Men`s Osteoporosis Support Group
Volume IV, Issue 3	July 1, 2000

Summer time greetings

FreeFind search engine added. The FreeFind search engine has been added to the Web site. This will allow you to search for a topic anywhere on the Web site by entering the word into the FreeFind query block. This will bring up all the pages with that word which will have an active link to easily get you to that page. Once on that Web page, go to Edit, Find (on this page) or use Ctrl-F, to bring up the next query block. Then enter the exact words you are looking for and click on the Find Next button. This will very quickly find every incidence of those words so you can read that section without reading the entire document. These directions are for Internet Explorer 5.0; other browsers may have slightly different page search methods.

E-mail from a member. Alex Greene e-mailed me recently with an interesting story that I wanted to pass on to others. A physician friend of his with osteoporosis and a history of two broken vertebrae that have been painful reports pain relief in an interesting manner. Although he had been on Fosamax for several years, at the suggestion of an associate, he added salmon calcitonin to his regimen with complete pain relief. Calcitonin is widely known to give pain relief and is often the first drug of choice for people after spinal compression fractures. But, this analgesic property is probably not given adequate consideration for many people with a history of osteoporotic fracture. Even with Fosamax or other therapies, it might be beneficial to try calcitonin, too, if your physician agrees. If there is no relief after a few weeks, the treatment could probably be discontinued. And if you get relief, it might be possible to discontinue calcitonin therapy later once there is an increase in BMD.

Statins may increase BMD. There was a recent study done on rodents by Mundy G and others, Science 1999 Dec 3:286(5446):1946-9, UI:20050954, showing promise for statins (cholesterol-lowering medications that are HMG-CoA reductase inhibitors) as a possible treatment for osteoporosis. This study showed the statins to be effective in animals at enhancing new bone formation either with subcutaneous injections over the bone or if given orally, Also, two recent Lancet articles show promise for statins in humans. The first, by Edwards CJ and others, Lancet 2000;355:2185-88, was a restrospective study on women showing a 52% reduction in fractures for women taking 13 or more statin prescriptions over the previous year. The authors, however, do not recommend prescribing statins yet until clinical trials are done. The other study, done in London by Spector TD and others,Lancet 2000;355:2218-2219, found 41 older women taking statins had significantly higher spine and hip BMD than women not taking it. So, there is one clinical study on rodents and two observational human studies indicating either increased BMD or reduced fracture rates in people taking statins. This is certainly highly suggestive of positive benefits from statins. There is a great need for controlled studies, particularly those that combine statins with Fosamax, calcitonin, or testosterone therapy, etc. Unfortunately, those studies are at best a few years away. If any men reading this newsletter are also taking statins, it would be interesting to receive e-mail indicating their response to therapy to see if there is a particularly high increase in BMD with the combination of medications they are using, including the statin.

World Congress on Osteoporosis. A lot of interesting information came out of the World Congress on Osteoporosis that was held in Chicago this month. There is considerable information on the studies presented at both the National Osteoporosis Foundation and Doctor’s Guide to the Internet (See the osteoporosis channel) Web sites. Topics include, Fosamax effective for men with osteoporosis, Parathyroid hormone–newest treatment on the horizon for osteoporosis, Actonel (risedronate) effectively prevents spinal fractures, Quarterly intravenous injections–a new paradigm for osteoporosis treatment?, Fosamax can be taken before lunch or dinner, Once-weekly Fosamax dosing may be on the way, Expert outlines when and for whom osteoporosis screening is needed, Dose, pattern, and duration of oral corticosteroid treatment affect osteoporosis risk, Thyroid supplementation does not increase osteoporosis risk, and many others.

On-line discussion. There was a very interesting discussion among the on-line members of the men`s support group this quarter. Evan Prost initiated the discussion which evolved around the topic of testosterone supplementation for men with osteoporosis. For an excellent paper on the entire topic of hypogonadism, see the American Association of Clinical Endocrinologists` Web page at http://www.aace.com/clin/guides/hypogonadism.html. This discussion made me aware that AndroGel(TM) has recently been approved by the FDA for use in men for conditions related to low testosterone. It is the first replacement gel ever approved and will not require patches to be used, it is just rubbed on to the exposed skin. It will be available in the U.S. via prescription by mid-summer. Also, there is recent notice of a study showing AndroGel(TM) significantly decreased the biochemical markers of bone turnover compared to the testosterone patch over a six-month period in men. (See the Clinical Pharmacology channel in Doctor`s Guide to the Internet, http://www.docguide.com/. It was also noted during the discussion that topical (0.1% corticosteroid cream) applied to the area where testosterone patches will be applied is effective in reducing inflammation and irritation that often develops under the patch. For more information, see Clin Ther 1998 Mar-Apr;20(2)299-306, Wilson DE and others. UI:98251732

