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

Fall greetings to everyone

What`s new?

This study is by Economides PA and others, Endocr Pract. 2000;6:351-6. The authors retrospectively reviewed cases of 142 females diagnosed with osteopenia or osteoporosis based upon BMD studies after referral by 50 internists or gynecologists. They found that 20.4% of the patients had no further diagnostic tests, while 27.8% had only mammography. Of all patients with osteoporosis, 10.6% received no therapy other than calcium or vitamin D. Only about 11% to 14% of patients were referred to a metabolic bone disease specialist for further testing. The authors conclude: "Our study indicates the need to emphasize that patients with the diagnosis of osteoporosis should always undergo assessment to rule out secondary causes of the bone loss. In addition, osteoporosis should be treated with pharmacological agents as well as calcium and vitamin D."

The American Association of Clinical Endocrinologists, AACE, recommended in 1996 that all patients diagnosed with osteoporosis should undergo laboratory testing to rule out secondary causes of osteoporosis. In women, the obvious conclusion is loss of hormone production due to menopause, but clinicians must be cautious to not overlook other not so obvious causes. In men there may be no obvious conclusion as to the cause, therefore, thorough testing is also extremely important. And, in either men or women, if osteoporosis is diagnosed, treatment should include something more than vitamin D and calcium supplements. Neither has been shown effective in treating osteoporosis, but are used only as adjuncts to other therapies such as hormone replacement therapy, bisphosphonates, or calcitonin.

There are probably many reasons for the problems noted in this study. It may not have been an oversight by the physician that prevented patients from receiving proper therapy. Possibly the women just refused it due to fear of complications or for other reasons. Patients might not have been referred to metabolic bone disease specialists because they refused the referral. I have heard from at least one female who reports the Web bulletin boards are full of negative comments about treatment women have received from their endocrinologists. They report not being listened to, not being able to ask questions, being treated with disrespect, etc. I can only say that I have seen five different endocrinologists about my osteoporosis and all have been professional, competent, and willing to listen to my thoughts.

My recommendation is that once you find you have osteoporosis, or suspect you have it, seek a referral to someone specializing in the diagnosis and treatment of that disease. That could include an endocrinologist, rheumatologist, orthopaedic physician, or others. Be sure you have a complete battery of testing done to find any and all causes of your osteoporosis. Preferably get started on therapy with the specialist, verify it is working, and then continue follow up care with your primary care (or other) physician. Men can reread the segment on the minimum number of diagnostic tests that should be done in the 13th newsletter: http://www.maleosteoporosis.org/13nl.htm. It is covered in the fourth paragraph entitled Osteoporosis in Men.

Fosamax effective for men. I reported that a study had shown Fosamax was effective for men in the January 2000 newsletter, http://www.maleosteoporosis.org/13nl.htm. At that time, the results were not yet published. Please note that the study by Orwoll E and others has been published in N Engl J Med 2000 Aug 31;343(9):604-10, UI:20403831. In conjunction with the August publication, I was asked to do a portion of a video for Merck to be used as a press release for the media. I have been informed that the video went out to 171 TV stations and was seen by about 50 million Americans. So, this study, and the video, should have done a lot to make men aware that they are at risk for osteoporosis and that effective treatment is available if they develop it.

Ask the experts

Question. I asked Dr. Karen Kolba, our expert on osteoporosis-related issues, about the significance of luteinizing hormone (LH) and follicle stimulating hormone (FSH) for men. These are generally thought of as important hormones for women, but their levels are also tested in men. I wondered about their function in men and if they could be depressed due to testosterone injections, and, if so, how much of a concern is that? Note that Dr. Kolba requested the input of Dr. Veronica Piziak, Chief of Endocrinology at Scott and White Clinic in Temple, TX for portions of this answer. Thanks to both doctors for their time and assistance to the men`s support group.

Answer. In males FSH stimulates sperm production and LH stimulates testosterone production. Yes, it could be that testosterone shuts off the pituitary, thus lowering both LH and FSH. But, they could have been low from the beginning. Many men develop secondary hypogonadism such that it is the pituitary and not the testes that have insufficient activity. There is no need to be concerned about low LH and FSH in males as long as the free testosterone level is normal and the individual feels fine. LH and FSH don`t follow the same rules as other brain hormones such as thyroid stimulating hormone (TSH) or Adrenocorticotropic hormone (ACTH). TSH will go up and down according to the amount of thyroid hormone the brain perceives it is sensing. ACTH also behaves this way in relation to cortisone levels. But, LH and FSH are odd and don`t always respond to circulating hormones normally. For instance, in post menopausal women, both of these hormones are very elevated. Yet they never come back down, even if a woman is taking adequate doses of estrogen.

