Sarcopenia or why we install railings by toilets

I attended a funeral last Friday. There was a fair amount of rising and falling to feet and to seats what with religious moments and a standing, whooping, foot-stomping ovation to Megan and her life well-lived. I've written before about funerals, and how I love a good one, but that is not the subject of this post.

My pew-mate was an older woman who carried more than a little extra weight and who struggled mightily to stand each time we were called upon to do so. In front of me sat a skinny woman, still older yet, who did not even attempt to get upright until it was time to leave the chapel. Two elderly friends of Megan, each losing physical ground in her own way, one to excess adiposity and osteoarthritis of knees and hips perhaps, the other to fraility and sarcopenia. The inability to rise from a seated position, however, be it in a kitchen chair, a living room recliner, or a toilet seat, is a big step on the road to dependence and demise.

Aging is filled with -penias as in osteopenia (loss of bone mass short of osteoporosis) and sarcopenia or loss of muscle mass. There are many factors that contribute to this age-related wasting away of muscles some of which not yet elucidated but not the least of which is inactivity brought on by injury, arthritis, and illness which in turn leads to weakness and fatigue which in turn fosters more inactivity.

In order to repair, regenerate, and develop muscles to propel ourselves up out of a chairs and off to the 'frig (or the gym!!), we depend on 'satellite' stem cells that reside on the surface of our muscle fibers. Reduced numbers of such cells coupled with their decreasing ability to do their job is the biological basis of sarcopenia. I've had patients seek out human growth hormone and human chorionic gonadotropin in order to boost muscle mass and reverse aging, but rats and researchers in Washington state and Israel have recently published findings that suggest a simpler, less expensive, more accessible way to get myogenic satellite cells. One word: Exercise!

Rodent models suggest nothing but bad news from aging satellite cells. Satellite cells are usually in a resting state in older animals but can be activated to repair and renew muscles after injury and illness. But satellite cells are more likely to generate fat (the lady next to me!) or fibrous connective tissue (the stringy, skinny lady in front of me!) than muscle fibers as they grow old. So what happens if rats work out instead of veg in front of the TV set?

The researchers confirmed that the older the rat, the fewer the satellite cells on their calf muscles. However, when the four-legged geezers were persuaded to hit the exercise wheel, this aging effect was corrected, and both males and females greatly increased the number of myogenic--muscle producing--cells. Better yet, this cellular change had a visible effect on the old coots with a favorable shift in their lean-to-fat content and on their level of "spontaneous locomotion." Svelte, toned, AND disinclined to sleep the day away in the wood shavings!

One of the ways I assess how my patients are faring is to greet them first in the waiting room. First of all, it's a good way to start the visit, but, in addition, I can watch them rise from their chairs and walk across the room and up two stairs to the hall. I am daily appalled by the way some of my long-time patients increasingly struggle with the task, even moreso by their seeming indifference or inattention to their inability to move with ease. Check out the way you spring from your pew, your toilet, your desk chair. Don't take "can't do it easily" for an answer.
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1) Shefer, G et al. Reduced Satellite Cell Numbers and Myogenic Capacity in Aging Can Be Alleviated by Endurance Exercise. www.plosone.org.

Swiss chard and lung cancer

If R is you or more specifically your DNA in charge
of cell proliferation, the CH3 or methyl group is your
potential road to ruin.

In the spring of 2008, one of my patients came back from a vacation to Mexico with "pneumonia". But I didn't really think it was pneumonia--the shadow on her x-ray wasn't quite pneumonia-ish, and her symptoms of fatigue and a non-productive cough weren't exactly right either. Anyway, we optimistically tried a course of antibiotics without any change in that infiltrate, and, alas, it was lung cancer after all. Mother of two boys still at home and an ex-smoker for more than a decade, my patient died at home six short months later.

Sometimes rogue DNA--perhaps damaged by aging, smoke, or an errant sunbeam--just gets the best of you despite all that water and veggies and walking at dawn. Still, a person keeps trying to do what she can to avoid the brick wall of mortality, and a recent study in the journal Cancer Research (1) further supports the value of leafy greens. But before we discuss the goodness of greens, a word or two on gene promoter hypermethylation events which are nothing you want occurring in your DNA.

Genes are minute strips of DNA. During a typical 'business-as-usual' day in the life of a normal cell, they are activated by external and internal events and transcribed via RNA to produce worthy proteins that carry on normal activities that include damage repair and control of cell proliferation. If, however, one instructional molecule of the DNA gets permanently tangled up with a methyl group, the entire gene is silenced and its work remains undone. Worse yet, as that cell with its load of methylated DNA replicates itself because no gene product was there to tell it not to, all its offspring cells are also methylated. As a result, an out of control, methylated mass of cells continues to grow unchecked. Sounds like cancer, doesn't it?

