Men`s Osteoporosis Support Group
Volume IV, Issue I	January 1, 2000

Happy New Year & Century!

What`s new?

Greetings and thanks. First, welcome to the new century. I hope the year 2000 is a great one for all of you and that we all see many new breakthroughs in the diagnosis and treatment of osteoporosis this year. Next, thanks for all the e-mails and updates that everyone has sent this quarter. Many of those have been to tell me about one of the several recent developments of considerable significance to those of us with osteoporosis. Perhaps the two most important were the findings that Fosamax is effective with once- or twice-weekly dosages and that it has also been found effective to increase bone mineral density (BMD) in men with osteoporosis.

New Fosamax Studies. The study results using Fosamax to treat osteoporosis in men have not been published yet. The results were, however, announced at the American Society of Bone and Mineral Research meeting in St. Louis, September 30 through October 4, 1999. See The Lancet, October 9, 1999, Issue 9186, Volume 354, for a discussion by Dr. Eric Orwoll. He notes, "There was a 7.1% improvement in lumbar spine bone mineral density in men given alendronate, compared with a 1.8% improvement in the placebo group. Treatment benefits for patients taking the drug were also seen in the femoral neck and the trochanter, and height declined less in men taking alendronate than in those taking placebo." On the Web, go to Doctor`s Guide to the Internet at http://www.pslgroup.com/dg/1347E2.htm to read about the study. There are no surprises with these results, just confirmation that alendronate works in men as it does in women. This should lead the way for the FDA to approve Fosamax for men. Currently it must be used in men as an off-label prescription. And, it should remove hesitancy on the part of physicians to prescribe or insurance companies to pay for Fosamax to treat men with osteoporosis.

The study on once-weekly Fosamax dosage is also not yet published. But, for a good summary, see Doctor`s Guide to the Internet, http://www.pslgroup.com/dg/14a1f6.htm. Those findings were first reported at the 6^th International Symposium on Clinical Disorders of Bone and Mineral Metabolism in Venice, Italy. The study involved 1,258 osteoporotic women aged 40-90. They randomly received either 70 mg of Fosamax once weekly, 35 mg Fosamax twice weekly, or 10 mg Fosamax daily. Additionally, all received calcium and vitamin D (if needed). When BMD was compared among all three groups of women, there was no statistical difference. All averaged about 5% and 3% increase in spine and hip BMD, respectively. Importantly, the safety and tolerability profiles were similar among treatment groups. If you feel you would benefit from once-weekly Fosamax dosing, speak to your physician about this new option.

As you`ll recall, in the July 1998 newsletter (see http://www.maleosteoporosis.org/nl7.htm), I first published the recommendation from Lunar News that, "A 40 mg tablet of alendronate given once per week could be as protective as a dose of 5 to 10 mg given daily." Their rationale was that "Since the half-life of bisphosphonates in vivo is many months, intermittent doses should be just as effective as daily dosing." Note, that the dosages used in the study mentioned above were for 35 mg of Fosamax twice weekly, or 70 mg once weekly. This differs from the Lunar News suggestion of using 40 mg of Fosamax once weekly. However, note that Dr. Kolba, in the Ask the Experts section of this newsletter, explains why she thinks that 35 mg once weekly (or probably 30 or 40 mg once weekly) should be adequate. Unfortunately, the above study did not test this 35 mg once-weekly dosage regimen. So, there are no studies to show the exact point where the various dosage and dosage intervals using Fosamax make a clinically significant change. To be safe, the cumulative dose should be roughly equal whether taking the Fosamax daily, weekly, or at some other interval.

Could licorice be a problem for men? Another news item that could be of interest to some of you concerns licorice and its effect on testosterone. This news comes from a letter to the editor of the New England Journal of Medicine, Armanini D and others, 1999 Oct 7;341(15):1158. Reduction of serum testosterone in men by licorice. The authors point out that one side effect of the active component of licorice is to block the conversion of androstenedione to testosterone. The authors showed that young men given 7 g daily of a commercial preparation of licorice had decreased serum testosterone concentrations. They state, "Thus, men with decreased libido or other sexual dysfunction, as well as those with hypertension, should be questioned about licorice ingestion." So, if you have a licorice habit, you might want to substitute something safer for your sex life, and potentially safer for your bones, too.