Literature review

Comment. A common theme in this newsletter is that men with osteoporosis should educate themselves about osteoporosis and become adept at using the Internet to that end. The reasoning for this is very apparent as I searched the PubMed literature this month and found twenty-one pages with 405 abstracts when I searched the last 90 days using the word osteoporosis. No one can keep up with that volume of information. I would hope that your physician would appreciate the fact that you care about your health if you bring in copies of abstracts that pertain to your condition and have questions about the articles as they pertain to your health

Milk basic protein (MBP). This is a very interesting article from Japan that shows that calcium isn`t the only constituent of milk that promotes bone health. See Toba Y and others, Milk basic protein: a novel protective function of milk against osteoporosis, in Bone 2000 Sep 1;27(3):403-8, PMID: 10962352. (Note: use the PMID, numeric portion only, just as you would use the UI number in the search query block at PubMed, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=&DB=PubMed). The authors found that, using an unfractionated bone cell culture system, the milk whey protein, especially its basic fraction (MBP), suppressed bone resorption. Using aged ovariectomized rats and controls, they found that rats fed 0.1% MBP diet had significantly higher BMD than controls and that more breaking energy was required to break the excised femurs of the MBP-fed rats. The authors conclude: "These results suggest that MBP suppresses the osteoclast-mediated bone resorption and prevents bone loss caused by ovariectomy." Future studies in humans should be interesting. Obviously, what works in rats doesn`t necessarily work in humans, too.

Nonresponders to alendronate. I get an occasional e-mail from men who appear not to be responding to Fosamax therapy. In fact, I have outlined in the April 2000 newsletter, http://www.maleosteoporosis.org/14nl.htm, several suggestions that might relate to that problem. One of those suggestions was to consider I.V. bisphosphonate therapy to bypass the G.I. tract. This issue is addressed in a study by del Puente A, and others, Intramuscular clodronate in nonresponders to oral alendronate therapy for osteoporosis. J Rheumatol 2000 Aug;27(8):1980-3, UI: 20410308. The authors studied 60 postmenopausal osteoporotic women who were not responding adequately to therapy after one year on oral alendronate. The women were divided into two groups: one to receive once-weekly I.M. ibandronate injections, and the others to continue with oral alendronate. After one year, the ibandronate group had statistically significant improvement in BMD compared to the oral alendronate group. So, if you are not responding adequately to oral Fosamax, discuss I.V. bisphosphonate with your physician. But, remember that studies have also shown a tendency to regress to the mean over time when using oral Fosamax. That is, slow responders speed up in subsequent years, or vice versa.

Intermittent alendronate therapy. This is an interesting study by Rossini M and others entitled, Effects of two intermittent alendronate regimens in the prevention or treatment of postmenopausal osteoporosis. Bone 2000 Jul;27(1):119-22, UI:20324970. The study was aimed at patients needing to preserve or maintain previous increases in BMD with lower drug doses that would produce fewer side effects and have improved compliance. It involved 123 postmenopausal women aged 52-75 with a BMD in the spine or femoral neck of -2 S.D. below young normal individuals and no history of a osteoporotic fracture. Patients were assigned to a group taking calcium and vitamin D alone, or along with two different intermittent oral alendronate regimens: 20 mg once weekly or 10 mg daily for one month out of three. Results after one year showed significant increases at both the spine and femoral neck in both treatment groups with very similar results for both intermittent treatment methods. The authors state: "In conclusion, intermittent alendronate administration at cumulative doses (and costs) three times lower than those currently recommended for osteoporosis treatment is very well accepted, and is able to significantly increase BMD at the spine and femoral neck and to decrease the markers of bone turnover." This treatment method would appear to be acceptable to treat individuals in the osteopenic range without a history of fracture. And, it seems to be a cheap and effective way to maintain BMD once adequate levels are attained for those who were at least -2.5 S.D. below young normal BMD at one time. The 20 mg once-weekly dosage should be the preferred method since it was as effective as taking 10 mg once daily for one out of every three months, is cheaper, and simpler.

