The CDC, most medical journals, and mainstream media have been covering the disastrous infections caused by the contamination of the steroid that was distributed by a compounding pharmacy in New England. Three potentially contaminated lots of this steroid were used by physicians in epidurals, and joint injections in over 14,000 persons. They have, so far, caused stroke, meningitis, bone infections and in some instances death, in over 137 patients.

The initial detection of this serious contamination reads like a detective story. On September 18, 2012 the Tennessee Department of Health was alerted by an observant physician that a patient had a confirmed fungal infection (to be exact, Aspergillus fumigatus) diagnosed 46 days after epidural steroid injection. By September 27, an investigation carried out by the Tennessee Department, in collaboration with the CDC and the North Carolina Department of Health, had identified 8 more cases. All nine patients had received epidural steroid injections with preservative free methyl prednisone acetate solution (MPA) compounded at the New England Compounding in Framingham, Massachusetts. And as of October 10 (when last reported in JAMA) a multistage investigation by the CDC together with local health departments and the FDA have identified 137 cases and 12 deaths associated with this outbreak in 10 states. The invoices from the pharmacy showed that approximately 17,500 vials of MPA were distributed to 75 facilities in 23 states!  By October 6, the vials not already used were recalled. And as of October 10, health departments reported that 90% of patients exposed to the medication from one of the suspected infected lots of MPA had been contacted at least once.

The patients and their doctors have been advised that they should get tested if they develop neurological symptoms such as headache, neck rigidity, fever, nausea, unsteady gait or sensitivity to light…and if so a lumbar puncture should be done to check for the fungal infection. Those patients that had joint injections should notify their physician if they develop increasing pain, redness or swelling, in which case fluid should be aspirated from the affected joint for culture. This all sounds ominous and in fact it is! Right now it’s postulated that the incubation periods for infection range from 4 to 42 days, but the maximum incubation for this infection is not known. Treatment with high dose anti-fungal therapy for months may be necessary.

If anyone doubts the importance of the epidemiological sleuthing carried out by our health departments and the CDC…this should dissuade them. And additionally, there is the issue as to whether products from compounding pharmacies are indeed safe. In an article published on December 6 in The New England Journal of Medicine, the authors summarized the evidence for compounding safety…. First, they explain what these pharmacies do: “Pharmaceutical compounding refers to the combining, mixing, or altering of ingredients of a drug by a licensed pharmacist to produce a drug that is tailored to an individual patient’s medical needs on the basis of a valid prescription from a licensed medical practitioner.” They go on to state that ” there are few reliable data on the prevalence of compounding, but it has been estimated that 0.25% to more than 2% of dispensed  prescriptions in the United States are compounded drugs. Under certain conditions, compounding may serve an important public health benefit by providing access to the needs of individual patients when a commercially available product is unavailable; however, compounded drugs are not approved by the FDA and should not be confused with generic drugs all of which must be approved by the FDA before marketing. Compounded drugs are not reviewed and approved by the FDA; therefore, their safety, efficacy, quality and conformance with federal manufacturing standards have not been established…. The regulatory authority of the FDA over compounding pharmacies is different and more limited than is its authority over pharmaceutical manufacturers.”

Bottom line: Thank you to the FDA and CDC. Even though regulations can be burdensome and costly they are worth it; they protect the purity and sterility of our medications. And if I do prescribe a compounded medication, I tell the patient and request that she fill the prescription in a closely monitored pharmacy.

It’s amazing to realize that it was just 10 years ago that the Women’s Health Initiative results were released with extraordinary media brouhaha, causing as many as 70% of women who were taking menopausal hormone therapy (usually Prempro) to cease and desist…and in many instances flush, flash and lose sleep. But with time, additional studies and empathy, the experts (members of the North American Medical Society, gynecology department heads at major universities, and editors of the American Society for Reproductive Medicine and The Endocrine Society to name just some) now agree on key points regarding the safety and efficacy of hormone therapy in menopause. And since the following is generally what I tell my patients, I am delighted to recap the recommendations just published in several of the major journals.