Welcome to our newest expert advisor . I would also like to welcome Evan as our newest expert advisor for the support group within his specialty of physical therapy. He has a certificate in massage therapy from Sherer`s Academy, Santa Fe, NM in 1984, a BS in physical therapy from the University of Missouri in Columbia, MO in 1988, and extensive experience in orthopedics in both the hospital and home health settings. In August 1999 he was diagnosed with severe osteoporosis and discontinued clinical PT work. Since then he has been tutoring at the University of Missouri PT program. Additionally, in September 1999 he attended a PT seminar on the treatment of osteoporosis taught by Sara Meeks, PT, a specialist for 15 years in the treatment of osteoporosis. If you have a question for Evan, please e-mail him at evanpro@juno.com. He will answer the e-mail and share the advice he gave (not the name of the sender) with other readers in a future newsletter. I also want to mention that Evan runs a list serve for men with osteoporosis at http://www.egroups.com/group/osteoporosismen. This is a great place to discuss osteoporosis issues with other men, so please check it out. We certainly welcome him to the group and look forward to his expert advice.

Evan offers some excellent general advice for men with osteoporosis regarding avoiding compression fractures while exercising. Movements that bring the spine into forward flexion are to be avoided because this places increased pressure on the anterior part of the vertebral bodies. This is the zone where compression fractures begin to occur. He notes that often compression fractures are asymptomatic and a degenerative process, although they certainly can occur suddenly with trauma. Thus, doing exercises such as touching your toes or sit ups can contribute to the very gradual collapsing of the anterior vertebral bodies. These vertebral bodies which were formerly square (from a lateral view) would now be wedge shaped, and eventually this manifests in the rounded upper back appearance that is associated with people with osteoporosis.

Book review

In a recent newsletter I reviewed the book Strong Women Stay Young. Miriam E. Nelson, Ph.D. and Sarah Wernick, Ph.D., have now written a follow-up book, Strong Women, Strong Bones that is published by G. P. Putnam and Sons, New York. The title makes you think this book is like all the others on osteoporosis relegating men to a word or two, but that is simply not the case. This is one of the few books or articles that I`ve read on osteoporosis that didn`t overlook men`s osteoporosis, and, in fact, covered the topic in adequate detail. Not only is there an entire chapter dedicated to men, but they are discussed in other chapters throughout the book.

Drs. Nelson and Wernick also have a Web site, http://www.strongwomen.com and they produce a newsletter that is e-mailed to interested people. I recommend both the Web site and the newsletter. I have found both authors to be extremely helpful and more than willing to answer questions and respond to suggestions. In fact, when I complained that men should have been included in their original book, they replied immediately to say they wanted to know if I could provide names of men they could interview for the new book on osteoporosis. You`ll notice this book is loaded with several comments in most of the chapters from both men and women with osteoporosis which adds greatly to its impact. The men are all members of the Men`s Osteoporosis Support Group who volunteered to tell their story. I`m also happy to say that the authors have listed the men`s support group Web site in a couple of different chapters in the book, thus giving more men and women access to the information that is available there.

The chapter on men`s osteoporosis is short, but covers all the important issues in very adequate detail. Where men`s issues are different than women`s, those items are highlighted. Where they are the same, that is noted, too. One important item they point out is that a recent Gallup poll found fewer than two percent of physicians had warned their male patients that they might be at risk for osteoporosis. This gives some idea of the potential problem that exists relative to educating both men and their physicians about the risk of osteoporosis. The chapter covers such items as how men`s bones develop, who is at risk, symptoms of osteoporosis, recommended tests for men, and adapting the Strong Women exercise program for men. Obviously, with the title of the book being about strength, exercise is the main point the authors are making. There is a table that lists the exercises that should be done according to the weight needed and the age of the men exercising. They have outlined an excellent routine that can be followed by men with osteoporosis that should be a helpful adjunct to other therapies being used to maintain or add bone density.

