Thin Bones

Osteoporosis is an equal opportunity disease. Everyone is at some risk for age- related thinning of the bones. Prevention is the best treatment, and understanding how osteoporosis happens is the key to prevention.

Bone is alive

Bone may resemble concrete, but it is vibrant, living tissue that is perpetually under reconstruction. From the time of birth, when bones are composed mostly of soft, pliable cartilage, they shape and reshape themselves. Cells called osteoblasts appear in the cartilage and begin to lay down a protein matrix, spinning it into flexible tendrils like fine rope. A mixture of minerals, mostly calcium and phosphorus, hardens the matrix, creating the blend of strength and flexibility needed for the forces the skeleton has to bear. Throughout life the bones restore, remodel and repair themselves in response to the stresses of life on a planet governed by gravity.

Bones are storage depots for calcium

The bones also store calcium for the rest of the body and respond to its constant demands for the mineral. Cells called osteoclasts break bone down to free calcium for use elsewhere, and to remodel bone where changes are needed. So there is a constant interplay of bone construction and bone destruction throughout life, with the material of you skeleton renewing itself completely every ten years or so.

Bones build, remodel and breakdown

In youth, bone construction goes full blast. Once maturity hits, the process evens out. In older age, breakdown begins to exceed construction. Just another sign of inevitable decline? Yes, but don’t give up hope. You control some things that influence how fast bone loss occurs, and science is making strides to help.

You are the general contractor

You are in charge of the building material that your bones use. A healthy balance of food, including protein, fat, calcium and Vitamin D makes healthy, well-mineralized bones. You need 1200 milligrams of calcium a day, the amount in about three glasses of milk, and 400 IU of Vitamin D, which is made in the skin when it is exposed to sunlight (10-15 minutes of sun on hands arms and face, or back, twice a week). Vitamin D deficiency is common in the elderly because of indoor lifestyles, and in northern climates. Many foods are fortified with Vitamin D, and cod liver oil and fish are excellent natural sources.

Childhood habits matter

The bone density that you achieve in youth is important because it is the starting point for the gradual losses that come later. Maximal bone density for life is achieved in the early twenties The generations of children that have opted for pop over milk are at a disadvantage, arriving at adulthood with less calcium than past generations have.  and pediatricians are already seeing more children with fractures than in the past. The cost of neglecting childhood nutrition is bound to rise as time passes.

Gravity and exercise matter

You are also in charge of the activity that stimulates bone formation. When you are upright and fighting gravity, the osteoblasts lay down more bone matrix where it is needed to bear weight, particularly in the pelvis, lower spine and hip. But as soon as the stresses diminish, the osteoclasts start their breakdown work. Just a few days of bed rest sets them in motion. Astronauts in the space lab, under minimal gravity, lose as much bone in a month as a post- menopausal woman loses in a year. Even the impaired movement of a bone under a cast causes localized osteoporosis.

The more you exercise against gravity – as in walking, running, doing yoga or calisthenics, or weight lifting – the more you will call osteoblasts into action. Sit out life, and your osteoclasts will dominate.

Who does osteoporosis affect?

Youth compensates for deficits in diet and activity, but as growth-related hormones fall with age, the cost comes due.  Genetic makeup counts too. Women lose more bone than men, smaller-framed people more than larger-framed people, and Caucasians,and Asians more than dark-skinned people. Smokers and heavy drinkers are also at higher risk for osteoporosis, as are people who are confined to bed or taking steroid medications.

The cost of thin bones

Thin bones break and fractures are costly, about $10 billion for the 1.5 million fractures a year in the USA. Spinal fractures, the most common breaks, are very painful and cause spinal deformity and loss of height. Of all the people who fracture hips, 50% are permanently disabled, and twenty percent are dead within a year, from the consequences of immobility. This mortality rate is even greater in men, who are 20% of the 44 million people who have or are at risk for osteoporosis.