So once hypermethylated, can you become demethylated? Such a demethylation process is the dream of scientists looking for chemopreventive strategies. As opposed to chemotherapy drugs which seek and destroy cancer cells, chemopreventive agents act to repair or prevent malignant change. Researchers from the University of New Mexico sorted through sputum from smokers (both current and ex-) seeing if certain dietary strategies were associated with lower levels of methylated genes in expectorated DNA.

Some 1,100 subjects dutifully hawked up their secretions and completed Harvard Food Frequency Questionnaires. As a result, the New Mexican docs were able to identify leafy greens (and we're not talking lettuce here), folate, and multivitamin use as three strategies that correlate with less methyl-generated mess. They proposed that further study might verify these and other agents as ways to reprogram our genome for life without cancer.

Now I'm all for this sort of research as a doctor and an ex-smoker. My problem is that a pile of steamed chard (or kale or greens) is an unappealing mess all its own. Any suggestions of different ways to prepare an appetizing, chemopreventive side dish of greens?
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1) Stidley, CA et al. Multivitamins, folate, and green vegetables protect against gene promoter methylation in the aerodigestive tract of smokers. Cancer Res. 2010 Jan 15;70(2):568-74.

Best personal trainer deal in Denver

Please note the corrected dates for this program

I have struggled mightily with back pain from scoliosis and degenerative arthritis. Thanks to a program of core strengthening courtesy of two knowledgeable young women--one a Pilates instructor with a strong background in physical therapy and yoga, the other an athletic trainer with a gift for modifying her workouts for older, less flexible non-athletes--my spasms and debility are yesterday's news.

I've put a lot of time and money into this program figuring properly that any bottom line beats crippling pain and decreased mobility. I am pleased to announce now that my trainer Tanya Martelli (Dr. Sykes goes to her too!) has assembled a low cost solution for those of you displeased with your aging spines.

She will be conducting a three class workshop for five participants Oct. 8, 15, and 22 at our office from 4-5 p.m. The focus will be on posture and core power, and at the end of the sessions, each person will have a home program to continue progress made during the class. The cost is $45. If these times do not work for you, Tanya plans another three week session mid-day Tuesdays at the end of this series.

You do not need to be our patient to attend these classes. Interested? Contact Tanya at tlyaskoff@mac.com to sign-up or inquire about future classes. She just designed a home program for me that I took on a recent road trip to California--worked just perfectly to keep me upright and buff while away from home. She could do that for you too!

Rose Kelly

Rosellen Kelly, 8/20/52-7/31/10

I lost my dear friend Rose yesterday to cancer. Mom, wife, friend extraordinaire, writer, artist, and Assistant Head of School at St. Anne's Episcopal here in Denver, she was a treasure to all who knew her. She collected friends like an endless strand of pearls--like the ones she wore at a time when our generation was mostly through with such traditional adornment.

Gracious, hilarious, and soothing, she told me that she viewed death as "just showing up for my next assignment. An angel in life, she has ample experience for her upcoming gig.

Window of Opportunity of Estrogen Therapy for Neuroprotection

Those of you who find this topic one of interest should check out the newest post at my other blog: Menopausemoments.blogspot.com.

Fractures and Fosamax

Dang, what was this 60-something year old lady(1) doing that resulted in her femur breaking like a branch across a gardener's knee? The unsettling answer? Nothing. She just felt a "giving away" sensation in her leg and then she gave way and went to ground. Of note, however, she had been taking medications for 17 years to prevent osteoporosis: first Fosamax and then Boniva.

Our bones are in a state of constant turnover. Breakdown of bone matrix by cells called osteoclasts is balanced by a corresponding build-up of bone mass undertaken by osteoblasts--a process that continually replaces old bone with new. In adults, bone formed equals bone broken down as osteoblasts fill areas along the bone surface previously resorbed by osteoclasts. Such dynamic restructuring in response to the forces of gravity and activity is essential to bone strength. In addition, this active bone metabolism repairs micro-traumas caused by everyday wear and tear as well as macro-traumas such as fractures.

As we grow older, we tend to breakdown faster than we build-up (well duh!). Ongoing osteoclastic activity is no longer countered in kind by reciprocal action from aging osteoblasts especially in women who are estrogen-deficient, inactive, on steroids, or deficient in calcium and vitamin D. Now bone resorbed by osteoclasts exceeds bone built by osteoblasts resulting in bones that are not only thinner but also architecturally unsound. As a result, vulnerable areas such as the hip, the vertebrae, and the bones of the forearms lose strength and fracture easily.

