Osteoporosis in Men. Thanks to Larry Schindler for faxing me information on the excellent and very thorough article entitled Osteoporosis in Men by Orwoll ES and Klein RF. It can be found in Endocrine Reviews, Vol. 16, No. 1, 1995, 87-116. If you want only one reference for osteoporosis in men, this would be the one to have. If you have access to a medical library, you will want to get a copy of this article.

IV Pamidronate. I was informed by one of our members that he has started IV pamidronate (Aredia) once every three months. He reports that the IV took about three hours and there were no side effects at all. He has tried Fosamax several times but has been unable to tolerate it due to gastrointestinal problems. Since he has severe osteoporosis and multiple vertebral fractures, his physicians decided to use the IV bisphosphonate at this time. The effectiveness of this treatment method was confirmed in a study by Sarli M et al, Medicina (B Aires) 1998;58(5 Pt 1):446-52. Treatment of post menopausal osteoporosis with intravenous pamidronate in patients with esophagogastric pathology. They found, "In conclusion, intravenous pamidronate is an effective and safe treatment for postmenopausal osteoporosis, especially in those patients with esophageal or gastric disorders." In this study, as with almost all bisphosphonate studies, the drug trials generally include only women. The action of all bisphosphonates is not dependent upon the gender of the patient, so expect equal effectiveness with men or women. Men will just have to use them as an off-label prescription until the FDA finally approves them for men. The important thing to remember is that an alternative bisphosphonate therapy is now available for men or women unable to tolerate oral Fosamax.

Fosamax for men. Speaking of including males in Fosamax studies, Doctors Guide to the Internet recently reported the first year results of a German clinical trial comparing Fosamax and alfacalcidol in 122 men with established osteoporosis. They report after 12 months of treatment with Fosamax, there was a 7.7 percent improvement in spinal BMD compared to 0.9 percent in the alfacalcidol group. The study is on going with additional results to be reported later. These are excellent results and are similar to what members of the Men`s Osteoporosis Support Group who are taking Fosamax have been finding. This report can be read at http://www.pslgroup.com/dg/106966.htm

MEDLINE Plus. If you`re a regular reader of this newsletter, you`ll realize that I refer to MEDLINE often. It is an outstanding source of medical research information. To quote the National Library of Medicine from their Web site, it is the". . .premier bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the health care system, and the preclinical sciences. The MEDLINE file contains bibliographic citations and author abstracts from approximately 3,900 current biomedical journals published in the United States and 70 foreign countries." The URL for MEDLINE is http://www.ncbi.nlm.nih.gov/PubMed/ which will bring you to the PubMed search page where you can look up medical information. What I want to point out is that there is a lot of other valuable information available on this Web site. You may not be aware of it, and I have only recently discovered it myself. If you`ll click on Consumer Health from the PubMed page, this brings you to http://www.nlm.nih.gov/medlineplus/ the site for MEDLINE Plus. Whereas PubMed is dedicated to medical professionals, MEDLINE Plus is meant for consumers. From here you can get information on the following topics: Health topics, Dictionaries, Databases, Clearinghouses, Directories (of doctors and hospitals), MEDLINE, Organizations (providing consumer information), Publications/news (of health interest to consumers), and Libraries (that are online with health information). So don`t overlook this excellent source of medical and health information for consumers. Whether you are looking for osteoporosis-related information or anything else concerning your health, MEDLINE Plus should be a priority Web site for your search.

Ask the experts

Ask the Experts. I would like to welcome Dr. Karen S. Kolba as one of our medical experts that support the members of the Men`s Osteoporosis Support Group. Dr. Kolba is in the private practice of Rheumatology in Santa Maria and San Luis Obispo, California. She is a Wisconsin native who went to the Medical College of Wisconsin in Milwaukee. Her internship was at Akron (Ohio) General Medical Center in Family Practice and this was followed by her residency in Internal Medicine, at the same center. Her fellowship in Rheumatology was at the University of Arizona Health Sciences Center in Tucson, AZ. She has served as the Senior Staff Physician, Divison of Rheumatology, Scott & White Clinic, Temple, TX, as Hospital Consultant at the VAMC, Temple TX, and Assistant Professor of Internal Medicine, Texas A&M University, College of Medicine, Temple, TX. Dr. Kolba is specialty certified by the American Board of Internal Medicine and the American Board of Rheumatology.

