ISSUES IN AGING
| CURRENT MANAGEMENT OF OSTEOPOROSIS —Dorcas C. Morgan, MD, Assistant Professor of Obstetrics, Gynecology
and Reproductive Sciences, Division of Reproductive Endocrinology and Infertility, University of Medicine
and Dentistry of New Jersey—Robert Wood Johnson Medical School, New Brunswick
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| General considerations: osteoporosis major public health problem in United States; affects ≈10 million Americans; affects
women 4 times more than men; increasing incidence of fractures in part due to increasing aging population
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| Bone physiology: osteoclasts—involved in bone resorption; osteoblasts—involved in bone formation; osteocytes—help
maintain bone; lining cells—cover bone; balance between bone formation and resorption exists until disruption occurs,
ie, loss of estrogen, aging; bone function—support and protection for heart and other internal organs; attachment
site for muscles, allowing for movement of limbs; reservoir for calcium and phosphorous; trabecular bone—bone of
axial skeleton, pelvis, and proximal femur; constitutes honeycomb structure filled with marrow and fat; cortical
bone—bone of peripheral skeleton; makes up ≈80% of bone mass; peak bone mass—achieved in women in late adolescence;
slight increase in bone mass until ≈30 yr of age; after 30 yr of age, 0.7% per year decrease in bone mass (influenced
by endocrine factors, eg, menopause); anorexic patient and patient with hypothalamic amenorrhea at high
risk; influenced by heredity; loss of bone mass accelerates with declining estrogen levels; ≈5% of trabecular bone lost
per year after menopause; after menopause, ≈1 to 1.5% of total bone mass can be lost per year; with decline in estrogen,
bone remodeling increases and resorption dominates
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| Diagnostic tests: dual energy x-ray absorptiometry (DEXA)—most common diagnostic modality; radius of hip and spine
measured to increase diagnostic accuracy; normal value at one site does not preclude abnormal value at another site;
ultrasonography—most cost-effective method; measured at calcaneus; hip and spine cannot be measured; quantitative
computed tomography—not standard of care; radiation exposure exceeds that of DEXA; poor reproducibility in spine
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| Definitions: osteoporosis— low bone mass and microarchitectural deterioration leading to increased bone fragility and increased
risk for fracture; symptomatic spinal osteoporosis can lead to loss of height, postural deformities, pain, and subsequent
pulmonary and gastrointestinal (GI) dysfunction; ≈50% of women ≥65 yr of age have unrecognized vertebral
compression fractures; ≈1 cm of height lost with each compression fracture; woman can lose ≈2.5 in of height in lifetime
if disease unrecognized; Caucasian woman has 15% lifetime risk of developing osteoporosis; 80% of all hip fractures associated
with osteoporosis; T score—SD between patient’s bone mass and average peak young adult bone mass; Z
score—SD between patient and average bone mass for patient of same age and weight; World Health Organization
(WHO) defines osteoporosis as bone mineral density of at least 2.5 SDs below young adult normal; osteopenia defined as
bone mineral density -1 to -2.5 SDs below young adult normal
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| Risk factors: female sex, advancing age, family and personal history of fracture and/or osteoporosis, white or Asian race,
small body habitus, estrogen deficiency at any point in lifetime, lifestyle issues, eg, excessive alcohol intake, diet poor
in calcium, smoking, and medical disease requiring patient to take glucocorticoids; excessive thyroid hormone can increase
bone turnover and increase risk for osteoporosis
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| Effects of hormones on skeletal metabolism: increase bone resorption—parathyroid hormone (used as treatment in small
doses, but excess can cause osteoporosis); glucocorticoids (advise patient to take multivitamin that includes vitamin
D); thyroid hormone and excess vitamin D; decrease bone resorption—calcitonin and gonadal steroids; increase bone
formation—growth hormone, vitamin D, and gonadal steroids; goal should be prevention; clinician at forefront of prevention;
educate patient about need for adequate calcium intake
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| Daily calcium needs of women: 11 to 24 yr of age—1200 to 1500 mg; 25 to 50 yr of age—≈1000 mg; ≥51 yr of age—1500
mg; pregnant or nursing—1200 to 1500 mg; vitamin D—influences calcium in GI tract; 400 to 800 IU recommended
dosage; 800 to 1000 IU reserved for patient with disease or patient not receiving adequate sun exposure
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Pharmacologic Treatment
| Estrogen: inhibits bone resorption in postmenopausal women; associated with reduction in hip and vertebral fractures;
decision about use of estrogen controversial and must be made on individual basis, weighing risks and benefits
