Men`s Osteoporosis Support Group
Volume 1, Issue 2	July 1, 1997

Second Quarterly Issue

Greetings from the editor

Phirst things phirst. A phunny thing happened with the phirst edition of the newsletter. Though I spell checked and reread the copies often, "Fosamax" somehow became "Phosamax." Phor this I am very sorry. In phuture editions of the newsletter you will phind Fosamax spelled correctly phor sure.

Thanks to everyone who responded after receiving the premier issue of our newsletter. The response was overwhelmingly in favor of continuing with its publication. I thought there was a chance that the information that the National Osteoporosis Foundation (NOF) furnishes might make our newsletter unnecessary. Their services and information are considerable; they, however, leave room for the type of information that our newsletter provides. I am going to discuss in this issue what NOF offers members because it is substantial.

I can still use good thorough profiles of your personal histories or your experiences with osteoporosis. Of those received, most do not provide enough detailed information. Please provide as much specific details about events that occurred before diagnosis, what diagnostic tests you had done, what the diagnosis was, what medications you have or are taking, how effective those have been at relieving symptoms or increasing bone mineral density (BMD), and any other information you feel is pertinent.

A couple of you reported after receiving the first newsletter that you would try to get us an expert to respond to our questions. One expert has recently said she would provide answers to our questions, but I haven`t received an actual response we could publish from her yet. A note posted on the medical bulletin board on Physician`s Online asking for osteoporosis expert volunteers was unsuccessful. I can find information on most questions in the medical library. There is no assurance, however, that I will interpret the literature the way an endocrinologist or other expert would. For now, please keep the search on for willing osteoporosis experts to support our group.

What`s new?

As noted in the first newsletter, I have been trying to track down the source of the cyclic Fosamax dose regimen. This search led me to buy an audio tape done at the annual meeting of the American Association of Orthopaedic Surgeons held in February 1997. Dr. J. M. Lane gave an excellent lecture entitled "Paget`s Disease of Bone and Osteoporosis: Medical and Surgical Management." He did not recommend taking Fosamax cyclically, but did have much other useful information. I would highly recommend purchase of the two audio tapes that cover the lecture for anyone interesting in knowing more about osteoporosis. Call or write National Audio Video, Inc., 4465 Washington Street, Denver, CO 80213, (800) 373-2952. The tape numbers are 241AB and the total cost is $25.50 for both, including shipping. The lecture covered mainly female osteoporosis issues, but much of the information was useful to anyone with osteoporosis. I cannot summarize all the useful information in the tapes, but will present a couple of highlights.

Some have reported instances of indigestion after taking Fosamax. For those individuals, Dr. Lane suggests taking only one pill the first week, two the next, three the next, etc., until they reach the normal daily dose. If you have had problems acclimating to Fosamax, you might ask your physician to try this method to get back on it. He suggests a similar method for women who have had difficulties with estrogen. Start at a lower dosage and slowly work up to the normal dose. He also notes that only four cigarettes a day destroy half the body`s estrogen.

Although studies have not proved it, estrogen and Fosamax used in combination may be more effective than using just one. Fosamax appears to give a greater boost to estrogen than vice versa. Additionally, no studies yet verify that Miacalcin (nasal calcitonin spray) and Fosamax work better together, but empirically it appears that they may be more effective than when used alone. Dr. Lane uses Miacalcin as a short-term medication after osteoporotic fracture until diagnostic tests determine the cause of osteoporosis. Then he switches the patient to estrogen or Fosamax for long-term therapy depending on test results, patient desires, etc.

Fosamax is a fantastic drug that can literally shut off bone resorption. Interestingly, the rate of fracture for people on Fosamax was the same without a detectable bone mass increase. The quality of bone thus increases with use of this medication. It has a ten-year half life that means you lose 50% of the drug in 10 years, 25% in 20 years, etc. In spite of this, it does not appear to interfere with bone remodeling or repair after fracture as shown in dogs.