First, I would like to thank Dr. Kolba for mailing me Part 1 and Part 2 of Managing Osteoporosis. These booklets are part of the American Medical Association (AMA) education program for primary care physicians. Part 1 is titled Detection and Clinical Issues in Testing, and Part 2 is Glucocorticoid-Induced Osteoporosis. Additionally, there is a part three to this series, Prevention and Treatment. These are an excellent source of information about osteoporosis for your primary care physician. Or, you might be interested in them for yourself. Your physician can get more information at the Division of Continuing Medical Education, Attn: Managing Osteoporosis, 515 N. State Street, Chicago, IL 60610. (312) 464-2588. Although there is a lot of excellent information in these booklets, I did feel that Part 1 was particularly lacking in its coverage of osteoporosis in men. I have written the AMA to express my concern about this problem. This problem nothwithstanding, I highly recommend these booklets for someone interested in a greater understanding of osteoporosis than you might get from typical handouts or brochures on osteoporosis.

This is complicated by the fact that young bodies recover better than old bodies. Acute bone loss (really calcium loss) under the age of 30 is PROBABLY completely reversible, but after the age of 60 it most certainly is not. Here I`m talking acute loss-not the slow loss over years and years. We don`t know the "threshold dose" for kids/teens where steroids will actually inhibit attainment of peak bone mass. I HOPE someone is looking at this-but it is a tough project! At least now there are some fairly decent bone metabolism markers that could be followed.

1. Robinson RJ et al, Aliment Pharmacol Ther 1997, Feb;11(1)201-4. Rectal steroids suppress bone formation in patients with colitis. MEDLINE UI:97195621.

2. Gram J et al, Bone 1998 Sep;23(3):297-302. Effects of short-term treatment with prednisolone and calcitriol on bone and mineral metabolism in normal men. MEDLINE UI:98407371.

Update from Dr. Kolba. She attended a Merck meeting on osteoporosis last weekend and sent a summary that follows.

1. While steroid-induced osteoporosis use of Fosamax is listed at 7.5 mg/day of prednisone or greater amounts, the Merck studies clearly showed excess bone loss at doses above 2.5 mg/day. Physicians need to become more sensitive to this when prescribing low-dose corticosteroids.

2. It is her understanding that the Merck study on Fosamax in men has just been completed with the expectation that about a year will be needed for data analysis and submission to the FDA. Rumor has that it confirms that Fosamax works in men.

3. Merck just submitted their data on 30 mg once-a-week dosing of Fosamax. They aren`t releasing the data, but Dr. Kolba understands it is positive since Merck submitted it to the FDA for approval. This is similar to the 40 mg once-a-week dose recommended by Lunar News that was mentioned in this newsletter quite some time ago. This may become an option for people who can`t or won`t take Fosamax daily. Discuss this option with your physicians if it applies to you.

4. Another suggestion for making Fosamax more tolerable is to take a proton-pump inhibitor such as Prilosec or Prevacid the night before taking Fosamax. This seems to decrease gastrointestinal complaints.

5. IV pamidronate is indeed an effective way to go. Since it is an off-label use, most insurance companies will not pay for it-and it is not cheap. Her understanding is that cost for the drug and infusion is about $200, about equal to three months of Fosamax. Dr. Kolba will be using this medication in her office.

Literature review

NOTE: MEDLINE searches can be done at http://www.ncbi.nlm.nih.gov/PubMed/ and be sure to enter only the numeric portion of the UI if you enter that in the search block.