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| Selective estrogen receptor modulators (SERMs): raloxifene—60 mg daily recommended; effect like estrogen on bone;
positive effect on lipids; decreases low-density lipoproteins (LDL); no effect on high-density lipoproteins (HDL);
Women’s Health Initiative (WHI) suggested evidence not strong enough to alleviate cardiovascular risk; no effect on
endometrium or vagina; some women experience vasomotor instability; increased risk for thrombolic events; speaker
does not recommend long-term use; data from Multiple Outcomes of Raloxifene Evaluation (MORE) study suggested
more studies needed to evaluate long-term effect; controversial therapy with potential risk for thrombolic events
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| Bisphosphonates: possible side effects associated with use >5 yr unknown; chemical compounds; no hormonal association
with estrogen or SERMs; impair bone resorption and bone formation; appears to be increase in bone formation
and decrease in resorption during initial 6 mo of use; formation may be impaired with >6 mo of use, eventually
leaving patient with low bone mass
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 | Etidronate: associated demineralization of bone, resulting in osteomalacia and GI effects; dosage 400 mg daily for 2 wk
every 3 mo; approved for treatment of Paget’s disease of bone; all bisphosphonates must be taken on empty stomach
with large amount of water first thing in morning; patient must remain upright for at least 0.5 to 1 hr; association between
bisphosphonates and jaw disease reported
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| Alendronate: second-generation bisphosphonate; weekly dosage encourages compliance; dosage 35 mg weekly for
prevention and 70 mg weekly for treatment; controversial whether beneficial to treat patient with osteopenia; literature
suggests alendronate should be reserved for patient with diagnosis of osteoporosis
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| Risedronate: second-generation bisphosphonate; dosage 35 mg weekly for treatment
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| Ibandronate: only bisphosphonate approved to be taken monthly; side effects similar to other second-generation bisphosphonates
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| Other treatment agents: sodium fluoride—not approved for use in United States; beneficial dosage undetermined; parathyroid
hormone—subcutaneous daily injections; expensive; use limited to 2 yr; increased bone formation and decreased
fracture risk; calcitonin—administered intramuscularly, subcutaneously, or nasally; expensive; possible
allergic reactions
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| Investigational treatments: tibolone—19-nortestosterone progesterone; similar to compound found in contraceptive
pills; appears to have effect similar to estrogen on bone; available in Europe; nitroglycerine
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| Question about medroxyprogesterone acetate (Depo-Provera): speaker concerned that patients using Depo-Provera not
being made aware of long-term risk associated with use; patient made hypoestrogenic at time when they would normally
be achieving peak bone mass; controversial as to when screening bone density should begin
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| OSTEOARTHRITIS: MORE THAN WEAR-AND-TEAR DAMAGE —Robert Tierney, MD, Clinical Associate Professor,
University of Minnesota, Minneapolis; Department of Rheumatology, Park Nicollet Medical Center, St. Louis
Park, Minneapolis
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| General considerations: 3 kinds of osteoarthritis; common to see spurs on x-rays of neck and low back; no symptoms unless
they impinge on nerve root, causing pain down arm and fingers; knobby knuckles—osteoarthritis affects proximal
interphalangeal and distal interphalangeal joints; appears often at base of thumb; woman has 50% chance of knobby
knuckles (13% for man) if parent or grandparent had osteoarthritis; unknown if treatment helps; osteoarthritis—
known as wear-and-tear arthritis; cartilage and padding of joint becomes denuded; cartilage does not regenerate; as
cartilage wears away, bone rubs on bone, causing pain; knee pain— generally not caused by osteoarthritis; most common
causes prepatellar bursitis, anserine bursitis, meniscal tear; pain comes from patellofemoral joint; quadriceps
strengthening exercises easy way to treat
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| Nonpharmacologic management: cane—used in right hand, takes 40% of weight off left knee; varus wedge—used in
heel of shoe prevents pronation of knee; changes knee from hinge joint to rotating hinge joint; weight reduction—5-lb
weight loss translates into 15 lb standing up, 25 lb going up and down stairs, and 35 to 50 lb running; Framingham
study showed 11-lb weight loss decreased risk for osteoarthritis 3 yr later by 50%; exercise—straight leg raises can increase
strength of quadriceps by 25% in 3 mo in woman (20% in man) and decrease risk for symptomatic osteoarthritis