Osteoporosis looms as a universal disease unless people are continually aware of preventive measures. People must get adequate calcium intake, proper exercise, and medications to prevent or deal with bone loss. Anytime in your life that you stop ingesting calcium, your bones will start dissolving to release calcium to the body. If you stop all exercise, your bones also dissolve. If you are a woman and not producing natural hormones or getting replacement hormones, your bones are losing 2% of their mineral content per year even if you are taking calcium supplements. So everyone needs to be vigilant to avoid the sorrow of osteoporosis. Prevention is the key word concerning this problem.

A Mayo Clinic study showed that sit ups could cause compression fractures, so avoid them if you have osteoporosis. Nevertheless, do perform some type of exercise. One study showed that women who square-danced 2-3 times per week and used calcium supplements added 2% of bone per year.

Hypothyroid patients on synthetic thyroid medications should be careful not to take more than the prescribed amount. This will make them clinically hyperthyroid, induce bone mineral loss, and can lead to osteoporosis.

Nutrition and medications

This segment will cover several questions about Fosamax and replaces the Ask the Experts segment, too, since Merck`s experts provided the information.

Merck & Co., Inc., the manufacturers of Fosamax, have a patient information phone line at 800-672-6372. You may call them if you have questions about any of their products. You will speak to a company representative that has access to a computerized database of information organized by topics. They then fax or mail answers to questions that include literature references. The following is a summary of what I received in answer to my questions.

1. Is there any research to show that Fosamax could interfere with healing or bone remodeling after surgical procedures or fractures? Fosamax binds to the bone and blocks osteoclasts from resorbing bone. Possibly this binding effect could prevent or slow the remodeling required after osseous surgery or fracture. The response was that there were no such studies yet. There is, however, a study by Shibutani el al (1), studying the effect of alendronate on alveolar bone remodeling after tooth extraction in dogs. Oral radiographs showed there was a significant increase in alveolar bone density of the extraction sockets in the alendronate-treated dogs after one month. The authors concluded that these results suggested alendronate may enhance alveolar bone formation following tooth extraction in dogs.

Although Merck did not send me the following study, I noted that it dealt with fracture healing after Fosamax in dogs. Peter et al (2) gave Fosamax to mature beagle dogs for nine weeks preceding fracture, 16 weeks after fracture, or both before and after fracture. Fracture healing was evaluated by radiography, gross and histological examination, and bone histomorphometry. They concluded: "...in this study, treatment with alendronate before or during fracture healing, or both, resulted in no adverse effects on the union, strength, or mineralization of bone in mature beagle dogs."

2. Is it possible to use Fosamax and calcitonin concomitantly to enhance benefits? There are no studies comparing the two drug regimens to treat osteoporosis. There are, however, studies about the concomitant use of bisphosphonates in patients with hypercalcemia (excess serum calcium). A study by Correa et al (3) evaluated the use of these drugs in patients with hypercalcemia of malignancy. Intravenous alendronate plus calcitonin was significantly more effective that either drug administered alone in reducing serum calcium levels. There is a need for studies to see if there is any benefit to combining calcitonin and alendronate to treat osteoporosis. The use of N-telopeptide as a marker of the effectiveness of stopping bone resorption may be a simple and effective way to readily check the efficacy of the combined drug regimens. N-telopeptide is a breakdown product from the collagen (organic) matrix of bone that is present in greater concentration as bone dissolves. If both drugs are more effective than either one alone, the N-telopeptide will decrease when the second drug is added to the initial one.

3. Is there any evidence to show that Fosamax should be administered in an intermittent or cyclic dosage? In the first issue of this newsletter I mentioned that one physician had recommended an intermittent Fosamax dosage to me. Merck makes no recommendations about the administration of Fosamax on an intermittent basis. Data obtained in a study to assess the effects of treatment withdrawal showed that the continuous daily treatment with Fosamax is required to maintain the effect of the drug. Pedrozzoni et al (4) conducted a study to evaluate the effects of cyclic alendronate on various biochemical parameters of bone metabolism in 10 postmenopausal women with osteopenia. They treated the women with a cyclic regimen of oral alendronate for one month followed by two months without treatment. The marker most responsive to alendronate was urinary N-telopeptide, which decreased by 40.5% at one month, increased by 33% at three months, decreased by 30% at four months, and increased by 42% at six months. These results show that bone resorption decreases during periods of alendronate dosage and that it increases when alendronate is stopped. No published studies show any indication for taking Fosamax in a cyclic regimen.