The remainder of the book is an excellent discussion of the details of osteoporosis and is highly recommended reading. I`ll just highlight some of the interesting findings that they mention that I`d not read in other articles. The first was that they point out that bone density can vary by as much as 3-4 percent depending upon the time of the year due to seasonal sun exposure`s effect on vitamin D levels. Thus, they recommend having your periodic bone densitometry test (DXA) done the same time of the year. They mention an interesting study done in rural areas of the former Yugoslavia in the late l960s and early 1970s. The study compared two regions with totally different dietary habits. People from Podravia had a high calcium intake from dairy products while people from Istra had a low calcium intake from dairy products and ate mostly vegetables and grains. The authors found a much lower fracture rate in the women from Podravia who averaged about 900 mg calcium per day compared to the women of Istra who averaged about 400 mg/day. They also found a higher peak bone mineral density on the higher daily calcium intake. (See Matkovic VK and others, Am J Clin Nutr 1979;32:540-9, UI:79121788) Another interesting presentation was the meaning of the information on food labels. I often read that a item has, e.g., 30 percent of the day`s calcium requirement, but what number is that 30 percent based upon? On page 105 there is a table showing the Daily Values (DVs) for calcium, vitamin C, D, K, potassium, and magnesium. The 100% DV for calcium is 1000 mg, so 30% of the DV would be 300 mg. Thus, you would need to adjust accordingly if your required daily intake of calcium is 1500 mg.

There are many pages of the book dedicated to exercise routines for men and women with osteoporosis. These highlight the importance of weight-bearing aerobic activity, high-impact exercises, strength training, balance training (to decrease the risk of falls), and stretching. The program is designed to cover a twelve-week progressive schedule. The exercises are done from three to six times per week and should take from twenty to forty minutes to complete. Men should read the entire book, including the exercise segment, and then follow the recommendations concerning changes that need to be made to make the exercises more effective for men because of their added strength.

In summary, Strong Women, Strong Bones offers extensive background information about osteoporosis as it affects both men and women. It then provides an excellent exercise routine geared to both sexes that has been proven effective to help build or maintain bone mineral density. It is highly recommended reading for both men and women.

Literature review

Note: To see abstracts of the following articles or any mentioned in this newsletter with the UI code, go to PubMed at http://www.ncbi.nlm.nih.gov/entrez/ and enter only the numerical portion of the UI into the search block, then click on Go or hit .

Inhaled corticosteroids are generally considered one of the safest forms of steroid therapy as concerns adverse effects on bone mineral density, but a recent study suggests they also can be problematical. See Wong CA and others, Lancet 2000;355:1399-403. UI:20250162. Inhaled corticosteroid use and bone-mineral density in patients with asthma. This study looked at the relation between cumulative inhaled corticosteroid dose and bone mineral density in 196 adults (119 women) with asthma aged 20-40 years. All patients had limited exposure to systemic steroids. The cumulative median dose was 876 mg and ranged from 87-4380. There was a negative association between cumulative dose of inhaled corticosteroid and BMD at the lumbar spine, femoral neck, Ward`s triangle, and trochanter. My interpretation of this study is that if you are on corticosteroids-inhaled or otherwise-you should be on some form of preventive therapy for osteoporosis. This could be increased calcium and vitamin D intake, or 5-10 mg alendronate daily (or, the weekly equivalent dosage), whichever you and your physician decide is appropriate for you.

Long acting testosterone injections. A couple of recent studies have shown that testosterone undecanoate (TU) can provide adequate testosterone levels for up to six weeks with a single injection. See Clin Endocrinol (Oxf) 1999 Dec;51(6):757-63, Nieschlag E and others. UI:20086801 and J Androl 1998 Nov-Dec;19(6):761-8, Zhang GY and others. UI:99091256. TU has been used as an oral testosterone supplement in Europe for several years, but it requires multiple daily doses, and has not been used in the U.S. With the apparent excellent testosterone levels attained with the six-week TU injections, it is hoped that there will be clinical trials of the new medication with eventual FDA approval to dispense it. It would be a definite benefit over the standard two-week injections now in use. I`m not aware of any clinical trials, but would appreciate hearing from anyone who knows any more details on TU and if or when it might be approved for clinical use.

Fosamax effective after seven years. A recent article on Doctors Guide to the Internet (Go to the Osteoporosis Channel to select the specific article to view) reports from Tampere, Finland and the 27th European Symposium on Calcified Tissue good results after seven years of continuous use of Fosamax. There are several interesting results from this study:

1. "Results of the study also showed that when treatment with Fosamax stopped after five years, bone density at the spine and hip remained generally stable for an additional two years and did not result in accelerated bone loss."