Osteoporosis in men. Two recent publications from the National Osteoporosis Foundation (NOF), http://www.nof.org, are of interest to men with osteoporosis. The Summer 1999 Osteoporosis Report, Vol 15, No 2, has an article on osteoporosis in men by Eric Orwoll, M.D. Additionally, the NOF publication, Osteoporosis, Clinical Updates, Volume II, Issue 1, September 1999, is dedicated entirely to the subject of osteoporosis in men. This periodical is provided mainly for medical practitioners, but you might be able to get a copy by contacting NOF. One important segment concerns what tests should be done by physicians to evaluate and properly diagnose a man who is suspected of having osteoporosis. You might want to see that you have had all the tests they suggest, which include : Hemoglobin and hematocrit; Serum calcium, albumin, phosphate, alkaline phosphatase; Serum 25-hydroxyvitamin D; Testosterone and LH; TSH; SPEP (if anemic); 24-hour urine collection for calcium; Bone mineral densitometry (spine and hip); Spine X-rays if fractures are suspected; Bone biopsy (rarely).

Ask the Experts

Questions to Dr. Karen Kolba, Rheumatologist, consultant to the Men`s Osteoporosis Support Group for osteoporosis-related questions. (NOTE: If you have questions for any of our experts, please e-mail them to the editor. I`ll forward them on to the experts for an answer).

Q. Dr. Kolba, as mentioned elsewhere in this newsletter, there has been a study showing that Fosamax is equally effective when taken in the 10 mg/day dose or when taken in 35 mg/twice-weekly or 70 mg once-weekly dosages. I also wonder if more research shouldn`t be done to find the real limits of Fosamax dosing. That is, perhaps the 70 mg dose would be adequate if given every two or three weeks, etc. The study did not try to find the point where effectiveness dropped off after a certain dosage interval. What are your thoughts on this topic?

A. I`m changing all my patients, with one exception, to once-a-week 30 mg Fosamax. My rationale, gleaned from a real bone expert, is this: In looking at the original Fosamax data, the difference between the 5 mg/day and the 10 mg/day doses was not that great in terms of fracture prevention, so 5 mg/day is probably adequate. Thus, the 35 mg/week would be equally as effective as 5 mg/day. But, don`t waste money on the 5 mg tablets, just take 30 mg once per week.

I`ve had NO complaints (what a switch!) about stomach upset with the once-a-week dose, even in people who previously complained. I think perhaps folks are willing to tolerate a bit of upset one day per week but not every day. The one person who wouldn`t change has her schedule all set around her pill taking and then going for a walk. So, a new system would change her lifestyle too much. (Yes, I pointed out that she could just DRINK THE WATER and go on her way, but. . .). What we have here is compulsion!

I agree with your comment completely about the limits of the dosing not really being established. I don`t think Merck is going to undertake the study since one of their comparison studies, FOSIT, cost them about fifty million dollars. The main reason for the once-a-week dosage is competition with Actonel (risedronate). The latest word has this new bisphonate being released in February or March of 2000. Merck has also put a new slippery coating on Fosamax, and these new pills are being stocked in pharmacies even as we chat. Samples will be in physicians` offices by the end of the year. This is also for competitive purposes as the Actonel folks have gone out of their way to show their drug gets into the stomach faster-but now it will be a tie.

Q. What do you think about IV pamidronate as an alternative to oral bisphosphonates?

A. IV bisphosphonates work great, but the problem is that since it is an off-label use of pamidronate, insurance companies do not feel compelled to cover it. This is especially true for Medicare, which is the category where most of the people fit who could use it. Pamidronate must be given as an IV drip in the office or outpatient clinic. The cost is just about what three months of Fosamax would cost, maybe a bit less. It is a great alternative, but the company will not be pursing the indication because rumor has it that there is another IV bisphosphonate coming next year that can be given IV push-directly into the vein in a matter of seconds-much more convenient for the physician and patient. Since it would be given in the office, it should be covered by Medicare.