in 3 yr by 50%; quadriceps support knee and hip; quadriceps strength independent risk factor for hip fractures;
quadriceps should be tight; senior runners—data show no increase in osteoarthritis of knee in senior runners running
42 mi weekly and no joint replacement in senior runner group, compared to 4 in control group; disability significantly
less; data concluded long-distance running neither protective nor causative of osteoarthritis in knee
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Pharmacologic Treatment
| Acetaminophen: 8 tablets daily of acetaminophen (Tylenol Extra Strength or 6 tablets of Tylenol Arthritis Pain) recommended;
discontinue if not effective after 2 wk; 4 Tylenol Extra Strength tablets can be used during day and 2 Tylenol
8-Hour (timed release) tablets at bedtime; not recommended for patients consuming >2 oz of alcohol daily or those
with hepatitis
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| Nonsteroidal anti-inflammatory drugs (NSAIDs): cyclooxygenase-2 (COX-2) specific inhibitors safer on GI tract than
other preparations; often, adverse GI effect caused by too high dosage; NSAIDs with misoprostol (Cytotec) or proton
pump inhibitors (PPIs); nonacetylated salicylates and tramadol (Ultram)
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| Intra-articular treatments: cortisone injections do not restore cartilage; limited to 3 injections annually; pain relief
should last 4 to 6 mo, but generally only effective for 1 wk (sign that inflammation treated); good pain relief at base of
thumb; injection should be effective for 1 yr
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| Tetracycline (Doxycycline): antibiotic and anti-inflammatory effect; inhibits tissue metalloproteinases (collagenases that
eat away at collagen); studies show dogs on doxycycline have less damage to their cartilage in knee, compared to
group not on doxycycline; dosage 100 mg bid; causes discoloration of skin
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| Topical capsaicin (cayenne pepper) cream: studies show treatment effective; prevents release of substance P (antiprostaglandin);
creams available containing 0.025% or 0.075% capsaicin; hands must be washed thoroughly after applying
cream to prevent transferring active agent to sensitive areas, eg, eyes (neutralized with milk)
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| Glucosamine and chondroitin: glucosamine isolated from shellfish; contraindicated in patient allergic to shellfish; chondroitin
isolated from cow trachea; combination chondroitin and glucosamine (Cosamin DS only preparation tested
and approved); amount of active drug may vary; may take 2 to 3 mo to become effective; 3-yr randomized double-
blind placebo-controlled trial involving 212 patients showed no cartilage lost in group taking glucosamine; 5-yr follow-up
study showed 18% of people on placebo and 5% of people taking glucosamine had knee replacement; combination
glucosamine-chondroitin shown more effective than individual compounds in people with moderate to severe
osteoarthritis; not statistically significant in people with mild to moderate osteoarthritis; recommended patient begin
with one preparation and allow 3 mo to determine effectiveness; most likely, therapy not going to be effective after
trying second preparation; if Cosamin DS not effective, second product likely will not be effective; mechanism of action
unclear
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| Viscosupplementation: hyaluronic acid produced in joint acts as joint lubricant; in osteoarthritis, patient lacks adequate
lubrication because of breakdown of cartilage; 3 injections of hyaluronic acid derivative (Hyalgan) and 5 injections of
hyaluronic acid derivative (Synvisc) into joint 1 wk apart cost ≈$1000; option for patient who fails steroid injections
or patient wanting to avoid surgery; approved only for osteoarthritis of knee; ineffective in hip, ankle, elbows, or base
of toe; eliminated from joint in 28 hr; effective for ≈8.4 mo; mechanism of action unclear; pseudoseptic arthritis can
occur with Synvisc; data show triamcinolone (Aristospan) not as effective as Synvisc at 12 wk, equal by 24 wk
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| Methyl sulfonyl methane (MSM): 3 g bid effective; data show significantly less pain and increased function in people using
MSN, compared to those using placebo
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| Alternative therapies: acupuncture—recommended for patients with refractory pain who desire unconventional therapies;
mud pack—used commonly in Europe; shown to improve physiologic antioxidant defenses in serum, reduce
damage to articular cartilage, and lower serum levels of prostaglandin E2 and leukotriene B4
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Educational Objectives
| The goal of this program is to educate the listener about current treatment for osteoporosis and osteoarthritis. After hearing
and assimilating this program, the clinician will be better able to:
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| 1. Describe the physiologic processes involved in bone formation and resorption.