1. Shibutani T et al. J Bone Min Res 1996;11-Suppl 1:S334

2. Peter CP et al. Effect of alendronate on fracture healing and bone remodeling in dogs. J Orthop Res 1996;14(1):74-9

3. Correa C et al. Treatment of Cancer-Associated Hypercalcemia with Alendronate Sodium: A Randomized Double-Blind Comparison with Calcitonin. J Bone Miner Res. 1994;9(Suppl 1):S294

4. Pedrazzoni M et al. Effects of a cyclic administration of oral alendronate. J Bone Miner Res. Aug 1996;11(Suppl. 1):S442.

Medical factors in osteoporosis

The member profile in this issue concerns a case of idiopathic osteoporosis. Exactly what is this condition and how is a diagnosis developed?

Perry and others (5) describe five young men who had a similar syndrome of osteopenia, hypercalciuria, and histomorphometric data suggesting decreased bone mass with an increased rate of bone formation. They could find no primary or secondary cause for the problems. The following describes the patients and what investigators checked to try to find the source of these men`s osteopenia.

The patients ranged in age from 27 to 57 years old. All patients were referred due to "osteoporosis" noted on routine x-rays. All five patients had generalized demineralization on x-ray and three had collapse of at least one lumbar vertebra. These individuals were active and employed as laborers or farmers with no previous therapy for their bone disease. Multiple serum, urine, histological, and bone mineral density (BMD) tests were done to try to find a source for the low BMD. The following tests had normal results:

1. Serum Calcium, Phosphate, and Alkaline Phosphatase (one individual had a slightly elevated Alkaline Phosphatase level).

2. Thyroxine, Testosterone, Urinary Free Cortisol, 1,25-Dihydroxyvitamin D, and 1,25-Hydroxyvitamin D.

3. Parathyroid function: Immunoreactive parathyroid hormone, Creatinine Clearance, Tubular Reabsorption of Phosphate, and TmPO4/GFR.

4. They measured BMD in the forearm with a dual photon densitometer at a mid-radius site. The normal forearm site BMD did not correlate well with demineralization apparent in spinal x-rays.

The following tests had abnormal results that showed the nature, but not the cause of the problem in these men.

1. Calcium Intake and Calcium Excretion. They tested patients first with an unrestricted calcium diet and then while receiving drastically reduced dietary calcium. All patients were hypercalciuric (excreted excess calcium in the urine) on the unrestricted diet and four of five were hypercalciuric on the restricted diet. Hypercalciuria can result from three sources: 1) increased intestinal absorption of calcium; 2) decreased kidney reabsorption of calcium; and 3) increased bone resorption. The authors attribute the test results to a combination of increased calcium absorption and increased bone resorption.

2. Histomorphometric analysis of trabecular bone. The microscopic appearance of the bone showed an accelerated rate of bone remodeling (turnover) with increased osteoid (the unmineralized precursor to bone) volume, increased active osteoid, increased osteoclast number, and increased cellular rate of mineralization. Apparently during all this remodeling, bone resorption was occurring more rapidly than bone formation leading to a net loss of bone. Although the authors could show what was happening, they could not explain why. They concluded, "The etiology of this problem continues to puzzle us."

Swedish investigators (6) report an interesting potential side effect of idiopathic osteoporosis: lead poisoning. A previously healthy 36-year-old Swedish man with more than ten years of work-related lead exposure developed musculoskeletal pain, and paresthesia of both arms. He was found to have lead poisoning. After treatment with chelating agents, he had a bone fracture in an accident. Subsequent examination led to a diagnosis of idiopathic osteoporosis. The authors felt that the combination of a moderately increased bone lead pool (the bone holds 90% of the body burden of lead) and the skeletal disease were the source of lead poisoning.