Post fracture pain control. Vertebral compression fractures can cause pain that ranges from slight to extremely severe. I have had e-mail from several men that have had great difficulty handling their pain after compression fractures. One of our members is just now having great difficulty weaning himself off the narcotics he has been given to try to relieve the pain. So, it is important to have ways to handle the extreme pain without using strong drugs or narcotics. A recent study done in Sweden reports excellent results on three patients suffering "refractory" pain. This study by Dahm PO et al, is reported in Reg Anesth Pain Med 1999 Jul-Aug;24(4):352-7. Intrathecal infusion of bupivacaine with or without buprenorphine relieved intractable pain in three patients with vertebral compression fractures caused by osteoporosis. The MEDLINE UI is 99372948. Intrathecal (i.t.), literally means to be ensheathed. Bupivacaine is a long-acting local anesthetic and buprenorphine is an opioid derived from thebaine that is 25-50 times more potent than morphine. Buprenorphine is addictive like morphine and patients can have similar withdrawal problems after its use. When given in very small doses via pain pumps, the narcotic complications are of less concern.

In this study, the 18-gauge nylon i.t. catheter was inserted in a lumbar interspace with the tip positioned at the level of the fractured vertebra. On one patient, bupivacaine was infused through the i.t. catheter from an external electronic pump. In two other patients, buprenorphine was also infused along with the bupivacaine. Satisfactory pain relief was obtained with daily doses of i.t. bupivacaine ranging from 10 to 70 (mean approximately 25) mg and buprenorphine from 0.02 to 0.2 (mean of 0.15) mg. [Editor`s note: For comparison, the normal IV dose of buprenorphine would be from1.8 to 2.4 mg/day.] Treatment lasted for 37, 387, and 407 days. One patient died of other causes, and the other two stopped treatment when it was no longer needed. They are still pain free after 1,074 and 1,476 days after stopping treatment. The authors concluded, "Continuous intrathecal infusion of bupivacaine, with or without buprenorphine, appeared to be an effective method for the long-term treatment (months to > 1 year) of `refractory` pain from vertebral compression fractures in this small group of patients." The small numbers makes this study less exciting. But, the pain control with relatively safe medications (especially if only bupivacaine is needed), and the long-term relief after stopping the treatment, are very encouraging. Those men who might benefit from this treatment should discuss this study with their physicians.

Reduced fracture risk after Fosamax. A recent study confirms the effectiveness of Fosamax to reduce fracture incidence. This study is by Hochberg MC et al, Arthritis Rheum 1999 June;42(6):1246-54. Larger increases in bone mineral density during alendronate therapy are associated with a lower risk of new vertebral fractures in women with postmenopausal osteoporosis. Fracture Intervention Trial Research Group. The MEDLINE UI is 99292240. Women in this study received 5 mg/day of alendronate for two years followed by 10 mg/day for the remaining 12-30 months of the study. The authors state, "Women who had larger increases in total hip BMD during the first 12 months had a lower incidence of new vertebral fractures during the entire followup period." In fact, 3.2% of the women with increases of > or =3% in total hip BMD experienced new vertebral fractures, whereas twice as many women (6.3%) whose BMD declined or stayed the same experienced new fractures. It is always reassuring to see increased BMD after taking a medication such as Fosamax. However, the most important factor is whether fracture risk is decreased by this increased BMD-and that is not always the case with some medications. This study is important in that it found that, ". . .greater increases in BMD are associated with lower risk of new vertebral fractures." Although men were not included in this study, there is no reason to expect any different results for them since Fosamax is not gender specific in its actions.

