Let me start with the scary and necessary-to-know statistics: Osteoporosis affects 10 to 12 million people in the US and forty million have low bone density (osteopenia). In 2005, over 2 million fractures were diagnosed. One in three Caucasian women over 50 will experience an osteoporotic fracture in her lifetime. (Whites and Asian women tend to have a lower bone mass than women of other ethnicities.) We also “out fracture” men (who have thicker bones) by a factor of 1.6.  And if a woman fractures her hip, she has a 20% chance of dying within a year. Osteoporosis is a very disabling, costly, and yes, mortal disease.

There has been a welcomed increase (both medically and financially) in pharmaceutical therapies that help avoid and/or treat osteoporosis. By now, you have all seen the ads and articles for the various bisphosphonates including oral alendronate (Fosomax), risedronate (Actonel) and ibandronate (Boniva) which can be used daily, weekly or monthly. There are also intravenous bisphosphonates that can be administered every 3 months or just once a year.

Then came the media outcry about potential side effects that these medications could cause….jaw necrosis, perhaps atrial fibrillation and more recently “atypical” fracture of the femoral shaft (long, upper leg bone), especially after long term use. I want to address the latter concern in this article.

Remember, these medications work by binding to the bone, preventing cells called osteoclasts from drilling minute cavities that make the bone porous. Cells called osteoblasts then do “their thing” and fill the cavities up. When stable, the drilling and filling are equal and thus maintain bone structure and strength. However if the drilling outpaces the filling, there is bone loss. This occurs with age (unfortunately after 30), and is accelerated by lack of estrogen (menopause) certain medications, especially steroids, diseases and the “wrong” genes. It is also aided and abetted by lack of proper nutrition.

Just to reiterate, bisphosphonates help stop the drilling and with time those minute cavities that made the bone porous get filled, diminishing the risk of fracture. We now know that these bisphosphonates attach and remain in the bone performing this job for years after being discontinued.

Recent cases have appeared in medical journals in which the femoral bone fractured in a horizontal fashion without prior significant trauma. In most instances, the patients were taking long term bisphosphonates.  How concerned should we be about this newly media reported “atypical” femur fracture?

An article in the May issue of The New England Medical Journal may help allay physician and patient concerns. It concludes that this type of fracture is truly rare. The authors used data from 3 randomized and placebo-controlled, prospective studies involving 14,195 women and 55,000 person years of observation. The risedronate data that they reviewed provided up to 10 years of study. All together, they found a total of 12 fractures in 10 patients that were classified as possible “atypical” femur fractures. (To be accurate, they were called subtrochanteric or diaphyseal fractures). The incidence came out to just 2.3 per 10,000 patient years. The authors also calculated that treating 1,000 women who had osteoporosis for 3 years would prevent about 100 fractures (including 11 hip fractures), a benefit that way exceeded the risk of “atypical” fracture, if indeed it was caused by the bisphosphonates.

So what does this mean? Well according to an editorial that followed the article, “physicians should not rush to judgment and stop prescribing bisphosphonates because of concern about atypical femoral fractures.” They should, however, reevaluate patients who have received long term therapy in the context of contemporary guidelines. (And for these please see my previous website article that discusses the use of FRAX to determine for whom and when to start therapy.)
I now review the FRAX indications for each patient who is at risk for osteoporosis. If she is a candidate for medication I will prescribe it, but carefully follow her with tests to check for bone loss. If she is stable for a number of years (usually 5 years) I suggest stopping the medication or at least taking a drug holiday. The good of the bisphosphonates still outweighs a possible bad, at least for those who need it.

Now, although I usually end my weekly newsletter with just one article, I have to mention another that just came out in JAMA. It also dealt with bone fractures. As we now all know, Vitamin D has become the vitamin “De jour”. The amount of D found in up to 70% of American is inadequate; low levels have been associated with osteoporosis, heart disease and a number of cancers. I ask all my patients about their Vitamin D intake (and exposure, remember you can get it though sun rays) and repeatedly advise them to take at least 1,000 international units (IU’s) daily.  I often check Vitamin D levels with a blood test, especially if there is a history of low bone density. For those whose level is found to be extremely low, I prescribe 50,000 units of Vitamin D-2 a week or every other week for several months, and then recheck their levels. If they have achieved a D level that is sufficiently high, I have them continue with an OTC supplement of up to 2,000 units daily.

