<\/p>\n
OSTEOPOROSIS by Ingrid Nelson (9\/16\/2003)<\/p>\n
<\/p>\n
<\/span>In recent years, <\/span>In some people, <\/span>It’s probably <\/span>Here’s the <\/span>A quick but <\/span><\/p>\n DEFINITION<\/p>\n <\/p>\n <\/span>Bone is <\/span>In any case, no <\/span>Now, while all <\/p>\n <\/p>\n <\/span>The chief risk <\/p>\n <\/span>Heredity<\/p>\n <\/span> <\/span>First-degree relative with a low trauma <\/span>Lifestyle<\/p>\n <\/span>Cigarette <\/span>Alcohol <\/span>Physical <\/span>Thin <\/span>Diet low in <\/span>Little <\/span>Menstrual status<\/p>\n <\/span>Early <\/span>Previous <\/span>Drugs<\/p>\n <\/span>Chronic <\/span>Anti-epileptic <\/span>Excessive substitution <\/span>Anti-coagulant <\/span>Endocrine diseases<\/p>\n <\/span>Hyperparathyroidism<\/p>\n <\/span>Thyrotoxicosis<\/p>\n <\/span>Cushing’s <\/span>Addison’s <\/span>Hematological <\/span>Rheumatologic <\/span>Rheumatoid <\/span>Ankylosing <\/span>GI diseases<\/p>\n <\/span>Malabsorption<\/p>\n <\/p>\n <\/p>\n *Some drugs reduce calcium retention—common ones are INH, <\/p>\n <\/span>In any case, by <\/span>Now, the loss of <\/p>\n <\/p>\n <\/span>How often does <\/p>\n <\/p>\n <\/span> <\/span>Vertebral<\/p>\n White Women White Men Black Women Black Men <\/p>\n <\/p>\n <\/span>What risk <\/p>\n <\/p>\n <\/span>Age<\/p>\n <\/span>*History of <\/span>No increase <\/span>Taller<\/p>\n <\/span>Self-rated <\/span>*Previous <\/span>Current use <\/span>*Current <\/span>High <\/span>Not walking <\/span>On feet <\/span>*Inability <\/span>Poor <\/span>Poor <\/span>*Resting <\/span>Any <\/p>\n (Other studies have included smoking)<\/p>\n <\/p>\n <\/span>Note some <\/p>\n <\/span>Heredity<\/p>\n <\/span>Lifestyle<\/p>\n <\/span>Medical conditions<\/p>\n <\/span>Falls (or fate)<\/p>\n <\/p>\n <\/span>The two most <\/span>Until the late <\/span>Note that BMD <\/span> <\/span>Now the use of BMD in studies isn’t ideal for <\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/span>The WHO has <\/p>\n 1. 2. 3. <\/p>\n <\/p>\n Any person who has sustained a fragility fracture has <\/p>\n <\/p>\n <\/span>Now keep a few <\/span>Measurement at <\/span>What do these <\/p>\n WHO GETS STUDIES?<\/p>\n <\/p>\n NEW FLASH: <\/span>As of the <\/p>\n <\/span>Those with risk <\/span>Note that, in <\/span>DEXA is a good <\/p>\n WHO GETS PHARMOCOLOGIC TREATMENT?<\/p>\n <\/p>\n <\/span>Well, everyone
\ndrug companies have been aggressive about marketing osteoporosis as a disease
\nthat their drugs can treat. <\/span>For some
\npeople, osteoporosis is a disease. <\/span>However,
\nthe thinning of bones is also a normal part of aging for both men and women, a
\ngenetically programmed process that begins—along with a multitude of other
\nphysiologic changes associated with growing older, rising blood pressure, for
\nexample—after age 30 or so, and kicks into high gear at 50 years old.<\/p>\n
\nthin bones fracture; perhaps this is when osteoporosis becomes a disease. <\/span>A corollary might be the unfortunate
\nindividual with high blood pressure who suffers a stroke. <\/span>Of course, not everybody with high blood
\npressure has a stroke, just as not everybody with thin bones sustains a
\nfragility fracture. <\/span>So, one way to
\nthink about osteoporosis might be as a risk factor for fracture (just as high
\nblood pressure is a risk factor for stroke).<\/p>\n
\npossible to predict such fractures and maybe even to prevent them. <\/span>And, future fractures in a patient with the
\ndisease of osteoporosis may also be preventable. <\/span>So, as a disease, osteoporosis is treatable, and as a potential
\ndisease, it may also be preventable.<\/p>\n
\nobligatory rundown on the costs of osteoporitic fractures: <\/span>it’s huge.