2. Relative to baseline bone densities at month zero, the following bone density changes occurred: "--At the lumbar spine, 11.4 percent for the Fosamax 10 mg once daily group and 8.2 percent for the Fosamax 5 mg once daily group; --At the hip trochanter, 9.5 percent for the Fosamax 10 mg once daily group and 5.6 percent for the Fosamax 5 mg once daily group; and --At the femoral neck of the hip, 4.9 percent for the Fosamax 10 mg once daily group and 2.6 percent for the Fosamax 5 mg once daily group."

3. "During years six and seven, bone mineral density at the lumbar spine significantly increased by about 1.5 percent relative to year five while bone mineral density at the hip was maintained (from year three) and total body and forearm bone mineral density was maintained (from year five). Decreases in biochemical marker levels of bone turnover also remained stable during years six and seven.

4. "Fosamax was well tolerated in the study. The incidence of upper gastrointestinal (GI) adverse events, both overall and those considered to be drug-related, was similar among the three treatment groups in the two-year extension. These findings are consistent with the three-year and five-year treatment studies and with other clinical studies with Fosamax in which the overall GI tolerability profile of Fosamax was found to be similar to placebo."

How long should patients be treated with bisphosphonates? There is a related article on this topic of duration of treatment with Fosamax from J Womens Health Gend Based Med. 2000 Mar;9(2):81-4, Cosman F and others. UI:20208298. This paper looks at theoretical considerations that surround the long-term use of bisphosphonates due to their long-acting nature, i.e., they have a ten-year half-life. At the time this paper was published the longest studies on the effectiveness of bisphosphonates was four years. It is probable that the seven-year results above would modify the recommendations of the authors.

The authors suggest that after ten years there will be 92 mg of accumulated alendronate in the bone. Normal remodeling would thus release 17 micrograms per day, about 25% of the continued oral dose of 10 mg/day. They suggest this additional release of alendronate could be either positive or negative as concerns fracture risk, and they would like to see longer-term studies to aid the decision on how long to treat. Here are their suggestions on treatment length with alendronate based upon the knowledge they have now:

1. Patients still osteoporotic after four years of therapy should continue on alendronate for at least one year.

2. For women whose bone density is now above -2.5 S.D., it may be reasonable to discontinue alendronate. They recommend DXA be repeated at 2-year intervals. If bone loss is indicated by DXA (>4% in the spine or >6% in the hip), the patient and physician should consider restarting the alendronate.

3. They suggest another alternative is to use biochemical markers of bone resorption to monitor the need to restart therapy. (Editor`s note: My review of the use of biochemical markers shows they are not a totally reliable indicator of bone turnover. See LunarNews, Winter 2000 page 21-23 for a current review of this topic).

4. Continue treatment with alendronate indefinitely, with no monitoring of bone density or bone turnover as there is no evidence-based guideline for determining when to stop or reinstitute therapy.

The authors suggest the FDA should require longer-term studies of the efficacy of drugs with cumulative effects, which seems very reasonable. They were particularly concerned about the four- and five-year results of alendronate as November 2000 will be the five-year anniversary of its use. It does appear that the seven-year results above may ameliorate their concerns somewhat and may have changed their recommendations. It also seems that there are other alternatives that they didn`t consider:

1. A gradual reduction in dosage of alendronate as an individual who has responded adequately to therapy approaches the ten-year half life period. For instance, the dosage could be reduced from 10 mg to 5 mg or 2.5 mg daily or the equivalent once-weekly dose, or even once monthly. Two-year DXA results could be done to monitor the efficacy of the dose reduction.

2. Clinical trials could be done on individuals that have responded to therapy to try to find an ideal maintenance dose of alendronate. Design the protocol so that some individuals, e.g.,

a. Continue on the same dose.

b. Stop the medication entirely.

c. Take the same dose once a month.

d. Take the same dose every two months.

e. Take the same dose every three months, etc. until a dose per time period is found that maintains the benefit indefinitely.

Bisphosphonates and cholesterol levels. I`ve had at least one enquiry from a member wondering whether or not alendronate can influence cholesterol levels. There is a recent study that indicates that indeed there can be an effect. See J Bone Miner Res 2000 Mar;15(3):599-604. Adami S and others. UI:20212614. In this study, 44 women received an IV bisphosphonate infusion every two months for one year with blood tests done at each infusion. The authors found, "In conclusion, aminobisphosphonates, at least when given IV, induce remarkable and unexpected effects on lipid metabolism with a final profile that might be clinically relevant." They found at the 12th month that HDL-cholesterol rose 17-18% and LDL-cholesterol and Apo B fell by 5-6%. They noted that previous studies have indicated that the inhibition of cholesterol biosynthesis by aminobisphosphonates may be a relevant action on bone osteoclasts that might account for its effectiveness. A quick check of Medline abstracts shows several animal studies that found some forms of bisphosphonates very effective at preventing cholesterol synthesis when taken either orally or IV, but I couldn`t find any studies in humans testing the effect of oral alendronate on cholesterol levels. This appears to be an area ripe for more research. It is possible that individuals with both osteoporosis and high cholesterol, may be candidates for IV bisphosphonate therapy or that some forms of oral bisphosphonates may also prove effective at improving cholesterol dynamics for these individuals.