Researches in Melbourne, Australia tried to maximize Vit D administration by giving elderly women considered to be at high risk of fracture  a dose of 500,000 IU of Vitamin D orally once a year.  They carried out a double-blind, placebo-controlled trial in 2256 women aged 70 or older. Half were given this very high yearly dose for 3 to 5 years; the others were given a placebo. There was no difference between the 2 groups with regard to calcium intake (indeed it increased for both). But contrary to expectations the group that received the high dose Vitamin D experienced 15% more falls and 26% more fractures than the placebo group. And the increase in falls was most apparent in the 3 months after they were given high dose Vit D! Frankly, the authors couldn’t explain this but went on to suggest that dosing should be more frequent and at lower doses. So far I (and most of my colleagues) will probably stick to advising daily 1,000 units or more of D and if your levels are low that you increase the dose (with a prescription) on a weekly or biweekly schedule. But I doubt we will prescribe that single oral dose once a year. So please continue to use D and calcium on a regular basis for better bones. And if necessary, go ahead and take that bisphosphonate that I or another doctor may have prescribed. The bones you strengthen will be there to stand you in good stead!

A major concern for the majority of women in their late 40’s and early 50’s has been whether and when to start hormone therapy. (Note it used to be called hormone replacement therapy, but the experts now agree that this term suggests that the menopause transition is an endocrine deficiency disorder and not a natural change in our hormonal and reproductive status, so the word “replacement” is out.)  I concur with the current PC terminology, but should point out that 80% of women experience symptoms related to this menopause transition as their estrogen levels plummet. The most common symptoms are hot flashes and night sweats (called vasomotor symptoms or VMS).  Add vaginal dryness, sleep problems (either due to the hormonal transition or to the stresses we face in mid life), mood changes and even a sense of diminished focus and quality of life and it’s clear that for many women, lack of estrogen production in the menopause creates sufficient physiologic and psychological havoc that they want to do something about it. That most effective something has been hormone therapy; estrogen (as pills, patches, creams, sprays. vaginal tablets and rings) and if a uterus is present (i.e. no hysterectomy) some form of progesterone (again as pills, patches, creams, drops or vaginal gels).

Since the Women’s Health Initiative was publicized, women have been encouraged by the FDA and just about every other official agency that reviews the research on hormone therapy, that if they chose to take hormones, they take the smallest effective dose for the shortest duration, preferably no more than 5 years. That “magic|” 5 year mark has been suggested because it’s felt that menopausal symptoms resolve in most women after 5 years. (Much of the “this-won’t last” data comes from women who have chosen not to take HT and have been followed for years to see what happened to their symptoms.)

Many women don’t want to wait for symptoms to resolve, especially if they are not guaranteed a finish date. Indeed some research has shown that 15% of women continue to have symptoms in their 70’s. Twenty five to 50% of women who stopped hormone therapy after the Women’s Health Initiative resumed therapy. Those most likely to do so had severe symptoms before they started HT, were obese, younger at time of menopause, African American, smokers or physically inactive.

When it comes to “it’s time to stop your hormones” advice I generally suggest that quality of life vs. risk be considered: will you feel lousy enough without hormone therapy to counter the possibility of an increase in your risk for breast cancer with long term (probably more than those 5 years) use of HT?  I also explain that estrogen has positive effects on bone mass and in the first years of use is probably heart protective. |But as the years pass and other factors affect our cardiovascular system, estrogen may no longer afford the same cardiovascular protection.

So what is a woman (who has been happy on her hormone therapy) to do? Should she try to “wean off” or just stop after that arbitrary 5 years?  A new article in the Journal Menopause tried to address this in a scientific fashion.  A study was conducted in Sweden in which the researchers recruited women to stop their hormone therapy “cold turkey” or do so gradually by taking it every other day. They wanted 200 women for the study, but when faced with the idea of stopping their hormones, many refused and they could only find 87 volunteers!  At the end of 4 weeks there was no difference in the symptoms of the women who abruptly stopped and those who tapered and then discontinued.  And because vasomotor symptoms came back for many, within 4 months 30% of the participants resumed their hormone therapy and after 1 year that number had risen to 50%!

