Men`s Osteoporosis Support Group
Volume III, Issue II	April 1, 1999

April Fools Day Greetings

What`s new?

When I received these results, I was relieved, but felt the hospital where the faulty test was done should be informed so an effort could be made to find the source of the problem. I wrote the chief of nuclear medicine explaining what had happened. She replied, "On examination of our report, we found the locum tenens physician in attendance erroneously reported the left femoral neck wards area value of 0.660 g/cm2 rather than the neck area value of 0.806 g/cm2." Additionally, they reprocessed the left femoral data on newer software and found the neck value to be 0.903 g/cm2. I was not familiar with software that could change the results of the tests, but mention it for your information.

I`m particularly concerned about the effects of corticosteroid use and its negative effect on BMD. Some recent studies even implicate fairly short-term use and low doses with an increase in markers of bone destruction. I wondered who, if anyone, sets standards for giving patients bone-forming or antiresorptive medications in conjunction with corticosteroids. So, I e-mailed the Centers for Disease Control to ask if they were involved with this. I did receive an answer and was informed that there are recommendations from the American College of Rheumatology Task Force on Osteoporosis. If you are interested, go to http://www.rheumatology.org/guidelin/osteo/osteo.html to read the entire article.

Thanks to all the members who called, e-mailed, or sent in items of interest this quarter. Recently, I even had a longtime friend mail a story from the Denver Post that concerned men with osteoporosis. I didn`t realize he was that aware of osteoporosis, although I had sent him our Web site information previously. Remember, this is your newsletter, so I appreciate hearing from you about its content.

As mentioned in the last newsletter, Dr. Jeffrey Jackson, our men`s osteoporosis expert, has consented to answer some questions from the men in the support group. If you have a question for Dr. Jackson, please e-mail the editor`s address at the end of this newsletter and questions will be forwarded to Dr. Jackson. This quarter Dr. Jackson answers a question e-mailed to me from one of our members concerning the risk of prostate cancer.

Question: A recent study links excessive calcium intake with increased risk of prostate cancer. Additionally, testosterone injections or patches have also been related to an increased prostate cancer risk. Do those men with osteoporosis taking calcium supplements and/or on testosterone therapy require extra diagnostic tests for prostate cancer, such as routine transrectal ultrasound?

Answer: There is only one study linking high calcium intake to prostate cancer, particularly amounts greater than 1,000 mg per day. Additional confirmation from other studies will be needed to completely assess the effect of calcium intake on prostate cancer risk. In the mean time, I normally do recommend men limit their supplemental calcium intake to 1,000 mg per day. In some instances, based upon specific needs of certain patients, I have them take 1,500 or 2,000 mg daily. An annual PSA (prostate-specific antigen) and digital rectal exam, which I recommend for all men over age 50 who are in normal risk categories, are adequate to detect prostate cancer. Men with osteoporosis under age 50 taking calcium supplements and/or testosterone therapy may want to start the annual PSA and digital rectal exam before age 50 as an added precaution after discussions with their physician. But, there is no need for transrectal ultrasound or any other prostate cancer screening technique unless the PSA and/or digital exam are abnormal. In summary, normal routine prostate cancer screening using the PSA test and digital rectal exam are the only tests needed for men with osteoporosis taking calcium supplements and/or on testosterone therapy.

LunarNews update

I was unable to summarize all the noteworthy topics from the Autumn 1998 issue of LunarNews in the last issue of the newsletter. Here are a few other topics from it that were interesting.

Vitamin D update. LunarNews is very positive on the effect of vitamin D in treating osteoporosis and not particularly positive about the effect of calcium supplementation on improving BMD. On page 25, it is noted that: "Many studies over the past 20 years have shown that calcium supplementation alone has no effect on spine, femur, or peripheral BMD. In contrast, vitamin D alone increased axial BMD, including femur BMD, by 1 to 2% over a two-year period. As with bisphosphonates, there is no effect on forearm BMD. In the immediate postmenopausal period, there is a smaller effect on spine BMD, but still a substantial effect on femur neck BMD." They show a diagram that displays the effect of 24 months of treatment with placebo, calcitriol (0.5 micrograms/day) alendronate (10 mg/day), and calcitriol and alendronate (n=30 in each group). (See Frediani et al, 1998, Clin Drug Invest 15;235-244). They compared the effect on the arms, spine, and total body. In every case, there was a net loss of BMD when placebo was used. With all test medications there was a gain. Calcitriol had the least effect, followed by alendronate, and then the combination of alendronate and calcitriol. So, this study, along with several others they cite, shows that "Supplementation with vitamin D decreases bone turnover, improves axial BMD in the elderly, and halves the rate of fracture."