\n<\/span>But consider also the pain, disfigurement, depression, and declining
\nproductivity that the disease of osteoporosis inflicts on those it affects, and
\nI think you’ll agree that these numbers pale in comparison. <\/span>A frequently quoted statistic that your
\naverage white woman has a one in six chance of fracturing her hip during her
\nlifetime. <\/span>She may have a one in two
\nchance of fracturing something.<\/p>\n
\nimportant note: <\/span>most of the figures
\nI’ll cite were taken from studies of white, post-menopausal women living in
\ndeveloped nations. <\/span><\/p>\n
\nconstantly being formed and reformed.
\n<\/span>It’s a coupled process—first resorption and then formation. <\/span>During the years of skeletal growth, the
\namount of new bone formed exceeds the amount resorbed. <\/span>There’s a big burst in growth during puberty
\nwith a slower rate of growth after that until peak bone mass is reached—at
\nabout the age of 30 or so. <\/span>The
\ndeterminants of this mass are several.
\n<\/span>Genetics are probably most significant, probably accounting for 50% of
\nthe final bone mass reached. <\/span>This may
\nbe why white women are far more likely to become osteoporetic than African
\nAmerican women. <\/span>But, diet, exercise,
\nand co-morbid conditions also play a role (clearly an opportunity for early
\nintervention). <\/span><\/p>\n
\nmatter how terrific your bones are they begin to lose mass eventually. <\/span>This happens because in each cycle, the rate
\nof resorption begins to overtake the rate of formation. <\/span>In an adult, the coupled cycle can take a
\nyear or so to complete, a useful thing to know when one considers how to
\nevaluate the success of therapy. <\/span>In any
\ncase, this gradual age-related decline accounts for about a one percent loss in
\nbone mass a year. <\/span>This loss can be
\naccelerated by decreased activity, poor diet, increased bad habits (smoking,
\ndrinking, etc.), and an age-related increase in co-morbid conditions with
\nincreasing drug use. <\/span>Women have a
\nadditional period of bone-loss—the post-menopausal years when, due to a drop in
\nestrogen levels, they may lose 10-25% of their bone mass. <\/span>This occurs in the 10 to 15 years following
\nmenopause and is independent of age-related bone loss. <\/span>Note that the loss of bone is not just
\nvolumetric; bony architecture is also affected. <\/span>The trabeculae that support the mineralized bone are weakened,
\nand fragility fractures become more likely.<\/p>\n
\nwomen lose bone after menopause, not all (perhaps 20% of white women) become
\nosteoporitic. <\/span>It’s unclear why they do,
\nbut, again, the reasons are probably several—lower peak bone mass, lower
\npost-menopausal estrogen levels (or higher levels of sex hormone binding globulins),
\nor impaired bone formation processes. <\/span><\/p>\n
\nfactors for getting osteoporosis (as summarized in a review article in the NEJM
\nin 1998) are:<\/p>\n
\nfracture<\/p>\n
\nsmoking<\/p>\n
\nabuse<\/p>\n
\ninactivity<\/p>\n
\nhabitus<\/p>\n
\ncalcium<\/p>\n
\nexposure to sunlight<\/p>\n
\nmenopause (before 45 yrs. old)<\/p>\n
\nperiods of amenorrhea (at least one year)<\/p>\n
\nsteroid use<\/p>\n
\ndrugs<\/p>\n
\ntherapy (i.e., thyroxin, corticosteroids)<\/p>\n
\ndrugs<\/p>\n
\nsyndrome<\/p>\n
\ndisease<\/p>\n
\ndiseases<\/p>\n
\ndiseases<\/p>\n
\narthritis<\/p>\n
\nspondylitis<\/p>\n
\nheparin, tetracyclines, and lasix.<\/p>\n
\nage 80 women have lost on average 40% of their peak bone mass and men have lost
\nabout 25%. <\/span>Moreover, the bone that
\nremains has distorted architecture, a synergistic effect to absolute loss of
\nmass that further contributes to structural weakness.<\/p>\n
\nbone mass isn’t a bad thing per se.