Baltzer and others (7) in a recent study state: "A hereditary genesis of the idiopathic osteoporosis seems to be sure." They conclude that the vitamin D receptor (VDR) has an important role for the mineralization of the bones. This study showed the allelic variants of the VDR gene correlated with the bone density of the lumbar spine (p<0.009). Note: An allele is any one of a series of two or more different genes that may occupy the same position on a specific chromosome

COMMENT: Dealing with something that has no known explanation is hard. It is possible that more research into a genetic or biochemical source of this puzzling form of osteoporosis will eventually lead to new treatment options. Until then, those with idiopathic osteoporosis should get optimal calcium, vitamin D, and other required nutrients from the diet or supplements; avoid all known osteoporosis risks factors such as smoking, excess alcohol, excess protein ingestion, and certain medications; exercise moderately routinely; and take calcitonin or alendronate to reduce the effects of excessive bone resorption.

5. Perry HM, Fallon, MD, Bergfeld, M, Teitelbaum SL, Avioli, MV.: Osteoporosis in Young Men, Arch Inter Med 1982;142:1295-6.

6. Berlin K, et al: Lead intoxication caused by skeletal disease, Scan J Work Environ Health 1995;21(4):296-300.

7. Baltzer A, et al: Genetic determination of bone density, Z Orthop Ihre Grenzgeb 1996 May-Jun;134(3):198-200.

Member profile

This 44-year-old man was diagnosed just over a year ago with idiopathic low turnover osteoporosis. He used to be an avid jogger in reasonably good condition until his joints, bones, and muscles began to ache in 1993 so much that he could not run anymore. At that time he also began to have chronic diarrhea. Two years of tests followed while physicians looked for Inflammatory Bowel Disease. They made no such diagnosis, with the conclusion that he had an idiopathic functional bowel.

On January 1, 1996, he was riding down a snow-packed hill on an inner tube and hit a bump that shattered the L-1 vertebra into about 15 pieces. This type of fracture was unexpected in the presence of healthy bones. The physician mostly removed L-1 along with the discs above and below. They inserted a piece of cadaver femur into the space, along with a plate and screws. The physician remarked that the bones seemed abnormal upon inspection and suggested densitometry upon arrival home. This test showed that 39% of normal BMD had been lost compared with the patient`s age group.

Next a bone biopsy was done with tetracycline markers. The microscopic picture made the physicians conclude the diagnosis was Idiopathic Low Turnover Osteoporosis. They told the member his osteoblasts were working, however, the osteoclasts were working overtime, causing a net bone loss. In fact, they told him that the disease was probably present since childhood considering his history of thirteen bone fractures.

The patient started nasal calcitonin for a six-month trial. Tests then showed an additional 4% of bone had been lost. At this time another back surgery was done due to migration of the first fixation and failure of the bone to heal. After surgery, they started a 90-day trial of nasal calcitonin alternating with Neutra-Phos, a phosphorous compound. After six additional months, BMD tests again showed another 4% loss of BMD--a total loss of 8% for the year.

They started Fosamax in January 1997 and the member has high hopes for that medication. His physicians have told him that he has a hereditary aggressive form of osteoporosis that may or may not respond to treatment. Several sources told him that he may end up in a wheel chair if future treatments are not successful. He used to be a chiropractor and is now looking for a new career.

Comment: I am sure I speak for all our members when I say that we wish this member all the best luck in the world. Anyone that has information that may provide any assistance to this member, please contact me and I will send it on to him.

Osteoporosis on the Internet

Pharmacists Caring for Osteoporosis is an excellent site with a variety of information and the ability to e-mail those who wrote the data. All my e-mail questions have been answered promptly and in detail. The URL for this very informative World Wide Web site is: http://www.uop.edu/pharmacy/asp/osteoporosis/osteo_home.htm. Broad topics covered include: Introduction, Bone Scans, Calcium, Exercise, Estrogen, New Drugs, Your Pharmacist. There are many other narrower topics covered, also, including Fosamax and Men with Osteoporosis.