Bisphosphonate update. This topic is discussed on page 28 and 29. As you probably know, "Bisphosphonates decrease bone turnover and increase axial BMD in osteoporotic patients even at low doses. In a recent study of Japanese women, the effects of 2.5 mg/day of alendronate were identical to 10 mg/day." (See Shiraki M, et al, (1998). Endocr J 45:191-201). They point out that, "Studies in US and European women showed similar responses of the 5 and 10 mg/day doses, and also showed larger increases in older women than those near the menopause." (Editor`s comment: This could be very important for individuals having problems tolerating the 10-mg/day dose of alendronate, e.g., gastric or esophageal discomfort. After stopping alendronate a few days or weeks to relieve any discomfort, it could be restarted at either 5 or 2.5 mg/day doses. This very well might not cause any gastric distress while adequately improving BMD. A previous edition of LunarNews also suggested a once weekly dose of 40 mg of alendronate should be effective for osteoporosis. This single weekly dose might not cause any gastric distress either while still improving BMD. These options should be discussed with your physician if problems develop on 10 mg/day of alendronate. Also, note that Fosamax apparently is only made in 10 and 40 mg tablets. Cutting 10 mg tablets in half to create the 5-mg dose would create a rough pill that could more easily stick in the esophagus causing symptoms. So another way to get the 5- or 2.5-mg dose should be investigated and discussed with your physician if you decide to try this method).

They also point out that, "Bisphosphonates can be combined with other agents such as estrogen or calcitriol to obtain additive effects. . ." (See the comment above on the Frediani study in the Vitamin D update). Also, "A recent study showed alendronate could be given together with human PTH to better stimulate bone formation." (Editor`s comment: Human parathyroid is available only in clinical trials at this time).

There are newer third-generation bisphosphonates being developed and tested now. "Ibandronate and zolendronate are even more potent than alendronate and pamidronate. The former is being developed for injection every 3 months, while the latter has been developed as a patch. Long-term administration of ibandronate increased bone mass in rats and maintained bone quality."

Estrogen update. See page 31 and 32 for this discussion. Low estrogen is normally only thought of as a problem for postmenopausal women, and as the cause of their osteoporosis. However, "New studies are suggesting that estrogen also may play a role in the skeletal state of older men as well as women." (See Khosla S et al (1998) J Clin Endocrinol Metab 83;2266-2274 and Riggs BL et al (1998) J Bone Miner Res 13:763-773. (Editor`s comment: The finding of a link between male estrogen levels and osteoporosis suggests that it may be necessary to test both serum estradiol and testosterone levels when looking for a cause of male osteoporosis. This is new enough that men may have to ask their physicians to perform these tests. Some physicians may not be aware of the possible link between low male estrogen and osteoporosis).

Literature review

In the interest of brevity, I`ll list only the author`s names and the Medline UI number as the means of finding the abstracts for the articles that are reviewed here. Here is how to use the UI number. Go to Medline at http://www.ncbi.nlm.nih.gov/PubMed/ and enter only the numbers in the search block, not the letters "UI." Then click on "Search" to find the referenced article.

Sex steroids and BMD in men. This topic was mentioned in the LunarNews section, but I wanted to highlight some articles that you might want to review to get more information. The first is by Slemenda CW et al, UI 97460000. This study tried to determine whether bone density in older men (older than 65) was associated with serum sex steroids (estrogen [E2] and/or testosterone) or sex hormone binding globulin (SHBG). They found that, "Bone density was significantly positively associated with greater serum E2 concentrations. . ." Additionally, "There were weak negative correlations between serum testosterone and bone density. . ." The authors concluded: "These data suggest that estrogens may play an important role in the development or maintenance of the male skeleton, much as is the case in the female skeleton. These data also indicate that, within the normal range, lower serum testosterone concentrations are not associated with low bone density in men." Note that this study only looked at men older than 65. You should not necessarily correlate these findings to men younger than 65-they may or may not hold true.

In a study done at the Mayo Clinic, Khosla S et al, UI 98326239, the authors looked at sex steroid levels in 346 men aged 23-90 years. They concluded: "These studies suggest that in contrast to traditional belief, age-related bone loss may be the result of E (estrogen) deficiency not just in postmenopausal women, but also in men."