Q. I recently received e-mail from a man who asks if Fosamax could be causing or contributing to his headaches.

A. My general answer is that anything can cause anything, and WILL cause it in somebody. Fosamax does cause severe bone pain in some people, for reasons no one (including Merck) understands. And, I suppose that if someone had a skull bone problem (such as Paget`s Disease), that Fosamax could cause headaches. As always, the only way for a person to know is to stop the Fosamax, then start it again. If the headaches stop and then recur, it is a pretty sure bet the Fosamax is to blame. Remember, the bone pain ALWAYS goes away, so there`s no real danger in trying it again-just discomfort.

Questions for Dr. James Schuster, Radiologist, consultant to the Men`s Osteoporosis Support Group for questions on radiology or bone densitometry.

Q. What is new in the fields of radiology and bone densitometry that men with osteoporosis would be interested in?

A. There is a lot to tell you about. As I may have mentioned before, we are testing a new version of Hologic`s heel sonometry unit, and finding pretty good results (fifty patients to date). So far, I`m seeing a better correlation of heel T-score and lateral lumbar spine DEXA than AP (anterior-posterior) lumbar spine DEXA with lateral lumbar spine DEXA. The same is happening with hip DEXA, in fact. This is important because (though controversial) I believe lateral lumbar spine DEXA is our most sensitive test for osteoporosis diagnosis at this time. I`m struggling with a "cut-off" value to assign to a significant heel T-score (probably between 0 and negative 0.7). I will gather at least another fifty patients before making any conclusions.

I just returned from the annual radiology convention in Chicago (RSNA) where there was only one scientific session on osteoporosis. It was very interesting, with some lively discussion regarding heel sonometry, lateral DEXA utility, high resolution calcaneal (heel) MRI (looking at trabecular thickness and "porosity"), etc. My take-home jury`s still out on so much of this field, however, it seems dangerous to consider DEXA the "Gold Standard" against which other modalities are measured. The problem is that each modality can be optimized for looking at certain components contributing to bone strength.

There were some interesting developments at the vendor areas, too. These included a shift towards total femur scanning (Lunar, I think) and morphometry-assessment of vertebral body shape/compression. One Danish company is coming out with a very simplified PC-based system that uses a stock scanner to evaluate cortical thickness of hand bones, an old idea (radiation absorptiometry) with a new twist. They are claiming excellent results, but I`m withholding judgement until I see more. This could be a good way to get densitometry testing out to those areas without more sophisticated equipment. All that is needed is a hand/wrist X-ray, a PC, and a scanner (along with the company`s proprietary software, of course).

Dr. Schuster also sent me a copy of the once-weekly dosing report on Fosamax. He reports that he is happy to have switched to the weekly dosage. After six weeks he is doing fine and enjoying his morning coffee with his wife, instead of having only an 8-ounce glass of water! Additionally, after 1.5 years on Fosamax therapy, he reports that he is no longer osteoporotic, but only osteopenic now, and continuing on all therapies awaiting a return to normal BMD. From 6/98 to 11/99, his lateral lumbar spine BMD went up 6.3%, an annual rate of change of 4.9%. His AP lumbar spine BMD went up 8.2%, 6.6% annualized with a current T-score of -1.64 that was -2.27. The left hip BMD went up 4.7%, 3.5% annualized, but the hip BMD was actually higher 4/99 when it had increased 7.2% over baseline. The hip T-score is -1.19 now and was -1.45. So, this is excellent news and once again shows the effectiveness when using alendronate in men with osteoporosis.

Case history

This case history is both interesting and frightening as it involves a psychologist (I`ll call him Paul, not his real name) who was seen for back pain at the campus medical school where he was teaching at the time. It is scary to think that someone this educated could get such questionable diagnosis and treatment in our modern era.

Paul was in his mid-fifties when his back problems first surfaced. The physicians insisted that his pain was psychological, a reassuring diagnosis for a psychologist. Eventually, he was forced to take early retirement when excruciatingly painful compression fractures of the spine (T-10 and 11) were noted in December 1996.

After moving to northwestern North Carolina, Paul saw several physicians during the next year about the back problems and had several x-rays taken. The radiologist noted that osteoporosis was present in his notes, but never mentioned it to Paul. Paul only discovered these notes later when checking through his medical records to try to find the cause of his problems. Everyone he saw assured him he would soon heal and recommended counseling and therapy to help with the pain.