Prevention of  osteoporosis and fractures

The best treatment for osteoporosis is prevention, starting in childhood. Prevention means solid diet and habitual weight bearing exercise throughout life, and, as the risk of falling increases, exercises to maintain speed and balance. Canes, walkers, hip protectors (padded garments worn over the hips), and attention to the living environment (clear walkways, even surfaces, handrails, etc.) are forms of external prevention.

The role – and the problems – of pharmacologic attempts at prevention

Doctors often recommend bone density tests and sometimes they prescribe drugs to slow the loss of bone. At menopause, bone loss accelerates, and estrogen supplements for a few years have been common practice. Newer drugs such as Evista mimic estrogen’s effects on bone alone and may be safer than the older hormone supplements, which are associated with increased risks of strokes and some cancers, especially when used for many years. The biphosphanates, like Fosamax, slow the work of the osteoclasts by attaching to bone to block breakdown. But they bond to the bone and cannot be released. Some unusual and serious side effects such as sudden, unprovoked leg bone fractures and death of jaw bone after dental procedures. Fortunately these have been fairly rare occurrences.   Calcium and Vitamin D supplements improve bone-building supplies, but calcium absorption is not as good from pills as it is from whole foods, and sunlight exposure produces much more Vitamin D than pills can provide. More severe osteoporosis warrants more unusual treatments like shots of calcium-regulating hormones.

You job

Your skeleton will outlast you. Your job is to do your best to make sure it supports you while you are here, and to pass the word to the younger generations who are still building their bones.

Sleep Debt: The Hidden Costs

Everyone has a sleep bank. Each night your accounts get credited with 7-8 hours of the physical and mental benefits of sleep and each day the accounts pay out those benefits in the form of emotional, intellectual and physical energy. Just like in any bank account, withdrawals can’t exceed deposits without incurring debt. Sleep debt, though, is easy to ignore because physical activity keeps alertness high. As long as you move around instead of reading or watching TV, you won’t nod off and you can keep thinking that 5 or 6 hours of sleep a night meets your needs. But covering the debt with activity is like keeping a bank balance out of the red by borrowing money and paying interest. Sleep debt exacts a toll on the body that goes beyond depressed mood, irritability and lack of ability to concentrate and learn, not to mention the potential for causing motor vehicle accidents.

The biological clock

As sleep debt mounts, the body’s biologic clock goes awry. This clock, located deep in the brain, controls circadian rhythms – regular ups and downs in behavior, body temperature, appetite, hormone production, alerting mechanisms, and the urge to sleep. When the clock malfunctions chronically, the results show up in the form of weight gain, high blood pressure, diabetes and diminished immunity to infection.

Setting the clock

Regular periods of darkness are required to set the brain’s internal clock to keep the body in synch with the 24-hour day set by the sun. Sleep researchers have shown that, when living in a research setting where there are no external clues about time of day or night, subjects’ internal clocks actually work on a 25-hour cycle. Normal peaks of sleepiness and alertness work themselves into the wrong time of the  24-hour day and night outside the sleep lab, producing weeks of daytime sleepiness and nighttime insomnia in the research subjects. Over time, the peaks cycle back into synchrony with day and night producing several weeks of normal daytime alertness and nighttime sleepiness.

Laboratory settings may exaggerate these patterns, but most people know that during some weeks they simply perform better during the day and sleep better at night  than during other weeks, indicating that in the modern, artificially lit world, the 24-hour day is more like a 24-25 hour day as far as the body’s natural rhythms are concerned. This clock drift is very sometimes very evident. Cyclical insomnia and daytime sleepiness are in common in blind people, in people at very high latitudes where the summer sun circles the sky for almost 24 hours, and in shift workers who are up all night in brightly lit environments. These problems, while distressing, respond to maintaining regular sleeping schedules and closing out all light during sleep periods, which resets the clock.

