HIDDEN DISEASES
| IRON DEFICIENCY ANEMIA (IDA)—Lisa Weissmann, MD, Chief of Hematology and Oncology, Cambridge
Hospital, Clinical Instructor in Medicine, Harvard Medical School, Harvard University, and Attending Physician,
Mount Auburn Hospital, Cambridge, MA
|
| Introduction: IDA most common form of anemia worldwide; mean corpuscular volume (MCV)—classifies anemia as
microcytic (red blood cells [RBCs] too small [microcytosis]), macrocytic (RBCs too big), or normocytic (RBCs
normal size); causes of microcytosis—thalassemia; genetic defect (ruled out in patient who ever had normal MCV);
lead poisoning (rare in adults); consider diagnosis of IDA in patient with evidence of microcytic anemia
|
| Iron requirements: in menstruating women, 15 mg daily; pregnant or nursing women require 30 mg daily; men and
postmenopausal women, 5 to 10 mg; meat (heme iron) primary source of bioavailable iron; vegetarians must make
conscious effort to obtain iron-rich foods
|
| Causes of iron deficiency: alteration in stomach acid— iron requires acidic environment; iron deficiency common
with aging (stomach produces less acid; achlorhydria); medications (eg, proton pump inhibitors) or diseases can alter
acidic conditions of stomach; blood loss—most common cause of iron deficiency; 0.5 mg of iron in each milliliter
of blood; blood loss of ≈10 mL can lead to deficiency; 250 mL can be lost in normal menstrual period;
consider bleeding as cause of iron deficiency in men and postmenopausal women; gastrointestinal evaluation warranted
in this group
|
| Distinguishing IDA from anemia of chronic disease: anemia of chronic disease—chronic inflammatory process; hepcidin
(peptide hormone) likely suppresses body’s ability to use iron stores in bone marrow; mimics iron deficiency
|
 | Iron studies: serum iron—measures amount of iron in patient’s bloodstream at time needle inserted into vein; results
distorted by vitamin intake or fasting; relevant only when reported as ratio to total iron-binding capacity
(TIBC); TIBC—measures ability of transferrin to carry iron from intestinal wall to bone marrow; patient with
IDA has high TIBC, regardless of serum ratio; patient with anemia of chronic disease has low TIBC (iron stored
in bone marrow, but unable to be mobilized into RBCs); serum ferritin—measures amount of iron stored in bone
marrow; low level in IDA; high level in anemia of chronic disease
|
| Treatment: iron supplementation—identify possible dietary causes of iron deficiency (eg, vegetarian diet, avoidance of
certain foods because of cholesterol problem); 7.5 mg of iron in 3 oz of liver, 2.5 mg in ≈l lb of spinach; difficult to
correct iron deficiency using diet alone; most patients with IDA require iron supplementation to build up iron stores;
60 to 1290 mg of elemental iron daily recommended; iron stores become depleted before RBCs become microcytic
and patient becomes symptomatic; reverse occurs when patient takes iron supplementation (hematocrit rises, condition
still borderline); continue iron supplementation for another 6 wk after MCV becomes normal; counsel patient
about dietary issues to avoid becoming iron deficient again; iron supplements—ferrous fumarate; many patients unable
to tolerate standard recommendation of 3 pills daily; polysaccharide iron complex (Niferex), 1 pill daily; iron requires
acidic environment for absorption; absorption enhanced by vitamin C (eg, orange or cranberry juice)
|
| OSTEOPENIA AND OSTEOPOROSIS: DIAGNOSIS AND TREATMENT —Michael A. Levine, MD, Department
of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic Foundation, and Staff Physician, Department
for Pediatric Endocrinology, Cleveland Clinic Children’s Hospital, Cleveland, OH
|
| General considerations: bone mass peaks in late 20s; maintained until estrogen deficiency occurs (≈50-55 yr of age);
estrogen deficiency disturbs balance between bone formation by osteoblasts and bone resorption by osteoclasts; increased
bone resorption (due to development of secondary hyperparathyroidism and other biochemical changes favoring
activity of osteoclasts) leads to increase in rate of bone resorption (which exceeds rate of bone formation);
thinning of trabecular plates and loss of connectivity occurs at histologic level; osteoporosis characterized by low
bone mass; low bone mass and deterioration of bone causes fragility and increased risk for fracture; significant
problem worldwide; expected to increase because of aging population; 30 million women in United States with low