In the fall of 1998, Paul re-injured the same vertebrae and broke some ribs. At this time, he insisted on getting a bone density test done. This over the strong objections and disgust of his physician who insisted, "Men don`t get osteoporosis." The test showed he had severe osteoporosis, so the physician started him on Fosamax. Paul found that no one in the small town where he lived had ever treated a man with osteoporosis, so he sought out an endocrinologist in Winston-Salem, NC. After doing blood tests and an MRI of the pituitary, the physician diagnosed Paul as having hypogonadism and prescribed testosterone. This endocrinologist insisted that Fosamax would be counter productive in his case and stopped that medication. He explained to Paul and his wife that the Fosamax builds a lattice of hard bone on the exterior and, prevents whatever benefit to bone increase that comes from the testosterone`s bone stimulation? Paul goes on to say, "He seemed so sure, so informed, that we took him at his word , until seeing the Men`s Osteoporosis Support Group Newsletters."

Paul noticed no improvement in his chronic pain and immobility, so urged on by friends in medical schools, he had a vertebroplasty (the injection of a rapid-setting plastic into compressed or broken vertebrae). This resulted in increased pain and immobility, now well beyond the time period where improvement has apparently occurred with every previous patient in the southeast. The surgeon excuses the result as a combination of T-10 being too compressed to admit a full portion of cement/filler and of Paul`s calm demeanor and healthy appearance ("You may not have wanted to get better"). The surgeon has just written Paul to say that he cannot help further; the only referral he could/would make was to the endocrinologist Paul was already seeing. That endocrinologist admits that he has never seen osteoporosis in a man younger than 70 and Paul is 58.

Here are some comments from Paul about questions I sent him about his condition. I am taking Celebrex (even though my general practitioner had never heard of it), but with no apparent results. I am being careful to supplement my diet with vitamin D and calcium, and I spend time in the sun every day when I can. I had suggested that Paul see if he could get an implanted pain pump to help alleviate his symptoms in a safe and effective manner. The beauty of the pain pump is that it stops pain by putting very small amounts of narcotics or local anesthetics directly on the affected nerves, giving relief with virtually no side effects. Paul had seen a local physician who is the only one locally who typically prescribes narcotics to pain patients not yet in terminal stages of illnesses. She put him through a series of five different narcotics (such as opium patches), all of which had severe side effects, e.g., nausea and vomiting, and all of which he stopped cold turkey. She then concluded that his problem was psychological. He noted that his problem was that none of the physicians in his small town will prescribe anything related to his osteoporosis unless the specialists in Winston-Salem recommend it. His experience with the endocrinologist there has him looking for another endocrinologist or expert on osteoporosis and to get back on Fosamax. He also hopes to see a physician in Virginia that is touted to be the leading practitioner of vertebroplasty in the US.

Just before publishing the newsletter, I called Paul for an update. He told me that he will be going in for a radical prostatectomy in January. Although he had been put on testosterone therapy, none of his physicians had recommended doing a periodic PSA. As you probably know, testosterone therapy is implicated in increased development of prostate cancer. Paul asked his physician to do one and it was 8.4, up from 1 when he started testosterone therapy one year previously. (NOTE: If you are on testosterone therapy, you may want to ask your physician about having PSA tests done more frequently than once a year based upon Paul`s experience. Subsequent biopsies were positive for stage II prostate cancer (cancer cells confined to the prostate gland). He reports that he has had no luck getting a pain pump installed and that he has had many problems dealing with the narcotics that have been prescribed to alleviate his back pain. But, he has finally been put on Fosamax for the osteoporosis. I know we all wish him the best in dealing with the osteoporosis and prostate problems.

Here`s another example of the importance of taking part in your own health care. These newsletters have shown many examples where your knowledge about osteoporosis and other health problems can prevent you from receiving questionable diagnosis or treatment. Remember, it is your health, take it seriously and do what you can to see that you are getting high quality medical care for your problem. Only through knowledge is this possible. Today, the Internet makes learning about your medical condition easier than ever before, leaving no excuse for not educating yourself.

Literature review

Risedronate. This third-generation bisphosphonate is more potent that alendronate. That means it can be given in smaller doses to achieve the same effect, whether there are any other benefits remains to be seen. There were two studies published in the fall of 1999 showing risedronate to be effective in either treating or preventing osteoporosis.