Why the clock matters

The internal clock is easily disrupted by one or two day episodes of sleep deprivation that people experience for reasons as varied as extra work loads, exams, brief periods of emotional upheaval, or any of the other myriad problems that keep people awake, but studies have repeatedly demonstrated that a few days of “catching up” on sleep restore the body to normal rhythms, contributing to a widely held impression that sleep deprivation, while responsible for serious accidents, doesn’t cause real health problems.
However, bigger problems do come from disturbing circadian rhythms more chronically. In recent years research attention has shifted from short term sleep deprivation to the chronic, partial sleep deprivation that is so common in our modern society, where nodding off during monotonous and sedentary activities like reading or watching TV are almost expected. Many people think they need no more than 5-7 hours of sleep at night, but while a few truly short sleepers exist, most people require around 8 hours of sleep each night to achieve maximal alertness throughout the day. Chronically shortchanging sleep by even an hour a day changes the timing and levels of multiple hormones, causing other metabolic changes and weakening the immune system.

Lack of sleep wreaks havoc on hormones

One of the first hormonal changes produced by chronic short sleep involves cortisol, the stress hormone produced by the adrenal gland. Normally cortisol levels decline during late evening hours, but without enough sleep, production continues unabated, Cortisol then begins to contribute to immune stress and to insulin resistance, which leads to diabetes and fat deposition. A second contributor to insulin resistance is a change in growth hormone secretion from one large burst during sleep to two, smaller bursts before and after sleep. A third change comes from failure of the pituitary gland to produce its normal night-time rise in thyroid stimulating hormone, the stimulus for the thyroid gland to produce more thyroid hormone. All of these changes are consistent with the fact that as little as one week of 4 hour sleeping nights can convert healthy young people to a pre-diabetic state. Observational studies do show higher rates of diabetes in chronically sleep-deprived women.

Lack of sleep and obesity

If these hormone changes are not enough to convince a short sleeper to turn out the lights earlier, studies on the appetite influencing hormones leptin and ghrelin, produced by fat tissue and the stomach respectively, might help. Leptin, which signals when to stop eating, diminishes markedly after 6 days of four- hour sleeping nights, despite no change in caloric intake. Ghrelin, which stimulates appetite, particularly for high carbohydrate foods, goes up when sleep is short.

Sleep debt is all around you

    All of these hormonal factors are significant in society where people lead overscheduled lives in stimulating, loud and bright environments without regard to natural day and night. We do not need sleep studies to tell us that we are in an age of significant sleep debt – just count the number of people, including children, asleep on planes and buses, over books and newspapers, and on couches in front of TVs. If you fall asleep regularly under these circumstances, you are in chronic sleep debt. Given the increase in obesity and diabetes over the last few decades, sleep is another potential therapeutic avenue – a fruitful and inexpensive area of health over which we have considerable control.

Managing the sleep budget: factors under your control

Environmental
1. Take the television out of the bedroom.
2.Darken the room completely, or wear a comfortable, opaque eye mask.
3. If noise is a problem were soft ear plugs.
4. Keep the temperature low at night and invest in a comfortable mattress that does not move.

Behavioral
1. Keep the biologic clock in sync with the sun by getting outside regularly.
2. Get regular exercise like walking, but avoid exercise in the last 3-4 hours before bedtime.
3. Keep naps short – 45 minutes or so – and confined to early afternoon hours.
4. Avoid heavy meals and alcohol in the last 4 hours before sleep.
5. Aim for the same bedtime every night, well before midnight, and develop a quiet bedtime ritual

Internal factors
1. Empty your bladder right before getting in bed.
2. Seek medical treatment for heartburn if causes frequent awakening. Ditto for urination.
3. Evaluation for sleep apnea is a must for someone who snores and suffers from daytime sleepiness.
4. Treatment of arthritis with exercise, physical therapy and medications, if necessary.
5. Try to get weight down to normal: sleep apnea, heartburn, and arthritis pain all benefit