bone mass; spectrum of disease from osteopenia to osteoporosis; annual cost associated with disease ≈ $14 to
≈$17 billion dollars
|
| Evaluating patient’s risk factors: weight and height—measure height using wall-mounted stadiometer rather than
height rod attached to scale; height loss of >1.5 in indicative of clinical osteoporosis; reflects vertebral crush fracture
(symptomatic in 30% of patients); history of fragility fracture—defined as fracture occurring from fall from
standing height; typically sustained in long bone, spine, or hip; other risk factors—poor independent mobility (eg,
getting out of chair, walking [patient has ≈25% chance of sustaining fracture within next 12 mo]); weight <127 lb;
poor health; T score <1.8
|
| Vitamin D: ≈25% of patients have abnormality in serum 25- hydroxyvitamin D; measure serum 25-hydroxyvitamin
D (not serum 1,25-dihydroxyvitamin D) to determine serum level of vitamin D; ≈50% of Americans >50 yr of age
have vitamin D deficiency, based on new definition of normal range
|
| Bone densitometry: most important modality for measuring bone mineral density (BMD); used to establish or confirm
diagnosis of osteoporosis; request complete (4-page) report from radiologist showing pictogram of spine and
hip when ordering dual-energy x-ray absorptiometry (DEXA); request recalculation of BMD if evidence of osteophytes
seen at intervertebral junctions; 25% to 30% of patients >65 yr of age have sufficient osteoarthritis to distort
result of DEXA to indicate normal result (when patient actually has low BMD); greatest power to predict hip fracture
associated with central bone densitometry; tests at peripheral sites (eg, proximal or distal radius, heel) option if
central bone densitometry not available
|
| Screening recommendations: United States Preventive Services Task Force—women ≥65 yr of age should be screened
routinely (every other year); routine screening should begin in women 60 yr of age at risk for osteoporosis; risk
factors—low body weight, no estrogen use or early menopause, diabetes, use of high doses of thyroid hormone or
prednisone or prednisone equivalent (>5 mg daily), personal history of fracture or history of hip fracture in parent
(increases risk 50%), current smoking (bone loss after menopause significantly more rapid in women who smoke
than in women who do not smoke); World Health Organization’s criteria for interpreting DEXA—T score represents
standard deviation above or below average for patient’s sex and race; normal T score defined as bone density >-1;
with osteopenia, T score -1 to -2.5; with osteoporosis, T score -2.5; spectrum of increasing risk, with no safe point;
BMD and assessment of risk factors used to determine fracture risk
|
| National Osteoporosis Foundation (NOF) guidelines for initiating treatment: patients with T score of -2.0 at any site
(eg, spine, hip, peripheral bone) and no risk factors; patients with risk factors and T score between -1.5 and -2.0;
T score of -1.0 with fracture risks supports treatment recommendations of NOF; recommended that women at high
risk (eg, 70 yr of age with multiple risk factors) be treated even without performing bone densitometry; diagnosis of
clinical osteoporosis based on patient’s age and history of fragility fracture (20% risk for second vertebral fracture
in next 12 mo); evidence of kyphosis provides rationale for starting treatment
|
| Calcium and vitamin D: calcium—recommendations for daily intake differ; 1200 to 1500 mg of elemental calcium
recommended for postmenopausal women; dietary sources, rather than calcium supplements, preferred; no evidence
of increased risk for kidney stones in women obtaining 1200 to 1500 mg calcium daily from dietary sources;
increased risk for kidney stones with calcium supplements; vitamin D—increases efficiency of calcium absorption
50%; ensure patient has normal level of serum 25-hydroxyvitamin D; most laboratories report 10 ng/mL as lower
limit of normal for 25-hydroxyvitamin D; <30 ng/mL indicates secondary hyperparathyroidism and decreased absorption
of calcium; physiologically, lower limit of normal for 25-hydroxyvitamin D actually 30 ng/mL; ≈45% of
women taking vitamin D supplements shown to have low levels of vitamin D; for women between 50 and 70 yr of
age, 400 U daily most likely too low; majority of patients not receiving adequate levels of vitamin D in diet or