\n<\/span>It’s only bad when the bone breaks.
\n<\/span>And, that can be terrible. <\/span>You
\nare all probably aware of the morbidity and mortality associated with hip
\nfractures, with the chronic pain that comes with vertebral fractures, the
\ninconvenience associated with wrist fractures—the three types most commonly
\nassociated with osteoporosis.<\/p>\n
\nosteoporosis lead to fracture?
\n<\/span>Impossible to say, but here is a chart of the lifetime risk of various
\nfractures at age 50 in this country:<\/p>\n
\n<\/span>Hip <\/span>Forearm <\/span>Clinical <\/span>Radiographic<\/p>\n
\n<\/span>17% <\/span>16% <\/span>16% <\/span>35%<\/p>\n
\n<\/span>6% <\/span>3% <\/span>5% <\/span>?<\/p>\n
\n<\/span>6% <\/span>? <\/span>? <\/span>?<\/p>\n
\n<\/span>3% <\/span>? <\/span>? <\/span>?<\/p>\n
\nfactors make one person more likely to sustain a non-traumatic fracture than
\nanother? <\/span>A 1995 survey of ambulatory
\nwomen, average age 72, and almost all white, identified 16 independent ones;
\nthose that are starred were most significant:<\/p>\n
\nmaternal hip fracture<\/p>\n
\nin weight since age 25<\/p>\n
\nhealth<\/p>\n
\nhyperthyroidism<\/p>\n
\nof benzodiazepines<\/p>\n
\nuse of anti-convulsant drugs<\/p>\n
\ncurrent caffeine intake<\/p>\n
\nfor exercise<\/p>\n
\nless than four hours a day<\/p>\n
\nto rise from a chair<\/p>\n
\ndistant depth perception<\/p>\n
\ncontrast sensitivity<\/p>\n
\npulse greater than 80<\/p>\n
\nfracture since age 50<\/p>\n
\noverlap between the two lists, and note also that all of the above fit into
\nfour basic categories:<\/p>\n
\nreadily modifiable are, obviously, lifestyle and falls. <\/span>You’ll hear more about falls in another
\ntalk; suffice it to say that most hip fractures are a result of falls. <\/span>And, with a bit of consideration, you can
\nsee that low bone mass density is a final common pathway in all three groups.<\/p>\n
\n1980’s it was difficult to measure bone density accurately. <\/span>However, most hospitals now have dual energy
\nx-ray absorptiometry machines that, with a dose of radiation just a tenth of
\nthat of a regular chest x-ray, can measure bone density accurately to within a
\nfew percentage points. <\/span>With the
\ndevelopment of these machines it became possible to augment the way women are evaluated
\nfor risk, and to see which treatments work.
\n<\/span>Instead of using just fracture as an endpoint, which involved following
\nvery large groups of people for many years, it was possible to design
\nprospective, randomized studies to see how one treatment or another affect bone
\ndensity and, thus, presumably, risk of fracture.<\/p>\n
\nreadings give a picture of how the bones are now. <\/span>There are certain biochemical markers that may be more
\npredictive; that is, give a picture of how the bones may be in years to
\ncome. <\/span>None have been rigorously tested,
\nbut one in common use is N-telopeptides, a fairly specific marker for bone
\nbreakdown that appears in the urine.