The first study was by Harris ST and others, JAMA, 1999 Oct 13;282(14):1344-52. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. MEDLINE UI:99454305 (Note to search for an article using the UI, go to MEDLINE at http://www.ncbi.nlm.nih.gov/PubMed/ and enter only the numeric portion of the UI and click on Search to find the article). This study involved 2458 postmenopausal women with at least one vertebral fracture. Initially women received either placebo, 2.5 mg or 5 mg of risedronate, along with calcium and vitamin D supplements. The 2.5 mg trial was discontinued after one year. The authors found that, "Treatment with 5 mg/d of risedronate, compared with placebo, decreased the cumulative incidence of new vertebral fractures by 41%. . ." Additionally, they found, "Bone mineral density increased significantly compared with placebo in the lumbar spine (5.4% vs. 1.1%) . . ." The authors concluded, "These data suggest that risedronate therapy is effective and well tolerated in the treatment of women with established postmenopausal osteoporosis."

The second study was by Cohen S and others, Arthritis Rheum 1999 Nov;42(11):2309-18. Risedronate therapy prevents corticosteroid-induced bone loss: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. M EDLINE UI:20021496. This study was conducted using 224 men and women who were initiating long-term corticosteroid treatment. They received either 2.5 or 5 mg of risedronate or placebo daily for 12 months. Neither risedronate group lost BMD over the length of the study, while it decreased significantly in the placebo group. The authors concluded: "Risedronate therapy prevents bone loss in patients initiating long-term corticosteroid treatment." One side light to both of these studies, risedronate was well tolerated, with the incidence of upper gastrointestinal adverse events comparable between test and placebo groups. Virtually every bisphosphonate study has found this, yet esophageal/gastric problems are often reported by individuals not involved in studies. A very strange occurrence indeed.

Update on bisphosphonates. For an excellent summary of what`s new in bisphosphonates (including risedronate), read the MEDLINE abstract by Gatti D and Adami S, Drugs Aging Oct;15(4):285-96. New bisphosphonates in the treatment of bone diseases. MEDLINE UI:20047600.

The authors note that when using risedronate to prevent bone loss, "Similar effects [full prevention of bone loss seen in the placebo group] have been observed with an intermittent dosage regimen of oral risedronate 30 mg/day for 2 out of 12 weeks, which corresponds to 5 mg/day in terms of cumulative dose. With lower doses [5 mg on alternate fortnights (2 weeks)] the prevention of bone loss was half that observed with continuous 5 mg/day therapy, indicating that this might not yet be the maximum effective dose." They also mention that another new bisphosphonate, ibandronate, has been shown to increase spinal bone mass by 5.2% after one year of administration as an IV bolus every three months. (See Dr. Kolba`s mention of the importance of this IV method of administration in the Ask the Experts section of this newsletter). As concerns the newer generation of bisphosphonates, the authors conclude, "The new generation of bisphosphonates are likely to increase clinical options in terms of administration regimens, but their real advantage over those already available in terms of clinical efficacy remains uncertain." The results on the intermittent use of risedronate appear to apply to the once-weekly results with Fosamax reported earlier in this newsletter. That is, the cumulative dose over the time period is probably more important than the interval at which the drugs are taken.

Exercise and BMD. We have all heard about the importance of weight-bearing exercise in maintaining BMD. A recent article shows just how important this can be by comparing the BMD of world-class internationally top-ranked athletes to age-matched controls. Twenty-eight weight lifters had Ward`s triangle BMD 23% greater than controls. Six sport-boxers had an increase up to 17% (lumbar spine), 9% (hip), and 7% (Ward`s triangle). Six Tour de France bikers showed BMD decreased by 10% in the lumbar spine, 14% in the hip and 17% in the Ward`s triangle. So you can be extremely physically fit and active, and still have low BMD if your activity is not weight bearing. Sabo D and others. Z Orthop Ihre Grenzgeb 1996 Jan-Feb;134(1):1-6. Modification of bone quality by extreme physical stress. Bone density measurements in high-performance athletes using dual energy x-ray absorptiometry. MEDLINE UI:96209389.