Dietary protein deficiency. This article is pertinent in view of the dietary discussions in this current newsletter wherein excess protein is implicated by some as a means of loss of BMD. It is by Bourrin S and others, Dietary protein deficiency induces osteoporosis in aged male rats. J Bone Miner Res 2000 Aug;15(8):1555-63, UI:20390311. Older rats were fed either a diet with 15% casein or 2.5% casein for 1-7 months. BMD, bone ultimate strength, stiffness, and absorbed energy were measured in tibial proximal metaphysis and diaphysis. Also, histological analysis was done at the same sites. The authors found that, "In proximal tibia, isocaloric low-protein diet significantly decreases BMD (12%), cancellous bone mass (71%), and trabecular thickness (Tb.Th; 30%), resulting in a significant reduction in ultimate strength (27%). In cortical middiaphysis, a low-protein diet decreases BMD (9%) and enlarges the medullary cavity (36%), leading to cortical thinning and lower mechanical strength (20%). In cancellous bone, protein deficiency transiently depresses the bone formation rate (BFR; 60%), osteoid seam thickness (15%), and mineral apposition rate (MAR; 20%), indicating a decrease in osteoblast recruitment and activity." This certainly confirms Dr. Heaney`s statements on the importance of protein to bone formation mentioned in this newsletter`s discussion of diet and osteoporosis. So, although there is potentially some risk of excess protein negatively impacting bone formation, the far greater risk appears to be inadequate protein consumption.

Adverse effects of corticosteroid therapy. I have often mentioned the need for greater awareness of the adverse effects of corticosteroid therapy on bone formation by the medical community when prescribing corticosteroids. Another Australian study confirms this problem, finding only 11% of all patients on oral corticosteroids and 21% of those who had been taking oral corticosteroids for at least one year had documented evidence of bone mineral density testing being performed in the past in the hospital. See Hougardy DM and others, Is enough attention being given to the adverse effects of corticosteroid therapy? J Clin Pharm Ther 2000 Jun;25(3):227-34, UI:20344858. I`m afraid that a concerted effort to educate physicians is needed starting with the medical schools, medical associations, and disease-related associations such as the National Osteoporosis Foundation. It is unacceptable to have patients develop osteoporosis due to corticosteroid use in this day and age.

Diet and osteoporosis

Protein, dairy, and osteoporosis. I occasionally get e-mail from people who believe that dairy products either don`t help prevent osteoporosis or actually might help cause it. A brief look around the Internet will show that there is a vocal anti-dairy group out there. There are some recent articles that apply to this topic that I will discuss in this segment. Since all but one of these are quite comprehensive reviews, I will certainly not discuss them in detail. For you to get the most out of them, I suggest you get copies and read the entire articles. You can take the information I supply below to your local library and they should be able to get free copies from the National Library of Medicine if they aren`t otherwise available to you locally.

A common thread I`ve heard or seen in anti-dairy materials is that dairy`s protein content causes loss of bone mineral density. So the first articles will discuss this issue. They were presented at the annual meeting of the American Society for bone and Mineral Research, September 10, 1997, Cincinnati, OH. There are three articles in the entire review and all are published in J Nutr 1998;(12). Does Excess Dietary Protein Adversely Affect Bone? Symposium Overview by Massey LK, is on pages 1048-50, UI: 98279110. Excess dietary protein can adversely affect bone, by Barzel US and Massey LK, is on pages 1051-53, UI:98279111. Excess Dietary Protein May Not Adversely Affect Bone, by Heaney RP is on pages 1054-57, UI: 98279112 . I`ll start with a summary of the reasoning from Barzel and Massey of how excess dietary protein can adversely affect bone.

They point out that previous studies have shown that the typical American diet is an acid-ash diet, meaning it creates acid in the process of metabolism because it is high in protein and low in fruits and vegetables. The acid formed is mainly phosphate and sulfate and can create more than 100 mEq of acid daily. The body`s buffering system to neutralize acids is the skeleton, which dissolves calcium as the source of positive ions to handle the acid. The acid generated is excreted in the urine, with some foods able to generate much more acid than others. A 1994 article by Remer T and Manz F, J Am Dietetic Assn 1995;95:791-7, UI:95318420, describes the potential renal acid load (PRAL) of foods and lists that figure for many commonly eaten foods (the higher the number the more renal acid it generates-and the more calcium that could be lost from bone). For example, fats and oils have a PRAL of zero, fish has 7.9, meat has 9.5, milk has 1.0, high-protein cheese has 23.6, and most vegetables and fruits give a negative number of about -1.0 to -5, but with some has high as -21. This means they actually act to neutralize the body fluids in and of themselves and would thus have no ability to cause loss of calcium from bones.