Vitamin D insufficiency and osteoporosis. Vitamin D supplements are routinely recommended for people with osteopenia or osteoporosis. Generally, the vitamin D is considered an adjunct to the alendronate or calcitonin that is given as the primary treatment medication. A recent study shows that there are times when vitamin D alone is adequate therapy. Adams JS et al J Clinc Endocrinol Metab 1999 Aug;84(8):2729-30. Resolution of vitamin D insufficiency in osteopenic patients results in rapid recovery of bone mineral density. MEDLINE UI 99371268. The authors evaluated 118 consecutive, free-living patients with osteopenia or osteoporosis and identified 18 subjects with depressed serum 25-hydroxyvitamin D. These subjects received 50,000 IU vitamin D2 twice weekly for five weeks. This vitamin D repletion was associated with a significant 4-5% annualized increase in bone mineral density at both the lumbar spine and femoral neck. This study is a reminder to look for the true cause of the decreased BMD. Just because you have bone densitometry that shows low BMD, it doesn`t necessarily mean that alendronate or calcitonin is definitely needed. It means a thorough work up is needed with multiple blood and urine tests (and other tests, if needed) to find the cause of the problem. In the case of a patient with low vitamin D levels, other lab values will tend to be abnormal, too. For example, the fasting urinary calcium/creatinine excretion ratio, serum parathyroid level, and osteocalcin level should also indicate a problem is present.

High milk intake and osteoporosis. In much of the lay press there is often mention of the fact that some of the countries with the highest milk consumption (and therefore the highest calcium intake), also have a very high incidence of osteoporosis. Particularly in the vegetarian literature, this fact is used to promote the vegetarian lifestyle-especially one free of milk products. This appears to be a case of "shooting the messenger" rather than finding the root cause of the problem. This point is made in a recent study by Whiting SJ and Lemke B in Nutr Rev 1999 Jun;57(6):192-5, Excess retinol intake may explain the high incidence of osteoporosis in northern Europe. MEDLINE UI 99368487. The authors conclude, "Retinol [vitamin A] in fortified milk could explain also the association of high calcium intake and hip fracture incidence in northern Europe because milk is an important source of both nutrients." The problem occurs from a chronic intake of greater than 1.5 mg/day of vitamin A, which in Northern Europeans comes from milk supplemented with Vitamin A in the same manner we supplement ours with vitamin D. I have warned of this relationship between high vitamin A intake and osteoporosis before. Be careful if you take lots of vitamins and supplements as this relationship appears quite strong. You could be going backwards in your goal to attain higher BMD in spite of taking all your prescribed medications if you are overriding them with too much vitamin A. See the January 1999 newsletter, http://www.maleosteoporosis.org/9nl.htm.

Calcaneous Ultrasonometry. Although dual X-ray absorptiometry (DXA) is the standard diagnostic test to determine osteoporosis of the spine or hip, there has been considerable research into the use of quantitative sonography of the calcaneus (the heel). This method is approved by the FDA and there are almost 5000 units in use around the world. The latest edition of Lunar News (to download this edition go to http://www.lunarcorp.com/ or call 608-828-2663 to subscribe) has an extensive discussion of the Lunar ultrasonometry unit, the Achilles, and indicates that it is comparable to DXA in diagnostic ability. Indeed the graph in their advertisement shows a virtual exact duplication of the diagnostic capability of DXA. These units are light, fast, very mobile, and relatively inexpensive to operate compared to DXA, so comparable diagnostic results would be quite a plus for patients and physicians. There is an August 1999 abstract in MEDLINE (UI 99357198) where the authors tested just this ability of the calcaneous ultrasonometer to match the diagnostic results of DXA. They were unable to get agreement between the two as often as Lunar News suggests is possible. The study by Grampp S et al is in Am J Roentgenol 1999 Aug;173(2):329-34, Diagnostic agreement of quantitative sonography of the calcaneus with dual X-ray absorptiometry of the spine and femur. They concluded, "The considerable diagnostic disagreement between quantitative sonography and DXA could cause confusion in the daily practice of radiology and make establishing the correct diagnosis a difficult task. The choice of imaging technique influences which patients are diagnosed as osteoporotic." The are several manufacturers of heel ultrasonography units, and the MEDLINE abstract doesn`t tell if they used the Lunar unit or another brand. But, it indicates that there are still questions as concerns using these devices as diagnostic tools for osteoporosis. They may also be useful for monitoring the effects of treatment, as Lunar suggests is an acceptable capability of the Achilles unit. To my knowledge, the DXA is the method of choice, however, when it comes to assessing how effective osteoporosis treatment has been. Should testing ultimately prove the ultrasonography equivalent to DXA for this purpose, it would be a great boon to patients, and maybe more so to the HMOs, and Medicare in reduced fees for the diagnostic tests. The figures I have seen show ultrasonography is about 3.6 times cheaper than a central DXA, which is the standard diagnostic DXA.