A Primer on Steroids

Ask around among your friends and you will find that many of them, at one time or another, have been given “steroids” by their doctors. They have taken pills, inhaled the drugs, had injections, smeared creams on their skin, dropped liquid into their eyes, or received the drugs in an enema. They may have been treated for pain, swelling, rashes, cancer, slipped discs, vision problems, arthritis, colitis or vasculitis.  At the same time, you hear stories of athletes “doping” with “steroids” to enhance athletic performance and losing titles they won for having done so. You read ads for body building “steroids” and see the results in pictures of massively muscled men – and women. And sometimes you hear that testosterone, widely advertised for aging men, is a “steroid.” Are these all the same drugs? Yes, and no.  They are all manufactured versions of human steroid hormones.

What makes a steroid hormone?

All steroid hormones begin as molecules with the same core structure made from cholesterol. Various carbon, hydrogen and oxygen combinations added to the core make different chemical structures with different functions in the body. Those steroid hormones made in the testes and ovaries are called sex hormones. Those made in the adrenal glands are called corticosteroids and mineralocorticoids. Steroid hormones trigger a large number of different and vital chemical responses throughout the body.

Which steroids are used for which problems?

The steroids you hear about most frequently are synthetic versions of some of the adrenal glands’ corticosteroid hormones. Because they block immune system function, they are very powerful anti-inflammatory agents, commonly prescribed for allergic responses, autoimmune diseases, catastrophic situations involving trauma and shock, some cancers, and pain problems in which inflammation is thought to be the culprit. The steroids used for body building and performance enhancement are usually derivatives of the male sex hormones, or are nutritional supplements which are thought to increase the body’s own production of the male hormones.

Catabolic and anabolic effects: breaking down and building up

The first corticosteroids used in humans were animal adrenal gland extracts. They were lifesaving treatments for shock in people who had lost adrenal gland function. Incidental observations about their powerful anti-inflammatory effects propelled their widespread use and the Nobel Prize in Medicine in 1950 went to the men who elucidated their physiologic effects. With increased use, however, corticosteroids proved to have many serious long term effects because they are catabolic hormones, achieving their results by breaking down the body’s proteins and diverting them for different purposes.

The male sex steroids are anabolic hormones because they signal the body to build proteins. They have much narrower medical applications than the adrenal corticosteroids do. Anabolic steroids are useful in patients who have impaired male hormone production for reasons such as pituitary gland (the master gland) failure or testicular failure. But anabolic steroids are not medically needed in healthy people, and their use in amounts required to increase muscle mass above the body’s natural endowment courts significant risks. They are not medically available for healthy people. The male hormone testosterone is sometimes prescribed for men who have low testosterone levels later in life, with the aim of restoring libido and maintaining muscle mass, though there is some controversy about the risks versus benefits of this practice.

Powerful drugs with powerful side effects

Side effects of adrenal corticosteroids are related to the dose, delivery mechanism and especially to length of time used.  With oral and intravenous delivery, changes in glucose metabolism shift the pattern of fat storage in the body to the trunk, the neck and the face, producing the characteristic “moon facies” of someone treated with steroids over long periods of time, in relatively high does. Skin thins. Muscles shrink. Bones lose calcium and may fracture. Cataracts commonly develop. Insomnia and sometimes a form of mania signal brain effects. Suppression of the immune system, the source of the powerful anti-inflammatory effects of the corticosteroids, allows some infections to blossom. And very soon after steroid treatment starts, the adrenal glands begin to curb their own production of steroids, making stopping the drugs dangerous unless they are slowly tapered, a process that sometimes takes months.

Injections of corticosteroids into painful, presumably inflamed areas cause breakdown of the collagen structure of in connective tissue. Injections directly into tendons can cause enough degeneration at the site to lead to tendon rupture, causing some orthopedists to ban steroid injections anywhere near the Achilles tendon. Steroid inhalation for asthma and chronic obstructive lung disease is similar to topical use for skin problems – very effective at relieving inflammation, and not associated with much absorption into the body, so not as likely to produce adverse effects.