Prevention of glucocorticoid-induced osteoporosis. A constant theme running through these newsletters is my concern for patients receiving chronic steroid therapy, such as cortisone or prednisone. It has been known for many years that these people are at risk for osteoporosis. Osteoporosis can now be prevented in these people by approved medications, such as Fosamax, or just calcium and vitamin D supplements. Another new study has shown there is still much room for improvement in getting physicians to prescribe appropriate prophylactic medications when they prescribe long-term steroids to patients. See Aagaard EM and others. Am J Med 1999 Nov;107(5):456-50. Prevention of glucocorticoid-induced osteoporosis: provider practice at an urban county hospital. MEDLINE UI:20034588. The study involved chart review of 215 adult outpatients at San Francisco General Hospital who received a prescription for prednisone (or its equivalent) at a daily dose of at least 5 mg for at least one month. The authors found, "Prophylaxis for glucocorticoid-induced osteoporosis was prescribed to 58% of patients." Males need to be particularly aware that their needs are more often overlooked as those prescribed prophylaxis were, ". . .more likely to be female (69% vs. 40%, P<0.0001)." Additionally, patients attending the rheumatology clinic were 1.6 times more likely to receive prophylaxis than patients going to other clinics. The authors conclude, "Educational efforts should be directed toward increasing awareness of the importance of glucocorticoid-induced osteoporosis and its prevention." It is unfortunate, but particularly if you are young and male, you need to be aware that you have about a 60% chance that your physician will not prescribe the needed prophylactic medications if you are placed on long-term corticosteroid therapy.

A new bone densitometry technique to monitor effects of osteoporosis treatment. Currently the results of osteoporosis treatment are most commonly monitored by DEXA of the lumbar spine and hip to evaluate improvement in BMD. The forearm would be easier to monitor if reliable results were possible when testing it for increases in BMD. The forearm is normally considered to be too cortical in nature, and thus not capable of demonstrating the effectiveness of drugs like alendronate that work best on cancellous bone. A recent study, however, suggests that the forearm may be an effective site to use. The study is by Ravn P and others, Osteoporos Int 1999;9(4):277-83. Bone densitometry: a new, highly responsive region of interest in the distal forearm to monitor the effect of osteoporosis treatment. MEDLINE UI:20019839. The authors describe a new model for bone densitometry at the distal forearm. They say, "By computerized iteration of single X-ray absorptiometry forearm scans, we defined a region with 65% trabecular bone." Analyzing this region, the authors found, ". . .a highly statistically significant dose-related response and increased [BMD] of 3-5% per year with 2.5 mg ibandronate, 10 mg alendronate or HRT, whereas the decrease in the placebo groups was 1-3% (p<0.001)." They indicate that the response in the distal forearm was similar to the response at the lumbar spine and hip. About this new method, the authors state, "The method is more accessible clinically and has potential as an alternative for monitoring bone mass changes during antiresorptive treatment." So, this could be an interesting new way to monitor the effectiveness of medications used to treat osteoporosis. It will be interesting to see if there is follow up to this article by others.

Internet osteoporosis information

I found several articles or Web sites that have interesting information about osteoporosis that you may want to explore. I won`t go into great detail on them, but will list the URL and the subject in case that topic interests you:

1. Testosterone therapy effective for men with osteoporosis. Doctor`s Guide to the Internet, http://www.pslgroup.com/dg/147e1e.htm.

2. Ron Simpkin`s personal Web site: http://people.mail2me.com.au/~apollo/. Ron was diagnosed with osteoporosis before there were any approved therapies for it. His story on the About Me link will make you glad there are medications available to treat this condition today.

3. There are three articles on Medscape that you might want to read. You must sign in and register at Medscape, (it is free), so I can`t take you directly to the URLs for the articles. Instead, go to Medscape`s home page at http://www.medscape.com/, register, and then search for the articles using their search engine by the title of the article. Here they are:

a. Effective Treatment of Osteoporosis in Men Still to be Established.

b. Scientific and Clinical Developments in Osteoporosis. Conference Report of 21st Annual Meeting of the American Society for Bone and Mineral Research.

c. Advances in the Treatment of Osteoporosis. Conference Report of 21st Annual Meeting of the American Society for Bone and Mineral Research.

EDITOR