their quality of life with only minor side effects is quite significant.
Deterioration of bone architecture in hypogonadism
In many of the fracture studies, there is often a decrease in fracture rate that isn't explained solely by the increase in BMD when patients are taking the medication tested in the trial. Investigators mention that bone quality is also important and that improvement in that bone quality probably explains the lower fracture rate. Here is a study in men by Benito M and others, PMID: 12679429, that demonstrates that rather large changes in bone quality can occur without a detectable change in BMD. Using magnetic resonance microimaging (MRM) on 10 men with severe untreated hypogonadism, and comparing their bone to eugonadal controls, the authors found a 36% change (reduction in quality) in the quality parameters tested in the hypogonadal men. They stated, "We conclude that male hypogonadism is associated with marked deterioration of trabecular architecture and to a greater degree than bone densitometry of the spine and hip suggests." Many of the men I hear from are very worried because their BMD hasn't improved as much as they expected after taking bisphosphonates for a year or more. This study shows that in spite of that lack of increase in BMD, men are probably at lower risk of fracture if they have been on an approved therapy for osteoporosis, such as one of the bisphosphonates and/or testosterone. The addition of MRM, or some similar qualitative bone test, if it is feasible, would be a nice addition to the diagnostic regimens now available for osteoporosis.