The last study on this topic by Gillberg P et al, UI 99147953, compared 12 men with idiopathic osteoporosis, aged 27-55 years with 12 age-matched men, with respect to serum levels of sex steroids, and other factors. They found that there were decreased estradiol levels and decreased free androgen index along with elevated sex hormone-binding globulin levels in the men with idiopathic osteoporosis. Even the abstract of this article is difficult for the lay person to decipher. But, its finding may be significant for any man with idiopathic osteoporosis. He should probably be tested for the various significant factors found in this study, and then treated if they are found to be abnormal. It is one to print and take to your physician if you are in doubt.

Hypercalciuria and osteoporosis. A recent study by Giannini S et al, UI 98391619 may have significance for men with osteoporosis and hypercalciuria. Once again, this is a difficult study to interpret and one I suggest you print and take to your physician if you think it may apply to you. My interpretation may be completely wrong, so please don`t rely upon it without confirmation from your physician. That being said, here is my understanding of the study. The authors looked at 49 patients, aged 19-60 with calcium kidney stones and idiopathic hypercalciuria (excess urine calcium). They did DXA measurements to determine BMD at the spine and femur. Patients were classified as either fasting hypercalciuria (FH) or absorptive hypercalciuria (AH). The authors concluded: "A disordered bone metabolism and bone loss are present only in patients with fasting hypercalciuria. An excessive acid load, possibly of dietary origin, might be involved as a pathogenic factor." Osteoporosis patients are often treated with diuretics if they are found to have hypercalciuria. From the findings of this study, it would appear that only if hypercalciuria is noted after a fasting (as defined in this study) urine test, should diuretic treatment be started. Otherwise, the hypercalciuria would apparently be unrelated to the loss of BMD. This could be due to excess calcium, vitamin D, sodium, protein, or a potassium- or phosphate-deficient diet which would increase serum calcium levels, thus increasing urine calcium levels. Hypercalciuria noted while fasting would indicate that the hypercalciuria is due to excessive bone mineral breakdown. The non-fasting hypercalciuria should not need diuretic therapy, but the fasting type should. So, a properly conducted 24-hour urinalysis for calcium is important before starting diuretic therapy. If a fasting test was not done, I would be suspicious of the results. Another study that is a review of the topic, and that describes the details of correct urinalysis testing, is by Bataille P et al, UI 98392723.

Sunscreens and vitamin D level. I have been warned by my endocrinologist that wearing sunscreen while outside could be blocking production of vitamin D, and I`ve read or heard similar warnings elsewhere. A search of the literature turned up three articles that concluded that proper vitamin D level can be maintained while using sunscreen and protective clothing. These include studies by Farrerons J et al, IU 99069002, Sollitto RB et al, UI 98079984, and Marks R et al, UI 95243665 . Although the protocols in all three studies were different, they all involved regular use of sunscreen (at least SPF 15) and protective clothing. All subjects maintained serum vitamin D level within the reference range throughout the studies which ranged from one summer to six years in duration. Patients were getting adequate dietary vitamin D during the studies. So, regular use of sunscreen does not appear to hinder serum vitamin D level if dietary intake is adequate. Protect your skin and take your vitamins.

Tetracycline and osteoporosis. I`m always interested in new therapies that might be on the horizon to treat osteoporosis. In the past several years many research studies have shown that tetracycline (TC) has multiple positive effects on bone and other body tissues. This involves a non-antimicrobial property that allows inhibition of matrix matalloproteinases (MMPs) such has collagenase. TC can be useful for treating periodontal disease, arthritis, osteoporosis, and cancer. Additionally, there are now studies involving chemically-modified TC (CMT). The modification removes the antimicrobial effect, which in the case of treatment of arthritis or osteoporosis, is an unwanted property. Two recent studies are of interest on this topic. The first is by Sasaki T et al, UI 99138073. Using a modified TC (CMT-8) on three-month-old female ovariectomized (OVX) rats, the authors found: "CMT-8 therapy produced a significant (p<0.05) inhibition of trabecular bone loss and also induced bone formation in the OVX rats." The authors conclude, ". . .CMT-8 therapy effectively inhibits bone loss after OVX, not only by inhibiting bone resorption but also by inducing new bone formation in the trabecular areas of long bones. The other paper is by Golub LM et al, UI 99138064. It is a review of the effectiveness of TC and particularly describes the recent FDA approval of a low-dose TC (doxycycline) to treat periodontal disease ( the break down of bone that supports the teeth). The exciting potential of the CMTs for treating osteoporosis evolves around the notion that they both prevent bone break down and simulate bone formation. This might make them a good adjunct to use with alendronate or calcitonin which only block resorption, or they may be effective when used alone. Unfortunately, the wheels of science move slowly. The potential of the CMTs has been known for many years and it still is not even in clinical trials. I wish I knew some way to speed the process of clinical trials and FDA approval of these medications, but I have no idea. If anyone has any ideas, I`d love to hear them. Another point to consider is that TC could be used now to treat osteoporosis since it is an FDA-approved mediation. This would be an off-label use and your physician could prescribe it as such. If you are not responding to currently accepted therapies, I recommend a thorough search of the literature to educate yourself about TC to treat osteoporosis. Then take your information to our physician to discuss the possibility of using it as an off-label prescription. TC has been used for many years to treat acne and rheumatoid arthritis with minimal side effects from that long-term use.