\n<\/span>Elevated levels suggest that bone is being resorbed and, when patients
\nare of the age where rates of resorption exceed rates of formation, such levels
\nmay suggest that the patient is headed for osteoporosis, or at least is at
\nhigher risk of getting there. <\/span>So some
\ncenters use these markers prospectively in patients at risk for the
\ndisease. <\/span><\/p>\n
\nour purposes. <\/span>In making clinical
\ndecisions it’s best to rely on studies that look at clinical outcomes rather
\nthan surrogates. However, BMD is highly predictive of the risk of fracture; in
\nfact the predictive power is stronger than that of hypertension for stoke, or
\nof hyperlipidemia for coronary artery disease.
\n<\/span>BMD readings have given rise to a definition of osteoporosis, based on
\nthe so-called T-score, or a comparison of any set of readings to those for a mean
\nfor young women (or man) which is arrived at by manufacturers by pooling
\nreadings from a large base of racially diverse people (divided by gender). <\/span>DEXA readings are also graded by a Z-score,
\nwhich compares your patient’s reading to age matched controls.<\/p>\n
\nproposed three categories:<\/p>\n
\n<\/span>Osteopenia, with BMDs between 1 and 2.5 SD below the mean.<\/p>\n
\n<\/span>Osteoporosis, with BMD values more than 2.5 below the mean.<\/p>\n
\n<\/span>Severe osteoporosis, with BMD values at least 2.5 SD below the
\nmean and a history of nonviolent fracture.<\/p>\n
\nosteoporosis.<\/p>\n
\nthings in mind. <\/span>Low BMD is a risk
\nfactor for a fracture, not a fracture itself, and the risk of having a disease
\n(that is, osteoporitic fractures) is not the same as having the disease. <\/span>Low BMD is specific, but not especially
\nsensitive, in predicting fracture.
\n<\/span>Osteo-arthritis may give falsely high BMDs; one way around this is to
\nmeasure the hip not at the joint but at the femoral neck. <\/span>Finally, older women are at higher risk for
\nfracture than younger women with a comparable BMD. <\/span><\/p>\n
\nany site is predictive, but measurement of the trochanter is most accurate in
\npredicting a hip fracture, and measurement at the vertebrae is best to assess
\ntreatment efficacy.<\/p>\n
\nnumbers mean in terms of bone mass?
\n<\/span>Well, a decline of one standard deviation below the mean at the spine
\nrepresents a loss of bone mass of about 10%.
\n<\/span>How about in terms of fracture? <\/span>Well,
\nthe risk of fracture increases about 2 times for each decrease of one SD. <\/span><\/p>\n
\nnew issue of the US guide to preventative services, screening for osteoporosis
\nis recommended for all women over 65 yo, and for women between 60 and 65 yo
\nwith risk factors.<\/p>\n
\nfactors. <\/span>Those considering
\npharmacological treatment. <\/span>Those with
\nclinical signs of osteoporosis—one of the most common is excessive loss of
\nheight (greater than two inches); also those with non-traumatic fractures of
\nthe wrist, hip, or vertebrae. <\/span><\/p>\n
\naddition to a DEXA scan, your work-up should also include thyroid tests, a PTH,
\nand urine calcium to diagnose hypercalciuria.
\n<\/span>You might also consider protein electrophoresis and cortisol levels, if
\nindicated.<\/p>\n
\nway to follow treatment, too. <\/span>But,
\nbecause of the long bone remodeling cycle, don’t repeat the test more
\nfrequently than each 18 months or so.<\/p>\n
\nin whom it is not contra-indicated should take calcium (1200 to 1500 mg per
\nday) and Vitamin D (400 to 800 IU per day).