Now to my clinical experience… I try to lower the dose of HT for most of my patients after they have taken it for 5 years. (This necessitates a discussion of the possible risks associated with long term use). If a patient is amenable, I prescribe a dose that is lower than that which she has taken and suggest she try it for 4 to 6 weeks. Some of my patients can then keep lowering their dose until they successfully stop and have no symptoms. Others state that although their symptoms resumed “they were not that bad” and they try to stop HT for good. But I do have patients (about 30%) who feel pretty awful, either on a lower dose or once they stop. I then suggest that they continue at the very lowest dose that allows them to keep their symptoms under control.  (And in their next visit I will revisit the risks and benefits of long term hormone therapy. Basically we are agreeing to procrastinate.) As long as we have a frank discussion about the pros and cons of long term HT, the final decision should be made on an individual basis.  Unless there is a truly health threatening reason that dictates that she stop, issues regarding her quality of life (and life style) have to be considered.

The terror of osteoporosis has by now, been embedded in our female (and male) psyche. Hip fractures can lead to death and/or permanent disability. Spinal fractures lead to severe pain and loss of physical stature which has helped lead to that demeaning portrayal of aging women as “little old ladies”. There are a plethora of ads that make us want to do something. So I thought I would try to do my part by writing this 101 on bone loss. Don’t forget osteoporosis is a life altering disease with huge financial burdens. There are foundations and institutes that solely deal with this disease. For more information you can go to http://www.nof.org

Our bones comprise a living tissue that is always under flux. Their form and composition is determined by cells that lay down new bone (osteoblasts) and cells that act as “pac-men” and chop away causing bone resorption (osteoclasts). Put simply there is on-going filling and drilling. If all is well in our bones’ environment (normal menstrual cycles and estrogen production, adequate nutrition, no underlying disease and no adverse medications) the filling usually outpaces the drilling, at least until we reach the age of 30. This is our age of best bone mass. But when the drilling overcomes the filling, our bone mass diminishes and our bones become weakened (osteopenia), eventually porous (osteoporosis) and may finally may break.

The process of drilling and bone loss is somewhat complicated. Forgive me if I use some technical terms here. There are pro-resorptive hormones that act via their receptors on the bone building cells to induce something called RANKL. When there is enough “free” RANKL, it is able to activate RANK on precursors of the bone eating cells (remember they are called osteoclasts). RANK then stimulates these pre-osteoclasts to fuse together and differentiate into mature osteoclasts. Free RANKL also activates these mature osteoclasts “telling” them to resorb bone. To make matters worse free RANKL then protects these bone gobbling cells from dying! They can keep going on and on…like that energizer bunny.

We seem to have a bad guy in this bone story…it’s excessive free RANKL which gives the go ahead for bone eating cells to develop, multiply and resorb bone. It can get nasty. Although destruction of bone may be necessary for formation of new bone, its unopposed course has been countered.  RANKL can be rendered inactive if it is bound up. (Think Samson with his hair shorn.) The substance that does the binding and deactivation of RANKL is called OPG (I know this gets too full of initials, but it’s easier to use than the full word… osteoprotgerin).

Estrogen reduces RANKL production and increases the synthesis of OPG (at this point I have to say OMG). The estrogens we produce during our reproductive lives have helped prevent free RANKL from encouraging osteoclasts to eat away at bone. Indeed when we lose our estrogen production at menopause, free RANKL is released and during the first 5 to 6 years of menopause, most women lose 2 to 3% of their bone mass each year.

The most commonly used medications for osteoporosis, the bisphosphonates (Fosomax, Actinel, Boniva and Reclast to name a few) reduce the function but not the number of activated osteoclasts. The FDA is currently considering a medication that actually targets the RANKL pathway and stops osteoclast development. More on this (and comparisons of therapeutic medications) in future newsletters….