The article by Remer and Manz (which is one that I highly recommend you get) shows the PRAL for many foods and beverages. But, it also has a simplified list of the most commonly consumed items with the PRAL for 100 grams consumed (3 oz. would be about 90 g). This short list could be used to figure the PRAL of meals and has been shown to correspond pretty well with the more complex total food list PRAL. For example: Fats and oils have no PRAL; fish have 7.9; fruits and juices have -3.1 (except dried fruits have a much lower number, e.g., raisins -21); bread has 3.5; flour 7.0; noodles 6.7; meat has 9.5; milk has 1.0; soft cheese has 8.0; hard cheese has 23.6, and vegetables have -2.8. Figure the PRAL of several of your meals to get an idea how much calcium you might be losing daily. The higher the number the more you are losing if you are keeping calcium intake at a constant rate.

The Barzell and Massey article also alludes to a recent study that showed the effect of acidosis from protein in the diet by comparing urine calcium levels in vegetarian, ovovegetarian, and animal protein diets. The animal protein diet contained 6.8 mmol more sulfate and the urine pH was more acidic, 6.17 vs. 6.55. Daily urinary calcium was 47 mg higher when those young adults were consuming an animal protein diet vs. the vegetarian diet. Thus implying that 47 mg of calcium was lost from the bones of those eating the animal protein diet daily. They cite another study showing a similar effect when older adults were fed a high protein diet, showing that the calcium balance was positive on the low protein diet, but then became negative when participants consumed the high protein diet. And, they show that when people are maintained on a constant-protein diet, and then fed triple the amount of fruits and vegetables, the calcium loss in the urine dropped from about 157 to 110 mg/day. This shows the power of fruits and vegetables to act as buffers, too.

So how do you interpret this urine calcium loss into an understandable form? The authors state, "The long-term consequence of a small change in calcium balance is substantial. A 50-mg increase in urinary calcium loss per day will result in a 18.25-g loss per year, or 365 g over 20 y. Because the average adult female skeleton contains 750 g calcium at its peak, this is a loss of one half of total skeletal stores! For a male with a store of 1000 g calcium, this is about one third of the total."

The authors conclude: "In summary, a diet high in acid-ash protein causes excessive urinary calcium loss because of this acid content; calciuria (urine calcium loss) is directly related to urinary net acid excretion. Alkali buffers, whether chemical salts or dietary fruits and vegetables, reverse this urinary calcium loss." But, as I said, this symposium has another viewpoint, so now let`s go on to hear the other side of this issue from the Heaney paper.

First, it is noted that bone is made up of about one-third protein and is one of the most protein dense tissues in the body. Bone growth is stunted if the diet has inadequate protein, and elderly patients heal much better after hip fracture if given protein supplements. For these and other reasons, Heaney notes, "Far from having an adverse effect, protein intake would seem to be good for bone."

Heaney shows a diagram to explain the biphasic nature of protein intake and explains that it is similar with almost all nutrients. That is, too small a dose is harmful, a wide range of doses in the mid-range is helpful, and too large a dose is harmful, too. The question is then, "Is there harm associated with high [protein] intakes?" Then he rewords this question to be more appropriate, ". . .are protein intakes at the upper end of the range likely to be found in the population harmful?" It is accepted that high protein intakes can affect bone minerals, but do they do so in the real world?

An important issue in this problem is that, ". . .protein intake is strongly positively associated with calcium intake in mixed diets (Holbrook and Barret-Connor 1991)." So it is reasonable to assume that the negative effect of increased metabolic acidosis caused by high protein meals in real world situations might be overcome by the added calcium eaten with the protein. That is, the extra calcium is absorbed into the body and makes up for that lost in the acidic urine.

Heaney shows a table of eight recently published observational studies and explains the results. "Two showed no association between protein intake and either osteoporosis or bone loss; three showed a positive association between protein intake and bone mass, i.e., high protein was associated with better bones; three showed a negative association." So, the prospective study data is not clear on this topic. However, the research in metabolic laboratory studies is much clearer, showing that a doubling of protein intake produces a 50% increase in urinary calcium. Some feel that real foods might produce a different result than that of protein isolates that were used in these studies. Through an intricate and complex argument Heaney explains that thinking is not valid. He also cites a study done in his lab on middle-aged women eating real foods that gave the exact same mathematical relationship in relation to protein intake and urinary calcium excretion as those using protein isolates. Heaney concludes, "Thus, there is reasonable certainty that calcium excretion rises as protein intake increases. Therefore, the question must be the following: does this change adversely affect bone? I have already alluded to one reason why it may not, i.e., the fact that increased protein intake in self-selected diets is often associated with increased calcium intake as well. Therein lies the clue to answering this question."