The effect of essential fatty acids on bone metabolism. There are three recent articles that discuss a new and natural way to decrease bone turnover and perhaps to increase BMD. In 1994, Sakaguchi K et al, UI 94224923 conducted an interesting study on rats supplementing their diets with eicosapentaenoic acid (EPA). This is a polyunsaturated fatty acid that has a wide variety of beneficial biological functions. The authors divided ovariectomized rats into four groups: (1) normal diet, (2) low calcium diet, (3) EPA-enriched diet, (4) EPA-enriched and low calcium diet. They concluded: "These results suggest that an EPA-enriched diet prevents the loss of bone weight and strength caused by oestrogen deficiency or inadequate nutrition. There is a possibility that EPA could be developed to be a novel anti-osteoporosis drug." In 1995, Claassen N et al, UI 95406249, supplemented male Sprague-Dawley rats with gamma-linolenic acid (GLA) and eicosapentaenoic acid (EPA) in ratios of 3:1, 1:1 and 1:3. They found that "Intestinal calcium absorption (mg/24 h) increased by 41.5% in the 3:1-supplemented group, compared with the control group." They also noted that, "The calcium balance (mg/24 h) and bone calcium (mg/g bone ash) increased significantly in the 3:1 (41.5% and 24.7%) group, compared with the control." The third study is by Kruger MC et al, UI 99130934, and involves a pilot study using the EFAs GLA and EPA on sixty-five women (mean age 79.5). These women had a background diet low in calcium, and were randomly assigned to GLA + EPA or coconut oil placebo capsules while they all received 600 mg/day of calcium carbonate. Markers of bone formation/degradation and bone mineral density (BMD) were measure at baseline, 6, 12, and 18 months. The authors found, "Over the first 18 months, lumbar spine density remained the same in the treatment group, but decreased 3.2% in the placebo group. Femoral bone density increased 1.3% in the treatment group, but decreased 2.1% in the placebo group. During the second period of 18 months with all patients now on active treatment, lumbar spine density increased 3.1% in patients who remained on active treatment, and 2.3% in patients who switched from placebo to active treatment; femoral BMD in the latter group showed an increase of 4.7%. The authors concluded: "This pilot controlled study suggests that GLA and EPA have beneficial effects on bone in this group of elderly patients, and that they are safe to administer for prolonged periods of time."

Certain other essential fatty acids have been shown to reduce the risk of coronary heart disease, so it is possible for essential fatty acids to have positive health benefits. It would not be proper to generalize based upon two studies on lab rats and a pilot study on humans. But, like the CMTs mentioned above, EFAs may be a weapon that can be used to treat or prevent osteoporosis in the future after further studies clarify the effectiveness of using them to modify bone mineral metabolism.

Correct diagnosis and treatment of osteoporosis. A common theme in this newsletter is that patients should become knowledgeable about osteoporosis so they can become involved in the diagnosis and treatment of their case. Your health is too important to assume that someone else will always know everything about your disease and provide the best therapy. Here`s an article from France to reinforce this theme. Laroche M and Mazieres B, UI 98303214 used questionnaires to patients and general physicians to determine if the diagnosis and treatment of newly discovered osteoporosis were correct. The disturbing results were that, "The initial biological investigation was correctly carried out by only 6% of physicians. Treatment was correctly prescribed in only 34% of cases of osteoporosis with fractures, 50% of osteoporosis without fractures, and 50% of senile cortical osteoporosis." Also, "More than half the general practitioners started treatment of osteoporosis without fractures on the basis of standard spinal X-rays where the radiologist suggested bone mineral loss." Please note that is a French study and the results certainly can`t be applied directly to this or any other country. But, they are disturbing enough to make me want to know all I can about osteoporosis, or any other disease I have to see a physician about. They substantiate the need to question anything that does not seem proper according to your understanding of the diagnosis or treatment of osteoporosis. I hope this study makes you want to become more knowledgeable and to not be afraid to ask appropriate questions, too.

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
Email