Corticosteroids and osteoporosis. One of the most frustrating areas of osteoporosis for me is the relationship between corticosteroid use and low BMD. I had corticosteroids given to me in my twenties which I feel are somehow related to my osteoporosis. And, many of the e-mails I get are from men with a history of steroid use before finding they had osteoporosis. Here`s a quote from an e-mail I got not too long ago from a 34-year-old man to give you an idea about the problems with corticosteroids and osteoporosis. "In retrospect, I`m as you would expect, devastated when I consider that my doctor, who is recognized as an expert in the field of allergy and asthma, never once mentioned to me the effects that prednisone has on bones in all the times I have seen him. What happened to me is that I was playing basketball and went to suddenly run down court and heard a pop in my foot. When it was X-rayed, they said there were no breaks but that I had a rupture of the plantar fascia. Everyone thought this was quite odd and when I asked my orthopedic doctor could this be related to steroid use, he said probably no. That is when I started to read more about the effects of prednisone. I was shocked to find out that almost all of the literature clearly states that this medication causes osteoporosis. I then called my doctor and after being told, `Oh, don`t worry yours will be normal,` he ordered a DXA for me. Anyhow, after getting the test results, my doctor says he doesn`t remember what all the numbers mean but that I`m not in any danger now. He says I have plenty of calcium in my bones." This man`s DXA results showed T-scores of -1.67 S.D. for the hip and -2.76 S.D. for the spine. I can tell you from our correspondence that he was highly concerned by these numbers and by the fact that he wasn`t forewarned of the possibility of getting osteoporosis from the use of corticosteroids-and rightfully so. Here is some of the latest research that applies to corticosteroid use and its relationship to low BMD.

A patient survey. There are very interesting results of a telephone survey done by Buckley LM et al, Arthritis Rheum, 1999 Aug;42(8):1736-9, Prevention of corticosteroid-induced osteoporosis: results of a patient survey. MEDLINE UI 99374541. The authors contacted 147 patients receiving a mean prednisone dose of 10 mg per day for an average of 1-2 years. Twenty-nine percent reported having a bone density test, 29% were taking calcium supplements, and 45% were receiving vitamin D. Forty percent of postmenopausal women were receiving hormone replacement therapy and 14% bisphosphonates. Patients who were evaluated by primary care physicians and rheumatologists were more likely to have undergone bone density testing and preventive treatments than other specialists. The authors conclude, "Many patients receive inadequate treatment to prevent corticosteroid-induced osteoporosis, and physician specialty is an important predictor of bone density testing and treatment." Note that the American College of Rheumatology has published recommendations for prevention and treatment of glucocorticoid-induced osteoporosis. A pretreatment bone densitometry is the foundation of this recommendation and should be part of the early work-up of patients who are initiating glucocorticoid treatment. This establishes a baseline BMD and determines what type of preventive or treatment therapy is needed. From this study it is obvious that more than 70% of patients are not getting the standard of care when starting glucocorticoids. Once again, it is important that patients educate themselves so they can be partners with their physician in their medical care. Don`t trust your health only to your physician, it is your life and your health, no one should care more about your health than you. Don`t be like the 34-year-old man above who had to ask for a DXA six years after treatment started. Get the DXA at the beginning and then get proper preventive therapy to avoid the problems he is having now.