Some of the side effects of anabolic, male hormone steroids are related to their androgenic properties – the ability to produce and enhance male characteristics, and at the same time to shut down the body’s own production of testosterone in the testicles. Female users have deepened voices and develop acne and facial hair, but lose scalp hair. Males develop decreased sperm counts and shrunken testicles and also get acne and lose scalp hair (remember how many bald cyclists there were in the Tour de France during the height of the doping scandals?) But the most dangerous side effects are not visible: they include heart disease, liver cancer, anger, aggression and irritability and depression, as well as abnormalities in liver and kidney function.

Exercise caution in legitimate use of steroids and avoid illegitimate use

Alternate day dosing schedules for corticosteroids may help prevent side effects, as will the development of newer, more targeted versions of the drugs. But steroids should always be approached with caution, and used with great care. The most important things for doctors and patients to consider are the certainty of the diagnosis and likelihood that the condition will improve with less risky treatment. For instance, if orthopedic pain comes from muscular imbalance and not from inflammation, steroid injections will not help. If the condition being treated – say a bad case of poison ivy – will resolve with other types of care, steroid risks are unnecessary. Always remember that some severe steroid side effects can occur with just a few weeks use.

Sidebar: Case History illustrating Risk/Benefit Judgment in Corticosteroid Use

A 60 y.o. woman undergoes successful surgery for a benign brain tumor, but awakens with a paralyzed facial nerve, a well-known and feared complication of surgery in this type of tumor.  She has a severely drooping mouth and lower eyelid. High dose steroids over the next week reduce the swelling in the nerve, resolving the facial nerve paralysis. But the treatment also causes degeneration of the tops of the hip bones – a well-known steroid complication called aseptic necrosis. She then needs two hip replacements. Was the side effect worth the treatment result? In this case, most people would say yes. But if the steroid treatment had been for something that would have resolved with other treatment, the hip complication would have been much harder to accept.

The Master Gland and its Tumors

“When you hear hoof beats think of horses before zebras.”
Adage familiar to most doctors, reminding them that most symptoms come from common problems. Author unknown.

Pituitary gland tumors are common, often found as unsuspected abnormalities in brain scans and in autopsies, and counted as the most common “brain tumors” removed by neurosurgeons. Technically though, the most common pituitary tumors – the horses – are not brain tumors, but gland tumors called adenomas, usually benign and eminently treatable. While more dangerous tumors arising from nearby parts of the brain or skull may closely mimic pituitary adenomas, they are rare – the zebras of pituitary problems. This column is about the horses and for simplicity will refer to pituitary adenomas as pituitary tumors.

What and where is the pituitary gland?

    The pituitary gland hangs like a little globe from the base of the brain. The back half of the gland is neural tissue, connected to the deepest regions of the brain above. The front half is glandular tissue, which, like other glands, makes hormones, secretes them directly into the blood, sends them out to perform many functions in other parts of the body and is prone to adenoma formation as life goes on.

Types of pituitary tumors

    Pituitary tumors which are “non-functioning,” i.e. producing no hormones, may never cause symptoms. Larger tumors or those that produce hormones typically come to attention in midlife, more often in women than men because female reproductive cycles is exquisitely sensitive to hormonal variations. Small, unsuspected tumors turn up in about 10% of MRI scans of the head done for unrelated reasons like sinus disease or head trauma, and in 20-25% of autopsies.

     The factors which determine whether or not a pituitary tumor produces symptoms and requires treatment include its size, its ability to produce hormones of its own, and the degree to which it compresses and damages normal pituitary gland tissue and other surrounding structures. Damage to the normal parts of the gland that diminishes production of pituitary hormones is a condition called pituitary insufficiency. Production of a hormone by a pituitary tumor is called pituitary hypersecretion, which causes predictable signs and symptoms related to the effects of hormonal overdose on the given hormone’s target organs and tissues. Pressure on nearby brain structures by a large pituitary tumor is a phenomenon called tumor mass effect.