One strategy developed to combat this scenario is a class of drugs called bisphosphonates (Fosamax, Actonel, Boniva, Reclast, and others) which inhibit normal bone-remodeling through inhibition of osteoclasts. Since bone resorption triggers bone formation, these drugs are better suited to slowing loss rather than gaining mass. While population studies show decreased risk of fractures in persons using bisphosphonates, disturbing patient histories, such as that from the unfortunate lady pictured above, suggest that extended use of Fosamax and friends may result in bone fragility through the accumulation of microdamage in bones weakened by a loss of the normal reparative functions.

Texas researchers had a look at bone chips from persons who had spontaneous--i.e. no antecedent trauma--fractures while on Fosamax(2) most of whom had delayed or absent healing at the site of the break. Scary stuff on microscopic exam--many of the patients showed "markedly suppressed bone formation" with little or no osteoblastic activity and diminished mineralized bone. Even those patients on concurrent estrogen therapy demonstrated decreased bone formation. While Fosamax was the first bisphosphonate 'out of the gate' and thus most likely to be associated with fractures related to long-term use, scientists believe that this brittle bone thing may well be found with ongoing use of the other agents in this class.

Well yikes, is it time to boycott Boniva? Act not on Actonel? Consider first, this meta-analysis of several bisphosphonate trials.(3) These scientists from four different countries supported by Merck (Fosamax) and Novartis (Aredia, Zolmeta) analyzed data from three large studies looking for risk of fractures of the femoral shaft (considered atypical when compared with the more common fractures of the femoral head) as they were associated with use of bisphosphonates. Most reassuringly, they found such drug-related breaks to be rare, occurring at a combined rate of 2.3 per 10,000 patient-years. In other words, of 1,000 women using a bisphosphonate for 10 years, 2.3 would have an unexpected fracture of their thigh bone. There was no elevated risk of this type of fracture between those on Actonel and those on placebo, and a relative risk of 1.5 for women on Zolmeta (an IV bisphosponate most often used in serious situations such as in women with metastatic cancer where the drug slows down the spread of the tumor through the bones).

In an editorial that accompanies this study(4), Dr. Elizabeth Shane of Columbia University emphasizes that such atypical fractures are extremely rare, and particularly unlikely in persons on bisphosphanates. In fact, she cites studies that show, on average, that these femoral shaft fractures are more commonly caused by osteoporosis than the medications that treat the condition, and high adherence to this drug regimen more often decreases the risk of this type of bone breakage. She concludes: "many more common and equally devastating hip fractures are prevented by bisphosphonates than are potentially caused by the drugs."

Several authors have suggested that women on bisphosphonates be given a drug holiday in order to allow for a time of normal bone remodeling. Bisphosphonates bind to bone and are slowly released by osteoclastic activity. Fosamax is present in the body long after its use is discontinued--one study found bone turnover suppressed for three years after five years of regular Fosamax use. There are no official guidelines to follow with respect to intermittent bisphosphonate use, but one year off does not seem to diminish the positive effects on fracture risk.

What should you do? Talk with your doctor about taking a drug holiday (no, not THAT kind of drug holiday) if you've been on bisphosphonates for more than five years.
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(1) X-ray and case history from:
Goddard MS, et al. Atraumatic Bilateral Femur Fracture in Long-Term Bisphosphonate Use. Orthopedics. 2009 Aug;32(8). pii: orthosupersite.com/view.asp?rID=41933. doi: 10.3928/01477447-20090624-27.
(2) Odvina, CV, et al. Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab. 2005 Mar;90(3):1294-301. Epub 2004 Dec 14.
(3) Black, DM, et al. Bisphosphonates and Fractures of the Subtrochanteric or Diaphyseal Femur. Published Online March 24, 2010 (DOI: 10.1056/NEJMe1003064).
(4) Shane, E. Evolving Data about Subtrochanteric Fractures and Bisphosphonates. Published at www.nejm.org March 24, 2010 (10.1056/NEJMe1003064)

The changing face of primary care

My medical partner and I are facing big decisions about the future of our medical practice. I urge all of you--particularly our patients--to head over to Denver Doc Online and read about our dilemma and leave your thoughts behind.