In a overview, they agree that systemic therapy is an “acceptable” option for relatively young (up to 59 or within 10 years of menopause) and healthy women who are troubled by moderate to severe menopausal symptoms. There is no one therapy fits all, and consideration should be given to a woman’s quality- of- life priorities as well as her risk factors such as age, time since menopause risk of blood clots, heart disease, and stroke and breast cancer. Their consensus then deals with individual issues

Hormone Therapy Risks

Vascular risks Although both estrogen and estrogen with progestogen increase the chance of clots (deep vein thrombosis and pulmonary embolism as well as certain types of strokes) the risk is rare in the 50- to 59- year old age group. Moreover, observational studies have found that transdermal estrogen therapy ( with patches, creams, and sprays) and lowdose oral estrogen therapy have been associated with lower risks of these type of clot caused events.
Breast cancer
An increased risk of breast cancer is seen within 5 years or more of continuous estrogen and progestogen therapy. The risk is not great and risk declines after hormone therapy is discontinued. There is even less risk for women who have had a hysterectomy and don’t need to add progestogen to their estrogen therapy. Use of estrogen alone for a mean of 7 years does not seem to increase risk of breast cancer.
Duration of therapy

This is where everyone sites the same sentence: ” The lowest dose of therapy shouldbe used for the shortest anoint of time to manage menopausal symptoms.” they thenadd that duration should be individualized. I add that if more or longer therapy is neededto achieve quality of life, the patient and her physician should discuss this laststatement. And estrogen therapy alone, allows more flexibility in duration. There arereports of increased risk after 10 or 15 years of use in large observational studies.
Additional information

Evidence is lacking that custom compounded bio identical hormone therapy is safe oreffective. Many medical organizations and societies agree in recommending againsttheir use, particularly given concerns regarding content, purity and labeling. Finally thereis a lack of safety data supporting the use of estrogen or estrogen and progestogentherapy in women who have had breast cancer.

Conclusion

Leading medical societies devoted to the care of menopausal women agree that the decision to initiate hormone therapy should be for the indication of menopause-related symptoms.

Bottom line: there is no question that hormone therapy plays an important role in
managing the symptoms so many women experience during menopause. As usual, we
all recommend that therapy be individualized. So talk to your doctor!

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I thought I would start the New Year with a somewhat positive article that came out in the journal published by the North American Menopause Society. The journals’ name is appropriately, “Menopause”. Its cover is bright red…  I am not sure if this is meant to make it stand out or if the color represents hot flashes! I read the journal while trying to catch up on relevant articles during the holidays…these and my recent copies of the New Yorker have kept me mentally occupied. (I know that reading medical literature sounds boring, but actually I like it!)

So here is what caught my eye, and take a deep breath before reading the title; “Hip fracture in postmenopausal women after cessation of hormone therapy: results from a prospective study in a large health management organization”.

This was a study of 80,955 postmenopausal women who were 60 years old or older and had filled hormone therapy (HT) prescriptions at least once between January 2002 and June 2002. They were then followed through December 2008. (It takes years to gather the statistics, so most large studies will have concluded a few years before all of the results are actually published.)  The data on whether the women used HT, for how long,  and whether any antiosteoporotic medication was used, as well as the occurrence of hip fractures were collected from an electronic medical record system. The women in the study population were followed through Kaiser Permanente Southern California, which included 11 Southern California medical centers. (Yes they are huge!)  Bone mineral density was assessed with a DEXA scan in 54,209 women at least once  during the study period.

The results demonstrated that  during the 6.5 years of follow-up   (and after accounting for age, race and other medications), the women who discontinued HT were at a 55% greater risk of hip fracture than the women who continued to use HT.  The use of hormone therapy helped prevent fracture as long as it was used. But, within 2 years of stopping HT, hip fracture increased and the risk of fracture rose incrementally the longer the women discontinued this therapy. Every year that the women stopped HT was associated with a lower BMD (The T score which compare BMD to a 30 year old decreased on average – 0.13 a year.)

The authors concluded that “the public health message to women and physicians is that discontinuation of HT is associated with increased hip fracture risk and lower BMD compared to women who continue to take HT.”