Heaney cites an example of the body`s ability to adapt to high protein intake by secretion of parathyroid hormone which stimulates additional intestinal absorption of calcium to replace that lost by the bone while neutralizing the protein-caused acidity. The body`s ability to adapt to the excess protein depends upon the amount of calcium in the diet since calcium is absorbed at a set fraction of the amount eaten. For example, for someone eating an extra 140 g of beef every day, protein intake would increase by 40 g, and endogenous calcium loss would increase by 36-40 mg/day. In this example, if 1500 mg calcium is ingested during the day, 27 mg of extra calcium would be absorbed. But if only 250 mg/d calcium is eaten, then the additional amount absorbed would only be 4.5 mg. This clearly shows the importance of relating calcium intake with that of protein to understand the entire issue. As long as high protein intake and high calcium intake go together, then there will be no problem with bone loss in a population. It is only when they are out of balance that excessive bone loss can occur.

It is suggested that diets be recommended not on their protein content but on the calcium-to-protein ratio. A suggested ratio (not necessarily ideal) would be 20:1 (mg calcium/g protein) which is derived from the Food and Nutrition Board 1997. Heaney points out that several studies that evaluated women`s dietary intakes found an actual ratio of 9.3:1 for median intakes in 50-59 year-old women. This is less than half the suggested ratio. Is protein the villain or calcium? Heaney concludes, "The population intakes of protein would have to be reduced to frank deficiency to reach a 20:1 ratio at prevailing calcium intakes."

So, I`d now like to take a look at milk and dairy products from the standpoint of their ratio of calcium to protein and their ability to evoke increased urinary acid excretion as indicated by the PRAL numbers as mentioned in the Remer and Manz article above.

PRODUCT	PROTEIN/G	CALCIUM/MG	PRAL	RATIO*
Buttermilk	3.5	109	0.5	31
Cheddar Cheese	31.5	840	26.4	26.6
Cottage Cheese	13.8	73	8.7	5.2
Soft Cheese	8.6	110	4.3	12.7
Whole Milk	3.2	115	0.7	35
Parmesan	39.4	1,200	34.2	30
Yogurt	5.7	200	1.5	35
Ice Cream	3.6	130	0.6	36
Skim Milk	9	300	1.2**	33

NOTES:

1. *Any number greater than 20 would mean this meets Heaney`s recommended standard ratio for protein/calcium content of at least 20:1.

2. **The article didn`t include skim milk and I am estimating its PRAL

From the discussion in the review, what stands out in this table is the scarcity of dairy items with an inadequate calcium-to-protein (CP) ratio. There are several that have high PRALs, but the highest of those also have excellent CP ratios. That would mean a higher absorbed calcium dose that should more than make up for the higher renal acid load, thus still maintaining relatively positive calcium balance. I interpret this data as meaning that milk or dairy products in and of themselves would thus have little ability to decrease bone mineral density. Someone eating nothing but soft cheese or cottage cheese would be more at risk. Note that this cottage cheese is full-fat cottage cheese, and I assume that fat-free would have more protein and calcium. What the final PRAL and CP ratio would be, I don`t know for sure.

The last study I want to discuss is also by Heaney RP, Calcium, Dairy Products and Osteoporosis. J Am Coll Nutr, 2000 Apr, 19(2 Suppl) 83S-99S, UI:20220885. This article reviews 139 papers published since 1975 concerning studies on the relationship of calcium intake and bone health. It includes an excellent summary of the difference between observational studies and investigator-controlled studies and the significance and importance of each. Basically, investigator-controlled studies allow causal inferences to be made. Observational studies are not nearly as strong concerning cause and effect conclusions. Heaney points out that all but two of the 52 controlled studies showed better bone balance, greater bone gain during growth, reduced bone loss in the elderly, or reduced fracture risk at high intakes of calcium. About three-fourths of the observational studies were also positive. Heaney points out that osteoporosis is a multifactorial disease, with dietary calcium (from dairy or other sources), or from supplements, being just one of many possible adjuncts to maintaining good bone health.

In summary, if you are concerned about calcium, protein, and dairy intake and the effect of diet on osteoporosis in general, I highly recommend these five articles. Since all but the article by Remer and Manz are reviews, you will have hundreds of other references should you wish to investigate those, 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