Pituitary insufficiency

    Some pituitary hormones such as thyroid stimulating hormone (TSH) prompt other glands to produce their hormones. Other pituitary hormones work directly on many body tissues. Growth hormone, for instance, affects all tissues in the body, controlling growth in early life and many aspects of tissue repair later. Still others control menstrual function, ovulation, and production of sperm, testosterone and breast milk. The rear half of the pituitary gland, which arises from the brain, makes one hormone that helps concentrate urine and another, called oxytocin which stimulates uterine contraction during labor, and has recently been suspected to play a role in some moods and behaviors.

When insufficiency becomes failure

    If a pituitary tumor compresses the normal parts of the gland, causing it to fail, wide-ranging symptoms such as fatigue, headache, weakness, abnormal menstrual cycles, decreased libido, decreasing muscle mass and body hair, weight loss or weight gain and mood alterations may appear long in advance of a correct diagnosis. These are all symptoms which might easily be passed off as lifestyle problems, nutritional deficiencies and aging.

Pituitary Hypersecretion 

    If pituitary tumors are functional, i.e. producing hormones,  symptoms come from excessive hormonal effects on the body. For instance, growth hormone (GH) and the adrenal gland stimulating hormone ACTH are the most common tumor-produced hormones. In someone still growing, too much growth hormone produces a giant – someone whose proportions are normal, but who far exceeds the normal range of sizes. Think Andre the Giant. Once growth ceases, overabundant growth hormone still causes overgrowth in certain bones and tissues, especially the jaw, hands and feet, the nose, heart and tongue, and the heel pads. This condition is called acromegaly.

    ACTH overproduction produces Cushing’s disease, named after Harvey Cushing, the father of neurosurgery in the US, one of the first to try surgically removing a pituitary tumor. Weight increases around the trunk and in the face and neck; muscles and tendons weaken and atrophy. Bones lose calcium. Eyes bulge. Skin bruises and thins. Blood pressure goes up.

Tumor Mass Effect 

    A large tumor in the pituitary may compress not only the normal gland around it but also the surrounding structures in the brain and skull. The gland sits right below the junction of the optic nerves carrying visual information from the eyes to the brain, and in between the bones where the nerves that control eye movements enter the orbits. In addition, the large veins which drain blood from the brain travel beside the pituitary on their way out of the skull. The optic nerves fibers that carry vision from the sides of the visual field are most vulnerable to pressure, which impairs sight on both sides of the patient’s field of vision. Pressure on the nerves to the eye muscles causes double vision. Headache, eye pain, or eye redness comes from mass effect on the large veins coursing beside an enlarged pituitary. Very large tumors may affect the deep brain structures above, resulting in a host of emotional symptoms or seizures.

Diagnosis 

    Symptoms which suggest pituitary gland insufficiency, hypersecretion or tumor mass effect warrant hormonal testing, an ophthalmologist’s examination of the visual fields, and imaging studies of the base of the brain. Tumors found incidentally on scans done for other reasons should prompt a good medical history and physical examination, and possibly some hormonal testing to evaluate the functional status of the tumor.

Treatment 

    Surgical removal of the pituitary tumor is the treatment for functional tumors or those that damage surrounding structures. After surgery, patients might require either temporary or permanent supplementation with pituitary hormones. On rare occasion, abrupt pituitary failure called pituitary apoplexy is the result of a pituitary tumor bleeding. this is a medical emergency, requiring  emergency surgery with meticulous attention to fluid balance and blood pressure because of failure of the hormones that modulate those functions. Non-functioning, small pituitary tumors call for regular follow-up imaging to monitor the tumor size – and should not carry the fearsome designation of brain tumor. They are horses, not zebras.

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