Morton's Foot

Dr. Dudley Morton practiced in the 1930's, first describing a number of foot ailments including Morton's foot (aka Morton's toe), and Morton's neuroma. Morton's foot is a common but dysfunctional variant of foot structure occurring in more than 25% of the population. By the time one hits middle-age, however, the instability caused by this condition can lead to pain and an inability to walk pain-free into the golden years.

Check out the sketch below from The Trigger Point Therapy Workbook for a look at Morton's Foot which is also known as short first metatarsal syndrome. The metatarsals are the longish bones beneath each toe, and the first metatarsal meets up with the big toe at a most critical juncture known as the 1st MTP (metatarsal phalangeal) joint which should be one of the primary weight-bearing areas of your foot.

If you've been issued a stumpy first metatarsal (arrow B), your weight is transferred to the 2nd MTP joint (arrow A) beneath your 2nd toe (arrow C). As a result, your weight can wobble inward towards the arch or outwards towards the little toe which has been likened to 'walking on ice skates'. The 2nd toe may extend beyond the big toe in persons with this Morton's business; while some call this long 2nd toe a sign of nobility. In my experience, it's a sign that you may give up walking for exercise.

Then look out, it's like a veritable aging house of cards cascading down your midline. The arches fall, a bunion may pop out, the ankles hyperpronate (see below), your calf muscles start working overtime to hold up your body,your knees knock together in the midline causing arthritis and collapse of your lateral knee joint,


you start to hate walking, gain weight, and plummet into old age way before your time.

So if that info knocked your socks off, check yourself for Morton's foot thusly:By pulling your toes downwards, you'll be able to see the locations where the metatarsals end and Morton's mayhem begins.

Got Morton's? I do. Custom-made orthotics and Pilates have changed my life. If you've been short-changed on your first metatarsal and are starting to hobble with pain, a trip to the podiatrist is definitely worthwhile. For more information, check out Mortonsfoot.com.

Milk thistle for liver protection

I had a patient in yesterday whose medical records show a long history of elevated liver function tests. These enzymes, namely aspartate aminotransferase (ALT) and alanine transaminase (AST), are part of routine blood test panels often ordered to screen for disease. Normally present in liver cells, elevated levels in the blood can indicate disruption of the cells by inflammation or disease. Even minor elevations are taken seriously if they persist over time as progressive destruction of the liver from hepatitis or other disease can occur without major changes in the transaminase values.

Further testing indicated she might be suffering from auto-immune liver disease wherein a misguided immune response against one's own tissue can cause damage to the organ. She wondered what she could do to promote liver health while pursuing a definitive diagnosis with a specialist. I recommended milk thistle only to read the following today on the Consumer Lab web-site.

Consumer Lab is an independent organization that tests nutritional supplements for quality, assuring that these products are pure, contain what they claim, and are free of contamination. The nominal yearly subscription fee is well worthwhile if you are a fan, as am I, of supplements. One of their recent reviews covered milk thistle.

Only one brand was found on testing to contain the amount of active ingredient indicated on the label. Furthermore, the evidence that milk thistle changed the course of chronic liver disease caused by hepatitis or alcohol was weak. The research suggesting that the herbal preparation protects against liver toxicity from acetaminaphen and anti-seizure meds was stronger. The active ingredient in milk thistle--silibinin--has been the subject of recent cancer research and seems to have some promise as a chemotherapeutic agent.

I don't feel quite so enthusiastic about my recommendation now. If you're considering milk thistle supplements, have a look at the ConsumerLab site to choose the best brand.

Rheumatoid arthritis, disability, and dismay

One of my favorite patients struggles mightily with the pain and disability of rheumatoid arthritis. Unfortunately, she got hooked on Oxycontin that she started taking for the pain of infected foot ulcers brought on by the immune-suppressive drugs she takes to control her disease.

Each time I see her, I'm dismayed with 1) how quickly life can unravel due to disease and disability, and 2) how difficult it is to be taken seriously when you take too many pain meds no matter how legitimate your need for same. I spent over an hour on the phone today with the patient and a pain specialist she consulted last month. The latter never even examined her when she came to his office seeking help with pain control and narcotics withdrawal. "I could have you committed," he told her, "for your illegal use of drugs. What on earth did he think he'd accomplish with nonsense like that except to drive her to tears (which he did).

So now she's fallen and sustained four compression fractures of vertebrae made thin from steroid use. The orthopedist she sees for degenerative disk disease never mentioned to her that her new, dreadful pain was due to fractures. I have no idea what my colleagues think they're doing here. But I do know if you're malnourished, angry, and you look older than you are due to the ravages of pain and illness, it's extraordinarily hard to be taken seriously.