There are many reasons to consider hormone therapy at the onset of menopause. For most women it is prescribed to help them deal with severe hot flashes, night sweats, sleep problems, mood changes and for some a feeling of “walking around in a fog”. There are also reasons to consider stopping after several years…. these include risk of breast cancer as well as a potential decrease in cardiovascular benefits.  The pros and cons of continuing HT for decreased risk of bone fracture should now also be considered. Who said this was easy! But it’s a subject that reaches epidemic proportions as approximately 1 million women enter the menopause each year in the United States.

In the year to come I’ll try to keep you up-to-date on the most recent published articles and studies on this and many other topics.

Have a healthy 2012!

I’ve written several newsletters about potential side effects of bisphosphonates medications used to treat osteopenia and osteoporosis (Fosomax, Boniva, and Actonel….just to remind you of some brand names). This time I want to share some potentially good news about this bone density enhancing class of medications. And I am especially happy to share the report because it comes from a study conducted in Israel. (As many of you know, I have taught and worked there and indeed will be in Tel Aviv when this article appears.)

The Israeli researchers conducted a study entitled The Molecular Epidemiology of Colorectal Cancer. It was supported by the National Cancer Institute and published in the February issue of the American Journal of Clinical Oncology. (I hope I haven’t lost most of my readers by this point…just bear with me. So many of you or your relatives take bisphosphonates so that your skeletons can successfully bear your weight without an osteoporetic fracture)

They found that postmenopausal women who had taken an oral bisphosphonates longer than one year had a 59% reduced risk of colorectal cancer. Like the Scandinavian countries, pharmaceutical records in Israel are extremely well documented. (All the citizens have health insurance and most of their prescription medications are covered…I wish I could say the same for us!) The researchers used computerized pharmacy records and identified almost 2000 women who had colorectal cancer.

They found that in these women, compared to controls who were matched for age, weight, and religion, the use of bisphosphonates longer than 1 year, but not less than 1 year, reduced the risk of colorectal cancer by half, even when they adjusted for other factors that could perhaps lower colorectal cancer risk. (Here is where I list these factors to remind you that they too count in our “war on colorectal cancer”…as does screening. They include vegetable consumption, physical activity, and weight control, use of low-dose aspirin, statins, vitamin D and postmenopausal hormones.)

Ongoing research indicates that oral bisphosphonates may exert a cancer-protective effect (including breast and prostate cancer.)  Clearly this study is not large enough to persuade the FDA to approve any official indication that this class of medication will diminish colorectal cancer. So I’ll end with the phrase that is used in the conclusions of most medical articles: “Further studies are needed”. I felt , however, that a bit of good news about the medications that can lower the huge toll of osteoporotic fractures in women (and men) is welcome.

In addition to my usual Friday website article, I felt it was necessary to address the recent JAMA article on estrogen-only therapy (in women who have had a hysterectomy.) The women were followed and results have just been published years after the Women’s Health Initiative (WHI) was stopped. The American Menopause Society (NAMS) said it best and hence I am simply forwarding the message that appeared on their website in response to this article. Once more, their conclusions reinforce the fact that estrogen (without a progestin) did not increase, but actually decreased breast cancer, in follow-up of over 10 years. Premarin (CEE) therapy was found to be beneficial vis a vis heart disease, colorectal cancer and overall, all-cause mortality for women under the age of 70 but appeared to lose its benefits and indeed worsen mortality rates after the age of 70. So here is the data and the NAMS conclusion:

Brief summary of the article: The final results of the Women’s Health Initiative Estrogen-Alone Trial, reflecting a median of 6 years of treatment and an average of 10.7 years of follow-up, are published in this article. The long-term follow-up and post-stopping findings for this trial have not been previously reported. The authors examined health outcomes in 10,739 women with prior hysterectomy, comparing those randomized to receive CEE treatment versus placebo. The median duration of adherence (taking >80% of study pills) to CEE was 3.5 years.

The main outcomes were CHD and invasive breast cancer. In addition, a global index of risks and benefits included CHD, stroke, pulmonary embolism, breast cancer, colorectal cancer, hip fracture, and death.