Several months ago I wrote a newsletter on the current recommendations for osteoporosis therapy based on the World Health Organization (WHO) Fracture Risk Algorithm, (FRAX). We no longer use a bone density test as the sole indicator of fracture risk. (See the article titled “Assessing Our Bone Strength” in the newsletter archives).

Now where does calcium and Vitamin D come into our bone health picture? Deficiencies of either will prevent bone formation by the osteoblasts. Both calcium and Vitamin D are necessary for the complex pathway that leads to bone “creation” and maintenance.

Let’s start with Vitamin D… It is produced in our skin as a result of UV radiation from sun rays. The darker our skin, the less the UV rays get absorbed. Those of us, who are dark skinned, are not sun exposed (think winter on the East Coast) or who effectively block the sun with clothing or sun block will get less than the recommended Vitamin D. Vitamin D is added to milk products, calcium supplements and multivitamins but the amount is often not enough. More than half of healthy adults have blood Vitamin D levels that are lower than that which is recommended for fracture risk reduction (30ng/mL of 25 OH Vitamin D). Many bone experts now recommend that we take at least 1,000 IU of D3 (which is over the counter type of Vitamin D) and if older than 65, to take 2,000 IU a day.

Because of the high prevalence of Vit D deficiency, I check 25OH Vitamin D levels on many of my patients, especially those who are found to have low bone densities. If a deficiency is found I prescribe 50,000 IU of D2 weekly for 2 to 3 months, then recheck the blood; if the level has risen sufficiently I tell my patient to resume standard dosing. If, however she has had a fractured hip, I increase Vitamin D until her blood level is 40 to 60 ng/ml.

Now what about calcium? Some of the newer studies seem to show no benefit of calcium intake greater than 800mg per day in women who are NOT vitamin D deficient. But when we talk about essential intake of calcium we have to consider its absorption and bioavailability. Many medications interfere with calcium absorption. These include (especially when taken at the same time as a calcium supplement) fiber, H2 blockers and protein-pump inhibitors (that treat acid reflux), corticosteroids and anticonvulsants. Moreover, there can be adverse interactions between calcium supplements and several medications if they are taken together: Calcium may cause a decreased absorption of iron, zinc and magnesium. Calcium also reduces thyroid, tetracycline and quinine antibiotic absorption.  And it turns out that caffeine increases urinary calcium excretion.

The amount of calcium we absorb in supplements also depends on the type of calcium we take. The most common, calcium carbonate, requires stomach acid for absorption. (Hence the manufacturers recommend taking it with food). But as we get older we naturally produce less stomach acid. And to add insult to getting an older and crankier GI system, gastric acid is reduced by all those medications we take to treat our acid reflux. So I recommend that my older patients and those who take acid reflux meds supplement their calcium intake with calcium citrate for better bioavailability.

Yes this is complicated…But now that you understand a bit more about what your bones go through to carry you though your life, I hope you will treat them with respect and provide them with their essentials. If you are at risk for bone loss and fracture make sure you discuss tests and therapies with your physician (and if you are my patient, with me). It’s never too late to support your support.

Ask any woman…as she traverses her “”f” years…the forties and fifties and then gets to the “S” decades (or watches her Mother or Grandmother get there) she worries about memory loss, Alzheimer disease or other forms of dementia. Surely there is something we can take to prevent or at least forestall these dreaded disorders of maturity! And wouldn’t it be great if that something were obtainable without a prescription…and, to use that magic marketable word, natural. Well according to the advertisers (and the salesperson at the vitamin and herb counter) there is; and many of us (including me a few years back) dutifully took it saying, “You never know, maybe it will help”. We now know a bit more. A study of over 3,000 volunteers aged 75 and older with normal or mild cognitive impairment volunteered for a study carried out in five medical centers in the United States between 2000 and 2008. They received either a 120 mg extract of G. Biloba or placebo twice daily. Neither they nor the investigators knew which they were taking. They were assessed every 6 months over the next 6.1 years for development of dementia. The end result: Ginko Biloba did not prevent Alzheimer disease or other forms of dementia.

We would all like a simple herb or medication to keep our minds in thinking, enjoying, remember and adapting order. This important study indicates that Ginko Bilboa is probably not that mind preserver.