Inhaled corticosteroids. This paper suggests the safest inhaled corticosteroids to use for asthma to prevent side effects with long term use and is by Jackson LD et al, Can J Clinc Pharmacol Spring 1999;6(1):26-37, Comparative efficacy and safety of inhaled corticosteroids in asthma. MEDLINE UI 99395357. The authors suggest that regular treatment with the following drugs in adults and children is unlikely to result in any clinically significant effects on the parameters of growth retardation in children, adrenal suppression, reduction in bone mineral density, and cataract formation. They list the safest inhaled corticosteroids as (the first figure is for adults, the second for children`s dosage, all in micrograms): beclomethasone dipropionate less than 1500 and 400, budesonide less than 1600 and 400, flunisolide less than 2000 and 1000, fluticasone propionate approximately 500 and 200, and triamcinolone acetonide less than 1600 and 1200. They also suggest that, "Patients requiring continued high doses by the inhaled route should be monitored for systemic effects and be considered for osteoporosis prevention therapy if appropriate."

Vitamin D as a preventive for corticosteroid-induced osteoporosis. If something as cheap and readily available as vitamin D plus calcium is effective in preventing osteoporosis in steroid therapy patients, then why not use it in all such cases-even when using corticosteroid inhalers? Vitamin D with calcium was moderately effective as shown in a meta-analysis of studies posted on MEDLINE from 1966 to 1997 according to Amin S et al, Arthritis Rheum 1999 Aug;42(8):1740-51, The role of vitamin D in corticosteroid-induced osteoporosis: a meta-analytic approach. MEDLINE UI 99374542. The authors looked at all studies of randomized controlled trials lasting at least six months for patients receiving oral corticosteroids and that compared vitamin D with either 1) no therapy or calcium alone, or 2) bisphosphonates, calcitonin, or fluoride. The outcome measure of interest was the change in lumbar spine bone mineral density. Vitamin D plus calcium was better than no therapy or calcium alone. It was similar to calcitonin, but worse than bisphosphonates or fluoride. In view of the cost and safety, it would appear that all patients receiving corticosteroids should be on vitamin D and calcium supplements as a preventive measure for osteoporosis. This doesn`t preclude additional therapy as determined by the condition of the patient and the opinion of the physician. And, it doesn`t mean that initial and follow-up DXAs aren`t needed to evaluate the baseline BMD and effectiveness of the treatment to prevent or reduce the loss of BMD. But, this meta-analysis suggests there is evidence that it is better than taking no preventive measures at all.

An additional study by Reginster JY et al confirms the value of vitamin D or its metabolites in corticosteroid patients. It can be found in Osteop Int 1999;9(1):75-81, Prophylactic use of alfacalcidol in corticosteroid-induced osteoporosis. MEDLINE UI 99295108. In 145 patients taking an average of about 46 mg/day of prednisolone, it was found that 1 microgram/day of alfacalcidol was significantly better than placebo at maintaining BMD after one year. There was +0.39% change in BMD in the alfacalcidol group and -5.67% change in the placebo group. Alfacalcidol is a metabolite of vitamin D and is not the form normally found in vitamin D supplements. But, it appeared relatively effective at these high doses of corticosteroids, so it could be an important medication for people on this steroid dosage. If you feel this study relates to your condition, you may want to discuss it with your physician. There are other alternatives as well for men now in treating glucocorticoid-induced osteoporosis.

Fosamax gets FDA approval for glucocorticoid-induced osteoporosis. This summer the FDA approved Fosamax (alendronate sodium) for the treatment of glucocorticoid-induced osteoporosis in men and women. This is important for those with steroid-induced osteoporosis and because it is the first time Fosamax has been approved by the FDA for treatment of men for any form of osteoporosis. It is one step closer to approval for its use (without an off-label prescription) in men for all forms of osteoporosis.

The FDA-approved indication is for men and women receiving glucocorticoids is a daily dosage equivalent to 7.5 mg or greater of prednisone and who have low BMD. You can read more about this on the Doctor`s Guide to the Internet at http://www.pslgroup.com/dg/10c15a.htm and get additional information about the studies done that led to acceptance by the FDA. There is a lot of osteoporosis-related information at this Web site that you will want to read, too. If you do some surfing around there, it will be educational.

Jerome C. Donnelly
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