An example of important information that I found at this site is the discussion of DEXA scans. Included in the discussion is the fact that the "Bone Matters Tour," co-sponsored by the Lunar Corporation and Sandoz Pharmaceuticals, is currently going around the country giving free bone scans. To get more information, call 800-347-BONE. Sandoz produces Miacalcin, the nasal calcitonin spray and Lunar makes the DEXA machines.

Mayo Health O@sis is not dedicated to osteoporosis coverage, but includes a broad range of health matters. It is, however, an excellent site that is always current and of the highest quality. The URL for the site is: http://www.mayo.ivi.com/ivi/mayo/common/htm/index.htm. The most important aspect of the site is that you have the ability to ask the Mayo Dietitians or Physicians questions. You will not receive a direct answer, but if they find your question has broad appeal, you can find the answer posted on their "Ask the Experts" section of the Web page. There are libraries of past questions and recommendations about medical problems that you can access, including those about osteoporosis and related dietary concerns. In summary there is a wealth of information available at these Web sites. You won`t regret visiting them often.

Miscellaneous

I have spoken or written to several people at the National Osteoporosis Foundation (NOF) over the last couple of years. Somehow, during all these discussions, I never realized what was involved with membership in NOF, and somehow overlooked membership applications or did not receive one. Recently, Liz Stone, who is in charge of coordinating the various support groups for NOF, sent me an NOF information packet. If others of you are also unaware of all that NOF offers, I want to share what I have discovered with readers.

NOF is dedicated to providing information to patients, healthcare professionals, and organizations seeking up-to-date, medically sound information on the causes, prevention, diagnosis, and treatment of osteoporosis. Call (202) 223-2226 to receive a membership application form. Membership costs as little as $15.00 per year or you can contribute additional money that goes toward osteoporosis research. You can also join at NOF`s Web Site, http://www.nof.com.

Members receive a 60-page handbook, Boning Up on Osteoporosis, a quarterly newsletter, The Osteoporosis Report, and invitation to contact the National Osteoporosis Patient Information Center (NOPIC). The NOPIC gives patients a point of contact if they have medically-based questions about osteoporosis. People calling NOF requesting information are usually sent a basic packet of materials explaining about osteoporosis that also gives them a chance to join NOF. People who call NOF with questions for a healthcare professional are directed to NOPIC. There is some discussion about including an Ask the Expert topic in future issues of The Osteoporosis Report. If you are a member or join, call or write NOF if you would like to have this topic added to the newsletter.

NOF also cosponsors the Osteoporosis and Related Bone Diseases National Resource Center (ORBD~NRC). You can contact ORBD~NRC at (202) 466-0344 to obtain information fact sheets, video materials, and brochures on metabolic bones disease risk factors, and prevention strategies. For health professionals, or patients interested in details of osteoporosis, bibliographies showing abstracts of pertinent research studies are available, also.

NOF also publishes Osteoporosis Clinical Updates, a newsletter dedicated to health care professionals. Each issue covers one important clinical issue about osteoporosis. Past issues have covered the role of rehabilitation in the management of osteoporosis, medications to treat osteoporosis, and other topics. Additionally, NOF publishes Osteoporosis Public Policy Update covering NOF`s efforts to have Medicare cover bone density testing, Congressional allotment of funding for osteoporosis research, and similar issues. This is sent to volunteers who become "Key Contacts" and NOF support group leaders. Key Contacts are osteoporosis advocates from around the country who communicate with organizations and individuals in their area to make osteoporosis issues a priority on state and federal health care agendas. If you are interested in becoming a Key Contact, call Paige Berry at (202) 223-2226.

NOF produces several brochures and information pamphlets for its members and for the public. If you call NOF with questions about osteoporosis, someone can send you the appropriate brochure to answer your questions.

In summary, NOF gives people with osteoporosis an abundance of information, both for themselves, and to share with others. I have joined and suggest all of you examine what NOF membership might offer you, too.

Disclaimer

Jerome C. Donnelly
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