through exposure to sunlight; Women’s Health Initiative (WHI) substudy analysis demonstrated fracture reduction
in women compliant in taking vitamin D daily (noncompliance rate 20%-40%, regardless of which medication
used to treat osteoporosis); recommended that patient take vitamin D3 (cholecalciferol); ≈3 times more effective
than vitamin D2 (ergocalciferol); most multivitamins contain vitamin D2
|
| Lifestyle modification: weight-bearing exercise best for building bone; swimming and bicycling not beneficial for
improving skeleton; prevention of falls important; suggest use of hip pads for patient with balance problem; can reduce
risk for hip fracture; counsel on smoking cessation for patients who smoke
|
| Pharmacologic agents: antiresorptive agents—reduce bone loss; bisphosphonates, estrogen, selective estrogen receptor
modulators (SERMs), and calcitonin; anabolic agents—stimulate osteoblasts to form new bone; parathyroid
hormone (PTH)
|
| Bisphosphonates: first-line therapy for prevention of fractures; therapy most often prescribed for women with postmenopausal
osteoporosis; alendronate, risedronate, and ibandronate increase BMD in spine and hip in ≈70% to
95% of patients at end of 1 yr; all reduce risk for fractures; tolerability profiles similar; frequency of administration
biggest difference among medications; issue of compliance problem in prescribing; consider frequency of
administration when selecting medication; ibandronate—data show ≈50% reduction in subsequent vertebral
fractures in patients with history of vertebral fracture; no evidence showing similar reduction in hip or nonvertebral
fracture; risedronate—data show nearly 50% reduction in subsequent vertebral fractures in patients with
history of vertebral fracture; data show ≈40% reduction in risk for hip fracture in women 70 to 79 yr of age; no
statistically significant reduction in hip fractures in women >80 yr of age (subjects may have been healthy and
had high T scores); alendronate—data show reduction in vertebral fractures comparable to reductions seen with
risedronate and ibandronate; data show 50% reduction in hip fractures, regardless of patient’s age or fracture risk
|
| Osteonecrosis of jaw: all bisphosphonates carry precaution about risk for osteonecrosis of jaw; poor dental hygiene
or history of dental problems risk factors (assess patient’s dental hygiene before prescribing); reported in patients
receiving all forms of bisphosphonates, but primarily in patients using intravenous forms, eg, zoledronic acid
(Zometa), pamidronate (used in cancer therapy); chemotherapy, dental procedures, coagulopathy, and infection
also risk factors; risk ≈1 in 100000 patient-years; dental work should be performed before starting bisphosphonate
treatment; no data on whether to discontinue bisphosphonate treatment in patient having dental procedure;
long half-life makes discontinuing impractical; dental surgery not recommended for treating condition (can
worsen condition)
|
| Estrogen: remains treatment option despite “Black-Box” warning; data show estrogen in standard doses significantly
reduces risk for fracture by 35%
|
| SERMs: raloxifene (Evista) associated with 30% to 35% reduction in risk for subsequent vertebral fractures among
women with preexisting vertebral fractures, and ≈50% reduction among women without preexisting vertebral
fracture; no data showing raloxifene reduces risk for hip fracture
|
| Anabolic agents: PTH (1-34); approved for treatment of postmenopausal osteoporosis in patients with severe disease;
data show 65% reduction in vertebral fractures in patients using 20 µg PTH injected subcutaneously daily
(no significant difference with 40-µg dose); no evidence of reduction of hip fractures; adverse effects—
hypercalcemia reported in 11% of patients taking 20-µg dosage; unacceptably high incidence of hypercalcemia
with 40-µg dose; monitor serum and urine calcium every 6 mo; recommended benefits of PTH quickly lost after
therapy discontinued; PTH should not be used for >2 yr and should be immediately followed with antiresorptive
medication (eg, bisphosphonate); no advantage to using PTH simultaneously with bisphosphonate; data show
≈50% increase in BMD in patients receiving PTH after using bisphosphonate
|
| Conclusion: low bone mass and increased fracture risk common in postmenopausal women; average woman 50 yr of
age has 40% risk of sustaining fracture in lifetime; risk-fracture analysis and bone densitometry can identify patients