Incomplete renal tubular acidosis as a cause of osteoporosis. There are a couple of interesting studies that implicate incomplete renal tubular acidosis (RTA) as a possible heretofore unsuspected cause of osteoporosis. Since there is effective treatment for this problem, men should be aware of it so they can ask their physicians if they might have the problem. The first study is in Medicina (B Aires) 1995;55(3):197-202 by Sanchez A and Libman J. Renal acidification mechanism disorders in patients with osteoporosis. UI:96093514. Through various complex tests described in the articles, 6 women and 2 men were found to have incomplete renal acidosis that was related to osteoporosis. The six patients in this study were treated for one year with oral sodium bicarbonate and potassium citrate with a total skeletal calcium increase of 3-10%. The authors note, "Whereas the high prevalence of renal acidification defects among renal stone formers with or without hypercalciuria is well acknowledged, renal tubular acidosis is not included in the list of entities causing secondary osteoporosis. As shown in 6 patients in this series, incomplete RTA should be considered as another disease capable of causing osteoporosis or worsening involutional bone loss." The other article is in Osteoporos Int 1999;10(4):325-9 by Weger M and others. Incomplete renal tubular acidosis in `primary` osteoporosis. UI:20157372. This study examined the prevalence of renal acidification defects in patients with `primary` osteoporosis. It involved 32 women and 16 men and excluded patients with obvious or possible secondary osteoporosis. Urine pH on 12/48 patients showed a pH below 5.5 so these patients were excluded as they had normal renal acidification. Other patients then received a short course of ammonium chloride load which initiates systemic metabolic acidosis. Seven men and 2 premenopausal women failed to reach a urine pH of at least 5.5 indicating incomplete distal renal tubular acidosis (RTA I). These patients had several serum factors that were abnormal, and lower Z-scores in bone densitometry (-2.18 vs. -1.40) compared with normal renal acidification. The authors suggest, "Because of possible therapeutic consequences (e.g. administration of alkali salts and high doses of vitamin D,) we propose that measurements of urinary pH and, if necessary, ammonium chloride testing, should be included in the diagnostic investigation especially of male and of premenopausal female patients with osteoporosis." My interpretation is that for all forms of otherwise "idiopathic" osteoporosis in males, RTA I should be considered as a possible cause and appropriate testing performed to exclude it from consideration. If it is found to be the cause, then alkali salts and high-dose vitamin D will apparently resolve the problem.

Update on premature greying of the hair as it relates to osteoporosis. In the first newsletter in April 1997, I mentioned that a study had possibly implicated prematurely grey hair with osteoporosis. This apparently is not a true risk factor for osteoporosis as shown in a study in Osteoporos Int 1999;10(4):290-4 by Beardsworth SA and others. UI:20157366. This study compared 52 prematurely grey-haired women with controls. These women actually had a nonsignificantly higher bone density than age-matched population controls whether they were pre- or postmenopausal. Since men were not included in this study, I suppose it still can`t be completely ruled out that they are somewhat at greater risk for osteoporosis with prematurely grey-hair. But, it appears for now that is not of great concern and that early greying should not be a marker for bone density problems.

Once- or twice-weekly Fosamax dosing. I have reported on this new regimen in the last couple of newsletters, but didn`t have a reference article at that time. So, I wanted to include the recently published article in case you want to refer to it for more details about the research. See Aging (Milano) 2000 Feb;12(1):1-12, Schnitzer T and others. UI:20208195.

Disclaimer. Diagnosis and treatment of osteoporosis are the responsibility of the patient and his or her physician. Nothing in this newsletter is to be interpreted as a recommendation for treatment or to change treatment that your physician has prescribed. Although we attempt to assure that information in this newsletter is factual, errors will occur. It is the responsibility of the reader to verify that information they are acting on is factual. There is no relationship between this newsletter and any national osteoporosis group, including the National Osteoporosis Foundation. All references to any such groups are for informational purposes only.

EDITOR

Jerome C. Donnelly
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