Results: For the overall study population, there was a significantly reduced risk of invasive breast cancer among women randomized to CEE versus placebo over the 10.7 years of follow-up (23% reduction; HR 0.77; 95% CI, 0.62-0.95). Risk reductions were similar in the treatment and post-stopping periods. In the overall study population, there was no significant effect of CEE on CHD, deep vein thrombosis, stroke, hip fracture, colorectal cancer, or total mortality. However, younger women (ages 50-59 at enrollment) tended to have much more favorable outcomes on CEE than the older women for CHD, heart attack, colorectal cancer, all-cause mortality, and the global index. For heart disease endpoints, risks were 40% to 50% lower with CEE than placebo in women ages 50 to 59 but were higher with CEE than placebo in women ages 70 to 79. For example, for every 10,000 women per year taking CEE, there were 12 fewer heart attacks, 13 fewer deaths, and 18 fewer adverse events for women ages 50 to 59. In contrast, for every 10,000 women per year ages 70 to 79, there were 16 extra heart attacks, 19 extra deaths, and 48 extra adverse events for women taking CEE (P values for interaction by age were statistically significant).

Conclusions: In this randomized trial, conjugated equine estrogens (CEE) use was associated with a decreased risk of invasive breast cancer and much more favorable results for coronary heart disease (CHD), all-cause mortality, and several other outcomes in younger than in older women. Overall, the observed pattern provides more support for the “timing hypothesis.” The findings highlight the differences between estrogen alone and estrogen plus progestin in terms of breast cancer risk and other chronic disease outcomes, as well as important differences by age group. Whether the reduction in breast cancer risk with CEE alone will apply to all women at menopause and to estradiol or other formulations of estrogen, and whether it will persist with longer-term estrogen use, remains unknown.

What’s your bone density? This query is almost as frequent as: What’s your cholesterol level? (Or it should be if you are postmenopausal.)

I know that I have written about the need to consider risk factors for fractures due to osteoporosis. A quick reminder, these include being female, older age, lack of estrogen in menopause, certain medications, previous fractures, smoking, family history of osteoporosis, and low bone density. All these are put together in the FRAX score which should be calculated before considering treatment with bisphosphonates (such as Fosomax, Actonel, Boniva, Reclast) or other osteoporosis medications. And I’ve also addressed the rare complications that can occur as a result of bisphosphonate therapy; more specifically, jaw bone necrosis and atypical fractures of the femur. (If you want a full description, go to the website and you can look it up in the archived articles.)

But before you read about the potential bad stuff that can occur with bisphosphonate therapy (hey, I can use “stuff” to describe things and events, President Obama does!), I want to report on a study that recently came out in The Journal of Clinical Endocrinologic Metabolism. The authors of the article rightly point out that there is substantial morbidity (illness) and mortality associated with osteoporotic fractures. Between 10% and 20 % of individuals who suffer hip fractures die within 1 year. They analyzed all the placebo-controlled randomized trials of osteoporosis treatment in the literature. They eliminated trials that included women who were on estrogen or SERMS such as Evista (which help maintain bone density) and focused only on those trials that were conducted for more than a year with “approved doses of medication”. Based on these criteria, 8 studies were eligible for analysis.

And here is what they found: There was a greater than 10% reduction in mortality for those individuals who were treated with osteoporosis medications when compared to those on placebo. Surprisingly, the reduction in deaths was neither related to age nor to incidence of hip or other non-vertebral fracture.  Now, even if we consider that treatment for osteoporosis reduces fractures by 5%, and hence an approximate reduction in hip fracture mortality of 2% to 3%, this does not explain the total mortality reduction that was found for osteoporosis therapy in these studies.

Bottom line: There may be more to “just” decreasing fracture rates with osteoporosis treatment. Osteoporosis medications can reduce mortality by over 10%, especially when used to treat older, frailer individuals. So before we shy away from their use because of rare (albeit, scary) side effects, we have to remember that osteoporosis therapy can do more than stave off debilitating fractures… it may help save lives.

It’s nice to occasionally report on a positive finding.

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.