who should be considered for specific pharmacology; calcium and vitamin D foundations of treatment and
management strategy; important that patient have sufficient vitamin D intake to normalize 25-hydroxyvitamin D
level; bisphosphonates first-line drugs in treatment and prevention of fractures in patients with postmenopausal osteoporosis;
therapy does not need to be indefinite; assess patient’s BMD after 5 yr and consider whether medication
can be discontinued; PTH should be reserved for patients for whom bisphosphonate therapy ineffective or for those
who have severe osteoporosis; patient should receive antiresorptive medication after discontinuation of PTH; sequential
approach of using bisphosphonate followed by PTH appears promising
|
| Osteoporosis and medroxyprogesterone (Depo-Provera): increased risk for bone loss and increased risk for fractures
associated with medroxyprogesterone and leuprolide (eg, Lupron); bone densitometry recommended for patients
taking agents >6 mo; adequate calcium and vitamin D recommended if BMD normal; consider bisphosphonate if T
score <1.5; concern about use in women of reproductive age; animal studies demonstrate defects in skeletal development
with high doses of bisphosphonates; 5 reported cases of women in United States who became pregnant
while taking bisphosphonate showed no skeletal defects in neonate; American College of Rheumatology recommends
bisphosphonate therapy for patients receiving 5 mg prednisone daily for >3 mo
|
| Combination therapy: slightly greater increase in BMD shown when 2 forms of antiresorptive therapy combined; no
compelling data demonstrating combining 2 antiresorptives provides enhanced antifracture benefit; theoretic data
showing oversuppression of bone may increase risk for fracture; speaker does not recommend combination therapy
|
| Frequency of bone densitometry: speaker recommends every year if patient treated and every other year if patient not
treated; 15% to 30% of women lose BMD in first year on bisphosphonate; determine whether patient compliant in
taking medication and assess level of vitamin D; data show women losing BMD or who do not gain BMD in first
year on therapy have greatest increases in second year; look for other causes of osteoporosis in women whose loss
of BMD does not stabilize or who do not gain BMD; some women may require higher doses or may be candidates
for anabolic therapy with PTH
|
Suggested Reading
Bilezikian JP: Osteonecrosis of the jaw—do bisphosphonates pose a risk? N Engl J Med 355:2278, 2006; Brady PG:
Iron deficiency anemia: a call for aggressive diagnostic evaluation. South Med J 100:966, 2007; Muldowney FP: Alendronate
and parathyroid hormone. N Engl J Med 353:2618, 2005; Neer RM et al: Effect of parathyroid hormone (1-
34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434,
2001; Rockey DC: Occult gastrointestinal bleeding. Gastroenterol Clin North Am 34:66, 2005; Zimmermann MB,
Hurrell RF: Nutritional iron deficiency. Lancet 370:511, 2007.
Educational Objectives
| The goal of this program is to improve the diagnosis and management of iron deficiency anemia (IDA) and osteoporosis.
After hearing and assimilating this program, the clinician will be better able to:
|
| 1. Distinguish IDA from anemia of chronic disease.
|
| 2. Treat patients with IDA.
|
| 3. Identify patients with low bone mineral density who are at risk for osteoporosis.
|
| 4. Counsel patients about preventive strategies for maintaining bone health.
|
| 5. Prescribe the appropriate medication for patients with osteoporosis.
|
Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty members to disclose relevant financial relationships
within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure
that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the
following has been disclosed: Dr. Levine is on the Speakers’ Bureaus of Merck, Eli Lilly, and Genentech. Dr. Weissmann and the planning committee reported that they had nothing to disclose.
Acknowledgments
Dr. Weissmann was recorded at Women in Medicine 2007, held July 25-29, 2007, in Burlington, VT, and sponsored by the University
of Vermont College of Medicine. Dr. Levine spoke at Women’s Health Conference, held December 1, 2006, in Baltimore, MD, and
sponsored by Johns Hopkins University School of Medicine. The Audio-Digest Foundation thanks the speakers and the sponsors for their
cooperation in the production of this program.
|