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| 2. List the diagnostic modalities for measuring bone mineral density (BMD) and identify the one most commonly
used.
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| 3. Discuss treatment options for low BMD and the controversy surrounding those treatments.
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| 4. Counsel patients about nonpharmacologic remedies for osteoarthritis.
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| 5. Prescribe pharmacologic therapies for patients with osteoarthritis.
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Discussed on this Program
Acetaminophen (N -acetyl-P -aminophenol; APAP) [Tylenol Arthritis, Tylenol Caplets, Tylenol Children’s, Tylenol
Extended Relief, Tylenol Extra Strength, Tylenol Regular Strength Tablets and other trade names]
Alendronate sodium [Fosamax]
Calcitonin-salmon [Calcimar, Fortical, Miacalcin, Osteocalcin, Salmonine]
Capsaicin [Capsin, Capzasin·P, Dolorac, No Pain-HP, Pain Doctor, Pain-X, R-Gel, Zostrix, Zostrix-HP]
Chondroitin sulfate and glucosamine HCl [Cosamin DS]
Etidronate disodium [Didronel, Didronel IV]
Glucosamine sulfate
Hyaluronic acid derivatives [Hyalgan, Supartz, Synvisc, Orthovisc]
Ibandronate sodium [Boniva]
Medroxyprogesterone acetate [Amen, Curretab, Cycrin, Depo–Provera, Depo-subQ Provera, Hematrol, Provera]
Methy Sulfonyl Methane (MSM)
Misoprostol [Cytotec]
Nitroglycerin [Nitrobid, Nitrobid IV, Nitrogard, Nitroglyn, Nitrol, Nitrolingual, Nitrong, NitroQuick, Nitrostat,
Nitrotab, Nitro-Time, Tridil]
Raloxifene [Evista]
Risedronate sodium [Actonel]
Tamoxifen citrate [Nolvadex]
Teriparatide acetate (rDNA origin; parathyroid hormone) [Forteo]
Tibolone [Xyvion]
Triamcinolone hexacetonide [Aristospan Intralesional, Aristospan Intra-articular]
Tramadol HCl [Ultram] Tramadol and acetaminophen [Ultracet]
Suggested Readings
Baler CL et al: Future treatment of osteoarthritis. Orthopedics 28(2 Suppl):s 227, 2005; Cunningham GF: Screening for
osteoporosis. N Engl J Med 353(18):1975, 2005; Holick MF et al: Prevalence of vitamin D inadequacy among postmenopausal
north american women receiving osteoporosis therapy. Obstet Gynecol Surv 60(10):658, 2005; Modawal A et al:
Hyaluronic acid injections relieve knee pain. J Fam Pract 54(9):758, 2005; No authors listed: Summaries for patients.
Hormone therapy to prevent chronic conditions in postmenopausal women: recommendations for the U.S. Preventive
Services Task Force. Ann Inter Med 142(10):159, 2005; Reginster JY et al: The treatment of severe postmenopausal osteoporosis:
a review of current and emerging therapeutic options. Treat Endocrinol 5(1):15, 2006; Reginster JY et al:
Naturocetic (glucosamine and chondroitin sulfate) compounds as structure-modifying drugs in the treatment of osteoarthritis.
Curr Opin Rheumatol 15(5):651, 2003; Reginster JY et al: The treatment of severe postmenopausal osteoporosis: a
review of current and emerging therapeutic options. Treat Endocrinol 5(1):15, 2006; Reginster JY: Treatment of postmenopausal
osteoporosis. BMJ 330(7496):859, 2005; Towheed TE et al: Glucosamine therapy for treating osteoarthritis.
Cochrane Database Syst Rev (2):CD002946, 2005.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. For this issue, the
faculty reported nothing to disclose.
Dr. Morgan was recorded at the 20th Annual Issues & Controversies in OB/GYN sponsored by University of Medicine and
Dentistry of New Jersey, and recorded on November 10-12, 2005 in Lake Buena Vista, Florida. Dr. Tierney was recorded
at the 6th Annual Women’s Health Conference: The Challenges of the Changing Body, sponsored by HealthPartners
Institute for Medical Education, Center for Continuing Professional Development, and recorded on November 4,
2005 in Minneapolis, Minnesota. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation
in the production of this program.
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